鼠神经生长因子对急性脑梗死血清神经元烯醇化酶和S100β蛋白的影响

目的探讨鼠神经生长因子对急性脑梗死血清神经元烯醇化酶(NSE)和S100β蛋白的影响。方法 128例急性脑梗死患者随机分为两组,观察组64例,对照组64例,对照组采用常规治疗,观察组在常规治疗的基础上加用鼠神经生长因子。治疗前后测定血清NSE和S100β蛋白。结果两组治疗前ESS和ADL评分无明显差异(P>0.05);两组治疗后ESS和ADL评分均有明显升高(P<0.05),并且与对照组治疗后比较,观察组治疗后升高更明显(P<0.05)。两组治疗前患者血清NSE和S100β蛋白无明显差异(P>0.05);两组治疗后患者血清NSE和S100β蛋白均明显降低(P<0.05,P<0.01),并且与对照组治疗后比较,观察组治疗后降低更明显(P<0.05)。结论鼠神经生长因子可以明显降低急性脑梗死血清NSE和S100β蛋白的表达。

Prognostic significance of S100A4 and vascular endothelial growth factor expression in pancreatic cancer

AIM: To investigate the expression of vascular endothelial growth factor (VEGF) and calcium-binding protein S100A4 in pancreatic cancer and their relationship to the clinicopathological parameters and prognosis of pancreatic cancer. METHODS: Expression status of VEGF and S100A4 was examined in 62 surgical specimens of primary pancreatic cancer by immunohistochemistry. Correlation between the expression of VEGF and S100A4 and clinicopathological parameters was analyzed. RESULTS: Thirty-eight of 62 (61.3%) specimens of primary pancreatic cancer were positive for S100A4. Thirty-seven (59.7%) specimens showed positive expression of VEGF. The positive correlation between S100A4 and VEGF expression was significant in cancer tissues (P < 0.001). S100A4 expression was significantly correlated with tumor size, TNM stage and poorer prognosis. VEGF expression had a significant correlation with poorer prognosis. The prognosis of 17 S100A4-and VEGF-negative cancer patients was significantly better than that of other patients (P < 0.05). Distant metastasis (P = 0.001), S100A4-(P = 0.008) and VEGF-positive expression (P = 0.016) were significantly independent prognostic predictors (P < 0.05). CONCLUSION: Over-expression of S100A4 and VEGF plays an important role in the development of pancreatic cancer. Combined examination of the two molecules might be useful in evaluating the outcome of patients with pancreatic cancer.

Neurotrophic factor-based pharmacological approaches in neurological disorders

Aging is a physiological event dependent on multiple pathways that are linked to lifespan and processes leading to cognitive decline.This process represents the major risk factor for aging-related diseases such as Alzheimer’s disease,Parkinson’s disease,and ischemic stroke.The incidence of all these pathologies increases exponentially with age.Research on aging biology has currently focused on elucidating molecular mechanisms leading to the development of those pathologies.Cognitive deficit and neurodegeneration,common features of aging-related pathologies,are related to the alteration of the activity and levels of neurotrophic factors,such as brain-derived neurotrophic factor,nerve growth factor,and glial cell-derived neurotrophic factor.For this reason,treatments that modulate neurotrophin levels have acquired a great deal of interest in preventing neurodegeneration and promoting neural regeneration in several neurological diseases.Those treatments include both the direct administration of neurotrophic factors and the induced expression with viral vectors,neurotrophins’binding with biomaterials or other molecules to increase their bioavailability but also cell-based therapies.Considering neurotrophins’crucial role in aging pathologies,here we discuss the involvement of several neurotrophic factors in the most common brain aging-related diseases and the most recent therapeutic approaches that provide direct and sustained neurotrophic support.

S-100预防大鼠术后腹腔粘连的实验研究

目的:观察不同浓度S-100防粘连冲洗液预防腹腔粘连的效果及其对血清TGF-β1水平的影响。方法:60只Wistar大鼠随机分为6组,每组10只。包括模型组(A组)、透明质酸钠组(B组)、0.5%S-100组(C组)、3%S-100组(D组)、5%S-100(E组)和泰陵组(F组)。通过粘连分级、HE染色、免疫组织化学染色、羟脯氨酸测定观察S-100预防腹腔粘连效果的同时,测定血清TGF-β1水平。结果:B、C、D、E及F组在粘连分级、HE染色及羟脯氨酸测定方面均优于A组(P<0.05);B、C组之间,D、E、F组之间差异无统计学意义(P>0.05);D、E、F3组与B、C2组比较差异有统计学意义(P<0.05)。免疫组织化学染色结果显示B、C、D、E、F组粘连组织内CollagenⅠ含量比A组低(χ2=11.098,P=0.049)。各组大鼠血清TGF-β1水平差异无统计学意义(F=0.161,P=0.976)。结论:S-100防粘连冲洗液具有明显预防腹腔粘连形成的作用,其作用优于透明质酸钠,最佳作用浓度区间为3%～5%。

GDNF、GAP-43、NSE及S-100蛋白在先天性巨结肠患儿中的表达水平及意义

目的探讨与分析胶质细胞源性神经生长因子(GDNF)、生长相关蛋白-43(GAP-43)、神经元特异性烯醇化酶(NSE)、S-100蛋白在先天性巨结肠(HD)患儿中的表达水平及意义。方法选择2019年9月至2022年10月诊治的先天性巨结肠患儿72例作为巨结肠组,选择同期因其他非肠神经节病变而行结肠手术的患儿72例作为参照组。取两组的结肠全层病理标本并进行GDNF、GAP-43、NSE及S-100蛋白表达免疫组化分析,同时进行先天性巨结肠相关性小肠结肠炎(HAEC)诊断评分与相关性分析,取巨结肠组的不同肠段组织标本进行检测。结果巨结肠组的结肠全层GDNF、GAP-43、NSE、S-100蛋白表达阳性率分别为77.8%、73.6%、81.9%、83.3%,显著高于参照组的22.2%、26.4%、20.8%、22.2%(P<0.001)。先天性巨结肠患儿不同结肠区域(狭窄段、移行段、扩张段、正常段)的GDNF、GAP-43、NSE、S-100蛋白表达阳性率对比差异有统计学意义(P<0.001)。巨结肠组的HAEC诊断评分与参照组相比明显提高(P<0.001)。在巨结肠组中,Spearman分析显示HAEC诊断评分与结肠全层GDNF、GAP-43、NSE、S-100蛋白表达阳性率呈正相关(P<0.001)。结论先天性巨结肠患儿多伴有GDNF、GAP-43、NSE、S-100蛋白的高表达,与患儿病情存在相关性,值得临床关注。

S100A8 promotes epithelial-mesenchymal transition and metastasis under TGF-β/USF2 axis in colorectal cancer

Background:The transforming growth factor-β(TGF-β)pathway plays a pivotal role in inducing epithelial-mesenchymal transition(EMT),which is a key step in cancer invasion and metastasis.However,the regulatory mechanism of TGF-βin inducing EMT in colorectal cancer(CRC)has not been fully elucidated.In previous studies,it was found that S100A8 may regulate EMT.This study aimed to clarify the role of S100A8 in TGF-β-induced EMT and explore the underlying mechanism in CRC.Methods:S100A8 and upstream transcription factor 2(USF2)expression was detected by immunohistochemistry in 412 CRC tissues.Kaplan-Meier survival analysis was performed.In vitro,Western blot,and migration and invasion assays were performed to investigate the effects of S100A8 and USF2 on TGF-β-induced EMT.Mouse metastasis models were used to determine in vivo metastasis ability.Luciferase reporter and chromatin immunoprecipitation assay were used to explore the role of USF2 on S100A8 transcription.Results:During TGF-β-induced EMT in CRC cells,S100A8 and the transcription factor USF2 were upregulated.S100A8 promoted cell migration and invasion and EMT.USF2 transcriptionally regulated S100A8 expression by directly binding to its promoter region.Furthermore,TGF-βenhanced the USF2/S100A8 signaling axis of CRC cells whereas extracellular S100A8 inhibited the USF2/S100A8 axis of CRC cells.S100A8 expression in tumor cells was associated with poor overall survival in CRC.USF2 expression was positively related to S100A8 expression in tumor cells but negatively related to S100A8-positive stromal cells.Conclusions:TGF-βwas found to promote EMT and metastasis through the USF2/S100A8 axis in CRC while extracellular S100A8 suppressed the USF2/S100A8 axis.USF2 was identified as an important switch on the intracellular and extracellular S100A8 feedback loop.

S100钙结合蛋白B在骨性关节炎软骨损伤修复中的作用及机制研究

目的探讨S100钙结合蛋白B(S100B)在骨性关节炎(osteoarthritis,OA)软骨损伤修复中的作用及机制。方法取20只新西兰兔随机分为对照组和模型组,每组10只。模型组兔右膝关节制动法制备软骨损伤模型,对照组不作任何处理。4周后采用ELISA法检测关节液IL-1β、TNF-α水平,实时荧光定量PCR(real-time fluorescence quantitative PCR,qRT-PCR)和Western blot检测软骨组织S100B、FGF-2、FGF受体1(FGF receptor 1,FGFR1)基因及蛋白表达。分离培养人滑膜成纤维细胞(synovial fibroblasts,SF),观察过表达、干扰S100B以及拮抗FGFR1对细胞IL-1β和TNF-α水平(ELISA法)以及FGF-2和FGFR1基因(qRT-PCR检测)和蛋白(Western blot检测)表达的影响。结果 ELISA检测示模型组兔关节液中IL-1β和TNF-α表达水平均明显高于对照组(P<0.05);qRT-PCR和Western blot检测示,模型组兔软骨组织S100B、FGF-2、FGFR1 mRNA和蛋白表达量均显著高于对照组(P<0.05)。过表达和干扰S100能够分别显著升高和降低脂多糖(lipopolysaccharides,LPS)诱导的IL-1β和TNF-α水平及FGF-2和FGFR1 mRNA和蛋白表达,差异均有统计学意义(P<0.05)。而拮抗FGFR1能够显著降低LPS诱导的IL-1β和TNF-α水平及FGF-2和FGFR1 mRNA和蛋白表达,差异均有统计学意义(P<0.05)。结论 S100B能够调节SF炎性反应并可能影响OA软骨损伤修复,其机制可能与激活FGF-2/FGFR1信号通路有关。

Enriched gestation activates the IGF pathway to evoke embryo-adult benefits to prevent Alzheimer’s disease

Background:Building brain reserves before dementia onset could represent a promising strategy to prevent Alzheimer’s disease(AD),while how to initiate early cognitive stimulation is unclear.Given that the immature brain is more sensitive to environmental stimuli and that brain dynamics decrease with ageing,we reasoned that it would be effective to initiate cognitive stimulation against AD as early as the fetal period.Methods:After conception,maternal AD transgenic mice(3×Tg AD)were exposed to gestational environment enrichment(GEE)until the day of delivery.The cognitive capacity of the offspring was assessed by the Morris water maze and contextual fear-conditioning tests when the offspring were raised in a standard environment to 7 months of age.Western blotting,immunohistochemistry,real-time PCR,immunoprecipitation,chromatin immunoprecipitation(ChIP)assay,electrophysiology,Golgi staining,activity assays and sandwich ELISA were employed to gain insight into the mechanisms underlying the beneficial effects of GEE on embryos and 7–10-month-old adult offspring.Results:We found that GEE markedly preserved synaptic plasticity and memory capacity with amelioration of hallmark pathologies in 7–10-m-old AD offspring.The beneficial effects of GEE were accompanied by global histone hyperacetylation,including those at bdnf promoter-binding regions,with robust BDNF mRNA and protein expression in both embryo and progeny hippocampus.GEE increased insulin-like growth factor 1(IGF1)and activated its receptor(IGF1R),which phosphorylates Ca^(2+)/calmodulin-dependent kinase IV(CaMKIV)at tyrosine sites and triggers its nuclear translocation,subsequently upregulating histone acetyltransferase(HAT)and BDNF transcription.The upregulation of IGF1 mimicked the effects of GEE,while IGF1R or HAT inhibition during pregnancy abolished the GEE-induced CaMKIV-dependent histone hyperacetylation and BDNF upregulation.Conclusions:These findings suggest that activation of IGF1R/CaMKIV/HAT/BDNF signaling by gestational environment enrichment may serve as a promising strategy to delay AD progression.