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Comment by Dr. Krishna Kumari Challa on May 22, 2025 at 1:24pm

How a mold can unbalance the lungs

An invisible intruder puts the delicate balance in our lungs to the test: the mold Aspergillus fumigatus, harmless in nature, can become a serious danger if the immune system is weakened—and change the entire bacterial world in the lungs. But that's not all: The intestines and metabolism also appear to be affected by a lung infection.

Aspergillus fumigatus can be found almost everywhere—in soil, compost or in the air. It is usually harmless for healthy people. However, in patients with a weakened immune system, it can cause severe lung infection, known as invasive aspergillosis.

The fungus may potentially alter the oxygen levels in the lungs to a degree that it creates a more suitable environment for certain bacteria—such as Ligilactobacillus murinus, typically found in the intestines, oral cavity and lungs of mice—to better survive and potentially thrive. This interaction could possibly influence disease progression and enable new treatment strategies.

It has long been known that the gut and lungs are closely connected. New data from a research team in Jena has now deepened this understanding.

Researchers found evidence that not only the lung microbiome, but also the gut microbiome and certain metabolic products in the blood change during infection of the lungs with Aspergillus fumigatus. This so-called "gut-lung axis" could play an important role in future therapy.

A key finding of the study was that the fungal infection unbalances both the lung and gut microbiome. In the lungs, this leads to an accumulation of anaerobic bacteria. Particularly striking was the increased growth of Ligilactobacillus murinus, suggesting that the fungus creates a microaerophilic niche (low oxygen concentrations) that favors this bacterium.

Fungal infections are a serious problem, especially for immunocompromised people or those who are already seriously ill—for example in intensive care units or with cancer. The new findings provide important information on how such infections can be better understood and possibly prevented.

In the future, it may be possible to specifically influence the microbiome in order to support the body in its fight against the fungus—or to develop new drugs that target precisely this area.

Liubov Nikitashina et al, The murine lung microbiome is disbalanced by the human-pathogenic fungus Aspergillus fumigatus resulting in enrichment of anaerobic bacteria, Cell Reports (2025). DOI: 10.1016/j.celrep.2025.115442

Comment by Dr. Krishna Kumari Challa on May 22, 2025 at 1:18pm

How the placebo effect tricks the mind into relieving pain

The detailed mechanism of how the placebo effect reduces the perception of pain in rats has been uncovered by  neuroscientists. These findings, published in Science Advances, could potentially lead to ways to harness the placebo effect in therapy.

If you're convinced you are taking a powerful painkiller, it could well reduce your perception of pain, even if the painkiller turns out to be a sham.

That's the power of the placebo effect. The brain, tricked into anticipating a benefit, produces the benefit itself.

Harnessing the placebo effect for pain relief could help to reduce dosages of painkillers, lowering the risk of both side effects and becoming dependent on medication.

Because it's a psychological effect, the placebo effect is much easier to induce and monitor in humans than in animals. But since only relatively noninvasive techniques can be used on people, it's hard to determine what's happening on a neural-circuit level.

The researchers conditioned rats by injecting them with a painkiller over four days. The animal came to associate injections with pain relief, so that when they were injected with a saline solution, the placebo effect kicked in. Many researchers didn't think that animals could experience the placebo effect. But the researchers succeeded in inducing it in rodents by using Pavlovian conditioning.

About a third of the rats exhibited the full placebo effect, another third had a partial placebo effect, and the remaining third hardly experienced any pain relief.

The research team was then able to study what was going on in the animal brains using neuroimaging methods that are too invasive to use on people.

Several brain regions were found to activate in response to placebo in neuropathic animals. That's very similar to results in humans. 

The team found that the placebo effect occurred as a result of brain signals related to the endogenous opioid system in the medial prefrontal cortex, a region at the front of the brain, which in the presence of the placebo injections set off the descending pain inhibitory system.

They strongly suspect that the same mechanism operates in people. The mechanism is similar to how pain relief occurs in humans.

Hiroyuki Neyama et al, Opioidergic activation of the descending pain inhibitory system underlies placebo analgesia, Science Advances (2025). DOI: 10.1126/sciadv.adp8494

Comment by Dr. Krishna Kumari Challa on May 22, 2025 at 1:11pm

The study is the first to examine the effects of removing cysteine, or any of the nine of the essential amino acids, which must be obtained through diet and are required for building proteins that make up most of the body's enzymes, tissues, and signaling molecules. The findings revealed that eliminating cysteine from the mammalian body led to far greater weight loss than the removal of any other essential amino acid.

Specifically, cysteine deprivation disrupted oxidative phosphorylation, the main process for producing adenosine triphosphate (ATP), the molecule that serves as cells' energy currency. Oxidative phosphorylation is known to be tightly dependent on CoA.

As a result, sugar-derived intermediate molecules (carbon skeletons) such as pyruvate, orotate, citrate, and α-ketoglutarate were no longer used efficiently, and were instead lost in the urine. In response, the body turned to stored lipids (fats) to make energy.

Further, the team found that cysteine restriction activates both the integrated stress response (ISR), a signaling network that restores cellular balance after stress, and the oxidative stress response (OSR), which is triggered by higher levels of reactive oxygen species (ROS) following depletion of glutathione, the body's primary antioxidant. ROS can oxidize (take away electrons from) and damage sensitive cell parts like DNA.

Remarkably, this simultaneous activation of ISR and OSR—previously observed only in cancer cells—was shown to occur in normal tissues in mice in the cysteine-restriction group, with the two stress responses reinforcing each other.

The study also shows that ISR and OSR, acting independently of CoA depletion, increase production of the stress hormone GDF15, which contributes to food aversion and degradation of acetyl-CoA-carboxylase, a key enzyme in lipid synthesis. This increased weight loss further in the study mice by preventing the replenishment of their fat stores.

Evgeny Nudler, Unravelling cysteine-deficiency-associated rapid weight loss, Nature (2025). DOI: 10.1038/s41586-025-08996-y. www.nature.com/articles/s41586-025-08996-y

Part 2

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Comment by Dr. Krishna Kumari Challa on May 22, 2025 at 1:10pm

Newfound mechanism rewires cellular energy processing for drastic weight loss

Mice genetically engineered to lack the ability to make the amino acid cysteine, and fed a cysteine-free diet, lost 30% of their body weight in just one week, a new study shows.

Published online in Nature, the work found that cysteine depletion disrupts the normal metabolic pathways used by mammalian to convert food into energy, forcing the animals to rapidly burn fat stores in a futile attempt to meet energy demands.

 The study reveals key details about how cells process fuels like carbohydrates and fats (metabolism), and how cysteine depletion affects tissues. Experiments showed that lowering cysteine levels caused a drop in levels of the small molecule called coenzyme A (CoA), which rendered inefficient mechanisms that convert carbohydrates and fats into energy.

Despite CoA being involved in more than 100 intermediate metabolic reactions and serving as a partner (cofactor) for 4% of all enzymes in the body, scientists had previously been unable to study its function directly. This is because mice with defective CoA synthesis typically do not survive beyond three weeks of age. The current findings detail, for the first time, how CoA shapes metabolism in adult mice.

The current finding does not immediately suggest a new approach to weight loss, the authors caution, as cysteine is found in nearly all foods.

Achieving a truly cysteine-free diet would require patients to consume a specially formulated solution that would be challenging for most. Moreover, because cysteine is involved in numerous cellular pathways, eliminating it—such as through a drug that inhibits cysteine production—could make organs more vulnerable to everyday toxins, including medications.

That said, the study authors say it is worth considering that fruits, vegetables, and legumes contain much lower levels of cysteine and its precursor, the sulfur-containing amino acid methionine, than red meat. While earlier studies have linked low sulfur amino acid intake to health benefits, this study clarifies that these benefits are due to cysteine depletion specifically, and not methionine restriction.

Part 1

Comment by Dr. Krishna Kumari Challa on May 22, 2025 at 11:54am

In preclinical animal studies, a two-dose oral regimen generated blood-borne (systemic) antibody levels comparable to intramuscular mRNA vaccination. Notably, it produced markedly higher levels of secretory immunoglobulin A (IgA) in the gut and airways—the antibodies that underlie mucosal immunity, considered critical for blocking infection at the point of entry.
While vaccines are delivered before a person is infected with a virus, antiviral therapies such as monoclonal antibodies are given as a treatment after infection.

The team developed another version of engineered E.coli Nissle 1917 to display therapeutic proteins on the surface. To create a post-exposure therapy, the team encoded anti-spike nanobodies: antibodies that are one-tenth the size of conventional monoclonal antibodies.

Although full viral-challenge studies are pending, nanobodies released from the engineered bacteria reached the bloodstream, likely facilitated by OMVs, and accumulated in lung tissue, where they neutralized SARS-CoV-2 in ex-vivo assays.
Clinical trials will validate the safety and efficacy of this delivery system for new engineered bacteria targeting other viruses.
So far the engineered bacteria have been found to be safe to use and do not generate any adverse immune response or side effects in animal models. Moreover, the parent strain of bacteria has decades of safe use as a probiotic.

Nitin S. Kamble et al, Engineered bacteria as an orally administered anti-viral treatment and immunization system, Gut Microbes (2025). DOI: 10.1080/19490976.2025.2500056

Part 2

Comment by Dr. Krishna Kumari Challa on May 22, 2025 at 11:51am

Engineered bacteria can deliver antiviral therapies and vaccines

New research  demonstrates how specially engineered bacteria taken orally can operate as a delivery system for antiviral therapies and vaccines. The research is published in the journal Gut Microbes.

The work focuses on engineering probiotic bacteria to accomplish a wide variety of functions, from breaking down cancer's defenses to imaging and diagnosing lung infections.

A few years ago, researchers asked whether the same chassis, using the bacterium E.coli Nissle 1917, could ferry antiviral therapeutic agents or vaccine antigens directly to the gut, a major portal of viral entry. They focused on the COVID-19 virus, SARS-CoV-2, for the proof-of-concept research.

Oral delivery lets us target the mucosal surfaces where pathogens first gain a foothold while avoiding needles and cold-chain logistics.

Most engineered bacteria keep their therapeutic cargo inside the cell, but vaccines work best when antigens are presented to the immune system. The researchers therefore displayed viral proteins on the bacterial surface and harnessed outer-membrane vesicles (OMVs)—nano-sized spheres that bacteria naturally shed—to act as self-propelled delivery vehicles. Once released, OMVs traffic through the gut epithelium, enter blood circulation and distribute their payload to distant tissues.

The researchers systematically screened anchor motifs and expression cassettes to optimize antigen density on the probiotic surface. For the vaccine version, the bacteria was designed to express the spike protein found on the surface of the virus that causes COVID-19. This same spike protein is currently delivered through mRNA COVID-19 vaccines.

Current vaccines are safe and effective at providing what is called systemic immunity, as antibodies move throughout the whole body in the bloodstream. But there are gateways in the body where viruses typically enter—through mucosal lining in the gastrointestinal system, lungs and other organs—that can be targeted to provide what is called mucosal immunity.

Part 1

Comment by Dr. Krishna Kumari Challa on May 22, 2025 at 11:24am

Why are men usually taller than women?

A recent study, analyzing genetic data from nearly a million individuals, sheds light on why men are typically taller than women. Researchers focused on the SHOX gene, located on both X and Y chromosomes, and its role in height determination.

While scientists have long suspected that genetics contribute to these differences, the biological mechanisms behind this sexual dimorphism independent of hormones remained unclear, until a team of researchers from the U.S. shed some light onto it with their study published in PNAS.

The team analyzed a large-scale dataset with 928,605 adult participants, including 1,225 adults with sex chromosome aneuploidies (SCAs)—genetic conditions where individuals have an abnormal number of X or Y chromosomes, either extra or missing.

They found that having an extra Y chromosome led to a greater increase in height compared to an additional X chromosome, regardless of the influence of male hormones.

The sex chromosomes X and Y are non-homologous, meaning they do not share many gene sequences or structures, but both contain a gene called SHOX located in pseudoautosomal region 1 (PAR1), a small section where X and Y chromosomes share sequence identity and work like a regular chromosome. The SHOX gene is a key player in influencing height.

In human females, most of the X chromosome is inactivated, except for PAR1, which escapes X-inactivation, and both human males and females typically have two active copies of PAR1 genes.

Research indicated that the SHOX and other genes in the PAR1 region have lower levels of expression in the inactive X chromosome (Xi), suggesting they are only partially protected from silencing.

This partial silencing means that males (46,XY) may have higher levels of SHOX since it is expressed in both the X and Y chromosomes, compared to females (46,XX) with two X chromosomes. This difference in gene expression is especially noticeable in musculoskeletal tissues, thus explaining sex differences in growth and height.

The findings indicated that the height contribution of the Y chromosome was larger than that of a second X chromosome, irrespective of hormonal differences.

The researchers highlight that understanding genetic underpinnings of sex dimorphisms is crucial not just for traits like height, but also for uncovering the biological mechanisms behind sex-based disparities in the occurrence of autoimmune, neuropsychiatric, and other medical conditions.

Alexander S. F. Berry et al, X and Y gene dosage effects are primary contributors to human sexual dimorphism: The case of height, Proceedings of the National Academy of Sciences (2025). DOI: 10.1073/pnas.2503039122

Comment by Dr. Krishna Kumari Challa on May 22, 2025 at 9:50am

Could Mitochondria Be Rewriting the Rules of Biology?

Comment by Dr. Krishna Kumari Challa on May 21, 2025 at 8:59am

Markers in blood and urine may reveal how much ultra-processed food we are eating

Molecules in blood and urine may reveal how much energy a person consumes from ultra-processed foods, a key step to understanding the impact of the products, a new study finds.

It's the first time that scientists have identified biological markers that can indicate higher or lower intake of the foods, which are linked to a host of health problems. The study is published   this week in the journal PLOS Medicine.

It can potentially give us some clues as to what the underlying biology might be between an ultraprocessed food association and a health outcome.

Ultraprocessed foods—sugary cereals, sodas, chips, frozen pizzas and more—are products created through industrial processes with ingredients such as additives, colours and preservatives not found in home kitchens. 

The scientists found that hundreds of metabolites—products of digestion and other processes—corresponded to the percentage of energy a person consumes from ultra-processed foods. From those, they devised a score of 28 blood markers and up to 33 urine markers that reliably predicted ultra-processed food intake in people consuming typical diets.

The researchers  found this signature that was sort of predictive of this dietary pattern that's high in ultra-processed food and not just a specific food item here and there.

A few of the markers, notably two amino acids and a carbohydrate, showed up at least 60 times out of 100 testing iterations. One marker showed a potential link between a diet high in ultraprocessed foods and type 2 diabetes, the study found.

The research team found that they could use the metabolite scores to tell when the individual participants were eating a lot of ultra-processed foods and when they weren't eating those foods.

The results suggested the markers were "valid at the individual level".

With more research, these metabolic signatures can begin to untangle the biologic pathways and harms of UPF and also differences in health effects of specific UPF food groups, processing methods and additives.

Abar L, et al. Identification and validation of poly-metabolite scores for diets high in ultra-processed food: An observational study and post-hoc randomized controlled crossover-feeding trial.PLOS Medicine (2025). DOI: 10.1371/journal.pmed.1004560

Comment by Dr. Krishna Kumari Challa on May 21, 2025 at 8:33am

Stopping infections before they can start: Promising approach blocks bacteria from binding to cells

As concerns about waning antibiotic effectiveness grow, researchers are using unique tools to search for new ways to keep bacteria from causing infections in both humans and animals.

Researchers used the Canadian Light Source (CLS) at the University of Saskatchewan to visualize the structure of long, thin proteins called adhesins, which most bacteria have, and which bind to a sugar molecule on the surface of a cell. Once attached, the bacteria start to form a colony and then eventually a biofilm. This is how they get started in an infection.

The goal of the research, recently published in the journal mBio, is to find a way to interrupt that attachment process—to "put something in there that would fool them (bacteria) and not allow them to bind to the host cells."

Researchers  learned how to recognize those parts of the protein that stick to the surface of cells and begin causing infections. The researchers noted one spot on the protein that attaches to a simple sugar called fucose found on human blood cells and other organisms.

Special imaging at the CLS—called crystallography—confirmed the model and revealed a possible way to inhibit bacteria from binding to cells. 

Adding more fucose in with the bacterium disrupts the binding process "because they're confused by all of this free fucose floating around" . The protein sensorsrs "that are looking out for the sugar on our cells" are unable to bind "because we're flooding the market with fucose."

The next steps in the research will be to produce compounds that mimic fucose "but that cannot be metabolized by either the bacteria or by the human cells that scientists are trying to protect" .  We won't have to put so much sugar in the system.

Qilu Ye et al, Aeromonas hydrophila RTX adhesin has three ligand-binding domains that give the bacterium the potential to adhere to and aggregate a wide variety of cell types, mBio (2025). DOI: 10.1128/mbio.03158-24

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