脑梗死合并肺部感染患者TNF-α、HMGBl、TLR4-NF-κB信号通路改变研究

目的探究脑梗死合并肺部感染患者的肿瘤坏死因子-α(Tumor necrosis factor-α,TNF-α)和高迁移率族蛋白Bl(High mobility group protein Bl,HMGBl)水平及其临床价值研究。方法2018年1月-2019年2月儋州市人民医院收治的急性脑梗死患者作为研究对象,其中急性脑梗死合并肺部感染患者30例作为感染组,急性脑梗死无肺部感染患者80例作为非感染组,选择同期于此医院体检的健康者30名作为对照组。采用酶联免疫吸附法(Enzyme-linked immuno sorbent assay,ELISA)检测血清HMGB1和细胞因子IL-6、TNF-α水平,采用Western Blot法检测血清Toll样家族受体-4(Toll like receptor-4,TLR4)、核因子κB(nuclear factor kappa-B,NF-κB)、髓样分化因子(myeloiddifferentiationfactor88,MyD88)表达水平。结果感染组的血清HMGB1、TLR4、NF-κB、MyD88表达及细胞因子IL-6、TNF-α水平均高于非感染组和对照组(P<0.05);感染组患者大梗死灶、中等梗死灶、小梗死灶各指标总体水平差异具有统计学意义(P<0.05)。大梗死灶、中等梗死灶两亚组患者的血清HMGB1、TLR4、NF-κB、MyD88表达及细胞因子IL-6、TNF-α水平均高于小梗死灶亚组(P<0.05);急性脑梗死合并肺部感染患者的血清HMGB1和TNF-α水平呈正相关(r=0.523,P<0.001)。结论脑梗死合并肺部感染患者伴随TNF-α、HMGBl、TLR4-NF-κB信号通路的明显改变,且与梗死灶大小具有相关性,其机制有待进一步研究。     

Role for the membrane estrogen receptor alpha in the sexual differentiation of the brain

Estrogens exert pleiotropic effects on multiple physiological and behavioral responses. Male and female sexual behavior in rodents constitutes some of the best‐characterized responses activated by estrogens in adulthood and largely depend on ERα. Evidence exists that nucleus‐ and membrane‐initiated estrogen signaling cooperate to orchestrate the activation of these behaviors both in short‐ and long‐term. However, questions remain regarding the mechanism(s) and receptor(s) involved in the early brain programming during development to organize the circuits underlying sexually differentiated responses. Taking advantage of a mouse model harboring a mutation of the ERα palmitoylation site, which prevents membrane ERα signaling (mERα; ERα‐C451A), this study investigated the role of mERα on the expression of male and female sexual behavior and neuronal populations that differ between sexes. The results revealed no genotype effect on the expression of female sexual behavior, while male sexual behavior was significantly reduced, but not abolished, in males homozygous for the mutation. Similarly, the number of kisspeptin‐ (Kp‐ir) and calbindin‐immunoreactive (Cb‐ir) neurons in the anteroventral periventricular nucleus (AVPv) and the sexually dimorphic nucleus of the preoptic area (SDN‐POA), respectively, were not different between genotypes in females. In contrast, homozygous males showed increased numbers of Kp‐ir and decreased numbers of Cb‐ir neurons compared to wild‐types, thus leading to an intermediate phenotype between females and wild‐type males. Importantly, females neonatally treated with estrogens exhibited the same neurochemical phenotype as their corresponding genotype among males. Together, these data provide evidence that mERα is involved in the perinatal programming of the male brain.     

寻常痤疮发病机制相关信号通路的研究进展

寻常痤疮是一种毛囊皮脂腺单位的炎症疾病,在青少年中的发病率高达85%,发病机制与雄激素、皮脂分泌、嗜脂性微生物感染、免疫-炎症反应等密切相关。本文从炎症信号通路、皮脂分泌通路方面,综述与痤疮相关的信号转导通路。     

The role of Wnt/mTOR signaling in spinal cord injury

Spinal cord injury (SCI) is the most common disabling spinal injury, a complex pathologic process that can eventually lead to severe neurological dysfunction. The Wnt/mTOR signaling pathway is a pervasive signaling cascade that regulates a wide range of physiological processes during embryonic development, from stem cell pluripotency to cell fate. Numerous studies have reported that Wnt/mTOR signaling pathway plays an important role in neural development, synaptogenesis, neuron growth, differentiation and survival after the central nervous system (CNS) is damaged. Wnt/mTOR also plays an important role in regulating various pathophysiological processes after spinal cord injury (SCI). After SCI, Wnt/mTOR signal regulates the physiological and pathological processes of neural stem cell proliferation and differentiation, neuronal axon regeneration, neuroinflammation and pain through multiple pathways. Due to the characteristics of the Wnt signal in SCI make it a potential therapeutic target of SCI. In this paper, the characteristics of Wnt/mTOR signal, the role of Wnt/mTOR pathway on SCI and related mechanisms are reviewed, and some unsolved problems are discussed. It is hoped to provide reference value for the research field of the role of Wnt/mTOR pathway in SCI, and provide a theoretical basis for biological therapy of SCI.     

Stage-specific regulation of oligodendrocyte development by Hedgehog signaling in the spinal cord

Elucidation of signaling pathways that control oligodendrocyte (OL) development is a prerequisite for developing novel strategies for myelin repair in neurological diseases. Despite the extensive work outlining the importance of Hedgehog (Hh) signaling in the commitment and generation of OL progenitor cells (OPCs), there are conflicting reports on the role of Hh signaling in regulating OL differentiation and maturation. In the present study, we systematically investigated OPC specification and differentiation in genetically modified mouse models of Smoothened (Smo), an essential component of the Hh signaling pathway in vertebrates. Through conditional gain-of-function strategy, we demonstrated that hyperactivation of Smo in neural progenitors induced transient ectopic OPC generation and precocious OL differentiation accompanied by the co-induction of Olig2 and Nkx2.2. After the commitment of OL lineage, Smo activity is not required for OL differentiation, and sustained expression of Smo in OPCs stimulated cell proliferation but inhibited terminal differentiation. These findings have uncovered the stage-specific regulation of OL development by Smo-mediated Hh signaling, providing novel insights into the molecular regulation of OL differentiation and myelin repair.     

妊娠期糖尿病孕妇胎盘组织Akt和GLUT-1的表达与新生儿体重的相关性

目的探讨妊娠期糖尿病(GDM)孕妇胎盘组织Akt和GLUT-1的表达与新生儿体重的相关性。方法选取我院收治的40例GDM患者作为研究组,另选取40例健康孕妇作为对照组,检测两组孕妇的孕期BMI、孕期增重、 FPG、 FINS、HbA1c水平,分析胎盘组织Akt和GLUT-1表达情况及其与新生儿体重的相关性。结果研究组胎盘组织Akt和GLUT-1表达明显低于对照组(P <0.05)。Pearson相关性分析显示,Akt表达(r=-0.697, P=0.035)、 GLUT-1表达(r=-0.768, P=0.029)均与新生儿体重呈负相关。结论 GDM孕妇胎盘组织中Akt和GLUT-1表达水平下降可能是造成新生儿体重上升的原因。     

Melatonin alleviates brain injury in mice subjected to cecal ligation and puncture via attenuating inflammation,apoptosis, and oxidative stress: the role of SIRT1 signaling

Sepsis is a systemic inflammatory response to infection that causes severe neurological complications. Previous studies have suggested that melatonin is protective during sepsis. Additionally, silent information regulator 1 (SIRT1) was reported to be beneficial in sepsis. However, the role of SIRT1 signaling in the protective effect of melatonin against septic encephalopathy remains unclear. This study aimed to investigate the role of SIRT1 in the protective effect of melatonin. EX527, a SIRT1 inhibitor, was used to reveal the role of SIRT1 in melatonin's action. Cecal ligation and puncture or sham operation was performed in male C57BL/6J mice. Melatonin was administrated intraperitoneally (30 mg/kg). The survival rate of mice was recorded for the 7‐day period following the sham or CLP operation. The blood–brain barrier (BBB) integrity, brain water content, levels of inflammatory cytokines (TNF‐α, IL‐1β, and HMGB1), and the level of oxidative stress (superoxide dismutase (SOD), catalase (CAT), and malondialdehyde (MDA)) and apoptosis were assessed. The expression of SIRT1, Ac‐FoxO1, Ac‐p53, Ac‐NF‐κB, Bcl‐2, and Bax was detected by Western blot. The results suggested that melatonin improved survival rate, attenuated brain edema and neuronal apoptosis, and preserved BBB integrity. Melatonin decreased the production of TNF‐α, IL‐1β, and HMGB1. Melatonin increased the activity of SOD and CAT and decreased the MDA production. Additionally, melatonin upregulated the expression of SIRT1 and Bcl‐2 and downregulated the expression of Ac‐FoxO1, Ac‐p53, Ac‐NF‐κB, and Bax. However, the protective effects of melatonin were abolished by EX527. In conclusion, our results demonstrate that melatonin attenuates sepsis‐induced brain injury via SIRT1 signaling activation.