Notes

LncRNA SCIRT is actually downregulated throughout atherosclerosis and also inhibits the actual spreading involving human aortic clean muscle tissues (HAOSMCs) through sponging miR-146a within cytoplasm.
A key regulator of energy metabolism, PGC-1α, and the products of downstream target genes that encode for glyceraldehyde-3-phosphate dehydrogenase and glucose-6-phosphatase, were constitutively at high levels in the KO mice. SIGNIFICANCE The genetic ablation of AKR1A activates the PGC-1α pathway and spare glucose, which would consequently confer exercise endurance. AIMS Doxorubicin (DOX) is an effective anthracycline anticancer drug. However, the clinical usage of it is limited due to its severe cardiotoxicity side effects. Metformin (Met) is a kind of first-line antihyperglycemic drug which has a potential protective effect on the heart，it is often used for oral treatment of type 2 diabetes. In this study, we explored whether Met could attenuate cardiotoxicity induced by DOX. MATERIALS AND METHODS For the sake of exploring the Met protective effect and mechanism, we established the DOX-induced cardiotoxicity models both in H9C2 cells incubated with 5 μM DOX in vitro and Sprague-Dawley rats treated with 20 mg/kg cumulative dose of DOX. KEY FINDINGS Met is able to inhibit growth inhibition and apoptosis of H9C2 cells induced by DOX. The heart indexes of rats were examined to evaluate the Met cardiotoxicity protection. Met improved the abnormal indexes, serum markers of cardiac heart injury, echocardiography, electrocardiogram, cardiac pathology, cardiomyocyte apoptosis, and oxidative stress markers induced by DOX. Furthermore, in vivo and in vitro studies demonstrated that Met protected against DOX-induced increasing cleaved caspase-3 and Bax. Met also prevented the downregulation of Bcl-2, activated the AMPK pathway, and inhibited the MAPK pathway. SIGNIFICANCE Met showed protective effects on DOX-induced cardiotoxicity by reducing oxidative stress and apoptosis, as well as regulating AMPK and MAPK signaling pathways. AIMS Sepsis is defined as a life-threatening organ dysfunction caused by a dysregulated host response against infection that triggers systemic inflammatory response syndrome. selleck inhibitor l-theanine (LT), a glutamate derivative, is a non-protein amino acid derived from tea (Camellia sinensis), and a valuable nutraceutical product used as an additive in the food industry. This study we aimed to investigate whether LT would exert any therapeutic effect on liver and kidney tissues in Sprague Dawley rats with sepsis induced with cecal ligation and puncture (CLP). MAIN METHODS Rats were divided into four groups; sham, CLP, CLP+LT1 (2x250 mg/kg) and CLP+LT2 (2 × 750 mg/kg). Liver and kidney tissues were subjected to histopathological examination. Apoptotic index percentages (AI%) were examined using the TUNEL method. The oxidized glutathione to total glutathione (GSSG/TGSH) ratio (as a marker of oxidative stress, levels of caspase-3 (a marker of apoptosis), glutathione peroxidase (GPx) and glutathione S-transferase (GST) (as antioxidant enzymes), inducible nitric oxide synthase (iNOS) and the tumor necrosis factor-α to Interleukin-10 ratio (TNF-α/IL-10) (as markers of inflammation) were investigated using commercial kits. Levels of malondialdehyde (MDA) (a marker of oxidative stress) were determined spectrophotometrically. KEY FINDINGS A high dose of LT exhibited more significant effects in reducing oxidative stress, inflammation and apoptosis than a low dose of LT in liver and kidney tissues with CLP-induced sepsis (p  less then  0.05). SIGNIFICANCE Our results indicated that LT significantly and dose-dependently inhibited sepsis induced liver and kidney injury. This effect may be attributed to the antioxidant, anti-inflammatory, and anti-apoptotic activities of LT. AIMS Since several factors are involved in the tumorigenesis process, targeting only one factor most probably cannot overwhelm cancer progression. Therefore, it seems that combination therapy through targeting more than one cancer-related factor may lead to cancer control. The expression and function of p68 (DDX5; DEAD-Box Helicase 5) are dysregulated in various cancers. P68 is also a co-activator of many oncogenic transcription factors such as the signal transducer and activator of transcription-3 (STAT3), which contributes to cancer progression. This close connection between p68 and STAT3 plays an important role in the growth and development of cancer. MATERIALS AND METHODS We decided to suppress the p68/STAT3 axis in various cancer cells by using Polyethylene glycol-trimethyl Chitosan-Hyaluronic acid (PEG-TMC-HA) nanoparticles (NPs) loaded with siRNA molecules. We assessed the impact of this combination therapy on apoptosis, proliferation, angiogenesis, and tumor growth, both in vitro and in vivo. KEY FINDINGS The results showed that siRNA-loaded NPs notably suppressed the expression of p68/STAT3 axis in cancer cells, which was associated with blockade of tumor growth, colony formation, angiogenesis, and cancer cell migration. In addition to apoptosis induction, this combined therapy also reduced the expression of several tumor-promoting factors including Fibroblast growth factors (FGF), vascular endothelial growth factor (VEGF), transforming growth factor-β (TGF-β), matrix metallopeptidases-2 (MMP-2), MMP-9, hypoxia-inducible factor-(HIF-1α), interleukin-6 (IL-6), IL-33, Bcl-x, vimentin, and snail. SIGNIFICANCE These findings indicate the potential of this nano-based anti-cancer therapeutic strategy for efficient cancer therapy which should be further investigated in future studies. Sepsis is the leading cause of death in hospitalized patients and is characterized by a dysregulated inflammatory response to infection and multiple organ failure, including the liver. Transglutaminase 2 (TG2) is a multifunctional enzyme that exhibits transamidase, GTPase, and integrin-binding activities and has opposing roles in the regulation of cell growth, differentiation, and apoptosis. TG2 plays both pathogenic and protective roles in liver diseases, revealing the need to examine the activities of TG2. Here, we introduced an ex vivo imaging approach to examine the in vivo transamidase activity of TG2 based on the combination of intraperitoneal injection of 5-biotinamidopentylamine (5BAPA), a biotinylated substrate for TG2, and fluorescent streptavidin staining in frozen liver sections. Increased 5BAPA signals was observed in the livers of lipopolysaccharide (LPS) and cecal ligation and puncture (CLP)-induced sepsis mice. Pharmacological inhibition of TG2 activity ameliorated LPS-induced liver injury. 5BAPA signals were observed in TG2-expressing and F4/80-positive midzonal macrophages, providing direct evidence that activated macrophages are the major cellular source of active TG2 in the livers of sepsis mice.
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