Myocardial ischemia‑reperfusion injury (I/R) is a major contributor to adverse outcomes in ischemic heart disease. Mitochondrial dysfunction plays a central role in I/R, and modulating mitophagy has shown potential in attenuating such injury. Nevertheless, whether puerarin influences mitophagy during I/R remains poorly understood. An in vivo I/R (30 min/24 h) model was established in C57BL/6 mice after 7 day puerarin pretreatment. In vitro, a hypoxia‑reoxygenation H/R (8 h/4 h) model was constructed using H9c2 cardiomyocytes. Cardiac function was assessed by echocardiography, infarct size was determined via Evans Blue‑TTC staining, mitophagy was visualized by transmission electron microscopy, and expression of mitophagy‑related proteins was evaluated by western blot. Puerarin significantly reduced I/R‑induced damage in both models. It attenuated mitochondrial depolarization and reactive oxygen species generation, increased mitophagic activity, and upregulated the mitophagy receptor FUNDC1. Puerarin alleviates myocardial ischemia‑reperfusion injury by enhancing FUNDC1‑mediated mitophagy, particularly during early reperfusion. These results reveal a key mechanism underlying the cardioprotective effect of puerarin and support its further development as a therapeutic agent for I/R.

Hepatocellular carcinoma (HCC) remains a leading cause of cancer-related death worldwide. Doxorubicin (Dox), a conventional chemotherapeutic agent, exhibits unsatisfactory efficacy in HCC due to its poor tumor response, severe cardiotoxicity, and drug resistance. It is urgent to develop strategies to mitigate the side effects and enhance the chemosensitivity of conventional chemotherapy drugs. Traditional Chinese medicine has gained research interest in cancer treatment due to its homology with food and minimal side effects. Puerarin (Pue) has been identified as an effective inhibitor of tumor cell proliferation. However, puerarin's poor water solubility and bioavailability limit its pharmaceutical application. In this study, a novel puerarin nanoparticle (nanoPue) was developed to overcome its limitation. NanoPue could significantly inhibit tumor growth and enhance the chemotherapeutic effect of Dox in HCC models. NanoPue could increase the perivascular coverage within the tumors; decrease the expressions of NSUN2, p-AKT, VEGFA, and MMP-9; and reduce endothelial cell tube formation. In summary, nanoPue improves Dox therapeutic efficacy by decreasing angiogenic factors via regulating NSUN2 in HCC. This study may provide a potential avenue for advancing nanoPue to enhance chemotherapeutic agents in HCC therapy and supply a theoretical support for the clinical application of nanoPue.

BACKGROUND:Myocardial remodeling is a primary contributor to the development and progression of heart failure. Reversing this process is crucial for the prevention and treatment of heart failure. Puerarin (Pue), a traditional Chinese medicine, has been widely utilized in the management of cardiovascular diseases; however, its potential mechanisms for reversing myocardial remodeling remain unclear. AIM OF THE STUDY:To investigate the effect of Pue in myocardial remodeling and the potential mechanism with m5C methylation. MATERIALS AND METHODS:A transverse aortic coarctation (TAC)-induced myocardial hypertrophy model was established in vivo, while angiotensin II (AngII)-induced cardiomyocyte hypertrophy was examined in vitro using H9c2 and NRCM cells. Various doses of Pue were administered to assess their effects. Myocardial remodeling was evaluated through echocardiography, H&E staining, WGA staining, Masson staining, PSR staining, and Western Blot (WB) analysis in mice, alongside mean cell area measurement and WB analysis in cultured cells. The m5C level was quantified using Dot Blot and immunohistochemistry (IHC). RNA sequencing, molecular docking, microscale thermophoresis (MST), transfection, immunofluorescence (IF), and WB were employed to confirm that Pue reverses myocardial remodeling via NSUN2-mediated m5C methylation modification in both in vitro and in vivo settings. The methylation modification was further validated using methylation immunoprecipitation (MeRIP-qPCR). RESULTS:In both in vitro and in vivo experiments, we found that long-term administration of Pue can alleviate myocyte hypertrophy and fibrosis while improving both diastolic and systolic function in mice. Additionally, Pue was shown to upregulate the m5C modification level in cardiomyocytes. RNA sequencing, along with docking and MST assays, revealed that Pue upregulates and targets NSUN2. Furthermore, the protective effect of Pue was diminished by the knockdown of NSUN2 expression. Pue was found to inhibit the activation of NF-κB, and the knockdown of NSUN2 prolonged the half-life of NF-κB mRNA. The enrichment of m5C mRNA was confirmed through MeRIP-qPCR. CONCLUSION:This study suggests that Pue enhances the m5C methylation of NF-κB mRNA by targeting NSUN2. The m5C methylation facilitates the degradation of NF-κB mRNA and suppresses NF-κB activation, thereby modulating the expression of factors related to myocardial remodeling. Consequently, this process alleviates myocardial remodeling and prevents the progression of heart failure, providing a novel perspective for the clinical treatment of heart failure.

Background Autophagy plays an important role in maintaining the stability of intracellular environment, abnormal autophagy is associated with the occurrence and progression of cancer, the role of STIM1 in regulating cancer autophagy remains controversial, and its clinical relevance is unclear. Our study aimed to investigate the effect and mechanism of STIM1 on cervical cancer, thus to provide new molecular therapeutic targets for cervical cancer in clinic. Methods We collected CIN III, FIGO IB and IIA fresh Specimens without chemotherapy from patients in Renmin Hospital of Hubei University of Medicine (n = 10). STIM1, TFEB and autophagy related proteins of different stage tissues were detected. In vitro, SKF96365 and AncoA4 were used to inhibit STIM1-administrated Ca2+ entry of SiHa cells, Cyclosporine A (calcineurin inhibitors) were used to inhibit CaN/TFEB pathway, Ad-mCherry-GFPLC3B was used to detect autophagy flux, shSTIM1 was used to knockdown STIM1 expression. Results The expression levels of STIM1, TFEB and autophagy related proteins were positively correlated with the progression of cervical cancer. Inhibition of STIM1-mediated SOCE can decrease proliferation and migration, and promoted the apoptosis of cervical cancer cells. Knockdown STIM1 can inhibit autophagy and TFEB nuclear translocation. Conclusion STIM1 can promote autophagy and accelerate cervical cancer progression by increasing TFEB nuclear translocation of cervical cancer cells.

2018年教育部"新时代高教40条"明确提出要"加强考试管理,严格过程考核,加大过程考核成绩在课程总成绩中的比重",提高本科教育水平是当前本科教育面临的首要任务.系统解剖学是研究人体形态和功能的科学,是医学生的最重要专业基础课,也是医学院校学生入校后的第一门核心课程.为了积极响应及落实教育部文件精神,教研室积极重构系统解剖学考核体系,文章简要介绍系统解剖学考核体系构建的改革与实践.

天然三萜类抗肿瘤药物熊果酸(ursolic acid, UA),又名乌苏酸,其广泛存在于木犀科植物女贞叶、杜鹃科植物熊果、唇形科夏枯草的全草、中药山楂、山茱萸等植物中[1] . 现已证实其具有抗炎、抗氧化、抗肿瘤等多种生物学效应[1-3] . 尤其,UA 可以抑制多种癌细胞生长,可通过诱导其凋亡,抗肿瘤血管生成,提高化疗药物敏感性,调节肿瘤微环境等机制发挥抗癌作用[4-9] .

Puerarin (Pue) has been widely used in the treatment of hypertension and cardiovascular diseases, but the basic mechanism of Pue on myocardial remodeling (MR) of hypertension is not clear. The purpose of this study was to investigate the effect and mechanism of Pue on MR and provide the basis for the clinical application. Thirty male spontaneously hypertensive rats (SHR) and six male Wistar Kyoto rats (WKY) aged 3 months were used in this study, SHR rats were randomly divided into 5 groups, Pue (40 or 80 mg/kg/d, ip) and telmisartan (TELMI) (30 mg/kg/d, ig) were administrated for 12 weeks. We used Echocardiography to detect the cardiac function. Morphology and structure of myocardium were observed. H9C2 cells were subjected to 1 μM Ang Ⅱ in vitro, 100 μM Pue, 0.5 μM Calmodulin-dependent calcineurin (CaN) inhibitor Cyclosporin A (CsA) and 1 μM specific transient receptor potential channel 6 (TRPC6) inhibitor SAR7334 were used in H9C2 cells. Long-term administration of Pue could significantly improve cardiac function, improve morphology and structure of myocardium in vivo. Pue could reduce MR related proteins expression (ACTC1, TGF-β1, CTGF, β-MHC and BNP), attenuate ROS, restore MMP and decrease Ca2+-overload in vitro. Further study indicated that Pue could decrease TRPC6 expression and inhibit nuclear factor of activated T cells 3 (NFATc3) nuclear translocation in vitro. These results suggested that puerarin could ameliorate myocardial remodeling through inhibiting TRPC6-CaN-NFATc3 in spontaneously hypertensive rats.

目的:探讨动脉粥样硬化性脑梗死患者外周血对氧磷酶1(paraoxonase-1,PON1)活性与颈动脉内中膜厚度(carotid intima-media thickness,CIMT)的相关性.方法:纳入128名动脉粥样硬化性脑梗死患者,根据颈动脉彩超CIMT检测结果将患者分为非CIMT增厚组(n=44)和CIMT增厚组(n=84),检测两组患者的血压、血糖、血脂和PON1活性等指标,并进行对比分析.结果:基线资料比较结果显示,两组患者仅吸烟史差异有统计学意义(P=0??047),其余指标差异均无统计学意义.与非CIMT增厚组相比,CIMT增厚组患者的PON1活性明显降低,差异具有统计学意义(P<0.001).线性相关分析显示,CIMT严重程度与PON1活性呈负相关(r=-0.428,P<0.001).结论:外周血PON1活性与颈动脉内-中膜厚度具有相关性,可以作为反映脑梗死患者颈动脉粥样硬化程度的一个潜在指标.

Background An emerging body of evidence indicates that puerarin (PUE) plays an important role in the treatment of angina pectoris, myocardial ischemia-reperfusion injury, hypertension and other cardiovascular diseases, but how PUE affects the vascular remodeling of hypertensive rats has not been reported yet. This study aimed to investigate the effect and mechanism of PUE on carotid arteries of spontaneously hypertensive rats (SHR) to provide the basis for the clinical application of PUE. Methods Thirty male SHR and six male Wistar Kyoto rats (WKY) aged 3 months were used in this study, SHR rats were randomly divided into 5 groups, PUE(40 or 80 mg/kg/d, ip) and telmisartan (TELMI) (30 mg/kg/d, ig) were administrated for 3 months. We use DMT myography pressure-diameter system to investigate biomechanical properties of carotid arteries, 10 μM pan-classical transient receptor potential channels (TRPCs) inhibitor SKF96365, 200 nM specific TRPC6 inhibitor SAR7334 and 100 μM Orai1 inhibitor ANCOA4 were used in the mechanical test. Results PUE can significantly decrease systolic and diastolic blood pressure, long-term administration of PUE resulted in a mild reduction of thickness and inner diameter of carotid artery. PUE ameliorate NE-response and vascular remodeling mainly through inhibiting TRPCs channel activities of VSMC. Conclusion PUE can ameliorate biomechanical remodeling of carotid arteries through inhibiting TRPCs channel activities of VSMC in spontaneously hypertensive rats.

癫痫是临床常见的神经系统疾病,约30％ 的患者对传统抗癫痫药物耐药而成为难治性癫痫.癫痫的发病机制复杂,且尚无有效治疗方法,给家庭和社会带来极大负担.多年来的基础与临床研究表明,钙离子通道异常是癫痫发病的重要机制之一;神经元死亡和神经炎症是难治性癫痫的重要特征.焦亡是近年发现并证实的一种炎症性程序性细胞死亡方式,细胞焦亡发生的关键是炎性体的激活,而钙动员对炎性体激活至关重要.焦亡参与多种疾病过程,包括难治性癫痫海马神经元的死亡.该文主要综述癫痫与神经元死亡、神经炎症、钙离子通道异常之间的关联,分析神经元焦亡与癫痫之间的关系,为进一步研究癫痫发病机制提供新的视角.

目的 探究钙调蛋白在骨骼肌损伤内质网应激相关性自噬中的作用及机制.方法 制备小鼠肌损伤内质网应激(ERS)模型,采用钙调蛋白激动剂/拮抗剂干扰该信号;同时体外以衣霉素化学诱导C2C12细胞分化的肌管发生ERS,继而添加钙调蛋白干扰剂刺激.检测未折叠蛋白反应(UPR)标志物mRNA和UPR通路关键分子蛋白表达水平,以及ERS诱导自噬相关蛋白的表达.结果 肌损伤后,肌内UPR标志物(BiP、XBP1-S和ATF6)mRNA显著上调(P<0.05),ERS激活的UPR关键通路分子eIF2α、IRE1α和ATF6蛋白活性显著上调(均P<0.05),自噬标志物LC3Ⅱ/Ⅰ增加,采用钙调蛋白激动剂CALP1可增强此反应.结论 钙调蛋白参与了未折叠蛋白反应,并可能通过调节ERS相关性自噬促进骨骼肌损伤修复过程.

An emerging body of evidence indicates that transient receptor potential TRP channels act as important mediators for a wide variety of physiological functions and are potential targets for drug discovery. Our previous study has identified transient receptor potential channel 3 (TRPC3) and TRPC6 as cation channels through which most of the damaging calcium enters, aggravates pathological changes in vivo and increases ischemia/reperfusion (I/R) injury in mice. This study aimed to verify the effects of TRPC3 inhibitor Pyr3 on myocardial I/R injury in mice. C57BL/6J wild-type male mice (8 to 12 weeks old) were anesthetized with 3.3% chloral hydrate. A murine I (30 min)/R (24 h) injury model was established by temporary occlusion of the left anterior descending (LAD) coronary artery. Pyr3 was administered at concentrations of 0, 2.5, 5, or 10 mg/kg via the right jugular vein 5 min before reperfusion. We observed that the selective TRPC3 inhibitor, 10 mg/kg Pyr3, significantly decreased the infarct size of left ventricle, and reduced the myocardial cell apoptosis rate and inflammatory response in mice. In a conclusion, TRPC3 can function as a candidate target for I/R injury prevention, and Pyr3 may directly bind to TRPC3 channel protein, inhibit TRPC3 channel activity, and improve TRPC3-related myocardial I/R injury. Pyr3 may be used for clarification of TRPC3 functions and for treatments of TRPC3-mediated diseases.

目的 探讨TRPC6在宫颈癌组织中的表达及其抑制剂SAR7334对Siha(人宫颈鳞癌细胞)增殖和迁移的影响.方法 选取2017年9月至2019年9月在十堰市人民医院确诊为宫颈鳞癌的11例病例作为实验组,对照组取同一患者正常宫颈组织,免疫印迹法和免疫荧光法等检测宫颈组织中TRPC6蛋白表达;使用20、100、1000 nmol/L SAR7334处理Siha细胞,CCK8法和Hoechst染色检测细胞增殖与凋亡;划痕实验和Transwell法验检测细胞迁移.免疫印迹法检测TRPC6通道阻断后Siha细胞自噬程度的改变.结果 宫颈癌组织中TRPC6表达上调;与对照组相比,用100nmol/LSAR7334阻断TRPC6后,Siha细胞的增殖和迁移减少,划痕愈合率降低,凋亡率增加(P＜0.05).TRPC6通道阻断后,Siha细胞自噬减弱.结论 TRPC6在宫颈癌中表达上调,其抑制剂SAR7334可能通过影响细胞自噬抑制宫颈癌Siha细胞的增殖与迁移.