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Evidence for the Worldwide Distribution of a Bile Salt Hydrolase Gene in Through Horizontal Gene Transfer.
Int J Mol Sci
January 2025
Bioproduction Research Institute, National Institute of Advanced Industrial Science and Technology, Tsukuba 305-8566, Ibaraki, Japan.
Bile salt hydrolase (BSH), a probiotic-related enzyme with cholesterol-assimilating and anti-hypercholesterolemic abilities, has been isolated from intestinal bacteria; however, BSH activity of bacteria in bile-salt-free (non-intestinal) environments is largely unknown. Here, we aimed to identify BSH from non-intestinal and characterize its enzymatic function. We successfully isolated a plasmid-encoded () from , and the recombinant EfpBSH showed BSH activity that preferentially hydrolyzed taurine-conjugated bile salts, unlike the activity of known BSHs.
View Article and Find Full Text PDFThe Real-World Clinical Outcomes of Heavily Pretreated HER2+ and HER2-Low Metastatic Breast Cancer Patients Treated with Trastuzumab Deruxtecan at a Single Centre.
Curr Oncol
December 2024
Jewish General Hospital, Montreal, QC H3T 1E2, Canada.
Background: Trastuzumab deruxtecan (TDXd) is an antibody-drug conjugate that has demonstrated impressive activity in randomized controlled clinical trials in the context of patients with HER2-amplified and HER2-low metastatic breast cancer. We aimed to review the activity and adverse event profile of TDXd in heavily pretreated breast cancer patients in real practice.
Methods: We describe a single-center retrospective case series of metastatic breast cancer patients who were treated with TDXd.
Bile acid synthesis impedes tumor-specific T cell responses during liver cancer.
Science
January 2025
NOMIS Center for Immunobiology and Microbial Pathogenesis, Salk Institute for Biological Studies, La Jolla, CA, USA.
The metabolic landscape of cancer greatly influences antitumor immunity, yet it remains unclear how organ-specific metabolites in the tumor microenvironment influence immunosurveillance. We found that accumulation of primary conjugated and secondary bile acids (BAs) are metabolic features of human hepatocellular carcinoma and experimental liver cancer models. Inhibiting conjugated BA synthesis in hepatocytes through deletion of the BA-conjugating enzyme bile acid-CoA:amino acid -acyltransferase (BAAT) enhanced tumor-specific T cell responses, reduced tumor growth, and sensitized tumors to anti-programmed cell death protein 1 (anti-PD-1) immunotherapy.
View Article and Find Full Text PDFHomopregnane-type ferrocene-steroid conjugates exhibit immunomodulatory activity.
Bioorg Chem
February 2025
Department of Chemistry, Faculty of Sciences and Mathematics, University of Niš, Višegradska 33, 18000 Niš, Serbia. Electronic address:
Article Synopsis
- Researchers developed new compounds by linking ferrocene to natural steroid structures to enhance their biological activity.
- The team created 8 new conjugates from various progestogens and characterized them using advanced techniques like NMR and UV-Vis.
- Although the conjugates weren't highly toxic to rat spleen cells, they elicited diverse immune responses, likely due to the presence of the ferrocene component.
Enhanced expression of Cyp17a1 and production of DHEA-S in the liver of late-pregnant rats.
Gen Comp Endocrinol
January 2025
Laboratory of Veterinary Biochemistry, Department of Veterinary Medicine, Rakuno Gakuen University, Ebetsu, Hokkaido, Japan.
Cytochrome P450 17A1 (CYP17A1) catalyzes two enzymatic reactions in the biosynthesis of dehydroepiandrosterone (DHEA) from pregnenolone. In pregnant humans, the adrenal gland is responsible for DHEA biosynthesis, which is then sulfated by SULT2A1 and released into the bloodstream. This sulfated DHEA is subsequently taken up by the placenta and deconjugated to serve as a precursor for estrogen biosynthesis.
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