Epigenetic Activation of Cytochrome P450 1A2 Sensitizes Hepatocellular Carcinoma Cells to Sorafenib.

Cytochrome P450 1A2 (CYP1A2) is a known tumor suppressor in hepatocellular carcinoma (HCC), but its expression is repressed in HCC and the underlying mechanism is unclear. In this study, we investigated the epigenetic mechanisms of CYP1A2 repression and potential therapeutic implications. In HCC tumor tissues, the methylation rates of CpG island (CGI) and DNA methyltransferase (DNMT) 3A protein levels were significantly higher, and there was a clear negative correlation between DNMT3A and CYP1A2 protein expression.

Docosahexaenoic acid administration improves diabetes-induced cardiac fibrosis through enhancing fatty acid oxidation in cardiac fibroblast.

Diabetes mellitus can lead to various complications, including organ fibrosis. Metabolic remodeling often occurs during the development of organ fibrosis. Docosahexaenoic acid (DHA), an essential ω-3 polyunsaturated fatty acid, shows great benefits in improving cardiovascular disease and organ fibrosis, including regulating cellular metabolism.

CYP2E1 plays a suppressive role in hepatocellular carcinoma by regulating Wnt/Dvl2/β-catenin signaling.

Objective: Knowledge of the role of CYP2E1 in hepatocarcinogenesis is largely based on epidemiological and animal studies, with a primary focus on the role of CYP2E1 in metabolic activation of procarcinogens. Few studies have directly assessed the effects of CYP2E1 on HCC malignant phenotypes.

Methods: The expression of CYP2E1 in HCC tissues was determined by qRT-PCR, western blotting and immunohistochemistry.

CRB-SWATH: A Method for Enhancing Untargeted Precursor Ion Extraction and Automatically Constructing Their Tandem Mass Spectra from SWATH Datasets by Chromatographic Retention Behaviors.

Sequential window acquisition of all theoretical spectra (SWATH) as a typical data-independent acquisition (DIA) strategy is favorable for untargeted metabolomics. It could theoretically acquire product ions of all precursor ions, including precursor ions showing chromatographic peaks of rather poor qualities. However, existing data processing methods present limited capabilities in capturing poor-quality peaks of precursor ions.

Chlorogenic Acid Alleviates Hyperglycemia-Induced Cardiac Fibrosis through Activation of the NO/cGMP/PKG Pathway in Cardiac Fibroblasts.

Scope: Hyperglycemia-induced cardiac fibrosis is one of the main causes of diabetic cardiomyopathy (DM). Chlorogenic acid (CGA) found in many foods has excellent hypoglycemic effectiveness, but it is not known whether CGA can improve DM by inhibiting cardiac fibrosis caused by hyperglycemia.

Methods And Results: Type I diabetic mice are induced by streptozotocin, and after treatment with CGA for 12 weeks, cardiac functions and fibrosis are determined.

Ginsenoside-Rb1 Improved Diabetic Cardiomyopathy through Regulating Calcium Signaling by Alleviating Protein O-GlcNAcylation.

Ginsenoside-Rb1 (Rb1), a major active component of ginseng, has many benefits for cardiovascular disease and diabetes mellitus (DM), but the effect and mechanism on diabetic cardiomyopathy are not clear. In the present study, we found that Rb1-feeding significantly improved cardiac dysfunction and abnormal cardiomyocytes calcium signaling caused by diabetes. This improved calcium signaling was because Rb1 reduced Ca leakage caused by overactivated ryanodine receptor 2 (RyR2) and increased Ca uptake by sarcoplasmic reticulum Ca-ATPase 2a (SERCA 2a).

miR-29a attenuates cardiac hypertrophy through inhibition of PPARδ expression.

Although cardiac hypertrophy is widely recognized as a risk factor that leads to cardiac dysfunction and, ultimately, heart failure, the complex mechanisms underlying cardiac hypertrophy remain incompletely characterized. The nuclear receptor peroxisome proliferator-activated receptor δ (PPARδ) is involved in the regulation of cardiac lipid metabolism. Here, we describe a novel PPARδ-dependent molecular cascade involving microRNA-29a (miR-29a) and atrial natriuretic factor (ANF), which is reactivated in cardiac hypertrophy.

Downregulation of lncRNA suppresses growth and metastasis in human osteosarcoma cells.

Background: This study was designed to research the potential function of lncRNA in osteosarcoma (OS).

Materials And Methods: Quantitative real-time PCR, cell counting kit-8, wound healing assay, Transwell assay, flow cytometric analysis, caspase activity analysis, and Western blot were carried out.

Results: was remarkably upregulated in human OS tissues and cells, and knockdown of significantly suppressed MG63 cell proliferation, migration, and invasion and promoted apoptosis.

MicroRNA-192 inhibits the proliferation, migration and invasion of osteosarcoma cells and promotes apoptosis by targeting matrix metalloproteinase-11.

MicroRNAs (miRNAs) are small non-coding RNAs that regulate gene expression during stem cell growth, proliferation and differentiation. miRNAs are also involved in the development and progression of a number of cancer types, including osteosarcoma (OS). miR-192 is significantly downregulated in various tumors, including lung, bladder and rectal cancer.

Ion-pulling simulations provide insights into the mechanisms of channel opening of the skeletal muscle ryanodine receptor.

The type 1 ryanodine receptor (RyR1) mediates Ca release from the sarcoplasmic reticulum to initiate skeletal muscle contraction and is associated with muscle diseases, malignant hyperthermia, and central core disease. To better understand RyR1 channel function, we investigated the molecular mechanisms of channel gating and ion permeation. An adequate model of channel gating requires accurate, high-resolution models of both open and closed states of the channel.

Velvet antler peptide prevents pressure overload-induced cardiac fibrosis via transforming growth factor (TGF)-β1 pathway inhibition.

Velvet antlers (VAs) are commonly used in traditional Chinese medicine and invigorant and contain many functional components for health promotion. The velvet antler peptide sVAP32 is one of active components in VAs; based on structural study, the sVAP32 interacts with TGF-β1 receptors and disrupts the TGF-β1 pathway. We hypothesized that sVAP32 prevents cardiac fibrosis from pressure overload by blocking TGF-β1 signaling.

Channel Gating Dependence on Pore Lining Helix Glycine Residues in Skeletal Muscle Ryanodine Receptor.

Type 1 ryanodine receptors (RyR1s) release Ca(2+) from the sarcoplasmic reticulum to initiate skeletal muscle contraction. The role of RyR1-G4934 and -G4941 in the pore-lining helix in channel gating and ion permeation was probed by replacing them with amino acid residues of increasing side chain volume. RyR1-G4934A, -G4941A, and -G4941V mutant channels exhibited a caffeine-induced Ca(2+) release response in HEK293 cells and bound the RyR-specific ligand [(3)H]ryanodine.

Pore dynamics and conductance of RyR1 transmembrane domain.

Ryanodine receptors (RyR) are calcium release channels, playing a major role in the regulation of muscular contraction. Mutations in skeletal muscle RyR (RyR1) are associated with congenital diseases such as malignant hyperthermia and central core disease (CCD). The absence of high-resolution structures of RyR1 has limited our understanding of channel function and disease mechanisms at the molecular level.

Stabilization of the skeletal muscle ryanodine receptor ion channel-FKBP12 complex by the 1,4-benzothiazepine derivative S107.

Activation of the skeletal muscle ryanodine receptor (RyR1) complex results in the rapid release of Ca(2+) from the sarcoplasmic reticulum and muscle contraction. Dissociation of the small FK506 binding protein 12 subunit (FKBP12) increases RyR1 activity and impairs muscle function. The 1,4-benzothiazepine derivative JTV519, and the more specific derivative S107 (2,3,4,5,-tetrahydro-7-methoxy-4-methyl-1,4-benzothiazepine), are thought to improve skeletal muscle function by stabilizing the RyR1-FKBP12 complex.

Structural determinants of skeletal muscle ryanodine receptor gating.

Ryanodine receptor type 1 (RyR1) releases Ca(2+) from intracellular stores upon nerve impulse to trigger skeletal muscle contraction. Effector binding at the cytoplasmic domain tightly controls gating of the pore domain of RyR1 to release Ca(2+). However, the molecular mechanism that links effector binding to channel gating is unknown due to lack of structural data.

Acute electrical stimulation of nucleus ambiguus enhances immune function in rats.

Background: Up to now, many "immunoactive" brain areas have been identified, such as hypothalamic nuclei, brain reward system; but the nucleus ambiguous (Amb), a nucleus nervi vagis of medulla oblongata, was less well studied in neuroimmunomodulation.

Methods: In order to obtain more profound comprehension and more knowledge on Amb, we studied the effect of acute electrical stimulation of Amb on thymus and spleen activity in rat. A stimulator was applied to stimulate the Amb of the anaesthetic rats using the parameter at 100 microgA x 5 ms x 100 Hz every 1 s for 1 min.