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Category: biotech/medical

Abstract: For those interested in fertility regulation, endometriosis, adenomyosis, and endometrial cancer…

Francesco J. DeMayo & team discover uterine ZMIZ1 co-regulates estrogen receptor to establish and maintain pregnancy and general uterine health via cell growth responses and preventing uterine fibrosis:

The figure shows epithelial cell DNA synthesis (reflected by EdU incorporation) was inhibited by Zmiz1 deletion.

1Pregnancy & Female Reproduction Group, Reproductive and Development al Biology Lab, NIEHS, Research Triangle Park, North Carolina, USA.

2Inotiv-RTP, Durham, North Carolina, USA.

3Division of Hematology-Oncology, Department of Internal Medicine, University of Michigan School of Medicine, Ann Arbor, Michigan, USA.

Plant used in folk medicine has anti-inflammatory anti-arthritic effects, study confirms

In Brazil, researchers from the Federal University of Grande Dourados (UFGD), the State University of Campinas (UNICAMP), and São Paulo State University (UNESP) have conducted a study that confirmed the safety and anti-inflammatory, analgesic, and anti-arthritic properties of the Joseph’s Coat plant (Alternanthera littoralis).

Native to the Brazilian coast, this plant has been used in folk medicine to combat inflammation, microbial infections, and parasitic diseases. Until now, there has been little pharmacological evidence to support these applications or analyze their safety.

The study is published in the Journal of Ethnopharmacology.

PreTA-mediated metabolism of 5-fluorouracil by intratumoral Citrobacter freundii drives chemoresistance in pancreatic cancer

Xu et al. report that intratumoral Citrobacter enrichment correlates with poor overall survival in pancreatic cancer patients. An intratumoral Citrobacter freundii strain metabolizes 5-fluorouracil (5-FU) into inactive products via PreTA. Gimeracil, an inhibitor of human dihydropyrimidine dehydrogenase, preserves 5-FU efficacy by blocking PreTA activity.

Targeting Human Proteins for Antiviral Drug Discovery and Repurposing Efforts: A Focus on Protein Kinases

Despite the great technological and medical advances in fighting viral diseases, new therapies for most of them are still lacking, and existing antivirals suffer from major limitations regarding drug resistance and a limited spectrum of activity. In fact, most approved antivirals are directly acting antiviral (DAA) drugs, which interfere with viral proteins and confer great selectivity towards their viral targets but suffer from resistance and limited spectrum. Nowadays, host-targeted antivirals (HTAs) are on the rise, in the drug discovery and development pipelines, in academia and in the pharmaceutical industry. These drugs target host proteins involved in the virus life cycle and are considered promising alternatives to DAAs due to their broader spectrum and lower potential for resistance.

AI identifies key mpox protein for new vaccine and antibody therapies

With the help of artificial intelligence, an international team of researchers has made the first major inroad to date toward a new and more effective way to fight the monkeypox virus (MPXV), which causes a painful and sometimes deadly disease that can be especially dangerous for children, pregnant women and immunocompromised people.

Reporting in the journal Science Translational Medicine, the team found that when mice were injected with a viral surface protein recommended by AI, the animals produced antibodies that neutralized MPXV, suggesting the breakthrough could be used in a new mpox vaccine or antibody therapy.

In 2022, mpox began to spread around the world, causing flulike symptoms and painful rashes and lesions for more than 150,000 people, while causing almost 500 deaths. Vaccines developed to fight smallpox were repurposed amid the outbreak to help the most vulnerable patients, but that vaccine is complicated and costly, due to its manufacture from a whole, weakened virus.

Multiple modes of transcriptional regulation by the nuclear hormone receptor RARγ in human squamous cell carcinoma

Vitamin A metabolism and signaling through nuclear retinoic acid receptors (RARs α,β,γ) regulate embryogenesis, immune functions, and cell differentiation in most cell types. RARγ is highly expressed in stratified squamous epithelial cells of the oral cavity and skin. While data indicate that RARγ agonism is anti-tumorigenic in oral cavity squamous cell carcinoma (OCSCC), the specific, primary gene targets of RARγ remain poorly characterized. Here, we define RARγ signaling pathways through integrating genome-wide RARγ binding by Cleavage under Targets and Release Using Nuclease (CUT&RUN), chromatin histone marks, and global transcriptomics ± agonists in human OCSCC cells and in human OCSCC cells with deletion of RARG (RARGKO).

Medications change our gut microbiome in predictable ways

The bacteria in our poop are a reasonable representation of what’s living in our digestive system. To understand how different drugs can impact the gut microbiome, the team cultured microbial communities from nine donor fecal samples and systematically tested them with 707 different clinically relevant drugs.

The researchers examined changes in the growth of different bacterial species, the community composition, and the metabolome – the mix of small molecules called metabolites that microbes produce and consume. They found that 141 drugs altered the microbiome of the samples and even short-term treatments created enduring changes, entirely wiping out some microbial species. The primary force behind how the community responds to drug inhibition was competition over nutrients.

“The winners and losers among our gut bacteria can often be predicted by understanding how sensitive they are to the medications and how they compete for food,” said the first author on the paper. “In other words, drugs don’t just kill bacteria; they also reshuffle the ‘buffet’ in our gut, and that reshuffling shapes which bacteria win.”

Despite the complexity of the bacterial communities, the researchers were able to create data-driven computer models that accurately predicted how they would respond to a particular drug. They factored in the sensitivity of different bacterial species to that drug and the competitive landscape – essentially, who was competing with whom for which nutrients.

Their work provides a framework for predicting how a person’s microbial community might change with a given drug, and could help scientists find ways to prevent these changes or more easily restore a healthy gut microbiome in the future.

Our gut microbiome is made up of trillions of bacteria and other microbes living in our intestines. These help our bodies break down food, assist our immune system, send chemical signals to our brain, and potentially serve many other functions that researchers are still working to understand. When the microbiome is out of balance – with not enough helpful bacteria or the wrong combination of microbes – it can affect our whole body.

Continue reading “Medications change our gut microbiome in predictable ways” | >

Real-time imaging captures what happens to cancer cells arriving in the brain

Metastasis occurs when cancer cells break away from the original tumor and travel through the bloodstream to form new tumors in other parts of the body. It is the leading cause of cancer-related death. Brain metastasis is particularly severe and affects 10–30% of patients with advanced lung, breast, and melanoma cancers.

While therapies exist for established brain tumors, there are limited strategies that directly target the very first cancer “seed cells” that enter and lodge in the brain.

Our brains, however, are equipped with immune cells called microglia that rapidly respond to pathogens and cancer cells by engulfing and digesting them. Yet scientists could not explain why microglia sometimes fail to destroy incoming seed cells because they could not watch this critical interaction in real-time in the living brain.

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