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Archive for the ‘Fat Stem Cells’ Category

New Stem cell conveying hydrogel could assist the heart with recuperating myocardial ischemia – Microbioz India

Tuesday, August 17th, 2021

When blood vessels that feed the heart become blocked, damage to the heart muscle can occur and this can affect cardiac function. By stimulating the formation of new blood vessels, a new stem-cell-carrying gel helps mice overcome this condition called myocardial Infarction. The stem cell delivery system was developed by scientists from Kansai University, Japan. It is published in Science and Technology of Advanced Materials.

The hydrogel acts like a scaffold to hold the stem cells in place at injection site and keep them alive longer. The stem cells release cytokines, which stimulate the formation blood vessels and help the heart to recover. The gel is biodegradable so that it eventually dissolves and can be discarded by the body. Image credit: Kansai University

In their application, the team used stem cells from fat tissue. These stem cells, also known as adipose derived stem cells, have been used in the treatment of damaged cardiac tissue due to reduced blood flow. This is called myocardial Ischemia. Once injected into damaged tissue, the stem cells are supposed to release stimulants that can help regenerate blood vessels. However, they are not able to be retained in the tissue or survive long enough. Scientists have also found that injecting biodegradable hydrogels, which are cell-free, into damaged heart tissue can help partial recovery.

They first created hydrogels that could hold stem cells in place longer at the site where there is tissue damage. They are best used at room temperature. This allows you to easily mix the stem cells. The solution reacts with the body to heat and transforms into a gel when it is injected into the organ.

One hydrogel was particularly good at keeping its gel state. It was made from a mixture of molecules called tri-PCG with acrolyl group attached. The tri-PCG-acryl mixture was then combined with a polythiol derivative.

The team also added stem cells from adipose tissue to the hydrogel. They then observed how long they lived in petri dishes as well as the production of different genes and substances.

The stem cells were able to survive in our injectable hydrogel and released molecules that stimulate blood vessel formation, improving heart function and making it effective for treatment of ischemic heart.

Yuichi Ohya, Bioengineer, Kansai University

After confirming safety, the team plans to next test the therapy on larger animals and then conduct clinical trials in humans. They plan to use their injectable hydrogel for immune cells to treat cancer and in vaccines against viral infections.


Journal reference:

Yoshizaki, Y.,et al.(2021) Cellular therapy for myocardial ischemia using a temperature-responsive biodegradable injectable polymer system with adipose-derived stem cells.Science and Technology of Advanced

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New Stem cell conveying hydrogel could assist the heart with recuperating myocardial ischemia - Microbioz India


Participants Diagnosis Halts Gene Therapy Clinical Trial – The Scientist

Tuesday, August 17th, 2021

Aclinical trial testing a novel gene therapy for a rare neurological disease has been put on hold after one of the participants in a Phase 3 trial developed a bone marrow disorder that can lead to cancer. The pause, announced Monday by the trials sponsor, bluebird bio, and mandated by the US Food and Drug Administration (FDA), was taken out of an abundance of caution, the companys president of rare genetic diseases, Andrew Obenshain, said in a recent quarterly call.

The therapy targets cerebral adrenoleukodystrophy, which is caused by a mutation in the gene for an enzyme called adrenoleukodystrophy protein (ALDP) that breaks down fats. The mutation causes fat to build up in the brain, where it breaks down the insulating myelin that allows neurons to communicate with one another. Because the gene is on the X chromosome, women typically have a least one good copy, so the disease primarily strikes men. Left untreated, it causes damage to hearing, vision, cognition, and coordination. It is often fatal.

Bluebirds gene therapy uses an engineered lentivirus to correct the mutation associated with the disease. Lentiviruses belong to the same family as HIVretrovirusesand have been widely used in gene therapies and other medical applications for many years. While other virus-based platforms using retroviruses had previously been linked to cancer among patients, it is only recently that a lentivirus has been implicated in such an outcome: in February of this year, bluebird bio paused another trial, one for a blood disorder, after two patients developed leukemia-like cancer, Sciencereports, although it was later determined that the virus was likely not the cause, and the trial resumed.

Most in the field were hoping that we would not see such an event with lentiviral vectors, Harry Malech, a gene therapy researcher at the National Institutes of Health, tells Science, adding, I dont think anybodys been . . . saying this couldnt happen.

The cerebral adrenoleukodystrophy therapy involves taking samples of a patients bone marrow and treating the stem cells therein with the modified virus that contains a corrected copy of the gene that encodes ALDP. After a round of chemotherapy to reduce the persons bone marrow cells, the treated cells are infused back into the patient. Thereafter, the patients stem cells produce healthy blood cells with a functional copy of the gene for ALDP. The therapy entered the market in Europe last month following a previous safety and efficacy trial that included 32 patients. A second trial, the one that has now been paused, was set to finish in 2024.

Speaking on the call, bluebird bios Chief Scientific Officer Philip Gregory said that one patient in the second trial developed myelodysplastic syndrome (MDS), a blood disorder that sometimes leads to leukemia, and another two had abnormal bone marrow cells that could progress to MDS. When scientists examined their cells, they found lentiviral DNA inserted at a site in the genome that has previously been linked to MDS in retrovirus-based therapies, suggesting that the virus may have caused the changes.

Specifically, Gregory said the issue is likely caused by the virus promoter, the DNA sequence that turns on the therapeutic copy of the gene. To ensure the gene produces enough ALDP in the brain to be an effective treatment, the researchers needed a strong promoter, but as a consequence, the promoter had off-target effects, turning on other genes in the area around the mutation, including cancer genes, Gregory speculated.

Donald Kohn, a gene therapy researcher at the University of California, Los Angeles, who helped design the viral vector, tells Sciencethat in the time since bluebird bio first began developing the therapy, researchers have identified other promoters that might be able to do the job with a lower risk of causing cancer. He adds that this particular incident shouldnt preclude scientists from pursuing other lentivirus treatments, as the issue seems to come down to design, and Kohn doesnt know of any other lentivirus therapies that use the same type of promoter.

Panam Malik, a hematologist at Cincinnati Childrens Hospital who was not involved in the work, similarly tells Science that virus-based platforms should be highlighted for the good they have done. This is a severe adverse event, she says, but adds, we should never lose sight of the fact that so many patients . . . have been helped. Despite this rare incident, the findings could help scientists and researchers design safer and better vectors for the future.

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Participants Diagnosis Halts Gene Therapy Clinical Trial - The Scientist


The Involuted Palate, or the Savage Crinkle of Future Snacks – lareviewofbooks

Tuesday, August 17th, 2021

AUGUST 11, 2021

FOR THE ARCHITECTURAL HISTORIAN and critic Reyner Banham, the bag of potato chips (or crisps as he, an Englishman, put it) was a remarkable technological innovation. But it was an emotional object rather than a practical one. The sound of the bag crinkling and tearing as you ripped it open and consumed every greasy chip and then the shards at the bottom, expressed the temper of the late 20th century: Its the first and most familiar of Total-Destructo products and probably sublimates more aggression per annum than any quantity of dramaturgical catharsis, Banham wrote in his short essay The Crisp at the Crossroads (1970). Banham speculated about the possibilities for flavored chips: not just cheese-and-onion or barbecued bacon, but toad in the hole, crme de menthe, and more, all of them flavor stations along the expanding snacking frontier. But flavor seemed to interest him less than form. The relationship between chip and bag seemed to him almost vernacular: the bag of chips was like some survivor from a lost golden age of peasant technologies that have matured long in the wood and hand: the oar, the axe, the rolling pin. The chip glows golden when you hold it up to the light but it is unlike the oar, axe, or rolling pin, because its vernacular quality stems from the way it pairs with its packaging, the proper use of both involving a crinkling burst. The chip is an impractical food if the task is to get the most nutrition possible out of the potato; but if the task is to pleasurably wreck something, then the chip-and-bag is very good design indeed.

Fifty years later, the chip retains its basic shape, although some chips are now chili mango flavored. And the world of snacking R-and-D has not run out of steam. Entrepreneurs, working to transform food through technology, seem to promise new innovations every day, not all of them intended as mere snacks. There are pea protein puffs, and new kinds of plant-based burgers, and bunches of kale leaves grown hydroponically in vertical farms. The most ambitious of them all, the dream of growing meat in labs, hovers at the horizon, gaining headline coverage as companies promise to produce it soon but cultured meat never quite arrives in the supermarkets. The entrepreneurs call all these things innovations. But what if the best metaphor for describing new food-tech products was not innovation but involution? That latter term stems from the Latin involutio and carries the meaning of curling inwards (as a chip curls) but has more common meanings, which the OED provides: the state of being complicated; the shrinkage of old or inactive tissue in the body; a mathematical function, transformation, or operator that is equal to its inverse, or in other words, that continues to be itself when applied to itself. This should sound counterintuitive, for we are used to thinking of technological changes as introducing novelty into a system, perhaps changing that system fundamentally, rather than causing it to curl in on itself. In any case, involution may seem like a lofty term to apply to crunchy protein bars made with cricket flour, ersatz meat made by extruding pea protein, or powdered algae, but I will argue for the terms explanatory power bite by bite.

In his 1936 essay Loose Ends of a Theory on the Individual Pattern and Involution in Primitive Society, the anthropologist Alexander A. Goldenweiser put involution on anthropologys map. While meditating on the relationship between individual expression and cultural patterns, Goldenweiser used involution to describe an enduring condition in which patterns both in the sense of physical symbols but also forms of social behavior run through every aspect of a human communitys life, providing both a fabric of meaning and a limiting, even restrictive force. In primitive societies, Goldenweiser wrote, pattern is particularly conspicuous in rituals and the forms of religious objects, where the tenacity of pattern is enhanced by social inertia or a sacred halo. Pattern limits development, and Goldenweiser seemed to imply that an intimate relation with pattern was part of what kept primitive societies primitive. It inhibited the technical, social, and intellectual developments that could eventually lead to modernization.

But patterns also set limits in a more positive sense, as a canvas edge or a frame establishes the boundary for a painting. Thus Goldenweiser characterized the traditional art of the Maori, in which simple units of design recombine in multiple ways within a delimited space: The inevitable result is progressive complication, variety within uniformity, virtuosity within monotony. This, too, is involution. Involution wasnt limited to primitive contexts; Goldenweiser also found its inward curling in late Gothic art, whose structures and component parts may be fixed but still express play and creativity in elaborations on basic themes. But Goldenweiser saw involutions limits as ultimately negative:

Expansive creativeness having dried up at the source, a special kind of virtuosity takes its place, a sort of technical hairsplitting. No longer capable of genuine procreation, art here, like a seedless orange, breeds within itself, crowding its inner structure with the pale specters of unborn generations.

Like a seedless orange? Or like a protein bar made with cricket flour, its basic design already set by the architects of snacking, but filled with the bodies of insects? Crunch! Complexity. Crunch! Sameness.

Larissa Zimberoff, in her admirably skeptical book Technically Food: Inside Silicon Valleys Mission to Change What We Eat, describes the contemporary food-tech nexus, surveying a wide range of startup companies, mostly based in the San Francisco Bay Area. She interviews dozens of entrepreneurs, encountering them at tech conferences or in the warehouses and labs where they try to grow the future. She hears their pitches and then examines those pitches to see if they survive close scrutiny. Many of Zimberoffs entrepreneurs claim that their products will replace existing foods that are environmentally unsustainable or cruel to nonhuman animals. Their mission, then, is one of supersession. What if you could eliminate animal agriculture, with its massive environmental footprint and relatively inefficient transformation of plants into animal protein? Sensitive to concerns about the environment, and about animal cruelty, Zimberoff keeps human health at the books center: are these new foods really going to be better for us, especially given that so many of them are ultra-processed, a category linked to bad health outcomes? How about the well-known plant-based Impossible and Beyond Meat burgers? They are far more fatty and caloric than, say, a meal of chickpeas. Coconut oil, a key ingredient used in most plant-based meat, is about 90 percent saturated fat. Memorably, Zimberoff compares the creation of these burgers to fabricating a Slim Jim, which is made from chicken scraps through the same technique, extrusion. Are these different products? Yes. Are they similarly made? Yes. Zimberoffs book is marbled with detail, and performs a useful analytic service for readers trying to understand new tech foods: while many novel food companies claim to break out of the paradigms set by Big Food (those huge international companies that fill the central aisles of grocery stores with processed stuff ), Zimberoff shows that many of their founders hope to sell ingredients to Big Food, and use processing techniques that Big Food perfected or they may plan to sell the whole company to Big Food, lock, stock, and bioreactors.

As I followed Zimberoffs journey from one warehouse-based company to another, from algae to fungi, from pea protein to vegan milk and eggs, from plant-based burgers to vertical farming, and all the way to cultured meat, I found myself thinking back to Goldenweisers essay. How can we tell if a given novel food technology represents innovation, the change that changes everything, or if it represents involution, a change that ultimately changes nothing within enduring cultural, economic, and social patterns? Disclosure: I appear briefly in Technically Food as an expert on cultured meat, the subject of my own 2019 book, Meat Planet: Artificial Flesh and the Future of Food; Zimberoff spoke with me several times during her research. I spent years conducting fieldwork with tissue engineers and other scientists, as well as with entrepreneurs and futures consultants, who hope to grow animal muscle and fat, consumable as meat, from biopsies of cells, obviating the need for industrial animal agriculture. Hypothetically, cultured meat would require vastly fewer natural resources, and cause no cruelty to animals at all. We could visit a pig on a farm, eat meat grown from a biopsy of its cells, and then play with that same pig. If this effort succeeds, I believe it will constitute the largest and fastest shift in human subsistence strategies in history. Watch your step. That initial if is a doozy.

Innovation or involution? Form is the first clue. The wonder foods in Zimberoffs book mostly imitate familiar foods like chips, puffs, bars, shakes, and burgers. They may be made of new materials, but those materials do not dictate their shape. A plant-based sausage, with its arbitrary relationship between form and material, is in fact a skeuomorph, a Greek term which more or less means vessel-form. Its shape is like a container that used to be filled with other stuff, stuff that dictated the original form of the container consider those lintels of ancient Greek temples that rendered, in stone, the ends of protruding wood beams. Where pig intestines once gave sausage its shape, cultural expectation now dictates a cylinder, tapered where the traditional length of intestine was tied off at the ends. The compass in a smartphone doesnt work the way a magnetized needle does, but the digital representation of the compass on the phones screen is familiar, expected. The shapes of meat surrogate products, whether they are based on plant or animal cells, now come not from the bodies of animals, nor from the inspiration of corporate sculptors (should such a professional category exist outside my fantasy life), but from the imagined desires of consumers: burgers, sausages, chicken nuggets. Formally speaking, then, there is something involuted about the new food products Zimberoff documents. Apparently, when you ask consumers to think of plants as meat, you first must make the plants meat-shaped. And in the process you realize that meat, in our era of industrial mass-produced cheapness, has taken on arbitrary shapes. Nuggets do not appear on the bodies of chickens, at least not healthy ones.

Theres a great deal of repetition at the food-tech nexus. Soylent, the well-known meal replacement shake, closely resembles SlimFast, the diet drink targeted at women from 1977 onward. When the company Hampton Creek, which now calls itself Eat Just, released a vegan mayonnaise product, it was nearly identical to another 1977 product (odd coincidence) called Vegenaise, resembling it so closely that the creators of Vegenaise were shocked. Some of this repetition is probably conscious; Follow Your Heart, the maker of Vegenaise, has been around for a long time. And some of it may stem from entrepreneurs simply following a common pattern of thinking, according to which the problem with our food system is not our eating habits, but the nature of our food itself. Why not keep mayonnaise but make it vegan? Why not keep drinking milk, or eating ice cream, but make it from milk proteins we grow in a lab? What if we could get our artificial dyes, not to mention our protein powder, from algae? Some companies are making mycelium steaks, working with the fungus, related to mushrooms, that looks a bit like an underground network of threads. If you abstracted mycelium from the earth in which it lives, it might look like a mystical fairy network. From the standpoint of the anthropology of food, it is fascinating to notice that entrepreneurs first instinct was not to work with the natural form of those mycelium threads, to see what kind of food product might follow from that form, but instead to ask if mycelium could become an ingredient in something perceived as marketable. Throughout my research into cultured meat, I was bemused by the striking combination of inventiveness in the lab, as scientists adapted tissue culture techniques, widely used in medical research, to food production and the topological sameness of the burgers, hot dogs, and chicken nuggets that entrepreneurs hoped to produce. Theres a lot of copycat innovation not a lot of real innovation, says one of Zimberoffs interviewees, the CEO of a fungi-based meat company. Again, I recall Goldenweiser: The inevitable result is progressive complication, variety within uniformity, virtuosity within monotony.

Does all this count as involution? Taking stock, we are looking at an intense mimetic tendency, with food makers producing products that resemble each other, even if they differ in surprising ways in their raw ingredients or how they are processed. We have consistency within the pattern of seeking ever more clever ways to process foods in pursuit of value (because the greatest profit lies, as the work of food scholar Marion Nestle has shown, in processed foods). We have entrepreneurs seeking to change our products rather than the way we consume them. We have sector-wide ideological agreement that our food systems problems must be essentially technical, perhaps because technical solutions are the ones we can imagine using (and getting funded). In Meat Planet, I argue that this represents a form of imaginative closure, in which the economic, social, and ultimately political character of our food system gets obscured, because of the appeal of technological tools. This does not mean that technologies wont change our food system (indeed, if cultured meat works, it really could change everything) but that what makes the whole system of food-tech entrepreneurship work, imaginatively speaking, is the idea that technology, plus the workings of the consumer market, can provide all the change human civilization needs. Another way to express this imaginative closure may be in terms of involution. I must consider a straightforward objection to such claims. Goldenweiser thought that involution means that pattern checks creativity and development. But much of the work done at the food-tech nexus is mightily creative, and sometimes involves new ways of solving problems having to do with texture and flavor. Innovation surely describes this. Snackland is not bereft of ideas. A fair view of involution and innovation at the food-tech nexus might be that the nexus displays both traits at once. And yet involution always seems to win, because the creativity and inventiveness of food scientists takes place within economic systems they cannot contest, and usually do not want to. The nature of involution, for Goldenweiser, is that we cannot see outside a pattern, and here the salient pattern is a model of production, consumption, and value seeking that we often shorthand to capitalism.

In his 2006 book Meals to Come: A History of the Future of Food, historian Warren Belasco chronicles a set of long-running debates about the future of food, debates that have run through universities, think tanks, and into the public realm of journalism. A few major schools of thought have dominated those debates. There are Malthusians, who believe that increases in agricultural yields (due to technological progress, perhaps) tend to fall behind increases in population, because the former rises arithmetically and the latter geometrically. This means that the poorest members of any society will be exposed to malnutrition and that we have compelling reasons to impose artificial limits on population growth. There are Cornucopians who believe that technological progress will in fact outpace population growth, producing enough for all, possibly without limit. Then there is a third group, more equality-minded, who believe that the solution to problems in the food system is not a matter of managing supply and demand, but achieving more equal distribution of what we produce through better governance. The debate between the three positions began in the late 18th century, and while Malthusianism has always been influential it helped shape the food policy of the British Empire, since Thomas Robert Malthus himself taught at the school run by the British East India Company it is in Cornucopianisms belly that we effectively live and work today, getting slowly ceviched by its digestive juices. Those who work at the food-tech nexus are trying to keep Cornucopianism alive (although they may not identify with that term at all) in a new millennium, as the pressures of environmental crisis loom large. Cornucopians dream of a world with nothing but upside we save the environment and our market economies, predicated on growth, all at once. I was reminded of this when one of the companies trying to make cultured meat, previously called Memphis Meats (but based in Berkeley) rebranded as UPSIDE Foods. If you uncase a Pringles Wavy Potato Crisp and examine it from the right angle, it looks like a smiley face.

Cultured meat displays involution and innovation at once. Its researchers display great creativity in their technical efforts to take animal muscle stem cells, as well as fat cells, and induce them to grow in vitro, adapting a technique called tissue culture, which itself dates back to the early 20th century, to food production. They play with scaffolds on which animal cells can grow; they search for ideal growth media to feed their cells; they ask if it might be advantageous to combine the cells of different species in a single piece of meat, because one speciess cell line seems to produce better fat, the other better muscle, under laboratory conditions. And yet this work unfolds within a set of assumptions about the shape of meat, and appetites for meat, not to mention the assumptions that the combined powers of technology and the market will solve our human problems. In 2019, a chemical engineer named Dave Humbird was hired to conduct a feasibility study for cultured meat. I spoke with Humbird as he pursued his research and wrote his report. While other researchers have conducted feasibility studies and lifecycle analyses for cultured meat, Humbirds was the first by a scientist with no material or ideological investment in the proposition of cultured meat. His conclusions were not encouraging for anyone who hopes that cultured meat will work at scale, its costs eventually decreasing enough that it undercuts and supersedes conventional meat. Humbird found challenges both economic and technical some of the latter derived from the kinds of physical stresses on cells grown in very large bioreactors, and some of the former derived from the costs of raw ingredients. Both strongly suggest that cultured meat might never scale effectively. But I was also intrigued by Humbirds observation, relayed to me conversationally, that very few people involved with the nascent cultured meat industry either as entrepreneurs or as investors contacted him about his study, or spoke openly about his findings, even to challenge them. This fit a pattern I had long observed during my fieldwork, namely that despite the considerable hype around cultured meat, there is relatively little balanced public discussion of its technical feasibility. This could be because the startups would find no strategic advantage in such discussion, or because they simply do not have the time or resources for it.

The anthropologist Clifford Geertz turned Goldenweisers involution into agricultural involution in a 1963 book of that title, Agricultural Involution: The Process of Ecological Change in Indonesia. That book, vastly better known than Goldenweisers original essay (and challenged by many critics over the years), applies involution to Indonesian rice paddy farming from the 19th century into the 20th, with Geertz observing how Javanese peasants tried to adapt themselves to a Dutch colonial system that sought to extract value from their land and labor. According to Geertz, agricultural involution happens when farming technology and technique remain at a standstill, even as more labor flows into the system, ultimately yielding ever more complex social arrangements around work. The result is a kind of shared poverty as more and more laborers subdivide the available work. Social arrangements become Byzantine. Where Goldenweiser focused on ritual and aesthetic examples of involution, Geertz used the concept to describe how one kind of innovation, namely shifting social arrangements between peasant workers and landowners, unfolded within the limitations of Javanese agricultures technological standstill. The food-tech nexus that Zimberoff charts displays a different style of involution: technological innovation, to the point of virtuosity, within a larger limiting pattern. Call that pattern our collective difficulty recognizing the political and social character of the food system itself.

Involution is a capacious metaphor. In the work of the anthropologist Xiang Biao, involution (neijuan) describes the predicament of contemporary Chinese society, in which the middle classes and elites are locked in a struggle to pass wealth and advantage on to the next generation: only certain jobs can facilitate this process, and only certain paths of training and accomplishment lead to those jobs. Here the frame or pattern in which involution curls into complexity is determined by the narrow set of conditions for an acceptable life. The social, psychological, and material costs of failure of falling off the social treadmill are very high. Xiang Biaos version of involution shares, with Geertz and Goldenweiser, a sense of stuckness. Every story about involution implicitly conjures a form of change or progress that involution blocks. In Zimberoffs Technically Food, food-tech entrepreneurs pursue value in niches and crevasses that Big Food previously ignored, but rather than progress, their work seems like a desperate effort to keep food habits, forms, and economies afloat as climate change diminishes our available farmland and water. Every strategy in food futurism is a form of imaginative closure. The question facing us in food technology is how to tell innovation from involution and recognize how the two modes feed upon each other.

I have been saving the hardest part for last: when I say that a new food technology counts as innovation or involution, I am making a value claim, just as Goldenweiser and then Geertz and then Xiang Biao have done. But food systems are complex and social things, and political too; an individuals value claim does next to nothing. The challenge is to establish conversations about what human communities find valuable in food. Agreeing about norms is often harder than agreeing about facts. Some approaches to the future of food try to advance individual human health; others try to feed as many as possible, based on their assumptions about what counts as a sufficient diet; others presume that there are natural limits to how many of us can share the planet at once. Why not end with a question: was Reyner Banhams bag of chips a case of innovation or involution? The brilliance of his short essay was to show that the vernacular meaning of industrial foods the curling chip; the bursting, crinkling bag escapes our designs.

Benjamin Aldes Wurgaft is the author of Meat Planet: Artificial Flesh and the Future of Food.

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The Involuted Palate, or the Savage Crinkle of Future Snacks - lareviewofbooks


Time to Go Sushi With Cellular Salmon; When Pet Owners Tire of Their Minions – The SandPaper

Tuesday, August 17th, 2021

Sushi-loving diners in Callie will soon be partaking of test-tube salmon, compliments of San Francisco-based firm Wildtype. The company touts itself as Building a better food system by pioneering cellular agriculture to grow delicious cuts of our favorite seafood no fishing or fish farming required. I know, just when you think life cant get any weirder.

The companys website hypes its cutting-edge efforts as reinventing seafood, with a clever emphasis on inventing, since the entire process has come about through lab experimentation on handpicked cells of salmon, in the vein of stem cell exploration.

The seeds of Wildtypes chunks seed money has already been gotten aplenty comes via the choicest cells of the finest wild salmon, including king salmon, the finest and fattiest known. Once cells have been adroitly procured, the cellular growing process is on, as the meat of the matter is grown upon a type of organic plant-based scaffolding until done or ripe or something.

The plant-based scaffolding we provide for the cells to grow on, along with all the necessary nutrients like sugars, amino acids, and fats we deliver in solution, allows for the formation of the complex textures that were able to create for all types of sushi products spanning sashimi, nigiri and maki rolls, explains the companys cofounder Ary Elfenbein, a cardiologist and molecular biologist.

Wildtypes test-tube salmon is rather frighteningly identical to the real swimming thing, with a fat composition like the donor fish, including levels of healthy omega-3 fatty acids, but none of the heavy metals, microplastics, parasites, or antibiotics found in most salmon, per the companys website.

One of this methods claims to fame is how it might reduce the need for environmentally suspect fish farming.

Net pens used in fish farming pollute sensitive coastal waterways with concentrated excrement. Many farms have had escape events, introducing invasive species into sensitive ecosystems that compete with local fish populations, company cofounder Justin Kolbeck recently told Forbes magazine.

It should be emphasized this grown-in-house fish product is not even remotely related to soy-based imitation seafood and meats. The end products DNA makeup is salmon all the way; theres simply no energy wasted on the little things, like growing skeletons, scales, internal organs or brains.

Anyone remember the sci-fi thriller The Blob? Just asking for no particular reason.

To buttress Kolbecks point about escape, its profoundly unlikely that a chunk of Wildtype salmon will ooze out of the lab, leaving behind a telltale slime trail along the escape route before seeping seaward to freedom. Of course, should that happen, it would be quite a hook-up sight for any angler reeling in a big chunk of raw salmon meat. Anyone know how to clean this thing? Oh, wait, now that I think about it

OK, should we buy into this New Age salmon meat when it hits close to home? It will hit select market by next month or so, after which the company hopes to eventually produce tons and tons of its highly salmonesque stuff. Also, reports indicate other companies are champing at the test tube to get in on cellular seafood.

Personally, I somewhat prefer my seafood has seen the sea. That said, there is no doubt lab-grown seafood could be a healthy alternative to our overfishing of the worlds oceans. I can even foresee both wild-caught salmon and the beaker-based variety being served at a meal and folks clearly preferring the Wildtype offering, calling the natural too gamey.

As to the early taste tests of freshly picked/harvested Wildtype salmon, even educated buds are giving it flying colors speaking of which, the color of Wildtype salmon is identical to the donor fishs flesh color since it is the exact same fish again with the DNA thing.

For you travelers, if youre out San Fran way, the Wildtype company is all but begging folks to stop on in.

Wildtype wants to establish a high standard of education, trust, and transparency with our customers and the public. We want to show people where their food comes from and how its made, offer the owners.

Ill wax snarky by wondering if it might not be best to place test-tube salmon making in the same realm as, say, scrapple making. Philly folks get my dont ask/dont tell drift.

By the by, there have been some unique growing pains to developing a better bodiless salmon. For some unknown cell binding reason, the first chunks did not take at all well to cooking. The meat broke into what might be called individual component parts hundreds of tiny undefinable pieces of salmon essence. I cant imagine what that would have looked like and I would surely have been the only one in the lab laughing my ass off.

The last I heard, the creative minds of the company are tweaking the growing process so we can someday buy San Fran salmon for more than just sashimi, sushi and sausages.

I will absolutely be among the early-on buyers of salmon a la lab. One problem I see is naming the stuff with full disclosure in tow. There must be a distinct, immediately recognizable terminology. Ill be the first to admit that test-tube salmon would be off-putting. Less so would be manmade salmon or sea-free salmon. The company itself might run with cellular salmon, based on its self-hype that Wildtype is pioneering cellular agriculture to grow delicious cuts of our favorite seafood no fishing or fish farming required.

ECO-UGLY ABANDONMENT: I need to combine two tales in one since both have to do with mankind unloosing nonindigenous species into our delicate Pinelands environment.

The more recent of the two comes via a jungle-ish find by Division of Fish and Wildlife conservation officers. While on patrol, the officers came across your everyday boa constrictor crossing a dirt road. Yes, its everyday if you live in frickin Central America!

The 4-footer was found in a state Wildlife Management Area. Id safely venture to say it was not simply taking in the sights of our outback before making the long slither back to some tropical rainforest.

Forgoing the other minuscule possibility that the boas owner had simply been out walking it only to have his minion slip its leash, this was an all too familiar case of someone ignobly abandoning a faithful critter even after it had dedicated its entire life to being a family-member pet.

OK, that might sound a bit overemotional, but such dump-offs are a lousy trick by incompetent-as-s*** pet owners.

As to what would have become of the tropical snake had it not come back to the road looking for its human buddy, I believe it was Jack London who morbidly suggested that freezing to death isnt the worst way to go. Winter would have ended the snakes unwanted flirtation with untamed freedom.

There was no chance the lone boa could have led to the Pinelands becoming a covey of constrictors even if the captured boa wore a boa, meaning it was a female.

That tale roundaboutly leads to a twinish tale of the time piranhas swam about in Stafford Forge Lake.

It was July 2007 when I got word of weird fish being caught in the historic lake, former home to a forge and cranberry bogs. As I wrote back then, A number of piranhas were recently taken by an angler using Bass Stoppers, a favorite freshwater rig. And these werent minor models of this highly nonindigenous species. One piranha was way hefty.

I recall my well-founded disbelief upon seeing the first photo of the landing. At mere first glance, I knew this hookup was a member of a world-renowned fish family that includes piranha, pacu and oscars. To me, it was clearly a piranha.

So, what in bloody hell was such a species doing in the tannin-laced, temperate zone waters of the Forge?

The answer was all too obvious: Some numbnut had released it after it had outgrown its aquarium and its welcome. Such dumpings, while displaying a touch of compassion when compared to a toilet flush-down, are quite common. In fact, many state waters are now plagued by introduced carp, the leave-behinds from anglers using cheap so-called feeder goldfish to live-line for largemouth bass and pickerel.

The sacrificial goldfish, small carp in essence, either get off the hook or are poured into lakes at the end of a fishing session. They grow rapidly into immense vegetation bottom feeders. Once established, they create such a bottom stir that it can muck up the water, impacting gamefish, which feed by sight. They also inadvertently mosey over bass and sunfish nests hollows in the sand inadvertently sucking up eggs and newborns.

As to the Forge piranhas, the hookups led to an utterly surprising finding that they had surely been there more than just one season. The hardy little devils were showing signs of prospering, likely going into a torpor state when the lake froze in winter. Fears arose as to what they were thriving upon, assuredly indigenous species.

The realization that piranhas were making themselves at home in a New Jersey lake led to fear regarding the many people and pets commonly wading right where the fish were caught. Such frets were a bit unfounded. While packs of piranhas can go gruesomely gonzo over the smell of blood and raw flesh, Ive seen naked native children in Brazil freely swim among them, with nary a single natural bris being reported. Nonetheless, N.J. Fish and Wildlife folks went on one weird-ass search-and-destroy mission by electrocuting the lake. The method shocked the hell out of the lakes inhabitants, causing them to rise woozily to the surface, where any species non grata could be removed and apologies offered to acceptable lake occupants, which quickly recovered from the buzz, all wondering What the hell was that all about?!

RUNDOWN: Weirdly, the blowfish are back in town, mainly the far west side of Barnegat Bay where they had been, then left, only to be replaced by a ton of all new puffers moving in from waters to our north. It is once again possible to best a hundred or more per chumming session.

There are also small weaks and kingfish entering the chum slick.

Weirdest chum-related hookup was a massive black drum estimated by Paul P. at 50 pounds. It was almost landed, net hovering above, before the tiny hook gave way. That is pretty far north for Barnegat Bay black drum.

Speaking of drum, its about time for red drum to make beachline passes. The state record remains at 55 pounds, a fish taken in Great Bay by Daniel Yanino in 1985.

This is an amazing time of year to chum with grass shrimp in places like Myers Hole and surely some deeper waters toward Little Egg Inlet. Such panfishing often offers as great a variety of fish species as youll ever hook during one Jersey sitting.

Considering most of the fish drawn to a shrimp chum will be juveniles, you must use circle hooks and unhook undersized fish as quickly and gently as possible. Best bet is to not even bring them aboard. A nice series of photos can be taken without fish having to pass over the gunnel.

Surfside fluking is fair. Its best when waters are at least a bit roiled. Calm, crystal-clear water periods seem to knock down the flattie action. Every now and again there is a sudsy doormat taken.

Stingrays have glided a bit north, though a few are still quite obvious along the clear-water shoreline. Ive gotten two emails regarding ways to cook ray wings. Ill give them a try. If my taste buds salute, Ill pass them on.

Triggerfish are making their typical late-summer presence known. Some nice-sized ones mixed in, way larger than they usually show down south, re-begging the question of whether these fish go back to the Deep South or move off shore for the winter. The average sheepshead size up here dwarfs the typical sheepsheads in places like the Indian and Banana rivers in Florida.

Please do not try to fillet triggers. Too much meat is utterly wasted. After gutting, simply cook them whole. Once done and they bake very quickly with skin still on pull off the now easily removed skin and dine on the delicate white meat within. Of note, there are some filefish being labeled triggerfish. They are different to a degree, but are surprisingly similar in taste.

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Time to Go Sushi With Cellular Salmon; When Pet Owners Tire of Their Minions - The SandPaper


Adipose-derived Stem Cell Market Analysis, Key Company Profiles, Types, Applications and Forecast To 2027 The Courier – The Courier

Thursday, May 27th, 2021

Adipose tissue-derived stem cells are currently being used for a broad spectrum of applications such asregenerative medicine,tissue engineering, cell therapy, and stem cell differentiation studies. ADSCs have a massive potential for regenerative medicine and demonstrate more robust yields than other stem cells. This can be attributed to its anti-inflammatory, immunomodulatory, anti-scarring, and anti-apoptotic properties, among others.

Stem cells derived from adipose tissues confer several advantages. The significant advantage is that fat tissues consist of over 100 to 1000 times more mesenchymal stem cells than the bone marrow. Moreover, the method of isolating these adipose tissue-derived stem cells is minimally invasive and relatively easier than bone marrow collection.

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Over the last couple of years, companies and academic institutions have adopted new business strategies and expansion plans to gain a robust footing in the market. Some of the prominent players of the industry include:

Market Segmentation:

The report categorizes the market into different key segments based on types and applications, along with key regional segmentation. The report offers insights into the segment expected to garner traction during the forecast period, and the region expected to dominate the market in the coming years.

Cell Type

Product Type

Disease Indication

End-user Industries


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Regional Analysis:

The global Adipose-derived Stem Cell market consists of various significant regional segments. Under this section of the report, the product demand, output, and estimated revenue share of each region have been ascertained. The most prominent regions dictating the global market include:

Some Fundamental Market Parameters Elucidated in the Report:

Market dynamics: The Adipose-derived Stem Cell market report explains the scope of various commercial possibilities over the next few years and further estimates revenue build-up over the forecast years. It analyzes the key market segments and sub-segments and provides deep insights into the market to assist readers in developing vital strategies for profitable business expansion.

Competitive Outlook: The established market players operating in the Adipose-derived Stem Cell industry have been listed in this report, with a major focus on their geographical reach and production facilities. To gain a competitive advantage over the other players in the Adipose-derived Stem Cell industry, the leading players are focusing more on offering products at rational prices.

Objectives of the Report: The chief aim of the research report is to provide the manufacturers, distributors, suppliers, and buyers engaged in this sector with access to a deeper and improved understanding of the global Adipose-derived Stem Cell market.

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Thank you for reading our report. For further information or queries regarding the report or its customization, please get in touch with us. Our team will ensure you get a report well-suited to your requirements.

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Adipose-derived Stem Cell Market Analysis, Key Company Profiles, Types, Applications and Forecast To 2027 The Courier - The Courier


Global Cell Therapy Markets, Technologies, and Competitive Landscape Report 2020-2030: Applications, Cardiovascular Disorders, Cancer, Neurological…

Thursday, May 27th, 2021

DUBLIN, May 21, 2021 /PRNewswire/ -- The "Cell Therapy - Technologies, Markets and Companies" report from Jain PharmaBiotech has been added to's offering.

This report describes and evaluates cell therapy technologies and methods, which have already started to play an important role in the practice of medicine. Hematopoietic stem cell transplantation is replacing the old fashioned bone marrow transplants. The role of cells in drug discovery is also described. Cell therapy is bound to become a part of medical practice.

The cell-based markets was analyzed for 2020, and projected to 2030. The markets are analyzed according to therapeutic categories, technologies and geographical areas. The largest expansion will be in diseases of the central nervous system, cancer and cardiovascular disorders. Skin and soft tissue repair, as well as diabetes mellitus, will be other major markets.

The number of companies involved in cell therapy has increased remarkably during the past few years. More than 500 companies have been identified to be involved in cell therapy and 316 of these are profiled in part II of the report along with tabulation of 306 alliances. Of these companies, 171 are involved in stem cells.

Profiles of 73 academic institutions in the US involved in cell therapy are also included in part II along with their commercial collaborations. The text is supplemented with 67 Tables and 26 Figures. The bibliography contains 1,200 selected references, which are cited in the text.

Stem cells are discussed in detail in one chapter. Some light is thrown on the current controversy of embryonic sources of stem cells and comparison with adult sources. Other sources of stem cells such as the placenta, cord blood and fat removed by liposuction are also discussed. Stem cells can also be genetically modified prior to transplantation.

Cell therapy technologies overlap with those of gene therapy, cancer vaccines, drug delivery, tissue engineering, and regenerative medicine. Pharmaceutical applications of stem cells including those in drug discovery are also described. Various types of cells used, methods of preparation and culture, encapsulation, and genetic engineering of cells are discussed. Sources of cells, both human and animal (xenotransplantation) are discussed. Methods of delivery of cell therapy range from injections to surgical implantation using special devices.

Cell therapy has applications in a large number of disorders. The most important are diseases of the nervous system and cancer which are the topics for separate chapters. Other applications include cardiac disorders (myocardial infarction and heart failure), diabetes mellitus, diseases of bones and joints, genetic disorders, and wounds of the skin and soft tissues.

Regulatory and ethical issues involving cell therapy are important and are discussed. The current political debate on the use of stem cells from embryonic sources (hESCs) is also presented. Safety is an essential consideration of any new therapy and regulations for cell therapy are those for biological preparations.

Key Topics Covered:

Part One: Technologies, Ethics & Regulations

Executive Summary

1. Introduction to Cell Therapy

2. Cell Therapy Technologies

3. Stem Cells

4. Clinical Applications of Cell Therapy

5. Cell Therapy for Cardiovascular Disorders

6. Cell Therapy for Cancer

7. Cell Therapy for Neurological Disorders

8. Ethical, Legal and Political Aspects of Cell therapy

9. Safety and Regulatory Aspects of Cell Therapy

Part II: Markets, Companies & Academic Institutions

10. Markets and Future Prospects for Cell Therapy

11. Companies Involved in Cell Therapy

12. Academic Institutions

13. References

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Research and Markets Laura Wood, Senior Manager [emailprotected]

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Global Cell Therapy Markets, Technologies, and Competitive Landscape Report 2020-2030: Applications, Cardiovascular Disorders, Cancer, Neurological...


What is lab grown meat? A scientist explains the taste, production and safety of artificial foods – BBC Focus Magazine

Thursday, May 27th, 2021

How is artificial meat made?

Also known as cultured or cell-based meat, artificial meat is grown from animal cells in a laboratory. Start-up companies have grown artificial beef, pork, chicken and even fish. However, none is commercially available yet.

There are different ways to grow artificial meat, but most use adult stem cells from a live animal. For beef, a tiny muscle sample is taken from a cow, under local anaesthesia. The muscle is chopped into smaller pieces, using enzymes to digest it and release the stem cells.

In a huge vat called a bioreactor, the stem cells are immersed in a broth containing salts, vitamins, sugars and proteins, as well as growth factors. The oxygen-rich, temperature-controlled environment allows cells to multiply dramatically. The stem cells then differentiate into muscle fibres that bunch together, aided by scaffolding material. The meat is ready for processing or cooking in a matter of weeks.

Producing a thick piece of steak is still some way off, with minced meat far easier to replicate. 3D printing is one possible option for creating a juicy steak layer by layer, but this technology is still in its infancy.

The first artificial beef burger (unveiled to great fanfare in 2013 and developed at a cost of 250,000) was reported to be rather dry and dense, consisting solely of muscle fibres.

A good meat replacement needs to mimic smell, texture and taste, which is no mean feat. In an animal, muscle comprises organised fibres, blood vessels, nerves, connective tissues and fat cells. Thousands of flavour molecules contribute to real meats rich taste. Its possible to add synthetic flavours to artificial meat, but balancing and distributing them is tricky.

Progress has been made since 2013 and a Dutch company called Meatable now claims to be able to reprogram stem cells collected from bovine umbilical cord blood, turning them into master cells that can differentiate into fat or muscle. This allows muscle and fat cells to grow together as they do in animals. In theory, cells from different species could be grown together to create completely new flavours.

Artificial meat is touted as being as safe or safer than the real thing, produced in a highly controlled environment.

It is highly unlikely to become contaminated with harmful bacteria such as E. coli because there are no digestive organs to worry about. With whole animals, theres always a risk of meat becoming contaminated with bacteria after slaughter.

Having said that, artificial meat producers do need to take extra care to keep everything sterile because the nutrient-rich environment in the bioreactors is a perfect breeding ground for bacteria.

Some people have raised concerns over the growth factors added to stem cells, which include hormones. These hormones are naturally present in animals as well as in real meat. However, overexposure can have adverse health effects in humans. This is why growth hormones have been banned in agriculture in the EU since 1981.

Artificial meat is packed with protein and newer versions also contain fat. The nutritional content can be controlled to a certain extent by adjusting fat levels and playing with the levels of saturated fatty acids and healthier polyunsaturated fatty acids.

Saturated fats can be replaced with other types of fats, such as omega-3s, found naturally in fish or flaxseed oil. Its also possible to add extra micronutrients such as vitamin B12 to artificial meats, as is routinely done to breads and breakfast cereals.

The fact remains that eating too much red meat is bad for our health, increasing the risk of cardiovascular disease, type 2 diabetes and some cancers. With its controlled fat levels, artificial meat may be slightly healthier, but it would still need to be eaten in moderation.

Plant-based meat alternatives may be the healthiest option, with similar protein levels and lower levels of saturated fat compared to conventional meat burgers.

The global food system is under huge pressure from climate change, a growing population and increasing demand for animal products. As such, investors have poured vast sums into artificial meat start-ups in recent years. One estimate by US consultancy firm Kearney suggests that 35 per cent of all meat consumed globally will be cell-based by 2040.

Artificial meat can be produced faster and more efficiently than traditional meat, requiring a tiny fraction of the land. But it faces competition from insect-derived products and plant-based imitation meats, which consumers are already buying in increasing numbers.

Livestock produce a big proportion of global greenhouse gas emissions. Large numbers of people switching to artificial meat, could lead to big cuts in these gases, particularly methane. But a study at Oxford University has suggested that the CO2 emissions from powering artificial meat production facilities could be more damaging over the next 1,000 years.

Emma is a science writer specialising in environment, food and toxicology.

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What is lab grown meat? A scientist explains the taste, production and safety of artificial foods - BBC Focus Magazine


Rheumatoid Arthritis Stem Cell Therapy Market share, growth drivers, demand, supply, challenges, and investment opportunities by 2028 – WhaTech

Thursday, May 27th, 2021

Rheumatoid arthritis stem cell therapy has been demonstrated to induce profound healing activity, halt arthritic conditions, and in many cases, reverse and regenerate joint tissue. Today, bone marrow transplant, adipose or fat-derived stem cells, and allogeneic mesenchymal stem cells (human umbilical cord tissue) are used for rheumatoid arthritis stem cell therapy. As the rheumatoid arthritis worsens, the body initiates autoimmune response and attacks the cells. Rheumatoid arthritis stem cell therapy is growing in popularity across hospitals, ambulatory surgical centers, and specialty clinics, as it increases the healing of joints and further treats the entire system that causes the joint pain and inflammation.

The latest research report published by Fact.MR on the Rheumatoid Arthritis Stem Cell Therapy Market is intended to offer reliable data on various key factors shaping the growth curve of the market. This report works as a rich source of information for key entities such as policy makers, end-use industries, investors, and opinion leaders.

The segment accounted for a considerable share in the Rheumatoid Arthritis Stem Cell Therapy Market in forecast period 2018-2028. The share in this segment comes with a wide range of opportunities including manufacturing products, distribution, retail, and marketing services.Extensive rounds of primary and a comprehensive secondary research have been leveraged by the analysts at Fact.MR to arrive at various estimations and projections forDemand of Rheumatoid Arthritis Stem Cell Therapy Market, both at global and regional levels.

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The analysts have used numerous industry-wide prominent business intelligence tools to consolidate facts, figures, and market data into revenue estimations and projections in the Rheumatoid Arthritis Stem Cell Therapy Market. Key stakeholders in the Rheumatoid Arthritis Stem Cell Therapy Market including industry players, policymakers, and investors in various countries have been continuously realigning their strategies and approaches to implement them in order to tap into new opportunities.

Many in recent months have overhauled their strategies to remain agile in the backdrop of worldwide disruptions caused by the COVID-19 pandemic.

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Rheumatoid Arthritis Stem Cell Therapy Market: Segmentation

Tentatively, the global rheumatoid arthritis stem cell therapy market can be segmented on the basis of treatment type, application, end user and geography.

Based on treatment type, the global rheumatoid arthritis stem cell therapy market can be segmented into:

Based on application, the global rheumatoid arthritis stem cell therapy market can be segmented into:

Based on distribution channel, the global rheumatoid arthritis stem cell therapy market can be segmented into:

Based on geography, the global rheumatoid arthritis stem cell therapy market can be segmented into:

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Rheumatoid Arthritis Stem Cell Therapy Market share, growth drivers, demand, supply, challenges, and investment opportunities by 2028 - WhaTech


Obesity-Related Inflammation and Endothelial Dysfunction in COVID-19: | JIR – Dove Medical Press

Thursday, May 27th, 2021

Obesity, COVID-19 and Inflammation

The coronavirus disease 2019 (COVID-19) pandemic has put into evidence another pandemic obesity, an increasing threat to societies around the world.1 The first studies of COVID-19 did not provide body mass index (BMI) data,2 and the association between disease severity and obesity was not perceived initially. Subsequent data from several countries, however, cast light on this association,3,4 and several studies have documented the association between obesity and COVID-19 severity.47 Currently, obesity may be considered a true independent risk factor for COVID-19 mortality.8

The mechanisms underlying the increased risk of complications and mortality in obese patients with COVID-19 are many, and of diverse nature (Figure 1). Obesity is associated with several disorders, related to defective homeostasis of the dysfunctional adipose tissue, in which local and systemic chronic inflammation, oxidative stress, altered release of cytokines, and impaired immune response play important roles911; all of these have been demonstrated to be associated with higher risk and worse prognosis of infectious diseases in this patient population.1214

Figure 1 The mechanisms underlying the increased risk of complications and mortality in obese patients with COVID-19 based on the association of low-grade inflammation, adipose tissue dysfunction and endothelial dysfunction: In obese patients with COVID-19 or SARS-CoV-2, as well as, the bacterial endotoxins (LPS) of the intestinal bacterial translocation promote the activation of TLR4 in favor of the MyD88-dependent pro-inflammatory pathway. The activation of NF-B is linked to the production of TNF-, IL-1, IL-6, IL-12 and other cytokines, contributing to the activation of NLRP3 inflammasomes and increased expression of ECA2. In the adipose tissue of patients with COVID-19, there is an increase in the expression of ECA2, promoting greater entry of SARS-CoV-2, making this tissue a viral reservoir. Metabolic inflammation in obese patients is characterized by dysfunctional adipose tissue, with mitochondrial dysfunction and decreased fatty acid oxidation, causing an amount of inflammatory cells showing an increase in the influx of M1 macrophages and chemotactic signaling, via MCP-1 and release of IL-8 by adipocytes, associated with an increase in reactive oxygen species. Associated with this process of immune activation, obese patients with COVID-19 have systemic microvascular dysfunction and a predisposition to thrombus formation that is exacerbated by higher levels of circulating inflammatory cytokines, such as TNF-, IL-1 and IL-6, worsening the outcomes in COVID-19.

Inflammation plays a central role in obesity.15 Obesity promotes profound changes in the structure and function of adipose tissue, as adipocytes undergo hypertrophy and hyperplasia, increasing oxygen need, which remains unmet due to the insufficient vascularization relative to the enlarged adipose tissue. This leads to tissue hypoxia and immune cell infiltration that perpetuates local inflammation.1618 Insulin resistance is also a link between obesity-related metabolic disorders and inflammation, as the remodeling of the adipose tissue leads to activation of NLRP3-inflammasome, which ultimately impairs of the insulin-signaling pathway and insulin resistance, a key factor in the development of the metabolic syndrome.19

Additionally, mitochondrial dysfunction in adipocytes may be a cause of adipose tissue inflammation and insulin resistance. The defective mitochondrial function and decreased fatty acid oxidation in adipocytes increase triglyceride accumulation, adipocyte enlargement and consequent adipose tissue hypoxia; this, in its turn, leads to accumulation of hypoxia-inducible factor-1 (HIF-1), which promotes adipose tissue inflammation and fibrosis.20 This continuous inflammatory cycle also contributes to a neuro-immuno-endocrine dysregulation in the context of the metabolic syndrome.21 The inflammatory state affecting obese individuals is called metabolic inflammation or metainflammation, in which there is also an increased influx of M1 macrophages occurring, as well as decreased M2 macrophages and Treg cells in the visceral adipose tissue22 through chemotactic signaling, via MCP-1 and IL-8 released by adipocytes.23

The excessive intake of carbohydrates is an important trigger for these processes.24 In addition, peripheral inflammation and various pro-inflammatory signals in the nucleus accumbens, including reactive gliosis, increased expression of cytokines, antigen-presenting markers and transcriptional activity of NFB25 contribute to the activation of the innate immune response, mainly through activation of Toll-type receptors (TLR), specifically TLR-4, considered an intersection of dysfunctional metabolism and activated immunity in obesity.26 NF-B is a molecular hub for pro-inflammatory gene induction both in innate and adaptive immune responses since it is highly regulated and regulates the expression of a vast array of genes.27 Among many different immune effects, NF-B activation is linked to the production of TNF-, IL-1, IL-6, IL-12 and other cytokines, and is also involved in NLRP3 inflammasome regulation and activation of CD4+ T-helper cells.28 It is noteworthy that there is evidence that the virus can bind and activate TLR4 signaling in favor of the proinflammatory MyD88-dependent and contributing to increased expression of ACE2 and promoting greater viral entry.29

The chronic impairment of systemic vascular endothelial function in patients with cardiovascular and metabolic disorders, including hypertension, obesity, diabetes mellitus, coronary artery disease and heart failure, when intensified by the detrimental effects of the severe acute respiratory syndrome coronavirus (SARS-CoV-2) over the endothelium, may explain their worse outcomes in COVID-19.3033 Regarding obesity, a community-based clinical trial (n=521; mean follow-up of 8.5 years) showed that increases in weight, body mass index, waist circumference and body-fat percentage over time were associated with worsening of microvascular endothelial function, assessed by flow-mediated dilation in the brachial artery.34 Most subjects (84%) were overweight or obese at baseline; those who lost weight over time had improved vascular endothelial function.34

In fact, vascular endothelial dysfunction and increased arterial stiffness are thought to contribute to a unfavorable response of the endothelium to the infection by SARS-CoV-2, whereas alterations in cardiac structure and function and the prothrombotic environment in obesity could provide a link for the augmented cardiovascular events in these patients.35 Moreover, fast increasing evidence from basic science, imaging and clinical observations suggest that COVID-19 could be considered as a vascular disease.36,37

Obesity is accompanied by functional and structural systemic microvascular dysfunction,38 and endothelial-dependent microvascular vasodilation is severely impaired in obesity.3941 Endothelial-dependent capillary recruitment, induced either by reactive hyperemia or by shear stress, is blunted in obese subjects, compared to non-obese counterparts.42,43 In the clinical setting, endothelial function and reactivity can be assessed using different technologies that evaluate microvascular flow and tissue perfusion coupled to physiological or pharmacological stimuli,44,45 to activate different vasodilator pathways resulting in increased microvascular conductance. The most commonly used provocations are the administration of endothelial-dependent vasodilators by transdermal iontophoresis,4648 thermal hyperemia49,50 and post-occlusive reactive hyperemia.5153 In this context, the cutaneous microcirculation is now considered as an accessible and representative vascular bed for the assessment of systemic microcirculatory reactivity.45,5456 A reduced vasodilation response to these different stimuli is indicative of microvascular endothelial dysfunction and is also considered to be predictive for cardiovascular and metabolic diseases and clinical prognosis.5760

In patients with established cardiovascular disease, the reduction of microvascular endothelial-dependent vasodilation (ie, endothelial dysfunction) is associated with increasing BMI, even after adjustment for treated diabetes mellitus, hypertension, hypercholesterolemia, and smoking.61 In that study, BMI was classified in three different intervals: <25, 25-to 30 and >30 kg/m2.61 Moreover, Csipo et al showed that weight loss (reduction of BMI from 31.8 to 27.5 kg/m2, accompanied by a reduction of serum cholesterol, LDL, triglycerides, and increased HDL) after a low-carbohydrate, low-calorie diet, resulted in improvement of microvascular endothelial function in geriatric obese (class 1) patients,62 assessed by laser speckle contrast imaging in the skin, after post-occlusive reactive hyperemia. Additionally, endothelial function of resistance arterioles of the gluteal subcutaneous tissue is impaired in non-diabetic subjects with moderate levels of obesity (BMI 34.7 4.0 kg/m2), in association with systemic inflammation. In women, BMI was significantly associated with high-sensitivity C-reactive protein.63

Regarding mechanisms of microvascular dysfunction, using a new methodology of microdialysis in the skeletal muscle, La Favor et al showed a significant increase in superoxide anions, as well as in NADPH oxidase subunit expression, associated with microvascular endothelial dysfunction in obese subjects relative to lean and overweight/mildly obese subjects.64 Interestingly, 8 weeks of aerobic exercise training resulted in decreased H2O2 levels and improved microvascular endothelial function in the muscle tissue of obese subjects.64 The study therefore linked NADPH oxidase, as a source of reactive oxygen species, to microvascular endothelial dysfunction in obese individuals, with amelioration induced by aerobic exercise.

Microvascular dysfunction has been considered to be a pathophysiological link between overweight/obesity and cardiometabolic diseases, including arterial hypertension, insulin resistance, and glucose intolerance.43,6569 Acknowledged mechanisms include changes in the secretion of adipokines, leading to increased levels of free fatty acids and inflammatory mediators, and decreased levels of adiponectin, all of which may impair endothelial insulin signaling.7073 It is also of note that there are changes at the level of the microvascular network in obesity, involving a reduction in the number of arterioles or capillaries within vascular beds of various tissues (such as the skeletal muscle and skin), which is defined as vascular (capillary) rarefaction.7477 In fact, obese individuals have both structural and functional alterations in skin microcirculation that are proportional to the increase in the degree of global and central obesity, arterial pressure levels and with the degree of insulin resistance.42 In non-diabetic, untreated hypertensive patients, reduced capillary density has also been related to obesity and other cardiometabolic risk factors.78 In addition, in adults and also in prepubertal children, visceral adiposity measured with magnetic resonance imaging is inversely associated with endothelial-dependent skin capillary recruitment, and is accompanied by increased plasma levels of inflammatory markers.79

Impaired left ventricular diastolic function and higher risk of heart failure in obese individuals has been suggested to be associated with myocardial microvascular dysfunction.80 In obese patients undergoing coronary artery bypass graft surgery, coronary microvascular density is significantly lower, compared to non-obese patients, and accompanied by increased body mass index and percent body fat together with increased left ventricular filling pressures.80 Moreover, in patients with suspected coronary artery disease, increasing body mass index is associated with reduced microvascular endothelial function, even after adjustment for treated diabetes mellitus, hypertension, hypercholesterolemia, and smoking.61 Interestingly, the study evaluated microvascular endothelial function three different technologies, including peripheral arterial tonometry, laser Doppler flowmetry and digital thermal monitoring.61

Reduced skeletal muscle capillary density and microvascular reactivity in obese subjects improved after 4 weeks of either sprint interval training, or moderateintensity continuous training, together with increased endothelial eNOS content.81

It has also been shown that bariatric surgery improves microvascular dysfunction in obese patients who were free of metabolic syndrome after surgery, in association with postoperative increases in HDL-cholesterol levels and decreases in oxidized LDL levels.82

Another clinical study investigated microvascular endothelial function using flow-mediated dilation in arterioles isolated from subcutaneous adipose tissue in young women presenting with obesity (age: 33 2 years, body mass index: 33.0 0.6 kg/m2).83 The results showed that a 6-week low-carbohydrate diet, associated or not with caloric restriction, improve endothelial-dependent microvascular function through increases in nitric oxide bioavailability.83 On the other hand, this nutritional intervention did not affect macrovascular endothelial function, evaluated using brachial artery flow-mediated dilation.83

Regarding putative pathophysiological mechanisms, a study by Dimassi et al84 in young individuals with obesity (BMI >30 kg/m2, n = 69), compared with controls with normal weight, suggested that the expression of circulating microparticles containing endothelial nitric oxide synthase (eNOS) is significantly reduced in obesity individuals with endothelial-dependent microvascular dysfunction characterized using cutaneous laser Doppler flowmetry.84

Low-grade inflammation is the common feature that encompasses all the high-risk patients for developing severe COVID-19. Obesity is associated with a fivefold increased risk of developing SARS in SARS-CoV-2 infected individuals, and the well-documented increased susceptibility of obese patients to develop severe forms of COVID-19 may be linked to the elevated systemic metabolic inflammation in these patients.19 Metabolic alterations seen in obese and in diabetic patients are related to an inflammatory response,85,86 and several studies report elevated levels of circulating inflammatory cytokines such as TNF-, IL-1 and IL-6 in obese patients.87 Furthermore, visceral fat shows significant univariate association with the need for intensive care in COVID-19 patients,15 and deregulated expression of adipokines, such as leptin and resistin, increases the expression of vascular adhesion molecule 1 (VCAM-1) and intercellular adhesion molecule 1 (ICAM-1) that contribute to increased vascular leukocyte adhesiveness and additional oxidative stress.88 To further complicate the scenario, adipose-derived mesenchymal stem cell (ASCs), a specialized cell population in adipose tissue, are functionally compromised in obesity and changes its regulatory protective activity to a pro-inflammatory profile increasing its ability to secrete TNF-, IL-8, IL-6 and MCP-1.89,90 Therefore, ASCs from obese patients may not be able to modulate the immune response and tissue repair in SARS-CoV-2 infection contributing to more severe tissue injury.10

SARS-CoV-2 uses its viral spike (S) protein to invade target cells, such as epithelial cells, through binding to angiotensin-converting enzyme 2 (ACE2) after proteolytic activation by transmembrane protease serine 2 (TMPSS2).91 Others enzymes like furin, trypsin and elastase may also activate the S protein and facilitate cellular entry by the virus.9294 Interestingly, adipose tissue highly expresses ACE2 and the expression is even higher in visceral adipose tissue.95 Of relevance, ACE2 expression is upregulated in obesity.96 Also, another suggested receptor for SARS-CoV-2, dipeptidyl peptidase 4 (DPP4), is expressed in adipose tissue and is upregulated in obesity.97,98 Finally, CD147, the alternative receptor for SARS-CoV-2, is positively correlated with an increase in body mass index.99 Taken together, the evidence of high expression of different SARS-CoV-2 receptors in adipose tissue may be the basis for increased severity of COVID-19 in obese patients involving at least two different possibilities: First, infection of adipocytes with SARS-CoV-2 may exacerbate the innate immune response through pathogen recognition receptors in an already inflammation-primed tissue, increasing the magnitude of the response. Second, adipocytes may function as a reservoir for the SARS-CoV-2 and therefore may fuel the inflammatory response in adipose tissue and elsewhere in the organism by releasing viral NA and antigens that, by reaching the circulation generate ripple inflammatory effects across the organism. Importantly, these two possibilities are not mutually exclusive and may well combine their pathophysiological potential towards a deregulate systemic inflammatory response with widespread tissue injury and consequent organ dysfunction. It is important to add that as the pandemic evolves, new mechanistic interactions may unravel. For instance, new virus variants with mutations at the receptor-binding domain of the S protein may change the infectivity of the virus by changing its interactions with cellular receptors. In Brazil, a variant designated as P1, with multiple mutations in the S protein, was recently identified and is seemingly more infective than previous lineages of the virus.100 How this variant may interact with adipocytes increasing infectivity to these cells or potentiating the formation of an adipocyte reservoir of the virus causing a more severe disease in obese individuals is yet unknown. What is known is that a second wave caused by this new P1 variant is promoting devastating effects in Brazil with apparently higher mortality and a faster progression of the disease.

Severe COVID-19 is characterized by a massive production of pro-inflammatory mediators, in special cytokines. Frequently, the term cytokine storm is called up to describe the massive production of cytokines that occurs in viral infections (including SARS-CoV and MERS-CoV), in sepsis and more recently, in severe COVID-19.101 Increased levels of IL-6, TNF-, IP10 are commonly found in patients with severe COVID-19.102 It is reasonable to propose that obese patients who already have an underlying chronic inflammation when infected with SARS-CoV-2 are prone to develop a more intense and deregulated response, and in doing so, developing a severe presentation of the disease. In addition, dysfunctional metabolism, endothelium, and overall immune response would further contribute to an unfavorable evolution of the disease in the obese patients. The questions about the molecular mechanisms behind this disproportional response remain unanswered, but our knowledge about this disease is growing in an unprecedented velocity and we may soon have the answer. However, a few possibilities may be put forward (Figure 1).

As stated above, obesity is characterized by the induction of a low-grade chronic proinflammatory state and NF-B is described as a key factor in the low-grade inflammation state in atherosclerosis and hypertension.103,104 Also, the NF-B pathway is involved in insulin resistance, a condition frequently seen in obese patients, and in -cell dysfunction.105 In addition, free fatty acids can also promote inflammation and activate the NF-B and JNK1 pathways.106 All those pieces put together may point to NF-B being a key player in obese patients with COVID-19. Importantly, cell culture experiments combined with system biology approach showed that overexpression of Nsp1 during infection with SARS-CoV-2 strongly increases signaling through the nuclear factor of activated T cells (NFAT) and increases cytokine production and immune-dependent pathogenesis. Both NF-B and NFAT pathways share common regulation signals, such as Foxp3 and Foxd1, and a similar mechanism of activation against infection.107

We must also consider that binding of SARS-CoV-2 to ACE2 leads to receptor internalization and high cytosolic levels of angiotensin II, which is a recognized activator of NLP3 inflammasome in the lung108 and other tissues. The NLRP3 inflammasome regulates pyroptosis through gasdermin D, along with the release of cytosolic contents into the extracellular spaces. The release of alarmins, ATP, ROS, cytokines, chemokines, LDH and viral particles elicits an immediate reaction from surrounding immune cells, inducing a pyroptotic triggered reaction further fueling inflammation. Interestingly, different studies have reported elevated levels of LDH, a cytosolic enzyme that is measured for monitoring pyroptosis in patients with the severe form of COVID-19.109 On the other hand, diet-induced alterations in the gut leading to increased gut permeability to bacterial endotoxins are known to promote activation of NLRP3 inflammasomes via Toll-like receptors (TLRs). This event is followed by the accumulation of IL-1 family cytokines, which modulate insulin production by pancreatic beta cells.110 Importantly and at the same time, a decrease in endogenous protective mechanisms occurs.111 NLRP3 inflammasome activation is involved in endothelial lysosome membrane permeabilization, cathepsin B release, and impaired glycocalyx thickness,112 thus further contributing to the endothelial cell dysfunction, enhanced susceptibility to cardiovascular injury and thrombotic events, a common complication in severe COVID-19 patients.

In fact, thrombotic events are now recognized as a common feature in COVID-19 patients, and COVID-19 has recently been suggested to be a thrombotic viral fever.113 Obese patients are prone to thrombotic events for many different reasons,113 and COVID-19 may contribute even further to this complication. The imbalance of the ACE/ACE2 system caused by internalization of ACE2 after binding to virus S protein causes a switch towards pro-thrombotic activity by decreasing Ang-(1-7)-Mas axis (antithrombotic) and increasing angiotensin II (prothrombotic). This mechanism may be of central pathogenic relevance explaining the poor outcome of obese patients with COVID-19.113

In summary, there are many different ways by which low-grade inflammation caused by metabolic changes in obesity may contribute to the worse prognosis of obese patients infected by SARS-CoV-2, in a combination of factors and mechanisms leading to a subversion of the defensive responses of the organism against the virus.

The authors report no conflicts of interest in this work.

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Obesity-Related Inflammation and Endothelial Dysfunction in COVID-19: | JIR - Dove Medical Press


The hunt for the master cow that will feed the world –

Thursday, May 27th, 2021

Patent applications only hint at what companies might be working on, but both Flack and Stout agree that genetically-engineered cells might be the only way to drive down the costs of cultured meat. I think that getting from $300,000 (211,000) for a burger to $50 (35) for a burger is going to be easier than getting from $50 to $2 (1.40), Stout says. Im not at all confident that, without improving the cells themselves, you can get to $2.

But why stop at gene-editing cells to make them grow more efficiently? There are all kinds of funky things you could do with engineered cell lines. One idea Stout has is to edit chicken cells so they can express limonene the oil that gives citruses their fruity aroma to make lemon chicken at a cellular level. In 2020, he published a study detailing how he inserted three genes into cow muscle cells so they produced antioxidants that mitigate some of the negative effects of eating red meat. Take them out of an animal, and cells could become a blank canvas for new kinds of culinary creativity.

WITHOUT CELL LINES to start with, researchers are having to go it alone. Stout got his cow stem cells from his universitys veterinary school, but not every lab has that kind of access, and even that source of cow stem cells is much less useful than the holy grail: a cell bank of immortalised cow cells that anyone can access.

There are at least 40 companies vying to bring cultured meat to the market and venture capital funding is pouring in from all angles. Eat Just, which became the first cultured meat company to sell its products in a restaurant after Singapore approved its cultured chicken at the end of 2020, has raised 318 million in funding in 2021 alone. In February, Mosa Meat closed its Series B funding round after securing 59m and a month later another Dutch firm, Meatable, announced it had raised a further 33m.

Cell lines are the secret sauce of the cultured meat industry, so its unsurprising that most companies are keeping theirs under wraps. A spokesperson for Eat Just said that the company could not share details about its cell lines for intellectual property reasons. Neta Lavon at Aleph Farms said that the company is working with pre-embryonic stem cells, but that it had no plans to share its cell lines in the short-term. Other cultured meat companies contacted did not make themselves available for interview.

One of the things I dont like about the cultured meat industry is how lots of the best research, probably the furthest-advanced research, is all locked up in companies that arent saying anything, says Flack. Swartz says three cultured meat firms have contacted him about taking part in the GFIs cell line banking project, which lets companies retain their intellectual property, but none of them have deposited cell lines yet. Companies are likely to only use the best-performing cell lines for their meat production, Swartz says, leaving other less developed cell lines unused. This gives them an opportunity, in my opinion, to share those cell lines at no cost.

In the meantime, companies that specialise in cell lines might fill the gap. Edinburgh-based Roslin Technologies usually produces cell lines for toxicology and drug screening, but now sells pig stem cells to the cultured meat industry. It already has a contract with one cultured meat firm and has evaluation licenses with other companies that are trialling its stem cells. The cells the company is licensing are called induced pluripotent stem cells cells that have been reprogrammed back into a state where they can develop into many different types of cells. Because this reprogramming doesnt alter the genetic makeup of the cell they might escape European Union regulations that limit the sale of any genetically modified foods, says Richard Freeman, commercial manager at Roslin Technologies.

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The hunt for the master cow that will feed the world -


Australia’s Magic Valley On How to Turn Cells From "Cell Volunteer" Lucy the Lamb Into Lamb Steaks and Chops – vegconomist – the vegan…

Thursday, May 27th, 2021

Founded to meet the future protein demands of an expanding global population, Australias Magic Valley is developing cell-cultured lamb products including mince, strips, steaks and chops. With lambs currently slaughtered at an incredibly young age using traditional farming methods, its founder tells us this particular meat became the obvious choice for the companys first product range.

There is absolutely no need for the mass slaughter of animals for food and hopefully intensive animal agriculture will soon be a thing of the past

Vegconomist spoke with Founder Paul Bevan, who says that he had become frustrated by the pace of change and effectiveness of his own activism so he turned his attention to technology, specifically the development of slaughter-free cultured meat, beginning with lamb.

Utilising induced pluripotent stem-cells and FBS-free media, Magic Valley is able to grow real animal meat from animal cells, using animals such as Lucy, who Paul refers to as cell volunteers.

Eventually we would like to expand into developing cultured meat products for all other animal species

Lucy the lamb is our very special cell donor. From just a tiny skin biopsy less than 4mm in diameter we are able to generate an infinite number of muscle and fat cells without ever having to interfere with an animal again. That is one of the distinct advantages of our technology and using induced pluripotent stem cells.

Meanwhile, Lucy gets to live out the entirety of her natural life (up to 20 years of age) happy and unharmed, blissfully unaware that her cell donation has potentially saved the lives of billions of lambs that would otherwise have been slaughtered at just 6 months of age.

Magic Valleys team consisting of Australias leading scientists have extensive experience in both stem cell biology and livestock production. As part of its ambitions to become a leader in the field, the company also announced this week the onboarding of industry pioneer Dr. Sandhya Sriram, PhD, Co-Founder & CEO of the cell-based crustacean producers Shiok Meats, to its advisory board.

Eventually we would like to expand into developing cultured meat products for all other animal species that have traditionally been farmed for human consumption. With the advancement of this technology, there is absolutely no need for the mass slaughter of animals for food and hopefully intensive animal agriculture will soon be a thing of the past, Bevan commented to vegconomist.

Our immediate goal is to develop the safest, healthiest and tastiest cultured lamb products possible. We know that to be successful, cultured meat products have to become the obvious choice for consumers and that means taste, price & convenience are paramount. We know that ethical or environmental concerns alone are not enough to change consumer behaviour it has to be a better product.


Australia's Magic Valley On How to Turn Cells From "Cell Volunteer" Lucy the Lamb Into Lamb Steaks and Chops - vegconomist - the vegan...


Clearing Cellular Dead Wood | In the Pipeline – Science Magazine

Thursday, May 27th, 2021

For many years now, the topic of senescent cells has been the subject of plenty of research work. Back in the 1960s the Hayflick limit was noticed in cell culture: there was an apparent limit to the number of cell divisions that could take place before the cells just sort of stalled out. For human fibroblasts, that kicks in at around fifty divisions. Over time it was worked out that a primary mechanism involved is the shortening of telomeres with each cell division, specialized nucleotide sequences out at the ends of the chromosomes, and this cellular clock phenomenon has been making its way into the public consciousness ever since.

Its strange to think, but before these experiments human cells were considered to be more or less immortal and capable of unlimited numbers of divisions. Now, there are cells like that, but that (outside of some stem cell populations and a few other special cases) is a very short working definition of cancer. Those cells do indeed seem to be able to carry on for as long as conditions permit which in the artificial world of cell culture labs, means apparently forever. Henrietta Lacks died in 1951, but HeLa cells are still with us, and can be all too vigorous when they contaminate other lines. Tumor cells can pile up mutations that will make them die off, but short of that the jams have indeed been kicked out.

Its gradually become apparent that many aging or damaged tissues have a (sometimes substantial) population of cells that have reached their limit. Theyre alive and metabolically active but not really contributing much, in a stage of permanent growth arrest. Cellular senescence is a complex phenomenon, but its importance in aging, cancer, and tissue damaged by other factors (radiation, oxygen stress, etc.) is by now undeniable. Many of these non-aging states can be traced back to early telomere damage by other mechanisms, emphasizing that as a key countdown mechanism. But its clear that senescent have a different secretory profile (cytokines, growth factors and more) from the more vigorous cells around them and a number of other protein expression differences that can be used the characterize them.

Naturally enough, thoughts have turned to targeting such cells for therapy. There are a couple of very easy-to-picture hypotheses: first, could you keep telomeres from shortening (or shortening so much) and therefore keep cells in a non-senescent state for longer, potentially delaying biological aging? And second, could you somehow target cells that have already become senescent, and would doing so improve the health of the surrounding tissue? Though pretty obvious ideas, both of these are still very much in play. For now, Im going to talk about the second one, in light of a new paper.

That ones on the kidney. Younger people can regain some kidney function after an injury, but that ability goes down with aging, as youd imagine. It also goes down in states of chronic kidney disease, or after radiation damage. This new paper shows that targeting and removing senescent cells actually starts to reverse this phenotype once youve done that, the kidney tissue after injury shows increased function, increased regenerative ability, and less development of fibrosis. This is demonstrated both in aged tissue and in younger tissue exposed to radiation damage, in human cell culture and in mouse animal models.

You may well ask: how exactly does one target senescent cells? That takes us to ABT-263 (navitoclax), shown at right. This rather hefty molecule is part of a series of AbbVie protein-protein inhibitors for the Bcl-2 (B-cell-lymphoma) family. There are several of those, and navitoclax inhibits the function of Bcl-2, Bcl-xL, and Bcl-w. All of these proteins are intimately tied up in the pathways of apoptosis, programmed cell death, which is another monstrously huge pathway all its own. But one of the questions about senescent cells is why they dont go down some apoptotic pathway and just fall on their on cellular swords, instead of hanging around forever gumming up the works.

This one, like the others in its class, was developed to cause this to happen to tumor cells as an adjunct to other types of chemotherapy, but these have also turned out to be useful against senescent cells (although not all types of them). Similar to the kidney results reported in the new paper linked above, there have been reports in lung, CNS, muscle and other tissues of broadly similar enhancements (many of these summarized in this paper). So at this point you might be wondering why we dont just go ahead and put these things into the water supply already.

Theres a problem, unfortunately. It was clear from the clinical studies of the AbbVie compounds that platelet effects were dose-limiting. Cells in that pathway are sensitive to messing with these apoptosis pathways, and while you might be able to deal with that side effect in a chemotherapy situation, it doesnt exactly make for a good-for-what-ails-you drug. Navitoclax has alsorecently been shown to have profoundly bad effects on bone density and deposition, which is the exact opposite of what youd want for an aging population.

AbbVies next generation of such compounds, though, includes venetoclax, at right, also a lunker of a molecule and now approved for several types of leukemia. It still has platelet effects, but they arent nearly as disastrous as with navitoclax, thanks to deliberately lower binding to Bcl-xL. That also makes it a bit less of a mighty sword across senescent cell types for example, it appears that you need that pathway for activity against glioblastoma cells. But it has been reported to show strong protective effects against the development of Type I diabetes through the elimination of senescent cells in the islets of Langerhans. Meanwhile, other groups are looking at turning these ligands into targeted protein degraders, which (at least in some cases) seems to decrease the platelet problems and increase senolytic activity.

And before leaving the topic, it has to be noted that there are plenty of other ways to target these cells other than the Bcl pathway (although that one seems to be one of the most developed so far). What can I say? Im 59, and I doubtless have more senescent cells than I want or need, so I (and plenty of others) are interested in the idea. The whole cellular senescence pathway presumably developed as a way to avoid slipping into a tumor phenotype the more cellular divisions, the greater the chance of something going wrong along the way. Its a tradeoff, and evolution seems more than willing to shortchange older members of the species who have generally passed on their genes to all the offspring that theyre going to. But humans have other goals. We are looking at a rather rapidly aging planet, if current demographic trends hold up, and it would be extremely desirable to have that associated with less of a disease burden. Can we split the difference?

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Clearing Cellular Dead Wood | In the Pipeline - Science Magazine


University of Pittsburgh Won’t Explain its Planned Parenthood Ties | Opinion – Newsweek

Thursday, May 27th, 2021

I testified at the Pennsylvania House Health Committee's hearing on "Fetal Experimentation" earlier this month.

Pennsylvania has a pro-life reputation, yet the University of Pittsburgh hosts disturbing and barbaric government-sponsored experiments on aborted babies: infant scalping, exporting fetal kidneys and killing live-aborted infants by organ harvesting. Mounting evidence connects Planned Parenthood to it all.

Despite the serious questions about these experiments and Pitt's inextricable relationship with Planned Parenthood, Pitt stonewalled lawmakers with an unprepared, newly hired witness who could not answer basic questions. Perhaps Pitt could not send a qualified witness to defend these programs, because what takes place in them is indefensible.

In one study published last year, Pitt scientists described scalping 5-month-old aborted babies to stitch onto the backs of lab rats. They wrote about how they cut the scalps from the heads and backs of the babies, scraping off the "excess fat" under the baby skin before stitching it onto the rats. They even included photos of the babies' hair growing out of the scalps. Each scalp belonged to a little Pennsylvania baby whose head would grow those same hairs if he or she were not aborted for experiments with lab rats.

Pitt's explanation? "Lab mice, not lab rats," the university's witness told the committee indignantly.

In fact, the published study used both rats and mice to grow the babies' scalps. How was this paid for? With a $430,000 grant from Dr. Anthony Fauci's NIAID office at the NIH. Pitt's witness implied that government NIH grants somehow did not concern taxpayers in Pennsylvania.

Previously, I wrote about another Pitt scientist who developed a nightmarish "protocol" for harvesting the freshest, most pristine livers from 5-month-old aborted babies in order to isolate massive numbers of stem cells for experimental transplants. This technique calls for aborting late-term fetuses alive via labor induction, rushing them to a sterile laboratory, washing them and then cutting them open to harvest the liver. This Pitt scientist received $3 million from the NIH.

At the hearing, Pitt asserted, without evidence, that this experiment was done only in Italy and ended in 2013. But the Pitt scientist responsible published further research in 2019 and described obtaining the same uniquely massive, two-billion-stem-cell yield from "complete" fetal livers harvested in Pittsburghindicating the same technique he outlined was still being used in America.

Starting in 2016, Pitt received $1.4 million in NIH grants to operate a distribution "hub" for aborted fetal kidneys and other organs in NIH's GenitoUrinary Development Molecular Anatomy Project. Pitt's grant application advertises the university's unique access to a large number of high-quality aborted fetuses and that "collections can be significantly ramped up."

Pennsylvania law makes experimentation on a living fetus or failure to provide immediate medical care to a born-alive infant a third-degree felony. Sadly, fetal experimentation, including on babies delivered alive in late-term abortions, has been documented at Pitt for decades.

Astonishingly, at and after the hearing, Pitt doubled down on a demonstrably false talking point: "There is no procurement relationship for tissue with Planned Parenthood."

Pitt's fetal research projects generally obtain fetal tissue through the university's tissue bank from local abortion providers. Two years ago, sources told me Pittsburgh was one of the major hubs of the FBI's investigation into Planned Parenthood's human trafficking of aborted fetuses. Planned Parenthood Western Pennsylvania (PPWP) abortion providers, who were on staff at Pitt, confirmed this information. When I was undercover, they told me they supply the university's tissue bank.

What is Pitt so afraid of admitting?

Since 2005, Pitt has been a major location for Planned Parenthood's Ryan Residency and Family Planning Fellowship abortion training programs. Some of the most notorious Planned Parenthood abortion doctors came up through the program.

Dr. Jennefer Russo, VP of Planned Parenthood Orange and San Bernardino Counties, supplied the aborted fetuses to the criminal company DaVinci Bioscienceswhich admitted to illegally selling the fetal body parts and was shut down by local law enforcement. She did her abortion training fellowship at Pitt. And there are many others.

Today, Dr. Beatrice Chen, PPWP's medical director, also runs the abortion programs at Pitt. Dr. Sharon Achilles, the laboratory director at PPWP and a prominent Pitt faculty member, is on Planned Parenthood Federation of America's National Medical Committee.

Shockingly, Dr. Chen is also vice chair of the university's Institutional Review Board, which reviews and supervises all fetal research projects. This obvious conflict of interest makes the Pitt-and-Planned-Parenthood lead abortionist a supervising participant in every fetal research project, contravening federal requirements that fetal researchers be separated from clinical abortion practice.

Planned Parenthood Western Pennsylvania, meanwhile, is a "contracted care" site for Pitt, receiving access to medical students, medical resources, medical infrastructure, patient population and referrals at the university.

We know this much, just from public sources: first, Planned Parenthood abortionists supply fetuses to Pitt; second, Pitt uses its access to fetal tissue and organs to get major NIH grant money; third, Planned Parenthood enjoys access to people and resources at Pitt.

Needless to say, a quid pro quo over aborted fetal body parts, funded by taxpayers, would be illegal. If what we know publicly about Pitt is damning, imagine what we do not know. Public officials at every level of government must unearth the full scope of the human trafficking and experimental use of aborted infants, and stop enabling these atrocities.

David Daleiden leads The Center for Medical Progress and is responsible for the multi-year undercover video reporting that exposed the trafficking of aborted fetal body parts at Planned Parenthood and other institutions.

The views expressed in this article are the writer's own.

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University of Pittsburgh Won't Explain its Planned Parenthood Ties | Opinion - Newsweek


Smart Stem Cells Made From Fat Have the Power to Heal – Freethink

Sunday, February 14th, 2021

New smart stem cells show a promising power to heal.

Researchers have reprogrammed human fat cells into adaptive smart stem cells that can lie dormant in the body until they are needed to heal various tissues. They demonstrated the cells' effectiveness at healing damaged tissue in a mouse study.

To create the smart stem cells, the team from UNSW Sydney exposed human fat cells to a compound mixture. After about three and a half weeks, the cells lost their original identity and began acting like stem cells, or iMS (induced multipotent stem cells).

"The stem cells acted like chameleons. They followed local cues to blend into the tissue that required healing."

"The stem cells we've developed can adapt to their surroundings and repair a range of damaged tissues," said UNSW hematologist John Pimanda, and co-author of the study, which they published in Science Advances.

"To my knowledge, no one has made an adaptive human multipotent stem cell before. This is uncharted territory."

Next, they injected the experimental iMS cells into healthy mice to see how the cells would respond. The cells remained dormant for some time, but they activated when the mouse was injured. Because of the cells' regenerative ability to act as "smart stem cells," they transformed themselves into whatever tissue was needed to heal the injured mouse --- like bone tissue, heart, or skin.

"The stem cells acted like chameleons," said Avani Yeola, lead author on the study at UNSW Medicine & Health. "They followed local cues to blend into the tissue that required healing."

All cells in a human body contain the same DNA. To differentiate between tissues, like a skin cell versus a bone cell, the cells only use a small portion of their total DNA. The rest of the DNA is shut down naturally by local modifications.

"The idea behind our approach was to reverse these modifications," said Pimanda. "We wanted the cells to have the option of using that part of the DNA if there was a signal from outside the cell."

Tissue-specific stem cells, like those that are restricted to becoming parts of the liver or lung, are limiting. But smart stem cells that can respond to their environment and become any tissue, like multipotent stem cells, will have many uses.

In the future, doctors could take a patient's fat cells, incubate them with the compound, and inject them into the patient to heal heart damage or trauma injuries.

But applications like this could be a long way off. The team needs to do much more research to prove this is safe in humans for different kinds of trauma before it becomes a real therapy.

We'd love to hear from you! If you have a comment about this article or if you have a tip for a future Freethink story, please email us at [emailprotected]

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Smart Stem Cells Made From Fat Have the Power to Heal - Freethink


Network-based screen in iPSC-derived cells reveals therapeutic candidate for heart valve disease – Science

Sunday, February 14th, 2021

Machine learning for medicine

Small-molecule screens aimed at identifying therapeutic candidates traditionally search for molecules that affect one to several outputs at most, limiting discovery of true disease-modifying drugs. Theodoris et al. developed a machine-learning approach to identify small molecules that broadly correct gene networks dysregulated in a human induced pluripotent stem cell disease model of a common form of heart disease involving the aortic valve. Gene network correction by the most efficacious therapeutic candidate generalized to primary aortic valve cells derived from more than 20 patients with sporadic aortic valve disease and prevented aortic valve disease in vivo in a mouse model.

Science, this issue p. eabd0724

Determining the gene-regulatory networks that drive human disease allows the design of therapies that target the core disease mechanism rather than merely managing symptoms. However, small molecules used as therapeutic agents are traditionally screened for their effects on only one to several outputs at most, from which their predicted efficacy on the disease as a whole is extrapolated. In silico correlation of disease network dysregulation with pathways affected by molecules in surrogate cell types is limited by the relevance of the cell types used and by not directly testing compounds in patient cells.

In principle, mapping the architecture of the dysregulated network in disease-relevant cells differentiated from patient-derived induced pluripotent stem cells (iPSCs) and subsequent screening for small molecules that broadly correct the abnormal gene network could overcome this obstacle. Specifically, targeting normalization of the core regulatory elements that drive the disease process, rather than correction of peripheral downstream effectors that may not be disease modifying, would have the greatest likelihood of therapeutic success. We previously demonstrated that haploinsufficiency of NOTCH1 can cause calcific aortic valve disease (CAVD), the third most common form of heart disease, and that the underlying mechanism involves derepression of osteoblast-like gene networks in cardiac valve cells. There is no medical therapy for CAVD, and in the United States alone, >100,000 surgical valve replacements are performed annually to relieve obstruction of blood flow from the heart. Many of these occur in the setting of a congenital aortic valve anomaly present in 1 to 2% of the population in which the aortic valve has two leaflets (bicuspid) rather than the normal three leaflets (tricuspid). Bicuspid valves in humans can also be caused by NOTCH1 mutations and predispose to early and more aggressive calcification in adulthood. Given that valve calcification progresses with age, a medical therapy that could slow or even arrest progression would have tremendous impact.

We developed a machine-learning approach to identify small molecules that sufficiently corrected gene network dysregulation in NOTCH1-haploinsufficient human iPSC-derived endothelial cells (ECs) such that they classified similar to NOTCH1+/+ ECs derived from gene-corrected isogenic iPSCs. We screened 1595 small molecules for their effect on a signature of 119 genes representative of key regulatory nodes and peripheral genes from varied regions of the inferred NOTCH1-dependent network, assayed by targeted RNA sequencing (RNA-seq). Overall, eight molecules were validated to sufficiently correct the network signature such that NOTCH1+/ ECs classified as NOTCH1+/+ by the trained machine-learning algorithm. Of these, XCT790, an inverse agonist of estrogen-related receptor (ERR), had the strongest restorative effect on the key regulatory nodes SOX7 and TCF4 and on the network as a whole, as shown by full transcriptome RNA-seq.

Gene network correction by XCT790 generalized to human primary aortic valve ECs derived from explanted valves from >20 patients with nonfamilial CAVD. XCT790 was effective in broadly restoring dysregulated genes toward the normal state in both calcified tricuspid and bicuspid valves, including the key regulatory nodes SOX7 and TCF4.

Furthermore, XCT790 was sufficient to prevent as well as treat already established aortic valve disease in vivo in a mouse model of Notch1 haploinsufficiency on a telomere-shortened background. XCT790 significantly reduced aortic valve thickness, the extent of calcification, and echocardiographic signs of valve stenosis in vivo. XCT790 also reduced the percentage of aortic valve cells expressing the osteoblast transcriptional regulator RUNX2, indicating a reduction in the osteogenic cell fate switch underlying CAVD. Whole-transcriptome RNA-seq in treated aortic valves showed that XCT790 broadly corrected the genes dysregulated in Notch1-haploinsufficient mice with shortened telomeres, and that treatment of diseased aortic valves promoted clustering of the transcriptome with that of healthy aortic valves.

Network-based screening that leverages iPSC and machine-learning technologies is an effective strategy to discover molecules with broadly restorative effects on gene networks dysregulated in human disease that can be validated in vivo. XCT790 represents an entry point for developing a much-needed medical therapy for calcification of the aortic valve, which may also affect the highly related and associated calcification of blood vessels. Given the efficacy of XCT790 in limiting valve thickening, the potential for XCT790 to alter the progression of childhood, and perhaps even fetal, valve stenosis also warrants further study. Application of this strategy to other human models of disease may increase the likelihood of identifying disease-modifying candidate therapies that are successful in vivo.

A gene networkbased screening approach leveraging human disease-specific iPSCs and machine learning identified a therapeutic candidate, XCT790, which corrected the network dysregulation in genetically defined iPSC-derived endothelial cells and primary aortic valve endothelial cells from >20 patients with sporadic aortic valve disease. XCT790 was also effective in preventing and treating a mouse model of aortic valve disease.

Mapping the gene-regulatory networks dysregulated in human disease would allow the design of network-correcting therapies that treat the core disease mechanism. However, small molecules are traditionally screened for their effects on one to several outputs at most, biasing discovery and limiting the likelihood of true disease-modifying drug candidates. Here, we developed a machine-learning approach to identify small molecules that broadly correct gene networks dysregulated in a human induced pluripotent stem cell (iPSC) disease model of a common form of heart disease involving the aortic valve (AV). Gene network correction by the most efficacious therapeutic candidate, XCT790, generalized to patient-derived primary AV cells and was sufficient to prevent and treat AV disease in vivo in a mouse model. This strategy, made feasible by human iPSC technology, network analysis, and machine learning, may represent an effective path for drug discovery.

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Network-based screen in iPSC-derived cells reveals therapeutic candidate for heart valve disease - Science


Their Goal: Meat That’s Better Than Meat | Tufts Now – Tufts Now

Sunday, January 31st, 2021

There are plenty of reasons to want to shift away from eating meat: its better for the planet and certainly better for animals that would otherwise be eaten. But meat is still a big draw, both in the U.S. and increasingly in medium-income countries like China.

At the Tufts School of Engineering, a team of scientists led by Professor David Kaplan is exploring another avenue to feed this trendmeat grown directly from animal cells. It could be the start of an entirely new agricultural industryas humane and green as plant-based meat substitutes, but providing taste, texture, and nutrition that is even closer to the experience of eating real meat.

The technology is already familiar to cell biologistsgrowing and harvesting cells from a single sample of tissue from a live anesthetized animal, but doing it in ways that may help the cells transform into something similar to the muscle tissue people enjoy eating from beef, chicken, and fish, including shrimp and scallops.

Meat from animals contains connective tissue, vascular networks, fat, and other cell types, as well as blood, biological fluids, and a complex mix of proteins and sugars, all of which contribute to the unique taste and texture of the meat. Replicating that structure and content is the technical challenge that the Tufts team is working on using the tools of tissue engineering.

A variety of flavors and textures can be achieved by growing different types of cells together, like skeletal muscle, fat cells and fibroblasts (the most common type of cell in connective tissue), adding nutrients to the surrounding media (the soup in which the cells grow), or using genetic modification to add components that not only introduce flavors, but can modify color or even improve on the nutritional quality of natural meat.

Andrew Stout, a doctoral student in biomedical engineering, has explored adding myoglobin to the cell growth media, for example. Myoglobin, a natural component of muscle, is a protein that carries iron and oxygen, and is associated with the bloody flavor of meat. He found that its addition to the mix helps improve the color of the cell mass, and even enhanced the growth rate of the meat substitute.

Stout has also been working to enhance the nutritional content of cell-based meat. In a recent journal publication, he reported how he had modified muscle cells from cows by genetically adding enzymatic machinery to produce the antioxidants phytoene, lycopene, and beta-carotene, normally found in plants.

Think of it as a way to make cell-based meat more plant-like in the healthy nutritional components it offers. Adding beta-carotene, for example, could have protective effects against colorectal cancer, which tends to be more prevalent among those with a high intake of red meat. Another benefit of this type of metabolic engineering is that the antioxidants could improve the quality and shelf-life of the meat.

How far can they take this nutritional engineering? I think other nutrients would definitely work, said Stout. Thats one of the things that I am the most excited about. Putting plant genes into mammalian cells is pretty un-travelled scientific territory, and so theres a lot of space to explore other nutrients, flavor, and color compounds. In addition, he adds, the cell-based meat can be engineered as a therapeutic food.

Most cell-based approaches have emulated processed meat such as hamburger, sausage, and nuggets. Replicating the appearance and texture of whole cuts of meat, like steak, is a different kind of challenge.

Tissue engineering experts in the Kaplan lab bring a lot of experience to the task of aligning cells and creating fibers resembling real meat structure, using things like mechanical tension and micropatterned substrates to help align cells into fibers.

Natalie Rubio, a Ph.D. student in biomedical engineering, found that switching from cows to caterpillars as a source of cells can have some advantages. The muscle and fat stem cells originating from the eggs of the tobacco hornworma beefy little caterpillarcan be used to generate tissue that resembles other invertebrates that were used to eating, like shrimp and scallops.

A vast amount of knowledge has already developed around large scale invertebrate cell culture, since insect cells are widely used in the production of pharmaceuticals. Suspended in a liquid medium, they tend to grow to very high density and have simpler requirements for maintenance and growth. Yields could be greater and production costs lower than from mammalian cells.

But Rubio explains that there is a very important step remaining to transform a soup of cells into something resembling real meatproviding a scaffold to shape and orient the cells.

The scaffold is the backbone of the meatit provides structure and texture, said Rubio. If we did not have that support structure, the meat would just look like slime.

Rubio generates scaffolds from chitosana polymer found in a closely related form (chitin) in exoskeletons such as crab shells and fungi. Chitosan is a great material to make scaffolds from because it is edible, abundant, and inexpensive, she said.

Chitin can be isolated from fungi and easily converted to chitosan and then formed into films, fibers, or sponges to act as scaffolding for cell culture. Rubio grows insect muscle and fat cells on the chitosan scaffolds to generate small, structured meat constructs.

Kaplans lab has been a hub and catalyst for cellular agriculture research and development in the academic sector for many years, he said. That continues with an annual course for undergraduates on cellular agriculture, which is again being offered this spring semester.

Cell-based meat has not yet been commercialized, but the first cultured beef burger was produced by Maastricht University in 2013, and a number of start-up companies are now working to create new products to sell.

Alumni from our group have fanned out across the globe to help create the foundation of a nascent cell-based agricultural industry, Kaplan said. They include Laura Domigan, who is a principal investigator at University of Auckland; research scientist Amanda Baryshyan at Gloucester Marine Genomics Institute; Ryan Pandya, CEO of Perfect Day Foods; Viktor Maciag, head of tissue engineering at Mission Barns; and Robin Simsa, CEO of Legendary Vish.

Mike Silver can be reached at

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Their Goal: Meat That's Better Than Meat | Tufts Now - Tufts Now


Gut microbiota: How does it interact with the brain? – Medical News Today

Wednesday, December 30th, 2020

Through studies in mice, researchers find evidence that having a healthful balance of gut microorganisms is important for good health.

Researchers from the Institut Pasteur, French National Center for Scientific Research (CNRS), and Inserm have found evidence that gut microbiota also plays a role in mood regulation and brain function.

Gut microbiota is the community of bacteria, fungi, and viruses that live in the digestive tract.

These findings in mice suggest that changes to gut bacterial communities may lead or contribute to depression. If humans have a similar mechanism, doctors might be able to use bacteria strains to treat mood disorders, such as depression.

A group of 16 researchers from several prominent French research institutions conducted the study, which appears in Nature Communications.

Studies have found that some people with depression experience dysbiosis, which is an imbalance or change in their intestinal microbiota.

Research conducted on rodents also shows that gut dysbiosis has associations with neurological changes linked with depression, such as:

Animal studies also show that gut microbiota helps regulate anxiety. It may also influence the development of neurological conditions caused by circuit dysfunctions, such as Parkinsons disease, Alzheimers disease, depression, and obsessive-compulsive disorder.

Researchers think this is because gut bacteria release metabolites, tiny bits of food broken down by digestion that influence brain function. Metabolites may impact mood regulation by acting on the endocannabinoid system.

The endocannabinoid system is a complex cell-signaling system consisting of lipid (fat)-based neurotransmitters and their receptors.

It is found throughout the body and plays a role in important aspects of health, such as immune and nervous system function and cellular communication in the nervous system. It also regulates emotions, moods, and stress responses by activation of the systems main receptor, CB1.

Previous research supports the idea that restoring gut microbial health may help treat depression. In animal studies, prebiotic treatment influenced emotional behavior. In human studies, prebiotic supplementation also improved mood in people with depression.

But despite educated theories, researchers still do not know precisely how gut bacteria impact brain function.

Researchers in the recent study set out to find the mechanisms linking gut microbiota and mood disorders. A team of researchers from some of these same French institutions published a report earlier this year, which found that stress-induced changes in gut microbiota reduced the efficacy of the antidepressant fluoxetine in mice.

In the study, researchers submitted genetically identical mice to unpredictable chronic mild stress (UCMS), a mouse model of stress-induced depression, for 8 weeks.

This treatment caused the mice to develop depressive-like behaviors, such as reduced eating, grooming, weight loss, and hippocampal neurogenesis. The hippocampus is responsible for learning and memory and is heavily affected by several psychiatric and neurological conditions.

Researchers then transplanted fecal samples containing gut microbiota from control and UCMS-exposed mice into healthy mice. To serve as a control, mice that received fecal transplants were germ-free mice or received treatment with antibiotics for 6 days.

After 8 weeks, mice that received transplants from UCMS mice developed depression-like symptoms. The mice also experienced a reduction in the number of new brain stem cells and neurons in their hippocampus.

These findings show that transferring gut microbiota from stress-induced depressive mice to healthy mice induced depression-like behaviors.

Surprisingly, simply transferring the microbiota from an animal with mood disorders to an animal in good health was enough to bring about biochemical changes and confer depressive-like behaviors in the latter.

Pierre-Marie Lledo, head of the Perception and Memory Unit at the Institut Pasteur (CNRS/Institut Pasteur), joint last author of the study

To figure out how this occurred, researchers explored the possibility that UCMS-exposed microbiota may trigger depression by altering metabolism. They found that mice with UCMS microbiota had significantly reduced levels of certain fatty acids in their blood and brain.

The reduced fatty acids included monoacylglycerols (MAG), diacylglycerols (DAG), polyunsaturated fatty acid (PUFA), and linoleic acid. monoacylglycerols (MAG), diacylglycerols (DAG), polyunsaturated fatty acid (PUFA), and linoleic acid. Variations of two of these fatty acids, DAD and PUFA, are converted into endocannabinoids (eCB).

The researchers speculate that gut dysbiosis may cause these changes in fatty acid levels. Studies link the dysregulation of the endocannabinoid system and its central receptor, CB1, with depression in both UCMS-model mice and humans.

In the study, the researchers found that mice with UCMS microbiota had greatly reduced levels of eCBs in their hippocampus and blood. They also found that mice with UCMS microbiota had reduced levels of Lactobacillus bacteria.

The researchers were able to reduce the depressive impact of the UCMS microbiota by enhancing CB1 levels and giving the mice a strain of Lactobacillus bacteria orally.

These findings suggest that chronic stress, diet, and the gut microbiota contribute to the development of depression-like behaviors via the endocannabinoid system.

This discovery shows the role played by the gut microbiota in normal brain function, says Grard Eberl, Head of the Microenvironment and Immunity Unit (Institut Pasteur/Inserm) and joint last author of the study.

More specifically, imbalances in the gut bacterial community that reduce fatty acid levels vital to the endocannabinoid system and brain function seem to encourage the development of depression-like behaviors.

These findings mean certain bacteria could act as a natural antidepressant, treating mood disorders by restoring gut microbial health. And this is promising news, considering the slew of potential adverse side effects and relatively low efficacy rate of most current antidepressants.

To confirm their results, the researchers will need to test their findings in humans. The researchers say that new research will also need to explore whether changes to the gut microbiota impact other brain targets of the endocannabinoid system in the same way.

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Gut microbiota: How does it interact with the brain? - Medical News Today


The 10 Best Herbs for Liver Health: Benefits and Precautions – Healthline

Saturday, December 19th, 2020

Many people around the world live with conditions that affect the liver, including cirrhosis, nonalcoholic fatty liver disease (NAFLD), alcoholic liver disease, liver cancer, liver failure, and hepatitis (1).

Every year, liver disease accounts for nearly 2 million deaths worldwide (2, 3).

Risk factors for liver disease include heavy alcohol intake, high blood sugar levels, obesity, high blood pressure, viruses, elevated triglyceride and cholesterol levels, and more (4, 5).

Liver disease is treated in a number of ways, including medication, nutritional therapy, immunotherapy, lifestyle change, surgical resection, and even liver transplant in end stage liver disease (6, 7, 8, 9).

In addition to standard treatments, many people turn to alternative therapies, including herbal supplements, in hopes of improving and protecting their liver health. In fact, around 65% of people in the United States and Europe with liver diseases take herbal supplements (10).

Here are the 10 best herbs that have been shown to improve liver health.

Many herbs, including some on this list, may be unsafe for those with certain liver conditions.

Some herbs have been connected to liver damage and other complications, which is why its critical to check with your healthcare provider before adding any herbal supplements, including the ones on this list, to your diet.

Silymarin, often called milk thistle, consists of a group of compounds extracted from milk thistle (Silybum marianum) seeds, including silybin, silychristin, and silydianin (10).

Milk thistle has been used for over 2,000 years to treat bile duct and liver conditions, and research shows that it may have liver-protective properties (11).

It has been suggested that silymarin has strong antioxidant effects and may help promote liver cell regeneration, reduce inflammation, and benefit those with liver disease. However, results from human studies have been mixed (12).

For example, some studies have shown that taking a silymarin supplement may help protect against liver disease progression, prolong life in people with alcoholic cirrhosis, and enhance overall quality of life in people with liver disease (13, 14, 15, 16).

Yet, other studies indicate that silymarin is no more effective than placebo treatments, highlighting the need for additional research (13, 17, 18, 19).

Regardless, silymarin is considered safe and has not been associated with adverse side effects, even when used at high doses (19).

Silymarin may benefit people with certain liver conditions, including alcoholic cirrhosis. Still, more research is needed.

Ginseng is a popular herbal supplement known for its powerful anti-inflammatory properties (20).

A number of test-tube and animal studies have demonstrated that ginseng has antioxidant effects and may help protect against liver injury caused by viruses, toxins, and alcohol. Plus, it may boost liver cell regeneration after surgery (21).

Whats more, some human studies have shown that ginseng treatment may improve liver function and reduce fatigue and inflammation in people with liver disease and liver dysfunction (22, 23, 24).

For example, a 2020 study in 51 men with elevated levels of alanine transaminase (ALT), a marker for liver damage, found that those who took 3 grams of ginseng extract per day for 12 weeks experienced significant reductions in ALT, compared with a placebo group (24).

Levels of gamma-glutamyl transferase (GGT), another marker for liver damage, were also reduced significantly (24).

Although these results are promising, more research investigating the effects of ginseng on liver health is needed.

When used on its own, ginseng is thought to be relatively safe for liver health. However, ginseng has the potential to react with medications, which can lead to liver injury and other potentially dangerous side effects (25, 26, 27).

Ginseng may help protect against liver damage and is generally considered safe. Yet, it has the potential to react with certain medications, which can lead to dangerous side effects.

Although it isnt technically an herb, green tea and its main polyphenol compound epigallocatechin-3-gallate (EGCG) are often included in literature reviews focusing on herbal remedies for liver conditions (28).

Some studies have found that supplementing with green tea extract may help treat those with liver disease.

A study in 80 people with nonalcoholic fatty liver disease (NAFLD) found that supplementing with 500 mg of green tea extract per day for 90 days significantly reduced the liver damage markers ALT and aspartate aminotransferase (AST) (29).

Although the placebo group also noticed a reduction in AST and ALT levels, they were not significant (29).

Another 12-week study in 80 people with NAFLD observed that those who took 500 mg of green tea extract daily experienced significant improvements in AST, ALT, and inflammatory markers, compared with a placebo. The treatment also reduced fatty changes in the liver (30).

Green tea intake has likewise been shown to protect against various liver conditions, including liver cancer, hepatitis, cirrhosis, fatty liver (hepatic steatosis), and chronic liver disease (31).

While drinking green tea is considered safe for most people, in rare cases, green tea extract supplements have been linked to acute liver injury (32).

Green tea and green tea extract have been linked to powerful liver-protective effects. Keep in mind that green tea extract has been associated with liver injury in rare cases.

Although chewy candy often comes to mind when thinking of licorice (Glycyrrhiza glabra), its really an herb with powerful medicinal properties (33).

Licorice root has been shown to have anti-inflammatory, antiviral, and liver-protective effects in scientific studies (33).

The main active component in licorice root is the saponin compound glycyrrhizin, which is commonly used in traditional Chinese and Japanese medicine to treat many ailments, including liver disease (33).

Some studies have demonstrated that treatment with licorice extract may benefit those with certain liver conditions.

A study in 66 people with fatty liver disease found that supplementing with 2 grams of licorice root extract per day for 2 months significantly reduced ALT and AST, compared with a placebo treatment (34).

In another small study, 6 healthy people took a glycyrrhizin product before drinking vodka every night for 12 days, and 6 people only drank vodka nightly for 12 days.

In the vodka-only group, liver damage markers, including ALT, AST, and GGT, significantly increased. In the glycyrrhizin group, these markers did not significantly increase, suggesting that glycyrrhizin may help protect against alcohol-related liver damage (35).

Although these findings are promising, more research is needed.

Whats more, some people are more sensitive to licorice, and the chronic use of licorice products can result in dangerous side effects, including high blood pressure and low blood levels of potassium (36).

Licorice supplements may benefit those with NAFLD and protect against alcohol-related liver damage. Its important to note that certain people may be more sensitive to licorice supplements, as well as that they can lead to adverse side effects.

Turmeric and its main active component curcumin have been linked to a variety of impressive health benefits.

Its well documented that turmeric has powerful anti-inflammatory, antioxidant, and anticancer properties, which makes this herb a popular choice for those with liver disease (37).

A study in people with NAFLD demonstrated that daily treatment with 500 mg of a curcumin product for 8 weeks significantly reduced liver fat content and levels of AST and ALT, compared with a placebo group (38).

Another study in 70 people with NAFLD found that those who supplemented with 500 mg of curcumin and 5 mg of piperine per day for 12 weeks had significant reductions in ALT, AST, LDL (bad) cholesterol, and inflammatory markers, compared with a placebo group (39).

Piperine is a compound found in black pepper that enhances curcumin absorption.

It was also observed that the curcumin treatment significantly improved NAFLD severity, compared with the placebo group (39).

Supplementing with turmeric and curcumin is generally considered safe. However, some cases of acute liver injury have been reported. Still, its unclear whether these cases were due to the contamination of curcumin products or the products themselves (40).

Studies show that turmeric supplements may help treat NAFLD and reduce inflammation. Turmeric is generally considered safe, but some cases of liver injury have been reported.

Although garlic is botanically considered a vegetable, its a popular component of many herbal remedies. Its packed with potent antioxidant and anti-inflammatory plant compounds, such as allicin, alliin, and ajoene, which may help support liver health (41, 42).

A 2020 study in 98 people with NAFLD found that those who took 800 mg of garlic powder per day for 15 weeks experienced significant reductions in ALT, AST, LDL (bad) cholesterol, and triglyceride levels, compared with a placebo group (42).

Whats more, 51% of the participants in the garlic group showed improvements in the severity of liver fat accumulation, compared with just 16% of the control group (42).

Another study in over 24,000 adults found that men who consumed raw garlic over 7 times per week had up to a 29% reduced risk of developing fatty liver disease. Although raw garlic intake was inversely associated with NAFLD in men, this association was not seen in women (43).

Additionally, a study linked raw garlic intake to a lower risk of liver cancer. Eating raw garlic twice or more per week was associated with a 23% reduced risk of liver cancer, compared with consuming raw garlic less than twice per week (44).

Although raw garlic is generally considered safe, concentrated garlic supplements may induce liver injury in some people (45).

Raw garlic and garlic powder have liver-protective properties and may improve liver health in those with NAFLD. Eating raw garlic may protect against liver cancer. Garlic is generally considered safe but may cause liver injury in some people.

Ginger root is a popular culinary ingredient and also commonly used as a medicinal treatment for many health conditions, including liver disease.

A 12-week study in 46 people with NAFLD found that supplementing with 1,500 mg of ginger powder per day significantly reduced ALT, total and LDL (bad) cholesterol, fasting blood sugar, and the inflammatory marker C-reactive protein (CRP), compared with placebo treatment (46).

Another study observed similar results. People with NAFLD who supplemented with 2 grams of ginger for 12 weeks experienced significant reductions in ALT, GGT, inflammatory markers, and fat accumulation in the liver, compared with a placebo group (47).

Ginger root contains powerful compounds, including gingerols and shogaols, that help inhibit inflammation and protect against cellular damage, which may help support liver health. Plus, ginger may help protect your liver against toxins like alcohol (48, 49).

Ginger is generally considered safe, even for those with liver conditions. However, you should always check with your healthcare provider before supplementing with high-dose ginger products (50).

Taking ginger supplements may help reduce liver damage and lower cholesterol, blood sugar, and inflammation in people with NAFLD. Ginger is generally considered safe.

In addition to the treatments listed above, many other herbs have been linked to improved liver health.

Danshen is a substance thats commonly used in traditional Chinese medicine. Its the dried roots of the herb Salvia miltiorrhiza Bunge. Human and animal studies have shown that danshen may have positive effects on liver health.

Animal studies indicate danshen may help protect against alcohol-related liver disease and promote liver tissue regeneration, while some human studies suggest danshen injections may help treat liver fibrosis when used alongside other herbal remedies (51, 52, 53).

Ginkgo biloba is a popular herbal supplement that has been linked to improved liver health. For example, a rodent study showed that ginkgo biloba injections reduced liver fibrosis and enhanced liver function (54).

Although ginkgo biloba has been associated with mild adverse side effects, it hasnt been linked to liver injury specifically (55).

Astragalus is an edible herb commonly used in traditional Chinese medicine. Its loaded with medicinal compounds, including saponins, isoflavonoids, and polysaccharides, which have powerful therapeutic properties (56).

Its generally considered safe and hasnt been associated with liver injury. However, it can interact with certain medications (57).

Rodent studies indicate that astragalus may help protect against fibrosis and high fat diet-induced fatty liver when used alone or in combination with other herbs (58, 59, 60).

Danshen, ginkgo biloba, and astragalus have all been associated with improved liver health in some animal and human studies. However, more research is needed.

Although some herbal treatments may help treat or prevent liver conditions, its critical for anyone interested in using herbal remedies for liver health to speak with a qualified healthcare provider first.

This is because many herbal treatments have been shown to be toxic to the liver and may be dangerous to take, especially for those with liver diseases or other medical conditions (61).

In fact, herbal medicines have been associated with liver damage and even death. Both singular herbs and herbal mixtures have the potential to cause serious damage to your liver (62).

Whats more, herbal supplements can be contaminated with heavy metals, pesticides, pharmaceuticals, and bacteria that can harm your liver (63).

Additionally, many herbs can interact with common medications, which can lead to liver injury and even death (63).

Even though certain herbs may be safe for you to use, many others arent, so you should always check with your healthcare provider before taking any herbal supplement.

Because many herbs can cause liver damage and interact with common medications, you should always check with your healthcare provider before taking any herbal supplement, especially if you have a condition that affects the liver.

Certain herbs have been associated with improved liver health, making them a popular natural remedy choice for those with liver conditions, as well as those who want to support their liver health.

Although some herbal supplements are considered safe and may even treat certain liver diseases, many others can harm liver health.

If you have questions about herbal therapies for liver disease or are interested in taking herbal supplements in hopes of supporting your liver health, always consult a knowledgeable healthcare provider for advice.

See the rest here:
The 10 Best Herbs for Liver Health: Benefits and Precautions - Healthline


Startups are racing to reproduce breast milk in the lab – MIT Technology Review

Saturday, December 19th, 2020

Biomilq was on the brink of shuttering when Strickland and Egger were promised $3.5 million in funding from a group of investors led by Breakthrough Energy Ventures, which Bill Gates had established to back technologies that could reduce carbon emissions. Upending the formula industry held the promise of doing just that. As the spring of 2020 gave way to summer, the money arrived in Biomilqs bank account.

Biomilq is not the only company aiming to make a new kind of baby formula. Using a broadly similar approach, TurtleTree Labs in Singapore eventually hopes to replace all milk currently on the market, according to cofounder Max Rye. In addition to other projects, the company is working to create fortifiers that can be added to formula to duplicate the properties of breast milk. Some formulas are already fortified with proteins and carbohydrates derived synthetically or from cows milk. Another cofounder, Fengru Lin, explains that, in contrast to Biomilq, TurtleTree plans to work with the formula industry and hopes to get its products to market in 2021.

Meanwhile, Helaina, a company based in New York, will emulate breast milk through fermentation. Laura Katz, the companys founder, plans to use microbes to synthesize the milks constituent compoundsproteins, carbohydrates, and fatsand then recombine them into a nutritious liquid. Since similar processes have already won approval from the US Food and Drug Administration for products like Impossible Burgers, which are made from fermented soy protein, she hopes to face fewer regulatory hurdles than her competitors. Like Strickland and Egger, she is motivated by indignation at the lack of options for new parents.

I think the best thing we can do is support women to breastfeed, Katz says. But if thats impossible, mothers deserve something better than current infant formula. She adds, I see all this innovation happening in cell-based meat production for people who just want to eat a burger, but the products that we feed babies have stayed static over the past 20, 30 years.

None of these propositions will be scientifically simple, in part because relatively little is known about breast milk. Most studies of human mammary epithelial cells tend to focus on their role in breast cancer rather than milk production.

As for the milk itself, its a rich and bewildering stew of thousands of chemicals. We know nutritionally about the proteins, the carbohydrates, and the fat in there. We know about some particular bioactive molecules in there, like oligosaccharides [complex sugars that feed healthy bacteria in a babys gut], IgA [the main antibody found in breast milk], bile-salt-stimulated lipase [an enzyme that aids in the digestion of fats]these things that people always bring up as being good in breast milk, says Tarah Colaizy, the research director of the Human Milk Banking Association of North America, who also teaches at the University of Iowa. But, she notes, breast milk also contains short strands of RNA, whose presence was only discovered in 2010, and whose role in infant development is not yet well understood.

Go here to read the rest:
Startups are racing to reproduce breast milk in the lab - MIT Technology Review


The facts about the danger of melanoma – The Hudson Reporter

Saturday, December 19th, 2020

Dr. Faye Yin

Dr. Faye Yin

Melanoma is a serious and life-threatening form of cancer that begins in the skin but can spread rapidly if not treated early. We sat down with board-certified oncologist Dr. Faye Yin, an oncologist at Jersey City Medical Center, to learn more about this disease, its causes and risk factors, and why its important to protect yourself from excessive sun exposure even during the cold winter months.

What are the main risk factors for developing melanoma?

Ultraviolet, or UV, light exposure is the major risk factor. Melanoma is associated with both UVB rays, which are present in sunlight, and UVA rays, which are generated by tanning beds. Other risk factors include the presence of moles on the skin. Most are benign, but those with excessive moles should consult a dermatologist, especially if they observe any changes. Often, a mole will be removed as a precautionary measure. Age is also a risk factor; the older the person, the higher the risk. People with fair skin, freckles, and lighter hair are also more susceptible, which is why melanoma is more common in white and light-skinned people. Other risk factors include family history and the presence of a weakened immune system. Those with xeroderma pigmentosum, or XP, a rare genetic disorder, are particularly at risk because the condition affects the ability of skin cells to repair themselves after UV light exposure.

What should people do if they have any of these risk factors?

As with most risk factors impacting health, there are things you can change, and things you cannot. You cant change your skin color or family history, and you cant avoid getting older. But you can limit your exposure to UV rays. A popular catchphrase that I tell my patients, which has been promoted by the American Cancer Society, is Slip, Slop, Slap, and Wrap. Slip on a shirt, slop on some sunscreen, slap on a hat, and wrap on some sunglasses. I also recommend that people avoid using tanning beds and sun lamps. Teaching children about sun safety is especially important, because they tend to spend more time outdoors and can burn more easily. It is also important for people with risk factors to pay closer attention to their skin. Keep an eye out for abnormal moles or other skin features that appear to be unusual or changing over time, and consult a dermatologist if necessary.

Can sunlight still be dangerous during winter?

Yes whether youre skiing or just going for a walk, it is great to enjoy the sun and being outdoors in the winter, but its just as important to protect yourself from excess sun exposure in winter as it is in summer. Harmful ultraviolet rays are present year-round. They can even filter through dark cloud coverage to reach your skin, increasing your risk of melanoma. Some people may experience a bad sunburn on a winter vacation, especially if they ski in high altitudes, because UV rays are usually more intense in higher regions with a thinner atmosphere. When youre outside, any uncovered areas of your body are exposed to UV rays. So, its important to wear sunscreen even in the winter months.

Is smoking a risk factor for developing melanoma, and if so, is it mostly if youre currently smoking (for instance, what if you smoked for years and stopped?)

As an oncologist, every day I tell my patients: dont smoke! Smoking is a contributing factor for many cancers, and I believe that it also affects overall skin health; I can often look at someones skin and tell whether they smoke. That having been said, we dont have evidence that smoking directly contributes to melanoma. But I always encourage patients not to smoke to stay healthy and minimize their cancer risk.

Why does having a weakened immune system count as a risk factor for melanoma?

Having a weakened immune system increases the risk of melanoma and other cancers. I have worked with many patients whose immune systems have been compromised, either by illness or in some cases due to medical treatment for other conditions. For example, immunosuppressive drugs are used after stem cell and organ transplants, to prevent the body from rejecting the transplant. Certain diseases also compromise the immune system, such as HIV. A weakened immune system increases cancer risk for two reasons. First, because the body has less ability to detect and destroy cancer cells. And secondly, because the body is more susceptible to infections that may lead to cancer.

Is gender a risk factor? If so, do we know why?

In the United States, men typically have a higher rate of melanoma than women, though this varies by age. Before age 50, the risk is higher for women, and after age 50, the risk is higher in men. We believe that this discrepancy relates to the fact that men are likely to spend more time in the sun over the course of their lifetimes. I also think that women are more likely to wear sunscreen than men, so this may play a role. In addition, men tend to have thicker skin with less fat beneath it and more collagen, and some research shows that this can make the skin more susceptible to sunlight damage. Also, some studies have shown that estrogen, which is more prevalent in women, can increase resistance to melanoma.

Are older people at higher risk for melanoma?

The risk of melanoma increases as you age. The average age for a melanoma diagnosis is age 65. But melanoma is not uncommon even among those younger than age 30. In fact, it is one of the most common cancers in young adults, especially young women. Melanoma is also more common in younger people whose families have a history of melanoma.

How does having a family history of having melanoma impact someone?

Family history is definitely a melanoma risk factor; the risk is higher among those who have one or more first-degree relatives who have had melanoma. About 10 percent of people diagnosed with melanoma have a family history. Families tend to have shared lifestyle habits, such as more frequent sun exposure, and in addition they typically have similar skin types and share certain genetic characteristics. You cant change your skin color or your genes, but you can change some factors. If you know that you are higher risk, and have a family history, pay close attention to your skin. Avoid excessive sunlight and tanning beds, and consult a dermatologist if you have concerns.

Why is UV light exposure a risk factor?

Numerous studies have shown that sun and UV light exposure is a major melanoma risk factor, especially for children and teens. Research shows that early sun exposure can damage the DNA in skin cells. Melanocytes are the cells that produce melanin, which gives skin its pigmentation, and damaging these cells can start the path to melanoma. Melanoma commonly occurs on the thighs of women, and on the trunks of men, as well as on arms and faces, which are the areas that most often receive chronic sun exposure in young people. In addition to limiting UV light exposure, people should also examine their own skin at least monthly, especially if there are high risk factors. If you see something unusual, such as a large mole or a spot youre not sure about, I will often encourage patients to take a photograph of it. You might not notice small changes over time because you get accustomed to them. But if you take a picture of a spot on your skin and compare it a month or a few months later, and you see a change, you should see a dermatologist.

See more here:
The facts about the danger of melanoma - The Hudson Reporter


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