Dysglycemia and arrhythmias

Disorders in glucose metabolism can be divided into three separate but interrelated domains, namely hyperglycemia, hypoglycemia, and glycemic variability. Intensive glycemic control in patients with diabetes might increase the risk of hypoglycemic incidents and glucose fluctuations. These three dysglycemic states occur not only amongst patients with diabetes, but are frequently present in other clinical settings, such as during critically ill. A growing body of evidence has focused on the relationships between these dysglycemic domains with cardiac arrhythmias, including supraventricular arrhythmias (primarily atrial fibrillation), ventricular arrhythmias (malignant ventricular arrhythmias and QT interval prolongation), and bradyarrhythmias (bradycardia and heart block). Different mechanisms by which these dysglycemic states might provoke cardiac arr-hythmias have been identified in experimental studies. A customized glycemic control strategy to minimize the risk of hyperglycemia, hypoglycemia and glucose variability is of the utmost importance in order to mitigate the risk of cardiac arrhythmias

Effectiveness of Acupuncture for Early Recovery of Bowel Function in Cancer: A Systematic Review and Meta-Analysis

Objectives. The aim of this study was to evaluate the effects of acupuncture therapy to reduce the duration of postoperative ileus (POI) and to enhance bowel function in cancer patients. Methods. A systematic search of electronic databases for studies published from inception until January 2017 was carried out from six databases. Randomized controlled trials (RCTs) involving the use of acupuncture and acupressure for POI and bowel function in cancer patients were identified. Outcomes were extracted from each study and pooled to determine the risk ratio and standardized mean difference. Results. 10 RCTs involving 776 cancer patients were included. Compared with control groups (no acupuncture, sham acupuncture, and other active therapies), acupuncture was associated with shorter time to first flatus and time to first defecation. A subgroup analysis revealed that manual acupuncture was more effective on the time to first flatus and the time to first defecation; electroacupuncture was better in reducing the length of hospital stay. Compared with control groups (sham or no acupressure), acupressure was associated with shorter time to first flatus. However, GRADE approach indicated a low quality of evidence. Conclusions. Acupuncture and acupressure showed large effect size with significantly poor or inferior quality of included trials for enhancing bowel function in cancer patients after surgery. Further well-powered evidence is needed

catena-Poly[[bis­(μ2-4-amino­benzene­sulfonato-κ2 O:O)disilver]-bis­(μ2-4,4′-bipyridine-κ2 N:N′)]

In the title compound, [Ag2(C6H6NO3S)2(C10H8N2)2]n, the AgI atom is four-coordinated by two N atoms from two symmetry-related 4,4′-bipyridine (bipy) and two O atoms from two independent 4-amino­benzene­sulfonate (ABS) ligands. The two inter-chain AgI atoms are bridged by two independent ABS ligands through weak Ag—O bonds and Ag⋯Ag attractions, forming a ladder-like chain coordination polymer [Ag2(ABS)2(bipy)2]n parallel to [001], which is further linked to generate a two-dimensional structure via N—H⋯O hydrogen-bonding inter­actions

Dysglycemia and arrhythmias.

Disorders in glucose metabolism can be divided into three separate but interrelated domains, namely hyperglycemia, hypoglycemia, and glycemic variability. Intensive glycemic control in patients with diabetes might increase the risk of hypoglycemic incidents and glucose fluctuations. These three dysglycemic states occur not only amongst patients with diabetes, but are frequently present in other clinical settings, such as during critically ill. A growing body of evidence has focused on the relationships between these dysglycemic domains with cardiac arrhythmias, including supraventricular arrhythmias (primarily atrial fibrillation), ventricular arrhythmias (malignant ventricular arrhythmias and QT interval prolongation), and bradyarrhythmias (bradycardia and heart block). Different mechanisms by which these dysglycemic states might provoke cardiac arr-hythmias have been identified in experimental studies. A customized glycemic control strategy to minimize the risk of hyperglycemia, hypoglycemia and glucose variability is of the utmost importance in order to mitigate the risk of cardiac arrhythmias. [Abstract copyright: ©The Author(s) 2023. Published by Baishideng Publishing Group Inc. All rights reserved.

Shugan Xiaozhi Decoction Attenuates Nonalcoholic Steatohepatitis by Enhancing PPAR α

This study aimed to investigate the effects of Shugan Xiaozhi decoction (SX) on nonalcoholic steatohepatitis (NASH) induced by high-fat diet in rats. The rats were randomly divided into 6 groups, namely, control, model, fenofibrate, and three different dosage of SX (10, 20, and 40 g/kg/day, p.o.). After establishing the NASH model, at 8 weeks of the experiment, treatments were administrated intragastrically to the fenofibrate and SX groups. All rats were killed after 4 weeks of treatment. Compared with the model group, alanine aminotransferase (ALT), aspartate aminotransferase (AST), free fatty acid (FFA), total cholesterol (TC), triacylglycerol (TG), and low-density lipoprotein cholesterol (LDL) serum in the serum were significantly reduced in all SX treatment groups in a dose-dependent manner. Evidence showed that SX could protect the liver by upregulating the gene and protein expressions of peroxisome proliferator-activated receptor alpha (PPARα) and liver fatty acid binding protein (L-FABP) in a dose-dependent manner. Chemical constituents of SX were further analyzed by ultraperformance liquid chromatography coupled with electrospray ionization mass spectrometry (UPLC-ESI-MS) and 30 chemicals in the ethanolic extract were tentatively identified. To conclude, our results clearly indicated that SX could protect liver functions and relieve hepatic steatosis and inflammation

Structure-Activity Relationships of Pentacyclic Triterpenoids as Potent and Selective Inhibitors against Human Carboxylesterase 1

Human carboxylesterase 1 (hCE1), one of the most important serine hydrolases distributed in liver and adipocytes, plays key roles in endobiotic homeostasis and xenobiotic metabolism. This study aimed to find potent and selective inhibitors against hCE1 from phytochemicals and their derivatives. To this end, a series of natural triterpenoids were collected and their inhibitory effects against human carboxylesterases (hCEs) were assayed using D-Luciferin methyl ester (DME) and 6,8-dichloro-9,9-dimethyl-7-oxo-7,9-dihydroacridin-2-yl benzoate (DDAB) as specific optical substrate for hCE1, and hCE2, respectively. Following screening of a series of natural triterpenoids, oleanolic acid (OA), and ursolic acid (UA) were found with strong inhibitory effects on hCE1 and relative high selectivity over hCE2. In order to get the highly selective and potent inhibitors of hCE1, a series of OA and UA derivatives were synthesized from OA and UA by chemical modifications including oxidation, reduction, esterification, and amidation. The inhibitory effects of these derivatives on hCEs were assayed and the structure-activity relationships of tested triterpenoids as hCE1 inhibitors were carefully investigated. The results demonstrated that the carbonyl group at the C-28 site is essential for hCE1 inhibition, the modifications of OA or UA at this site including esters, amides and alcohols are unbeneficial for hCE1 inhibition. In contrast, the structural modifications on OA and UA at other sites, such as converting the C-3 hydroxy group to 3-O-β-carboxypropionyl (compounds 20 and 22), led to a dramatically increase of the inhibitory effects against hCE1 and very high selectivity over hCE2. 3D-QSAR analysis of all tested triterpenoids including OA and UA derivatives provide new insights into the fine relationships linking between the inhibitory effects on hCE1 and the steric-electrostatic properties of triterpenoids. Furthermore, both inhibition kinetic analyses and docking simulations demonstrated that compound 22 was a potent competitive inhibitor against hCE1-mediated DME hydrolysis. All these findings are very helpful for medicinal chemists to design and develop highly selective and more potent hCE1 inhibitors for biomedical applications

AIDA directly connects sympathetic innervation to adaptive thermogenesis by UCP1

AIDA最早是由林圣彩教授团队首先鉴定和命名的。2007年林圣彩教授团队与孟安明院士团队合作发现AIDA在斑马鱼体轴发育中的功能(Rui, 2007)。2018年，林圣彩教授团队首次发现了AIDA在哺乳动物中的功能，即AIDA介导的内质网降解途径通过降解脂肪合成途径中的关键酶，而限制膳食脂肪在肠道的吸收这一内在抵御肥胖(Luo, 2018)。而本次成果揭示了AIDA在棕色脂肪组织中特定的功能。这些工作将AIDA引入了脂质应激代谢的重要环节，包括脂质吸收和依赖于脂质的产热过程。该论文的共同第一作者为生命科学学院博士生史猛和硕士生黄晓羽，林圣彩教授和林舒勇教授则为共同通讯作者。【Abstract】The sympathetic nervous system–catecholamine–uncoupling protein 1 (UCP1) axis plays an essential role in non-shivering adaptive thermogenesis. However, whether there exists a direct effector that physically connects catecholamine signalling to UCP1 in response to acute cold is unknown. Here we report that outer mitochondrial membrane-located AIDA is phosphorylated at S161 by the catecholamine-activated protein kinase A (PKA). Phosphorylated AIDA translocates to the intermembrane space, where it binds to and activates the uncoupling activity of UCP1 by promoting cysteine oxidation of UCP1.Adipocyte-specific depletion of AIDA abrogates UCP1-dependent thermogenesis, resulting in hypothermia during acute cold exposure. Re-expression of S161A-AIDA, unlike wild-type AIDA, fails to restore the acute cold response in Aida-knockout mice.The PKA–AIDA–UCP1 axis is highly conserved in mammals, including hibernators. Denervation of the sympathetic postganglionic fibres abolishes cold-induced AIDA-dependent thermogenesis. These findings uncover a direct mechanistic link between sympathetic input and UCP1-mediated adaptive thermogenesis.We thank Y. Li, E. Gnaiger, T. Kuwaki, J. R. B. Lighton, E. T. Chouchani and D. Jiang for technical instruction; X. Li and X.-D. Jiang (Core Facility of Biomedical, Xiamen University) for raising the p-S161-AIDA antibody; the Xiamen University Laboratory Animal Center for the mouse in vitro fertilization service and all the other members of S.C.L. laboratory for their technical assistance. This work was supported by grants from the National Key Research and Development Project of China (grant no. 2016YFA0502001) and the National Natural Science Foundation of China (grant nos 31822027, 31871168, 31690101, 91854208 and 82088102), the Fundamental Research Funds for the Central Universities (grant nos 20720190084 and 20720200069), Project ‘111’ sponsored by the State Bureau of Foreign Experts and Ministry of Education of China (grant no. BP2018017), the Youth Innovation Fund of Xiamen (grant no. 3502Z20206028), the Natural Science Foundation of Fujian Province of China (grant no. 2017J01364) and XMU Training Program of Innovation and Entrepreneurship for Undergraduates (grant no. 2019×0666). 该工作得到了厦门大学实验动物中心和生物医学学部仪器平台的重要协助和国家重点研究和发展项目，国家自然科学基金，厦门大学校长基金等的支持