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Rheumatoid arthritis is an autoimmune disease with prevalence all over the world. Several therapeutics with different modes of action are available to deal with the disease but have failed to produce universal response leaving a large proportion of patients untreated. This is due to complex pathogenesis comprising a network of signaling pathways. By controlling one pathway, the pathogenesis continues through complementary pathways. Janus kinase and bruton's tyrosine kinase regulates a number of T-cell and B-cell mediated signaling pathways ranging from cytokine expression and antibody production to the bone resorption and cartilage destruction. We propose a dual trap to control this pathogenesis in the form of dual JAK3/BTK inhibitor. Using the computer-aided drug designing techniques, we developed dual JAK3 and BTK inhibitors based on quinoxaline derivatives which show appreciable dual inhibition in enzyme assays. To our knowledge, this is the first-ever report on dual JAK3/BTK inhibitors. [ABSTRACT FROM AUTHOR]

Sweet potato (Ipomoea batatas L. Lam.), known as "Shakarqandi" in Pakistan, is an imperative root vegetable with large size, traditionally used as aphrodisiac, antiprostatic, anti-inflammatory, antidiabetic, cardiotonic, and anticancer agent. Present study was conducted to gauge aphrodisiac potential of Ipomoea batatas ethyl acetate (IPT-EA, IPA-EA) and methanol (IPT-M, IPA-M) extracts from tuber and aerial part, respectively, via behavioral and biochemical tests and their possible protective role in BPA-induced gonadotoxicity at the dose 300 mg/kg in male Sprague Dawley rats. Phytochemical analysis was done qualitatively and quantitatively through total phenolic and flavonoid content (TPC and TFC) and high performance liquid chromatographic (HPLC-DAD) fingerprinting while antioxidant profiling used multimode in vitro assays. To calculate sexual excitement mount latency, intromission latency, mount frequency, intromission frequency, ejaculatory latency, and postejaculatory interval were examined while for biochemical ratification semen characteristics, levels of testosterone, follicle stimulating hormone (FSH), luteinizing hormone (LH), and estradiol were measured. Gonadoprotective ability was assessed through comet assay and histomorphological examination of testes. Qualitative analysis ensured the presence of phenols, flavonoids, tannins, anthocyanin, saponins, coumarins, terpenoids, and betacyanin. Quantitatively maximal TPC (304.32±7.20 μg GAE/mg dry extract) and TFC (214.77±4.09 μg QE/mg DE) were estimated in IPA-EA extract. IPT-EA yielded maximum rutin (7.3±0.12) and myricetin (2.7±0.14 μg/mg DE) while IPA-EA and IPA-M yielded maximum caffeic acid (4.05±0.22 and 1.92±0.17 μg/mg DE, respectively) in HPLC-DAD analysis. Extracts enhanced sexual excitement, improved semen quality, levels of testosterone, FSH, LH, and estradiol, and successfully attenuated toxic effects of BPA. Levels of endogenous antioxidant enzymes (CAT, SOD, POD, and GSH) were restored and NO abundance was minimized. Significant stimulation in sexual behavior, amelioration of toxicity symptoms, elevated spermatic production, raised viability, vitalized levels of gonadal hormones, maintained endogenous enzymes, genoprotection, and reformed testicular histology endorsed I. batatas as a better aphrodisiac alternative and gonadoprotective agent. [ABSTRACT FROM AUTHOR]