United States: In a set of cell and animal experiments, a team has found out who is mainly to blame for worsening symptoms in patients suffering from fibrodysplasia ossificans progressiva, a rare hereditary disease. 

The team was headed by CiRA’s Associate Professor Makoto Ikeya and the Owner of Chongqing Medical University, Cheng Chu Zhao, who is a former researcher at CiRA’s Department of Clinical Application. The results of their study are presented in the EMBO Molecular Medicine scientific journal. 

A Rare and Complex Disease 

Fibrodysplasia ossificans progressiva (FOP) is a rare hereditary disease characterized by the fact that muscles and connective tissue are replaced by bone tissue due to a mutation in the gene encoding a bone morphogenetic protein (BMP) type I receptor in more than 95% of FOP patients, which leads to the activation of BMP signaling by Activin A, a TGF-β ligand, as reported by Medicalxpress. 

This heterotopic ossification (HO) is peculiar to flare, which is episodes of painful soft tissue swelling that are traceable to a minor injury. Reno-activated FAPs, a mesenchymal stromal cell (MSC) population, give rise to most of the newly formed bone tissue associated with HO. 

Consequently, any measure that would hamper the growth of the FAPs may slow down the progression of the disease. Nevertheless, the exact molecular pathways related to flare-ups are still not well understood. 

Study Identifies Key Driver 

In order to study the flare-up mechanisms in more detail, the research team initially aimed at defining molecules that might be associated with the stimulation of MSC proliferation in FOP patients. For this, they used a panel of potential ligands to treat FOP-iMSCs and resFOP-iMSCs, induced pluripotent stem cells derived from an FOP patient and detected with mutated or corrected ACVR1, respectively. 

In terms of the effect on proliferation, most of the TGF-β and BMP ligands exhibited a similar trend on FOP- and resFOP-iMSCs, with the exception that BMP-9 stimulated the proliferation of FOP-iMSCs, an effect that was validated using a second set of iMSCs from another FOP patient. Other experiments which analyzed more for a cell proliferative marker and the ability of the FOP-iMSCs to progress through the cell cycle also provided significant evidence for a particular role of BMP-9 in FOP-iMSCs. 

The researchers then investigated the in vivo function of BMP-9 by injecting it into the muscles of FOP model mice that possess the FOP mutation. Most notably, the intramuscular injection of BMP-9 caused changes in the tissue that mimicked flare-ups in regard to the formation of abnormal cartilage and bones as well as the uptick of FAP accumulation, but only in mice with expressed mutant ACVR1. 

In order to learn more regarding the involvement of BMP-9 in FOP pathogenesis, the research group also performed experimental muscle damage by injecting cardiotoxin into the calf muscle of FOP model mice. Morphological analysis of the injury site demonstrated that proliferative BMP-9-positive cells and BMP-9-rich extracellular matrix in the surrounding area may contribute to the increase in serum BMP-9 levels. 

On the other hand, the isoform used for the intramuscular cardiotoxin injection into healthy mice promoted the appearance of BMP-9-positive cells within the lesion area; however, their density seemed to decrease while muscle regeneration began, and there was also no significant change in serum BMP-9 levels. In addition, the authors pointed out that monocytes and macrophages, which constituted the first line of inflammation in the investigated FOP, were the major source of BMP-9 responsible for the ectopic FAP deposition in the subsequent phases of muscle damage and HO in the FOP model mice. 

The researchers used genetic and pharmacologic analyses to establish the significant role of BMP-9 in HO of FOP and assess whether these results might have impacts as potential treatments for FOP. As in FOP model mice with a deletion of the BMP-9 gene or treated with a BMP-9 neutralizing antibody, HO progression following intramuscular cardiotoxin injection was reduced. 

Moreover, the antibody-based BMP-9 neutralizing study indicated that BMP-9 is best neutralized in the early hours to curtail the progression of HO. 

Potential Therapeutic Breakthroughs 

Lastly, to know how BMP-9 induces FAP proliferation, the research team compared the gene expression of treated and untreated FOP- and resFOP-iMSCs. As anticipated, this analysis pointed towards an improvement in TGF-β signaling; this research also tested for TGF-β activation explicitly; it used techniques to test SMAD2/3 phosphorylation. 

On the basis of these observations, the researchers used gain and loss of function studies to determine whether targeting ACVR1-SMAD signaling through genetic downregulation or pharmacological inhibition would inhibit FOP-iMSCs proliferation. From these experiments, they concluded that in BMP-9 stimulated FOP-iMSC, DMH1 small molecule that targets only the SMAD binding site in ACVR1 abrogated the proliferation; however, it had no effects on TGF-β stimulated FOP- and resFOP-iMSC, as reported by Medicalxpress. 

Hope for FOP Patients 

Moreover, they found that TGF-β signaling repressed the enhanced proliferation of FOP-iMSCs due to the genetic inhibition of SMAD2/3 by siRNA-mediated knockdown. 

In carrying out this study, the research team showed the significant BMP-9-mediated MSC proliferation in flare-ups in patients with FOP. In addition, the researchers prove the therapeutic potential of several prospective approaches to prevent losses due to this detrimental signaling activates by BMP-9 so that the patients who suffer from FOP can expect some improvements in reducing the severity of flare-ups. 

United States: It has happened to everyone during the holidays: You cannot avoid tempting foods during the festive season, and your stomach gives you a hard time, as reported by HealthDay. 

Festive Foods and Your Gut 

Thankfully, one such expert does have some bravo dos on how to ideally survive the gluttonous parade of foods that merrymaking brings. 

Overindulging in festive food can knock the digestive system out of whack and result in things like bloating, discomfort, and more serious and chronic issues for the gastrointestinal system. 

“As we enjoy our favorite dishes with our family this holiday season, it is important to remember that moderation is key,” said Jessica Scoffield, an associate professor at the University of Alabama at Birmingham Department of Microbiology. “Pay attention to when you’re full, and make time for exercise during the holidays to kick off the new year on the right track.” 

Here are five tips to keep you safe this festive season: 

Choose fiber: Many festive foods are high in carbs, meaning that your digestive system must still be given a workout through vegetables and whole grains. Fiber is good for digestion and health and aims to eliminate constipation by encouraging the growth of good bacteria in the colon, as per Scoffield Did. 

Drink plenty of water: Since everybody enjoys taking alcoholic beverages, especially during festive times such as the holidays there is a realization of many sumptuous and rich drinks such as egg nog and Christmas punch, among others, hence the common trend of people forgetting about taking water.. But then it aids in digestion and ensures that no materials get stuck within your intestines. Try to ensure that before you take any meal, you take at least one glass of water and switch between the water and any other holiday drinks. 

Go slow: Holiday meals often make you eager to start eating fast; if you do, your digestive system may take a long time to break it down. Taking your meals slowly allows the body, specifically the stomach, to indicate that it is full. Scoffield also pointed out that mindful eating makes it possible to avoid becoming bloated and overeating — and still indulge in all the tasty foods of the holidays. 

Embrace probiotics: Prebiotics are conditions that promote the growth of symbiotic beneficial bacteria and help regulate an ideal balance in the human body. Different vitamins and foods like yogurt and kombucha contain probiotics, and incorporating them helps the gut during the holidays. 

Keep moving: Although people may find it easier to nap after a meal, they should exercise lightly to help digestion. As aforementioned, any movement, including simply walking, can assist the digestive system and alleviate bloating. If possible, during the holidays, try to exercise gently during the day for better gut bacteria, as reported by HealthDay. 

United States: On Friday, the US gave a federal order ordering that the national milk supply be tested for bird flu. Vilsack of Agriculture told Reuters that authorities are desperate to deal with an equally increasing rate of the virus among dairy herds, as reported by Reuters. 

Bird Flu Outbreak Hits U.S. Dairy Herds 

The outbreak of Bird flu has affected over 500 dairy herds in top milk state California and more than 700 in the United States since March as per the U.S Department of Agriculture raising concerns about the effects it has on farmers and the available milk supply as well as the chances it poses to human health as it continues to spread. 

More than 50 people have been affected by the deadly virus since April, and most of the workers handling poultry and dairy industries have affected farms, the U.S Center for Disease Control confirmed. The symptoms have been rather mild, and CDC officials have stated that the threat of bird flu is not high for ordinary citizens. 

The USDA had said it would formally start national milk testing in October, following pressure from industry and vet groups for increased surveillance of the virus, but had yet to specify exactly what shape the plan would take. 

USDA Implements Comprehensive Milk Testing Plan 

The testing plan, which calls for sampling from the bulk milk tanks at least monthly, and from the dairy processors at least weekly, will first be implemented in California, Colorado, Michigan, Mississippi, Pennsylvania, and Oregon, Vilsack said. 

The last three states have not disclosed bird flu in dairy cattle. 

“It gives us the opportunity to get potentially a heads up about potentially new virus in areas of a state that currently has the virus, or new states,” Vilsack said of the testing. 

The agency will start the testing on Dec. 16, Vilsack said. 

The rate at which testing is conducted will depend on whether the virus is found on initial screening, according to Rosemary Sifford USDA’s chief veterinarian. 

New Requirements for Farms and Processors 

The order has compelled farms and processors into offering raw milk for sampling alongside farm owners who have positive results of the virus to report to the agency on animal movement and many others. 

The USDA currently only mandates testing of lactating dairy cattle crossing state lines, a provision it has in its only other federal avian flu order established in April. 

The two federal orders will continue indefinitely, Vilsack said, and the testing plan was constructed in cooperation with industry groups and veterinarians, state officials. 

California issued a recall of milk and cream products made by raw milk company Raw Farm this week after bird flu was detected in its retail products and bulk milk. 

California Takes Action Amid Dairy Outbreak 

The Food and Drug Administration frowns at the consumption of raw milk for the purpose of drinking because the milk may contain pathogens such as bird flu, but there is no harm in taking milk products that have been pasteurized because pasteurization kills those pathogens, as reported by Reuters. 

There are roughly 1,100 dairies in the state, according to the California Milk Advisory Board, which indicates that 44% of them have been affected by bird flu.