AAV mediated carboxyl terminus of Hsp70 interacting protein overexpression mitigates the cognitive and pathological phenotypes of APP/PS1 mice

The E3 ubiquitin ligase,carboxyl terminus of heat shock protein 70(Hsp70)interacting protein(CHIP),also functions as a co-chaperone and plays a crucial role in the protein quality control system.In this study,we aimed to investigate the neuroprotective effect of overexpressed CHIP on Alzheimer’s disease.We used an adeno-associated virus vector that can cross the blood-brain barrier to mediate CHIP overexpression in APP/PS1 mouse brain.CHIP overexpression significantly ameliorated the performance of APP/PS1 mice in the Morris water maze and nest building tests,reduced amyloid-βplaques,and decreased the expression of both amyloid-βand phosphorylated tau.CHIP also alleviated the concentration of microglia and astrocytes around plaques.In APP/PS1 mice of a younger age,CHIP overexpression promoted an increase in ADAM10 expression and inhibitedβ-site APP cleaving enzyme 1,insulin degrading enzyme,and neprilysin expression.Levels of HSP70 and HSP40,which have functional relevance to CHIP,were also increased.Single nuclei transcriptome sequencing in the hippocampus of CHIP overexpressed mice showed that the lysosomal pathway and oligodendrocyte-related biological processes were up-regulated,which may also reflect a potential mechanism for the neuroprotective effect of CHIP.Our research shows that CHIP effectively reduces the behavior and pathological manifestations of APP/PS1 mice.Indeed,overexpression of CHIP could be a beneficial approach for the treatment of Alzheimer’s disease.

Effect of Ultraviolet Radiation on Hsp70 Protein Expression in HaCaT Cells

Ultraviolet radiation by its wavelength is divided into: UVA, UVB and UVC. Only UVA and UVB manage to penetrate the ozone layer, but due to anthropological activities, all of them are capable of interacting with humans to a greater or lesser extent, and can generate adverse effects such as cellular stress when interacting with intra-and extracellular biomolecules. The skin is the first organ in contact with UV radiation, and the stress it generates can be analyzed by the expression of a bioindicator of cellular damage such as Hsp70. Therefore, the objective of the project was: to determine the effect of UVA, UVB and UVC radiation on HaCaT epithelial cells, by analyzing the expression of Hsp70. Materials and methods: HaCaT cells were cultured in vitro, which were irradiated with UVA, UVB and UVC light at different doses, to subsequently determine the degree of Hsp70 expression by Immunodetection by PAGE-SDS and Western Blot. Results: Basal expression of Hsp70 was observed in no irradiated HaCaT cells. When HaCaT cells were irradiated with UVA, UVB, UVC, an increase in this Hsp70 protein was observed. With UVA, a higher degree of expression was observed at a time of 30 minutes of irradiation. With UVB the highest expression shifted to a time of 20 minutes. With UVC, overexpression was observed after 10 minutes. Conclusion: UV radiation generates cellular stress on HaCaT cells, evaluated by the stress bioindicator Hsp70. According to the wavelength of UV radiation, those that have a shorter wavelength have a greater potential for cellular damage, such as UVC.

超重/肥胖合并2型糖尿病患者血清ANGPTL4、HSP70、IL-34水平与胰岛素抵抗的相关性

目的 探讨超重/肥胖合并2型糖尿病(T2DM)患者血清血管生成素样蛋白4(ANGPTL4)、热休克蛋白(HSP)70、白细胞介素-34(IL-34)水平与胰岛素抵抗的相关性。方法 选取2020年5月—2022年5月保定市第一中心医院T2DM患者182例(T2DM组)。参考相关诊断标准,将T2DM患者分为超重/肥胖T2DM组(90例)和体重正常T2DM组(92例)。另选取同期健康体检者90名作为正常对照组,其中超重/肥胖者40名(超重/肥胖对照组)、体重正常者50名(体重正常对照组)。检测所有研究对象血清ANGPTL4、HSP70、IL-34、胰岛素和血糖水平,计算稳态模型胰岛素抵抗指数(HOMA-IR)。T2DM患者治疗3个月后,再次检测其血清ANGPTL4、HSP70、IL-34水平和HOMA-IR。采用Pearson相关分析评估血清ANGPTL4、HSP70、IL-34与HOMA-IR的相关性。结果 与正常对照组和体重正常T2DM组比较,超重/肥胖T2DM组血清ANGPTL4和HSP70显著降低(P<0.05),血清IL-34和HOMA-IR显著升高(P<0.05)。与正常对照组比较,体重正常T2DM组血清ANGPTL4和HSP70显著降低(P<0.05),血清IL-34和HOMA-IR显著升高(P<0.05)。Pearson相关分析结果显示,血清ANGPTL4、HSP70与HOMA-IR呈负相关(r值分别为-0.733、-0.758,P<0.001),IL-34和HOMA-IR呈正相关(r=0.705,P<0.001)。治疗后,超重/肥胖T2DM组和体重正常T2DM组血清ANGPTL4和HSP70均明显升高,血清IL-34和HOMA-IR明显降低;且相对于超重/肥胖T2DM组,体重正常T2DM组血清ANGPTL4和HSP70升高更显著(P<0.05),血清IL-34和HOMA-IR降低更显著(P<0.05)。结论 超重/肥胖合并T2DM患者ANGPTL4、HSP70和IL-34与胰岛素抵抗显著相关,或可作为超重/肥胖合并T2DM的疗效监测指标。

老年重症急性胰腺炎继发胰腺感染的病原菌分布及其与血清PCT、PA、FIB、HSP70和HMGB1的相关性

目的探讨老年重症急性胰腺炎继发胰腺感染患者的病原菌分布及其与血清降钙素原(PCT)、前白蛋白(PA)、纤维蛋白原(FIB)、热休克蛋白70(HSP70)、高迁徙率族蛋白1(HMGB1)水平的相关性。方法选择2019年1月至2022年12月东莞东华医院收治的62例老年重症急性胰腺炎患者作为研究对象,根据是否继发胰腺感染分为感染组20例和未感染组42例,另选择同期健康体检的80例健康者作为对照组。记录感染组患者病原菌分布情况,比较三组受试者及感染组不同病原菌感染类型患者的血清PCT、PA、FIB、HSP70和HMGB1水平,并采用Pearson相关性分析法分析血清PCT、PA、FIB、HSP70及HMGB1水平和胰腺感染的相关性。结果感染组患者病原菌感染类型主要为细菌感染,占90.00%,其中细菌感染类型中革兰阴性菌占55.00%,革兰阳性菌占35.00%;感染组患者血清PCT、HSP70、HMGB1水平分别为(2.49±0.53)μg/L、(9.12±1.86)ng/mL、(18.33±2.61)ng/mL,明显高于未感染组的(1.56±0.41)μg/L、(5.73±1.45)ng/mL、(13.62±2.47)ng/mL和对照组的(0.23±0.06)μg/L、(0.97±0.13)ng/mL、(0.73±0.15)ng/mL,PA、FIB分别为(0.17±0.02)g/L、(2.06±0.21)g/L,明显低于未感染组的(0.23±0.04)g/L、(2.75±0.30)g/L和对照组的(0.30±0.03)g/L、(3.23±0.36)g/L,且未感染组患者的血清PCT、HSP70、HMGB1水平均高于对照组,PA、FIB均低于对照组,差异均有统计学意义(P<0.05);感染组细菌感染患者的血清PCT、HSP70、HMGB1水平分别为(2.74±0.31)μg/L、(11.06±1.43)ng/mL、(20.68±2.05)ng/mL,明显高于真菌感染患者的(2.13±0.25)μg/L、(7.93±1.05)ng/mL、(16.27±1.76)ng/mL,PA、FIB水平分别为(0.11±0.02)g/L、(1.91±0.24)g/L,明显低于真菌感染患者的(0.17±0.04)g/L、(2.58±0.34)g/L,差异均有统计学意义(P<0.05);经Pearson相关性分析结果显示,血清PCT、HSP70、HMGB1与胰腺感染呈正相关(r=0.581、0.613、0.567,P<0.05),与PA、FIB呈负相关(r=-0.463、-0.531,P<0.05)。结论老年重症急性胰腺炎继发胰腺感染患者的病原菌类型主要为细菌感染,患者血清PCT、HSP70、HMGB1水平明显升高,PA、FIB明显降低,且与胰腺感染的发生有明显相关性,临床上应予以密切关注。

春尺蠖热激蛋白AcinHsp70基因的克隆、分子特性与表达分析

【目的】克隆春尺蠖热激蛋白Hsp70基因,分析其理化性质与表达情况,探究该基因在春尺蠖应对外界不利环境中的作用。【方法】基于前期所测转录组数据(春尺蠖幼虫不同低温胁迫),克隆获取Hsp70基因,命名为AcinHsp70(GenBank登录号:OP750249);利用生物信息分析软件对Hsp70基因的理化性质进行分析;采用qPCR技术检测AcinHsp70基因在不同温度(-10、-5、0、5和25℃)胁迫中回温与不回温及4℃不同时间处理下的表达谱。【结果】春尺蠖AcinHsp70基因完整CDS序列全长1899 bp,编码633个氨基酸,蛋白质预测分子量为69.91 kDa,预测等电点为5.51。在N端均不含信号肽且无跨膜区。磷酸位点检测分别发现丝氨酸、苏氨酸和酪氨酸磷酸位点24、26和8个;未发现糖基化位点。该蛋白的平均亲水性为-0.507,预测不稳定系数为33.19,故该蛋白属于亲水稳定蛋白,亚细胞定位结果显示,其主要位于细胞质。序列一致性比对与系统进化树分析结果显示,春尺蠖与庆网蛱蝶(Melitaea cinxia)亲缘关系最近,序列一致性达92.91%。基因表达结果显示,不同温度(-10℃除外)胁迫下,AcinHsp70基因表达量均无明显差异,回温后表达量显著上调。AcinHsp70基因表达量总体呈先升后降趋势,在4℃处理1 h后表达量达到最大值。【结论】AcinHsp70基因与春尺蠖应对低温胁迫的响应密切相关,结果有助于揭示该基因在低温胁迫下的分子功能。

Glutamine supplementation attenuates intestinal apoptosis by inducing heat shock protein 70 in heatstroke rats

BACKGROUND:Heatstroke is the most hazardous heat-related illness and has a high fatality rate.We investigated whether glutamine supplementation could have a protective effect on heatstroke rats.METHODS:Twenty-five 12-week-old male Wistar rats(weight 305±16 g)were randomly divided into a control group(n=5),heatstroke(HS)group(n=10),and heatstroke+glutamine(HSG)group(n=10).Seven days before heat exposure,glutamine(0.4 g/[kg·d])was administered to the rats in the HSG group by gavage every day.Three hours after heat exposure,serum samples were collected to detect white blood cells,coagulation indicators,blood biochemical indicators,and inflammatory cytokines in the rats.The small intestine tissue was stained to analyze pathological structural changes and apoptosis.Finally,immunohistochemistry and Western blotting were used to analyze the expression levels of heat shock protein 70(HSP70).Multiple comparisons were analyzed by using one-way analysis of variance,and the Bonferroni test was conducted for the post hoc comparisons.RESULTS:After heat exposure,the core temperature of the HS group(40.65±0.31°C)was higher than the criterion of heatstroke,whereas the core temperature of the HSG group(39.45±0.14°C)was lower than the criterion.Glutamine supplementation restored the increased white blood cells,coagulation indicators,blood biochemical indicators,and inflammatory cytokines that were induced by heatstroke to normal levels.The intestinal mucosa was injured,and the structure of tight junctions was damaged in the HS group;however,the structure of intestinal mucosal epithelial cells was stable in the HSG group.Glutamine supplementation alleviated intestinal apoptosis and up-regulated HSP70 expression.CONCLUSION:Glutamine supplementation may alleviate intestinal apoptosis by inducing the expression of HSP70 and have a protective effect on heatstroke rats.

血清HSP70、PKD1、YKL-40对绝经后早期子宫内膜癌淋巴结转移的预测效能

目的:探讨血清热休克蛋白70(HSP70)、蛋白激酶D1(PKD1)、甲壳质酶蛋白40(YKL-40)与绝经后早期子宫内膜癌淋巴结转移的关系及预测效能。方法:选取2021年3月至2023年3月中国人民解放军联勤保障部队第九八〇医院收治的126例绝经后早期子宫内膜癌患者(研究组),根据术后病理诊断结果分为淋巴结转移组(n=22)和非淋巴结转移组(n=104)。另选取114例健康体检者作为对照组。比较各组血清HSP70、PKD1和YKL-40水平。采用多因素logistic回归分析方法分析影响患者发生淋巴结转移的因素,受试者工作特征(ROC)曲线分析血清HSP70、PKD1和YKL-40水平对患者淋巴结转移的预测价值。结果:研究组血清HSP70、PKD1和YKL-40水平均高于对照组(P<0.05)。淋巴结转移组患者低分化、子宫肌层浸润≥50%及血清CA125、HE4、HSP70、PKD1和YKL-40水平高于非淋巴结转移组(P<0.05)。多因素logistic回归分析显示,血清HE4、HSP70、PKD1和YKL-40水平及子宫肌层浸润≥50%均为绝经后早期子宫内膜癌患者发生淋巴结转移的独立危险因素(均P<0.05)。血清HSP70、PKD1和YKL-40水平预测绝经后早期子宫内膜癌患者发生淋巴结转移的最佳截断点分别为90.82μg/L、132.23μg/L、75.32μg/L,三者联合预测的灵敏度、特异度和ROC曲线下面积(AUC)分别为81.82%、96.15%、0.940。结论:早期子宫内膜癌患者血清HSP70、PKD1、YKL-40水平可作为预测淋巴结转移的敏感指标,且三者联合预测的预测效能更高。

血清ANXA1、Hsp70、Hsp90α与局部晚期宫颈癌患者新辅助化疗疗效的关系分析

目的探讨血清膜联蛋白A1(ANXA1)、热休克蛋白70(Hsp70)、热休克蛋白90α(Hsp90α)与局部晚期宫颈癌(LACC)患者新辅助化疗(NACT)疗效的关系。方法选择2020年1月至2023年1月在该院进行NACT治疗的157例LACC患者为研究对象,根据NACT疗效分为有效组和无效组。比较两组化疗前血清ANXA1、Hsp70、Hsp90α水平,采用多因素Logistics回归分析NACT疗效的影响因素,采用受试者工作特征(ROC)曲线分析血清ANXA1、Hsp70、Hsp90α对LACC患者NACT无效的预测价值。结果有效组(126例)血清ANXA1水平高于无效组(31例),血清Hsp70、Hsp90α水平低于无效组,差异有统计学意义(P<0.05)。单因素分析显示,有效组国际妇产科联盟大会(FIGO)分期为ⅡA2期患者占比、低/未分化患者占比、有淋巴结转移患者占比,以及化疗前CA125、CA199水平低于无效组,差异有统计学意义(P<0.05)。多因素Logistic回归分析显示,血清Hsp70水平升高、血清Hsp90α水平升高、FIGO分期为ⅡA2期和CA199水平升高是影响LACC患者NACT疗效的独立危险因素(P<0.05),ANXA1水平升高是保护因素(P<0.05)。血清ANXA1、Hsp70、Hsp90α及3项指标联合检测预测LACC患者NACT无效的曲线下面积(AUC)分别为0.836、0.789、0.717和0.941。结论血清ANXA1、Hsp70、Hsp90α与LACC患者NACT疗效有关,3项指标联合检测对LACC患者NACT疗效具有较高的预测价值。

来曲唑联合地塞米松对多囊卵巢综合征患者血清Galectin-3及HSP70的影响

目的 探讨来曲唑联合地塞米松对多囊卵巢综合征(PCOS)患者血清半乳糖凝集素-3(Galectin-3)及热休克蛋白(HSP70)表达的影响。方法 选择2019年6月—2021年6月在我院治疗的PCOS患者220例为研究对象,按随机数表法分为对照组(n=110)和观察组(n=110),对照组常规给予来曲唑治疗。观察组在对照组的基础上加用地塞米松联合治疗。观察并比较两组患者的激素水平,促排卵情况,血清抗苗勒管激素(AMH)、Galectin-3、HSP70及单核细胞趋化蛋白-1(MCP-1)水平及不良反应发生率。结果 治疗后两组患者的性激素水平均改善,且观察组变化幅度高于对照组(P<0.05)。观察组患者雌二醇(E_(2))用量低于对照组,成熟卵泡数量和最大卵泡直径均高于对照组(均P<0.05)。两组患者的早期流产率差异无统计学意义(P>0.05);观察组患者的妊娠率高于对照组(P<0.05)。治疗前两组患者AMH、Galectin-3、HSP70、MCP-1水平差异无统计学意义(P>0.05),治疗后两组患者的AMH、Galectin-3、HSP70、MCP-1水平均降低,且观察组低于对照组(P<0.05)。观察组和对照组分别有35例和34例出现胃肠道反应、头痛、乳房胀痛等不良反应,两组差异无统计学意义(χ^(2)=0.021,P=0.885)。结论 来曲唑联合地塞米松可能减轻氧化应激反应,减轻胰岛素抵抗,调节激素水平,促进排卵,安全性高,值得推广应用。

原发性肝癌患者高强度聚焦超声治疗前后HSP70、PTN、PIVKA-Ⅱ水平变化及对早期复发的预测效能

目的探究原发性肝癌(PHC)患者在高强度聚焦超声(HIFU)治疗前后热休克蛋白70(HSP70)、多效生长因子(PTN)、异常凝血酶原Ⅱ(PIVKA-Ⅱ)水平变化及对早期复发的影响和预测效能。方法选取2021年1月—2023年1月收治的PHC 120例,均行HIFU治疗,根据术后6个月是否复发分为复发组(26例)与未复发组(94例)。比较2组临床资料、治疗前后血清HSP70、PTN、PIVKA-Ⅱ水平及变化值(ΔHSP70、ΔPTN、ΔPIVKA-Ⅱ值),分析ΔHSP70、ΔPTN、ΔPIVKA-Ⅱ与HIFU治疗后早期复发的相关性,并评价预测效能。结果2组治疗后血清HSP70、PTN、PIVKA-Ⅱ水平较治疗前下降(P<0.05);复发组治疗前、治疗后血清HSP70、PTN、PIVKA-Ⅱ水平高于未复发组(P<0.01)。复发组血清ΔHSP70、ΔPTN、ΔPIVKA-Ⅱ值低于未复发组(P<0.01)。Spearman相关性分析显示,治疗前血清HSP70、PTN、PIVKA-Ⅱ与肿瘤直径、CNLC分期呈正相关,与分化程度呈负相关(P<0.01)。多因素Logistic回归分析显示,校正肿瘤直径、CNLC分期、分化程度因素前后血清ΔHSP70、ΔPTN、ΔPIVKA-Ⅱ值均与PHC患者HIFU治疗后早期复发独立相关(P<0.01);血清ΔHSP70、ΔPTN、ΔPIVKA-Ⅱ值联合预测PHC患者HIFU治疗后早期复发的曲线下面积为0.916(95%CI:0.851,0.958),敏感度为0.923,特异度为0.872,优于三者单独预测。结论PHC患者HIFU治疗前后HSP70、PTN、PIVKA-Ⅱ水平变化值与早期复发独立相关,且联合预测效能较高。

Hcy、HSP70、H-FABP对脑梗死患者的疗效评估作用

目的探讨同型半胱氨酸(Hcy)、热休克蛋白70(HSP70)、心型脂肪酸结合蛋白(H-FABP)对丁苯酞联合通窍活血汤治疗脑梗死患者的疗效评估作用。方法选取鹿邑县人民医院2021年10月至2022年10月收治的82例脑梗死患者作为研究对象,给予丁苯酞联合通窍活血汤治疗。比较有效组和无效组的临床资料及血清学指标,Logistic回归分析影响治疗效果的因素,分析血清Hcy、HSP70、H-FABP单独及联合检测预测治疗效果的价值并编制ROC曲线。结果治疗14 d后,显效38例、有效30例、无效14例,治疗有效率为82.93%。其中有效组68例,无效组14例;有效组Hcy、HSP70、H-FABP水平均低于无效组;Hcy、HSP70、H-FABP均是影响脑梗死患者治疗效果的危险因素;血清Hcy、HSP70、H-FABP联合检测预测治疗效果的AUC值高于单项检测,差异有统计学意义(Z_(Hcy)=3.038,Z_(HSP70)=2.411,Z_(H-FABP)=2.352,P<0.05)。结论血清Hcy、HSP70、H-FABP联合检测对丁苯酞联合通窍活血汤治疗的脑梗死患者的临床疗效具有一定预测价值。

Contraction of Heat Shock Protein 70 Genes Uncovers Heat Adaptability of Ostrea denselamellosa

The milin oyster Ostrea denselamellosa is a live-bearing species with a sharp decline in the natural population.Unlike other oysters,O.denselamellosa lives in the subtidal zone and its adaptability to heat,salinity,etc.is different from most other oys-ters.Heat shock proteins 70(HSP70)are a family of conserved ubiquitously expressed heat shock proteins which are produced in re-sponse to stressful conditions,especially heat.In this study,we identified Hsp70 genes through bioinformatic analysis in five species of oyster.Among them,O.denselamellosa holds the fewest number of Hsp70 genes,which may be one of the reasons why O.den-selamellosa cannot tolerate high temperatures.The conserved motifs and gene structures of Hsp70B2 sub-family and other types of Hsp70 in O.denselamellosa were different from that of Hspa12 sub-family,which may be due to performing necessary multiple phy-siological functions.Transcription profile analysis for Hsp70 genes of O.denselamellosa indicated that gills play an important role in responding to multiple external challenges.In addition,synteny analysis of Hsp70 genes among O.denselamellosa,O.edulis and Cras-sostrea ariakensis showed that Hsp70 genes in genus of Ostrea genome might have evolved from a common ancestor with genus of Crassostrea.In short,our results lay the foundation for further investigation of the evolution of O.denselamellosa Hsp70 genes and heat adaptability.

Effect of chaperone–client interaction strength on Hsp70-mediated protein folding

Protein folding in crowding cellular environment often relies on the assistance of various chaperones. Hsp70 is one of the most ubiquitous chaperones in cells. Previous studies showed that the chaperone–client interactions at the open state tend to remodel the protein folding energy landscape and direct the protein folding as a foldase. In this work, we further investigate how the chaperone–client interaction strength modulates the foldase function of Hsp70 by using molecular simulations. The results showed that the time of substrate folding(including the whole folding step and substrate release step) has a non-monotonic dependence on the interaction strength. With the increasing of the chaperone–client interaction strength, the folding time decreases first, and then increases. More detailed analysis showed that when the chaperone–client interaction is too strong, even small number of chaperones–client contacts can maintain the substrate bound with the chaperone. The sampling of the transient chaperones–client complex with sparse inter-molecule contacts makes the client protein have chance to access the misfolded state even it is bound with chaperone. The current results suggest that the interaction strength is an important factor controlling the Hsp70 chaperoning function.

Heat-shock protein 70 expression in shrimp Fenneropenaeus chinensis during thermal and immune-challenged stress

Using western immunoblotting, we obtained heat-shock protein 70 (HSP70) induction data and distribution in different tissues from shrimp Fenneropenaeus chinensis during thermal and immune-challenged stresses. This is probably the first report of the effects of various stressors on the expression of HSP70 in shrimp. HSP70 was prominently induced in hepatopancreas and gills, but not in muscle, eyestalk and hemolymph, when the shrimp were exposed to heat shock and Vibrio anguillavium-challenged stresses. Cold shock and WSSV treatment had no significant effects on the levels of HSP70 expression in all tissues examined. HSP70 induction was greatest after 2 h exposure to heat shock stress, which was elevated after acute heat shock exposure of 10℃ above ambient temperature.

Expression of Heat Stress Protein 70 mRNA in Patients with Chronic Obstructive Pulmonary Disease and Its Significance

The effects of cigarette smoke extract (CSE) on the expression of heat stress protein 70 (Hsp70) in human bronchi smooth muscle cells were investigated in vitro, and the changes in Hsp70 mRNA in the patients with chronic obstructive pulmonary disease and their significance were explored. Human bronchi smooth muscle cells were cultured with CSE at the different concentrations. The expression of Hsp70 mRNA and Hsp70 was detected by reverse translation-polymerase chain reaction (RT-PCR) and Western blotting respectively. Levels of Hsp70 mRNA and Hsp70 in lymphocytes from 20 patients with COPD and 20 healthy smoking control subjects were measured by RT-PCR and Western blotting. The results showed the expression of both Hsp70 mRNA and Hsp70 was decreased conformably in human bronchi smooth muscle cells treated with CSE at certain concentration in vitro. The A values of the Hsp70 mRNA expression were 0.24±0.11 and 0.42±0.13 respectively in COPD patients and healthy smoking controls with the difference being significant (P<0.01). There was also significant difference in the A values of the Hsp70 expression between COPD patients and healthy smoking controls (20.9±9.9 vs 44.8±15.3, P<0.01). The levels of Hsp70 mRNA had strongly positive correlation with Hsp70 protein (r = 0.85, P<0 01). It was suggested that the expression of Hsp70 mRNA was in concordance with the expression of Hsp70, which could provide a basis on the study of Hsp70 gene regulation and Hsp70 gene in the development of COPD.

Novel heat shock protein Hsp70L1 activates dendritic cells and acts as a Th1 polarizing adjuvant

Heat shock proteins (HSPs) are reported to act as effective adjuvants to elicit anti-tumor and anti-infection immunity. Here, we report that Hsp70-like protein 1 (Hsp70L1), a novel HSP derived from human dendritic cells (DCs), has potent adjuvant effects that polarize responses toward Th1. With a calculated molecular weight of 54.8 kDa, Hsp70L1 is smaller in size than Hsp70 but resembles it both structurally and functionally. Hsp70L1 shares common receptors on DCs with Hsp70 and can interact with DCs, promoting DC maturation and stimulating secretion of the proinflammatory cytokines interleukin 12p70 (IL-12p70), IL-1beta, tumor necrosis factor-alpha (TNF-alpha), and the chemokines IP-10, macrophage inflammatory protein-1alpha (MIP-1alpha), MIP-1beta, and normal T cell expressed and secreted (RANTES). The induction of interferon-gamma-inducible protein 10 (IP-10) secretion by Hsp70L1 is not shared by Hsp70, and other functional differences include more potent stimulation of DC IL-12p70, CC-chemokine, and CCR7 and CXCR4 expression by Hsp70L1. Immunization of mice with the hybrid peptide Hsp70L1-ovalbumin(OVA)(257-264) induces an OVA(257-264)-specific Th1 response and cytotoxic T lymphocyte (CTL) that results in significant inhibition of E.G7-OVA tumor growth. The ability of Hsp70L1 to activate DCs indicates its potential as a novel adjuvant for use with peptide immunizations; the Hsp70L1 antigen peptide hybrid may serve as a more effective vaccine for the control of cancer and infectious diseases.

EXPERIMENTAL STUDY ON MOXIBUSTION AT ZUSANLI(ST 36) AND LIANGMEN (ST 21) INDUCING HEAT SHOCK PROTEIN 70 (HSP70) EXPRESSION TO RESIST OXIDATIVE INJURY OF GASTRIC MUCOSA

Objective: To observe effect of moxibustion at Zusanli (足三里 ST 36) and Liangmen (梁门 ST 21) on expression of heat shock protein 70 (HSP70) in gastric mucosa of the rat of stress ulcer (SU) to explore the mechanism of moxibustion in resisting oxidative injury of the gastric mucosa. Methods: Sixty SD rats were evenly randomized into 4 groups, a blank group, a model group, an acupoint moxibustion group and a non-acupoint moxibustion group. Water restraint stress (WRS) method was used to make stress gastric ulcer rat model. The ulcerative index (UI) of gastric mucosa was evaluated by using GUTH method, the gastric mucosa blood flux (GMBF) was detected by a laser Doppler bloodflow monitor, and HSP70 expression and malondialdehyde (MDA) content in the gastric mucosa were determined respectively with immunohistochemical and thiobarbiturate methods. Results: Moxibustion at Zusanli (ST 36) and Liangmen (ST 21) significantly decreased UI, up-regulated HSP70 expression, increased GMBF, and decreased MDA content in the gastric mucosa in the rat of stress gastric ulcer, with significant differences as compared with the model group and the non-acupoint moxibustion group (P<0.05 or P<0.01). Conclusion: Moxibustion at Zusanli (ST 36) and Liangmen (ST 21) can induce high expression of HSP70 and decrease MDA content in the gastric mucosa, so as to resist oxidative injury, with relative acupoint specificity.

G-17、SOX-2、HSP70在Hp感染胃炎中的表达及意义

目的 探讨胃泌素17(gastrin-17,G-17)、性别决定区Y框蛋白2(sex-determining region Y box protein-2,SOX-2)、热休克蛋白70(heat shock protein 70,HSP70)在幽门螺杆菌(helicobacter pylori, Hp)感染胃炎中的表达及意义。方法 选取慢性胃炎患者90例,根据是否合并Hp感染将其分为Hp阳性组和Hp阴性组,每组45例。比较2组一般资料,G-17、HSP70水平及SOX-2、HSP70表达情况。分析Hp阳性患者G-17、SOX-2、HSP70与各指标的相关性;多因素Logistic回归分析影响Hp感染胃炎的危险因素。结果 Hp阳性组共餐饮食方式比例、临床症状积分高于Hp阴性组,胃蛋白酶原Ⅰ(pepsinogenⅠ,PG-Ⅰ)、胃蛋白酶原Ⅱ(pepsinogenⅡ,PG-Ⅱ)水平低于Hp阴性组(P<0.05)。Hp阳性组G-17水平低于Hp阴性组,HSP70水平及SOX-2阳性、HSP70阳性表达率高于Hp阴性组(P<0.05)。Hp阳性患者中,G-17与PG-Ⅰ、PG-Ⅱ呈正相关,与临床症状积分呈负相关,SOX-2、HSP70与PG-Ⅰ、PG-Ⅱ呈负相关,与临床症状积分呈正相关(P<0.05)。Logistic回归分析结果显示,饮食方式、PG-Ⅱ、G-17、SOX-2、HSP70是影响Hp感染胃炎患者的危险因素(P<0.05)。结论 G-17在Hp感染胃炎患者中水平较低,SOX-2、HSP70阳性表达较高,饮食方式、PG-Ⅱ、G-17、SOX-2、HSP70是影响Hp感染胃炎患者的危险因素。

脑梗死合并OSAHS患者血清MCP-1、HSP70、AOPP的表达水平及临床意义

目的探讨脑梗死合并阻塞性睡眠呼吸暂停低通气综合征(OSAHS)患者血清单核细胞趋化蛋白-1(MCP-1)、热休克蛋白70(HSP70)、晚期氧化蛋白产物(AOPP)的表达水平及其临床意义。方法回顾性分析2019年1月至2021年1月在西安医学院第二附属医院诊治的153例脑梗死患者的临床资料,按照是否合并OSAHS分为合并OSAHS组96例和未合并OSAHS组57例。检测并比较两组患者的血清MCP-1、HSP70、AOPP水平及呼吸暂停低通气(AHI)指数。按照AHI指数将合并OSAHS组患者分为轻度OSAHS组(5≤AHI<15,27例)、中度OSAHS组(15≤AHI≤30,46例)和重度OSAHS组(AHI>30,23例)三个亚组,比较三组患者的MCP-1、HSP70、AOPP水平。选择Spearman相关分析MCP-1、HSP70、AOPP与AHI指数的相关性。结果合并OSAHS组患者的MCP-1、HSP70、AOPP、AHI指数分别为(168.87±21.65)ng/L、(2.79±0.36)μg/L、(115.27±25.26)μmol/L、(26.72±5.03)次/h,明显高于未合并OSAHS组的(143.25±15.54)ng/L、(1.47±0.25)μg/L、(87.15±12.94)μmol/L、(8.14±2.18)次/h,差异均有统计学意义(P<0.05);重度OSAHS组患者的MCP-1、HSP70、AOPP水平分别为(226.52±26.05)ng/L、(3.88±1.35)μg/L、(132.66±28.11)μmol/L,明显高于轻度OSAHS组的(109.58±19.27)ng/L、(1.94±0.80)μg/L、(85.83±18.20)μmol/L和中度OSAHS组的(165.29±22.38)ng/L、(2.68±0.94)μg/L、(110.37±23.73)μmol/L,差异均具有统计学意义(P<0.05);经Spearman相关分析结果显示,MCP-1、HSP70、AOPP水平与AHI指数呈正相关(r=0.525、0.609、0.506,P<0.05)。结论脑梗死合并OSAHS患者血清MCP-1、HSP70、AOPP的水平明显较高,同时伴随OSAHS的程度加重,MCP-1、HSP70、AOPP表达进一步提升;且MCP-1、HSP70、AOPP表达水平与AHI指数呈正相关。

超声心动图参数及HSP70基因多态性与老年慢性心力衰竭预后的相关性分析

目的:分析超声心动图参数、热休克蛋白70(HSP70)基因多态性与老年慢性心力衰竭患者预后的相关性。方法:选取2019年10月至2021年10月于我院治疗的老年慢性心力衰竭患者142例作为研究对象,对其进行1年随访观察,用是否发生心血管事件评估其预后情况,将其分为预后不良组(32例)、预后良好组(110例)。收集患者出院前超声心动图检测参数,采用聚合酶链反应(PCR)结合限制性内切酶分析检测HSP70-1基因+190G/C、HSP70-2基因+1267A/C、HSP70-hom基因+2437T/C多态性,结合患者临床人口学与病理资料,分析两组患者超声心动图参数及HSP70基因多态性差异。采用二元Logistic回归分析老年慢性心力衰竭预后与超声心动图参数及HSP70基因多态性的相关性,建立ROC曲线评估超声心动图参数及HSP70基因多态性预测预后不良的价值。结果:与预后良好组患者相比,预后不良组患者超声心动图参数左心室舒张末期直径(LVEDD)、左心室收缩末期直径(LVESD)均更高(P<0.05),左心室射血分数(LVEF)更低(P<0.05)。与预后良好组患者相比,预后不良组患者HSP70-2基因+1267A/C基因型、等位基因差异有统计学意义(P<0.05)。Logistic回归分析显示年龄、LVEDD、LVEF、HSP70-2基因+1267A/C多态性是预后不良的影响因素(P<0.05)。LVEDD、LVEF、HSP70-2基因+1267A/C多态性单独、联合预测预后不良曲线下面积分别为0.728、0.852、0.624、0.985。结论:LVEDD、LVEF、HSP70-2基因+1267A/C多态性是老年慢性心力衰竭患者预后的影响因素,LVEDD升高,LVEF降低以及GG基因型均可增加老年慢性心力衰竭预后不良风险,三者联合时预测预后不良效能更高。