Construction of eukaryotic expression vector of human S100A13 gene and its effect on proliferation of human thyroid cancer cell line TT

Objective To investigate the effect of exogenous S100A13 gene overexpression on the proliferation of human thyroid cancer cell line TT.Methods The recombinant ORF of S100A13 tagged with six histidines at the 5' end was subcloned into the pcDNA3.2/V5/GW/D-TOPO vector and sequenced.The eukaryotic expression plasmid pcDNA3.2/V5 /GW/D-S100A13 and empty vector pcDNA3.2/V5/GW/D were transfected into TT cells.The positive clones were selected by G418.The expressions of S100A13 mRNA and protein were detected by real time reverse transcription-polymerase chain reaction(RT-PCR) and Western blot.The effect of S100A13 on cell proliferation and cell cycle was evaluated by cell growth curve,MTT colorimetric assay and flow cytometry.Results S100A13 gene tagged with six histidines at the 5 ' end was confirmed to be inserted into the pcDNA3.2/V5/GW/D vector correctly.TT-S100A13-V5 cells,which over-expressed S100A13,were constructed successfully.TT-S100A13-V5 cells grew much faster than TT-V5 and TT cells(P <0.001).The proportions of both S and G2/M phase cells were significantly higher in TT-S100A13-V5 cells than those in TT-V5 and TT cells(P <0.001).Conclusion The eukaryotic expression vector containing human S100A13 gene has been successfully constructed,which highly expresses S100A13 in TT cells.Exogenous S100A13 gene overexpression accelerates TT cell proliferation and drives the cell cycle progression of TT cells from G0/G1 phase to S and G2/M phases.

S100b protects IMR-32 cells against Ab(1-42) induced neurotoxicity via modulation of apoptotic genes expression

Amyloid beta (1-42) peptide is considered responsible for the formation of senile plaques that accumulate in the brain of patients with Alzheimer’s disease (AD). In the past years considerable attention has been focused on identifying new protective substances that prevent or almost retard the appearance of amyloid beta (1-42)-related neurotoxic effects. In this study, human neuroblastoma cells (IMR-32) was used as system model to evaluate the protective role of S100b, a neurotrophic factor and neuronal survival protein, that is highly expressed by reactive astrocytes in close vicinity of beta-amyloid deposits, against amyloid beta (1-42)-dependent toxicity. Our results show that at nanomolar concentrations, S100b protects cells against Aβmediated cytotoxicity, as assessed by MTS vitality test. The protective mechanism seems to be related to the effect on bcl-2 (an anti-apoptotic gene) expression, which is highly down-regulated by amyloid beta (1-42) treatment, while resulted more expressed in the presence of S100b. On the contrary, Bax, a proapoptotic gene, resulted down-regulated by the treatment with S100 compared with the results obtained in the presence of amyloid beta (1-42) peptide. However, at micromolar doses, S100b is toxic for IMR-32 cells and its toxicity adds to that of the Aβpeptide, suggesting that additional molecular mechanisms may be involved in theneurotoxic process.

S100A6 gene have a positive influence on the growth and proliferation of gastric cancer cell MKN45

Objective： S100A6 （a.k.a., calcyclin） is over-expressed in several human tumors, including gastric carcinoma, human melanoma, pancreatic carcinoma, squamous cell carcinoma, malignant fibrous histiocytoma （MFH）, and carcinomas of the thyroid, breast, and colon. However, little is known about the role S100A6 plays in gastric adenocarcinoma. In the present study, we intended to investigate the influence of S100A6 on the growth, proliferation, apoptosis, invasion and cell cycle of the gastric cancer cell MKN45. Methods： As an important member of S100 family, S100A6 cDNAwas subcloned into a constitutive vector pcDNA3.1 followed by transfection in gastric cancer cell line MKN45 by using liposome. Then stable transfectants were selected and appraised. The apoptosis and cell cycles of these clones were analyzed by using flow cytometric assay. The growth and proliferation were analyzed by cell growth curves and colony-forming assay respectively. The S100A6 stable expression clones （MKN-S100A6） were detected and compared with their control groups respectively. Results： MKN- S100A6 grew faster than MKN45 and MKN-PC （MKN45 transfected with pcDNA3.1 vector）. The cell counts of MKN-SI00A6 in the fifth, sixth and seventh days were significantly more than those of control groups （P 〈 0.05）. Cell cycle analysis showed that proportions of MKN-S100A6 in G0-G1 and G2-M were different significantly with those of its control groups respectively （P 〈 0.05）. The apoptosis rate of MKN-S100A6 was significantly lower than those of control groups （P 〈 0.05）. Results of colony-forming assay showed that the colon formation rate of MKN-S100A6 was higher than those of control groups （P 〈 0.05）. Conclusion： S100A6 can promote the growth and proliferation of gastric cancer cells. It can help tumor cell maintain malignant phenotype. In gastric cancer, S100A6 could be thought as a tumor-enhancing gene in some distance, but its role could be complicated.

Upregulated expression of S100A8 in mice brain after focal cerebral ischemia reperfusion

BACKGROUND:Recent studies have showed that S100A8 has been implicated in the pathobiology of inflammatory disorders,and that cerebral ischemia reperfusion(l/R) rapidly activates inflammation responses via Toll-like receptor 4(TLR4).This study aimed to explore the expression of S100A8 and the relationship between S100A8 and TLR4 in focal cerebral ischemia reperfusion injury.METHODS:C3H/HeJ mice(n=30) and C3H/HeN mice(n=30) were divided randomly into a C3H/HeJ model group(n=18),a C3H/HeJ control group(n=12),a C3H/HeN model group(n=18),and a C3H/HeN control group(n=12).Middle cerebral artery l/R model in mice was produced using a thread embolism method.The brains of the mice were collected after ischemia for 1 hour and reperfusion for 12 hours.Stroke outcome was evaluated by determination of infarct volume and assessment of neurological impairment scores.Brain injury after cerebral l/R was observed by an optical microscope after TTC and HE dyeing.The immunofluorescence technique and real time PCR were used to test the expression level of S100A8 in brain damage.RESULTS:Compared with C3H/HeN mice,TLR4-deficient mice(C3H/HeJ) had lower infarct volumes and better outcomes in neurological tests.The levels of S100A8 increased sharply in the brains of mice after l/R injury.In addition,mice that lacked TLR4(C3H/HeJ) had lower expression of l/R-induced S100A8 than C3H/HeN mice in the model group,indicating that a close relationship might exist between the levels of S100A8 and TLR4.CONCLUSION:S100A8 interaction with TLR4 might be involved in brain damage and in inflammation triggered by l/R injury.

S100A8 mediates the activation of P65/HLA-B/S100A8/BCL-2/Caspase-9 (-3) pathway in laryngeal carcinogenesis

S100 calcium binding protein A8 (S100A8),a possible novel member of NF-kappa B signal pathway in laryngeal squamous cell carcinoma (LSCC),interacts with human leukocyte antigen B (HLA-B) which carries an NF-kappa B binding site within the enhancer A. The objective of this study was to explore the molecular mechanism of S100A8 in laryngeal carcinogenesis. RT-PCR,Western blotting and immuno-histochemistry staining were applied to evaluate the expression levels of IKKα,P65,REL-B,S100A8,APAF-1 and BCL-2 genes. The signal transduction passway in which S100A8 might participate was explored by RNA interference. Flow cytometry,TUNEL assay and cell invasion in vitro were used to detect the biological behavior of Hep2 cells induced by S100A8 gene. Our results showed that high expression of S100A8 was related to tumorigenesis in LSCC and negatively correlated with the degree of differentiation,indicating that S100A8 gene could inhibit apoptosis and promote metastasis in LSCC. Additionally,the suppression of S100A8 by RNA interference down-regulated BCL-2 but not APAF-1,P65 and IKKα,while,the suppression of P65 could significantly down-regulate the expression of S100A8 gene. In conclusion,S100A8 plays an important role in P65/HLA-B/S100A8/BCL-2/Caspase-9 (-3) pathway in laryngeal carcinoma.

血清S100A8、Ang-2水平与儿童重症肺炎病情严重程度和临床结局的关系

目的探讨血清S100钙结合蛋白A8(S100A8)、血管生成素2(Ang-2)水平与儿童重症肺炎病情严重程度和临床结局的关系。方法选择肺炎支原体肺炎儿童200例,其中重症肺炎88例(重症组)、普通肺炎112例(普通组),同期另选非肺炎支原体肺炎儿童80例作为对照组。采集所有研究对象清晨空腹外周静脉血,离心留取血清,采用ELISA法检测血清S100A8、Ang-2、IL-6、TNF-α,采用循环增强荧光免疫法检测血清PCT,采用免疫散射比浊法检测血清CRP。肺炎支原体肺炎儿童入院24 h内通过小儿危重病例评分(PCIS)评估病情严重程度。重症肺炎儿童入院后规范治疗并随访21天,至随访结束,死亡20例、存活68例。分析血清S100A8、Ang-2水平与重症肺炎儿童血清PCT、IL-6、TNF-α、CRP水平及PCIS的关系。采用受试者工作特征(ROC)曲线分析血清S100A8、Ang-2水平对重症肺炎儿童临床结局的预测价值。结果与对照组比较,普通组与重症组血清S100A8、Ang-2、PCT、IL-6、TNF-α、CRP水平均显著升高(P均<0.05);与普通组比较,重症组血清S100A8、Ang-2、PCT、IL-6、TNF-α、CRP水平均显著升高,PCIS显著降低(P均<0.05)。重症肺炎儿童血清S100A8水平与血清PCT、IL-6、TNF-α、CRP水平均呈正相关关系(r分别为0.746、0.797、0.718、0.730,P均<0.05),与PCIS呈负相关关系(r=-0.477,P<0.05);血清Ang-2水平与血清PCT、IL-6、TNF-α、CRP水平均呈正相关关系(r分别为0.724、0.825、0.679、0.693,P均<0.05),与PCIS呈负相关关系(r=-0.509,P<0.05)。重症肺炎儿童死亡者血清S100A8、Ang-2、PCT、IL-6、TNF-α、CRP水平均显著高于其存活者,而PCIS显著低于其存活者(P均<0.05)。ROC曲线分析显示,血清S100A8、Ang-2水平预测重症肺炎儿童死亡的曲线下面积分别为0.764、0.837,最佳截断值分别为136.55 pg/mL、5.48 g/L,其预测灵敏度分别为70.0%、85.0%,特异度分别为91.2%、79.4%。结论血清S100A8、Ang-2水平与重症肺炎儿童病情严重程度密切相关,并且还可作为预测其临床结局的生物标志物。

生物信息学及实验验证S100A8为溃疡性结肠炎的致炎基因

目的:寻找溃疡性结肠炎(UC)的致炎因子。方法:从GEO中纳入3组人类基因芯片数据集,R软件分析其中两组数据集中的差异表达基因(DEGs),结合研究前期UC大鼠基因芯片的前20个DEGs取交集后筛选UC的核心基因。在另一个人类芯片数据集中利用ROC曲线评估核心基因的敏感度和特异度,CIBERSORT分析核心基因与免疫细胞的关系,蛋白互作(PPI)网络图识别与核心基因共表达的蛋白并进行功能富集分析,将核心基因与治疗UC的抗炎中药进行分子对接,通过体外实验验证核心基因与炎症的相关性以及抗炎中药对核心基因的作用。结果:S100A8是UC的核心基因,具有高敏感度和特异度(AUC=0.953),S100A8与中性粒细胞、活化的肥大细胞和单核细胞等免疫炎症细胞呈正相关,PPI及功能富集分析发现S100A8与RAS信号通路、PI3K-AKT信号通路、mTOR信号通路等炎症通路相关,抗炎中药雷公藤红素、黄芩苷、小檗碱与S100A8均有较好的结合力,体外实验提示S100A8在炎症中发挥重要作用,雷公藤红素、黄芩苷、小檗碱均能降低S100A8表达。结论:S100A8可能是UC的致炎核心基因,有望成为新的治疗靶点。

S100A8/S100A9在视网膜退行性疾病中的作用及机制研究进展

S100蛋白家族属于损伤相关分子模式(DAMP),其在机体先天免疫反应中发挥着重要的炎症调节作用。其中S100A8/S100A9蛋白在众多疾病中发挥着广泛的抗菌、抗感染功能,并促进机体免疫及炎症反应的发生发展。在各类视网膜退行性疾病中,S100A8/S100A9蛋白在转录及翻译阶段均明显上调,可促进眼部组织炎症因子的激活、巨噬细胞和中性粒细胞等免疫细胞的激活与募集,促进眼部炎症发生发展。文章旨在阐述S100A8/S100A9蛋白的生物学功能及其在视网膜退行性疾病如糖尿病视网膜病变、年龄相关性黄斑变性和缺血性视网膜病变中的作用及可能的机制。

血清S100A8、S100A9水平与小儿难治性肺炎支原体肺炎病情严重程度及预后的关系

目的探讨血清S100钙结合蛋白A8(S100A8)、S100钙结合蛋白A9(S100A9)水平与小儿难治性肺炎支原体肺炎(RMPP)病情严重程度及预后的关系。方法选取70例RMPP患儿为RMPP组、80例普通肺炎支原体肺炎患儿为GMPP组、50例健康体检儿童为对照组。根据病情严重程度将RMPP患儿分为轻症组(n=36)、重症组(n=34),根据预后将RMPP患儿分为预后良好组(n=43)和预后不良组(n=27)。用酶联免疫吸附实验检测血清S100A8、S100A9并比较各组二者水平变化。分析S100A8、S100A9水平与RMPP患儿病情严重程度的关系;Logistic回归分析RMPP患儿预后不良的危险因素;绘制受试者工作特征曲线,用曲线下面积评价血清S100A8、S100A9水平对RMPP患儿预后的预测效能。结果RMPP组血清S100A8、S100A9水平均高于GMPP组和对照组(P均<0.05),GMPP组血清S100A8、S100A9水平均高于对照组(P均<0.05)。治疗前及治疗后7 d,重症组血清S100A8、S100A9水平均高于轻症组(P均<0.05);且两组治疗后7 d血清S100A8、S100A9水平均低于本组治疗前(P均<0.05)。治疗前及治疗后7 d,预后不良组血清S100A8、S100A9水平均高于预后良好组(P均<0.05)。预后良好组治疗后7 d血清S100A8、S100A9水平低于治疗前(P均<0.05);但预后不良组治疗后7 d的血清S100A8、S100A9水平与治疗前比较差异无统计学意义(P均>0.05)。S100A8、S100A9水平升高是RMPP患儿预后不良的危险因素(P均<0.05)。S100A8、S100A9及二者联合预测RMPP患儿预后不良的曲线下面积分别为0.944、0.907、0.968。结论血清S100A8、S100A9水平升高与小儿RMPP病情严重程度及预后相关。

血清sCD73、S100A8/A9水平与晚期子宫内膜癌患者临床病理特征及PD-1/PD-L1抑制剂治疗预后的关联性分析

目的 分析血清可溶性CD73(sCD73)、S100钙结合蛋白A8/A9(S100A8/A9)与晚期子宫内膜癌患者临床病理特征及程序性死亡受体-1(PD-1)/程序性死亡配体1(PD-L1)抑制剂治疗预后的关联性。方法 招募2020年3月至2021年2月于齐齐哈尔市第一医院接受PD-1/PD-L1抑制剂治疗的晚期子宫内膜癌患者142例,入院后于晨间采集空腹肘部静脉血5 mL,取血清,采用酶联免疫吸附法测定患者血清sCD73、S100A8/A9水平。在随访期间,有58例患者死亡(死亡组),84例存活(存活组)。采用受试者工作特征(ROC)曲线评估血清sCD73、S100A8/A9水平预测患者生存结局的效能。根据ROC曲线分析的最佳截断值将患者分为sCD73高表达组、sCD73低表达组以及S100A8/A9高表达组、S100A8/A9低表达组。采用Cox回归分析影响PD-1/PD-L1抑制剂治疗晚期子宫内膜癌生存预后的因素。分析血清sCD73、S100A8/A9表达水平与患者临床病理特征的关联性。结果 存活组血清sCD73、S100A8/A9水平低于死亡组,差异有统计学意义(P<0.05)。ROC曲线分析结果显示,血清sCD73、S100A8/A9均能有效预测PD-1/PD-L1抑制剂治疗晚期子宫内膜癌患者的生存结局(P<0.05),其最佳截断值分别为5.30μg/L、3.06μg/mL。sCD73、S100A8/A9低表达组的生存预后均优于其高表达组(log-rank检验:χ^(2)=91.367,P<0.001;χ^(2)=69.852,P<0.001)。多因素Cox回归分析结果显示,较高的血清sCD73[HR(95%CI)=2.511(1.497~4.214),P<0.001]、S100A8/A9[HR(95%CI)=1.806(1.106~2.948),P=0.018]水平是患者生存预后不良的独立危险因素。sCD73、S100A8/A9高表达组低分化程度占比显著大于其低表达组(P<0.05)。结论 晚期子宫内膜癌患者血清sCD73、S100A8/A9高水平可能提示其肿瘤分化程度低,是PD-1/PD-L1抑制剂治疗患者生存预后不良的危险因素。

S100A8在牙周炎症进程中的表达

目的 探究在牙周炎牙周组织中S100A8的表达,为其在牙周炎中作用机制的研究提供一定的理论基础。方法 选取6例进行牙周手术的牙周炎患者,另选取6例牙龈健康的成人,将进行牙周手术的患者及健康牙龈切除术的患者分为牙周炎组(n=6)和正常组(n=6)两组,对其切除的牙龈进行免疫组织化学染色,观察其中S100A8的表达情况。体外培养人牙周膜细胞,1μg/mL脂多糖(lipopolysaccharide, LPS)刺激诱导炎性微环境,细胞免疫荧光染色以及实时定量PCR检测人牙周膜细胞中S100A8的基因及蛋白表达水平。体外培养小鼠单核巨噬细胞白血病细胞(小鼠RAW264.7细胞),1μg/mL LPS刺激诱导炎性微环境,实时定量PCR检测观察小鼠RAW264.7细胞中S100A8生物基因表达水平。结果 正常组牙龈上皮细胞可见S100A8表达,牙周炎组牙龈上皮及固有层结缔组织中均可见炎症细胞浸润,其中可见S100A8表达。牙周炎组S100A8阳性表达的炎症细胞数量明显多于正常组(P<0.05)。S100A8在人牙周膜细胞中阳性表达,1μg/mL LPS刺激培养24 h后,S100A8表达降低。人牙周膜细胞在LPS刺激24、72 h后,S100A8基因表达水平均较对照组有所降低,且表达水平与LPS刺激持续时间有相关性;小鼠RAW264.7细胞在1μg/mL LPS刺激培养24、72 h后,S100A8基因表达水平较对照组有所升高。结论 S100A8参与牙周炎的发生发展过程。在炎症环境下,其在炎症细胞中的表达升高,在牙周膜细胞中的表达降低。S100A8可能参与牙周膜细胞在牙周炎症过程中的调控,其作用机制有待于进一步探索。

Seminal plasma S100A8/A9 as a potential biomarker of genital tract inflammation

Infections and inflammatory reactions in the male genital tract are the leading causes of male infertility with a prevalence of 6%-10%,primarily affecting testicular and epididymal function and ultimately compromising sperm quality.However,most infertile patients with genital infection/inflammation are asymptomatic and easily overlooked.Traditional indicators,including white blood cells,elastase,and other components in semen,can reflect inflammation of the genital tract,but there is still a lack of a uniform standard method of detection.Therefore,it is necessary to explore reliable markers in semen that reflect the inflammatory status of the genital tract.Using the experimental autoimmune orchitis(EAO)model to simulate noninfectious chronic orchitis,we successfully collected ejaculated seminal fluid from EAO rats using optimized electrical stimulation devices.Proteomic analysis was performed using isobaric tags for relative and absolute quantification(iTRAQ).Compared to the control group,55 upregulated and 105 downregulated proteins were identified in seminal plasma samples from the EAO group.In a preliminary screening,the inflammation-related protein S100A8/A9 was upregulated.We further verified that S100A8/A9 was increased in seminal plasma and highly expressed in testicular macrophages of the EAO model.In patients with oligoasthenospermia and genital tract infections,we also found that S100A8/A9 levels were remarkably increased in seminal plasma and testicular macrophages.S100A8/A9 in semen may be a potential biomarker for chronic genital inflammation.Our study provides a new potential biomarker for early diagnosis and further understanding of male infertility caused by genital inflammation.

Cmtm4 deficiency exacerbates colitis by inducing gut dysbiosis and S100a8/9 expression

The dysfunction of innate immunity components is one of the major drivers for ulcerative colitis(UC),and increasing reports indicate that the gut microbiome serves as an intermediate between genetic mutations and UC development.Here,we find that the IL-17 receptor subunit,CMTM4,is reduced in UC patients and dextran sulfate sodium(DSS)-induced colitis.The deletion of CMTM4(Cmtm4^(-/-))in mice leads to a higher susceptibility to DSS-induced colitis than in wild-type,and the gut microbiome significantly changes in composition.The causal role of the gut microbiome is confirmed with a cohousing experiment.We further identify that S100a8/9 is significantly up-regulated in Cmtm4^(-/-)colitis,with the block of its receptor RAGE that reverses the phenotype associated with the CMTM4 deficiency.CMTM4 deficiency rather suppresses S100a8/9 expression in vitro via the IL17 pathway,further supporting that the elevation of S100a8/9 in vivo is most likely a result of microbial dysbiosis.Taken together,the results suggest that CMTM4 is involved in the maintenance of intestinal homeostasis,suppression of S100a8/9,and prevention of colitis development.Our study further shows CMTM4 as a crucial innate immunity component,confirming its important role in UC development and providing insights into potential targets for the development of future therapies.

肛瘘术后病人血清钙结合蛋白S100A8、促红细胞生成素表达与创面愈合、肛门功能的关系

目的 探究肛瘘术后病人血清钙结合蛋白S100A8(S100A8)、促红细胞生成素(EPO)表达与创面愈合、肛门功能的关系。方法 以2020年5月至2022年3月河北中医学院第二附属医院收治的96例肛瘘病人为研究对象,所有病人均接受肛瘘手术治疗。对比治疗前后病人血清S100A8、EPO水平及肛门失禁Wexner评分,比较不同血清S100A8、EPO水平病人疗效、创面愈合时间、14 d创面愈合率及Wexner评分;Pearson相关性分析血清S100A8、EPO与创面愈合时间、14 d创面愈合率及Wexner评分的相关性;多因素logistic回归分析肛瘘术效果的影响因素。结果 术后,病人血清S100A8较术前明显降低[(65.34±6.21)μg/L比(83.15±8.92)μg/L,P<0.05],EPO水平较术前明显升高[(52.36±5.67)U/L比(33.67±4.86)U/L,P<0.05],Wexner评分较术前明显降低[(9.74±2.22)分比(21.02±5.31)分,P<0.05]。术后血清S100A8低表达者较高表达者疗效更优(P<0.05),EPO高表达者较低表达者疗效更优(P<0.05)。术后血清S100A8高表达者较低表达者创面愈合时间更长(P<0.05),14 d创面愈合率更低(P<0.05),Wexner评分更高(P<0.05),血清S100A8与创面愈合时间呈正相关,与创面愈合率呈负相关,与Wexner评分呈正相关(均P<0.05)。术后血清EPO高表达者较低表达者创面愈合时间更短(P<0.05),14 d创面愈合率更高(P<0.05),Wexner评分更低(P<0.05),血清EPO与创面愈合时间呈负相关,与创面愈合率呈正相关,与Wexner评分呈负相关(均P<0.05)。多因素logistic回归分析显示,S100A8高表达、EPO低表达是影响肛瘘术后效果的危险因素。结论 肛瘘术后病人血清S100A8、EPO与病人创面愈合时间、14 d创面愈合率、Wexner评分显著相关,能够反应病人创面愈合及肛门功能情况。

血清S100A8和PD-L1联合超声检测在子宫内膜癌诊断及预后中的价值分析

目的探究血清S100钙结合蛋白A8(S100A8)和程序性死亡配体-1(PD-L1)联合超声检测在子宫内膜癌诊断及预后中的价值。方法选取2020年4月至2022年4月于我院收治的确诊为子宫内膜癌的患者166例即为癌症组,按照国际妇产科联合会(FIGO)标准分为Ⅰ期48例、Ⅱ期52例、Ⅲ期42例、Ⅳ期24例。选择同期在我院确诊为子宫内膜增生的患者166例为对照组;使用酶联免疫吸附试验(ELISA)检测血清中S100A8和PD-L1水平;使用阴道超声获取血流频谱测得血流参数:搏动指数(PI)、阻力指数(RI)。采用受试者工作特征(ROC)曲线分析血清S100A8和PD-L1联合超声参数对子宫内膜癌的诊断价值以及预后的预测价值。结果与对照组相比,癌症组患者血清中S100A8和PD-L1水平显著升高(t=10.688、8.605,均P<0.001);与Ⅰ期相比,Ⅱ期、Ⅲ期、Ⅳ期患者血清中S100A8和PD-L1水平显著升高,与Ⅱ期相比,Ⅳ期患者血清中S100A8和PD-L1水平显著升高(P<0.05)。与对照组相比,癌症组PI和RI的值显著降低(t=7.183、6.799,均P<0.001);血清S100A8和PD-L1联合超声参数对子宫内膜癌诊断的曲线下面积(AUC)高于各指标单独诊断的AUC值(Z S100A8 vs.S100A8+PD-L1+PI+RI=6.472,Z PD-L1 vs.S100A8+PD-L1+PI+RI=6.903,Z PI vs.S100A8+PD-L1+PI+RI=7.072,Z RI vs.S100A8+PD-L1+PI+RI=5.987,均P<0.001);与预后良好组相比,预后不良组S100A8、PD-L1水平显著升高,PI、RI水平显著降低(P<0.001);血清S100A8和PD-L1联合超声参数对子宫内膜癌预后预测的AUC高于各指标单独预测的AUC值(Z S100A8 vs.S100A8+PD-L1+PI+RI=2.841,P=0.005;Z PD-L1 vs.S100A8+PD-L1+PI+RI=2.146,P=0.032;Z PI vs.S100A8+PD-L1+PI+RI=6.056,P<0.001;Z RI vs.S100A8+PD-L1+PI+RI=4.370,P<0.001)。结论子宫内膜癌患者血清中S100A8和PD-L1水平显著升高,血清S100A8和PD-L1联合超声能够提高对子宫内膜癌诊断及预后价值。

钙结合蛋白S100A8在扩张皮肤中的实验研究

目的探究扩张皮肤中钙结合蛋白S100A8的分布特征及其在皮肤扩张过程中的作用。方法构建大鼠头部皮肤扩张模型,利用免疫荧光染色、qPCR、Western blotting等方法检测皮肤中S100A8的分布及表达水平。随后,体外实验对人角质形成细胞拉伸,模拟扩张皮肤在机械应力下的状态,利用qPCR、酶联免疫吸附测定等实验检测细胞中及其上清液中S100A8的含量。应用S100A8重组蛋白或角质形成细胞拉伸后的上清液对人成纤维细胞增殖、迁移、胶原蛋白合成进行检测。结果大鼠扩张表皮层S100A8表达水平较高(P<0.01);角质形成细胞经体外拉伸后分泌大量S100A8(P<0.05,P<0.01);重组蛋白S100A8能促进成纤维细胞的增殖、迁移及胶原合成(P<0.05,P<0.01),并且角质形成细胞拉伸后的上清液也能促进成纤维细胞胶原合成(P<0.01)。结论机械应力能上调扩张表皮层中S100A8的表达,并通过旁分泌作用促进成纤维细胞增殖、迁移及胶原合成。

CURB-65评分联合S100A8可预测老年社区获得性肺炎患者住院死亡风险

目的:评估CURB-65评分联合S100钙结合蛋白A8(S100A8)预测老年社区获得性肺炎(CAP)患者住院期间死亡的临床价值。方法:通过住院患者电子病历系统收集276例老年CAP患者的临床资料,根据住院期间生存状态,将其分为死亡组(64例)和生存组(212例)。采用多因素Logistic回归法筛选CAP患者住院期间死亡的独立危险因素,并采用受试者工作特征(ROC)曲线评估CURB-65评分联合S100A8预测老年CAP患者住院期间死亡的临床价值。结果:单因素分析显示,死亡组年龄>70岁、意识改变的患者比例以及血乳酸、白介素-6、S100A8水平、急性生理与慢性健康状况评估(APACHE II)及CURB-65评分高于生存组(P均<0.05)。多因素Logistic回归分析结果显示,年龄>70岁、S100A8>109 pg/mL、APACHE II评分>25分、CURB-65>2.85分是老年CAP患者住院期间全因死亡的独立危险因素。ROC曲线显示,CURB-65评分联合S100A8预测老年CAP患者住院死亡的曲线下面积高于单一S100A8、CURB-65评分,预测性能最高。结论:CURB-65评分、S100A8水平与老年CAP患者住院期间临床预后关系密切,联合应用可预测其住院期间全因死亡风险。

创伤性休克伴SIRS患者血浆循环S100A8/S100A9相关通路蛋白的表达研究

目的:探讨创伤性休克伴SIRS患者血浆循环S100A8/S100A9相关通路蛋白表达及意义。方法:采用前瞻性研究方法,纳入我院2022年1月-2024年1月诊断为创伤性休克90例,其中伴SIRS患者43例,另征集健康体检者45例为对照组,检测各组血浆循环S100A8/A9和炎性因子的表达。建立创伤性休克伴SIRS的大鼠模型,采用qRT-PCR和Western Blot检测S100A8/A9水平。结果:创伤性休克伴SIRS患者血浆S100A8/A9及IL-6、TNF-β水平均明显高于创伤性休克组和对照组(P<0.05);模型组大鼠血浆S100A8/A9蛋白浓度和IL-6、TNF-β亦显著升高,同时肺、肝组织中S100A8-mRNA、S100A9-mRNA和S100A8/A9蛋白水平也明显高于对照组(P<0.05)。相关分析显示,大鼠循环血浆S100A8/A9水平与炎性因子IL-6、TNF-β均呈正相关(r=0.874,0.748,P=0.000)。结论:S100A8/A9作为新的炎症介质参与了创伤性休克患者SIRS的发生发展,其机制可能与促炎因子TNF-ɑ、IL-6产生协同作用,共同加剧创伤性休克伴SIRS的脏器损伤。

S100A8 promotes tumor progression by inducing phenotypic polarization of microglia through the TLR4/IL-10 signaling pathway in glioma

Background:S100A8 is a member of the S100 protein family and plays a pivotal role in regulating inflammation and tumor progression.This study aimed to comprehensively assess the expression patterns and functional roles of S100A8 in glioma progression.Methods:Glioma tissues were collected from 98 patients who underwent surgical treatment at Fudan University Shanghai Cancer Center.S100A8 expression in glioma tissues was analyzed using immunohistochemistry(IHC)to establish its correlation with clinicopathological features in patients.The expression and prognostic effect of S100A8 in glioma were analyzed using TCGA and CGGA public databases.Then,we investigated the role of S100A8 in glioma through a series of in vivo and in vitro experiments including Transwell,wound healing,CCK8,and intracranial tumor models.Subsequently,bioinformatics analysis,single-cell sequencing and coimmunopre-cipitation(Co-IP)were used to explore the underlying mechanism.Results:S100A8 was upregulated in gliomas compared to paracancerous tissues,and this phenotype was sig-nificantly correlated with poor prognosis.Subgroup analysis showed that S100A8 expression was higher in the high-grade glioma(HGG)group than that in the low-grade glioma(LGG)group.S100A8 overexpression in glioma cell lines promoted cell proliferation,migration and invasion,while silencing S100A8 reversed these effects.In vivo experiments showed that S100A8 knockdown can significantly reduce the tumor burden of glioma cells.Notably,S100A8 was observed to stimulate microglial M2 polarization by interacting with TLR4,which subse-quently induced NF-𝜅B signaling and IL-10 secretion within the tumor microenvironment.Conclusions:S100A8 promotes tumor progression by inducing phenotypic polarization of microglia through the TLR4/IL-10 signaling pathway in glioma.It might represent a therapeutic target for further basic research or clinical management of glioma.

S100A8在肿瘤细胞中的表达与结直肠癌增殖、侵袭和转移的关系

目的分析S100A8在肿瘤细胞中的表达与结直肠癌增殖、侵袭和转移的关系。方法收集结直肠癌患者90例,用免疫组织化学染色方式检测S100A8的表达水平与结直肠癌的关系,按照S100A8的表达情况分析结直肠癌的临床病理特征的关联性。结果S100A8在结直肠恶性肿瘤细胞中呈阳性,按照肿瘤细胞数统计S100A8阳性细胞。将S100A8的表达情况分为阳性与阴性两组,与性别、年龄、转移淋巴结、远处脏器转移以及TNM分期进行比较,S100A8表达为阳性组的患者更容易发生淋巴结迁移和远处脏器转移,肿瘤TNM分期更高,差异有统计学意义(P<0.05或<0.01)。同时,S100A8与性别和年龄无相关性,差异无统计学意义(P>0.05)。结论S100A8的表达水平可以间接地判断结直肠癌患者的预后以及检测结直肠癌患者复发情况。