Not only that, bicyclol markedly attenuated T2DM-NAFLD induced production of inflammation factors (IL-1β and TNF-α). Moreover, bicyclol suppressed the expression of insulin/gluconeogenesis signaling pathway (Akt, PGC-1α and PEPCK). These findings suggested that bicyclol might be a potentially effective drug for the treatment of T2DM-NAFLD and other metabolic disorders.In mammals, sexual hormones such as estrogens play an essential role in maintaining brain homeostasis and function. Estrogen deficit in the brain induces many undesirable symptoms such as learning and memory impairment, sleep and mood disorders, hot flushes, and fatigue. These symptoms are frequent in women who reached menopausal age or have had ovariectomy and in men and women subjected to anti-estrogen therapy. Hormone replacement therapy alleviates menopause symptoms; however, it can increase cardiovascular and cancer diseases. In the search for therapeutic alternatives, medicinal plants and specific synthetic and natural molecules with estrogenic effects have attracted widespread attention between the public and the scientific community. Various plants have been used for centuries to alleviate menstrual and menopause symptoms, such as Cranberry, Ginger, Hops, Milk Thistle, Red clover, Salvia officinalis, Soy, Black cohosh, Turnera diffusa, Ushuva, and Vitex. This review aims to highlight current evidence about estrogenic medicinal plants and their pharmacological effects on cognitive deficits induced by estrogen deficiency during menopause and aging.Peyronie's disease (PD) is a localized fibrotic lesion of the penis that has adverse effects on men's health. In this review, we summarized the molecular mechanisms and pharmacotherapies of PD. A literature search was conducted using PubMed and Cochrane Library during 2001-2020. Although no oral or topical medication demonstrated efficacy in monotherapy of PD, several intralesional medications have yielded promising results. Currently, the effective strategy in management of PD should be combined modality therapy, including but not limited to pharmacotherapy, mechanical therapy, and psychotherapy. Meanwhile, basic research is still necessary to facilitate the development of novel and more reliable treatments. In future, more attention should be given simultaneously to epigenetic changes, inflammatory cytokines, the abnormal wound-healing process, and profibrotic and anti-fibrotic factors to provide more options for this refractory disease.The contribution of the metabolites of linezolid to the associated myelosuppression is unknown in patients who are renal impairment. In this research, the purpose of our experiment was to explore and develop a quick and robust ultra performance liquid chromatography tandem mass spectrometry (UPLC-MS/MS) assay for the determination of linezolid and its metabolite PNU-142300 in human serum simultaneously. The analytes were prepared using a simple and convenient approach with acetonitrile for protein crash, and then separated from the matrix on a Waters Acquity Ultra performance liquid chromatography (UPLC) BEH C18 (2.1 mm × 50 mm, 1.7 μm) column in a program of gradient elution, where the mobile phase was consisted of water with 0.1% formic acid and acetonitrile, and was placed at 0.40 ml/min flow rate. Multiple reaction monitoring (MRM) was employed and conducted for UPLC-MS/MS detection with ion transitions at m/z 338.01 → 296.03 for linezolid, m/z 369.96 → 327.98 for PNU-142300 and m/z 370.98 → 342.99 for tedizolid (Internal standard, IS), respectively. This method had good linearity respectively in the calibration range of 0.01-20 μg/ml for linezolid, and 0.05-100 μg/ml for PNU-142300. In the intra- and inter-day, the precision of linezolid and PNU-142300 was below 14.2%, and the accuracy in this method was determined to be from -9.7 to 12.8%. In addition, recovery and matrix effect of the analytes were all found to be acceptable, and the analytes during the assay and storage in serum samples were observed to be stable. The novel optimized UPLC-MS/MS assay was also successfully employed to determine the concentration levels of linezolid and PNU-142300 in human serum. The results showed that linezolid-associated myelosuppression occurs more frequently in patients with renal insufficiency, and the metabolite-to-parent concentration ratio of PNU-142300 is predicted to reduce this toxicity of myelosuppression.During acute intestinal ischemia reperfusion (IR) injury, the intestinal epithelial barrier (IEB) function is often disrupted. Enteric glial cells (EGCs) play an important role in maintaining the integrity of IEB functions. However, how EGCs regulate IEB function under IR stimulation is unknown. The present study reveals that the adenosine A2A receptor (A2AR) is important for mediating the barrier-modulating roles of EGCs. A2AR knockout (KO) experiments revealed more serious intestinal injury in A2AR KO mice than in WT mice after IR stimulation. Moreover, A2AR expression was significantly increased in WT mice when challenged by IR. To further investigate the role of A2AR in IEB, we established an in vitro EGC-Caco-2 co-culture system. Hypoxia stimulation was used to mimic the process of in vivo IR. Treating EGCs with the CGS21680 A2AR agonist attenuated hypoxia-induced intestinal epithelium damage through up-regulating ZO-1 and occludin expression in cocultured Caco-2 monolayers. Furthermore, we showed that A2AR and metabotropic glutamate receptor 5 (mGluR5) combine to activate the PKCα-dependent pathway in conditions of hypoxia. This study shows, for the first time, that hypoxia induces A2AR-mGluR5 interaction in EGCs to protect IEB function via the PKCα pathway.Drug treatments available for the management of substance use disorders (SUD) present multiple limitations in efficacy, lack of approved treatments or alarming relapse rates. GSK621 concentration These facts hamper the clinical outcome and the quality of life of the patients supporting the importance to develop new pharmacological agents. Lately, several reports suggest that cannabidiol (CBD) presents beneficial effects relevant for the management of neurological disorders such as epilepsy, multiple sclerosis, Parkinson's, or Alzheimer's diseases. Furthermore, there is a large body of evidence pointing out that CBD improves cognition, neurogenesis and presents anxiolytic, antidepressant, antipsychotic, and neuroprotective effects suggesting potential usefulness for the treatment of neuropsychiatric diseases and SUD. Here we review preclinical and clinical reports regarding the effects of CBD on the regulation of the reinforcing, motivational and withdrawal-related effects of different drugs of abuse such as alcohol, opioids (morphine, heroin), cannabinoids, nicotine, and psychostimulants (cocaine, amphetamine).