Notes

To understand the detailed mechanism of actions of the purified compound, several molecular biology and structural biology experiments such as Western blot, siRNA transfection assay and molecular docking study were performed
RESULTS AND DISCUSSION: Bioactivity guided isolation of pure compound and spectral data analysis led us to identify the active component as Kaempferol 3-O-rutinoside (KOR) for the first time from the leaf of A. acidum. Over expression of NAD-dependent histone deacetylase, Sirtuin 1 (SIRT1) was observed following KOR treatment. SIRT1 plays an important role in the metabolic pathway and over expression of SIRT implies that it involves in insulin signaling directly or indirectly. Molecular docking and simulation study showed the strong involvement between KOR and SIRTTreatment with KOR resulted in significant over expression of SIRT1followed by upregulation of insulin-dependent p-IRS, AKT and AMPK signaling molecules, and stimulation of the GLUT4 translocation, which ultimately enhanced the glucose uptake in sodium palmitate-treated insulin resistant L6 myotubes. Further, the effect of KOR on IRS1, AKT and AMPK phosphorylation, GLUT4 translocation, and glucose uptake was attenuated in SIRT1-knockdown myotubes.

CONCLUSION: Overall, the results of this study suggest that Kaempferol 3-O-rutinoside is the active component presents in the leaf of A. acidum which increases glucose consumption by inducing SIRT1 activation and consequently improves insulin sensitization. These results may find future applications in Science and Technology (IASST), Vigyan Path, Paschim Boragaon, Garchuk, 781035, Guwahati, Assam, India; Department of Molecular Biology and Biotechnology, Cotton Study in Science and Technology (IASST), Vigyan Path, Paschim Boragaon, Garchuk, Science and Technology (IASST), Vigyan Path, Paschim Boragaon, Garchuk, 781035, Study in Science and Technology (IASST), Vigyan Path, Paschim Boragaon, Garchuk, Institute (THISTI), Faridabad, 121001, Haryana, India; Department of Science and Technology (IASST), Vigyan Path, Paschim Boragaon, Garchuk, 781035, Nagar, Panikhaiti, Guwahati, Assam, India. Electronic address: repurposable drug for atrial fibrillation. Effective drugs for atrial fibrillation (AF) are lacking, resulting in significant morbidity and mortality. Polysaccharide polymer demonstrates that network proximity analysis of differentially expressed genes from atrial tissue to drug targets can help prioritize repurposed drugs for AF. Using enrichment analysis of drug-gene signatures and functional testing in human inducible pluripotent stem cell (iPSC)-derived atrial-like cardiomyocytes, we identify metformin as a top repurposed drug candidate for AF.

Using the active compactor, a new design analysis of large-scale longitudinal electronic health record (EHR) data, we AF (odds ratio = 48, 95%, confidence interval [CI] 36-64, p < 001) compared with standard treatments for diabetes. This study utilizes network medicine methodologies to identify repurposed drugs for AF treatment and identifies metformin as a candidate drug. Metabolic Sciences, Lerner Research Institute, Cleveland Clinic, Cleveland, OH, Pancreatic ductal adenocarcinoma (PDAC) is an aggressive disease with a low 5-year survival rate and is associated with poor response to therapy. Elevated expression of the myeloid-specific hematopoietic cell kinase (HCK) is observed in HCK signaling in myeloid cells is involved in PDAC growth and metastasis, we established orthotopic and intrasplenic PDAC tumors in wild-type and HCK knockout mice. Genetic ablation of HCK impaired PDAC growth and metastasis by inducing an desmoplastic microenvironment and enhanced cytotoxic effector cell infiltration. Consequently, genetic ablation or therapeutic inhibition of HCK minimized metastatic spread, enhanced the efficacy of chemotherapy, and overcame resistance to anti-PD1, anti-CTLA4, or stimulatory anti-CD40 immunotherapy. Our results provide strong rationale for HCK to be developed as a therapeutic target to improve the response of PDAC to chemo- and immunotherapy.

Cancer Medicine, Melbourne, VIC 3084, Australia; Department of Computing and Cancer Medicine, Melbourne, VIC 3084, Australia. Electronic address: related to this work filed by The Olivia Newton-John Cancer Research Institute (PCT/AU2021/051073) on the 16(th) of September and interactions in the adaptive immune response. T cells mediate antigen-specific immune responses to disease through the specificity and diversity of their clonotypic T cell receptors (TCRs). Determining the spatial distributions of T cell clonotypes in tissues is essential to understanding T cell behavior, but spatial sequencing methods remain unable to profile the TCR repertoire. Here, Polysaccharide polymer developed Slide-TCR-seq, a 10-μm-resolution method, to sequence whole transcriptomes and TCRs within intact tissues. We confirmed the ability of Slide-TCR-seq to map the characteristic locations of T cells and their receptors in mouse spleen. In human lymphoid germinal centers, we identified spatially distinct TCR repertoires.

Profiling T cells in renal cell carcinoma and melanoma specimens revealed heterogeneous immune responses: T cell states and infiltration differed intra- and inter-clonally, and adjacent tumor and immune cells exhibited distinct gene expression.
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