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Objective To analyze the role of NOD-like receptor thermal protein domain associated protein 3(NLRP3)inflammasome in a therapeutic mild hypothermia(34℃)treated isolated rat myocardial ischemia-reperfusion model and explore its mechanism.Methods Sixty clean grade adult male SD rats,aged 7-10 weeks,weighing 250-300 g.Using a random number table method,the rats were divid-ed into five groups:blank control group(group S),myocardial ischemia-reperfusion group(group IR),34℃mild hypothermia post-treated myocardial ischemia-reperfusion group(group MH),34℃mild hypother-mia post-treated myocardial ischemia-reperfusion+3-TYP group(group HT),and 34℃mild hypothermia post-treated myocardial ischemia-reperfusion+3-TYP+MCC950 group(group HTM),12 rats in each group.Group S perfused the rat heart at 37℃with a balanced perfusion solution for 180 minutes.Group IR re-ceived balanced perfusion of the rat heart at 37℃for 30 minutes,followed by ischemia for 30 minutes and reperfusion with 37℃perfusion for 120 minutes.Group MH perfused the rat heart at 37℃for 30 minutes,followed by ischemia for 30 minutes and reperfusion with 34℃perfusion solution for 120 minutes.Group HT perfused the hearts of rats at 37℃for 30 minutes,followed by ischemia for 30 minutes,silent mating type information regulation 2 homolog 3(sirt3)inhibitor 3-TYP was added to the perfusate,and then per-fused at 34℃for 120 minutes.Group HTM perfused the hearts of rats at 37℃for 30 minutes,followed by ischemia for 30 minutes,sirt3 inhibitor 3-TYP and NLRP3 inhibitor MCC950 were added to the perfusate,and then perfused at 34℃for 120 minutes.The isolated heart was obtained 120 minutes after reperfusion,and the concentrations of IL-6 and IL-1β in the perfused cardiac fluid was measured using ELISA method,Western blot method for detecting the relative content of NLRP3 and sirt3 proteins in myocardial tissue,1%triphenyl tetrazolium chloride staining for calculating myocardial infarction area,and HE staining for observ-ing myocardial pathological changes.Results Compared with group S,HR were significantly slowed down,LVSP,±dp/dtmax were significantly decreased,and LVEDP were significantly increased 30,60,90,and 120 minutes after reperfusion,the concentrations of IL-6 and IL-1β in cardiac fluid leakage,and the per-centage of myocardial infarction area were significantly increased in groups IR,MH,HT,and HTM(P＜0.05),the content of sirt3 protein in myocardial tissue were significantly reduced,while the content of NLRP3 protein were significantly increased in groups IR,HT,and HTM(P＜0.05),the contents of sirt3 and NLRP3 protein in the myocardial tissue were significantly increased in group MH(P＜0.05).Com-pared with group IR,HR were significantly increased,LVSP,±dp/dtmax were significantly increased,and LVEDP were significantly decreased 30,60,90,and 120 minutes after reperfusion,the concentrations of IL-6 and IL-1β in cardiac fluid leakage and the percentage of myocardial infarction area were significantly decreased in groups MH and HTM(P＜0.05),the content of sirt3 protein in myocardial tissue was signifi-cantly increased,while the content of NLRP3 protein was significantly decreased in group MH(P＜0.05),the content of NLRP3 protein in myocardial tissue was significantly reduced in group HTM(P＜0.05).Compared with group MH,HR were significantly slowed down,LVSP,±dp/dtmax were significantly de-creased,and LVEDP were significantly increased 30,60,90,and 120 minutes after reperfusion,the con-centrations of IL-6 and IL-1β in cardiac fluid leakage,the percentage of myocardial infarction area,and the content of NLRP3 protein in myocardial tissue were significantly increased in group HT(P＜0.05),the content of sirt3 protein in myocardial tissue was significantly reduced in groups HT and HTM(P＜0.05).Compared with group HT,HR were significantly increased,LVSP,±dp/dtmax were significantly increased,and LVEDP were significantly decreased 30,60,90,and 120 minutes after reperfusion,the concentrations of IL-6 and IL-1β in cardiac fluid leakage,the percentage of myocardial infarction area,and the content of NLRP3 protein in myocardial tissue were significantly reduced in group HTM(P＜0.05).Conclusion Therapeutic mild hypothermia(34℃)can improve hemodynamic parameters of isolated hearts and reduce the concentrations of IL-6 and IL-1β,NLRP3 protein content in myocardial tissue,percentage of myocardial infarction area,improve myocardial pathological changes,and reduce myocardial ischemia-reperfusion injury in rats,the mechanism may be related to the mitochondrial mediated sirt3 pathway inhibiting the high expres-sion of inflammatory corpuscle NLRP3.
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BACKGROUND:Tendinopathy is a musculoskeletal disorder characterized by pain and decreased mobility,with pathological changes of disturbed collagen and hyperplasia of the vasculature.Tendinopathy tends to occur in athletes,physical workers,and the elderly.One of the mechanisms of tendinopathy is the"failed healing response",and part of what causes the failed healing response is the erroneous differentiation of tendon stem/progenitor cells. OBJECTIVE:By reviewing the relevant literature,we introduce the characteristics of tendon stem/progenitor cells,summarize the factors that affect the differentiation of tendon stem/progenitor cells to tendon cells and those that lead to mis-differentiation of tendon stem/progenitor cells(differentiation to adipocytes,osteocytes and chondrocytes),and also describe the limitations of tendon stem/progenitor cells in clinical applications. METHODS:PubMed and Web of Science databases were searched for the terms"tendon stem/progenitor cells,tendinopathy,tendon injury,differentiation".The relevant literature was screened by reading and 109 articles were included for the analysis of the results. RESULTS AND CONCLUSION:(1)Tendon stem/progenitor cells are a type of stem cells that can spontaneously differentiate into tendons and have the ability to self-renew,clone,and multi-differentiate.Various external conditions acting on tendon stem/progenitor cells can lead them to differentiate in diverse directions.The specific factors that regulate the fate of tendon stem/progenitor cells are not known with certainty.When stem cell renewal and differentiation in tendons becomes abnormal,it can lead to failure of tendon healing and consequently to tendinopathy.(2)Aging,changes in extracellular matrix composition,excessive mechanical stimulation,prostaglandin E2 and interleukin-6 as well as interleukin-10 and some systemic diseases may be important in regulating the mis-differentiation of tendon stem/progenitor cells.(3)Possible favorable factors that promote the differentiation of tendon stem/progenitor cells to tenocytes are:some growth factors and cytokines,moderate mechanical stimulation and topography of the extracellular matrix,low oxygen tension,drugs,and several transcriptional genes and proteins.(4)The most desirable therapeutic tools are the regulation of endogenous tendon stem/progenitor cells or the stimulation of endogenous tendon stem/progenitor cell proliferation and differentiation by exogenous tendon stem/progenitor cells.(5)Understanding the factors that regulate mis-differentiation of tendon stem/progenitor cells may provide insight into the pathogenesis of tendinopathy and identify therapeutic targets.Elaborating on the induction of tendon stem/progenitor cell differentiation into tendons could facilitate their use in tissue engineering.
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Objective@#To investigate the prevalence of overweight/obesity and its associations with sleep duration among children and adolescents aged 6-17 in Gansu Province, so as to formulate tailored prevention and control strategies and intervention measures.@*Methods@#Using a multi stage stratified cluster random sampling method, a questionnaire survey and physical examination were conducted among 2 172 students aged 6-17 from 2 monitoring points in Gansu Province from May to July 2022. Using Chi square test to analyze the inter group differences in the detection rates of overweight and obesity and the composition of sleep duration, and using Logistic regression model to analyze the correlation between overweight and obesity and sleep duration.@*Results@#The prevalence of overweight and obesity were 10.45% and 6.86%, respectively. The average sleep duration was ( 8.28 ±1.66)h/d. The detection rate of overweight was high among high school students aged 16-17 and those with sleep duration<8 h/d ( χ 2=12.51, 19.32, 14.96), while the detection rate of obesity was high among male and non residential students ( χ 2= 5.89 , 9.59)( P ＜0.05). For both boys and girls, the rates of overweight and obesity among primary school students increased with the decrease in sleep duration ( χ 2=38.84, 9.80, 19.61, 41.60, P <0.05). The rates of obesity in boys were higher than girls across varying sleep durations among the general population (sleep duration <8 h/d: 6.07%, 11.11%, 8~<9 h/d: 5.76%, 6.09 %, 9~<10 h/d: 6.02%, 8.19 %, ≥10 h/d: 4.04%, 6.90%). Multivariate Logistic regression analysis showed that insufficient sleep duration among primary school students was positively associated with the risk of overweight and obesity, and adequate sleep duration among high school students was negatively associated with the risk of overweight and obesity (sleep duration 8~<9 h/d: OR primary school students = 1.89 , 9~< 10 h/d: OR primary school students =1.54, 8~<9 h/d: OR high school students =0.30, P <0.05).@*Conclusions@#Insufficient sleep is a risk factor for overweight and obesity among primary and secondary school students at monitoring sites in Gansu Province. Prevention strategies and interventions should be developed for different populations to ensure adequate sleep duration and reduce the risk of overweight and obesity among primary and secondary school students.
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There are a large number of natural microbial communities in nature. Different populations inside the consortia expand the performance boundary of a single microbial population through communication and division of labor, reducing the overall metabolic burden and increasing the environmental adaptability. Based on engineering principles, synthetic biology designs or modifies basic functional components, gene circuits, and chassis cells to purposefully reprogram the operational processes of the living cells, achieving rich and controllable biological functions. Introducing this engineering design principle to obtain structurally well-defined synthetic microbial communities can provide ideas for theoretical studies and shed light on versatile applications. This review discussed recent progresses on synthetic microbial consortia with regard to design principles, construction methods and applications, and prospected future perspectives.
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Consórcios Microbianos/genética , Biologia Sintética , Microbiota , Modelos TeóricosRESUMO
Gelatin microspheres were discussed as a scaffold material for bone tissue engineering, with the advantages of its porosity, biodegradability, biocompatibility, and biosafety highlighted. This review discusses how bone regeneration is aided by the three fundamental components of bone tissue engineering-seed cells, bioactive substances, and scaffold materials-and how gelatin microspheres can be employed for in vitro seed cell cultivation to ensure efficient expansion. This review also points out that gelatin microspheres are advantageous as drug delivery systems because of their multifunctional nature, which slows drug release and improves overall effectiveness. Although gelatin microspheres are useful for bone tissue creation, the scaffolds that take into account their porous structure and mechanical characteristics might be difficult to be created. This review then discusses typical techniques for creating gelatin microspheres, their recent application in bone tissue engineering, as well as possible future research directions.
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Engenharia Tecidual/métodos , Alicerces Teciduais/química , Gelatina/química , Microesferas , Osso e Ossos , PorosidadeRESUMO
Objective: To study the mechanism of action of Danggui Shaoyao San (DSS) in the treatment of Alzheimer'sdisease (AD) from a systematic network level using network pharmacology. Methods: The active ingredients of DSS intreating AD was screened from the Traditional Chinese Medicine System Pharmacology Database (TCSMP), and thedrugs-targets-disease network was built. Target organ localization network, GO analysis and Pathway enrichmentanalysis were used for bioinformatics analysis. Results: 51 kinds of DSS active ingredients were screened by networkpharmacology, showing 377 predicted targets of active compounds. Among them, 197 targets were associated with AD, and the pharmacodynamic targets of DSS active compounds were highly enriched with AD-related signals. The pathwaywas closely related to the reduction of Aβ aggregation and inhibition of tau hyperphosphorylation and biological processessuch as anti-inflammatory and anti-apoptosis, and the mRNA expression of the targeted gene was mainly enriched in theliver, heart, and brain. Conclusion: DSS active compounds interact with multiple targets in multiple ways in a synergisticmanner, mainly to produce important therapeutic effects on AD with anti-inflammatory, anti-apoptotic, enhancingmetabolism and immune system.