Icariin improves oxidative stress injury during ischemic stroke via inhibiting mPTP opening.

BACKGROUND: Ischemic stroke presents a significant threat to human health due to its high disability rate and mortality. Currently, the clinical treatment drug, rt-PA, has a narrow therapeutic window and carries a high risk of bleeding. There is an urgent need to find new effective therapeutic drugs for ischemic stroke. Icariin (ICA), a key ingredient in the traditional Chinese medicine Epimedium, undergoes metabolism in vivo to produce Icaritin (ICT). While ICA has been reported to inhibit neuronal apoptosis after cerebral ischemia-reperfusion (I/R), yet its underlying mechanism remains unclear. METHODS: PC-12 cells were treated with 200 µM H2O2 for 8 h to establish a vitro model of oxidative damage. After administration of ICT, cell viability was detected by Thiazolyl blue tetrazolium Bromide (MTT) assay, reactive oxygen species (ROS) and apoptosis level, mPTP status and mitochondrial membrane potential (MMP) were detected by flow cytometry and immunofluorescence. Apoptosis and mitochondrial permeability transition pore (mPTP) related proteins were assessed by Western blotting. Middle cerebral artery occlusion (MCAO) model was used to establish I/R injury in vivo. After the treatment of ICA, the neurological function was scored by ZeaLonga socres; the infarct volume was observed by 2,3,5-Triphenyltetrazolium chloride (TTC) staining; HE and Nissl staining were used to detect the pathological state of the ischemic cortex; the expression changes of mPTP and apoptosis related proteins were detected by Western blotting. RESULTS: In vitro: ICT effectively improved H2O2-induced oxidative injury through decreasing the ROS level, inhibiting mPTP opening and apoptosis. In addition, the protective effects of ICT were not enhanced when it was co-treated with mPTP inhibitor Cyclosporin A (CsA), but reversed when combined with mPTP activator Lonidamine (LND). In vivo: Rats after MCAO shown cortical infarct volume of 32-40%, severe neurological impairment, while mPTP opening and apoptosis were obviously increased. Those damage caused was improved by the administration of ICA and CsA. CONCLUSIONS: ICA improves cerebral ischemia-reperfusion injury by inhibiting mPTP opening, making it a potential candidate drug for the treatment of ischemic stroke.

Characterization and correlation analysis of microbial flora and flavor profile of stinky acid, a Chinese traditional fermented condiment.

To explore the microbial diversity and flavor profiles of stinky acid, we utilized high-throughput sequencing, culture-based techniques, and bionic E-sensory technologies. The results revealed a significant correlation between the acidity levels of stinky acid and the richness of its microbial community. Ten core bacterial genera and three core fungal genera exhibited ubiquity across all stinky acid samples. Through E-nose analysis, it was found that sulfides constituted the principal odor compounds responsible for stinky acid's distinct aroma. Further insights arose from the correlation analysis, indicating the potential contribution of Debaryomyces yeast to the sour taste profile. Meanwhile, three genera-Rhizopus and Thermoascus and Companilactobacillus-were identified as contributors to aromatic constituents. Interestingly, the findings indicated that Rhizopus and Thermoascus could reduce the intensity of the pungent odor of stinky acid. In summary, this investigation's outcomes offer new insights into the complex bacterial diversity of stinky acid.

A novel signature of autophagy-related immunophenotyping biomarkers in osteoarthritis.

AIMS: We aimed to provide an autophagy-related signature to seek immunophenotyping biomarkers in osteoarthritis (OA). MATERIALS AND METHODS: Microarray expression profiling of OA subchondral bone samples and screening of an autophagy database for autophagy-related differentially expressed genes (au-DEGs) between OA and normal samples were performed. A weighted gene co-expression network analysis (WGCNA) was constructed using au-DEGs to identify key modules significantly associated with clinical information of OA samples. OA-related autophagy hub genes were identified based on the connectivity with the phenotypes of genes in key modules and the protein-protein interaction (PPI) network in which the genes in the modules are involved, followed by feasibility verification of autophagy hub genes by bioinformatics analysis and biological experiments. KEY FINDINGS: We screened 754 au-DEGs between OA and control samples, and co-expression networks were constructed using au-DEGs. Three OA-related autophagy hub genes (HSPA5, HSP90AA1, and ITPKB) were identified. Based on the hub gene expression profiles, OA samples were divided into two clusters with significantly different expression profiles and distinct immunological features, and the three hub genes were significantly differentially expressed between the clusters. Differences in hub genes between OA and control samples regarding sex, age, and grades of OA were examined using external datasets and experimental validation. SIGNIFICANCE: Three autophagy-related markers of OA were identified using bioinformatics methods, and these markers may be useful for the autophagy-related immunophenotyping of OA. The present data may facilitate the diagnosis of OA, as well as the design of immunotherapies and individualized medical treatments.

2-Methyl-1H-benzimidazol-3-ium hydrogen phthalate.

The asymmetric unit of the title compound, C(8)H(9)N(2) (+)·C(8)H(5)O(4) (-), contains two independent ion pairs. In each 2-methyl-1H-benzimidazolium ion, an intra-molecular O-H⋯O bond forms an S(7) graph-set motif. In the crystal, the components are linked by N-H⋯O hydrogen bonds, forming chains along [210]. Further stabilization is provided by weak C-H⋯O hydrogen bonds.

3-Carb-oxy-2-(2-cyclo-propyl-amino-4-methyl-pyridinium-3-yl-amino)-pyridinium dinitrate dihydrate.

The two benzene rings in the cation of the title compound, C(15)H(18)N(4)O(2) (2+)·2NO(3) (-)·2H(2)O, are almost perpendicular [dihedral angle = 91.6 (2)°]. In the crystal, the components are linked by O-H⋯O, N-H⋯O and C-H⋯O hydrogen bonds.