[ad_1]
“Certain foods can cause vaginal infections due to their effects on hormonal balance, immune function, and the vaginal microbiome,” says Melanie Bone, MD, a consultant OBGYN and US Medical Director at Daye. “For example, foods high in sugar can promote the growth of yeast, while processed foods can disrupt the balance of vaginal flora.”
[ad_2]
[ad_1]
“As the largest and most visible organ, the skin not only gives clues into what’s happening beneath the surface in terms of immune function, nutrition, oxidative stress, and metabolic issues, to name a few, but it’s the body’s first line of defense against infection, environmental stressors, and loss of nutrients and water, so addressing the skin is a gateway to overall health and well-being,” says board-certified dermatologist Keira Barr, M.D. “The skin microbiome is constantly interacting with our environment and works to support our health by protecting against infection, influencing the immune response, protecting against UV radiation, and helps provide nourishment to the skin cells.”
[ad_2]
[ad_1]
After years as a wellness writer, I’ve become all too aware of the fact that gut health is the foundation for a happy, healthy life. Because of this, I’m always looking for solutions to help me prioritize my gut and microbiome health—in ways that fit into my routine easily and effortlessly.
[ad_2]
[ad_1]
There haven’t been a lot of studies done on this directly, but the short answer is: maybe. “In theory, drinking black coffee may assist in reducing belly fat. The caffeine present in coffee has thermogenic properties, meaning it can stimulate the body’s metabolic rate and thus, boost fat-burning processes,” says Greenleaf. “Additionally, consuming coffee before engaging in physical exercise may enhance overall workout performance and increase the number of calories burned during the session, ultimately contributing to reduced belly fat.”
[ad_2]
[ad_1]
If you struggle with any of the signs mentioned above (or simply want to get a glimpse into your gut microbiome), then you may be interested in trying out a microbiome test.
Here’s who might find these tests interesting:
Individuals with digestive complaints: For those experiencing consistent gastrointestinal issues such as bloating, constipation, or irritable bowel syndrome (IBS)—all key signs of an unhealthy gut microbiome—an at-home test can help pinpoint potential microbial imbalances that could be causing these problems.
People with chronic conditions: Diabetes, obesity, and autoimmune disorders have all been linked to gut health. A microbiome test might offer valuable insights for better management of these diseases.
Wellness enthusiasts: Those keen on maximizing their health could use a gut microbiome test to better understand their unique gut flora and make informed dietary or lifestyle modifications. Wilde puts it best: “Since you are what you eat, you want to make sure your gut is healthy!”
Individuals with mental health concerns: Ongoing research suggests a relationship between gut health and mental health (known as the gut-brain axis). Individuals suffering from mood disorders, anxiety, or depression might benefit from examining their gut health more closely.
Long-term medication users: Certain medications can disrupt the gut microbiome. People on antibiotics specifically should keep an eye on their gut health.
Remember, while these tests offer insightful data, they are not a substitute for professional medical advice. It’s essential to consult with a health care provider about any health concerns.
[ad_2]
[ad_1]
Exposure to bright light synchronizes the central circadian clock in our brain, whereas proper meal timing helps sync the timing of different clock genes throughout the rest of our body.
One of the most important breakthroughs in recent years has been the discovery of “peripheral clocks.” We’ve known for decades about the central clock—the so-called suprachiasmatic nucleus. It sits in the middle of our brain right above the place where our optic nerves cross, allowing it to respond to day and night. Now we also know there are semi-autonomous clocks in nearly every organ of our body. Our heart runs on a clock, our lungs run on one, and so do our kidneys, for instance. In fact, up to 80 percent of the genes in our liver are expressed in a circadian rhythm.
Our entire digestive tract is, too. The rate at which our stomach empties, the secretion of digestive enzymes, and the expression of transporters in our intestinal lining for absorbing sugar and fat all cycle around the clock. So, too, does the ability of our body fat to sop up extra calories. The way we know these cycles are driven by local clocks, rather than being controlled by our brain, is that you can take surgical biopsies of fat, put them in a petri dish, and watch them continue to rhythm away.
All of this clock talk is not just biological curiosity. Our health may depend on keeping all of them in sync. “Imagine a child playing on a swing.” Picture yourself pushing, but you become distracted by what’s going on around you in the playground and stop paying attention to the timing of the push. So, you forget to push or you push too early or too late. What happens? Out of sync, the swinging becomes erratic, slows, or even stops. That is what happens when we travel across multiple time zones or have to work the night shift.
The “pusher” in this case is the light cues falling onto our eyes. Our circadian rhythm is meant to get a “push” from bright light every morning at dawn, but if the sun rises at a different time or we’re exposed to bright light in the middle of the night, this can push our cycle out of sync and leave us feeling out of sorts. That’s an example of a mismatch between the external environment and our central clock. Problems can also arise from a misalignment between the central clock in our brain and all the other organ clocks throughout our body. An extreme illustration of this is a remarkable set of experiments suggesting that even our poop can get jet lag.
As you can see below and at 2:31 in my video How to Sync Your Central Circadian Clock to Your Peripheral Clocks, our microbiome seems to have its own circadian rhythm.
Even though the bacteria are down where the sun doesn’t shine, there’s a daily oscillation in both bacterial abundance and activity in our colon, as you can see in the graph below and at 2:43 in my video. Interesting, but who cares? We all should.
Check this out: If you put people on a plane and fly them halfway around the world, then feed their poop to mice, those mice grow fatter than mice fed preflight feces. The researchers suggest the fattening flora was a consequence of “circadian misalignment.” Indeed, several lines of evidence now implicate “chronodisruption”—the state in which our central and peripheral clocks diverge out of sync—as playing a role in conditions such as premature aging and cancer, as well as ranging to others like mood disorders and obesity.
Exposure to bright light is the synchronizing swing pusher for our central clock. What drives our internal organ clocks that aren’t exposed to daylight? Food intake. That’s why the timing of our meals may be so important. Researchers removed all external timing cues by keeping study participants under constant dim light and found that you could effectively decouple central rhythms from peripheral ones just by shifting meal times. They took blood draws every hour and biopsies of the subjects’ fat every six hours to demonstrate the resulting metabolic disarray.
Just as morning light can help sync the central clock in our brain, morning meals can help sync our peripheral clocks throughout the rest of our body. Skipping breakfast disrupts the normal expression and rhythm of these clock genes themselves, which coincides with adverse metabolic effects. Thankfully, they can be reversed. Take a group of habitual breakfast-skippers and have them eat three meals at 8:00 am, 1:00 pm, and 6:00 pm, and their cholesterol and triglycerides improve, compared to taking meals five hours later at 1:00 pm, 6:00 pm, and 11:00 pm. There is a circadian rhythm to cholesterol synthesis in the body, too, which is also “strongly influenced by food intake.” This is evidenced by the 95 percent drop in cholesterol production in response to a single day of fasting. That’s why a shift in meal timing of just a few hours can result in a 20-point drop in LDL cholesterol, thanks to eating earlier meals, as you can see below and at 5:00 in my video.
If light exposure and meal timing help keep everything synced, what happens when our circumstances prevent us from sticking to a normal daytime cycle? We’ll find out in The Metabolic Harms of Night Shifts and Irregular Meals. If you’re just coming into the series, be sure to check out the related posts below.
[ad_2]
Michael Greger M.D. FACLM
Source link
[ad_1]
“You can change your gut microbiome within about a week just by altering your diet,” award-winning microbiome expert, author of Food for Life: The New Science of Eating Well, and co-founder of ZOE, Tim Spector, M.D., shares on this episode of the mindbodygreen podcast. There are trillions of bacteria residing in your gut, which are constantly evolving based on your inputs. Feed them what they crave, and the community will thrive—quickly.
[ad_2]
[ad_1]
Endotoxins can build up on pre-cut vegetables and undermine some of their benefits.
You may remember when I introduced the endotoxin theory literature in my video The Exogenous Endotoxin Theory, which sought to explain how a single Sausage and Egg McMuffin meal could cripple artery function within hours of consumption. Maybe it’s because such a meal causes inflammation within hours of consumption by inducing low-grade endotoxemia, endotoxins in the bloodstream, as I previously discussed in my video Dead Meat Bacteria Endotoxemia. Endotoxins are structural components of gram-negative bacteria like E. coli, as you can see below and at 0:35 in my video Are Pre-Cut Vegetables Just as Healthy?. Certain foods, like ground meat, have high bacterial loads, so the thought was that the endotoxins in the food were triggering the inflammation.
Critics of the theory argued that because we already have so many bacteria living in our colon, so many endotoxins just sitting down in our large intestine, a few more endotoxins in our food wouldn’t matter much in terms of causing systemic inflammation. After all, we have about two pounds of pure bacteria down there where the sun don’t shine, so there could be about a whole ounce of endotoxin. The lethal dose of intravenously injected endotoxin can be just a few millionths of a gram, so we could have a million lethal doses down there. However, the apparent paradox is explained by compartmentalization. It’s location, location, location.
Poop is harmless when it’s in your colon, but it shouldn’t be injected into your bloodstream or eaten for that matter, particularly with fat, as that can promote the absorption of endotoxins in the small intestine. That goes for well-cooked poop, too.
As you can see in the graph below and at 1:44 in my video, you can boil endotoxins for two hours straight with no detriment in their ability to induce inflammation. You could easily kill off any bacteria if you boiled your poop soup long enough, but you can’t kill off the endotoxins they make, just like you can’t cook the crap out of the meat. The consumption of meat contaminated with feces doesn’t just cause food poisoning. It can spill out onto the animal’s skin during the evisceration process when the digestive tract is ruptured.
Even when slaughterhouse workers trim off “visible fecal contamination,” the trimming itself can, ironically, sometimes lead to an increase in certain fecal bacteria, thought to be caused by “cross-contamination resulting from the handling to removal fecal contamination” from one carcass to the next. Then, even when properly stored in the fridge, endotoxins start accumulating along with the bacterial growth, as you can see in the graph below and at 2:30 in my video.
What about other foods? The highest levels of endotoxins were found in meat and dairy, and the lowest levels in fresh fruits and vegetables. That was testing whole fruits and vegetables, though. “Most spoilage organisms cannot penetrate the plant’s surface barrier and spoil the inner tissues.” That’s why fruits and veggies can sit out in the fields all day in the sun. But, once you cut them open, bacteria can gain access to the inner tissues, and, within a matter of days, your veggies can start to spoil. So, what does that mean for all those convenient pre-cut veggies these days?
While endotoxins were not detectable in the majority of unprocessed vegetables, once you damage the protective outer layers of vegetables, you diminish their resistance to microbial growth. So, while freshly cut carrots and onions start with undetectable levels, day after day after they’ve been chopped, you start to get the growth of bacteria and, along with them, endotoxin buildup—even if they’ve been kept chilled in the fridge. Not as much as meat, but not insignificant either, as you can see in the graph below and at 3:27 in my video. Enough to make a difference, though? You don’t know until you put it to the test.
What would happen if you switched people between foods expected to have a lower endotoxin load to foods containing more endotoxins? For instance, going from intact meat, such as a steak, and whole fruits and vegetables, to more like ground beef, pre-cut veggies, and more ready-made meals, as shown below and at 3:39 in my video. After just one week on the lower-endotoxin diet, people’s white blood cell count, which is an indicator of total body inflammation, dropped by 12 percent, then bumped back up by 14 percent after just four days on the higher-endotoxin diet. They also lost a pound and a half on the lower-endotoxin diet and slimmed their waists a bit. 
They weren’t eating otherwise identical diets, though. It looks like they were eating more meat and cheese on the higher-endotoxin diet and perhaps getting more food additives in the ready-made meals. So, how do we know endotoxins had anything to do with it? That’s where the onion study comes in. Another study was designed based on two meals that differed in their content of bacterial products but were otherwise nutritionally identical. So, researchers compared freshly chopped onion to prechopped onion that had been refrigerated for a few days. The pre-chopped onion wasn’t spoiled; it was still before the “best before” date. So, would it make any difference?
Within three hours of consumption, the fresh onion meal caused significant reductions in several markers of inflammation. That’s what fruits and vegetables do—they reduce inflammation—but these effects were not observed after eating the pre-chopped onions. For example, three hours after eating freshly chopped onions, researchers saw a significant drop in inflammatory status, but there was no significant change three hours after eating the same amount of pre-chopped onions, as you can see in the graph below and at 5:06 in my video. So, it’s not like the pre-chopped onions caused more inflammation, like in the meat, eggs, and dairy studies, but it did appear that some of the onion’s anti-inflammatory effects were extinguished. “In conclusion, the modern trend towards eating minimally processed vegetables”—pre-cut vegetables—“rather than whole [intact] foods is likely to be associated with increased oral endotoxin exposure.” It’s still better to eat pre-cut veggies than no veggies, but cutting your own might be the healthiest.
For some other practical veggie videos and blogs check out the related posts below.
[ad_2]
Michael Greger M.D. FACLM
Source link
[ad_1]
Elevated levels of pro-inflammatory, aging-associated oxylipins can be normalized by eating ground flaxseed.
I previously explored the “Potent Antihypertensive Effect of Dietary Flaxseed in Hypertensive Patients” study in my video Flaxseeds for Hypertension. That was a double-blind, randomized, placebo-controlled trial where researchers disguised ground flaxseed in baked goods versus flax-free placebo muffins and saw an extraordinary drop in high blood pressure. As you can imagine, the flaxseed industry was overjoyed, praising the “impressive” findings, as was I. After all, high blood pressure is “the single largest risk factor” for death in the world. Yes, we give people medications, lots and lots of medications, but most people don’t take them. Nine out of ten people take less than 80 percent of their prescribed blood pressure pills.
It’s not difficult to understand why. “Patients are asked to follow an inconvenient and potentially costly regimen, which will likely have a detrimental effect on health-related quality of life, to treat a mostly asymptomatic condition that commonly does not cause problems for many years.” So, they may feel worse instead of better, due to the side effects. Then, some think the answer is to give them even more drugs to counteract the effects of the first drugs, like giving men Viagra to counteract the erectile dysfunction caused by their blood pressure pills.
How about using a dietary strategy instead, especially if it can be just as effective? And, indeed, the drop in blood pressure the researchers saw in the flaxseed study “was greater than the average decrease observed with the standard dose of anti-hypertensive medications.” Flaxseeds are cheaper, too, compared to even single medications, and most patients are on multiple drugs. Plus, flaxseeds have good side effects beyond their anti-hypertensive actions. Taking tablespoons of flaxseed a day is a lot of fiber for people living off of cheeseburgers and milkshakes their whole lives, and your gut bacteria may need a little time to adjust to the new bounty. So, those who start with low-fiber diets may want to take it a little slow with the flaxseeds at first.
Not all studies have shown significant blood pressure–lowering effects, though. There have been more than a dozen trials by now, involving more than a thousand subjects. And, yes, when you put them all together, overall, there were “significant reductions in both SBP and DBP”—systolic blood pressure (the upper number) and diastolic blood pressure (the lower number)—“following supplementation with various flaxseed products.” But none was as dramatic as what the researchers had found in that six-month trial. The longer trials tended to show better results, and some of the trials just used flaxseed oil or some kind of flaxseed extract. We think this is because the whole is greater than the sum of its parts. “Each of the components of interest within flaxseed, ALA, lignans, fiber, and peptides”—the omega-3s, the cancer-fighting lignans, all the soluble fiber, and the plant proteins, for instance—“all contribute towards BP reduction.” Okay, but how? Why? What is the mechanism?
Some common blood-pressure medications like Norvasc or Procardia work in part by reducing the ability of the heart to contract or by slowing down the heart. So, might it be that’s how flaxseeds work, too? But, no. In my video Benefits of Flaxseeds for Inflammation, I profile the “Dietary Flaxseed Reduces Central Aortic Blood Pressure Without Cardiac Involvement but Through Changes in Plasma Oxylipins” study. What are oxylipins?
“Oxylipins are a group of fatty acid metabolites” involved in inflammation and, as a result, have been implicated in many pro-inflammatory conditions, including aging and cardiovascular disease. “The best-characterized oxylipins about cardiovascular disease are derived from the w-6 fatty acid arachidonic acid,” a long-chain omega-6 fatty acid. These are found preformed in animal products, particularly chicken and eggs, and can be made inside the body from junky oils rich in omega-6, such as cottonseed oil, as noted below and at 3:49 in my video. But, as this study is titled, “Elevated levels of pro-inflammatory oxylipins in older subjects are normalized by flaxseed consumption.”
That’s how we think flaxseed consumption reduces blood pressure in patients with hypertension: by inhibiting the enzyme that makes these pro-inflammatory oxylipins. I’ll spare you from acronym overload, but eating flaxseeds inhibits the activity of the enzyme that makes these pro-inflammatory oxylipins, called leukotoxin diols, which in turn may lower blood pressure. “Identifying the biological mechanism adds confidence to the antihypertensive actions of dietary flaxseed,” but that’s not all oxylipins do. Oxylipins may also play a role in the aging process. However, we may be able to “beneficially disrupt these biological changes associated with inflammation and aging” with a nutritional intervention like flaxseed. Older adults around age 50 have higher levels of this arachidonic acid–derived oxylipin compared to younger adults around age 20, as you can see in the graph below and at 4:56 in my video. “These elevated concentrations of pro-inflammatory oxylipins in the older age group…may…explain the higher levels of inflammation in older versus younger individuals.” As we get older, we’re more likely to be stricken with inflammatory conditions like arthritis. So, this “elevation of pro-inflammatory oxylipins…may predispose individuals to chronic disease conditions.”
What if you took those older adults and gave them muffins, like the ones with ground flaxseed? That’s just what a group of researchers did. Four weeks later, the subjects’ levels dropped down to like 20-year-olds’ levels, as seen in the graph below and at 5:32 in my video, “demonstrating that a potential therapeutic strategy to correct the deleterious pro-inflammatory oxylipin profile is via a dietary supplementation with flaxseed.”
What about flax and cancer? See the related posts below.
I also have a video on diabetes: Flaxseeds vs. Diabetes.
If you’re interested in weight loss, see Benefits of Flaxseed Meal for Weight Loss.
What about the cyanide content of flax? I answered that in Friday Favorites: How Well Does Cooking Destroy the Cyanide in Flaxseeds and Should We Be Concerned About It?.
What else can help fight inflammation? Check out in related posts below.
[ad_2]
Michael Greger M.D. FACLM
Source link
[ad_1]
Nina Sanford, M.D., Chief of Gastrointestinal Radiation Oncology Service, UT Southwestern Medical Center
Most people have a screening colonoscropy around age 50, however recent research has uncovered a rise in early onset colorectal cancer in patients younger than 50.
What can be causing this increase?
Dr. Sanford and colleagues at UT Southwestern Medical Center have found a clue in the microbiome of colorectal patients of Hispanic ethnicity, recently published in the Journal of Immunotherapy and Precision Oncology.
“The increasing incidence of early-onset colorectal cancer, defined as a diagnosis of CRC in patients aged less than 50 years, has become a growing concern over the last four decades.This trend is particularly associated with rectal tumors, with notable racial and ethnic disparities in presentation and outcome.For instance, Black individuals have the highest EOCRC incidence and mortality rates, whereas Hispanic patients, despite overall lower overall incidence, tend to be diagnosed at younger ages compared to non-Hispanic White individuals.”
For a copy of the full paper and interviews, please contact Lori Soderbergh.
[ad_2]
UT Southwestern Medical Center
Source link
[ad_1]
Newswise — On a study (doi:10.1093/burnst/tkad056) published in the journal Burns & Trauma, researchers employed a combination of techniques to analyze the effects of burn injury on the gut microbiota and mucus barrier in mice. A modified histopathological grading system assessed colon tissue and mucus barrier integrity. 16S rRNA sequencing revealed changes in gut microbial composition over 10 days post-burn. Metagenomic sequencing provided deeper insights into mucus-related bacteria and potential underlying mechanisms.
This study provides compelling evidence that burn injury disrupts the intestinal mucus barrier and alters the gut microbiota composition. Mucus-degrading bacteria appear to play a role in mucus breakdown, while probiotics may promote repair through short-chain fatty acids production.
Professor Xi Peng, the leading researcher of this study, emphasizes, “This study is a breakthrough in understanding the intricate relationship between gut microbiota and intestinal health post-burn injuries. It highlights the dual role of microbiota in both exacerbating and healing intestinal damage, offering a new perspective for targeted therapeutic strategies.”
This research holds significant promise for improving burn treatment outcomes. By targeting specific gut bacteria or their metabolites, it may be possible to protect the intestinal mucus barrier, prevent bacterial translocation, and ultimately improve patient survival and recovery. Further research is warranted to translate these findings into clinical applications.
###
References
DOI
Original Source URL
https://doi.org/10.1093/burnst/tkad056
Funding information
This research was funded by the National Natural Science Foundation of China (No. 82172202) and the Innovative Leading Talents Project of Chongqing, China (No. cstc2022ycjh-bgzxm0148).
Burns & Trauma is an open access, peer-reviewed journal publishing the latest developments in basic, clinical, and translational research related to burns and traumatic injuries, with a special focus on various aspects of biomaterials, tissue engineering, stem cells, critical care, immunobiology, skin transplantation, prevention, and regeneration of burns and trauma injury.
[ad_2]
Chinese Academy of Sciences
Source link
[ad_1]
We know through robust research that internal inflammation wreaks havoc on the body, and can lead to a myriad of issues such as cardiovascular disease, autoimmune conditions, and cognitive decline. This is why managing inflammation is one of the most important pillars of longevity and overall health.
[ad_2]
Source link
[ad_1]
Newswise — Contrary to how it may seem, most viruses do not want to kill their hosts. “They want to hang out as long as possible, make more viruses, and infect as many other hosts as they can,” says Karl Munger, the Dorothy Todd Bishop Research Professor and chair of developmental, molecular and chemical biology at Tufts University School of Medicine. Unfortunately, that nasty proclivity of viruses to multiply and infect has some unintended consequences.
In the battle between host and invader, cells produce responses to stop viruses from growing, and viruses try and commandeer the cells’ defense mechanisms and get them to replicate regardless. “There’s a fight between host and virus; because it needs to multiply, it tries to convince a non-dividing cell to divide,” Munger says, “which is one of the hallmarks of cancer.”
Munger has been studying the connections between viruses and cancer for more than 30 years, starting with his Ph.D. at the University of Zurich, and including stints at the National Institutes of Health (NIH) and Harvard University, before coming to Tufts in 2014. By conservative estimates, viruses are responsible for 15 percent of cancers. “It’s probably double that if you look at cancers in which viral infections have contributed,” says Munger, who focuses his work on human papillomavirus (HPV), the most common sexually transmitted infection. He joined Tufts with the intent of creating a nucleus for basic research into viruses and cancer, a relatively under-recognized and underfunded area of cancer research.
“Studying how viruses contribute to cancer is an opportunity to distinguish Tufts as a center of excellence in cancer research,” says Munger, who is also interim vice dean for research at the School of Medicine.
That focus plays to the Tufts’ strengths. Brian Schaffhausen, professor emeritus of developmental, molecular and chemical biology, has made seminal discoveries about the growth and suppression of tumors by focusing on murine polyomavirus. John Coffin, American Cancer Society Research Professor and Distinguished Professor in Molecular Biology and Microbiology, has long studied the connections between cancer and retroviruses such as HIV. Katya Heldwein, American Cancer Society, Massachusetts Division, Professor of Molecular Biology, examines how herpesviruses get in and out of cells—and how they might be stopped. Recently, Tufts hired two new researchers: Rui Guo, assistant professor of molecular biology and microbiology, who focuses on Epstein-Barr virus (EPV) and joined the university last July; and Aaron Mendez, assistant professor of molecular biology and microbiology, who is a specialist on Kaposi’s sarcoma-associated herpesvirus (KSHV) and joined Tufts in January.
Munger, who is also affiliated with the Graduate School of Biomedical Sciences, learned the power of collaboration early in his career. As a postdoctoral researcher at the NIH, he focused on two proteins, known as E6 and E7, that are expressed in cervical cancer associated with HPV. At that time, researchers didn’t know whether they were drivers of cancer or mere innocent bystanders. In helping to solve that question, Munger was inspired by an annual meeting of researchers working on a specific tumor suppressor protein held in a farmhouse in Western Massachusetts, organized by leaders in the field, including the late David Livingston, M65, who was physician-in-chief at Dana-Farber Cancer Research Institute.
“I learned that even though competition drives scientific progress, research should not be a blood sport, and in general it is more productive to solve problems with help from your friends,” Munger wrote in Viruses and Cancer: An Accidental Journey, an account of his research published in PLOS Pathogens in 2016.
Munger and his colleagues determined those tiny viral proteins did in fact cause cancer by subverting the cells’ usual signaling pathways to create uncontrolled division. “There are around 400 different kinds of HPV, and only a very small number of them are cancer-causing,” Munger says. His lab is now looking at ways to target these viral proteins.
A class of viruses known as retroviruses, including HIV, infects the body by implanting themselves directly into the chromosomes inside the cell nucleus, joining their DNA to that of the host’s. Years ago, people thought HIV couldn’t cause cancer, explains John Coffin, since HIV usually kills the cells that it infects.
Coffin’s lab has long been studying how retroviruses cause cancer, first in animals, and more recently with HIV in human cells. When genetic material gets integrated into the wrong gene, it can cause rampant cell division leading to cancer. “Researchers have identified hundreds of genes like this, where a gene involved in cellular growth is supposed to be turned on and off, but instead it’s turned on all the time,” says Coffin, who has spent decades studying HIV and other retroviruses. “Then the cell goes out of control and divides all the time, which is basically what cancer is.”
That’s important, he says, since this process often starts before an individual knows they are infected. HIV patients are also particularly susceptible to side effects of cancer treatments like chemotherapy and radiation, which can stress already weakened immune systems.
Coffin has shown that HIV can cause cancerous changes when integrating into a specific area of the cell’s DNA called the STAT3 gene. Identifying the specific cell and viral genes that can cause cancer can help scientists find a targeted treatment to prevent it. “If you can find a small molecule that turns off the expression of the virus, you can kill the cancer even long after it has started.”
These therapies are becoming even more important for HIV patients, who can now live much longer than they used to due to new antiretroviral treatments that can extend life. “Prior to the 1990s, patients were dying at a much younger age, and didn’t have a chance to develop these problems,” says Jose Caro, an attending physician at Tufts Medical Center and the Dr. Jane Murphy Gaughan Professor and assistant professor of medicine at the School of Medicine. In the late 1990s, physicians noticed many more HIV patients developing anal cancer, which is associated with HPV. While female patients are often screened for cervical cancer, he says, precursors to anal cancer were often left undetected until it was much farther along.
“Because HIV has an effect on the immune system, it is more likely that somebody would acquire another virus—or if they previously acquired the virus, that it would progress and replicate,” says Caro. While 80% of sexually active people acquire HPV, it may persist in tissues of HIV patients longer than it does in others, he says—and the longer it persists, the higher likelihood of causing cancer.
Anal cancer, he adds, is a very difficult cancer to treat, especially in HIV patients with weakened immune systems. “Chemo and radiation come with their set of difficulties and side effects, at the same time, there are also the emotional and psychological side effects of having a genital cancer that can affect someone’s sex life,” Caro says. Lately, there has been hope for the condition, with a landmark study last year that identified a precursor to anal cancer that can help doctors catch it early.
Another class of viruses that can cause cancer are herpesviruses—however, not the oral or genital herpes that usually come to mind. “There are nine different types of herpesviruses that infect humans, and only two cause cancer,” says Katya Heldwein. Those are EBV, better known for causing infectious mononucleosis or “mono,” and KSHV, which can cause a rare cancer affecting bone and soft tissue. Heldwein’s research focuses on how these viruses get inside and out of these cells.
“If they can’t get inside the cell, then the cell doesn’t get infected,” she says. Just as importantly, once viral material is inside the nucleus, “they still have to assemble all of the viral components, so the complete viral particle comes out to infect more cells. If you understand how this happens, you can identify weak points and target them.”
Heldwein says viruses—including HIV and influenza—fuse with the cell membrane by using a single protein to unlock the membrane and spill its contents inside. Herpesviruses, however, distribute that unlocking function across three or four different proteins, Heldwein says.
“Instead of one person using a key, it’s like one person picks up the key, another sticks it in the lock, another turns it, and another pushes open the door.” It’s a mystery why these viruses have evolved such a complicated method, she says, but it makes it much more difficult to target them with a vaccine. “You could raise antibodies against one protein, but in isolation, it might not look to the immune system the same way it does to its friends,” she says. She and other biologists are just beginning to understand how all these parts work together.
While Heldwein doesn’t focus specifically on the connection between herpesviruses and cancers, she is thrilled about the recruitment of Guo and Mendez to the School of Medicine, who work on cancer and EBV and KSHV, respectively.
Guo’s research focuses on how EBV transforms normal human cells into cancerous ones, particularly in immunocompromised individuals. “Some 95 percent of people have this virus, but in most people, their immune system can suppress it, pushing it into the direction of latency,” he says. In addition to mononucleosis, EBV can also cause certain types of cancer, such as Burkitt’s lymphoma, which hides within white blood cells and can cause abnormalities within those cells that lead to cancer development.
As a postdoctoral researcher at Brigham and Women’s Hospital and Harvard Medical School, Guo was interested in discovering how EBV manages such metabolic processes, performing genetic screens to see whether those genetic chances can be stopped. He and colleagues focused on how the virus uses certain nutrients, including a particular amino acid called methionine. In a paper published last year, they showed that in mice infected with Burkitt’s lymphoma, a diet low in methionine changed the makeup of tumor cells, causing EBV to become visible to the immune system—and therefore potentially subject to attack.
“Just by changing the diet, we could see the EBV gene got repressed in those mice, and the tumor stopped growing within two weeks,” Guo says. While treatment in humans is still a way off, the findings provide hope that a similar strategy could be followed as an alternative to more invasive chemo and radiation therapies, perhaps combined with T-cells that can target tumor cells in the blood.
While all these researchers are pursuing different viruses, exploring different pathways towards intervention, there are enough commonalities in their approach to make collaboration fruitful, says Munger. Each is examining the mechanism in which these viruses manipulate the body’s genetic processes and cause cells to become cancerous—and each is searching for a way to stop that malfunction with treatments that could potentially be a less invasive alternative to current cancer treatments.
While such research can be slow, and frustrating at times, the payoff could be huge, says Munger, who is often reminded of something his mentor Livingston, who passed away in 2021, used to say: “Even if you have bad days where your grants get rejected and your research doesn’t work, a cancer patient never has a good day.” That idea has always stuck with Munger and continues to motivate him to create a powerful center of excellence devoted to viruses and cancer. “There are a lot of commonalities between what these viruses do and the pathways they target,” he says. “This is definitely something we can examine together.”
[ad_2]
Tufts University
Source link
[ad_1]
Food virologists from the National University of Singapore (NUS) have successfully propagated the human norovirus using zebrafish embryos, providing a valuable platform to assess the effectiveness of virus inactivation for the water treatment and food industries.
Human norovirus (HuNoV) is currently the predominant cause of acute gastroenteritis worldwide, contributing to an estimated 684 million diarrhoea cases, resulting in 212,000 annual fatalities. For a substantial period, the absence of an in vitro culture system has been a major hurdle in norovirus research. The most recently optimised human intestinal enteroid model, designed to support HuNoV replication, relies on human biopsy specimens obtained from surgical or endoscopic procedures, which are typically scarce. Moreover, the maintenance of these cells is both labour and resource intensive.
A research team led by Assistant Professor Li Dan from the NUS Department of Food Science and Technology, in collaboration with Professor Gong Zhiyuan from the NUS Department of Biological Sciences, serendipitously discovered that zebrafish embryo can be used as a host for cultivating HuNoV. The zebrafish embryo model is easy to handle, robust and has a capacity to efficiently replicate HuNoVs. This study, to the best of their knowledge, represents an inaugural demonstration of the highest fold-increase over the baseline. Most notably, this model enables the continuous passaging of HuNoV within a laboratory setting. With this model, researchers can effectively propagate and sustain the presence of HuNoV over time, enabling them to study in more depth its behaviour, replication, and other properties.
Asst Prof Li said, “The zebrafish embryo model represents an essential improvement in the HuNoV cultivation method. With its high efficiency and robustness, this tool is able to enhance both the breadth and depth of HuNoV-related research. It is expected that this tool will not only benefit the advancement of epidemiological research on HuNoV but will also be invaluable in establishing HuNoV inactivation parameters. These parameters are highly needed by the water treatment and food industries to develop more effective methods for preventing the spread of the virus.”
This research was published in the journal Applied and Environmental Microbiology on 21 March 2023.
In the future, the research team plans to utilise the zebrafish embryo model to investigate inactivation methods for HuNoVs in food products. To date, the successful detection of infectious HuNoV in food products remains an elusive goal. While further refinement and optimisation efforts are still required, the research team’s ongoing work holds great promise in tackling this challenging task.
[ad_2]
National University of Singapore (NUS)
Source link
[ad_1]
Newswise — Viruses have limited genetic material—and few proteins—so all the pieces must work extra hard. Zika is a great example; the virus only produces 10 proteins. Now, in a study published in the journal PLOS Pathogens, researchers at Sanford Burnham Prebys have shown how the virus does so much with so little and may have identified a therapeutic vulnerability.
In the study, the research team showed that Zika’s enzyme—NS2B-NS3—is a multipurpose tool with two essential functions: breaking up proteins (a protease) and dividing its own double-stranded RNA into single strands (a helicase).
“We found that Zika’s enzyme complex changes function based on how it’s shaped,” says Alexey Terskikh, Ph.D., associate professor at Sanford Burnham Prebys and senior author of the paper. “When in the closed conformation, it acts as a classic protease. But then it cycles between open and super-open conformations, which allows it to grab and then release a single strand of RNA—and these functions are essential for viral replication.”
Zika is an RNA virus that’s part of a family of deadly pathogens called flaviviruses, which include West Nile, dengue fever, yellow fever, Japanese encephalitis and others. The virus is transmitted by mosquitoes and infects uterine and placental cells (among other cell types), making it particularly dangerous for pregnant women. Once inside host cells, the virus re-engineers them to produce more Zika.
Understanding Zika on the molecular level could have an enormous payoff: a therapeutic target. It would be difficult to create safe drugs that target the domains of the enzyme needed for protease or helicase functions, as human cells have many similar molecules. However, a drug that blocks Zika’s conformational changes could be effective. If the complex can’t shape-shift, it can’t perform its critical functions, and no new Zika particles would be produced.
An efficient machineResearchers have long known that Zika’s essential enzyme was composed of two units: NS2B-NS3pro and NS3hel. NS2B-NS3pro carries out protease functions, cutting long polypeptides into Zika proteins. However, NS2B-NS3pro’s abilities to bind single-stranded RNA and help separate the double-stranded RNA during viral replication were only recently discovered.
In this study, the researchers leaned on recent crystal structures and used protein biochemistry, fluorescence polarization and computer modeling to dissect NS2B-NS3pro’s life cycle. NS3pro is connected to NS3hel (the helicase) by a short amino acid linker and becomes active when the complex is in its closed conformation, like a closed accordion. The RNA binding happens when the complex is open, whereas the complex must transition through the super-open conformation to release RNA.
These conformational changes are driven by the dynamics of NS3hel activity, which extends the linker and eventually “yanks” the NS3pro to release RNA. NS3pro is anchored to the inside of the host cell’s endoplasmic reticulum (ER)—a key organelle that helps shepherd cellular proteins to their appropriate destinations—via NS2B and, while in the closed conformation, cuts up the Zika polypeptide, helping generate all viral proteins.
On the other side of the linker, NS3hel separates Zika’s double-stranded RNA and conveniently hands a strand over to NS3pro, which has positively charged “forks” to grab on to the negatively charged RNA.
“There’s a very nice groove of positive charges,” says Terskikh. “So, RNA just naturally follows that groove. Then the complex shifts to the closed conformation and releases the RNA.”
As NS3hel reaches forward to grab the double-stranded RNA, it pulls the complex with it; however, since the NS3pro is anchored in the ER membrane, and the linker can only extend so far, the complex snaps into the super-open conformation and releases RNA. The complex then relaxes back to the open conformation, ready for a new cycle.
Meanwhile, when NS3pro detects a viral polypeptide to cut, it forces the complex into the closed conformation, becoming a protease. The authors call this process “reverse inchworm,” because grabbing and releasing the single-stranded RNA resembles inchworm movements, but backward with the jaws (the protease) trailing behind.
In addition to providing a possible therapeutic target for Zika, this detailed understanding could be applied to other flaviviruses, which share similar molecular machinery.
“Versions of the NS2B-NS3pro complex are found throughout the flaviviruses,” says Terskikh. “It could potentially constitute a whole new class of drug targets for multiple viruses.”
###
Additional authors include Sergey A. Shiryaev, Piotr Cieplak, Anton Cheltsov and Robert C. Liddington.
This study was supported by grants from the National Institutes of Health (5R21AI134581 and R01 NS105969).
[ad_2]
Sanford Burnham Prebys
Source link
[ad_1]
What are the effects of ketogenic diets on nutrient sufficiency, gut flora, and heart disease risk?
Given the decades of experience using ketogenic diets to treat certain cases of pediatric epilepsy, a body of safety data has accumulated. Nutrient deficiencies would seem to be the obvious issue. Inadequate intake of 17 micronutrients, vitamins, and minerals has been documented in those on strict ketogenic diets, as you can see in the graph below and at 0:14 in my video Are Keto Diets Safe?.
Dieting is a particularly important time to make sure you’re meeting all of your essential nutrient requirements, since you may be taking in less food. Ketogenic diets tend to be so nutritionally vacuous that one assessment estimated that you’d have to eat more than 37,000 calories a day to get a sufficient daily intake of all essential vitamins and minerals, as you can see in the graph below and at 0:39 in my video.
That is one of the advantages of more plant-based approaches. As the editor-in-chief of the Journal of the American Dietetic Association put it, “What could be more nutrient-dense than a vegetarian diet?” Choosing a healthy diet may be easier than eating more than 37,000 daily calories, which is like putting 50 sticks of butter in your morning coffee.
We aren’t just talking about not reaching your daily allowances either. Children have gotten scurvy on ketogenic diets, and some have even died from selenium deficiency, which can cause sudden cardiac death. The vitamin and mineral deficiencies can be solved with supplements, but what about the paucity of prebiotics, the dozens of types of fiber, and resistant starches found concentrated in whole grains and beans that you’d miss out on?
Not surprisingly, constipation is very common on keto diets. As I’ve reviewed before, starving our microbial self of prebiotics can have a whole array of negative consequences. Ketogenic diets have been shown to “reduce the species richness and diversity of intestinal microbiota,” our gut flora. Microbiome changes can be detected within 24 hours of switching to a high-fat, low-fiber diet. A lack of fiber starves our good gut bacteria. We used to think that dietary fat itself was nearly all absorbed in the small intestine, but based on studies using radioactive tracers, we now know that about 7 percent of the saturated fat in a fat-rich meal can make it down to the colon. This may result in “detrimental changes” in our gut microbiome, as well as weight gain, increased leaky gut, and pro-inflammatory changes. For example, there may be a drop in beneficial Bifidobacteria and a decrease in overall short-chain fatty acid production, both of which would be expected to increase the risk of gastrointestinal disorders.
Striking at the heart of the matter, what might all of that saturated fat be doing to our heart? If you look at low-carbohydrate diets and all-cause mortality, those who eat lower-carb diets suffer “a significantly higher risk of all-cause mortality,” meaning they live, on average, significantly shorter lives. However, from a heart-disease perspective, it matters if it’s animal fat or plant fat. Based on the famous Harvard cohorts, eating more of an animal-based, low-carb diet was associated with higher death rates from cardiovascular disease and a 50 percent higher risk of dying from a heart attack or stroke, but no such association was found for lower-carb diets based on plant sources.
And it wasn’t just Harvard. Other researchers have also found that “low-carbohydrate dietary patterns favoring animal-derived protein and fat sources, from sources such as lamb, beef, pork, and chicken, were associated with higher mortality, whereas those that favored plant-derived protein and fat intake, from sources such as vegetables, nuts, peanut butter, and whole-grain bread, were associated with lower mortality…”
Cholesterol production in the body is directly correlated to body weight, as you can see in the graph below and at 3:50 in my video.
Every pound of weight loss by nearly any means is associated with about a one-point drop in cholesterol levels in the blood. But if we put people on very-low-carb ketogenic diets, the beneficial effect on LDL bad cholesterol is blunted or even completely neutralized. Counterbalancing changes in LDL or HDL (what we used to think of as good cholesterol) are not considered sufficient to offset this risk. You don’t have to wait until cholesterol builds up in your arteries to have adverse effects either; within three hours of eating a meal high in saturated fat, you can see a significant impairment of artery function. Even with a dozen pounds of weight loss, artery function worsens on a ketogenic diet instead of getting better, which appears to be the case with low-carb diets in general.
For more on keto diets, check out my video series here.
And, to learn more about your microbiome, see the related videos below.
[ad_2]
Michael Greger M.D. FACLM
Source link
[ad_1]
Hospital germs and pathogens are not always transmitted directly from person to person. They can also spread via germ-contaminated surfaces and objects.
[ad_2]
Empa, Swiss Federal Laboratories for Materials Science and Technology
Source link
[ad_1]
Newswise — Unexpected model was suggested by the scientist of The Federal Research Centre “Fundamentals of Biotechnology” of the Russian Academy of Sciences (Research Center of Biotechnology RAS). The author of the scientific review compared extracting of sounds by musical instrument with the process of synthesis of biologically active compounds by fungi. The model of regulation of secondary metabolism according to the piano principle simply and clearly explains a mechanism of activation of biosynthetic gene clusters (BGCs), that lead to biosynthesis of corresponding secondary metabolites, and also points to ways of increasing productivity of high-yielding strains. Results of the research were published in International Journal of Molecular Sciences.
Filamentous fungi, the main morphological form of which, the mycelium, resembles an accumulation of thin intertwined strands, are widely used in biotechnology for the production of drugs such as antibiotics, statins, and immunosuppressants. Certain species of these fungi are capable of synthesizing more than a hundred biologically active compounds called secondary metabolites.
However, in the concrete period of life only some of these substances are synthetized. It depends not only on a stage of development of microorganism but also on the environment. Synthesis of different secondary metabolites is controlled by “switch-on” and “switch-off” of a corresponding biosynthetic genes, assembled in so-called biosynthetic gene clusters (BGC) as a reaction on inner and outer signals.
As we know the principles of activation and suppression of these genes, scientists make attempts to manage the ability of fungi to synthetize compounds, important for biotechnology and medicine, thus improving producer strains. In the last decades researchers from all over the world have accumulated an enormous volume of information about synthesis of secondary metabolites in fungi. In this connection there is a necessity in summarizing all data and creating a model that is able to describe it simply and clearly.
Alexander Zhgun, Candidate of Sciences in Biology, head of the group of genetic engineering of fungi of The Federal Research Centre “Fundamentals of Biotechnology” of the Russian Academy of Sciences on the base of classification of fungal secondary metabolites, their gene clusters and hierarchical system of regulation offered a model, that summarizes a lot of complex processes, that take place in cells of Filamentous fungi during the synthesis of secondary metabolites. As a synthesis of every of these compounds “is started” as an answer for a certain signal, the scientist compared it with piano principle, that makes a definite sound as an answer for pressing of this or that key.
“Inside each cell of a fungi there is a kind of musical instrument, a specific piano, that enables by pressure on a definite key – activation of gene cluster – to make a certain sound – produce targeted secondary metabolite”, – tells Alexander Zhgun.
Thus, according to suggested model, when there are no signals from the environment, genes, that answer for the synthesis of secondary metabolites, are inactive and in position of so-called heterochromatin – tightly packed parts of DNA. RNA polymerase, responsible for reading information from genes (for subsequent synthesis of enzymes for biosynthetic pathway), cannot approach to such parts, and it can be compared with the case when piano lid is closed and music stand is lowered. As a musician cannot make sounds from a closed instrument, fungi’s cell won’t be able to synthetize secondary metabolites.
To start synthesis, genes are taken to the state available for regulatory proteins and proteins of tool of transcription. In this case, the part of DNA containing the BGC corresponding to the signal ceases to be tightly packed and becomes euchromatin. In the similar way when piano is prepared to work, a musician can press keys and that brings to sound production. By this in the presented model each key corresponds to a separate BGC, the activation of which leads to the synthesis of a specific low-molecular weight compound.
Interestingly that the author of the scientific review with the help of his model also explains the fact that outer signals, on which Filamentous fungi react, can differ in intensity.
“As a musician can get different sounds as far as length, loudness and character of sound’s attenuation by pressing one and the same piano key differently, so microorganisms can regulate the amount of synthesized by them compound. Naturally, in living cells this dependence is more complex and not always lineal, that is explained by complex and hierarchical system of regulation, coordinating reactions of metabolism”, – explains the author of the article.
In order to make this model clearer and more precise the scientist the scientist proposed comparing the regulation of the synthesis of secondary metabolites with a more complex musical instrument – an organ with several rows of keys or keyboards.
Such analogy seemed more concrete to the scientist, because Filamentous fungi usually have not one chromosome (as one row of keys on the piano), but several (from two to several tens). Accordingly, the activation of genes responsible for the synthesis of secondary metabolites and located on different chromosomes can be compared to pressing keys on different keyboards of an organ.
“To illustrate how this model works using an organ example, I examined information about the location of BGSc in the model organism Penicillium chrysogenum. This organism is used in biotechnology to produce one of the most important antibiotics for humans, penicillin G, the use of which made a coup in medicine in the early 1940s. P. сhrysogenum has 4 chromosomes, therefore, its “organ” contains 4 keyboards. I mapped the currently known gene clusters to show the mosaic nature of their location. Nature must be a virtuoso pianist to consistently play such distant keys in response to incoming signals”, -tells Alexander Alexandrovich.
The piano model also enables to explain how you can “make” fungi to produce a needed compound in enormous amount. Normally microorganisms have special “molecular limiters” that don’t enable them to produce abundant amount of a product. The same way a good piano has restrictions as far as strength and length of a sound, that is made by pressing on this or that key, is concerned. However, if you damage an instrument, you can make the only one needed key left and it will make a sound constantly and very loudly.
“In the case of Filamentous fungi such distortions can be made with the help of change in system of regulation of secondary metabolism and biosynthetic clusters, responsible for the production of alternative (extrinsic) metabolites. In biotechnology such distortions were found in high-yielding strains, obtained during the last 70-80 years as a result of random mutagenesis and selection. They enable to get antibiotics and other secondary metabolites, used in medicine and industry, in large quantities”, – tells Alexander Zhgun.
“The suggested by the scientist model offers a fresh look on principles of regulation of secondary metabolite among Filamentous fungi. It enables to understand better, how a human can artificially govern the activity of genes and productivity of microorganisms. Thanks to that fact therein expressed principles are of practical interest to biotechnology.
[ad_2]
Scientific Project Lomonosov
Source link
