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In recent years, obesity has become a global public health problem, and the incidence of obesity among children and adolescents in China has been gradually increasing.Obesity in childhood will affect the development and health of children and may lead to an increased incidence of multiple chronic diseases in adulthood.The current main strategy for weight reduction in obese children is to change their dietary habits and increase physical activity, but it is prone to relapseand has a high failure rate.Obese patients exhibit persistent hunger and lack of satiety.Glucagon-like peptide-1 receptor agonists, which suppress appetite and increase satiety, have successfully treated adult obesity with good results.This article will discuss the feasibility and safety of using glucagon-like peptide-1 receptor agonists for obesity in children and adolescents by reviewing the possible mechanisms of action of glucagon-like peptide-1 receptor agonists for weight reduction and the clinical data of glucagon-like peptide-1 receptor agonists on obesity in children and adolescents.
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OBJECTIVE@#To explore the role of calpain in pulmonary vascular remodeling in hypoxia-induced pulmonary hypertension and the underlying mechanisms. @*METHODS@#Sprague-Dawley rats were randomly divided into the hypoxia group and the normoxia control group. Right ventricular systolic pressure (RVSP) and mean pulmonary artery pressure (mPAP) were monitored by a method with right external jugular vein cannula. Right ventricular hypertrophy index was presented as the ratio of right ventricular weight to left ventricular weight (left ventricle plus septum weight). Levels of calpain-1, -2 and -4 mRNA in pulmonary artery were determined by real-time PCR. Levels of calpain-1, -2 and -4 protein were determined by Western blot. Primary rat pulmonary arterial smooth muscle cells (PASMCs) were divided into 4 groups: a normoxia control group, a normoxia+MDL28170 group, a hypoxia group and a hypoxia+MDL28170 group. Cell proliferation was detected by MTS and flow cytometry. Levels of Ki-67 and proliferating cell nuclear antigen (PCNA) mRNA were determined by real-time PCR. @*RESULTS@#RVSP, mPAP and right ventricular remodeling index were significantly elevated in the hypoxia group compared to those in the normoxia group. In the hypoxia group, pulmonary vascular remodeling was significantly developed, accompanied by up-regulation of calpain-1, -2 and -4. MDL28170 significantly inhibited hypoxia-induced proliferation of PASMCs concomitant with the suppression of Ki-67 and PCNA mRNA expression. @*CONCLUSION@#Calpain mediates vascular remodeling via promoting proliferation of PASMCs in hypoxia-induced pulmonary hypertension.
Subject(s)
Animals , Rats , Calpain , Genetics , Physiology , Cell Proliferation , Dipeptides , Physiology , Hypertension, Pulmonary , Genetics , Hypertrophy, Right Ventricular , Hypoxia , Ki-67 Antigen , Myocytes, Smooth Muscle , Physiology , Proliferating Cell Nuclear Antigen , Pulmonary Artery , Rats, Sprague-Dawley , Real-Time Polymerase Chain Reaction , Up-Regulation , Vascular Remodeling , Genetics , PhysiologyABSTRACT
Obesity is a major risk factor for the generation and development of diabetes, atherosclerosis, hyperlipidemia and cancer. Obesity is accompanied with remodeling of adipose tis-sue, such as changed cell component and function, angiogene-sis, extracellular matrix remodeling and infiltration of inflamma-tory cells. It is important for the prevention of obesity to study adipose tissue remodeling. This review summarizes recent ad-vances in adipose tissue remodeling.
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Aim To explore micro RNAs-integrated pathogenic signaling to control endothelial-mesenchy-mal transition ( EndMT ) in pulmonary hypertension ( PH) by a network bioinformatic approach. Methods Literature-mining method was used to find PH-relat-ed genes and EndMT/EMT-related miRNAs. Bioinfor-matic prediction approach ( DIANA3 , Miranda4 , PicT-ar5 , TargetScan6 , miRDB7 and microT-CDS8 ) was used for miRNA target prediction. Hypergeometric a-nalysis was used to predict miRNAs related to EndMT in PH. The analysis of interactions between PH-rele-vant genes( PH network) was performed with the use of Biological General Repository for Interaction Datasets ( BioGRID ) . These miRNAs were ranked with the highest probability of substantial overlap among their gene targets in the PH-network, the relationship be-tween their targets and the PH functional categories which include hypoxia, inflammation, and transforming growth factor/BMP signaling. Then, the part of results was validated by animal experiment. Lastly the miR-NA-Target network was built using Cytocape 3 . Results List of 230 genes was compiled that were directly im-plicated in the development of PH and 189 miRNAs were related to EndMT in PH. Among 189 miRNAs, only 22 microRNAs(miR-let-7 family, miR-124, miR-130 family, miR-135, miR-144, miR-149, miR-155, miR-16-1, miR-17, miR-181 family, miR-182, miR-200 family, miR-204, miR-205, miR-21, miR-224, miR-27, miR-29 family, miR-301a, miR-31, miR-361 and miR-375) were related to hypoxia, inflamma-tion, and transforming growth factor/BMP signaling. Among these miRNAs, the levels of let-7g, miR-21, miR-124 and miR-130 family were significantly changed in the pulmonary artery in hypoxia-induced PH rats. Conclusions Among numerous miRNAs,22 of which may be involved in hypoxia, inflammation, and transforming growth factor/BMP signaling and re-lated to EndMT in PH by network bioinformatic ap-proach, which provides a theoretical basis for further investigation of EndMT in PH.
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Objective To investigate whether the protection of ischemic preconditioning (IPC) against myocardial ischemia/reperfusion (I/R) injury is mediated by toll-like receptor 4(TLR4)/NF-kB pathway,and whether these effects are related to the release of calcitonin gene-related peptide (CGRP).Methods Sprague-Dawley rats were subjected to 60 min of ligation of the left anterior descending coronary artery followed by 3 h of reperfusion to induce I/R injury.IPC was performed by 4 cycles of 3-min left coronary artery occlusion followed by 5-min reperfusion before the I/R.The expression of TLR4 mRNA was determined by RT-PCR.TLR4 and NF-kB protein expression were analyzed by immunohistochemistry.Myocardial infarct size,CGRP concentration in plasma and activity of creatine kinase in serum were also measured.Results IPC significantly reduced the infarct size and creatine kinase activity concomitantly with the increase in plasma CGRP concentration.The expressions of TLR4 protein and mRNA and NF-kB protein were increased by myocardial I/R injury,and dramatically inhibited by IPC.Conclusion IPC protects against myocardial I/R injury by inhibition of TLR4/NF-kB pathway.These effects are related to the increased the release of CGRP.
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Experiment design has been added to the experiment class for pharmacological course.The topics of the experiment design were prepared by the teacher based on the contents of theory class.After finishing the experiment design with the help of literatures,the students introduced their proposal in the class,and then discussed with each other.The results of feedback showhed that most of the students think they have learned how to look up the literature and prepare the multimedia teaching materials in the course of completing the proposal.In addition,it also enhanced the spirit of team work,improved the students'ability of expression,aroused the students'awareness and interest for research as well as promoted the students'understanding for pharmacological theory.
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Research progress in pharmacological actions of evodiamine and rutaecarpine is reviewed, including cardiovascular effects, antiplatelet activity, antithrombotic activity, anti invasive and metastatic activity, anti inflammatory activity, antinociception, the effect on the endocrine system and non vascular smooth muscles, anti obese activity and thermoregulatory effect, etc.
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AIM To establish a new bioassay method for estimating the rat angiotensin Ⅰ converting engyme (ACE) activity in vivo by using ramipril (Ram), a ACE inhibitor. METHODS The change in mean arterial pressure induced by angioteuasin Ⅰ (AngⅠ) or bradykinin (BK) was measured before and 1, 24, 48 h after pretreatment with Ram (0 05,0 1 mg?kg -1 ,iv). The ACE activity was expressed by the pressor effect (%)of AngⅠ or the depressor effect (%) of BK. RESULTS The pressor effects of AngⅠ or the supernatant fraction of heart tissue homogenate containing AngⅠ were siginificantly reduced 1 h and 24 h after pretreatment with Ram, but not 48 h after pretreatment with Ram. In comparison of the depressor response of BK vs pressor response of AngⅠ 1 h after pretreatment with Ram,it was shown that the depressor effect of BK is more sensitive than the pressor effect of AngⅠ( P
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Nitric oxide is an important signalling and effector molecule which plays an indispensable role in modulating the function of platelets.Recent research revealed that a L-arginine/nitric oxide pathway presented in human platelets and nitric oxide derived from this pathway was called platelet-derived nitric oxide.The impaired synthesis and release of platelet-derived nitric oxide is closely related to the onset and development of some cardiovascular diseases,such as hypertension,atherosclerosis and diabetes.Recent progress in the relationship between platelet-derived nitric oxide and some cardiovascular diseases is reviewed in this article.Thorough research in PDNO not only has great clinical significance but also contributes to finding new ideas and new target for drug therapy.
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Aim To study the anti-inflammator y and antiallergic effects of polysaccharide nucleic acid fraction of bacillus cal mette guerin (BCG-PSN). Methods Effect of BCG-PSN on itch thr eshold of guinea pigs caused by phosphoric acid histamine, ear oedema of mice ca used by xylene, carrageenan-induced hind paw oedema in rats, delayed hypersensi tivity reaction induced by 2,4-dinitroflurobenzene in mice, homologous passive cutaneous anaphylaxis in rats and heterologous passive cutaneous anaphylaxis in mice were investigated. BCG-PSN was administered intramuscularly every other d ay for three weeks. Results BCG-PSN(0.1,0.2,0.4 mg?kg -1) had no effect on itch threshold of guinea pigs caused by phosphoric aci d histamine. In mice, BCG-PSN(0.15,0.30,0.60 mg?kg -1) significant ly inhibited ear oedema caused by xylene and heterologous passive cutaneous anap hylaxis in a dose-dependent manner. BCG-PSN at the dose of 0.60 mg?kg -1 also significantly inhibited delayed hypersensitivity reaction induced by 2,4 -dinitroflurobenzene in mice. In rats, BCG-PSN(0.1,0.2,0.4 mg?kg -1 )significantly inhibited carrageenan-induced hind paw oedema and homologous passive cutaneous anaphylaxis. Conclusion BCG-PSN inhibites ac ute inflammation, immediate type allergy and delayed type allergy.
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AIM: To evaluate the antihistamine effects of domestic azelastine hydrochloride. METHODS: Histamine increased skin vascular permeability and induced shock model in guinea pigs. In isolated guinea pig ileal rings, the contraction of smooth muscle induced by histamine was determined. RESULTS: Pretreament with azelastine hydrochloride( 0.05, 0.15,and 0.45 mg?kg -1,ig) significantly inhibited the increase in skin vascular permeability induced by histamine in a dose-dependent manner in guinea pigs. Pretreament with azelastine hydrochloride( 0.05, 0.1,and 0.2 mg?kg -1,ig)produced a significant improvement of shock, as shown by a decrease in reactivity degree, mortality and a prolongation of latency. In isolated guinea pig ileal rings, azelastine hydrochloride (10 -8,3?10 -8,10 -7,3? 10 -7 mol?L -1)significantly inhibited contraction of smooth muscle induced by histamine in a concentration-dependent manner and caused a parallel right shift of the dose-effect curve of histamine (pA 2= 8.55). CONCLUSION: Domestic azelastine hydrochloride shows significant the antihistamine effects.
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AIM: To observe the protective effects of shenmai injection on myocardial injury induced by 1,1-dipheyl-2-picryl hydrazyl (DPPH)free radic al in isolated rabbit hearts. METHODS: The isolated rabbit hear ts were perfused in a Langendorff model. Left ventricular pressure (LVP), the fi rst derivative of LVP (+dp/dt max ), left v entricular end-diastolic pressur e (LVEDP) and heart rate (HR) were recorded. Coronary flow (CF) and the activity of creatine kinase (CK) in coronary effluent were measured by timed collection of coronary effluent. RESULTS: Perfusion with DPPH ( 0.25 ?mol?L -1 ) for 10 min caused a significant impairment of cardiac functi on, as shown by a decrease in LVP, +dp/dt ma x and HR and an increase in LV EDP as well as the increased release of CK. After perfusion with DPPH ( 0.25 ?mol?L -1 ) for 10 min, treatment with shenmai injection (1320 or 1 160) for 10 min produced a significant improvement of cardiac function and a d ecrease in the release of CK. CONCLUSION: Shenmai injection prot ects against myocardial injury induced by DDPH free radical in isolated rabbit h earts.
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Ischemic preconditioning has been defined as a tolerance of the myocardium to subsequent sustained ischemic damage after the heart was insulted one or more brief periods of ischemic stress. The cardioprotective effect of ischemic preconditioning may be mediated by endogenous cardiovascular active substances. Neurotransmitters, including catecholamines, acethylcholine, calci-tonin gene-related peptide and opioids, may be endogenous myocardial protective substances, and participate in the mediation of ischemic preconditioning. Exogenous administration of neurotrans-mitters can mimic the cardioprotective effect of ischemic preconditioning. There is interactions of some neurotransmitters with other endogenous active substances. The mechanism by which neurotransmitters are involved in the cardioprotective effect of ischemic preconditioning is thought to activate their corresponding receptors, with a subsequent triggering cellular signaling pathway, resulting in myocardial protection.
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Profilin-Ⅰis a small actin monomer-binding protein involved in regulating actin polymerization.It plays an important role in cell proliferation,differention,motility and signals transduction in different cell types including endothelial cells and vascular smooth muscle cells.This article recapitulates the wealth of information on structure,function of profilin-Ⅰand its potential role in the genesis and development of cardiovascular diseases.