TIGIT及其配体CD155在“怒”应激大鼠胸腺细胞中的表达及其意义

目的探讨"怒"模型大鼠胸腺细胞中T细胞免疫球蛋白和ITIM结构域蛋白(TIGIT)及其配体CD155和血清促肾上腺皮质激素释放激素(CRH)、促肾上腺皮质激素(ACTH)、白细胞介素-2(IL-2)、白细胞介素-10(IL-10)表达情况,以及这些指标与胸腺细胞凋亡的相关性。方法将48只Wistar雄性大鼠随机分成对照组、模型7 d组、模型14 d组、模型21 d组,每组12只。除对照组外,其余各组以“社会隔离法”结合足底电击法复制精神应激“怒”模型大鼠。实验后测定大鼠体质量和胸腺指数,以苏木精-伊红(HE)染色观察大鼠胸腺组织的形态学改变,采用免疫印迹法检测各组大鼠胸腺细胞中TIGIT、CD155蛋白的表达水平,采用Tunel法检测胸腺细胞凋亡情况,采用酶联免疫吸附试验测定血清CRH、ACTH、IL-2、IL-10水平。结果实验后,4组大鼠体质量较试验前1 d升高(P<0.05),且“怒”模型各组大鼠体质量均低于对照组(P<0.05);实验后“怒”模型各组大鼠胸腺指数均低于对照组(P<0.05)。HE染色光学显微镜下(×400)可见“怒”模型各组大鼠大鼠胸腺皮质组织结构出现不同程度的损坏,幼稚T细胞布排紊乱无序或呈“条索状”堆积,细胞间隙缩小,细胞数量较对照组降低,细胞核染色变浅,呈淡紫色,并出现不同程度核固缩、核分裂、细胞溶解等凋亡细胞增多现象。4组大鼠胸腺细胞TIGIT蛋白表达水平比较,对照组<模型21 d组<模型14 d组<模型7 d组,其中模型7 d组、14 d组与其他各组胸腺细胞TIGIT蛋白表达水平差异均有统计学意义(P<0.05);“怒”模型各组大鼠胸腺细胞CD155蛋白表达水平高于对照组,差异均有统计学意义(P<0.05)。“怒”模型各组胸腺组织凋亡细胞吸光度高于对照组,差异有统计学意义(P<0.05)。模型7 d组、模型14 d组血清CRH、ACTH水平高于对照组及模型21 d组(P<0.05);“怒”模型各组IL-2水平低于对照组(P<0.05),且模型7 d组、模型14 d组低于模型21 d组(P<0.05);“怒”模型各组IL-10水平高于对照组(P<0.05),且模型14 d组高于模型7 d组及模型21 d组(P<0.05)。Pearson相关分析结果显示,TIGIT表达水平与CD155、ACTH、CRH及胸腺细胞凋亡程度呈正相关(P<0.05),与IL-2呈负相关(P<0.05),与IL-10及胸腺指数无相关性(P>0.05);CD155表达水平与TIGIT及胸腺细胞凋亡程度呈正相关(P<0.05),与IL-2呈负相关(P<0.05),与ACTH、CRH、IL-10及胸腺指数无相关性(P>0.05)。结论“怒”应激状态下,胸腺出现萎缩及凋亡细胞增多现象,可能是TIGIT-CD155与下丘脑-垂体-肾上腺轴、IL-10、IL-2共同作用所致,该研究为“怒”应激致使免疫损伤及疾病发生发展提供理论依据。     

Consequences of early life overfeeding for microglia – Perspectives from rodent models

The early life period is crucially important to how the individual develops, and environmental and lifestyle challenges during this time can lead to lasting programming effects on the brain and immune system. In particular, poor diet in early development can lead to long-term negative metabolic and cognitive outcomes, with those who over-eat in early development being at risk of obesity and poor learning and memory throughout their adult lives. Current research has identified a neuroinflammatory component to this metabolic and cognitive programming that can potentially be manipulated to restore a healthy phenotype. Thus, early life over-feeding in a rat model leads to microglial priming and an exacerbated microglial response to immune challenge when the rats reach adulthood. Microglial responses to a learning task are also impaired. To specifically investigate the role of microglia in these programming effects our group has developed a novel transgenic rat with a diphtheria toxin receptor insertion in the promoter region for the Cx3cr1 gene, expressed on microglia and monocytes; allowing us to conditionally ablate microglia throughout the brain. With this model we reveal that microglia have a direct role in regulating feeding behavior and modifying cognition, but are not likely to be the sole mechanism by which early life overfeeding confers lasting neuroimmune and cognitive effects. Additional work implicates changes to the hypothalamic-pituitary-adrenal axis in this. Together these data highlight the importance of dietary choices in early life and the potential for positive interventions targeting the neuroimmune and neuroendocrine stress systems to reverse such programming damage.     

Regulation of LH secretion by RFRP-3 – From the hypothalamus to the pituitary

RFamide-related peptides (RFRPs) have long been identified as inhibitors of the hypothalamus-pituitary-gonad axis in mammals. However, less progress has been made in the detailed roles of RFRPs in the control of LH secretion. Recent studies have suggested that RFRP-3 neurons in the hypothalamus can regulate the secretion of LH at different levels, including kisspeptin neurons, GnRH neurons, and the pituitary. Additionally, conflicting results regarding the effects of RFRP-3 on these levels exist. In this review, we collect the latest evidence related to the effects of RFRP-3 neurons in regulating LH secretion by acting on kisspeptin neurons, GnRH neurons, and the pituitary and discuss the potential role of the timely reduction of RFRP-3 signaling in the modulation of the preovulatory LH surge.     

Digging into blindsnakes' morphology: Description of the skull,lower jaw,and cervical vertebrae of two Amerotyphlops (Hedges et al., 2014) (Serpentes,Typhlopidae) with comments on the typhlopoidean skull morphological diversity

Scolecophidians are small fossorial snakes that exhibit several osteological innovations, most of which driven by their extreme body miniaturization. Considering that data on skull morphology has proven to be relevant in terms of scolecophidian systematics and morphofunctional evolution, herein, we aim to describe in detail the skull, lower jaw, and cervical vertebrae of Amerotyphlops brongersmianus and A. reticulatus. Our results suggest that the investigated osteology of Amerotyphlops resembles several new world typhlopid species, with reduced interspecific variation in the basicranium, lower jaw and cervical vertebrae. Both species exhibit characters states that are typically conserved intragenerically amongst typhlopoids, such as the presence of a single parietal, paired supraoccipitals, and otooccipitals that are in contact medially, and the basioccipital participating in the formation of the foramen magnum. We discuss possible systematically important osteological skull variations among typhlopoids and provide a comprehensive comparison of these taxa based on literature and data gathered herein.     

Exposure to chewing tobacco promotes primary oral squamous cell carcinoma and regional lymph node metastasis by alterations of SDF1α/CXCR4 axis

A high incidence of oral squamous cell carcinoma (OSCC) is observed in South‐East Asian countries due to addictions such as chewing tobacco. Local invasion and distant metastases are primary causes of poor prognosis in OSCC. This study aimed to understand the alterations in metastasis biomarkers, such as stromal cell–derived factor‐1α (SDF‐1 or SDF1α) and its receptor C‐X‐C chemokine receptor type 4 (CXCR4), in OSCC patient samples that were stratified based on the history of addiction to chewing tobacco. Targeted immunohistochemical staining and Western blotting were performed on primary tumour and metastatic lymph node (LN) tissues in parallel. Overexpression of hepatocyte growth factor (HGF), activated form of its cognate receptor tyrosine kinase, c‐Met (p‐Met), GRB2‐associated‐binding protein 1 (Gab1), phospho‐protein kinase B (pAkt), nuclear factor kappa B (NF‐κB) and cyclooxygenase‐2 (COX‐2) were observed in primary tumour and metastatic lymph nodes in both chewer and non‐chewer cohorts. Variance analysis showed significant positive correlation between them (P < .0001) indicating upregulation of these biomarkers upon ligand‐induced activation of c‐Met in both tobacco chewers and non‐chewers. Significantly higher expressions of SDF1α and CXCR4 were observed in both primary tumours and metastatic lymph nodes of tobacco chewers (P < .0001) and coincided with overexpressed HGF. In contrast, no significant correlation was observed between expression of HGF and that of SDF1α and CXCR4 in non‐chewers. Together, our findings provide important insights into the association of HGF/c‐Met and the SDF1α/CXCR4 axis in lymph node metastasis and to an aetiological link with the habit of chewing tobacco.     

Traumatic brain injury causing intestinal dysfunction: A review

Traumatic brain injuries (TBI) and its sequelae are becoming one of the most pressing public health concerns worldwide. It is one of the leading causes of increased morbidity and mortality. The primary insult to the brain can cause ischemic brain injury, paralysis, concussions, death, and other serious complications. Brain injury also involves other systems through a secondary pathway resulting in multiple complications during and after hospitalization. The focus of our article is to assess the literature available on traumatic brain injury and intestinal dysfunctional to highlight the aspects of epidemiology, pathophysiology, and different diagnostic approaches for early diagnosis of gut dysfunction. We review studies done in both humans and animals, to better understand this underrated topic, as it costs billions of dollars to the healthcare industry because of delayed diagnosis.     

加味酸枣仁汤治疗卒中后认知障碍伴失眠对患者HPA轴功能、睡眠质量及认知功能的影响

目的探讨加味酸枣仁汤治疗卒中后认知障碍伴失眠对患者下丘脑-垂体-肾上腺轴（HPA 轴）功能、睡眠质量及认知功能的影响。方法 选取2018 年1 月～2020 年3 月我院神经内科收治的100 例脑卒中患者，基于随机数字表简单随机分为研究组与对照组，每组各50 例，对照组行常规用药治疗，观察组在对照组基础上另给予酸枣仁汤加减治疗，比较两组临床资料、HPA 功能指标皮质醇（Cor）、促肾上腺皮质激素（ACTH）变化以及睡眠质量与认知功能变化。结果 两组的性别、年龄及分布、BMI、疾病类型、基础病、吸烟史与饮酒史、Cor、ACTH 比较，差异无统计学意义（P＞0.05）。时点（治疗1 个疗程、2 个疗程、3 个疗程、4 个疗程）上，研究组Cor 减少量、ACTH 减少量均明显高于对照组（P＜0.05）。根据PSQI 评分、Mo CA 评分、NIHSS 评分，治疗前两组比较，差异无统计学意义（P＞0.05），治疗4 个疗程，研究组Mo CA 评分明显高于对照组，PSQI 评分、NIHSS 评分均明显低于对照组（P＜0.05）。结论 加味酸枣仁汤辅助治疗卒中后认知障碍伴失眠效果显著，可显著提高患者HPA 轴功能，有效改善其睡眠质量，并提升认知功能。     

You’ve got male: Sex and the microbiota-gut-brain axis across the lifespan

Sex is a critical factor in the diagnosis and development of a number of mental health disorders including autism, schizophrenia, depression, anxiety, Parkinson’s disease, multiple sclerosis, anorexia nervosa and others; likely due to differences in sex steroid hormones and genetics. Recent evidence suggests that sex can also influence the complexity and diversity of microbes that we harbour in our gut; and reciprocally that our gut microbes can directly and indirectly influence sex steroid hormones and central gene activation. There is a growing emphasis on the role of gastrointestinal microbiota in the maintenance of mental health and their role in the pathogenesis of disease. In this review, we introduce mechanisms by which gastrointestinal microbiota are thought to mediate positive health benefits along the gut-brain axis, we report how they may be modulated by sex, the role they play in sex steroid hormone regulation, and their sex-specific effects in various disorders relating to mental health.