Endothelial TRPV4 channel mediates the vasodilation induced by Tanshinone IIA.

Tanshinone IIA (TSA), the main lipo-soluble component from the dried rhizome of Salvia miltiorrhiza, has been shown to induce vasodilation. However, the underlying mechanisms remains unclear. This study aimed to investigate the effect of TSA on the vasodilation of small resistant arteries ex vivo.

Zinc-doped and biochar support strategies to enhance the catalytic activity of CuFeO to persulfate for crystal violet degradation.

Sulfate radicals-based Fenton-like technology has placed more emphasis on effectively dealing with the threat of dye wastewater. In this work, the Zn-doped CuFeO@biochar composite (CuZnFeO@BC) was prepared through the convenient sol-gel pyrolysis process and applied as heterogeneous persulfate (PS) activator for crystal violet (CV) degradation. The crystal morphology and physicochemical properties of CuZnFeO@BC were investigated by scanning electron microscope (SEM), X-ray diffractometer (XRD), vibrating sample magnetometer (VSM), Brunauer-Emmett-Teller method (BET), and X-ray photoelectron spectroscopy (XPS).

Identification of oleoylethanolamide as an endogenous ligand for HIF-3α.

Hypoxia-inducible factors (HIFs) are α/β heterodimeric transcription factors modulating cellular responses to the low oxygen condition. Among three HIF-α isoforms, HIF-3α is the least studied to date. Here we show that oleoylethanolamide (OEA), a physiological lipid known to regulate food intake and metabolism, binds selectively to HIF-3α.

Simultaneous Detection of Seven Toxins in Mixed Fruit Puree by Ultra-High-Performance Liquid Chromatography-Tandem Mass Spectrometry Coupled with a Modified QuEChERS.

The presence of toxins (Ts) in fruit purees may cause potential harm to the life and health of consumers. As time passes, Ts have become the key detection objects in this kind of food. Based on this, a novel and rapid method was established in this paper for the simultaneous detection of seven TS (tenuazonic acid, alternariol, alternariol monomethyl ether, altenuene, tentoxin, altenusin, and altertoxin I) in mixed fruit purees using ultra-high performance liquid chromatography-tandem mass spectrometry.

Bathroom modifications among community-dwelling older adults who experience falls in the United States: A cross-sectional study.

Falls impose substantial health and economic burdens on older adults. Over half of falls in older adults occur at home, with many involving bathroom areas. Limited information is available on the presence of bathroom modifications for those who experience them.

Characterization of Microbial Community in Cold-Chain Hairtail Fish by High-Throughput Sequencing Technology.

Abstract: High-throughput DNA sequencing with the Illumina MiSeq platform was used to analyze the microbial communities in hairtail (Trichiurus haumela) muscle samples to study the diversity and dynamic changes in these communities during cold-chain circulation of these fish. The richness and diversity of the microbial community in hairtail muscle had a transient decline from 0 to 24 h and decreased after the first rise from 24 to 216 h. The diversity and richness of bacteria in cold-chain hairtail reached maximum at 168 h.

Author Correction: Bile acid metabolites control T17 and T cell differentiation.

An Amendment to this paper has been published and can be accessed via a link at the top of the paper.

Bile acid metabolites control T17 and T cell differentiation.

Bile acids are abundant in the mammalian gut, where they undergo bacteria-mediated transformation to generate a large pool of bioactive molecules. Although bile acids are known to affect host metabolism, cancer progression and innate immunity, it is unknown whether they affect adaptive immune cells such as T helper cells that express IL-17a (T17 cells) or regulatory T cells (T cells). Here we screen a library of bile acid metabolites and identify two distinct derivatives of lithocholic acid (LCA), 3-oxoLCA and isoalloLCA, as T cell regulators in mice.

Tanshinone IIA Can Inhibit Angiotensin II-Induced Proliferation and Autophagy of Vascular Smooth Muscle Cells via Regulating the MAPK Signaling Pathway.

To examine the effect of tanshinone IIA on Angiotensin II (Ang II)-induced proliferation and autophagy in vascular smooth muscle cells (VSMCs) and the related mechanism. VSMCs were treated with Ang II with or without tanshinone IIA (1, 5 and 10 µg/mL), and the proliferation, apoptosis in cells with different treatment were examined by methylthiazolyl tetrazolium (MTT) and flow cytometry methods. Moreover, the expression of autophagy related proteins and mitogen-activated protein kinase (MAPK) signaling molecules were examined by RT-quantitative (q)PCR and Western blot methods.

Bidirectional modulation of HIF-2 activity through chemical ligands.

Hypoxia-inducible factor-2 (HIF-2) is a heterodimeric transcription factor formed through dimerization between an oxygen-sensitive HIF-2α subunit and its obligate partner subunit ARNT. Enhanced HIF-2 activity drives some cancers, whereas reduced activity causes anemia in chronic kidney disease. Therefore, modulation of HIF-2 activity via direct-binding ligands could provide many new therapeutic benefits.

[Long-term outcome after cardioverter-defibrillator implantation in patients with Brugada syndrome].

Objective: To observe the long-term outcome of implantable cardioverter-defibrillator (ICD) implantation in Brugada syndrome patients and to explore how to reduce the frequency of ICD nappropriate schocks.

Methods: This study included 14 symptomatic patients (mean age (44.3 ± 8.

Structural integration in hypoxia-inducible factors.

The hypoxia-inducible factors (HIFs) coordinate cellular adaptations to low oxygen stress by regulating transcriptional programs in erythropoiesis, angiogenesis and metabolism. These programs promote the growth and progression of many tumours, making HIFs attractive anticancer targets. Transcriptionally active HIFs consist of HIF-α and ARNT (also called HIF-1β) subunits.

Sick sinus syndrome associated with hypopituitarism: a case report and literature review.

Though an association between autoimmune diseases and sick sinus syndrome has been reported, there has been no report on the association of hypopituitarism and sick sinus syndrome. Herein, we provide the first case report of hypopituitarism accompanying sick sinus syndrome in a 51-year-old woman presented to our hospital with syncope due to cardiac arrest. The patient was successfully managed by pacemaker installation and hormone replacement therapy.

Doc2b serves as a scaffolding platform for concurrent binding of multiple Munc18 isoforms in pancreatic islet β-cells.

Biphasic glucose-stimulated insulin secretion (GSIS) from pancreatic β-cells involves soluble N-ethylmaleimide-sensitive fusion protein-attachment protein receptor (SNARE) protein-regulated exocytosis. SNARE complex assembly further requires the regulatory proteins Munc18c, Munc18-1 and Doc2b. Munc18-1 and Munc18c are required for first- and second-phase GSIS respectively.

[Long-term outcomes and factors for predicting ventricular arrhythmia in patients with catecholaminergic polymorphic ventricular tachycardia].

Objective: To evaluate factors for predicting ventricular arrhythmia, the clinical effect of drugs on patients with catecholaminergic polymorphic ventricular tachycardia (CPVT), and their long-term outcomes.

Methods: Six patients diagnosed with CPVT underwent a series of electrocardiograms and 24-hour Holter monitoring. β-blockers were recommended for all patients, while some patients were also prescribed propafenone and 1 patient underwent catheter-based renal sympathetic denervation (RDN).

Serum miR-210 and miR-30a expressions tend to revert to fetal levels in Chinese adult patients with chronic heart failure.

Background: MicroRNAs (miRNAs) are widely involved in the process of chronic heart failure (HF), which is characterized by reactivation of the fetal gene program. Here, we examined whether the serum expression levels of some HF-related miRNAs in adult HF patients would tend to revert to fetal levels.

Methods And Results: Serum was obtained from the peripheral venous blood of 22 HF patients, 18 asymptomatic controls, and the umbilical venous blood of 9 fetuses from 9 independent parturitions.

[Clinical features of six patients with catecholaminergic polymorphic ventricular tachycardia].

Objective: To describe the clinical features of 6 patients with catecholaminergic polymorphic ventricular tachycardia.

Methods: Clinical data including signs and symptoms, electrocardiograms, Holter monitoring electrocardiograms and echocardiography was analyzed. Definite diagnosis was made based on the mutations of RYR2 and CASQ2.

Evidence of a role of inositol polyphosphate 5-phosphatase INPP5E in cilia formation in zebrafish.

Inositol phosphatases are important regulators of cell signaling and membrane trafficking. Mutations in inositol polyphosphate 5-phosphatase, INPP5E, have been identified in Joubert syndrome, a rare congenital disorder characterized by midbrain malformation, retinitis pigmentosa, renal cysts, and polydactyly. Previous studies have implicated primary cilia abnormalities in Joubert syndrome, yet the role of INPP5E in cilia formation is not well understood.

Structural analysis of bengamide derivatives as inhibitors of methionine aminopeptidases.

Natural-product-derived bengamides possess potent antiproliferative activity and target human methionine aminopeptidases (MetAPs) for their cellular effects. Several derivatives were designed, synthesized, and evaluated as MetAP inhibitors. Here, we present four new X-ray structures of human MetAP1 in complex with the inhibitors.

Structural analysis of inhibition of Mycobacterium tuberculosis methionine aminopeptidase by bengamide derivatives.

Natural product-derived bengamides possess potent antiproliferative activity and target human methionine aminopeptidases for their cellular effects. Using bengamides as a template, several derivatives were designed and synthesized as inhibitors of methionine aminopeptidases of Mycobacterium tuberculosis, and initial antitubercular activity were observed. Here, we present three new X-ray structures of the tubercular enzyme MtMetAP1c in complex with the inhibitors in the Mn(II) form and in the Ni(II) form.

Inhibition of Mycobacterium tuberculosis methionine aminopeptidases by bengamide derivatives.

Methionine aminopeptidase (MetAP) carries out an essential function of protein N-terminal processing in many bacteria and is a promising target for the development of novel antitubercular agents. Natural bengamides potently inhibit the proliferation of mammalian cells by targeting MetAP enzymes, and the X-ray crystal structure of human type 2 MetAP in complex with a bengamide derivative reveals the key interactions at the active site. By preserving the interactions with the conserved residues inside the binding pocket while exploring the differences between bacterial and human MetAPs around the binding pocket, seven bengamide derivatives were synthesized and evaluated for inhibition of MtMetAP1a and MtMetAP1c in different metalloforms, inhibition of M.

Atorvastatin protects against angiotensin II-induced injury and dysfunction in human umbilical vein endothelial cells through bradykinin 2 receptors.

The morphological and functional integrity of the endothelial cell (EC) is compromised in many cardiovascular diseases such as atherosclerosis, hypertension, and diabetes. Angiotensin II (Ang II) plays important roles in the initiation and progression of these diseases. 3-Hydroxy-3-methylglutaryl-coenzyme A reductase inhibitors (statins) may have cholesterol-independent pleiotropic effects on preventing the EC injury and dysfunction that occurs in these diseases, and the protective effects may relate to bradykinin 2 receptors (B2Rs).

Expression and characterization of Mycobacterium tuberculosis methionine aminopeptidase type 1a.

Methionine aminopeptidase (MetAP) carries out the cotranslational N-terminal methionine excision and is essential for bacterial survival. Mycobacterium tuberculosis expresses two MetAPs, MtMetAP1a and MtMetAP1c, at different levels in growing and stationary phases, and both are potential targets to develop novel antitubercular therapeutics. Recombinant MtMetAP1a was purified as an apoenzyme, and metal binding and activation were characterized with an activity assay using a fluorogenic substrate.

Catalysis and inhibition of Mycobacterium tuberculosis methionine aminopeptidase.

Methionine aminopeptidase (MetAP) carries out an important cotranslational N-terminal methionine excision of nascent proteins and represents a potential target to develop antibacterial and antitubercular drugs. We cloned one of the two MetAPs in Mycobacterium tuberculosis (MtMetAP1c from the mapB gene) and purified it to homogeneity as an apoenzyme. Its activity required a divalent metal ion, and Co(II), Ni(II), Mn(II), and Fe(II) were among activators of the enzyme.

Determination of binding affinity of metal cofactor to the active site of methionine aminopeptidase based on quantitation of functional enzyme.

Determination of metal affinity to the active site of metalloenzymes constitutes an integral part in the understanding of enzyme catalysis and regulation. Nonlinear curve fitting of metal titration curves using the multiple independent binding sites (MIBS) model was adapted to determine K(D) values based on functional enzyme concentrations. This approach provides a more accurate evaluation of K(D) compared with existing methods that are based on total protein concentrations.