TGR5 agonist inhibits intestinal epithelial cell apoptosis via cAMP/PKA/c-FLIP/JNK signaling pathway and ameliorates dextran sulfate sodium-induced ulcerative colitis.

Excessive apoptosis of intestinal epithelial cell (IEC) is a crucial cause of disrupted epithelium homeostasis, leading to the pathogenesis of ulcerative colitis (UC). The regulation of Takeda G protein-coupled receptor-5 (TGR5) in IEC apoptosis and the underlying molecular mechanisms remained unclear, and the direct evidence from selective TGR5 agonists for the treatment of UC is also lacking. Here, we synthesized a potent and selective TGR5 agonist OM8 with high distribution in intestinal tract and investigated its effect on IEC apoptosis and UC treatment.

Coronarin A modulated hepatic glycogen synthesis and gluconeogenesis via inhibiting mTORC1/S6K1 signaling and ameliorated glucose homeostasis of diabetic mice.

Promotion of hepatic glycogen synthesis and inhibition of hepatic glucose production are effective strategies for controlling hyperglycemia in type 2 diabetes mellitus (T2DM), but agents with both properties were limited. Herein we report coronarin A, a natural compound isolated from rhizomes of Hedychium gardnerianum, which simultaneously stimulates glycogen synthesis and suppresses gluconeogenesis in rat primary hepatocytes. We showed that coronarin A (3, 10 μM) dose-dependently stimulated glycogen synthesis accompanied by increased Akt and GSK3β phosphorylation in rat primary hepatocytes.

[Effects of Combined Application of Biogas Slurry and Straw on the Migration and Fractions of Soil Heavy Metals in Rice-wheat Rotation System in Coastal Reclamation Areas].

In order to reveal the impact of the application of biogas slurry instead of chemical nitrogen fertilizer on the environmental risk of heavy metals in the soil by returning straw to the field, four treatments, without biogas slurry and without straw applications (CK), biogas slurry application without straw (B), straw application without biogas slurry (S), and biogas slurry combined with straw applications (BS), were applied in a typical coastal reclaimed farmland (rice-wheat rotation) in Jiangsu province. The migration and morphological characteristics of Cu, Zn, Cd, and Pb in different soil layers were observed, and the potential environmental risks were estimated. The results showed that:① The total amounts of Zn and Pb in the surface soils (0-20 cm) in the rice and wheat fields under the BS treatment decreased significantly (<0.

SL010110, a lead compound, inhibits gluconeogenesis via SIRT2-p300-mediated PEPCK1 degradation and improves glucose homeostasis in diabetic mice.

Suppression of excessive hepatic gluconeogenesis is an effective strategy for controlling hyperglycemia in type 2 diabetes (T2D). In the present study, we screened our compounds library to discover the active molecules inhibiting gluconeogenesis in primary mouse hepatocytes. We found that SL010110 (5-((4-allyl-2-methoxyphenoxy) methyl) furan-2-carboxylic acid) potently inhibited gluconeogenesis with 3 μM and 10 μM leading to a reduction of 45.

The Hospital-Community-Family-Based Telemedicine (HCFT-AF) Program for Integrative Management of Patients With Atrial Fibrillation: Pilot Feasibility Study.

Background: The potential effectiveness of integrated management in further improving the prognosis of patients with atrial fibrillation has been demonstrated; however, the best strategy for implementation remains to be discovered.

Objective: The aim of this study was to ascertain the feasibility of implementing integrated atrial fibrillation care via the Hospital-Community-Family-Based Telemedicine (HCFT-AF) program.

Methods: In this single-arm, pre-post design pilot study, a multidisciplinary teamwork, supported by efficient infrastructures, provided patients with integrated atrial fibrillation care following the Atrial fibrillation Better Care (ABC) pathway.

Can men with atrial fibrillation really rest easy with a CHADS-VASc score of 0?

Background: Atrial fibrillation (AF) significantly increases the risk of ischemic stroke depending on various risk factors. The CHADS-VASc score is used widely to improve stratification of AF-related stroke to identify for whom anticoagulation could be safely withheld. As upstream therapy, the management of lifestyle for AF and related stroke prevention has been ongoing for past decades.

Andrographolide enhances hippocampal BDNF signaling and suppresses neuronal apoptosis, astroglial activation, neuroinflammation, and spatial memory deficits in a rat model of chronic cerebral hypoperfusion.

Andrographolide is a medical herbal compound with documented anti-inflammatory activity and therapeutic efficacy in animal models of Alzheimer's disease, traumatic brain injury, and ischemic stroke. The present study examined the potential therapeutic effects of andrographolide on chronic cerebral hypoperfusion (CCH)-induced hippocampal neuronal damage and cognitive dysfunction. A CCH model was established in male Sprague Dawley (SD) rats using 2-vessel occlusion (2VO).

Three cases of antibody-LGI1 limbic encephalitis and review of literature.

Purpose: Antibody-LGI1 limbic encephalitis (LGI1-Ab LE) is an anti-neuronal surface antigen-related autoimmune encephalitis. we report three cases of LGI1-Ab LE, describe the characteristics of clinical manifestation, course of evolution, imaging manifestation and treatment outcomes.

Methods: Data from patients diagnosed with LGI1-Ab LE in the Second Hospital, Hebei Medical University, from June 2016 to July 2017, were retrospectively collected and analyzed.

Magnesium lithospermate B improves the gut microbiome and bile acid metabolic profiles in a mouse model of diabetic nephropathy.

Magnesium lithospermate B (MLB) is a new drug marketed in China to treat angina, but its low oral bioavailability limits its clinical application to the intravenous route. Paradoxically, orally administered low-dose MLB was found to alleviate kidney injury in diabetic nephropathy (DN) rats, but its mechanism of action remains unknown. In recent years, the kidney-gut axis has been suspected to be involved in kidney damage pathogenesis, potentially representing a non-classical pathway for pharmacologic intervention.

2D Photonic Crystal Hydrogel Sensor for Tear Glucose Monitoring.

Photonic crystal (PC) materials have huge potentials as sensors for noninvasive and real-time monitoring glucose in tears. We developed a glucose-sensitive PC material based on monolayered colloidal crystals (MCCs). Polystyrene nanoparticles were first self-assembled into a highly ordered MCC, and this two-dimensional (2D) template was then coated by a 4-boronobenzaldehyde-functionalized poly(vinyl alcohol) hydrogel.

Functional Metabolomics Characterizes a Key Role for -Acetylneuraminic Acid in Coronary Artery Diseases.

Background: As new biomarkers of coronary artery diseases (CAD) emerge via metabolomics, the underlying functional mechanisms remain to be elucidated. Functional metabolomics aims to translate metabolomics-derived biomarkers to disease mechanisms.

Methods: A cohort of 2324 patients who underwent coronary angiography from 4 independent centers was studied.

Effect of telehealth interventions on major cardiovascular outcomes: a meta-analysis of randomized controlled trials.

Background: Telehealth interventions (THI) were associated with lower levels of cardiovascular risk factors in adults, whereas the effect of THI on cardiovascular disease (CVD) still remains controversial. A meta-analysis was conducted to summarize the evidence from randomized controlled trials (RCT) which investigated potential impact of THI on the incidence of CVD in patients with or without prior CVD.

Methods: PubMed, EmBase, and the Cochrane Library were searched to identify RCTs to fit our analysis through December 2016.

Orally Administrated Small Molecule Drugs with Intestine Targeted Profile: Recent Development and Prospects.

Background: Intestine targeted drugs are orally administered compounds exerting their therapeutic effects locally in the intestinal tract, thus avoiding side effects related to systemic exposure.

Objective: Both academic and pharmaceutical research has, therefore, focused on such agents, but the systematic methodology needed for their design and evaluation has been unclear. Thus, careful summary of this kind of drugs is vital for drug design.

A Gelated Colloidal Crystal Attached Lens for Noninvasive Continuous Monitoring of Tear Glucose.

Patients of diabetes mellitus urgently need noninvasive and continuous glucose monitoring in daily point-of-care. As the tear glucose concentration has a positive correlation with that in blood, the hydrogel colloidal crystal integrated into contact lens possesses promising potential for noninvasive monitoring of glucose in tears. This paper presents a new glucose-responsive sensor, which consists a crystalline colloidal array (CCA) embedded in hydrogel matrix, attached onto a rigid gas permeable (RGP) contact lens.

Assessment of usefulness of synchrotron radiation techniques to determine arsenic species in hair and rice grain samples.

The arseniasis in Southwest Guizhou, China has been identified as a unique case of endemic arseniasis caused by exposure to indoor combustion of high As-content coal. Present investigation targeted the microdistribution and speciation of the element arsenic in human hair and environmental samples collected in one of the hyper-endemic villages of arseniasis in the area. Analyses were performed by micro-beam X-ray fluorescence (μ-XRF) and X-ray absorption fine structure (XAFS).

Comprehensive Metabolomic Characterization of Coronary Artery Diseases.

Background: Pathogenesis and diagnostic biomarkers for diseases can be discovered by metabolomic profiling of human fluids. If the various types of coronary artery disease (CAD) can be accurately characterized by metabolomics, effective treatment may be targeted without using unnecessary therapies and resources.

Objectives: The authors studied disturbed metabolic pathways to assess the diagnostic value of metabolomics-based biomarkers in different types of CAD.

Intestinally-targeted TGR5 agonists equipped with quaternary ammonium have an improved hypoglycemic effect and reduced gallbladder filling effect.

TGR5 activation of enteroendocrine cells increases glucagon-like peptide 1 (GLP-1) release, which maintains glycemic homeostasis. However, TGR5 activation in the gallbladder and heart is associated with severe side effects. Therefore, intestinally-targeted TGR5 agonists were suggested as potential hypoglycemic agents with minimal side effects.

OL3, a novel low-absorbed TGR5 agonist with reduced side effects, lowered blood glucose via dual actions on TGR5 activation and DPP-4 inhibition.

Aim: TGR5 agonists stimulate intestinal glucagon-like peptide-1 (GLP-1) release, but systemic exposure causes unwanted side effects, such as gallbladder filling. In the present study, linagliptin, a DPP-4 inhibitor with a large molecular weight and polarity, and MN6, a previously described TGR5 agonist, were linked to produce OL3, a novel low-absorbed TGR5 agonist with reduced side-effects and dual function in lowering blood glucose by activation of TGR5 and inhibition of DPP-4.

Methods: TGR5 activation was assayed in HEK293 cells stably expressing human or mouse TGR5 and a CRE-driven luciferase gene.

The rs738409 (I148M) variant of the PNPLA3 gene and cirrhosis: a meta-analysis.

The human patatin-like phospholipase domain-containing-3 (PNPLA3) gene rs738409 C>G polymorphism is associated with several types of liver disease. The aim of this meta-analysis was to assess the risk of cirrhosis on the basis of rs738409 allele frequency and genotype. Medline, the Cochrane Library, EMBASE, and Google Scholar were searched for prospective and retrospective studies assessing the effect of the rs738409 polymorphism on liver cirrhosis.

[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.

N-Acetyltransferase 2 genotype, exfoliated urothelial cells and benzidine exposure.

Most studies report an association of the slow N-acetyltransferase 2 (NAT2) status with elevated bladder cancer risk. In this study, NAT2 genotypes and the decades-long records of Papanicolaou's grading of exfoliated urothelial cells in a former benzidine-exposed cohort of the Shanghai dyestuff industry (29 bladder cancer patients; 307 non-cancer cohort members, some of them presenting different grades of pre-malignant alterations of exfoliated urothelial cells) were investigated. The cohort members had been enrolled in regular medical surveillance since mid-1980s.

Co-occurrence of arseniasis and fluorosis due to indoor combustion of high fluorine and arsenic content coal in a rural township in northwest China: epidemiological and toxicological aspects.

A large number of fluorosis and arseniasis cases appeared in a mountainous area in northwest China. The residents relied on local inferior coal ("bone coal") of high fluorine and arsenic content for domestic heating and cooking. For deep-inside information about this rare case of co-endemia of fluorosis and arseniasis in the population in this special exposure scenario, a field investigation in one of the hyperendemic townships was conducted.

The occurrence of polycyclic aromatic hydrocarbons in Peking duck: Relevance to food safety assessment.

Peking duck is one of the most well-known Chinese dishes. GC-MS analysis revealed that, either benzo(a)pyrene alone, or the total amount of major PAHs with carcinogenic potential for humans, reached levels of 8.7 and 54.