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Stroke is the third leading cause of mortality and disability in the United States. Ischemic stroke constitutes 85% of all stroke cases. However, no effective treatment has been found to prevent damage to the brain in such cases except tissue plasminogen activator with narrow therapeutic window, and there is an unmet need to develop therapeutics for neuroprotection from ischemic stroke. Studies have shown that mechanisms including apoptosis, necrosis, inflammation, immune modulation, and oxidative stress and mediators such as excitatory amino acids, nitric oxide, inflammatory mediators, neurotransmitters, reactive oxygen species, and withdrawal of trophic factors may lead to the development of the ischemic cascade. Hence, it is essential to develop neuroprotective agents targeting either the mechanisms or the mediators leading to development of ischemic stroke. This review focuses on central nervous system agents targeting these biochemical pathways and mediators of ischemic stroke, mainly those that counteract apoptosis, inflammation, and oxidation, and well as glutamate inhibitors which have been shown to provide neuroprotection in experimental animals. All these agents have been shown to improve neurological outcome after ischemic insult in experimental animals in vivo, organotypic brain slice/acute slice ex vivo, and cell cultures in vitro and may therefore aid in preventing long-term morbidity and mortality associated with ischemic stroke.

HIV, HBV, and HCV are risk factors for the development of abnormal LFTs and mortality during anti-TB treatment. TB patients co-infected with HIV and hepatitis virus need close follow-up.

The development of three-dimensional, enzyme-modified electrodes capable of biochemical transformations at high rate is discussed. Reticulated vitreous carbon coated with poly(aniline) has been used as a substrate for the adsorption of horseradish peroxidase which was then immobilized with a layer of poly(1,2-diaminobenzene). More stable modified electrodes resulted if the horseradish peroxidase was also cross-linked with glutaraldehyde. Using the reduction of hydrogen peroxide (2.4 mM) as a model reaction, it is demonstrated that such electrodes operate under partial mass transport control and give a current of -40 mA cm 3 of 60 ppi reticulated vitreous carbon.

This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.

Diabetic cardiomyopathy (DCM), a common complication of diabetes mellitus, may eventually leads to irreversible heart failure. Metformin is the cornerstone of diabetes therapy, especially for type 2 diabetes. Statins are widely used to reduce the risk of cardiovascular diseases. In this study, we aimed to investigate whether the combined administration of metformin and atorvastatin could achieve superior protective effects on DCM and to elucidate its molecular mechanism. Here, db/db mice (9–10 weeks old) were randomly divided into four groups, including sterile water group (DM), metformin group (MET, 200 mg/kg/day), atorvastatin group (AVS, 10 mg/kg/day), and combination therapy group (MET + AVS). Mice were treated with different drugs via gavage once per day for 3 months. After 3 months of treatment, the pathological changes (inflammation, fibrosis, hypertrophy, and oxidative stress makers) were detected by histopathological techniques, as well as Western blotting. The H9C2 cardiomyocytes were treated with palmitate (PAL) to mimic diabetic condition. The cells were divided into control group, PAL treatment group, MET + PAL treatment group, AVS + PAL treatment group, and MET + AVS + PAL treatment group. The effects of MET and AVS on the cell viability and inflammation of H9C2 cells subjected to PAL condition were evaluated by terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling (TUNEL) assay, immunofluorescence staining, and Western blotting. Both MET and AVS prevented diabetes-induced fibrosis, hypertrophy, and inflammation. The combination therapy showed superior effects in protecting myocardial tissue against diabetes-induced injury. Mechanistically, the combination therapy significantly inhibited oxidative stress and the expression levels of inflammation-related proteins, e.g., NLRP3, caspase-1, interleukin-1β (IL-1β), Toll-like receptor 4 (TLR4), and P-p65/p65, in both cardiac tissues and H9C2 cells. TUNEL assay showed that the combination therapy significantly attenuated the apoptosis of cardiomyocytes; decreased the expression level of pro-apoptotic-related proteins, such as cleaved caspase-3 and BAX; and enhanced the expression level of anti-apoptotic protein (Bcl-2). Furthermore, the combination therapy remarkably upregulated the expression levels of 5′-AMP-activated protein kinase (AMPK) and SIRT1. Our findings indicated that the anti-inflammation and anti-apoptosis effects of the combination therapy may be related to activation of AMPK/SIRT1 signaling pathway.

The monotypic genus Platycarya (Juglandaceae) is one of the most widespread temperate tree species in East Asia. In this research, we implemented a phylogeographical study using chloroplast DNA (cpDNA) (psbA-trnH and atpB-rbcL intergenic spacer) sequences on Platycarya strobilacea, in order to identify the locations of the species' main refugia and migration routes. A total of 180 individuals of P. stobilacea from 27 populations from China and Jeju Island (Korea) were collected. The results revealed that P. strobilacea had 35 haplotypes for the two intergenic spacers and high genetic diversity (h T = 0.926). This surprisingly high diversity of haplotypes indicates its long evolutionary history, which is in agreement with previous phylogenetic analyses and fossil records. Significant cpDNA population subdivision was detected (G ST = 0.720; N ST = 0.862), suggesting low levels of recurrent gene flow through seeds among populations and significant phylogeographical structure (N ST > G ST , P < 0.05). The construction of phylogenetic relationships of the 35 chlorotypes detected four major cpDNA clades. Divergence dating analyses using BEAST suggest that the divergence of the major cpDNA clades occurred before the Miocene. Demographic analysis indicated that the Eastern clade underwent localized demographic expansions. The molecular phylogenetic data, together with the geographic distribution of the haplotypes, suggest the existence of multiple glacial refugia in most of its current range in China through Quaternary climatic oscillations.

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