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Nvidia, Harvard researchers use AI to find active areas in cell DNA – ZDNet

By daniellenierenberg

Researchers from Nvidia and Harvard are publishing research this week on a new way they've applied deep learning to epigenomics -- the study of modifications on the genetic material of a cell.

Using a neural network originally developed for computer vision, the researchers have developed a deep learning toolkit that can help scientists study rare cell types -- and possibly identify mutations that make people more vulnerable to diseases.

The new deep learning toolkit, called AtacWorks, "allows us to study how diseases and genomic variation influence very specific types of cells of the human body," Nvidia researcher Avantika Lal, lead author on the paper, told reporters last week. "And this will enable previously impossible biological discovery, and we hope would also contribute to the discovery of new drug targets."

AtacWorks, featured in Nature Communications, works with ATAC-seq -- a popular method for finding the parts of the human genome that are accessible in cells.

Just about every cell in your body carries a copy of your genome sequence -- a sequence of your DNA about 3 billion bases long. However, only certain parts of the genome sequence are accessible to certain cells. Every cell type -- whether it's liver, blood or skin cells -- can only access the regions of DNA they need for their respective function.

"That allows us to understand what makes every type of cell different from each other, or how every type of cell is affected in disease, or in other biological changes," Lal said.

ATAC-seq finds those accessible parts by producing a signal for every base in the genome. Peaks in the signal denote accessible regions of DNA. This method typically requires tens of thousands of certain kinds of cells to get a clean signal. This makes it challenging to study rare cell types, like the stem cells that produce blood cells and platelets.

However, by applying AtacWorks to ATAC-seq data, the researchers found they could rely on just tens of cells, rather than tens of thousands. In the research described in their new paper, the Nvidia and Harvard scientists applied AtacWorks to a dataset of stem cells that produce red and white blood cells. They used a sample set of just 50 cells to identify distinct regions of DNA associated with cells that develop into white blood cells, as well as separate sequences that correlate with red blood cells.

AtacWorks is a PyTorch-based convolutional neural network that was trained on labeled pairs of matching ATAC-seq datasets -- one high quality and one "noisy." The model learned to predict an accurate, high-quality version of a dataset and identify peaks in the signal.

Running on Nvidia Tensor Core GPUs, the model took under 30 minutes for inference on a whole genome, a process that normally takes 15 hours on a system with 32 CPU cores.

Lal noted that the researchers were able to train the model on any type of cell and then apply it to any different type.

"That's a really wonderful thing because it means that we can train models using whatever data we have available and then apply it to entirely new biological samples," she said.

The model could help deliver insights into a range of diseases, including cardiovascular disease, Alzheimer's disease, diabetes or neurological disorders. It's available on the NGC Software Hub, Nvidia's hub of GPU-optimized software, where any researcher can access it.

"We are hoping that once our paper comes out, other scientists working with different diseases would also pick up this technique and be interested in using it," Lal said. "And we are excited to see what new research and new developments that can enable."

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Transform Your Skin Into That Of A Greek Goddess (on A Budget) – GreekCityTimes.com

By daniellenierenberg

Weve all heard of French beauty products and how amazing they are.

But what if I told you that certain Greek beauty products were just as good (if not better) than the high flying ones?

Think La Mere or LaPrairie. These cult favourite beauty brands cost will set you back several hundred dollars.

You dont have to spend a fortune to look good. I always say you can have great skin even if youre on a budget, no matter how old you are.

Greek women have long used natural products from the earth, plants and animals to beautify themselves and look at how immaculate their skin and beauty was.

Heck, one Greek woman launched a thousand ships! (You know her name)

These hand-picked items for skin-care are loaded with Greek olive oil, wine, figsand donkey milk. (Tried and tested by me, GCT Lifestyle Writer Despina Karp)

$40.00

This nourishing cream-to-foam cleanser is good enough to eat and leaves the skin feeling clean, not stripped of everything. Its been formulated with incredible natural Greek Yoghurt and is gentle enough to be used on even the most sensitive of skin types, including psoriasis and acne-prone skin. It is super gentle, yet very effective at thoroughly cleaning the skin and removing daily impurities and makeup. After trying this cleanser, my skin was left feeling as smooth and supple as a babies bottom.

The key ingredients in this beauty are Greek yoghurt which delivers an almost instant dose of pre and probiotics to nourish the skin and kill surface bacteria.

Amaranth seed extract and honeysuckle: These two unique ingredients provide a soothing and calming comfort to the skin.

I always recommend using this twice per day, morning and night for the best results.

Buy here.

$110 (approximately)

Well, there are serums, and then theres this serum! A little pricey, but wait till I explain what this jar of ageless beauty contains.

This is one of the best antioxidant serums Ive tried and for good reason. For starters, its ingredients make it a high-end luxury antioxidant serum, but without the super costly price tag to match.

The heavenly golden fluid is infused with the famous antioxidant saffron, once known as the most expensive spice in the world.

The crimson threads of magic come from dried crocus flowers, grown in the Greek town ofKozani. It takes approximately 70,000 flowers to make one pound of saffron! Did I mention that they bloom only once a year? Plus they need to be picked exactly ONE day after theyve bloomed! Talk about time-sensitive.

The protecting power of the saffron, combined with the copper, peptides, and amino acids combine to make an incredibly effective collagen and elastin boost.

With consistent use, this serum will leave the skin feeling bright and glowing. I often use this serum on my mature-skinned clients before moisturiser and I massage it into the skin until it has been completely absorbed.

I highly recommend paying a little extra and indulging in this serum, it works wonders for mature skin.

Buy here.

$36.99

Here comes the donkeys milk! Dont worry I wont make you drink it but it is a staple ingredient in this product.

It doesnt sound very luxurious or fancy, but Cleopatra allegedly bathed in donkeys milk for softer skin.

In 2013, a study by researchers at the University of Camerino discovered that donkeys milk is very close in structure and composition to human breast milk (Maybe thats why babies skin is so soft!).

EvenPope Francis even drank it as a babyin his native Argentina.

Are you convinced yet?

This cream provides antioxidant, antimicrobial, and anti-inflammatory moisturisation.

The best part of this incredible product are the key ingredients (which according to their website are 97.1% natural ingredients): donkey milk (obviously), aloe vera juice, St. Johns wort, Centella, carob, cotton stem cells, moringa peptides, red seaweed and cross-linked hyaluronic acid (a superacid for the skin).

The donkey milk and Cretan organic olive oil are rich in omega fatty acids, which the skin craves.

It also contains vitamins and trace elements, which deeply nourish and strengthen the skins natural defence against pollution and UVA/UVB light.

The St. Johns wort and Centella extract calm redness and skin irritations.

I highly recommend this daily moisturiser (as donkeys milk is non-comedogenic) for any skin type, except very congested and cystic acne skin types.

Its important to always apply SPF 30+ to protect your skin from the harmful rays of the sun (especially true if you live in Australia).

Buy here at aphroditeusa.com.

So, Ive give you an entire skin routine worthy of Aphrodite herself.

These 3 products can be used one after the other as a bedtime skin routine for mature and dry skin types.

If you are using these products in the morning, be sure to apply an SPF 30+ after all your products to protect your skin.

You dont have to use a large amount of the products too, a little goes a long way with these beauties.

My donkeys milk day cream lasted me 3 months! So it turns out to be a very economical investment.

Its worth investing in your skin as its the largest organ in your body and the amount of chemicals we are exposed to these days can leave our skin in terrible shape if not looked after.

Our skin is also the first thing people look at, healthy and hydrated skin can completely alter your appearance if youve had dehydrated skin for a while.

So, what are you waiting for? Lets get radiant, and prepare to launch a thousand ships! (More like a thousand compliments)

Note: always ask a Dermatologists advice when in doubt, these products arent suitable for all skin types or skin conditions.

Thesauri Greek Caviar: available in Australia for the very first time

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How New Yorkers Are Battling the Zoom Effect: 6 Cosmetic Treatments That Are on the Rise – PureWow

By daniellenierenberg

With more folks spending time inside, working from home and literally under wraps (i.e., masks), now is the time for many for some sneaky beauty procedures that would normally require taking time off work, hiding from your social circle and going dark on social media. But now, all your redness, swelling, and post-op symptoms can go undetectedsans burning your vacation days.

In fact, derms and plastic surgeons across the city are seeing skyrocketing increases in invasive and non-invasive cosmetic treatments since the start of the pandemic, thanks to the Zoom boom or Zoom effect.

What the heck is the Zoom effect, you ask? Basically, Zoom and other digital web conferencing platforms have led people to seek out ways to lift and tighten their faces after seeing themselves so often screens. (Note: If your computer camera is positioned lower and pointing up, it actually makes things look worse than they areinvest in a laptop stand, and you wont regret it.)

Laura Altman, a physician assistant at Tribeca Medspa, explains that since her clients are no longer spending money on travel, dinners out or fancy clothing, this disposable income allows them to spend on beauty proceduresnot to mention the added benefit of flexible downtime while WFH. Our clients are spending more per visit and we continue to see about the same number of new clients every month along with current clients who visit us for more treatments, says Altman.

Here are some of the most popular beauty treatments New Yorkers have been taking advantage of while WFH, plus some things to consider in case youre curious about giving them a go yourself.

RELATED: 9 Beauty Trends That Will Be Huge in 2021

In fact, requests for jawline filler are up as much as 2,133 percent at BeautyFix Medspa, a clinic with locations in Flatiron and on the Upper East Side. This non-surgical facial contouring enhances the jawline to give the lower face and neck a more defined and slimmer appearance by helping create a V-shape structure, BeautyFix CEO Mark Greenspan tells us. Jawline fillers are usually completed with one 30-minute treatment with no recovery time necessary.

Dr. Alexander Blinksi of NYCs Plump cosmetics and injectables bar has seen about a 25 percent increase in patients with general concerns about facial structure, aging and wrinkles over the last 12 months.

Consultations related to Botox have been requested in all the major treatment areas. The most common areas for Botox treatment remain horizontal forehead lines, 11 lines, and crows feet. We have seen a slightly greater number of patients consulted for TMJ Botox (TMJ is a medical jaw issue from grinding the teeth at night) likely due to increases in stress, and beauty trends of giving the face more angularity and a higher cheekbone, Dr. Blinski tells us.

Intrigued? Side effects from injectables include minor swelling and bruising. (Psst: Read up on our beginners guide to botox here.)

CHAKRAPONG WORATHAT/EYEEM/GETTY IMAGES

In fact, reports show that more women in the US are using facial skincare products today compared to one year ago, and that lifestyle changes including the effects of COVID-19 have in many ways altered skin care routines in a positive way, says master esthetician and CEO of Repechage, Lydia Sarfati.

At-home peels feature professional-grade ingredients and step-by-step instructions to boost a dull complexion and address specific skin concerns such as aging, discoloration and blemishes without having to go in to see an esthetician or dermatologist. These peels use low percent acids (like this one from PCA SKIN) and require no downtime for healing.

According to new survey data by healthcare marketplace RealSelf, 36 percent of respondents noted theyve seen an increase in the number of pimples since the pandemic started. And those who have had an increase in breakouts noted their chin was the most likely spot, followed by the jawline and cheeks.

Some acne breakouts are a result of wearing masks and the occlusion it causes (dubbed maskne), and other forms of acne are a result of hormonal stress or stress in general. Patients who have had acne scars are using this period to have laser treatments to finally address the treatment of their acne scars, now that they have the downtime, NYC-based cosmetic dermatologist Dr. Michele Green tells us.

One such treatment is eMatrix, a laser that works by stimulating collagen formation and healthy cells. eMatrix reduces the appearance of acne scars, enlarged pores and mild to moderate wrinkles in addition brightening the skin and improving skin texture. Downtime is approximately 48 hours with mild roughness remaining for three to five days. Results continue over three to five months after the final treatment and can be maintained annually (Dr. Green suggests patients receive three to five treatments).

PhotoAlto/Frederic Cirou/Getty Images

There are multiple ways to treat hair loss, but Dr. Greens preferred method is PRP (Platelet Rich Plasma), a treatment that uses your own blood to promote healing and stimulate the hair follicle to begin a new growth cycle while making hair stronger and thicker. Side effects of PRP may include some tenderness on the scalp after injections and a slight headache or pressure in the treated area. Depending on the severity, Dr. Green recommends four consecutive monthly treatments of PRP injections followed by maintenance treatments every four to six months.

Places like Tribeca Medspa have seen a 50 percent increase in microneedling with stem cells compared to last year. This treatment is designed to reduce the appearance of wrinkles and skin imperfections, with stem cells added to stimulate the regeneration and healing of the skin.

Typically, patients would experience mild redness and swelling for a day followed by possible mild dryness for a few days, at most. Bruising can happen but tends to heal quickly as it is generally fairly superficial, says Tribeca Medspa clinical lead medical aesthetician Holly Montgomery.

RELATED: We Ask a Derm: What Is the Best Derma Roller to Use at Home?

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Evolution: Lab-Grown ‘Mini Brains’ Suggest One Mutation Might Have Rewired the Human Mind – Singularity Hub

By daniellenierenberg

How we humans became what we are today is a question that scientists have been trying to answer for a long time. How did we evolve such advanced cognitive abilities, giving rise to complex language, poetry, and rocket science? In what way is the modern human brain different from those of our closest evolutionary relatives, such as Neanderthals and Denisovans?

By reintroducing ancient genes from such extinct species into human mini brainsclusters of stem cells grown in a lab that organize themselves into tiny versions of human brainsscientists have started to find new clues.

Most of what we know about human evolution comes from the study of ancient fossils and bones. We know that Neanderthals and Denisovans diverged from humans around 500,000-600,000 years ago, and that the last Neanderthals didnt disappear from Europe until about 40,000 years ago.

Research has also shown that humans and Neanderthals interbred, and that Neanderthals were a lot more sophisticated than previously thought.

From studying the size and shape of fossilized skulls, we also know that brains from archaic humans were roughly the same size as modern human skulls, if not bigger, and appear to be different shapes. However, although such variations might be correlated with different cognitive abilities and functions, the fossils cannot alone explain how the shapes affect function. Luckily, recent technological advances have provided a new path to understanding how we differ from our extinct relatives.

Homo Sapiens versus Neanderthals. Source: WikipediaCC BY-SA

Sequencing of ancient DNA has allowed scientists to compare genes of Neanderthals and Denisovans with those of modern humans. This has helped identify differences and similarities, revealing that we share most of our DNA with Neanderthals and Denisovans.

Still, in specific regions, there are gene variants exclusively carried by modern humans. These human-specific DNA regions may be responsible for traits that separate our species from our extinct relatives. By understanding how these genes work, we can therefore learn about the traits that are unique to modern humans.

Studies comparing archaic and modern DNA sequences have pinpointed differences in genes important for the function, behavior, and development of the brainin particular genes involved in cell division and synapses (which transmit electric nerve impulses between cells). These have suggested the human brain matures more slowly than the Neanderthal one did.

Specifically, the development of the orbitofrontal cortex in infants, which is thought to be involved in higher-order cognition like decision-making, might have changed significantly but subtly since the split from Neanderthals. Humans also reach sexual maturity later than their ancestors did, which can help explain why we live longer.

It has long been unclear which evolutionary changes have been the most important. A team of scientists led by Alysson Muotri at the University of California, San Diego, recently published a study in Science that shed some light on this question.

They did this by growing mini brainswhich are known scientifically as organoidsfrom stem cells derived from skin. Brain organoids arent conscious in the way we arethey are very simple and do not reach sizes larger than around five or six millimeters, due to a lack of blood supply. But they can emit brainwaves and grow relatively complex neural networks that respond to light.

The team inserted an extinct version of a gene involved in brain development in the organoids using the Nobel-prize winning CRISPR-Cas9 technology, often described as genetic scissors, which allows precise editing and manipulation of genes.

Human brain organoid. Image Credit: NIH/Flickr

We know that the old version of the gene was present in Neanderthals and Denisovans, whereas a mutation later changed the gene into the current version that modern humans carry.

The engineered organoids displayed several differences. They expanded more slowly than the human organoids and had altered formation of connections between neurons. They were also smaller and had rough, complex surfaces compared to the smooth and spherical modern human organoids.

The study identified 61 genes that are different between modern and archaic humans. One of these genes is NOVA1, which has an essential role in regulating other genes activity during early brain development. It also plays a role in the formation of synapses.

Altered activity of NOVA1 has previously been found to cause neurological disorders such as microcephaly (leading to a small head), seizures, severe developmental delay, and a genetic disorder called familial dysautonomia, suggesting it is important for normal human brain function. The version that modern humans carry has a change in one single letter of the code. This change causes the genes product, the NOVA1 protein, to have a different composition and possibly a different activity.

When analyzing the organoids, scientists found that the archaic NOVA1 gene changed the activity of 277 other genesmany of them are involved in creating synapses and connections between brain cells. As a result, the mini brains had a different network of cells to those of a modern human.

That means that the mutation in NOVA1 caused essential changes in our brains. A change in a single letter of the DNA code possibly sparking a new level of brain function in modern humans. What we dont know is how exactly this happened.

The team has said they will follow up their fascinating finding by investigating the other 60 genes in more detail, to see what happens when you alter each one or a combination of several.

Its no doubt an intriguing area of research, with the organoids giving important insight into these ancient species brains. But we are only at the beginning. Manipulation of a single gene will not capture the true Neanderthal and Denisovan genetics. But it could still help scientists understand how some human-specific genes work.

This article is republished from The Conversation under a Creative Commons license. Read the original article.

Image Credit: Wikimedia Commons

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Tissue regeneration: Reserve or reverse? – Science Magazine

By daniellenierenberg

A cross section of mouse small intestine, showing intestinal crypts and villi, is visualized with immunofluorescence microscopy (nuclei in red, and F-actin, which marks the cytoskeleton, in blue). Intestinal stem cells reside at the base of crypts, where they maintain cell turnover.

Tissues with high intrinsic turnover, such as the skin and intestinal lining, rely on resident stem cells, which generate all native cell types. Intestinal stem cells (ISCs) are highly sensitive to damage, although they recover quickly. It is unclear whether this recovery (i.e., regeneration) occurs from less sensitive pools of reserve stem cells (1) or whether ISC progeny undergo reverse differentiation into stem cells (2). Recent studies in diverse organs highlight that dedifferentiation of specified cell types is a pervasive and dominant means for tissue regeneration. The findings have broad implications because all tissues experience some cell attrition over a lifetime, and knowing how tissues replenish those losses may help in preventing or treating organ failure. Moreover, it remains unclear whether incomplete differentiation, a common feature of cancer, reflects normal tissue plasticity, and it is unclear whether stem cells that arise by dedifferentiation may spawn cancers.

ISCs expressing leucine-rich repeatcontaining G proteincoupled receptor 5 (Lgr5) lie at the bottom of small bowel crypts (3). In the course of homeostatic tissue turnover, their immediate progeny adopt alternative enterocyte or secretory fates, then fill the crypts with replicating progenitors that migrate away from ISCs. Cell division ceases at the crypt tops, where postmitotic cells begin a 3- to 5-day journey along intestinal villi. When ISCs sustain irreparable damage, some source in the crypt must regenerate new ISCs. Other adult epitheliasuch as airways, prostate, and liverare organized differently from the intestine and from each other (see the figure). These epithelia also restore cells lost by damage or attrition, even though at rest they turn over at least a hundred times more slowly than the intestinal lining.

Airway epithelial structure varies from trachea to small bronchioles, and distinct progenitors in different segments produce assorted secretory and ciliated cell types. In the lining of human and mouse upper airways, flat basal cells lie beneath a layer of columnar differentiated cells and adjacent to submucosal myoepithelial glands. Stem cell activity in normal tissue turnover maps to a subpopulation of keratin 5 (Krt5)expressing basal cells (4). The trachea and bronchi are vulnerable to diverse injuries, including targeted destruction of Krt5+ stem cells and pervasive mucosal damage from noxious inhalants or viruses.

Adult human and mouse prostate glands also contain columnar luminal and flat KRT5+ basal cells. Distinct unipotent progenitors maintain both populations, and castration induces massive luminal cell loss. Androgen reexposure restores prostate mass within weeks, which implies the presence of castration-resistant progenitors. However, an unequivocal stem cell pool has not been identified. The liver also has notable regenerative abilities after chemical or surgical injury. The emerging consensus is that this organ lacks a dedicated stem cell compartment and recovers from damage through dedifferentiation of mature hepatocytes and biliary cells (5, 6).

Stem cell activity in vivo is demonstrated most persuasively by introducing into a tissue a permanent color or fluorescent label whose expression depends on Cre recombinasemediated excision of a STOP cassette. When Cre activity is restricted to stem cells, all the progeny of those cells exclusively carry the label. ISCs and tracheal stem cells were thus identified because targeted Cre activity in LGR5+ or KRT5+ mouse cells labeled the respective full lineages (3, 4). Investigation of tissue regeneration requires ablation of a stem cell compartment, followed by tracking of the restored ability to produce sufficient numbers of all native stem cell progeny. The canon of tissue repair rests heavily on such lineage-tracing experiments, but one limitation is that Cre recombinase is not often confined to a single defined cell type. This challenge lies at the heart of competing models for tissue recovery after lethal cell injuries.

Dividing cells take up labels such as [3H]thymidine or fluorescent histone 2B and shed these labels as they replicate further or their daughters die. In the intestine, however, rare cells located near the fourth tier from the crypt base retain [3H]thymidine for weeks. Given once-popular ideas that stem cells must be few in number and retain one immortal DNA strand when they replicate, +4 label-retaining cells (LRCs) were described as ISCs. In support of that idea, lineage tracing from Bmi1, a locus thought to be restricted to nonreplicating +4 LRCs, elicited an ISC-like response in vivo (7).

Physiologic cell turnover and recovery from injury occur from different cellular sources in diverse epithelia (intestine, upper airway, and prostate gland). Homeostatic turnover is driven by the stem cell pool, and tissue restoration from injury occurs through transient expansion and dedifferentiation of specified mature cells.

To reconcile the evidence for ISC properties in both LGR5+ crypt base columnar cells (CBCs) and +4 LRCs, researchers postulated that abundant CBCs serve as frontline ISCs, whereas the smaller +4 LRC population contains dedicated reserves. Indeed, intestinal turnover is unperturbed when LGR5+ CBCs are ablated because other crypt cells' progeny continue to repopulate villi and an LGR5+ ISC compartment is soon restored (1). Multiple candidate markers of +4 LRCs that regenerate ISCs after injury have been proposed (8). Although these cells are too few to explain the typical scale and speed of ISC restoration, the prospect of two stem cell pools carried the additional allure of a sound adaptive strategy in a tissue that requires continuous self-renewal.

ISC differentiation is, however, not strictly unidirectional. Cre expression in absorptive or secretory cell types tags those cells selectively, but upon ablation of LGR5+ CBCs, the label appears throughout (9). These observations imply that differentiated daughter cells have reverted into ISCs. Moreover, Bmi1 expression was found to mark differentiated crypt endocrine cells (10), and putative +4 markers are expressed in many crypt cells including LGR5+ CBCs. Accordingly, when Cre is expressed from these loci, the traced lineage might simply reflect CBC activity in resting animals and reverse differentiation of crypt cells after ISC ablation. But is dedifferentiation a rare and physiologically inconsequential event or the predominant mode of stem cell recovery? Dedifferentiation may obviate the need to invoke a dedicated reserve population, or it is possible that ISC recovery may reflect both dedifferentiation and contributions from a reserve stem cell population.

To investigate these issues, researchers activated a fluorescent label in LGR5+ CBCs and waited for this label to pass into progeny cells before ablating CBCs (11). Thus, only the CBCs that recover by dedifferentiation should be labeled, and any cells arising from reserve ISCs should not. Nearly every restored crypt and CBC was fluorescent, with substantial contributions from both enterocytes and secretory cells (11). Cells captured early in the restorative process coexpressed mature-cell and ISC genes, which is compatible with recovery by dedifferentiation. Another study found that damaged ISCs are reconstituted wholly by the progeny of LGR5+ CBCs (8). Thus, dedifferentiation would seem to be the principal mode of ISC regeneration, and prior conclusions about +4 ISCs likely reflect unselective Cre expression.

Different tissues might deploy distinct regenerative strategies, and recent studies in mouse airway, prostate, intestinal, and liver epithelia provide insightful lessons. After ablation of KRT5+ airway stem cells, specified secretory and club cell precursors were found to undergo clonal multilineage expansion and accounted for up to 10% of restored KRT5+ cells in vivo (12). Chemical or viral damage was subsequently reported to induce migration and dedifferentiation of submucosal gland myoepithelial cells into the basal layer to reconstitute the surface lining, including KRT5+ stem cells (13). Thus, dedifferentiation into native stem cells occurs upon injury to both airway and intestinal linings in mice.

Single-cell RNA sequencing (scRNA-seq) analysis of mouse prostate glands recently revealed distinct gene expression profiles in 3% of luminal cells, which are more clonogenic than others, express putative stem cell markers, and hence qualify as a pool enriched for native stem-like cells (14). After androgen reexposure following castration, however, the scale and distribution of cell replication and the location of restored clones were incompatible with an origin wholly within that small pool. Rather, the principal source of gland reconstitution in vivo, including new KRT5+ basal cells, was the dominant population of differentiated luminal cells (14). These observations parallel those in the liver, where recovery of organ mass after tissue injury occurs by renewed proliferation of mature resting hepatocytes (5), abetted by expansion of bile duct cells that transdifferentiate into hepatocytes (6). Cell plasticity is thus widespread, whether tissues have or lack native stem cell compartments.

Reverse differentiation in the intestine, airways, and prostate gland was generally observed after near-total elimination of resident stem or luminal cells, an extreme and artificial condition. However, several observations suggest that this dedifferentiation reflects a physiologic process designed to maintain a proper cell census. Contact with a single KRT5+ airway stem cell prevents secretory and club cell dedifferentiation in vitro (12), and tracheal submucosal glands exhibit limited stem cell activity even in the absence of injury (13). Live imaging of intestinal crypts reveals continuous and stochastic exit from and reentry into the ISC compartment (15), implying that barriers for differentiation or dedifferentiation are inherently low. However, the primary purpose of dedifferentiating airway, intestinal, liver, and prostate cells is not to enable tissue recovery. Therefore, they should be regarded as facultative stem cells; that is, they have other physiologic functions and realize a latent stem cell capacity only under duress.

This distinction from reserve stem cells is not merely semantic. Emphasis in regenerative therapy research belongs on any cell population with restorative potential; in vivo findings now direct attention away from putative reserve cells and toward dedifferentiation as a common means for tissue recovery. The absence of dedicated reserves and the inherent cellular ability to toggle between stem and differentiated states also inform cancer biology. Because mutations realize oncogenic potential only in longlived cells, both frontline and reserve stem cells represent candidate sources of cancer, in contrast to differentiated cells, which are generally short-lived. However, oncogenic mutations that arise in differentiated cells could become fixed upon dedifferentiation, thus enabling tumor development.

Notably, stem cell properties and interconversion with their progeny are not stereotypic. ISCs divide daily into two identical daughters, whereas hematopoietic stem cell replication is infrequent and asymmetric. Severe loss of blood stem cells does not elicit substantial dedifferentiation and is rescued only by adoptive stem cell transfer. Immature secretory precursors dedifferentiate more readily than terminally mature airway cells (12), whereas fully differentiated cells fuel liver and prostate regeneration. Cell plasticity in each case is determined by local signals. Unknown factors from KRT5+ tracheal stem cells, for example, suppress secretory cell dedifferentiation (12), and specific factors secreted from the prostate mesenchyme stimulate luminal cell dedifferentiation (14). The intestinal mesenchyme probably senses ISC attrition to trigger tissue recovery, but the spatial and molecular determinants remain unknown. Outstanding challenges are to identify the signaling pathways that ensure a stable cell census and to harness diverse regenerative responses to ameliorate acute tissue injuries or prevent organ failure. Knowing the cellular basis for stem cell recovery in different contexts brings us closer to those goals.

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Heres why natural ingredients and science-backed formulations are the perfect combination – Vogue India

By daniellenierenberg

Heres a fun fact about rosehip oil: it does not smell like roses. It does, however, heal. Known as the Himalayan musk rose, this wild flowering plant has only five petals, says Roshni Laura George, who discovered the elusive bloom during her honeymoon in Kashmir, as she was researching medicinal plants through the country in the remotest parts of the valley. Every May, the musk rose bushes burst into bloom, covering trees, tumbling over cliffs and blanketing the earth with their heady scent. The hip, a powerhouse of essential nutrients, is what is left once the petals fall. Thats where the oil is extracted from, explains George, who preserved this juice in Timekeeper, a vivid amber face oil that launched her skincare brand, Rasula. We do not bleach, colour or deodorise our rosehip oil as this would deplete its natural goodness. The oil is hardly oily, the red lingers for just a few seconds before your skin drinks it up, and its nutty smell is so distinct that you can only assume it came from the roses hip. George promised it would become my one-step skincare routine (followed by sunscreen in the day, of course) and my combination-dehydrated- acne-prone-moody skin might agree.

Rosehip oil can handle the fussiest skin types. Two reasons: vitamin F and beta carotene. Vitamin F is an essential fatty acid, rich in omega-6, which produces ceramide 1, a key part of a healthy skin barrier. Beta carotene is an antioxidant that gives the oil its rich orange hue. It can neutralise free radicals from the environment, protect against UVA damage, reduce oxidative stress, and enhance the appearance of skin. Essential fatty acids in the rosehip oil are absorbed by the skin to regenerate collagen and elastin fibres that keep the skin firm and youthful, explains George. In short, it helps your skin fight for itself.

George aimed to create category-defining natural skincare for photo-aged skin. Three years of research working closely with leading institutions like IIM Jammu and the Council of Scientific and Industrial Research in Bengaluru, led to Rasula, a clean beauty brand that comes without parabens, SLS, and artificial fragrance, among other nasties. Rasulas products are handcrafted and packed by hand in recyclable glassware, and its rosehip is hand-picked from the Himalayan Range by the local women of Kashmir. While common extraction practices include cold-pressing, George took a more expensive, environmentally friendly approach to ensure her oil was more concentrated, cleaner and superior, with a longer shelf life. We flush supercritical CO2 under high pressure through the seeds, which gently removes the oil, explains George. And if youre still not convinced, know this: rosehip oil is the most inclusive ingredient in skincare. Suitable for all skin types and age groups, including pregnant women and children, the oil helps eradicate a host of skin issuesscars, burns, fine lines, stretch marks, acne, dryness, sensitivity, sun damage, uneven skin tone, age spots, eczema and more. Most importantly, it is gender-neutral, says George.

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Trupure Organics Is First 50-Plus Brand Devoted to That Market’s Distinct Needs – PRNewswire

By daniellenierenberg

CLEVELAND, Feb. 19, 2021 /PRNewswire/ -- Paulette Kaplan noticed something different as she entered into her 50s. Her skin was now dryer, and looked older than just a couple years earlier. Looking at her cabinet full of products that were supposed to work, she thought, "Nothing really works well."

As a skincare advocate, she began to consider creating her own line exclusively for the needs of the 50-plus.

In an industry obsessed with youth, Paulette found there to be a tremendous lack of skincare products made for this market.

According to an AARP national survey, "Women over age 50 make a big investment of time and money on beauty and personal grooming products, spending a whopping $22 billion annually, yet they still think that the beauty industry ignores them as they age."

Paulette was determined and began her search and discovered that some ingredients could be damaging to how skin looks and cause inflammation that works against the skin's ability to heal.

She did not want to make more 'anti-aging' potions. Or use unhealthy ingredients but to offer a clean and nourishing age perfect skincare line that would strengthen mature skin.

Trupure Organics was born with the help of scientists, chemists, and multiple formulas. A100% natural plant-based line using stem cells, bio-retinol, extracts, peptides, oils and juices. Their TruPurity promise excludes ingredients like chemicals, fragrances, dyes, parabens, GMOs, and phthalates.

What are the key goals? Provide continuous moisture, soothe, firm, protect, lift, strengthen, plump, smooth, and nourish with specific delivery systems.

Paulette explains her 50-plus line, "The focus isn't to put yourself under a magnifying glass, but actually celebrate your age by focusing on healthier radiant skin. Because when skin is healthy, it naturally looks beautiful."

Retinol is a common ingredient in skincare products because of how well it can promote collagen production. Trupure Organics No More Crepe Neck and Dcolletage Cream ($65) uses a different approach through a plant-based bio-retinol. Itwon't cause peeling, irritation, itching, or make skin considerably more sensitive to sunlight like standard retinol.

This same kind of approach is used in formulating all their plant-based products for mature skin. Visit trupureorganics.com to view the full collection of serums and creams.

References

Women 50 and Older Feel Overlooked by the Beauty Industry

Contact:

Paulette Kaplan Founder and CEO, Trupure Organics216.702.0345[emailprotected]http://www.trupureorganics.com

SOURCE Trupure Organics

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The ultimate path to skin rejuvenation – Philstar.com

By daniellenierenberg

MANILA, Philippines Breach. Reanimate. Create. This is the mantra behind La Prairies Platinum Rare Haute Rejuvenation Protocol, a new anti-aging product that is the Swiss luxury skincare brands most groundbreaking innovation yet.

La Prairie sought to go beyond skin renewal, and for the first time, we will create new skin tissue, says Dr. Daniel Stangl, La Prairies director of innovation.

This ultimate path to rejuvenation has been designed to work in three steps: breach the skin barrier, reanimate cells, and create new skin tissue.

As the first step, and in analogy to (La Prairie founder) Dr. Paul Niehans cellular therapy, the formula temporarily softens the skin barrier in order to optimally deliver the active ingredients into the skin and enhance the full potential, Stangl says.

In the second step, Platinum Rare Haute Rejuvenation Protocol reanimates cells in all skin layers, specifically stem cells and differentiated cells, which make up the majority of skin cells.

To reanimate these cells, the formula of the serum contains an exclusive platinum multi-peptide combined with two essential growth factors and La Prairies exclusive Cellular Complex. These highly potent active ingredients reanimate stem cells to produce new cells and differentiated cells to synthesize a new extracellular matrix, including fibers of collagen and elastin, as well as the hyaluronic acid, Stangl continues.

Thirdly, as a result of breaching the skins barrier and reanimating cells, La Prairie creates new skin tissue. The creation of new skin tissue in all skin layers is the fundamental process of rejuvenation, Stangl says. It literally infuses the skin with youth, improving all signs of aging as never seen before.

The product is designed as a month-long protocol, consisting of three vials. One vial is used for 10 days, day and night. After this month-long phase of intense rejuvenation, the skin needs time to re-equilibrate, notes Stangl. We therefore recommend using it for one month, four times a year.

The unique packaging includes a mini pedestal on which you put the jewel-toned vial and twist it, releasing clouds of product that you then shake to mix into a fresh serum. It displays La Prairies merging of art and science at its finest, giving its clientele the most luxurious, magical experience.

La Prairies Platinum Rare Haute Rejuvenation Protocol will be on counter at Rustans The Beauty Source on Feb. 25.

Light and cooling: Kiehls Ultra Facial Oil-free Gel Cream

One of Kiehls hero products has always been its Ultra Facial moisturizer, which can hydrate even the driest of skins. In the tropical Philippines, however, that formula might be too rich, especially for people with oily, acne-prone skin.

So now Kiehls has formulated Ultra Facial as an oil-free gel cream, a lightweight, cooling moisturizer thats perfect for our humid weather, especially in the coming summer months. Glacial glycoprotein Antarcticine hydrates skin for 24 hours, while Micronized Amino Acid helps regulate excess oil for shine control, so its suited to those with oily and combination skin who have a tendency to break out with maskne, like I do. I also love that its fragrance-, alcohol- and paraben-free.

He hearts her: Nars Claudette Collection was inspired by Francois Nars mother and first muse.

Nars limited-edition Claudette Collection is Francois Nars tribute to his mother and very first muse, Claudette, and the bohemian spirit of Paris Rive Gauche (Left Bank) in the 70s. The prints on the packaging were inspired by the prints on the dresses his mom used to wear.

Claudettes eyeshadow palette, St. Germain Des Prs, is filled with six warm, neutral shades in matte, satin and shimmer finishes. You cant go wrong with the neutrals in this palette, which are so subtle and wearable youll always end up with an elegant look, no matter which color or combination you use.

Nars cult-favorite satin Audacious lipstick comes in four shades named after his mom Claudette is a striking rust red and the other inspiring women in his life, grandmothers La and Ginette.

New to Audacious is a Sheer Matte formula with a soft-focus finish and medium-sheer coverage: Sandrine is a scarlet red; Sylvie is a berry red, and they feel so comfy and soft on the lips.

The Claudette Collection is available at Nars boutiques and Rustans The Beauty Source.

Dress your lips: Rouge Dior comes in 75 shades and new, refillable logo cases.

Christian Diors most iconic lipsticks have been released in modern, refillable packaging, and ultra-flattering finishes.

Rouge Dior 999 Velvet is a crimson-red born from the first two lipsticks launched by Christian Dior 9 and 99 and 100 Nude Look, a reinterpretation of the greige new look of 1947. (The other two icons are 080 Red Smile, one of the first reds Dior created in 1950 thats been reinvented as an intensely luminous red; and 525 Chrie, a rosewood nude whose name conveys Diors love of women and his muses.)

The legendary fashion designer not only wanted to dress women but also their smiles, so he created his first couture lipstick in 1953, eventually releasing it in over a thousand shades. Ever the visionary, Rouge Dior was already sustainable back then, as the lipsticks came in refillable cases.

Today, Peter Philips, the creative and image director for Dior Makeup, has resurrected 75 shades in new, refillable logo cases, and satin, matte, velvet and metallic finishes to flatter all skin tones.

Flowers always inspired Dior, so the formula has been enriched with floral, lip-care ingredients like red peony and pomegranate blossom extract.

Rouge Dior is available at Dior boutiques and SM Makati.

Beauty bargains: Get discounts on beloved brands at Shopee Beauty.

I love Shopee for its amazing deals and steals, so I was really excited to learn that the e-tailer has launched Shopee Beauty, a one-stop online destination for the best deals from top makeup and skincare brands.

You can find well-established, beloved brands such as Dove, TRESemm, and Cream Silk, as well as exciting finds from up-and-coming brands like Face Republic, Beauty Avenue, Teviant, and Seoul White Korea.

Brands will curate based on the latest makeup trends, and recommend products based on your needs. Youll also get fun tutorials from their favorite Shopee KOLs, product reviews, makeup tips, and giveaways on Shopee Live.

But face it: we love the bargains, right? Aside from free shipping vouchers, limited-time deals and exclusive product launches, until March 24 theyre giving discounts of up to 90 percent off on their go-to lippies, mascaras, and skincare brands.

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The ultimate path to skin rejuvenation - Philstar.com

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Mouth Sores from Chemo: Symptoms, Causes, and Treatments – Healthline

By daniellenierenberg

While youre receiving treatment for cancer, some of the drugs you take can cause painful sores to develop inside your mouth. You can also get them if youve had a bone marrow (stem cell) transplant as part of your cancer care.

Although they often heal on their own, these mouth sores can make it uncomfortable to eat and talk. Well discuss what you can do to relieve the pain and prevent them from getting worse.

Mouth sores can be a common side effect of cancer treatment. The condition, known as stomatitis or mucositis, is an inflammation of the tissues inside your mouth.

Whitish, ulcer-like sores can form on your cheeks, gums, lips, tongue, or on the roof or floor of your mouth. Even if you dont develop mouth ulcers, you may have patches that feel inflamed and painful, as if theyve been burned.

Anyone who is receiving chemotherapy, radiation therapy, or a bone marrow (stem cell) transplant can develop mouth sores as a side effect of these treatments.

If you have dry mouth or gum disease, or if your teeth and gums are not well taken care of, you may be at a higher risk of getting mouth sores during your treatment. Women and people who smoke or drink alcohol are also at a higher risk, according to the Oral Cancer Foundation.

If youre receiving chemotherapy, the sores could begin forming anywhere from 5 days to 2 weeks after your treatment. Depending on the specific cause, the sores could go away on their own in a few weeks, or they could last longer.

Its important to find ways to manage your pain and to watch for signs of an infection. Cancer-related mouth sores can lead to weight loss, dehydration, and other serious complications.

Cancer cells can grow very quickly. The aim of cancer treatment is to stop or slow down that growth. The cells in the mucous membranes lining your mouth are also fast-growing cells, so cancer treatments affect them, too.

Cancer treatments also keep the cells in your mouth from being able to repair themselves efficiently when theyre damaged.

Radiation therapy can also damage the glands in your mouth that make saliva. A dry mouth is more susceptible to infections that cause mouth sores.

Chemotherapy and radiation can both change the microbiome in your mouth, upsetting the balance between good and bad bacteria. The growth of harmful bacteria in your mouth can also lead to mouth sores.

Sometimes cancer treatments suppress your immune system, which may make it more likely that youll get a bacterial, viral, or fungal infection that causes mouth sores. An older infection (such as the herpes simplex virus) can also suddenly flare up again.

If youve had a bone marrow (stem cell) transplant, sores may be a sign that youve developed a condition known as graft-versus-host disease (GVHD).

When this happens, the cells in your body are attacking the transplanted cells as though they were an unhealthy invader. According to research published in Journal of Clinical and Experimental Dentistry, short-term (acute) GVHD occurs in 50 to 70 percent of stem cell transplant cases and longer-term (chronic) GVHD is seen in 30 to 50 percent of cases.

The form of GVHD that causes mouth sores is usually mild, and doctors often treat it with corticosteroid medications.

Its important to talk with your doctor if you develop mouth sores after a stem cell transplant, as some kinds of GVHD can turn serious if left untreated.

There is a good chance that youll experience mouth sores at some point during your cancer treatment. Researchers estimate that 20 to 40 percent of those who have chemotherapy and 80 percent of those who have high-dose chemotherapy will develop mucositis afterward.

Still, there are steps you and your cancer care team can take to lower your risk, reduce the severity of the sores, and promote faster healing.

About a month before your cancer treatment begins, schedule an appointment with your dentist to make sure your teeth and gums are healthy. If you have cavities, broken teeth, or gum disease, its important to come up with a dental treatment plan to take care of these conditions so they dont lead to infections later, when your immune system may be vulnerable.

If you wear braces or dentures, ask your dentist to check the fit and remove any part of the device you dont need during your treatment.

Its very important to maintain good oral hygiene practices throughout your treatment to lower your risk of infection. Brush and floss gently but regularly, avoiding any painful areas. You can also ask your dentist whether a mouth rinse with fluoride is advisable in your case.

For certain kinds of chemotherapy (bolus 5fluorouracil chemotherapy and some high-dose therapies), your healthcare team may give you ice chips to chew for 30 minutes before your treatment. This type of cold therapy can lower your risk of getting mouth sores later.

During treatment of some blood cancers, doctors may give you injections of palifermin, also known as human keratinocyte growth factor-1 (KGF-1), to prevent mouth sores.

If youre scheduled to receive high-dose chemotherapy or radiotherapy, your cancer care team may prepare your mouth using low-level laser therapy beforehand to keep you from getting mouth sores.

For people who have radiation therapy for head and neck cancers, doctors may prescribe this medicated mouthwash to minimize mouth sores.

The length of time your mouth sores may last depends on the specific cancer treatment youve had. Here are some estimates broken down by treatment:

You may notice symptoms anywhere between a few days and a few weeks after your cancer treatment. Heres what you may see and feel as mucositis develops:

You may notice that the sores become slightly crusty as they heal. Its important to keep track of your symptoms and let your oncologist know if the sores arent healing on their own.

Contact your doctor right away if you:

Untreated mouth sores can lead to malnutrition, dehydration, and life-threatening infections.

There are a few different ways that you can help mouth sores heal and avoid prolonger pain or an infection.

While the sores are healing, its very important to keep the inside of your mouth clean to prevent an infection from developing.

The National Cancer Institute recommends that you gently clean your teeth every 4 hours and just before you go to sleep at night. Here are a few tips to consider:

If the pain from mouth sores is interfering with your ability to eat and drink, your doctor may treat the condition with a opioid mouthwash or one containing doxepin or lidocaine.

To ease discomfort and keep your mouth from feeling dry, you may want to try rinsing with a mild saltwater or baking soda solution. Heres how to make each of them:

Your cancer care team may recommend that you use a lubricating liquid (artificial saliva) to moisten the inside of your mouth if dryness is a problem. These liquids are usually gel-like. They coat your mouth with a thin film to help ease discomfort and promote healing.

Some people have found it useful to rinse with a blend of medications called the magic mouthwash. Formulas for this mouthwash vary, but most of them include a combination of medications to treat different symptoms, including:

Magic or miracle mouthwash solutions usually have to be prescribed by a doctor and prepared by a pharmacist, although some people mix up an over-the-counter version at home.

There isnt enough research to say for sure whether magic mouthwash works. If you think youd like to try it, talk with your oncologist or a healthcare professional about whether its a good idea for you.

Here are a few more things you can try at home that may help ease pain from mouth sores:

Mouth sores are one of the most common side effects of cancer treatment. Shortly after chemotherapy, radiation, or transplant treatments, painful, ulcer-like sores can form on the inside of your mouth.

These sores may go away on their own. If they dont, its important to seek medical treatment for them because they can lead to very serious complications.

Before you start cancer treatments, visit a dentist to make sure your teeth and gums are healthy. Keeping up good dental hygiene practices during and after cancer treatment will help limit mouth sores.

If the sores are keeping you from eating and drinking, talk with your oncologist about medications could relieve the pain and speed up the healing process, so you can enjoy a better quality of life during treatment.

Its really important to keep track of any sores in your mouth so you can reach out to your healthcare team if they dont improve. Sores that deepen or worsen can lead to serious even life-threatening complications.

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Research Associate in Stem Cells and Regenerative Medicine job with KINGS COLLEGE LONDON | 246711 – Times Higher Education (THE)

By daniellenierenberg

Job descriptionThe Centre for Stem Cells & Regenerative Medicine is located in Guys Hospital.It is internationally recognized for research on adult and pluripotent stem cells and is a focus for cutting-edge stem cell research currently taking place across the College and its partner NHS trusts, as part of Kings Health Partners. Through the Centre, Kings aims to drive collaboration between scientists and clinicians to translate the potential of stem cells into clinical reality for patients.Applications are invited for a postdoctoral researcher funded as part of the PIs Wellcome Clinical Fellowship, and will work with a dynamic group of scientists focussed on reproductive biology, early embryonic development and the causes of infertility. The post holder will contribute to the regenerative medicine theme and will be involved in the generation and processing of single cell experiments using a variety of techniques.This is an exciting opportunity following our recent work (Sangrithi et al. 2017, Dev Cell & Lau et al. 2020, Dev Cell). The project aims to discover the function of genes on the X-chromosome in male germline stem cells (spermatogonia) and their role in idiopathic and sex chromosome aneuploidy associated infertility. We aim to understand physiological gene regulatory networks functional in spermatogonial stem cells using a combination of single-cell methods, to explain how perturbation in X-gene dosage in SSCs may cause infertility. The postholder will also identify and validate candidate disease bio-markers.This post will be offered on an a fixed-term contract until 05/04/2026This is a full-time post - 100% full time equivalent

Key responsibilities Carry out world class research. Are adept at working in a wet lab setting with experience in designing and executing experiments. Familiarity in single cell work nucleic acid manipulation is desirable Communicate results effectively in writing and orally Contribute to publications arising from the research projects Keep clear and up-to-date records of work Attend and present at seminars, journal clubs and conferences Contribute to collaborative atmosphere of the department Share skills by training others Comply with all relevant safety legislation to ensure a safe working environment Take part in public engagement activities To support grant writing, for maintaining the continual research in this domain, e.g. Fellowships Post holder will be expected to plan and prioritise their own workload, with competing and shifting priorities under pressure of deadlinesThe above list of responsibilities may not be exhaustive, and the post holder will be required to undertake such tasks and responsibilities as may reasonably be expected within the scope and grading of the post.

Skills, knowledge, and experience

Essential criteria PhD awarded in the biological sciences Excellent general knowledge of molecular biology Knowledge of cell biology Knowledge of flow cytometry Relevant postdoctoral experience Experience in a molecular biology research lab Excellent record keeping / attention to detail Organized and systematic approach to research Pro-active, enthusiastic, positive attitude Self-motivated, with the ability to work under pressure & to meet deadlines Keen interest in infertility and regenerative medicine Ability to think strategically

Desirable criteria Understanding of the biology of germ cells and embryo development Previous experience in working with the laboratory mouse ES cell culture experience General knowledge of computational tools for single cell RNAseq Ability to make collaborative and independent decisions*Please note that this is a PhD level role but candidates who have submitted their thesis and are awaiting award of their PhDs will be considered. In these circumstances the appointment will be made at Grade 5, spine point 30 with the title of Research Assistant. Upon confirmation of the award of the PhD, the job title will become Research Associate and the salary will increase to Grade 6.Further informationABOUT THE SCHOOLThe School of Basic & Medical Biosciences is led by Professor Mathias Gautel and comprises five departments with a wide range of expertise and interests. Using a bench to bedside approach, the School aims to answer fundamental questions about biology in health and disease and apply this to the development of new and innovative clinical practise, alongside providing a rigorous academic programme for students.DepartmentsThe Centre for Human & Applied Physiological Sciences (CHAPS) uses an integrative and translational research approach focusing on fundamental questions about human physiological function in health and disease to explore 3 research themes: skeletal muscle & aging, sensory-motor control & pain and aerospace & extreme environment adaptation.The Centre for Stem Cells & Regenerative Medicine focuses on cutting-edge stem cell research, how stem cells interact with their local environment and how these interactions are important for developing effective cell therapies in the clinic.The Department of Medical & Molecular Genetics uses cutting-edge technologies and analysis techniques to explore the mechanistic basis of disease, improve diagnostics and understand the epigenetic mechanisms of gene regulation and RNA processing, working from whole population level to complex and rare disease genomesThe Randall Centre of Cell & Molecular Biophysics takes a multi-disciplinary approach at the interface of Biological and Physical Sciences to explore the underlying mechanisms behind common diseases.St Johns Institute of Dermatology seeks to improve the diagnosis and management of severe skin diseases, through a better understanding of the basic pathogenetic mechanisms that cause and sustain these conditions focussing on cutaneous oncology, genetic skin disorders, inflammatory & autoimmune skin disorders, and photomedicine.About the Department of Centre for Stem Cells & Regenerative MedicineThe Centre for Stem Cells & Regenerative Medicine is led by Professor Fiona Watt, whos laboratory comprises approximately 30 research staff and visiting scientists and is internationally recognised for research on adult and pluripotent stem cells. Along with Professor Watts group there are nine other research groups operating at the Centre, bringing the total number of staff to approximately 80 people.Research at the Centre is focused on how stem cells interact with their local environment, or niche. We believe that an understanding of these interactions is important for developing effective cell therapies in the clinic. Located on the Guys Hospital campus, the Centre acts as a focus for cutting-edge stem cell research taking place across the College and its partner NHS Trusts, as part of Kings Health Partners. To facilitate collaborations within Kings and with external partners, we have opened a Stem Cell Hotel where researchers can access specialist equipment and technical support to study stem cell behaviour at single cell resolution. We also host an international seminar series and run the Stem Cells @ Lunch seminar series to share ideas and unpublished data. Our researchers are committed to public engagement and take part in diverse outreach events.Detailed information about the Centre for Stem Cells & Regenerative medicine can be found in the link below:http://www.kcl.ac.uk/lsm/research/divisions/gmm/departments/stemcells/index.aspx

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Research Associate in Stem Cells and Regenerative Medicine job with KINGS COLLEGE LONDON | 246711 - Times Higher Education (THE)

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Gergis Explains the Differences Between Acute and Chronic GVHD – Targeted Oncology

By daniellenierenberg

Usama Gergis, MD, MBA Professor of Oncology Director, Bone Marrow Transplant and Immune Cellular Therapy Sidney Kimmel Cancer Center Thomas Jefferson University Hospital Philadelphia, PA, reviewed that difference in acute and chronic graft-versus-host disease (GVHD) and the treatment available for each.

Targeted OncologyTM: How would you treat a patient with GvHD in the second line?

GERGIS: If you [have a patient with] second-line acute GVHD, your answer should be ruxolitinib [Jakafi] because its the only drug that has been tried in phase 3 trials. If you get a [case of] chronic GVHD, your answer should be ibrutinib [Imbruvica].

What is the efficacy of peripheral blood stem cells (PBSC) versus bone marrow from unrelated donors in patients with acute and chronic GvHD?

[Results from] a phase 3 study of bone marrow versus stem cells for unrelated donors [showed] the acute GVHD population [cumulative incidence] was the same between both.1 For the chronic population, the bone marrow did better [PBSC 53% vs bone marrow 41%; P = .01]. This was published almost 8 years ago, [and it] was reported almost 10 years ago, but we still use stem cells.

This has not changed practices, and the reasons are, number 1, there was more primary graft failure on the bone marrow than the PBSC, and number 2, its pretty involved to do bone marrow harvest, although I have done it for 15 years, at least a few every month.

The benefit of bone marrow versus PBSCand this benefit was only studied in unrelated donors, not in matched related donorswas seen across all organs affected with chronic GVHD except lungs, [gut, and serosa].2 So, there was no real benefit in the lungs.

Can you explain the difference between acute and chronic GvHD?

Chronic GVHD is more complicated and involved than acute GVHD. In acute, you have the skin, gastrointestinal organs, and the liver [that may be affected]. Thats it. In chronic, all the patients other organs can be affected. The patients weight can be affected. [Chronic GVHD is] more debilitating over a long time and [can] go unrecognized for a while. [If a patient is] experiencing acute GVHD, you see them twice a week, whereas if the patient has chronic GVHD, you probably see them once a month. So you can see a very stark change in your patients within that month if they lose 10% of their body weight and they already lost a lot of weight in the period right after [transplantation], so that can be obvious to you.

[In my institution], we have the GVHD clinic where we [grade the patient based on] studying the degree of fibrosis, how many organs are affected, the patients range of motion, and the degrees in range of motion. We do frequent pulmonary function tests and various [other] testing. By looking at all the affected organs, you reach a grade, and that can be mild, moderate, or severe [chronic GVHD].

How do you treat moderate-to-severe chronic GVHD at initial presentation and in the second line?

First-line treatment for chronic GVHD are steroids. For second line, there are many agents [to consider]. Ive tried most of them. I like photopheresis because its not pharmacological, but its pretty involved. Your patient will need a permanent catheter, and they will need to come to the transplant center twice a week, and you see a response after a long time. It takes an average of 50 photopheresis sessions for a response. But the beauty of photopheresis [is that] you could try it with other agents, so its not mutually exclusive. You could use it with ruxolitinib, ibrutinib, or any other agents.

The answer will be ibrutinib [for chronic GVHD], and thats based on the [results of a] phase 2 clinical trial that treated 42 patients with steroid-refractory chronic GVHD, and the efficacy was 69% [best overall response rate], and 31% complete response rate.3

What do you think of these poll results?

Everybody agrees on giving ibrutinib. When I gave this talk a couple months ago, lenalidomide [Revlimid] was not included in the poll. I added it because [recently], a nice study in Blood came out from the National Institutes of Health where they tried lenalidomide at a small dose, 2 mg, in steroid-refractory chronic GVHD. Its a large trial; I think its about 100 patients. Theyve seen responses that are comparable with ibrutinib....I treated a patient for multiple myeloma; he received a transplant for multiple myeloma, and now, 6 months later, he has chronic GVHD and some clonal plasma cells. So for him, I was comforted to know the results of the lenalidomide trial.

How does ruxolitinib play a role in this setting?

Ruxolitinib was reported in the REACH3 trial [NCT03112603] with very good responses in chronic GVHD.4 I think it probably will get approved for that indication. Looking at this study about 2 years ago, nothing was studied well in this indication, and ibrutinib was approved.

REACH3 was a large trial, almost 300 patients, and everybody was randomized to ruxolitinib 10 mg twice a day versus best available treatment. They looked at everybody about 6 months later for response.

What should physicians keep in mind when treating?

Chronic GvHD is pretty involved. Your patients will need a multidisciplinary approach. You need to pay attention to their bones. In the first 100 days post transplant, the average bone aging is 17 years.

So although were trying to treat acute GVHD, viruses, and prevent relapses, [by putting] your patients on some steroids, you are aging your patients bones by 17 years only in the first 100 days. No matter what you do, give your patients vitamin D, calcium, and Fosamax [alendronate sodium].

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Gergis Explains the Differences Between Acute and Chronic GVHD - Targeted Oncology

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

By daniellenierenberg

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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Manageable Safety Profile Observed in Phase 1 Studies Examining UCART19 for Pediatric and Adult Patients with B-Cell ALL – Cancer Network

By daniellenierenberg

UCART19 produced a manageable safety profile in 2 separate phase 1 studies examining heavily pretreated pediatric and adult patients with relapsed or refractory B-cell acute lymphoblastic leukemia (ALL), according to data published in The Lancet.

For the first time, these studies support the feasibility of UCART19 and other genome-edited, donor-derived allogeneic anti-CD19 chimeric antigen receptor (CAR) T-cells to treat this group of patients with aggressive forms of ALL.

Phase 1 trials in paediatric and adult patients with late-stage relapsed or refractory B-cell acute lymphoblastic leukaemia have shown the feasibility, safety, and activity of UCART19, an off-the-shelf CAR T-cell product, wrote the investigative team. The results of these trials represent a substantial step forward in the development of CAR T cells and could herald a new, effective, and easily accessible cell therapy for patients with B-cell acute lymphoblastic leukaemia.

The results determined that the most common adverse event between both phase 1 studies was cytokine release syndrome (CRS), observed in 19 patients (91%). Three patients (14%) experienced grade 3/4 CRS.

More, 8 patients (38%) experienced grades 1/2 neurotoxicity, 2 (10%) experienced grade 1 acute skin graft-versus-host disease, and 6 (32%) had grade 4 prolonged cytopenia.

The research team recorded 2 treatment-related deaths between the 2 studies. The first was caused by neutropenic sepsis in a patient with concurrent CRS and the other was from pulmonary hemorrhage in a patient with persistent cytopenia.

Overall, 14 of 21 patients (67%) experienced a complete response or complete response with incomplete hematological recovery at 28 days following infusion. Median duration of response was recorded at 4.1 months, with 10 of 14 adult patients (71%) progressing to subsequent allogeneic stem cell transplant. The progression-free survival rate at 6 months was 27%, with an overall survival rate of 55%.

The adverse effects observed with UCART19 to date seem similar to those reported for autologous anti-CD19 CAR T cells, wrote the investigators. Cytokine release syndrome was encountered in the majority of patients in whom UCART19 expansion was detected and appeared no more severe than with approved autologous products.

The 2 ongoing, multicenter, clinical trials (NCT02808442 and NCT02746952) enrolled 7 pediatric and 14 adult patients from June 3, 2016, through October 23, 2018, to examine the safety profile and antileukemic activity of UCART19.

The dose-escalation studies began with patients undergoing lymphodepletion with fludarabine and cyclophosphamide, with or without alemtuzumab (Lemtrada), followed by different doses of UCART19 for adults and children. The primary end point of the data was adverse events.

The small sample size for the investigation is the leading limitation for the research, but the research team also mentioned the differing trial designs, lymphodepletion regimens, and UCART19 cell doses to be among limitations of both trials.

The results [of these studies] are an encouraging step forward for the field of allogeneic CAR T cells, and UCART19 offers the opportunity to treat patients with rapidly progressive disease and where autologous CAR T-cell therapy is unavailable, wrote the investigators.

Reference:

Benjamin R, Graham C, Yallop D, et al. Genome-edited, donor-derived allogeneic anti-CD19 chimeric antigen receptor T cells in paediatric and adult B-cell acute lymphoblastic leukaemia: results of two phase 1 studies. Lancet. 2020;396(10266):1885-1894. doi: 10.1016/S0140-6736(20)32334-5

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Platelet Rich Plasma Therapy: The answer to a rejuvenated body, skin, hair and sex life! – Longevity LIVE – Longevity LIVE

By daniellenierenberg

You might associate platelet rich plasma therapy (PRP) with the renowned vampire facial and youd be right. However, theres so much more to this ground-breaking treatment than what youve seen in mainstream media. Founder of Anti-Aging Art Medical Aesthetics, Dr Reza Mia, shares more on this cutting-edge procedure.

PRP, or platelet rich plasma therapy, as its technically known, is a non-invasive treatment performed to accelerate healing, minimise the signs of ageing, accentuate parts of the body and to relieve pain. Incredibly versatile, this therapy is used among athletes to accelerate the healing of injuries, it is used to treat arthritis and tendonitis and is also popularly used as an anti-ageing facial treatment. PRP is considered a long-lasting solution to the bodys natural healing process, with results ranging from instant, to appearing after a couple of weeks, and lasting up to several years.

The science behind it

Plasma is the liquid part of the blood, consisting mainly of water and protein. It allows red and white blood cells, as well as platelets (a type of blood cell responsible for making blood clot, as well as for facilitating healing) to move through the bloodstream. Platelets are rich in connective tissue growth and healing factors; they initiate repair in the body and attract stem cells to injuries. This amazing healing ability is what makes them so effective in platelet rich plasma therapy.

To collect plasma, we draw blood from the body and then inserts it into a machine called a centrifuge, which spins the blood at high speeds, separating platelet-rich plasma from the rest of the blood. The red blood cells are discarded, and one is left with a concentration of platelets above normal values. This concentration can then be injected into various areas of the body to treat injuries or concerns.

Sports-related injuries

PRP has become a popular therapy among athletes. It is used to treat injured tendons, ligament sprains and tears, damaged ligaments and joints. Not only does it stimulate the healing of cartilage but it also helps reduce pain. Soft tissue injuries are most responsive to PRP treatment. Depending on the type of injury and the severity of it, some athletes who would have been side-lined for months have seen major results after around 6 weeks.

The vampire facial or facelift gained worldwide fame when reality star Kim Kardashian famously posted about it on Instagram a few years ago. Today, it is a common anti-ageing treatment. PRP is injected into the face to reduce wrinkles and rejuvenate the skin. The treatment provides a gradual increase in volume by helping to stimulate the bodys natural collagen production. Other benefits of the treatment include skin tightening, lifting and smoothing, and a more even skin tone.

Also known as a vampire breast lift, PRP for breast enhancement is a non-surgical form of breast augmentation. Unlike a traditional breast lift or augmentation which requires incisions, this treatment is performed by utilising PRP injections to create a fuller and firmer bust. A vampire breast lift wont increase your cup size or change the shape of your breast. However, it will create a fuller and firmer appearance and minimise the appearance of wrinkles and stretch marks. The results have been likened to those achieved by wearing a great quality push-up bra.

PRP therapy can be used to improve sexual function in both men and women. Platelet rich plasma sexual rejuvenation, involves injecting your own activated blood into the vagina or penis. The v-shot can enhance clitoral orgasms; increase arousal and lubrication and vaginal tightness. The benefits of the p-shot are longer, firmer and more sustainable erections and proven penis enlargement. The question on everyones lips is, of course, whether or not the latter procedure is painful. No. It is completely painless!

Did you know that PRP therapy is also successful when used to enhance hair growth? The treatment has shown to effectively treat androgenic alopecia (also known as male pattern baldness). PRP injections trigger and maintain natural hair growth by stimulating blood flow to the hair follicles. This treatment may be combined with otherhair loss procedures or medications.

Undergoing PRP therapy is simple and painless. The entire procedure, from drawing the blood to solution preparation, takes around half an hour and is performed in your aesthetic practitioners office. The time spent on the treatment performed with the PRP afterwards, is dependent on the individual treatment. Generally speaking, PRP injections are not painful,. We make use of various pain management techniques to ensure the comfort of our patients during their procedures. Depending on your treatment, you may experience some swelling and bruising for a few days, but this clears up quickly.

While the vampire facial put PRP on the general publics map, theres so much more that can be achieved by making use of this incredible treatment. Whether youre looking to treat an injury, minimise your wrinkles, rejuvenate your sex life or increase your hair growth, Plasma rich platelet therapy is a safe and effective treatment option to consider.

Visit http://www.drreza.co.za or or follow Dr Mia on Instagram @drreza.sa and @antiagingart

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Paragon Biosciences Expands Cell And Gene Therapy Platform – Contract Pharma

By daniellenierenberg

Paragon Biosciences, a life science innovator that creates, invests in and builds life science companies in biopharmaceuticals, cell and gene therapy and synthetic biology utilizing artificial intelligence, has launched CiRC Biosciences, a cell therapy company developing treatments for serious diseases with high, unmet needs with an initial focus on the eye."The addition of CiRC Biosciences to our portfolio builds upon our cell and gene therapy platform, an area that has tremendous potential to address serious genetic diseases," said Jeff Aronin, founder, chairman and chief executive officer, Paragon Biosciences. "CiRC Biosciences gives us the science to target retinal diseases that could lead to vision restoration with numerous other applications in the years ahead."CiRC Biosciences is currently advancing pre-clinical development of chemically induced retinal cells for vision restoration in Geographic Atrophy Age-Related Macular Degeneration (Dry AMD), which is the most common cause of irreversible vision loss over the age of 65, and advanced Retinitis Pigmentosa (RP), a genetic disorder that causes tunnel vision and eventual blindness. There are no U.S. Food & Drug Administration (FDA) approved treatments to restore vision loss in Dry AMD or RP.The company's novel mechanism of action is designed for direct chemical conversion of fibroblasts into other cell types using a cocktail of small molecules in an 11-day chemical conversion process. Pre-clinical studies have shown efficacy in blind mice that demonstrated vision restoration. CiRC Biosciences has provisional patent applications to protect its platform."Our technology transforms ordinary skin cells into specialized retinal cells using a cocktail of small molecules," said Sai Chavala, M.D., co-founder and chief scientific officer, CiRC Biosciences. "This process is potentially safer, quicker, more cost effective and easier to manufacturer than using traditional stem cells. Working with Paragon Biosciences to build and advance CiRC Biosciences provides us the opportunity to efficiently progress this technology through research and development stages.CiRC Biosciences first reported its discovery in the highly respected scientific journal Nature (April 15, 2020). A recently published New England Journal of Medicine article (Nov. 5, 2020) discussed CiRC's technology of using chemically induced cells to restore retinal function. The article concluded, "The new and emerging strategies for the rescue, regeneration, and replacement of photoreceptors suggest a bright future in the fight to preserve and restore vision in blinding eye diseases."The abstract in Nature is available here.Access to the NEJM article is available here.

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[Full text] Successful Use of Nivolumab in a Patient with Head and Neck Cancer Aft | OTT – Dove Medical Press

By daniellenierenberg

Introduction

Head and neck squamous cell carcinoma (HNSCC) is one of the major causes of cancer-associated illness and death, with more than 600,000 newly diagnosed cases worldwide each year1 and a continuously increasing incidence rate.2 HNSCC includes cancers of the oral cavity, pharynx, and larynx. The anatomical structures of the head and neck can be damaged by the tumor itself or treatments such as surgical resection and chemoradiotherapy, which sometimes cause speech, swallowing, and breathing impairments.3,4 Patients with HNSCC have been shown to bear greater psychological distress than those with other types of cancer.5

Despite the currently available therapies, patients with advanced HNSCC still experience poor outcomes.68 For example >50% of patients with locoregionally advanced HNSCC experience recurrence or metastases development within 3 years of treatment.911 Treatment options for patients with the recurrent and metastatic disease following progression after a platinum-based regimen are limited, and the median overall survival of such patients is less than 7 months.1215

The recurrence and metastasis of HNSCC are facilitated by immune evasion;16 therefore, as one of the methods to inhibit immune evasion, the use of programmed death 1 (PD-1)/programmed death ligand 1 (PD-L1) pathway inhibitors is considered effective in the treatment of recurrent HNSCC.1719 Nivolumab, a fully human IgG4 antiPD-1 monoclonal antibody, has shown remarkable antitumor efficacy and safety when administered to patients with recurrent HNSCC whose disease had progressed within 6 months of platinum-based chemotherapy;19 Furthermore, nivolumab treatment has been shown to improve the quality of life of these patients.20 However, PD-1 inhibitors can upregulate T cells in vivo, which may lead to the development of graft-versus-host disease (GVHD) in patients after allogeneic hematopoietic stem cell transplantation (allo-HSCT).2123 To the best of the authors knowledge, no studies have investigated the safety and efficacy of nivolumab in patients with HNSCC after allo-HSCT. Here, we report the case of a patient who experienced excellent control of left buccal squamous cell carcinoma with nivolumab after the failure of platinum-based chemotherapy despite receiving allogeneic bone marrow transplantation.

Without any family history of tumor, a 33-year-old man was diagnosed with Philadelphia chromosome-positive T cell acute lymphoblastic leukemia on March 19, 2014. He received one course of vincristine and prednisone therapy and four courses of vincristine, daunorubicin, cyclophosphamide, and prednisone therapy. He was in complete remission at the end of therapy. Subsequently, allogeneic bone marrow transplantation was performed; the donor was his human leukocyte antigen (HLA)-haploidentical sibling (sister). He experienced chronic GVHD (c GVHD) of the oral cavity and skin 3 months after transplantation, for which he was treated with steroid hormone- and cyclosporine-based therapies. Skin rejection lasted for more than 3 years. Imatinib mesylate was administered for 2 years after transplantation, and his leukemia was well controlled.

In August 2018, the patient developed an ulcer of approximately 0.5 0.5 cm size in the left buccal mucosa; the ulcer was slightly painful and covered with white moss. In September 2018, the patient was admitted to Peking University Stomatological Hospital, where a biopsy of the buccal mucosa was performed. The pathology results showed the presence of squamous cell carcinoma in the left cheek. Unfortunately, this patient was not a right candidate for HNSCC in terms of exposure to risk factors, such as long terms of smoking and drinking. On October 10, 2018, 18F-fluorodeoxyglucose-positron emission tomography/computed tomography (CT) showed that the mass in the left cheek was metabolically active, which is consistent with the activity of a malignant tumor. One course of an adjuvant therapy regimen (nimotuzumab [200 mg d0] + docetaxel [60 mg d1, 8]+ nedaplatin [60 mg d2, 3]) was administered on October 26, 2018. Following this, the patient developed degree II thrombocytopenia and redness, swelling, and ulceration of the cheek, which had discharge with a peculiar smell. On November 29, 2018, a head and neck CT scan showed a left buccal malignant tumor with the destruction of the neighboring mandibular bone and lymph node enlargement in the left submaxillary region and right carotid sheath. The CT examination revealed disease progression. Following a multidisciplinary consultation in our hospital, surgery was not recommended; instead, a chemotherapy-based comprehensive treatment was recommended as a better option for the patient. The patient received chemotherapy with albumin paclitaxel (200 mg d1, 8)+ bleomycin (15,000 units d2, 9) from November 30, 2018 to January 9, 2019. On another CT scan, the curative effect was evaluated as partial remission (showed in Video 1, Figure 1A); subsequently, two courses of a chemotherapy regimen comprising nivolumab (140 mg d1) + albumin paclitaxel (200 mg d1, d8) were administered. A CT examination showed stable disease (SD) on March 12, 2019, following which the patient was administered 120 mg of nivolumab once every 2 weeks from March 15 to May 23, 2019. Another CT examination was performed on May 28, 2019 (showed in Video 2, Figure 1B). During the therapy course, the related tumor markers showed an overall downward trend, the new metastases did not appear, the patients status became better than before. Subsequently, another CT examination performed in August 02, 2019 showed the extent of the tumor was obvious reduction than before (showed in video 3, Figure 1C). And the corresponding CT report in August 02, 2019 was described as follows Compared with the CT on 28 May, 2019, the extent of the tumor in the left cheek became obviously smaller, the tubercle in the left submandibular and the lymph nodes in the left neck also became smaller. There were no other significant changes in this image. Most importantly, the patient did not develop any form of GVHD following nivolumab administration.

Figure 1 Head and neck CT images showing tumor before (A) and after treatment with nivolumab (B, C, respectively).

Abbreviation: CT, computed tomography.

Note: The arrows indicate the maximum length diameter of tumor or tumor site.

Reliable data on the clinical safety and efficacy of nivolumab in the treatment of recurrent or metastatic HNSCC have been obtained in a Phase III randomized clinical trial (CheckMate 141).19 In this trial, 361 patients with recurrent HNSCC for whom disease had progressed within 6 months after platinum-based chemotherapy were enrolled between May 29, 2014, and July 31, 2015. The median follow-up duration for overall survival (OS) was 5.1 months (range, 016.8 months). OS was significantly greater in patients randomized to receive nivolumab than in those who received standard second-line, single-agent systemic therapy with either methotrexate, docetaxel, or cetuximab (hazard ratio, 0.70; 97.73% confidence interval (CI), 0.510.96; P = 0.01). The median OS was 7.5 months (95% CI, 5.59.1) in the nivolumab group versus 5.1 months (95% CI, 4.06.0) in the standard therapy group. The one-year survival was also greater in patients who received nivolumab than in those who received standard therapy (36.0%vs. 16.6%). Furthermore, the response rate was higher in those who received nivolumab than in those who received standard therapy (13.3% vs 5.8%); however, the median progression-free survival was not significantly different between the groups (2.0 vs 2.3 months; P=0.32). In this study, patients who were treated with nivolumab had a longer OS than those treated with standard therapy, regardless of tumor PD-L1 expression or p16 status. Grade 3 or 4 treatment-related adverse events occurred in 13.1% of patients who received nivolumab and 35.1% of those who received standard therapy. Physical function, role functioning, and social functioning were stable in the nivolumab group, whereas they were substantially worse in the standard therapy group.20 Moreover, among Asian patients, the survival benefits were consistent with the global group.24

It was unclear whether nivolumab could be used in patients with recurrent HNSCC after allo-HSCT, though Khaddour et al proved the efficacy and safety of Pembrolizumab in patients who underwent allo-HSCT after relapsed and refractory Szary Syndrome and cutaneous squamous cell carcinoma.25 However, some case reports (Table 1) and clinical trials (Table 2) have reported the efficacy and safety of nivolumab when administrated to patients with recurrent hematological malignancies (mostly Hodgkins lymphoma) after allo-HSCT.

Table 1 Case Reports of Nivolumab Use After Allo-HSCT

Table 2 Studies on Nivolumab Use After Allo-HSCT

In Herbaux et al, nivolumab (3 mg/kg, once every 2 weeks) was administered to 20 patients with Hodgkins lymphoma who experienced relapse after allo-HSCT. The overall response rate was 95%, the 1-year progression-free survival rate was 58.2%, and the 1-year OS rate was 78.8%.26 Compared with other treatment options, nivolumab was more effective in these patients.2730 Haverkos et al reported results after a median follow-up duration was 428 days (range, 133833 days). After treatment with PD-1 inhibitors [nivolumab 3 mg/kg, once every 2 weeks (n = 28) and pembrolizumab (n =3)], the overall response rate of 31 patients with relapsed lymphoma after allo-HSCT was 77%, the median progression-free survival was 591 days (range,400644 days), and 68% of the patients survived to the end of the study.23 These two studies showed that nivolumab is effective when administered to patients with recurrent blood cancers after allo-HSCT, which is consistent with the results of several other case reports3134 and case series.35,36 The PD-1/PD-L1 pathway plays a key role in the regulation of the balance among T cell activation, T-cell tolerance, and immune-mediated tissue damage. This pathway protects healthy cells from excessive inflammatory or autoimmune responses.37,38 Some studies have shown that the activation of the PD-1/PD-L1 pathway can reduce acute and chronic GVHD, whereas its blockade can accelerate the graft-versus-host response and increase the associated mortality.21,22,39 It is unclear whether the PD-1 inhibitor nivolumab increases the risk of GVHD and the associated mortality in patients after allo-HSCT.23,26 Some clinical studies and case reports have shown that nivolumab treatment-related GVHD and consequent death in patients after allo-HSCT might be affected by the following factors. First, GVHD after antiPD-1 treatment has been observed most frequently in matched sibling donor transplants; for which Haverkos et al reported an incidence of 75%.23 In a Phase I pilot study, without GVHD or G3/G4 immune toxicity after receiving multiple doses of nivolumab was only among one patient whose donor source was Haploidentical+cord blood Fludarabine.40 Second, a history of GVHD, especially for the acute GVHD, may lead to an increased risk of nivolumab treatment-related GVHD after allo-HSCT. In a French cohort, all patients who presented with acute GVHD after nivolumab treatment had a prior history of acute GVHD, among which three patients presented with steroid-refractory nivolumab-induced GVHD, and GVHD was not observed among patients without a history of GVHD.26 This phenomenon was also observed in Steinerovs medical report.41 In the study by Haverkos et al, 63% of patients with a history of GVHD prior to antiPD-1 treatment developed treatment-emergent GVHD after receiving antiPD-1.23 Third, the shorter the interval between transplantation and nivolumab use, the greater the risk of GVHD. In the study by Herbaux et al, the median intervals between transplantation and nivolumab use in cases with the presence and absence of GVHD were 8.5 months and 28.5 months, respectively.26 In another study by Wang et al, the reported four patients all experienced immune-related adverse events following nivolumab treatment and the median time from transplantation to nivolumab use was 7.8 months.40 Fourth, dose is a risk factor for nivolumab treatment-related GVHD. In a case report, chronic skin GVHD was observed when the dose of nivolumab was adjusted from 0.5 mg/kg to 2 mg/kg.33 Other factors, such as immunosuppressive therapy at the time of nivolumab administration, may also influence nivolumab treatment-related GVHD. Recently, a comprehensive literature review was launched by Awais et al to assess the safety and efficacy of the use of checkpoint inhibitors (ipilimumab, nivolumab and pembrolizumab) in blood cancers before and after allo-HSCT. Collective data showed that checkpoint inhibitors use after allo-HSCT for post-transplant relapse had higher efficacy but the risk of GVHD was significant. Moreover, the investigation indicated that higher drug doses, shorter intervals between checkpoint inhibitors exposure and allo-HSCT and prior history of GVHD had a positive correlation with the risk of GVHD.42

In the present case, HNSCC was effectively controlled without any nivolumab treatment-related acute or chronic GVHD after nivolumab administration, while the weight loss being the only adverse event. After comprehensive analysis, we found that many factors may impede the development of nivolumab treatment-related GVHD in our patient. On one hand, the appropriate donor, no use of checkpoint inhibitors prior to allo-HSCT, the long interval between nivolumab administration and allo-HSCT (36 months) and the standard dose use of nivolumab were the negative factors for GVHD development. On the other hand, the chronic GVHD of the oral cavity and skin before nivolumab use might lead to the development of GVHD. However, it remained unknown what role the immunosuppressant therapy played in the occurrence of GVHD, though we definitely known that immunosuppressant was administered more than 2 years after allo-HSCT and discontinued for 2 years before treatment with nivolumab in our patient. Finally, whether the two primary cancers in our case affected the efficacy and safety of nivolumab by some unknown pathways were unclear, which needed further exploration.

Nivolumab has been shown to be effective in patients with HNSCC for whom platinum-based therapy has failed. However, little is known about the efficacy and safety of nivolumab in patients with HNSCC who have undergone allo-HSCT. Our case report shows that nivolumab could be used effectively and safely in such patients, however, more clinical trials are required to confirm these results.

This study was approved by the Medical Ethics Committee of Tianjin Medical University Cancer Institute and Hospital. The authors state that they have obtained verbal and written informed consent from the patient for the inclusion of their medical and treatment history within this case report.

This work was supported by the Tianjin Science and Technology Commission (18ZXXYSY00070), Key Task Project of Tianjin Health and Family Planning Commission (16KG128), Anticancer Key Technologies R&D Program of Tianjin (12ZCDZSY16200), and Natural Science Foundation of Tianjin (18JCYBJC91600).

The authors declare no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

1. Ferlay J, Soerjomataram I, Dikshit R, et al. Cancer incidence and mortality worldwide: sources, methods and major patterns in GLOBOCAN 2012. Int J Cancer. 2015;136(5):E359E386. doi:10.1002/ijc.29210

2. Jakobsen KK, Gronhoj C, Jensen DH, et al. Increasing incidence and survival of head and neck cancers in Denmark: a nation-wide study from 1980 to 2014. Acta Oncol. 2018;57:11431151. doi:10.1080/0284186X.2018.1438657

3. Sobecki-Ryniak D, Krouse HJ. Head and neck cancer: historical evolution of treatment and patient self-care requirements. Clin J Oncol Nurs. 2013;17(6):659663. doi:10.1188/13.CJON.659-663

4. Licitra L, Mesia R, Keilholz U. Individualised quality of life as a measure to guide treatment choices in squamous cell carcinoma of the head and neck. Oral Oncol. 2016;52:1823. doi:10.1016/j.oraloncology.2015.10.020

5. Singer S, Krauss O, Keszte J, et al. Predictors of emotional distress in patients with head and neck cancer. Head Neck. 2012;34(2):180187. doi:10.1002/hed.21702

6. Licitra L, Felip E. Squamous cell carcinoma of the head and neck: ESMO clinical recommendations for diagnosis, treatment and follow-up. Ann Oncol. 2009;20(Suppl 4):121122. doi:10.1093/annonc/mdp149

7. Adelstein D, Gillison ML, Pfister DG, et al. NCCN guidelines insights: head and neck cancers, version 2.2017. J Natl Compr Canc Netw. 2017;15(6):761770. doi:10.6004/jnccn.2017.0101

8. Warnakulasuriya S. Global epidemiology of oral and oropharyngeal cancer. Oral Oncol. 2009;45(45):309316. doi:10.1016/j.oraloncology.2008.06.002

9. Bernier J, Domenge C, Ozsahin M, et al. Postoperative irradiation with or without concomitant chemotherapy for locally advanced head and neck cancer. N Engl J Med. 2004;350(19):19451952. doi:10.1056/NEJMoa032641

10. Blanchard P, Baujat B, Holostenco V, et al. Meta-analysis of chemotherapy in head and neck cancer (MACH-NC): a comprehensive analysis by tumour site. Radiother Oncol. 2011;100(1):3340. doi:10.1016/j.radonc.2011.05.036

11. Tanvetyanon T, Padhya T, McCaffrey J, et al. Postoperative concurrent chemotherapy and radiotherapy for high-risk cutaneous squamous cell carcinoma of the head and neck. Head Neck. 2015;37(6):840845. doi:10.1002/hed.23684

12. Guardiola E, Peyrade F, Chaigneau L, et al. Results of a randomised Phase II study comparing docetaxel with methotrexate in patients with recurrent head and neck cancer. Eur J Cancer. 2004;40(14):20712076. doi:10.1016/j.ejca.2004.05.019

13. Vermorken JB, Herbst RS, Leon X, Amellal N, Baselga J. Overview of the efficacy of cetuximab in recurrent and/or metastatic squamous cell carcinoma of the head and neck in patients who previously failed platinum-based therapies. Cancer. 2008;112(12):27102719. doi:10.1002/cncr.23442

14. Argiris A, Ghebremichael M, Gilbert J, et al. Phase III randomized, placebo-controlled trial of docetaxel with or without gefitinib in recurrent or metastatic head and neck cancer: an eastern cooperative oncology group trial. J Clin Oncol. 2013;31(11):14051414. doi:10.1200/JCO.2012.45.4272

15. Saloura V, Cohen EEW, Licitra L, et al. An open-label single-arm, phase II trial of zalutumumab, a human monoclonal anti-EGFR antibody, in patients with platinum-refractory squamous cell carcinoma of the head and neck. Cancer Chemother Pharmacol. 2014;73(6):12271239. doi:10.1007/s00280-014-2459-z

16. Ferris RL. Immunology and Immunotherapy of head and neck cancer. J Clin Oncol. 2015;33(29):32933304. doi:10.1200/JCO.2015.61.1509

17. Chow LQM, Haddad R, Gupta S, et al. Antitumor activity of pembrolizumab in biomarker-unselected patients with recurrent and/or metastatic head and neck squamous cell carcinoma: results from the phase Ib KEYNOTE-012 expansion cohort. J Clin Oncol. 2016;34(32):38383845. doi:10.1200/JCO.2016.68.1478

18. Seiwert TY, Burtness B, Mehra R, et al. Safety and clinical activity of pembrolizumab for treatment of recurrent or metastatic squamous cell carcinoma of the head and neck (KEYNOTE-012): an open-label, multicentre, phase 1b trial. Lancet Oncol. 2016;17(7):956965. doi:10.1016/S1470-2045(16)30066-3

19. Ferris RL, Blumenschein G Jr, Fayette J, et al. Nivolumab for recurrent squamous-cell carcinoma of the head and neck. N Engl J Med. 2016;375(19):18561867. doi:10.1056/NEJMoa1602252

20. Harrington KJ, Ferris RL, Blumenschein G Jr, et al. Nivolumab versus standard, single-agent therapy of investigators choice in recurrent or metastatic squamous cell carcinoma of the head and neck (CheckMate 141): health-related quality-of-life results from a randomised, Phase 3 trial. Lancet Oncol. 2017;18:11041115. doi:10.1016/S1470-2045(17)30421-7

21. Blazar BR, Carreno BM, Panoskaltsis-Mortari A, et al. Blockade of programmed death-1 engagement accelerates graft-versus-host disease lethality by an IFN-gamma-dependent mechanism. J Immunol. 2003;171:12721277. doi:10.4049/jimmunol.171.3.1272

22. Saha A, Aoyama K, Taylor PA, et al. Host programmed death ligand 1 is dominant over programmed death ligand 2 expression in regulating graft-versus-host disease lethality. Blood. 2013;122:30623073. doi:10.1182/blood-2013-05-500801

23. Haverkos BM, Abbott D, Hamadani M, et al. PD-1 blockade for relapsed lymphoma post-allogeneic hematopoietic cell transplant: high response rate but frequent GVHD. Blood. 2017;130:221228. doi:10.1182/blood-2017-01-761346

24. Kiyota N, Hasegawa Y, Takahashi S, et al. A randomized, open-label, Phase III clinical trial of nivolumab vs. therapy of investigators choice in recurrent squamous cell carcinoma of the head and neck: a subanalysis of Asian patients versus the global population in checkmate 141. Oral Oncol. 2017;73:138146. doi:10.1016/j.oraloncology.2017.07.023

25. Khaddour K, Musiek A, Cornelius LA, et al. Rapid and sustained response to immune checkpoint inhibition in cutaneous squamous cell carcinoma after allogenic hematopoietic cell transplant for szary syndrome. J Immunol Cancer. 2019;7:338. doi:10.1186/s40425-019-0801-z

26. Herbaux C, Gauthier J, Brice P, et al. Efficacy and tolerability of nivolumab after allogeneic transplantation for relapsed hodgkin lymphoma. Blood. 2017;129:24712478. doi:10.1182/blood-2016-11-749556

27. Peggs KS, Kayani I, Edwards N, et al. Donor lymphocyte infusions modulate relapse risk in mixed chimeras and induce durable salvage in relapsed patients after T-cell-depleted allogeneic transplantation for hodgkins lymphoma. J Clin Oncol. 2011;29:971978. doi:10.1200/JCO.2010.32.1711

28. Anastasia A, Carlo-Stella C, Corradini P, et al. Bendamustine for Hodgkin lymphoma patients failing autologous or autologous and allogeneic stem cell transplantation: a retrospective study of the fondazione Italiana linfomi. Br J Haematol. 2014;166:140142. doi:10.1111/bjh.12821

29. Carlo-Stella C, Ricci F, Dalto S, et al. Brentuximab vedotin in patients with hodgkin lymphoma and a failed allogeneic stem cell transplantation: results from a named patient program at four Italian centers. Oncologist. 2015;20:323328. doi:10.1634/theoncologist.2014-0420

30. Tsirigotis P, Danylesko I, Gkirkas K, et al. Brentuximab vedotin in combination with or without donor lymphocyte infusion for patients with hodgkin lymphoma after allogeneic stem cell transplantation. Bone Marrow Transplant. 2016;51:13131317. doi:10.1038/bmt.2016.129

31. Angenendt L, Schliemann C, Lutz M, et al. Nivolumab in a patient with refractory Hodgkins lymphoma after allogeneic stem cell transplantation. Bone Marrow Transplant. 2016;51:443445. doi:10.1038/bmt.2015.266

32. Yared JA, Hardy N, Singh Z, et al. Major clinical response to nivolumab in relapsed/refractory hodgkin lymphoma after allogeneic stem cell transplantation. Bone Marrow Transplant. 2016;51:850852. doi:10.1038/bmt.2015.346

33. Onizuka M, Kojima M, Matsui K, et al. Successful treatment with low-dose nivolumab in refractory hodgkin lymphoma after allogeneic stem cell transplantation. Int J Hematol. 2017;106:141145. doi:10.1007/s12185-017-2181-9

34. Shad AT, Huo JS, Darcy C, et al. Tolerance and effectiveness of nivolumab after pediatric T-cell replete, haploidentical, bone marrow transplantation: a case report. Pediatr Blood Cancer. 2017;64. doi:10.1002/pbc.26257

35. Godfrey J, Bishop MR, Syed S, Hyjek E, Kline J. PD-1 blockade induces remissions in relapsed classical hodgkin lymphoma following allogeneic hematopoietic stem cell transplantation. J Immunol Cancer. 2017;5:11. doi:10.1186/s40425-017-0211-z

36. El Cheikh J, Massoud R, Abudalle I, et al. Nivolumab salvage therapy before or after allogeneic stem cell transplantation in hodgkin lymphoma. Bone Marrow Transplant. 2017;52:10741077. doi:10.1038/bmt.2017.69

37. Keir ME, Butte MJ, Freeman GJ, Sharpe AH. PD-1 and its ligands in tolerance and immunity. Annu Rev Immunol. 2008;26:677704. doi:10.1146/annurev.immunol.26.021607.090331

38. Francisco LM, Sage PT, Sharpe AH, The PD-1. pathway in tolerance and autoimmunity. Immunol Rev. 2010;236:219242.

39. Fujiwara H, Maeda Y, Kobayashi K, et al. Programmed death-1 pathway in host tissues ameliorates Th17/Th1-mediated experimental chronic graft-versus-host disease. J Immunol. 2014;193:25652573. doi:10.4049/jimmunol.1400954

40. Wang AY, Kline J, Stock W, et al. Unexpected toxicities when nivolumab was given as maintenance therapy following allogeneic stem cell transplantation. Biol Blood Marrow Transplant. 2020;26:10251027. doi:10.1016/j.bbmt.2020.01.021

41. Steinerov K, Jindra P, Lysk D, Karas M. Development of resistant GvHD in a patient treated with nivolumab for hodgkins lymphoma relapse after allogeneic unrelated transplantation. Klin Onkol. 2019;32:6669. doi:10.14735/amko201966

42. Ijaz A, Khan AY, Malik SU, et al. Significant risk of graft-versus-host disease with exposure to checkpoint inhibitors before and after allogeneic transplantation. Biol Blood Marrow Transplant. 2019;25:9499. doi:10.1016/j.bbmt.2018.08.028

43. Albring JC, Inselmann S, Sauer T, et al. PD-1 checkpoint blockade in patients with relapsed AML after allogeneic stem cell transplantation. Bone marrow transplantation. 2017. doi:10.1038/bmt.2016.274

44. Covut F, Pinto R, Cooper BW, et al. Nivolumab before and after allogeneic hematopoietic cell transplantation. Bone marrow transplantation. 2017. doi:10.1038/bmt.2017.44

45. Herbaux C, Gauthier J, Brice P, et al. Nivolumab Is Effective and Reasonably Safe in Relapsed or Refractory Hodgkin's Lymphoma after Allogeneic Hematopoietic Cell Transplantation: A Study from the Lysa and SFGM-TC. Blood. 2015. doi:10.1182/blood.V126.23.3979.3979

46. Schoch LK, Borrello I, Fuchs EJ, et al. Checkpoint Inhibitor Therapy and Graft Versus Host Disease in Allogeneic Bone Marrow Transplant Recipients of Haploidentical and Matched Products with Post-Transplant Cyclophosphamide. Blood. 2016. doi:10.1182/blood.V128.22.4571.4571

47. Davids MS, Kim HT, Costello C, et al. Optimizing Checkpoint Blockade As a Treatment for Relapsed Hematologic Malignancies after Allogeneic Hematopoietic Cell Transplantation. Blood. 2017. doi:10.1182/blood.V130.Suppl_1.275.275

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[Full text] Successful Use of Nivolumab in a Patient with Head and Neck Cancer Aft | OTT - Dove Medical Press

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Two Studies Shed Light on How and Where the Body Can Add New Fat Cells – Technology Networks

By daniellenierenberg

Gaining more fat cells is probably not what most people want, although that might be exactly what they need to fight off diabetes and other diseases. How and where the body can add fat cells has remained a mystery - but two new studies from UT Southwestern provide answers on the way this process works.

The studies, both published online in Cell Stem Cell, describe two different processes that affect the generation of new fat cells. One reports how fat cell creation is impacted by the level of activity in tiny organelles inside cells called mitochondria. The other outlines a process that prevents new fat cells from developing in one fat storage area in mice - the area that correlates with the healthy subcutaneous fat just under the skin in humans. (Both studies were done in mice.)

In the second study, a commonly used cancer drug was able to jump-start healthy fat cell creation in mice, a finding that raises the possibility of future drug treatments for humans.

While fat isn't popular, as long as people overeat they will need a place to store the excess calories, explains Philipp Scherer, Ph.D., director of the Touchstone Center for Diabetes Research at UT Southwestern and senior author of the first study focusing on mitochondria. There are two options, he says: squeezing more lipids (fat) into existing fat cells and ballooning their size, leading to problems such as inflammation and, eventually, diabetes; or creating new fat cells to help spread the load. Fat stored properly - in fat cell layers under the skin (subcutaneous fat) that aren't overburdened instead of around organs (visceral fat) or even inside organs - is the healthy alternative, he says.

Problems follow if existing fat cells are left on their own to become engorged, adds Rana Gupta, Ph.D., associate professor of internal medicine and senior author of the second study. "When these cells are so overwhelmed that they can't take it anymore, they eventually die or become dysfunctional, spilling lipids into places not intended to store fat."

Those lipids may move into the liver, leading to fatty liver disease; to the pancreas, resulting in diabetes; or even to the heart, causing cardiovascular disease, Gupta says. Visceral, or belly fat, may surround the organs, creating inflammation.

The healthiest place to store fat is in subcutaneous fat, adds Gupta. Ironically, that is where mice in his study were least able to create new fat cells, despite the fact that stem-cell-like progenitor cells primed to become fat cells were present there as well, he says.

Gupta's study identified a process that prevents progenitor cells from developing into fat cells in mouse subcutaneous inguinal fat.

The protein HIF-1a (short for hypoxia-inducible factor-1 alpha) is central to the process. It kicks off a series of cellular actions that ultimately inactivate a second protein called PPARgamma, the key driver of fat cell formation.

These proteins are found in both humans and mice. In fact, in a culture of human subcutaneous fat cell progenitors, HIF-1a also inhibited new fat cells from being created, according to Gupta.

In Gupta's mouse study, researchers used a genetic approach to inhibit HIF-1a and found that the progenitor cells could then make subcutaneous inguinal fat cells and fewer were inflamed or fibrotic.

Next, they tested the cancer drug imatinib (brand name Gleevec) and found it had the same effect. The cancer drug was tried because it was known to have beneficial effects against diabetes in cancer patients with both diseases, Gupta says.

In Scherer's study, researchers manipulated a protein called MitoNEET in the outer membrane of the precursor cells' mitochondria, organelles known as the cells' power plants. The resulting mitochondrial dysfunction and drop in cell metabolism caused precursor cells to lose the ability to become new fat cells and increased inflammation.

"This study shows we can manipulate the precursor cells' willingness to become fat cells," Scherer says. "The ability to recruit new fat cells by tickling these pre-fat cells to become fat cells is very important and has profound beneficial effects on health, particularly in the obesity-prone environment that we all live in."

He says his goal is now to design a drug that could stimulate mitochondrial activity.

"Understanding the mechanism is an important first step," Scherer says, referring to the findings from the two studies. "We will have to learn in the future how to manipulate these processes pharmacologically."

Reference: Joffin N, Paschoal VA, Gliniak CM, et aI. Mitochondrial metabolism is a key regulator of the fibro-inflammatory and adipogenic stromal subpopulations in white adipose tissue. Cell Stem Cell. doi:doi.org/10.1016/j.stem.2021.01.002

This article has been republished from the following materials. Note: material may have been edited for length and content. For further information, please contact the cited source.

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Heidi Klum loves to pamper her skin with goodies from Drunk Elephant and Glossier – woman&home

By daniellenierenberg

With her sun-kissed hair and flawless golden skin, it's easy to forget that Heidi Klum is in her mid 40s. Genetics certainly help. But so do Heidi Klum's favourite skincare products by Glossier and Drunk Elephant, plus a reminder of home courtesy of German beauty brand The Cream by Augustinus Bader.

In a rare selfie, Klum showed off the Perfectil Hair Skin And Nails Vitamins she takes daily, alongside this smorgasbord of beauty products, which proves the supermodel takes her skincare seriously.

Here are some of her favourite products:

More from womanandhome:

Drunk Elephant T.L.C. Framboos Glycolic Resurfacing Night Serum

This night serum contains a hefty dose of glycol acid to exfoliate built-up dead skin cells and resurface dull, uneven skin. Expect brighter, smoother skin when you wake.

Drunk Elephant T.L.C. Sukari Babyfacial 25% AHA + 2% BHA Mask

If you like to feel a product working, you'll positive love this mask. Like an AHA/BHA facial in a bottle, it resurfaces skin to reveal greater clarity and improved skin tone.

Drunk Elephant C-Firma Day Serum

This vitamin C day serum is packed with antioxidants to protect skin from urban aggressors.

Glossier Solution

A liquid exfoliator that you apply a bit like toner, it buffs away dead dulling skin with a single swipe.

Mario Badescu Drying Lotion

We know, we know, even supermodels get spots. This cult zit lotion contains salicylic acid, sulfur, and zinc oxide to dry up blemishes - fast.

Augustinus Bader The Rich Cream

The brainchild of a stem cell scientist no less, this overnight treatment uses amino acids and vitamins to re-energise cells to repair damage more effectively.

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When to take fish oil: Timing, dosages and side effects – Medical News Today

By daniellenierenberg

There is no incorrect time of day to take fish oil supplements. However, some evidence suggests that people absorb omega-3 fatty acids more effectively when they take them with a meal that contains dietary fat.

This comes from a study in Current Opinion in Clinical Nutrition and Metabolic Care.

Fish oil is a major source of omega-3 fatty acids, which may have a number of health benefits.

In this article, we will discuss when people should take fish oil, how to take it, dosage, and any health benefits and side effects.

There is no significant benefit to taking fish oil at a specific time of day. However, people may wish to take fish oil with a meal that contains dietary fat.

A 2019 study on omega-3 found that taking an omega-3 concentrate with food that contains fat increased bioavailability, making it easier for the body to absorb.

Additionally, an older 2015 study found that taking omega-3 fatty acids with a low fat meal reduced absorption.

Both of these studies looked at omega-3 fatty acids specifically, so the results may not apply to people taking fish oil. Additionally, the amount of omega-3 in fish oil can vary, depending on factors such as the type of fish, and the brand.

People can take fish oil capsules with water during a meal. If a person typically does not eat much fat at breakfast, they may wish to wait until lunch or their evening meal before taking it.

Some people experience gastrointestinal side effects when taking fish oil. If a person experiences this side effect, they may find it helpful to split their fish oil into two doses and take them at different times of the day.

People who split their dose in half may need to take each one at different mealtimes.

Researchers have found it difficult to define an optimal amount of omega-3 fatty acids to get per day.

The American Heart Association (AHA) recommend adults take between 5001,000 milligrams of omega-3 per day. However, other countries and organizations recommend different doses.

The Office of Dietary Supplements (ODS) note that while some types of omega-3 have no official recommended dose, alpha-linolenic acid (ALA) is an exception. This table shows the recommended daily amounts by age and sex:

The amount of ALA in omega-3 supplements can depend on the type of supplement and the manufacturer. Read the product label to determine how much a supplement contains.

Omega-3 fatty acids may have a positive effect on human health in a number of ways. Research into its benefits is ongoing, but there is evidence that it may:

However, many studies on omega-3s health benefits focus on getting these fatty acids from fish and seafood, rather than from fish oil capsules. If a person is thinking of taking fish oil for a health condition, they should speak with a doctor first.

Some specific conditions that may benefit from a higher intake of omega-3 include:

According to a 2015 review, there is some evidence that consuming omega-3 fatty acids may help prevent or manage cardiovascular conditions. Omega-3 fatty acids may help reduce triglyceride levels in the blood and reduce the risk of cardiovascular death.

Omega-3 fatty acids may also have antiarrhythmic effects, which means they help a persons heart beat in a regular pattern. The effect that omega-3 fatty acids have on arrhythmia may significantly reduce the risk of fatal ventricular arrhythmias.

However, more recent studies show that there may not be a clear benefit to taking omega-3 to prevent adverse effects of cardiovascular conditions. There is also some evidence that taking statins at the same time as omega-3 fatty acid supplements may reduce their protective effect on cardiovascular conditions.

Scientists need to carry out more research on omega-3 and its relationship with preventing or managing cardiovascular diseases.

Some studies have shown that a high omega-3 intake can reduce the risk of inflammatory disease mortality.

Some have also found that omega-3 fatty acids are beneficial for people with Crohns disease and ulcerative colitis, two types of inflammatory bowel disease.

However, there is no clinically significant evidence on whether omega-3 fatty acids help prevent relapses for people with these conditions.

Several in vitro studies show that omega-3 fatty acids have an effect on colorectal cancer stem cells (CCSC). CCSC have a long lifespan and can self-renew, leading to colon tumors.

CCSC can lead to cancer relapse and chemotherapy resistance. Omega-3 fatty acids may stop CCSC from growing and may reduce chemotherapy resistance.

Omega-3 fatty acids may have several positive effects with regards to prostate cancer, although research on this is mixed.

Several studies have found that consuming fish or omega-3 fatty acids reduces the risk of developing prostate cancer, including aggressive forms.

However, other studies suggest that there is no clear benefit to consuming omega-3 fatty acids to prevent prostate cancer.

Side effects of fish oil supplements are usually mild. They include:

Additionally, omega-3 supplements can have an adverse interaction with drugs that affect blood clotting.

People should contact their healthcare provider to ensure it is safe for them to take a supplement before trying it.

Some evidence suggests that taking supplements that contain omega-3 with a meal that contains fat can increase absorption. As a result, people may wish to take fish oil at breakfast, lunch, or dinner. However, there is no correct or incorrect time to take it.

Always speak with a doctor before starting a new supplement. If a person experiences side effects, they may benefit from splitting their dose in two.

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I Tried MAC’s Virtual Try-On Tool & Here’s What Happened – GLAMOUR UK

By daniellenierenberg

There's no better time than a national lockdown to test out the coolest new skincare/makeup/hair trends and snazzy innovations in beauty tech from the comfort of your own home. That said, there's nothing more frustrating than spending upwards of 100 on a snazzy new hair treatment or at-home facial system, only to find out it doesn't *actually* work.

Enter GLAMOUR Tries: the weekly Instagram series which sees GLAMOUR editors do all of the time-consuming (and expensive) work for you.

We've been busy trying out all of the (sometimes) wacky but always wonderful beauty crazes to take the internet by storm - from the FOREO's UFO 2 Smart Mask Treatment to Sarah Chapman's 138 Meso-Melt Infusion at-home facial and Toni&Guy's Hello Day! Secret Volumising Crimper. These are the products that every veteran beauty sleuth is talking about - but that you want to do a bit of research into before buying.

Thanks to GLAMOUR Tries, you won't need to waste your hard-earned pennies on testing these innovations yourself. We're getting in their first, giving you the lowdown and making sure you invest in products that genuinely work. Like what you see? You can shop all of the products seen on GLAMOUR tries, with the click of a button, down below. Don't say we don't treat you.

On GLAMOUR Tries this week, our Beauty Editor Lottie Winter tried MAC's brand new virtual try-on tool, in an attempt to find her perfect shade of the classic Studio Fix foundation - from the comfort of her sofa. But was the tool accurate? Was the selected foundation *actually* Lottie's exact match? Here's what happened...

First thing's first: how can you access the tool? "All you have to do is go to the MAC website, find the Studio Fix foundation and simply click on "find your shade match" - and it'll take you straight through to the virtual try-on tool," said Lottie. Click "start now", "allow access to your camera" and then - strike a pose!

"Within just a few seconds, it has selected not only my best match but options for a more golden, more rosy, darker and lighter finish," Lottie continued. "N6 is the shade of Studio Fix Fluid foundation that the virtual try-on tool has chosen for me. So, let's put it to the test..."

Buy It Now

"I'm using a MAC 170 brush to apply. I've just half of my face so we can compare the results - but it couldn't be a better match. It has blended so effortlessly and it has knocked out all the redness around my nose and my eyes.

"What I love most about this foundation is that it's super long-wearing and it helps to control shine throughout the day which is great if you're like me and you have very oily skin. But also the coverage is buildable which means you can get that believable finish."

Any final thoughts? "It couldn't have been easier to get my perfect shade match. It just makes shopping for foundation online so much easier and totally reliable," said Lottie. We're sold.

Would you MAC's virtual try-on tool a go? Have you already tried it? Let us know your thoughts over on Instagram @glamouruk.

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