OBJECTIVETo observe the effects of telmisartan on Kv1.3 and Kv1.5 potassium channels expressed in Xenopus oocytes.

METHODSKv1.3 and Kv1.5 potassium channel currents expressed in Xenopus oocytes were recorded and observed in the absence and presence of telmisartan using standard two-microelectrode voltage clamp techniques.

RESULTSTelmisartan resulted in a concentration- and voltage-dependent inhibition effect on Kv1.3 channel current (IC(50) 2.05 micromol/L)and on Kv1.5 channel current (IC(50) 2.37 micromol/L).

CONCLUSIONSTelmisartan blocks open-state Kv1.3 channel which could be one of the mechanisms related to its immunomodulatory and anti-atherosclerosis effect. Telmisartan also blocks open-state Kv1.5 channel which might partly account for its effect on reducing the incidence of atrial fibrillation.

Animals ; Benzimidazoles ; pharmacology ; Benzoates ; pharmacology ; In Vitro Techniques ; Kv1.3 Potassium Channel ; drug effects ; Kv1.5 Potassium Channel ; drug effects ; Oocytes ; drug effects ; metabolism ; Patch-Clamp Techniques ; Xenopus

Biomarkers, Tumor ; metabolism ; Carcinoma, Hepatocellular ; genetics ; metabolism ; CpG Islands ; Cyclin-Dependent Kinase Inhibitor p57 ; genetics ; metabolism ; DNA Methylation ; Gene Expression Regulation, Neoplastic ; Humans ; In Situ Hybridization ; Liver ; metabolism ; Liver Neoplasms ; genetics ; metabolism ; Polymerase Chain Reaction ; methods ; Promoter Regions, Genetic ; RNA, Messenger ; genetics ; metabolism

Objective To investigate the abnormalities of gray matter volume in obsessive-compulsive disorder (OCD) patients relative to controls using the method of voxel-based morphometry (VBM), and to analyze the extent of change relative to clinical symptom. Methods Using VBM to compare the MRI images of 31 adult OCD patients with 31 healthy controls. Correlation analyses were conducted between the structural abnormalities of gray matter volume in each brain area among patients relative to their clinical scores. Results Compared with the healthy controls, the OCD patients showed reductions of gray matter volume in left putamen, insula, premotor area, superior parietal and right angular gyrus (P<0.01, Alphasim corrected). The gray matter volumes of left putamen and insular in the OCD patients showed a negative correlation with the Beck anxiety inventory (BAI) scores. Conclusion The changes in gray matter volumes of left putamen, insula, premotor area, superior parietal lobule and right angular gyrus may be related to the pathogenesis of OCD. The declines of left putamen and insula are related to the abnormal anxiety in the OCD patients.

OBJECTIVE: To investigate the effects of Deoxygedunin on Aβ deposition, learning memory, and oxidative stress induced by D-galactose combined with AlCl in model rats with Alzheimer's disease and its possible mechanism. METHODS: Male SD rats were randomly divided into three groups (=12):control group, model group (AD) and intervention group (AD+Deo). Morris water maze test was used to detect learning/memory and cognitive function in rats.Glutathione peroxidase (GSH-Px), superoxide dismutase (SOD) and malondialdehyde (MDA) contents in homogenate of hippocampus were detected by enzyme-linked immunosorbent assay (ELISA).Tau protein expression in rat cerebral cortex was detected by immunohistochemistry.Western blot was used to detect the expressions of extracellular signal regulated kinase 1(ERK1), protein kinase B (PKB) and tropomyosin-related kinase B (TrkB) on TrkB signaling pathway. RESULTS: The results of water maze test showed that D-galactose combined with AlCl induced a significant increase in the escape latency compared with the control group (<0.05).Deoxygedunin could reverse the increase of the escape latency of the model group (<0.05).On the 7th day after removal of the platform, the model group showed an increase in escape latency compared with the control group and the intervention group (<0.01), and the number of crossing platforms was declined (<0.05); The results of immunohistochemistry and ELISA showed that the expressions of Aβ and tau protein in the model group were increased significantly compared with those of the control group (<0.01).The activities of SOD and GSH-Px were decreased significantly and the content of MDA was increased significantly.Compared with the model group, Deoxygedunin could reverse the increase of the expressions of Aβ and tau protein (<0.01), the decrease of SOD and GSH-Px activities (<0.05) and the increase of the MDA content (<0.05).Western blot results showed that Deoxygedunin treatment reversed the decreased phosphorylation levels of TrkB, AKT and ERK1 in hippocampus of the model group. CONCLUSIONS Supplement of Deoxygedunin can significantly reverse Aβ deposition, oxidative stress and cognitive deficits by activating the TrkB signal transduction pathway, which suggest that Deoxygedunin may serve as a promising therapeutic candidate for attenuating AD-like pathological dysfunction induced by D-galactose combined with AlCl.
Alzheimer Disease ; chemically induced ; Animals ; Disease Models, Animal ; Galactose ; Hippocampus ; Limonins ; Male ; Maze Learning ; Rats ; Rats, Sprague-Dawley

Objective: To analyze the clinical characteristics of children with multisystem inflammatory syndrome (MIS-C) associated with SARS-CoV-2 in China, and to improve the understanding of MIS-C among pediatricians. Methods: Case series study.Collect the clinical characteristics, auxiliary examinations, treatment decisions, and prognosis of 64 patients with MIS-C from 9 hospitals in China from December 2022 to June 2023. Results: Among the 64 MIS-C patients, 36 were boys and 28 were girls, with an onset age being 2.8 (0.3, 14.0) years. All patients suffered from fever, elevated inflammatory indicators, and multiple system involvement. Forty-three patients (67%) were involved in more than 3 systems simultaneously, including skin mucosa 60 cases (94%), blood system 52 cases (89%), circulatory system 54 cases (84%), digestive system 48 cases (75%), and nervous system 24 cases (37%). Common mucocutaneous lesions included rash 54 cases (84%) and conjunctival congestion and (or) lip flushing 45 cases (70%). Hematological abnormalities consisted of coagulation dysfunction 48 cases (75%), thrombocytopenia 9 cases (14%), and lymphopenia 8 cases (13%). Cardiovascular lesions mainly affected cardiac function, of which 11 patients (17%) were accompanied by hypotension or shock, and 7 patients (12%) had coronary artery dilatation.Thirty-six patients (56%) had gastrointestinal symptoms, 23 patients (36%) had neurological symptoms. Forty-five patients (70%) received the initial treatment of intravenous immunoglobulin in combination with glucocorticoids, 5 patients (8%) received the methylprednisolone pulse therapy and 2 patients (3%) treated with biological agents, 7 patients with coronary artery dilation all returned to normal within 6 months. Conclusions: MIS-C patients are mainly characterized by fever, high inflammatory response, and multiple organ damage. The preferred initial treatment is intravenous immunoglobulin combined with glucocorticoids. All patients have a good prognosis.
Male ; Child ; Female ; Humans ; Immunoglobulins, Intravenous/therapeutic use* ; Blood Coagulation ; COVID-19 ; China/epidemiology* ; Connective Tissue Diseases ; Coronary Aneurysm ; Fever ; Systemic Inflammatory Response Syndrome/therapy*

As a DNA receptor in the cytoplasm,cyclic GMP-AMP synthase (cGAS) can recognize abnormal DNA in the cytoplasm and activate stimulator of interferon genes (STING) to regulate the immune response. The recent studies have demonstrated that this pathway plays a role in non-infectious inflammatory diseases by promoting the expression of type Ⅰ interferon and interferon-stimulated gene.This article reviews the activation and regulation of cGAS-STING pathway in multiple systems and the effect of this pathway on the occurrence and progression of non-infectious inflammatory diseases,providing theoretical reference for future application of cGAS-STING pathway-related drugs in non-infectious inflammatory diseases.
Humans ; Interferons ; Membrane Proteins/metabolism* ; Noncommunicable Diseases ; Nucleotides, Cyclic ; Nucleotidyltransferases/metabolism* ; Signal Transduction

Cellular Senescence ; Heart ; Humans ; Ventricular Remodeling