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Psychological distress, including anxiety or mood disorders, emanates from the onset of chronic/unpredictable stressful events. Symptoms in the form of maladaptive behaviors are learned and difficult to treat. While the origin of stress-induced disorders seems to be where learning and stress intersect, this relationship and molecular pathways involved remain largely unresolved.

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To understand the action mechanism of probiotics against postmenopausal symptoms, we examined the effects of Lactococcus lactis P32 (P) and Bifidobacterium bifidum P45 (P), which suppressed interleukin (IL)-6 and receptor activator of nuclear factor-κB (RANK) ligand (RNAKL) expression in Gardnerella vaginalis (Gv)-stimulated macrophages, on vaginitis, osteoporosis, and depression/cognitive impairment (DC) in mice with vaginally infected Gv, ovariectomy (Ov), or Ov/Gv (oG). Oral administration of P or P decreased Gv-induced DC-like behavior and tumor necrosis factor (TNF)-α, IL-6, RANK, and/or RANKL expression in the vagina, bone, hypothalamus, hippocampus, and colon, while Gv-suppressed bone osteoprotegerin and brain serotonin and brain-derived neurotrophic factor (BDNF) levels increased. They partially shifted vaginal and gut dysbiosis in Gv-infected mice to the gut microbiota composition in normal control mice.

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Refining minimal engineered receptors for specific activation of on-target signaling molecules.

Sci Rep

December 2024

Laboratory of Cell Vaccine, Microbial Research Center for Health and Medicine (MRCHM), National Institutes of Biomedical Innovation, Health and Nutrition (NIBIOHN), 7-6-8 Saito-Asagi, Ibaraki-Shi, Osaka, 567-0085, Japan.

Since designer cells are attracting much attention as a new modality in gene and cell therapy, it would be advantageous to develop synthetic receptors that recognize artificial ligands and activate solely signaling molecules of interest. In this study, we refined the construction of our previously developed minimal engineered receptors (MERs) to avoid off-target activation of STAT5 while maintaining on-target activation of signaling molecules corresponding to tyrosine motifs. Among the myristoylated, cytoplasmic, and transmembrane types of MERs, the cytoplasmic type had the highest signaling efficiency, although there was off-target activation of STAT5 upon ligand stimulation.

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This study investigates the potential treatment of breast cancer utilizing Gentiana robusta King ex Hook. f. (QJ) through an integrated approach involving network pharmacology, molecular docking, and molecular dynamics simulation.

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A real-world pharmacovigilance analysis of potential ototoxicity associated with sacubitril/valsartan based on FDA Adverse Event Reporting System (FAERS).

Sci Rep

December 2024

Department of Comprehensive Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100021, China.

Sacubitril/valsartan, a first-in-class angiotensin receptor neprilysin inhibitor, is widely used to treat heart failure. Despite its efficacy, sacubitril/valsartan inevitably causes adverse events such as hypotension, renal dysfunction, hyperkalemia, and angioedema. Sacubitril/valsartan-associated ototoxicity is often underreported in clinical studies and real-world settings.

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