加味丹参饮通过PTEN/PI3K/Akt信号通路抑制IRI作用的研究

目的:探讨加味丹参饮预处理通过抑瘤基因/磷脂酰肌醇-3激酶/蛋白激酶B(PTEN/PI3K/Akt)信号通路对大鼠心肌缺血再灌注损伤(IRI)的保护作用及机制。方法:将75只雄性远交群(SD)大鼠随机分为5组:假手术组、模型组、加味丹参饮组、加味丹参饮+PI3K/Akt通路抑制剂(LY294002)组、LY294002组,采用结扎大鼠冠状动脉左前降支30min后再灌注60min的方法制备IRI模型。采用酶联免疫吸附测定(ELISA)法检测各组大鼠心肌肌钙蛋白I(c Tn I)表达;取心肌梗死边缘区心肌组织,采用脱氧核糖核苷酸末端转移酶介导的缺口末端标记(TUNEL)法检测心肌凋亡指数,采用免疫组化法检测各组大鼠心肌组织Akt、PTEN的表达。结果:与假手术组比较,模型组c Tn I水平显著升高,大鼠心肌凋亡指数增加,PTEN、Akt表达均显著升高(P<0.05);与模型组比较,加味丹参饮组c Tn I水平均显著降低,Akt表达升高,心肌凋亡指数和PETN表达降低(P<0.05);与加味丹参饮组比较,加入抑制剂后,c Tn I水平均明显降低,Akt表达降低,PTEN表达升高(P<0.05)。结论:大鼠心肌缺血再灌注时,加味丹参饮可以通过降低PTEN表达,激活PI3K/Akt信号通路,抑制大鼠心肌细胞的凋亡,从而减轻心肌损伤,保护心肌。     

鼠巨细胞病毒感染C57BL/6小鼠急性肝炎动物模型的建立与鉴定

目的：建立鼠巨细胞病毒（MCMV）感染C57BL/6小鼠急性肝炎模型并对其感染特点进行分析及鉴定。方法：将24 只C57BL/6小鼠随机分为阴性对照组（n =12）及病毒感染组（n =12），病毒感染组腹腔注射1.0×106 PFU（200 μL）MCMV悬液，阴性对照组注射等体积小鼠胚胎成纤维细胞（MEF）悬液。于感染后第3天和第7天取外周血分离血清检测谷丙转氨酶（ALT）及谷草转氨酶（AST）。同时进行肝组织病毒分离、组织病理学及MCMV IE和M55基因、细胞因子白细胞介素-6（IL-6）、白细胞介素-1β（IL-1β）、肿瘤坏死因子α（TNF-α）的检测。结果：病毒感染组肝组织匀浆病毒分离均为阳性，肝炎发生率为100%。在感染后第3天即发生肝炎病理改变，病毒感染组血清ALT及AST较阴性对照组明显升高（P ＜0.01）；病毒感染组肝脏HE染色第3天可见局灶性炎性细胞浸润及肝脏点灶状坏死，持续至第7天，Ishak评分较阴性对照组明显升高（P ＜0.01）；在感染后第3天病毒感染组肝组织内可检测到MCMV IE及M55基因，且在感染后第7天仍可测得IE基因；感染后第3天及第7天病毒感染组炎性细胞因子IL-6、TNF-α及IL-1β mRNA表达水平明显升高（P ＜0.05）。 结论：成功建立MCMV感染C57BL/6小鼠急性动物肝炎模型，其感染表现主要集中在急性感染前期。     

基于数据挖掘的深静脉血栓形成动物模型建立与分析

目的 探讨深静脉血栓形成（deep venous thrombosis，DVT）动物模型建立的要素，提高造模成功率，为深静脉血栓形成的研究提供规范化的动物模型。方法 以中国知网、万方数据库、维普数据库、PubMed数据库收录的期刊文献为资料来源，以动物模型的应用、实验动物种类、造模的方法、检测指标为分类依据建立数据库，使用SPSS Modeler 18.0、SPSS Statistics 22.0软件对导入的数据进行关联规则分析和因子分析。结果 对纳入的246篇符合标准的文献数据进行分析，造模主要用于DVT机制研究，实验动物使用雄性C57BL/6小鼠最多，通常运用下腔静脉结扎法造模，检测最多的指标为血栓质量/长度。通过关联规则及因子分析得出4组关联强度高的检测指标，并提取10个公因子。结论 结合现代信息技术，将实验动物模型的关键指标数据进行更深层次的整合与分析，有助于建立更加科学、标准化的动物模型，对进一步探究DVT的发病机制及治疗方法具有重要意义。     

药理学实验课融合课程思政的实践探索

药理学是一门医学专业的基础课程,药理学实验课在药理学教学中具有重要地位。通过实验教学,旨在使学生掌握基础的实验技能,加深对理论知识的理解,同时培养学生对科学严肃的工作态度和实事求是的工作作风、为毕业后从事科研或临床工作奠定基础。为实现专业课程和思政课程同向同行,形成协同效应,我们在药理学实验授课中进行了课程思政教学改革。在提升授课教师思想政治素质、挖掘蕴含于教学环节中的思政元素、创新考核模式和做好评教工作的基础上,探索课程思政在药理学实验课教学上的实施途径,旨在将药理学实验课建设成既传授专业知识技能,又培养学生高度的社会责任感、良好的人文素养和职业道德的好课。     

Prolyl and lysyl hydroxylases in collagen synthesis

Collagens are the most abundant proteins in the extracellular matrix. They provide a framework to build organs and tissues and give structural support to make them resistant to mechanical load and forces. Several intra‐ and extracellular modifications are needed to make functional collagen molecules, intracellular post‐translational modifications of proline and lysine residues having key roles in this. In this article, we provide a review on the enzymes responsible for the proline and lysine modifications, that is collagen prolyl 4‐hydroxylases, 3‐hydroxylases and lysyl hydroxylases, and discuss their biological functions and involvement in diseases.     

Pattern of injuries due to wild animal attack among patients presenting to the emergency department: A retrospective observational study

PurposeThe human-wildlife conflicts (HWCs) causing nuisances and injuries are becoming a growing public health concern over recent years worldwide. We aimed to study the demographic profile, mode of injury, pattern of injury, and outcome of wild animal attack victims presented to the emergency department.MethodsThis retrospective cross-sectional study was conducted in the emergency department of a tertiary-care hospital in Eastern India. Data were retrieved from the medical records from May 2017 to May 2021. Patients of all ages and genders attacked by wild animals and secondary injuries were included in this study. Patients with incomplete data, injuries due to the attack of stray and domestic animals and trauma due to other causes were excluded. Demographic profile, mode of injury, the pattern of injury, injury severity score (ISS), radiological pattern, and outcome were recorded. Statistical analysis with R (version 3.6.1.) was conducted.ResultsA total of 411 wild animal attack victims were studied, of which 374 (90.9%) were snakebite injuries and 37 (9.1%) were wild mammalian (WM) attack injuries. The mean age of WM attack victims was 46 years, and the male-to-female ratio was 4:1. Elephant attack injury (40.5%) was the most common WM attack injury reported. Most WM attacks (43.2%) occurred between 4:00 a.m. to 8:00 a.m. The median ISS was 18.5 (13–28), where 54.2% of patients had polytrauma (ISS>15). Elephant attack was associated with a higher ISS, but the difference was not significant compared to other animal types (p = 0.2). Blunt trauma was common pattern of injury in the elephant attack injury cases. Lacerations and soft tissue injuries were common patterns in other animal attacks. Among snakebites, neurotoxic was the most common type (55.4%), and lower extremity was the most common site involved.ConclusionThe young male population is the major victim of HWCs; and elephant is the most common animal involved. There is a need to design scientifically sound preventive strategies for HWCs and to strengthen the preparedness in health establishments to manage victims effectively.     

3‐O‐Acetyloleanolic acid inhibits angiopoietin‐1‐induced angiogenesis and lymphangiogenesis via suppression of angiopoietin‐1/Tie‐2 signaling

Tumor angiogenesis and lymphangiogenesis are important processes in tumor progression and metastasis. The inhibitory effects of 3‐O‐acetyloleanolic acid (3AOA), a pentacyclic triterpenoid compound isolated from Vigna sinensis K., on tumor‐induced angiogenesis and lymphangiogenesis in vitro and in vivo were studied. Angiopoietin‐1 is an important angiogenic and lymphangiogenic factor secreted from colon carcinoma CT‐26 cells under hypoxia conditions. 3AOA inhibited proliferation, migration, and tube formation of angiopoietin‐1‐treated human umbilical vein endothelial cells (HUVEC) and human lymphatic microvascular endothelial cells (HLMEC). 3AOA reduced angiogenesis and lymphangiogenesis in angiopoietin‐1‐stimulated Matrigel plugs. Also, 3AOA inhibited tumor growth and tumor‐induced angiogenesis and lymphangiogenesis in an angiopoietin‐1‐induced CT‐26 allograft colon carcinoma animal model. 3AOA inhibited activation of the angiopoietin‐1 receptor Tie‐2 and activation of the downstream signaling factors FAK, AKT, and ERK1/2 that are involved in the angiopoietin‐1/Tie‐2‐signaling pathway. Thus, 3AOA has an inhibitory effect on angiogenesis and lymphangiogenesis induced by angiopoietin‐1 both in vitro and in vivo, and the inhibitory effect of 3AOA is probably due to suppression of angiopoietin‐1/Tie‐2 signaling in HUVEC and HLMEC.     

Dysfunctional RNA-binding protein biology and neurodegeneration in experimental autoimmune encephalomyelitis in female mice

Altered stress granule (SG) and RNA-binding protein (RBP) biology have been shown to contribute to the pathogenesis of several neurodegenerative diseases, yet little is known about their role in multiple sclerosis (MS). Pathological features associated with dysfunctional RBPs include RBP mislocalization from its normal nuclear location to the cytoplasm and the formation of chronic SGs. We tested the hypothesis that altered SG and RBP biology might contribute to the neurodegeneration in experimental autoimmune encephalomyelitis (EAE). C57BL/6 female mice were actively immunized with MOG_35-55 to induce EAE. Spinal cords were examined for mislocalization of the RBPs, heterogeneous nuclear ribonucleoprotein A1 (hnRNP A1) and TAR-DNA binding protein-43 (TDP-43), SGs, neurodegeneration (SMI-32), T cells (CD3), and macrophages (CD68). In contrast to naive mice, mice with EAE showed SG formation (p < 0.0001) and mislocalization of hnRNP A1 (p < 0.05) in neurons of the ventral spinal cord gray matter, which correlated with clinical score (R = 0.8104, p = 0.0253). In these same areas, there was a neuronal loss (p < 0.0001) and increased SMI-32 immunoreactivity (both markers of neurodegeneration) and increased staining for CD3⁺ T cells and IFN-gamma. These findings recapitulate the SG and RBP biology and markers of neurodegeneration in MS tissues and suggest that altered SG and RBP biology contribute to the neurodegeneration in EAE, which might also apply to the pathogenesis of MS.     

Sleep,brain development,and autism spectrum disorders: Insights from animal models

Sleep is an evolutionarily conserved and powerful drive, although its complete functions are still unknown. One possible function of sleep is that it promotes brain development. The amount of sleep is greatest during ages when the brain is rapidly developing, and sleep has been shown to influence critical period plasticity. This supports a role for sleep in brain development and suggests that abnormal sleep in early life may lead to abnormal development. Autism spectrum disorder (ASD) is the most prevalent neurodevelopmental disorder in the United States. It is estimated that insomnia affects 44%–86% of the ASD population, predicting the severity of ASD core symptoms and associated behavioral problems. Sleep problems impact the quality of life of both ASD individuals and their caregivers, thus it is important to understand why they are so prevalent. In this review, we explore the role of sleep in early life as a causal factor in ASD. First, we review fundamental steps in mammalian sleep ontogeny and regulation and how sleep influences brain development. Next, we summarize current knowledge gained from studying sleep in animal models of ASD. Ultimately, our goal is to highlight the importance of understanding the role of sleep in brain development and the use of animal models to provide mechanistic insight into the origin of sleep problems in ASD.