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Human skeletal development and regeneration are shaped by functional diversity of stem cells across skeletal sites

Ambrosi and colleagues profile human skeletal stem cells (hSSCs) across ten fetal skeletal sites and from patients throughout adulthood, identifying, mapping, and functionally testing four distinct hSSC subtypes. Skeletal aging and disease are characterized by a dominant fibrogenic hSSC variant, but targeting defined gene regulatory networks reinstates functional hSSC diversity.

Scientists May Have Found a Natural Alternative to Ozempic

Scientists may have identified a way to naturally regulate blood sugar levels and sugar cravings in a similar fashion to drugs like Ozempic.

In mice and humans, the key to unlocking this natural process was found to be a gut microbe and its metabolites – the compounds it produces during digestion.

By increasing the abundance of this one gut microbe in diabetic mice, researchers led by a team at Jiangnan University in China showed they can “orchestrate the secretion of glucagon-like peptide-1”

Efficient Production of Enterovirus 71 (EV71) Virus-like Particles by Controlling Promoter Strength in Insect Cells

This study was conducted to efficiently produce virus-like particles (VLPs) of enterovirus 71 (EV71), a causative virus of hand, foot, and mouth disease (HFMD). The expression level of the P1 precursor, a structural protein of EV71, was modified to increase VLP production, and the optimal expression level and duration of the 3CD protein for P1 cleavage were determined. The expression level and duration of 3CD were controlled by the p10 promoter, which was weakened by repeated burst sequence (BS) applications, as well as the OpIE2 promoter, which was weakened by the insertion of random untranslated region sequences of various lengths. The cleavage and production efficiency of the P1 precursor were compared based on the expression time and level of 3CD, revealing that the p10-BS5 promoter with four repeated BSs was the most effective. When P1 and 3CD were expressed using the hyperexpression vector and the p10-BS5 promoter, high levels of structural protein production and normal HFMD-VLP formation were observed, respectively. This study suggests that the production efficiency of HFMD-VLPs can be significantly enhanced by increasing the expression of the P1 precursor and controlling the amount and duration of 3CD expression.

Gene-editing therapy shows early success in fighting advanced gastrointestinal cancers

Researchers at the University of Minnesota have completed a first-in-human clinical trial testing a CRISPR/Cas9 gene-editing technique to help the immune system fight advanced gastrointestinal (GI) cancers. The results, recently published in The Lancet Oncology, show encouraging signs of the safety and potential effectiveness of the treatment.

“Despite many advances in understanding the genomic drivers and other factors causing cancer, with few exceptions, stage IV remains a largely incurable disease,” said Emil Lou, MD, Ph.D., a gastrointestinal oncologist with the University of Minnesota Medical School, Masonic Cancer Center and M Health Fairview, and clinical principal investigator for the trial. “This trial brings a new approach from our research labs into the clinic and shows potential for improving outcomes in patients with late-stage disease.”

In the study, researchers used CRISPR/Cas9 gene-editing to modify a type of immune cell called tumor-infiltrating lymphocytes (TILs). By deactivating a gene called CISH, the researchers found that modified TILs were better able to recognize and attack .

AI identifies PHGDH as amyloid pathology driver in Alzheimer’s disease

Insomnia, depression, and anxiety are the most common mental disorders. Treatments are often only moderately effective, with many people experiencing returning symptoms. This is why it is crucial to find new leads for treatments. Notably, these disorders overlap a lot, often occurring together. Could there be a shared brain mechanism behind this phenomenon?

Siemon de Lange, Elleke Tissink, and Eus van Someren, together with their colleagues from the Vrije Universiteit Amsterdam, investigated brain scans of more than 40,000 participants from the UK Biobank. The research is published in the journal Nature Mental Health.

Tissink says, “In our lab, we explore the similarities and differences between , anxiety, and depression. Everyone looks at this from a : some mainly look at genetics and in this study, we look at brain scans. What aspects are shared between the disorders, and what is unique to each one?”

Gut microbes release cancer-fighting bile acids that block hormone signals

Bacteria naturally present in the human intestine (known as the gut microbiota) can transform cholesterol-derived bile acids into powerful metabolites that strengthen anti-cancer immunity by blocking androgen signaling, according to a preclinical study led by Weill Cornell Medicine investigators. The study was published on April 15 in Cell.

“I was very surprised by our findings. As far as I know, no one has previously discovered molecules like these bile acids that can interact with the androgen receptor in this way,” said co-senior author Dr. Chun-Jun Guo, an associate professor of immunology in medicine in the Division of Gastroenterology and Hepatology and a scientist at the Jill Roberts Institute for Research in Inflammatory Bowel Disease at Weill Cornell Medicine.

Dr. David Artis, director of the Jill Roberts Institute and the Friedman Center for Nutrition and Inflammation and the Michael Kors Professor in Immunology, and Dr. Nicholas Collins, assistant professor of immunology in medicine, both at Weill Cornell Medicine, are co-senior authors of the study. Drs. Wen-Bing Jin, formerly a postdoctoral associate, and Leyi Xiao, a current postdoctoral associate in Dr. Guo’s lab, are the co-first authors of the study.