Researchers have synthesized a key compound, pantetheine, under early Earth-like conditions, offering new insights into life’s origins. This breakthrough challenges previous notions about life’s beginnings in water, suggesting a simultaneous emergence of essential biological molecules, and paving the way for future explorations into the chemistry of life’s foundation.
A new study led by researchers at UCL has successfully synthesized a chemical compound in the laboratory under conditions that could have existed on early Earth, indicating its potential involvement in the emergence of life.
A new study led by researchers at UCL has synthesized a chemical compound critical to all forms of life under lab conditions that mimic those of early Earth, indicating its importance in the emergence of life.
The compound, pantetheine, is the active fragment of Coenzyme A. It is important for metabolism – the chemical processes that maintain life. Earlier studies failed to synthesize pantetheine effectively, leading to suggestions that it was absent at life’s origin.
In the new study, published in the journal Science, the research team created the compound in water at room temperature using molecules formed from hydrogen cyanide, which was likely abundant on early Earth.
Once formed, the researchers said, it is simple to envisage how pantetheine might have aided chemical reactions that led from simple forerunners of protein and RNA molecules to the first living organisms – a moment that is thought to have occurred 4 billion years ago.
The study challenges the view among some researchers in the field that water is too destructive for life to originate in it and that life more likely originated in pools that periodically dried out.
Driving the reactions that produced pantetheine were energy-rich molecules called aminonitriles, which are closely chemically related to amino acids, the building blocks of proteins and of life.
Members of the same team, led by Professor Matthew Powner (UCL Chemistry), have already used similar chemistry powered by aminonitriles to demonstrate how other key biological ingredients could be created at the origin of life, including peptides (protein-creating chains of amino acids) and nucleotides (the building blocks of RNA and DNA).
Professor Powner, senior author of the paper, said: “This new study is further evidence that the basic structures of biology, the primary molecules that biology is built from, are predisposed to form through nitrile chemistry.
“The ease with which different classes of biological molecules can be made using nitriles has convinced me that, rather than life being preceded by one molecule such as RNA, and there being an ‘RNA world’ before life began, the basic molecules of biology emerged alongside each other – a network of RNAs, proteins, enzymes and cofactors leading to the first living organisms.
“Our future work will look at how these molecules came together, how pantetheine chemistry talks to RNA, peptide, and lipid chemistry for instance, to deliver chemistry that the individual classes of molecule could not deliver in isolation.”
A notable earlier attempt to synthesize pantetheine was made in 1995 by the late American chemist Stanley Miller, who had started the field of origin of life experiments three decades earlier, creating amino acids from four simple chemicals in glass tubes.
However, in the later 1995 experiment, the yields of pantetheine were very low and required extremely high concentrations of chemicals that had been dried out and sealed in an airtight tube before they were heated to 100 degrees Centigrade.
Dr. Jasper Fairchild (UCL Chemistry), a lead author of the study, who conducted the work as part of his PhD, said: “The major difference between Miller’s study and ours is whereas Miller tried to use acid chemistry, we used nitriles. It’s the nitriles that bring the energy and the selectivity. Our reactions just run in water and produce high yields of pantetheine with relatively low concentrations of chemicals needed.”
Professor Powner added: “It had been assumed you should make these molecules from acids, because using acids appears to be biological, and that is what we are taught at school and at university. We are taught peptides are made from amino acids.
“Our work suggests this conventional view has ignored an essential ingredient, the energy required to forge new bonds. The reactions look a little different with nitriles but the end products – the basic units of biology – are indistinguishable whether formed through acid or nitrile chemistry.”
While the paper focuses solely on the chemistry, the research team said that the reactions they demonstrated could plausibly have taken place in pools or lakes of water on the early Earth (but not likely in the oceans as the concentrations of the chemicals would likely be too diluted).
New research reveals that replacing regular salt with a salt substitute can lower the risk of hypertension by 40% in older adults without increasing low blood pressure risks. Conducted among elderly residents in China, the findings highlight the efficacy of salt substitutes in managing blood pressure and suggest broader adoption in food processing to combat global hypertension challenges.
Salt substitutes present a healthy alternative for reducing salt intake, decreasing the risk of hypertension without increasing low blood pressure episodes, according to a new study.
Switching out regular salt for a salt substitute can lower the incidence of high blood pressure in the elderly without raising their chances of experiencing episodes of low blood pressure, a recent study in the Journal of the American College of Cardiology has found.
People who used a salt substitute had a 40% lower incidence and likelihood of experiencing hypertension compared to those who used regular salt.
According to the World Health Organization, hypertension is the leading risk factor for cardiovascular disease and mortality. It affects over 1.4 billion adults and results in 10.8 million deaths per year worldwide.
One of the most effective ways to reduce hypertension risk is to reduce sodium intake. This study looks at salt substitutes as a better solution to control and maintain healthy blood pressure than reducing salt alone.
“Adults frequently fall into the trap of consuming excess salt through easily accessible and budget-friendly processed foods,” said Yangfeng Wu, MD, PhD, lead author of the study and Executive Director of Peking University Clinical Research Institute in Beijing, China. “It’s crucial to recognize the impact of our dietary choices on heart health and increase the public’s awareness of lower-sodium options.”
Researchers in this study evaluated the impact of sodium reduction strategies on blood pressure in elderly adults residing in care facilities in China. While previous studies prove that reducing salt intake can prevent or delay new-onset hypertension, long-term salt reduction and avoidance can be challenging.
The DECIDE-Salt study included 611 participants 55 years or older from 48 care facilities split into two groups: 24 facilities (313 participants) replacing usual salt with the salt substitute and 24 facilities (298 participants) continuing the use of usual salt. All participants had blood pressure <140/90mmHg and were not using anti-hypertension medications at baseline. The primary outcome was participants who had incident hypertension, initiated anti-hypertension medications, or developed major cardiovascular adverse events during follow-up.
At two years, the incidence of hypertension was 11.7 per 100 people-years in participants with salt substitute and 24.3 per 100 people-years in participants with regular salt. People using the salt substitute were 40% less likely to develop hypertension compared to those using regular salt. Furthermore, the salt substitutes did not cause hypotension, which can be a common issue in older adults.
“Our results showcase an exciting breakthrough in maintaining blood pressure that offers a way for people to safeguard their health and minimize the potential for cardiovascular risks, all while being able to enjoy the perks of adding delicious flavor to their favorite meals,” Wu said. “Considering its blood pressure-lowering effect, proven in previous studies, the salt substitute shows beneficial to all people, either hypertensive or normotensive, thus a desirable population strategy for prevention and control of hypertension and cardiovascular disease.”
Limitations of the study include that it is a post-hoc analysis, study outcomes were not pre-specified and there was a loss of follow-up visits in many patients. Analyses indicated that these missing values were at random, and multiple sensitivity analyses supports the robustness of the results.
In an accompanying editorial comment, Rik Olde Engberink, MD, PhD, researcher, nephrologist, and clinical pharmacologist at Amsterdam University Medical Center’s Department of Internal Medicine, said the study provides an attractive alternative to the failing strategy to reduce the intake of salt worldwide, but questions and effort remain.
“In the DECIDE-Salt trial, the salt substitute was given to the kitchen staff, and the facilities were not allowed to provide externally sourced food more than once per week,” Olde Engberink said. “This approach potentially has a greater impact on blood pressure outcomes, and for this reason, salt substitutes should be adopted early in the food chain by the food industry so that the sodium-potassium ratio of processed foods will improve.”
Researchers have made a groundbreaking discovery about Long COVID’s neurological effects, including brain fog and cognitive decline. By identifying blood vessel disruption in the brain, they offer new insights for diagnosing and treating the condition, potentially transforming the approach to post-viral neurological syndromes.
Scientists uncover crucial links between Long COVID and brain blood vessel integrity, offering hope for new treatments and diagnostic methods.
A team of scientists from Trinity College Dublin and investigators from FutureNeuro announced a major discovery that has profound importance for our understanding of brain fog and cognitive decline seen in some patients with Long COVID.
In the months after the emergence of the novel coronavirus SARS-CoV2 in late 2019 a patient-reported syndrome termed Long-COVID began to come to the fore as an enduring manifestation of acute infection.
Long COVID has up to 200 reported symptoms to date, but in general, patients report lingering symptoms such as fatigue, shortness of breath, problems with memory and thinking, and joint/muscle pain. While the vast majority of people suffering from COVID-19 make a full recovery, any of these symptoms that linger for more than 12 weeks post-infection can be considered Long COVID.
Long COVID has now become a major public health issue since the outbreak of the pandemic in 2020. While international incidence rates vary, it is estimated to affect up to 10% of patients infected with the SARS-CoV2 virus. Of these patients suffering from Long-COVID, just under 50% of them report some form of lingering neurological effect such as cognitive decline, fatigue, and brain fog.
https://www.youtube.com/embed/5Msmbfy4mv4?feature=oembed
Researchers from Trinity College Dublin discover link between leaky blood vessels in the brain and Long Covid patients reporting brain fog.
Now, the findings reported by the Trinity team in the top international journal Nature Neuroscience showed that there was disruption to the integrity of the blood vessels in the brains of patients suffering from Long COVID and brain fog. This blood vessel “leakiness” was able to objectively distinguish those patients with brain fog and cognitive decline compared to patients suffering from Long-COVID but not with brain fog.
The team led by scientists at the Smurfit Institute of Genetics in Trinity’s School of Genetics and Microbiology and neurologists in the School of Medicine have also uncovered a novel form of MRI scan that shows how Long-COVID can affect the human brain’s delicate network of blood vessels.
“For the first time, we have been able to show that leaky blood vessels in the human brain, in tandem with a hyperactive immune system may be the key drivers of brain fog associated with Long COVID. This is critically important, as understanding the underlying cause of these conditions will allow us to develop targeted therapies for patients in the future,” said Prof. Matthew Campbell, Professor in Genetics and Head of Genetics at Trinity, and Principal Investigator at FutureNeuro.
This project was initiated by a rapid response grant funded by Science Foundation Ireland (SFI) at the height of the pandemic in 2020 and involved recruiting patients suffering from the effects of Long-COVID as well as patients who were hospitalized in St James’ Hospital.
“Undertaking this complicated clinical research study at a time of national crisis and when our hospital system was under severe pressure is a testament to the skill and resource of our medical trainees and staff. The findings will now likely change the landscape of how we understand and treat post-viral neurological conditions. It also confirms that the neurological symptoms of Long Covid are measurable with real and demonstrable metabolic and vascular changes in the brain,” said Prof. Colin Doherty, Professor of Neurology and Head of the School of Medicine at Trinity, and Principal Investigator at FutureNeuro.
In recent years, it has become apparent that many neurological conditions such as Multiple sclerosis (MS) likely have a viral infection as the initiating event that triggers the pathology. However, proving that direct link has always been challenging.
Prof. Campbell added: “Here, the team at Trinity was able to prove that every patient that developed Long-COVID had been diagnosed with SARS-CoV2 infection, because Ireland required every documented case to be diagnosed using the more accurate PCR-based methods. The concept that many other viral infections that lead to post-viral syndromes might drive blood vessel leakage in the brain is potentially game-changing and is under active investigation by the team.”
Dr. Chris Greene, Postdoctoral research fellow and first author of the study, added: “Our findings have now set the stage for further studies examining the molecular events that lead to post-viral fatigue and brain fog. Without doubt, similar mechanisms are at play across many disparate types of viral infection and we are now tantalizingly close to understanding how and why they cause neurological dysfunction in patients.”
High protein consumption may elevate atherosclerosis risk by activating immune cells that contribute to arterial plaque formation, with leucine playing a critical role, according to a study by the University of Pittsburgh School of Medicine
High protein consumption may elevate atherosclerosis risk by activating immune cells that contribute to arterial plaque formation, with leucine playing a critical role.
University of Pittsburgh School of Medicine researchers discovered a molecular mechanism by which excessive dietary protein could increase atherosclerosis risk. The findings were published on February 19 in Nature Metabolism.
The study, which combined small human trials with experiments in mice and cells in a Petri dish, showed that consuming over 22% of dietary calories from protein can lead to increased activation of immune cells that play a role in atherosclerotic plaque formation, driving the disease risk. Furthermore, the scientists showed that one amino acid – leucine – seems to have a disproportionate role in driving the pathological pathways linked to atherosclerosis, or stiff, hardened arteries.
“Our study shows that dialing up your protein intake in pursuit of better metabolic health is not a panacea. You could be doing real damage to your arteries,” said senior and co-corresponding author Babak Razani, M.D., Ph.D., professor of cardiology at Pitt. “Our hope is that this research starts a conversation about ways of modifying diets in a precise manner that can influence body function at a molecular level and dampen disease risks.”
Babak Razani, M.D., Ph.D. Credit: University of Pittsburgh
According to a survey of the average American diet over the last decade, Americans generally consume a lot of protein, mostly from animal sources. Further, nearly a quarter of the population receives over 22% of all daily calories from protein alone.
That trend is likely driven by the popular idea that dietary protein is essential to healthy living, says Razani. But his and other groups have shown that overreliance on protein may not be such a good thing for long-term health.
Following their 2020 research, in which Razani’s laboratory first showed that excess dietary protein increases atherosclerosis risk in mice, his next study in collaboration with Bettina Mittendorfer, Ph.D., a metabolism expert at the University of Missouri, Columbia, delved deeper into the potential mechanism and its relevance to the human body.
To arrive at the answer, Razani’s laboratory, led by first-authors Xiangyu Zhang, Ph.D., and Divya Kapoor, M.D., teamed up with Mittendorfer’s group to combine their expertise in cellular biology and metabolism and perform a series of experiments across various models – from cells to mice to humans.
“We have shown in our mechanistic studies that amino acids, which are really the building blocks of the protein, can trigger disease through specific signaling mechanisms and then also alter the metabolism of these cells,” Mittendorfer said. “For instance, small immune cells in the vasculature called macrophages can trigger the development of atherosclerosis.”
Based on initial experiments in healthy human subjects to determine the timeline of immune cell activation following ingestion of protein-enriched meals, the researchers simulated similar conditions in mice and in human macrophages, immune cells that are shown to be particularly sensitive to amino acids derived from protein.
Their work showed that consuming more than 22% of daily dietary calories through protein can negatively affect macrophages that are responsible for clearing out cellular debris, leading to the accumulation of a “graveyard” of those cells inside the vessel walls and worsening of atherosclerotic plaques over time. Interestingly, the analysis of circulating amino acids showed that leucine – an amino acid enriched in animal-derived foods like beef, eggs, and milk – is primarily responsible for abnormal macrophage activation and atherosclerosis risk, suggesting a potential avenue for further research on personalized diet modification, or “precision nutrition.”
Razani is careful to note that many questions remain to be answered, mainly: What happens when a person consumes between 15% of daily calories from protein as recommended by the USDA and 22% of daily calories from protein, and if there is a ‘sweet spot’ for maximizing the benefits of protein – such as muscle gain – while avoiding kick-starting a molecular cascade of damaging events leading to cardiovascular disease.
The findings are particularly relevant in hospital settings, where nutritionists often recommend protein-rich foods for the sickest patients to preserve muscle mass and strength.
“Perhaps blindly increasing protein load is wrong,” Razani said. “Instead, it’s important to look at the diet as a whole and suggest balanced meals that won’t inadvertently exacerbate cardiovascular conditions, especially in people at risk of heart disease and vessel disorders.”
Razani also notes that these findings suggest differences in leucine levels between diets enriched in plant and animal protein might explain the differences in their effect on cardiovascular and metabolic health. “The potential for this type of mechanistic research to inform future dietary guidelines is quite exciting,” he said.
A new study highlights the detrimental effects of yo-yo dieting, showing how societal pressures lead to a cycle of weight loss and regain, associated with psychological and interpersonal distress. It advises against dieting unless necessary and suggests focusing on health and healthy behaviors to break free from this harmful cycle.
A recent qualitative research emphasizes the adverse psychological and interpersonal effects linked to “yo-yo dieting,” or weight cycling. The study sheds light on the harmful nature of yo-yo dieting and the challenges individuals face in escaping this cycle.
“Yo-yo dieting – unintentionally gaining weight and dieting to lose weight only to gain it back and restart the cycle – is a prevalent part of American culture, with fad diets and lose-weight-quick plans or drugs normalized as people pursue beauty ideals,” says Lynsey Romo, corresponding author of a paper on the study and an associate professor of communication at North Carolina State University.
“Based on what we learned through this study, as well as the existing research, we recommend that most people avoid dieting, unless it is medically necessary. Our study also offers insights into how people can combat insidious aspects of weight cycling and challenge the cycle.”
For the study, researchers conducted in-depth interviews with 36 adults – 13 men and 23 women – who had experienced weight cycling where they lost and regained more than 11 pounds. The goal was to learn more about why and how people entered the yo-yo dieting cycle and how, if at all, they were able to get out of it.
All the study participants reported wanting to lose weight due to social stigma related to their weight, and/or because they were comparing their weight to that of celebrities or peers.
“Overwhelmingly, participants did not start dieting for health reasons, but because they felt social pressure to lose weight,” Romo says.
The study participants also reported engaging in a variety of weight-loss strategies, which resulted in initial weight loss, but eventual regain.
Regaining the weight led people to feel shame and further internalize the stigma associated with weight – leaving study participants feeling worse about themselves than they did before they began dieting. This, in turn, often led people to engage in increasingly extreme behaviors to try to lose weight again.
“For instance, many participants engaged in disordered weight management behaviors, such as binge or emotional eating, restricting food and calories, memorizing calorie counts, being stressed about what they were eating and the number on the scale, falling back on quick fixes (such as low-carb diets or diet drugs), overexercising, and avoiding social events with food to drop pounds fast,” says Romo. “Inevitably, these diet behaviors became unsustainable, and participants regained weight, often more than they had initially lost.”
“Almost all of the study participants became obsessed with their weight,” says Katelin Mueller, co-author of the study and graduate student at NC State. “Weight loss became a focal point for their lives, to the point that it distracted them from spending time with friends, family, and colleagues and reducing weight-gain temptations such as drinking and overeating.”
“Participants referred to the experience as an addiction or a vicious cycle,” Romo says. “Individuals who were able to understand and address their toxic dieting behaviors were more successful at breaking the cycle. Strategies people used to combat these toxic behaviors included focusing on their health rather than the number on the scale, as well as exercising for fun, rather than counting the number of calories they burned.
“Participants who were more successful at challenging the cycle were also able to embrace healthy eating behaviors – such as eating a varied diet and eating when they were hungry – rather than treating eating as something that needs to be closely monitored, controlled, or punished.”
However, the researchers found the vast majority of study participants stuck in the cycle.
“The combination of ingrained thought patterns, societal expectations, toxic diet culture, and pervasive weight stigma make it difficult for people to completely exit the cycle, even when they really want to,” Romo says.
“Ultimately, this study tells us that weight cycling is a negative practice that can cause people real harm,” Romo says. “Our findings suggest that it can be damaging for people to begin dieting unless it is medically necessary. Dieting to meet some perceived societal standard inadvertently set participants up for years of shame, body dissatisfaction, unhappiness, stress, social comparisons, and weight-related preoccupation. Once a diet has begun, it is very difficult for many people to avoid a lifelong struggle with their weight.”
As cases of diabetes, obesity, and hypertension continue to rise, more people are looking for solutions in the form of sugar substitutes. Sugar, after all, has been linked to a number of health issues, but going cold turkey on the sweet stuff can be difficult.
One sugar substitute in particular that has been making waves is allulose. This natural, low-calorie sugar was recently approved for use in food by the U.S Food and Drug Administration (FDA), a development that one industry report published in October 2023 noted was key to the $17 billion industry. Because allulose is said to offer the flavor and texture of sugar without the calories or blood sugar spike, many people see it as a promising alternative. Still, like any food or ingredient, there are reasons to be cautious. Read on to learn how allulose is made, the potential risks and benefits, and how to use it.
Is allulose healthier than sugar?
Allulose offers the same sweet taste and texture as sugar. Yet it packs only a fraction of the calories and doesn’t raise blood glucose (sugar) levels. This makes allulose a healthier choice than sugar.
Can you eat allulose if you have type 2 diabetes?
Is allulose keto-friendly?
What foods contain allulose?
What does allulose taste like?
Allulose, also known as D-allulose or D-Psicose, is a natural but rare monosaccharide (simple sugar), according to the American Chemical Society (ACS). It’s found in small amounts in foods such as raisins and figs, says Brittany Poulson, RDN, CDCES, who is based in Grantsville, Utah.
While allulose is technically a natural sugar, it occurs in such small amounts (it’s considered a rare sugar) that most of the allulose sold in grocery stores and online is artificially made, Poulson notes. It was originally produced from corn, but manufacturers now create it from cellulose (the primary substance in plant cell walls), starch (a type of carbohydrate), or other byproducts, per the ACS.
Allulose is chemically similar to fructose (a sugar in fruit) and glucose (a simple sugar), however, it isn’t metabolized by the body in the same way. About 70 percent of the allulose we consume is absorbed by the small intestine, eventually leaving the body via urine within 24 hours, according to Food Insight. The remaining 30 percent passes through the large intestine and is excreted within 48 hours. Therefore, unlike other sugars, allulose has no impact on blood glucose (sugar) or insulin levels, according to a review and meta-analysis published in November 2018 in Nutrients.
Allulose also contains significantly fewer calories than sucrose (table sugar): 0.4 calories per gram (or ¼ teaspoon) in allulose compared with 4 calories per gram in table sugar, per the FDA. Yet allulose still has the sweetness of sugar, Poulson says, albeit not the same intensity.
The authors of a separate study that was also published in November 2018 in Nutrients asked 40 people to rate the intensity of 16 sweeteners, including allulose and a sucrose-allulose mixture. Participants rated allulose as less sweet than sucrose, but they found that equal amounts of sucrose and allulose mixed together were nearly as sweet as sucrose alone.
You can find allulose in small amounts in foods like figs, raisins, wheat, and maple syrup, but it’s also added to sweeten foods, according to the Calorie Control Council. In addition, you can buy allulose online and in stores.
At this point, allulose isn’t widely used in commercial products, and it’s pricier than other sweeteners, says Frank Hu, MD, PhD, a professor of nutrition and epidemiology and the chair of the department of nutrition at the Harvard T.H. Chan School of Public Health in Boston.
Allulose is generally recognized as safe by the FDA. The FDA also reviewed allulose to determine if it needed to be accounted for in the grams of total sugars or added sugars on nutrition facts labels. In May 2016, the agency stated that allulose must be declared as a sugar on nutrition facts labels. But after further review, the FDA issued updated guidance for food manufacturers in October 2020 that reversed its initial statement. Currently, food manufacturers don’t have to account for allulose in the grams of total sugars or added sugars in foods. The FDA considers allulose a carb, however, meaning it has to be included in the total carbohydrate amounts on nutrition facts labels.
This alternative sweetener packs more than a pleasant flavor — it also offers potential benefits.
After looking over the research, the FDA concluded that allulose has no impact on blood sugar levels. But some studies suggest that allulose may help tame blood sugar spikes after eating. For example, a study published in 2021 in BMJ Open Diabetes Research & Care found that ingesting 10 grams of allulose dissolved in a glass of water led to a reduction in plasma glucose 30 minutes after eating 50 grams of table sugar, compared with plain water. In other words, the allulose was enough to counteract the blood sugar spike normally attributed to table sugar, researchers say. As this study included only 30 people, it’s hard to tell how allulose might affect the broader population. What’s more, the people in the study didn’t have diabetes. More research is needed to determine whether allulose offers short- or long-term benefits for people with diabetes.
Sugar contains carbs and is a no-no for those following the ketogenic (keto) diet. The keto diet is an eating pattern that involves limiting carb intake to fewer than 20 to 50 grams per day, according to Harvard Health Publishing. Allulose is a keto-friendly sweetener, according to Ketogenic.com. While allulose is considered a carb on nutrition facts labels, it’s not metabolized in the body and contributes very few calories to the diet, notes the Calorie Control Council. For that reason, allulose may not interfere with a ketogenic eating plan.
Allulose tastes and behaves like granulated sugar, making it a good choice for baked goods and ice cream, per the Calorie Control Council. While the end result won’t be as sweet (Food Insight notes that allulose is only 70 percent as sweet as table sugar), replacing table sugar with allulose when baking will lower the calories and prevent blood sugar spikes.
There has been a lot of controversy over the use of artificial sweeteners to aid weight loss, and in May 2023, the World Health Organization released guidelines recommending against the use of non-sugar sweeteners to control body weight or reduce the risk of noncommunicable diseases, citing the findings of a systematic review.
Research, however, is still ongoing and has been limited to small and short-term studies in humans. Few studies have looked at allulose specifically. In one that did, 121 overweight Korean adults supplemented with a placebo, a low dose of allulose (4 grams twice a day), or a high dose of allulose (7 grams twice a day). After 12 weeks, people who supplemented with high doses of allulose saw significant decreases in body fat percentage and body fat mass compared with the low-dose and control groups, according to the results, which were published in Nutrients in February 2018. Researchers don’t know why this might be, though previous research suggests that allulose regulates fat metabolism in mice.
While allulose is generally recognized as safe, it can carry side effects, mainly symptoms of gastrointestinal (GI) upset such as bloating, gas, diarrhea, and stomachache, Poulson says. In a study published in December 2018 in Nutrients, 30 adults with no chronic disease experienced severe diarrhea and GI symptoms such as bloating and nausea after ingesting 0.5 grams of allulose per kilogram of body weight in a single serving, but they had no symptoms at lesser amounts. These findings led researchers to suggest a maximum single serving of 0.4 grams of allulose per kilogram of body weight and a maximum daily total of 0.9 grams per kilogram. So a person with a body weight of 132 pounds (60 kilograms) can consume a maximum of 24 grams of allulose in a single serving and 54 grams daily. For reference, one packet of sugar — like the kind you’d add to coffee — is approximately 3 grams, per the U.S. Department of Agriculture.
People with diabetes who take insulin will want to be especially cautious, because those dosages are based on the carbohydrate content of foods. While allulose is included in the total carbohydrate content on food labels, it doesn’t affect blood sugar, which could lead someone to take more insulin than needed, causing low blood sugar. Make sure to consult your primary healthcare provider about allulose if you take insulin for diabetes.
Like many sugar substitutes, allulose is frequently used in baked goods. If you’re interested in using allulose to cook and bake at home, here are a few recipes featuring the sweetener:
Allulose is an alternative sweetener with the same taste and texture as table sugar. It has only a fraction of the calories and doesn’t raise blood sugar levels. While allulose is generally recognized as safe, it may cause GI upset when eaten in large amounts.
A new study by researchers from the Wellcome Sanger Institute and their collaborators at the UK Dementia Research Institute at the University of Cambridge sought to determine the biology of cellular health and identify genes keys to maintaining genome stability. The researchers uncovered 145 genes through systematic screening of nearly 1,000 genetically modified mouse lines, and possible strategies to curb progression of human genomic disorders.
The findings are published in Nature in an article titled, “Genetic determinants of micronucleus formation in vivo.”
“Genomic instability arising from defective responses to DNA damage or mitotic chromosomal imbalances can lead to the sequestration of DNA in aberrant extranuclear structures called micronuclei (MN),” the researchers wrote. “Although MN are a hallmark of aging and diseases associated with genomic instability, the catalogue of genetic players that regulate the generation of MN remains to be determined. Here we analyse 997 mouse mutant lines, revealing 145 genes whose loss significantly increases (n = 71) or decreases (n = 74) MN formation, including many genes whose orthologues are linked to human disease.”
Using a set of genetically modified mouse lines, the researchers discovered 145 genes that play key roles in either increasing or decreasing the formation of abnormal micronuclei structures.
The most dramatic increases in genomic instability were seen when the researchers knocked out the gene DSCC1, increasing abnormal micronuclei formation five-fold. Mice lacking this gene mirrored characteristics akin to human patients with cohesinopathy disorders.
Using CRISPR screening, researchers showed this effect triggered by DSCC1 loss could be partially reversed through inhibiting protein SIRT14.
Gabriel Balmus, PhD, senior author of the study at the UK Dementia Research Institute at the University of Cambridge, formerly at the Wellcome Sanger Institute, said: “Continued exploration on genomic instability is vital to develop tailored treatments that tackle the root genetic causes, with the goal of improving outcomes and the overall quality of life for individuals across various conditions. Our study underscores the potential of SIRT inhibitors as a therapeutic pathway for cohesinopathies and other genomic disorders. It suggests that early intervention, specifically targeting SIRT1, could help mitigate the biological changes linked to genomic instability before they progress.”
David Adams, PhD, first author of the study at the Wellcome Sanger Institute, said: “Genomic stability is central to the health of cells, influencing a spectrum of diseases from cancer to neurodegeneration, yet this has been a relatively underexplored area of research. This work, 15 years in the making, exemplifies what can be learned from large-scale, unbiased genetic screening. The 145 identified genes, especially those tied to human disease, offer promising targets for developing new therapies for genome instability-driven diseases like cancer and neurodevelopmental disorders.”
Researchers have known for decades that cisplatin achieves better objective response rates—and can even attain cure—in some patients with bladder cancer better than carboplatin. However, the mechanisms underlying those clinical observations have remained elusive until now. Investigators at the Tisch Cancer Institute at Mount Sinai Medical Center have learned that cisplatin-based chemotherapy improves the immune system’s ability to fight off bladder cancer, particularly when combined with immunotherapy, according to a study published in Cell Reports Medicine.
In in vitro experiments, the team demonstrated that cisplatin, compared with carboplatin, exerts direct immunomodulatory effects on cancer cells, promoting dendritic cell activation and antigen-specific T cell killing. These results underscore the key role of immune modulation in cisplatin’s efficacy in metastatic bladder cancer and highlight the importance of specific chemotherapy backbones in immunotherapy combination regimens.
“Our findings suggest that cisplatin does not likely induce an immune response but rather likely reboots a prior restrained immune response,” says lead author Matthew Galsky, MD, co-director of the Center of Excellence for Bladder Cancer at the Tisch Cancer Institute at Mount Sinai.
“This is not unlike what is hypothesized to occur with immune checkpoint blockade (ICB). The exact mechanisms might be different, but the result might be similar—here, we know that cisplatin the chemotherapy causes DNA damage in cancer cells,” he explains. “In turn, this DNA damage leads to downstream expression of antigen presentation machinery and danger signals which we think has a secondary impact on immune cells in the tumor microenvironment leading to activation of dendritic cells which then “reboot” restrained T cells.”
These downstream immune-stimulating effects are not observed with carboplatin-based chemotherapy. The new findings may explain why cisplatin chemotherapy can lead to cure in a small subset of patients with metastatic, or advanced, bladder cancer.
Previous large-scale studies like IMvigor130 and Keynote-361—which tested immunotherapy plus platinum-based chemotherapy with either carboplatin or cisplatin—did not appear to improve overall survival.
“However, when one dissects those studies, it looks like patients receiving cisplatin benefited from ICB,” adds Galsky. These results were validated in the recent Checkmate 901 study which showed a survival benefit with the addition of nivolumab immunotherapy to gemcitabine plus cisplatin in urothelial cancer.
“All of this data suggests that cisplatin may pair better than carboplatin with ICB in metastatic urothelial cancer given cisplatin’s ability to modulate the immune system and ICB likely has complementary immune-modulating effects,” Galsky says.
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