Neuroprotective effects of acteoside in a glaucoma mouse model by targeting Serta domain-containing protein 4

AIM:To explore the therapeutic effect and main molecular mechanisms of acteoside in a glaucoma model in DBA/2J mice.METHODS:Proteomics was used to compare the differentially expressed proteins of C57 and DBA/2J mice.After acteoside administration in DBA/2J mice,anterior segment observation,intraocular pressure(IOP)monitoring,electrophysiology examination,and hematoxylin and eosin staining were used to analyze any potential effects.Immunohistochemistry(IHC)assays were used to verify the proteomics results.Furthermore,retinal ganglion cell 5(RGC5)cell proliferation was assessed with cell counting kit-8(CCK-8)assays.Serta domain-containing protein 4(Sertad4)mRNA and protein expression levels were measured by qRT-PCR and Western blot analysis,respectively.RESULTS:Proteomics analysis suggested that Sertad4 was the most significantly differentially expressed protein.Compared with the saline group,the acteoside treatment group showed decreased IOP,improved N1-P1 wave amplitudes,thicker retina,and larger numbers of cells in the ganglion cell layer(GCL).The IHC results showed that Sertad4 expression levels in DBA/2J mice treated with acteoside were significantly lower than in the saline group.Acteoside treatment could improve RGC5 cell survival and reduce the Sertad4 mRNA and protein expression levels after glutamate injury.CONCLUSION:Sertad4 is differentially expressed in DBA/2J mice.Acteoside can protect RGCs from damage,possibly through the downregulation of Sertad4,and has a potential use in glaucoma treatment.

Knockdown of HE4 suppresses tumor growth and invasiveness in lung adenocarcinoma through regulation of EGFR signaling

It has been shown that the high expression of human epididymis protein 4(HE4)in most lung cancers is related to the poor prognosis of patients,but the mechanism of pathological transformation of HE4 in lung cancer is still unclear.The current study is expected to clarify the function and mechanism of HE4 in the occurrence and metastasis of lung adenocarcinoma(LUAD).Immunoblotting evaluated HE4 expression in lung cancer cell lines and biopsies,and through analysis of The Cancer Genome Atlas(TCGA)dataset.Frequent HE4 overexpression was demonstrated in LUAD,but not in lung squamous cell carcinoma(LUSC),indicating that HE4 can serve as a biomarker to distinguish between LUAD and LUSC.HE4 knockdown significantly inhibited cell growth,colony formation,wound healing,and invasion,and blocked the G1-phase of the cell cycle in LUAD cell lines through inactivation of the EGFR signaling downstream including PI3K/AKT/mTOR and RAF/MAPK pathways.The first-line EGFR inhibitor gefitinib and HE4 shRNA had no synergistic inhibitory effect on the growth of lung adenocarcinoma cells,while the third-line EGFR inhibitor osimertinib showed additive anti-proliferative effects.Moreover,we provided evidence that HE4 regulated EGFR expression by transcription regulation and protein interaction in LUAD.Our findings suggest that HE4 positively modulates the EGFR signaling pathway to promote growth and invasiveness in LUAD and highlight that targeting HE4 could be a novel strategy for LUAD treatment.

Immunotherapy for esophageal cancer:Where are we now and where can we go

Immune checkpoint inhibitor therapy has dramatically improved patient prognosis,and thereby transformed the treatment in various cancer types including esophageal squamous cell carcinoma(ESCC)in the past decade.Monoclonal antibodies that selectively inhibit programmed cell death-1(PD-1)activity has now become standard of care in the treatment of ESCC in metastatic settings,and has a high expectation to provide clinical benefit during perioperative period.Further,anti-cytotoxic T-lymphocyte–associated protein 4(CTLA-4)monoclonal antibody has also been approved in the treatment of recurrent/metastatic ESCC in combination with anti-PD-1 antibody.Well understanding of the existing evidence of immune-based treatments for ESCC,as well as recent clinical trials on various combinations with chemotherapy for different clinical settings including neoadjuvant,adjuvant,and metastatic diseases,may provide future prospects of ESCC treatment for better patient outcomes.

Quantitative trait loci identification reveals zinc finger protein CONSTANS-LIKE 4 as the key candidate gene of stigma color in watermelon(Citrullus lanatus)

Stigma color is a critical agronomic trait in watermelon that plays an important role in pollination.However,there are few reports on the regulation of stigma color in watermelon.In this study,a genetic analysis of the F2 population derived from ZXG1553(P1,with orange stigma)and W1-17(P2,with yellow stigma)indicated that stigma color is a quantitative trait and the orange stigma is recessive compared with the yellow stigma.Bulk segregant analysis sequencing(BSA-seq)revealed a 3.75 Mb segment on chromosome 6 that is related to stigma color.Also,a major stable effective QTL Clqsc6.1(QTL stigma color)was detected in two years between cleaved amplified polymorphic sequencing(CAPS)markers Chr06_8338913 and Chr06_9344593 spanning a~1.01 Mb interval that harbors 51 annotated genes.Cla97C06G117020(annotated as zinc finger protein CONSTANS-LIKE 4)was identified as the best candidate gene for the stigma color trait through RNA-seq,quantitative real-time PCR(qRT-PCR),and gene structure alignment analysis among the natural watermelon panel.The expression level of Cla97C06G117020 in the orange stigma accession was lower than in the yellow stigma accessions with a significant difference.A nonsynonymous SNP site of the Cla97C06G117020 coding region that causes amino acid variation was related to the stigma color variation among nine watermelon accessions according to their re-sequencing data.Stigma color formation is often related to carotenoids,and we also found that the expression trend of ClCHYB(annotated asβ-carotene hydroxylase)in the carotenoid metabolic pathway was consistent with Cla97C06G117020,and it was expressed in low amounts in the orange stigma accession.These data indicated that Cla97C06G117020 and ClCHYB may interact to form the stigma color.This study provides a theoretical basis for gene fine mapping and mechanisms for the regulation of stigma color in watermelon.

Prognostic and immunological roles of heat shock protein A4 in lung adenocarcinoma

BACKGROUND Heat shock protein A4(HSPA4)belongs to molecular chaperone protein family which plays important roles within variable cellular activities,including cancer initiation and progression.However,the prognostic and immunological significance of HSPA4 in lung adenocarcinoma(LUAD)has not been revealed yet.AIM To explore the prognostic and immunological roles of HSPA4 to identify a novel prognostic biomarker and therapeutic target for LUAD.METHODS We assessed the prognostic and immunological significance of HSPA4 in LUAD using data from The Cancer Genome Atlas database.The association between HSPA4 expression and clinical-pathological features was assessed through Kruskal-Wallis and Wilcoxon signed-rank test.Univariate/multivariate Cox regression analyses and Kaplan-Meier curves were employed to evaluate prognostic factors,including HSPA4,in LUAD.Gene set enrichment analysis(GSEA)was conducted to identify the key signaling pathways associated with HSPA4.The correlation between HSPA4 expression and cancer immune infiltration was evaluated using single-sample gene set enrichment analysis(ssGSEA).RESULTS Overexpressing HSPA4 was significantly related to advanced pathologic TNM stage,advanced pathologic stage,progression disease status of primary therapy outcome and female subgroups with LUAD.In addition,increased HSPA4 expression was found to be related to worse disease-specific survival and overall survival.GSEA analysis indicated a significant correlation between HSPA4 and cell cycle regulation and immune response,particularly through diminishing the function of cytotoxicity cells and CD8 T cells.The ssGSEA algorithm showed a positive correlation between HSPA4 expression and infiltrating levels of Th2 cells,while a negative correlation was observed with cytotoxic cell infiltration levels.CONCLUSION Our findings indicate HSPA4 is related to prognosis and immune cell infiltrates and may act as a novel prognostic biomarker and therapeutic target for LUAD.

Association between heat shock factor protein 4 methylation and colorectal cancer risk and potential molecular mechanisms:A bioinformatics study

BACKGROUND We previously demonstrated that heat shock factor protein 4(HSF4)facilitates colorectal cancer(CRC)progression.DNA methylation,a major modifier of gene expression and stability,is involved in CRC development and outcome.AIM To investigate the correlation between HSF4 methylation and CRC risk,and to uncover the underlying molecular mechanisms.METHODS Differences in β values of HSF4 methylation loci in multiple malignancies and their correlation with HSF4 mRNA expression were analyzed based on Shiny Methylation Analysis Resource Tool.HSF4 methylation-related genes were identified by LinkedOmics in CRC,and Gene Ontology and Kyoto Encyclopedia of Genes and Genomes enrichment analyses were performed.Protein-protein interaction network of HSF4 methylation-related genes was constructed by String database and MCODE algorithm.RESULTS A total of 19 CpG methylation loci were identified in HSF4,and their β values were significantly increased in CRC tissues and exhibited a positive correlation with HSF4 mRNA expression.Unfortunately,the prognostic and diagnostic performance of these CpG loci in CRC patients was mediocre.In CRC,there were 1694 HSF4 methylation-related genes;1468 of which displayed positive and 226 negative associations,and they were involved in regulating phenotypes such as immune,inflammatory,and metabolic reprogramming.EGFR,RELA,STAT3,FCGR3A,POLR2K,and AXIN1 are hub genes among the HSF4 methylation-related genes.CONCLUSION HSF4 is highly methylated in CRC,but there is no significant correlation between it and the prognosis and diagnosis of CRC.HSF4 methylation may serve as one of the ways in which HSF4 mediates the CRC process.

Anti-diabetic potential of apigenin,luteolin,and baicalein via partially activating PI3K/Akt/GLUT-4 signaling pathways in insulin-resistant HepG2 cells

Dietary flavonoids are abundant in natural plants and possess multiple pharmacological and nutritional activities.In this study,apigenin,luteolin,and baicalein were chosen to evaluate their anti-diabetic effect in high-glucose and dexamethasone induced insulin-resistant(IR)HepG2 cells.All flavonoids improves the glucose consumption and glycogen synthesis abilities in IR-HepG2 cells via activating glucose transporter protein 4(GLUT4)and phosphor-glycogen synthase kinase(GSK-3β).These fl avonoids signifi cantly inhibited the production of reactive oxygen species(ROS)and advanced glycation end-products(AGEs),which were closely related to the suppression of the phosphorylation form of NF-κB and P65.The expression levels of insulin receptor substrate-1(IRS-1),insulin receptor substrate-2(IRS-2)and phosphatidylinositol 3-kinase(PI3K)/protein kinase B(Akt)pathway in IR-HepG2 cells were all partially activated by the fl avonoids,with variable effects.Furthermore,the intracellular metabolic conditions of the fl avonoids were also evaluated.

Role of major adipokines in hypertension:A literature review

The incidence and prevalence of hypertension are increasing as a consequence of the obesity epidemic.Adipocytes and their variety of factors make contributions to the long-term regulation of blood pressure.The pathophysiologic states of hypertension,including obesity,are regulated by the production of adipocytederived factors.Increased body mass index was closely linked to elevated blood pressure.Mostly the hypertensive subjects were obese as well as overweight.There are numerous adipokines,however,this review article only focuses on the major adipokines including chemerin,visfatin,retinol-binding protein 4,plasminogen activator inhibitor-1,monocyte chemotactic protein-1,omentin-1,lipocalin-2,vaspin,progranulin,complement c1q tumor necrosis factor-related protein,and nesfatin-1 role in the pathogenesis of hypertension.This review article concludes the significant association of major adipokines in the pathogenesis of hypertensives.New research should be focused on other newly reported adipokine roles in hypertensive subjects and the management of these adipokines in hypertensive subjects.The discovery of this information could result in the creation of antihypertensive medications,particularly those that focus on obesity-related hypertension.

High expression of autophagy-related gene EIF4EBP1 could promote tamoxifen resistance and predict poor prognosis in breast cancer

BACKGROUND Breast cancer(BC) remains a public health problem. Tamoxifen(TAM) resistance has caused great difficulties for treatment of BC patients. Eukaryotic translation initiation factor 4E binding protein 1(EIF4EBP1) plays critical roles in the tumorigenesis and progression of BC. However, the expression and mechanism of EIF4EBP1 in determining the efficacy of TAM therapy in BC patients are still unclear.AIM To investigate the expression and functions of EIF4EBP1 in determining the efficacy of TAM therapy in BC patients.METHODS High-throughput sequencing data of breast tumors were downloaded from the Gene Expression Omnibus database. Differential gene expression analysis identified EIF4EBP1 to be significantly upregulated in cancer tissues. Its prognostic value was analyzed. The biological function and related pathways of EIF4EBP1 was analyzed. Subsequently, the expression of EIF4EBP1 was determined by real-time reverse transcription polymerase chain reaction and western blotting. Cell Counting Kit-8 assays, colony formation assay and wound healing assay were used to understand the phenotypes of function of EIF4EBP1.RESULTS EIF4EBP1 was upregulated in the TAM-resistant cells, and EIF4EBP1 was related to the prognosis of BC patients. Gene Set Enrichment Analysis showed that EIF4EBP1 might be involved in Hedgehog signaling pathways. Decreasing the expression of EIF4EBP1 could reverse TAM resistance, whereas overexpression of EIF4EBP1 promoted TAM resistance.CONCLUSION This study indicated that EIF4EBP1 was overexpressed in the BC and TAM-resistant cell line, which increased cell proliferation, invasion, migration and TAM resistance in BC cells.

联合检测血清CA125和HE4用于卵巢癌诊断及鉴别诊断

目的探讨人血清CA125和人附睾蛋白4(human epididymis protein 4,HE4)水平在卵巢良恶性肿瘤鉴别诊断中的价值。方法测定187例女性血清标本,其中卵巢癌92例,卵巢良性疾病39例,健康体检女性56例,用微粒子酶免疫法(MEIA)和ELISA法分别测定血清CA125和HE4含量。结果卵巢癌组CA125和HE4水平明显高于其他两组,差异有统计学意义(P<0.01)。健康对照组和良性疾病组HE4比较差异无统计学意义(P>0.05)。以卵巢良性疾病作参照,单独检测血清HE4水平对卵巢癌诊断的敏感性为57.6%,低于单独检测CA125的77.2%;但其特异性为97.0%,高于CA125的85.0%。以二者其中之一高于参考值即视为阳性时,联合检测HE4和CA125对卵巢癌诊断的敏感性为94.6%,特异性可达85.0%。结论联合检测血清CA125和HE4有助于卵巢良恶性肿瘤的诊断与鉴别诊断。

上皮性卵巢癌患者血清CA125、HE4、CEA水平表达及临床意义

目的探讨糖类抗原(CA125)、人附睾蛋白4(HE4)、癌胚抗原(CEA)在上皮性卵巢癌血清中的表达及临床意义。方法选取2013年1—12月新疆医科大学第二附属医院妇产科收治的上皮性卵巢癌50例、良性卵巢肿瘤45例及同期健康体检者45例为研究对象,检测并比较3组血清中CA125、HE4、CEA表达水平,并分析其与上皮性卵巢癌病理特征及预后的关系。结果上皮性卵巢癌组血清CA125、HE4、CEA水平高于健康体检组和卵巢良性肿瘤组(P<0.05),且血清CA125与HE4水平呈明显正相关(r=0.557,P<0.05)。上皮性卵巢癌组血清CA125水平与临床分期、淋巴结转移明显相关(P<0.05),HE4与临床分期、组织分化、淋巴结转移及腹水产生明显相关(P<0.05),而CEA仅与临床分期相关(P<0.05);不同预后患者血清CA125、HE4、CEA水平比较差异均有统计学意义(P<0.05)。结论上皮性卵巢癌患者血清CA125、HE4、CEA水平均与疾病进展相关,且各指标高表达均提示预后不良。

尿液HE4联合CA_(125)检测对卵巢癌的价值初探

目的:探讨人附睾分泌蛋白4(HE4)在血清及尿液中的表达水平及与血清糖类抗原癌抗原125(CA_(125))联合检测诊断卵巢癌的价值及其与卵巢癌临床病理特征的关系。方法:应用E LISA法检测41例卵巢癌、32例卵巢良性肿瘤、30例健康对照血清及尿液HE4含量,比较其单项及联合血清CA_(125)检测在卵巢癌诊断中的敏感性及特异性。结果:①卵巢癌组血清及尿液HE4含量与卵巢良性肿瘤组及健康对照组比较,差异均有统计学意义(P<0.05)。②卵巢癌组血清及尿液HE4含量在手术前后比较差异均有统计学意义(P<0.05)。③血清及尿液HE4含量子宫内膜样癌和浆液性腺癌均高于其他类型卵巢癌(P<0.05)。④血清及尿液HE4诊断卵巢癌的敏感性分别为58.5%和68.3%,特异性分别为83.9%和93.5%,两者间比较差异无统计学意义(P>0.05)。血清及尿液HE4联合血CA_(125)检查诊断卵巢癌的敏感性分别为85.4%和92.7%,特异性分别为85.5%和96.8%,两者间比较差异无统计学意义(P>0.05),尿液HE4联合CA_(125)检测的敏感性、特异性稍高。结论:卵巢癌患者血清及尿液HE4含量均高。尿液HE4联合血清CA_(125)检测可作为卵巢癌高危人群筛查及早期诊断的参考指标。

补中益气汤含药血清对A549/DDP细胞药物泵P-gp及LRP蛋白表达的影响

目的:用补中益气汤含药血清处理A549/DDP细胞,观测药物泵P-gp及LRP的表达,并同小干扰RNA片段(siRNA)靶向切除P-gp、LRP基因后对这两种蛋白表达的影响相比较.方法:补中益气汤含药血清处理A549/DDP细胞,设计并合成针对P-gp、LRP基因对应序列的siRNA,采用转染试剂对细胞进行转染.两种蛋白实验分组均为:空白对照组、含药血清处理组及siRNA处理组.采用RT-PCR检测P-gp及LRP mRNA,免疫细胞化学法检测蛋白表达及定位,WB检测蛋白表达.结果:补中益气汤含药血清可以降低两种药物泵的表达,效果同siRNA类似,具有统计学差异(P<0.05).结论:补中益气汤含药血清能降低A549/DDP细胞上P-gp和LRP的表达.

糖尿病、运动与血清视黄醇结合蛋白4关系的综述

通过文献法综述了糖尿病、运动与血清视黄醇结合蛋白4(RBP4)的关系。结果表明:胰岛素抵抗是2型糖尿病发生发展的重要因素之一。RBP4作为一个脂肪细胞来源的信使,与胰岛素抵抗和2型糖尿病密切相关,RBP4在2型糖尿病胰岛素抵抗机制中起重要作用。血清中RBP4水平的升高可能是导致高胰岛素血症的原因之一,RBP4可能影响胰岛素的敏感性。RBP4削弱骨骼肌的胰岛素信号通路是通过胰岛素受体底物的磷酸化实现的。运动手段是治疗2型糖尿病的主要方法,运动能够降低血清RBP4水平,改善胰岛素抵抗和脂代谢。

探讨血清HE4、CA125与TSGF检测对卵巢癌诊断的价值

目的探讨血清人附睾上皮分泌蛋白(HE4)、糖类抗原125(CA125)和肿瘤特异性生长因子(TSGF)检测在卵巢癌诊断中的价值。方法采用ELISA法检测HE4、化学发光法检测血清CA125,全自动生化法检测TSGF水平。采集85例卵巢癌患者、60例卵巢良性肿瘤患者及55例健康体检者血清,分析各标志物单项和联合检测对卵巢癌的诊断价值。结果卵巢癌患者血清HE4、CA125和TSGF水平均明显高于卵巢良性疾病患者组和健康对照组(P<0.05),HE4、CA125和TSGF在卵巢癌组的阳性检出率分别为64.7%、72.9%和77.6%,与良性卵巢肿瘤组和健康对照组相比,差异有统计学意义(P<0.05)。在卵巢癌单项标志物检测中,血清TSGF的灵敏度(77.8%)优于CA125、HE4;而血清HE4的特异度最高。HE4和TSGF联合检测的约登指数最高(64.8%)。血清HE4、TSGF联合检测对卵巢癌诊断的敏感度和阴性预测值均高于单项检测,分别为88.2%、82.1%,且高于HE4、CA125联合检测。结论在卵巢癌的早期诊断中血清HE4、TSGF联合检测比血清HE4、CA125联合检测更有意义。

人绒毛膜促性腺激素、人附睾蛋白4、糖类抗原199联合检测对卵巢肿瘤的诊断价值

目的:研究人绒毛膜促性腺激素(β-HCG)、人附睾蛋白4(HE4)、糖类抗原199(CA199)联合检测对卵巢肿瘤的诊断价值。方法:选择卵巢肿瘤患者143例作为观察对象。按照术后病理结果分成卵巢癌组68例和良性肿瘤组75例,另选同期接受健康体检的女性志愿者70例作为对照组。对比各组β-HCG、HE4、CA199水平,β-HCG、HE4、CA199单独及联合检测的阳性率,以及分析三者对卵巢癌的诊断价值。结果:卵巢癌组及良性肿瘤组的β-HCG、HE4、CA199水平均分别高于对照组,且卵巢癌组高于良性肿瘤组(P<0.05)。β-HCG、HE4、CA199联合检测卵巢癌的阳性率为89.71%,明显高于良性肿瘤组的48.00%及对照组的2.86%(P<0.05)。经ROC曲线分析发现,β-HCG、HE4、CA199联合诊断卵巢癌的价值最高,其灵敏度为82.34%,准确度为89.71%,曲线下面积为0.713。结论:β-HCG、HE4、CA199联合检测对卵巢肿瘤的诊断价值较高,值得引起临床的重视。

糖尿病肾病患者血清RBP4水平与颈动脉病变的相关性分析

目的：探讨糖尿病肾病（DN）患者血清RBP4水平与颈动脉病变的相关性。方法：收集2013年~2014年本院住院DN患者345例,应用独立样本间t检验、双变量相关分析以及Pearson’s检验对患者血清RBP4水平和颈动脉病变的相关性进行分析。结果：随着血清RBP4水平上升,颈动脉斑块、颈动脉狭窄发病率上升,平均颈动脉内膜中层厚度与颈动脉斑块、狭窄、e GFR相关（P〈0.05）;RBP4水平与CIMT差异无统计学意义（P〉0.05）。结论：血清RBP4水平与DN患者颈动脉斑块、狭窄发病率呈正相关。

重组人骨形成蛋白成熟肽4对急性放射损伤小鼠造血系统的修复作用

目的探讨重组人骨形成蛋白成熟肽-4(rhBMP-4m)对^(60)Coγ射线照射引起的小鼠造血系统损伤的修复作用。方法 90只BALB/c小鼠随机分为正常对照组、模型组和rhBMP-4m治疗组,每组30只。模型组和rhBMP-4m治疗组小鼠接受^(60)Coγ射线照射,照射剂量7 Gy,全身照射200 s;正常对照组小鼠不接受照射。模型组小鼠每日腹腔注射生理盐水1.0 mL,rhBMP-4m治疗组小鼠每日腹腔注射rhBMP-4m 0.5 mg,连续治疗6 d。分别于照射后第1、3、5、7、9天检测小鼠外周血白细胞数、骨髓单个核细胞数、骨髓单个核细胞中CD34^+细胞比例;照射后第9天进行脾结节计数,并计算脾脏质量与体质量的比值(脾体比)。结果照射后第1天3组小鼠外周血白细胞计数比较差异均无统计学意义(P>0.05);照射后第3、5、7、9天模型组小鼠外周血白细胞计数低于正常对照组(P<0.01);照射后第3、5天rhBMP-4m治疗组小鼠外周血白细胞计数与模型组比较差异无统计学意义(P>0.05),照射后第7、9天rhBMP-4m治疗组小鼠外周血白细胞计数高于模型组(P<0.05)。模型组小鼠照射后各时间点骨髓单个核细胞计数均低于正常对照组(P<0.01)。照射后第1、3天rhBMP-4m治疗组小鼠骨髓单个核细胞计数与模型组比较差异无统计学意义(P>0.05),照射后第5、7、9天rhBMP-4m治疗组小鼠骨髓单个核细胞计数高于模型组(P<0.05)。模型组小鼠照射后各时间点的单个核细胞中CD34^+细胞百分率均低于正常对照组(P<0.01)。rhBMP-4m治疗组小鼠照射后第1、3天单个核细胞中CD34^+细胞百分率与模型组比较差异均无统计学意义(P>0.05),照射后第5、7、9天rhBMP-4m治疗组小鼠单个核细胞中CD34^+细胞的百分率高于模型组(P<0.05)。照射后第9天,模型组小鼠脾结节计数高于正常对照组,脾体比低于正常对照组(P<0.05);rhBMP-4m治疗组小鼠脾结节计数和脾体比高于模型组(P<0.01)。结论辐射可引起小鼠骨髓造血系统损伤,rhBMP-4m能够促进骨髓造血系统的重建。

Critical role of cytochrome c1 and its cleavage in porcine reproductive and respiratory syndrome virus nonstructural protein 4-induced cell apoptosis via interaction with nsp4

Porcine reproductive and respiratory syndrome virus.（PRRSV） actively induces cell apoptosis both in vitro and in vivo, which can contribute critically to viral pathogenesis. Previous studies have shown that the PRRSV nonstructural protein 4 （nsp4） is an important mediator of this process, but the underlying molecular details remain poorly understood. In this study, we found that the PRRSV nsp4 interacted with the mitochondrial inner membrane protein cytochrome cl （cyto.cl） and induced its proteolytic cleavage. Interestingly, the cleaved N-terminal fragment of cyto.cl was found to exert apoptotic activity, which could cause mitochondrial fragmentation, resulting in apoptotic cell death. And RNA interference （RNAi） silencing experiments further confirmed the crucial role which cyto.cl played in nsp4- and PRRSV-induced cell apoptosis. Thus, our data provide an important piece of mechanistic clues for PRRSV-induced cell apoptosis and also elucidate a novel mechanism for the 3C-like proteases in this finding.

STIP1、HE4和CA125对卵巢癌的诊断(英文)

Although many tumor markers have been identified and studied in epithelial ovarian cancer,a potential and useful screening marker for ovarian cancer has not been yet clearly established. Ovarian cancer is considered as a "silent killer"because of the absence of specific symptoms until late stage. Several validated biomarkers are currently used to diagnose and monitor the progression of the cancer,but very few of them show adequate specificity and sensitivity for different population screening. There is therefore an urge need to find biomarkers with high diagnostic accuracy and set up screening programs which can help detect ovarian cancer early,predict the response of the patient to anticancer therapy and guide physicians in choosing the best treatment for the patient. CA125,HE4 and STIP1 have been proven to play an important role as biomarkers in detecting and monitoring ovarian cancer. In this paper,we review evaluate,and highlight the role of CA125,HE4 and STIP1 in the detection of ovarian cancer.Potential biomarkers can help us distinguish malignancy from benign pelvic mass.