Prognosis value of heat-shock proteins in esophageal and esophagogastric cancer:A systematic review and meta-analysis

BACKGROUND Heat shock proteins(HSPs)are molecular chaperones that play an important role in cellular protection against stress events and have been reported to be overex-pressed in many cancers.The prognostic significance of HSPs and their regulatory factors,such as heat shock factor 1(HSF1)and CHIP,are poorly understood.AIM To investigate the relationship between HSP expression and prognosis in esophageal and esophagogastric cancer.METHODS A systematic review was conducted in accordance with PRISMA recommend-ations(PROSPERO:CRD42022370653),on Embase,PubMed,Cochrane,and LILACS.Cohort,case-control,and cross-sectional studies of patients with eso-phagus or esophagogastric cancer were included.HSP-positive patients were compared with HSP-negative,and the endpoints analyzed were lymph node metastasis,tumor depth,distant metastasis,and overall survival(OS).HSPs were stratified according to the HSP family,and the summary risk difference(RD)was calculated using a random-effect model.RESULTS The final selection comprised 27 studies,including esophageal squamous cell carcinoma(21),esophagogastric adenocarcinoma(5),and mixed neoplasms(1).The pooled sample size was 3465 patients.HSP40 and 60 were associated with a higher 3-year OS[HSP40:RD=0.22;95%confidence interval(CI):0.09-0.35;HSP60:RD=0.33;95%CI:0.17-0.50],while HSF1 was associated with a poor 3-year OS(RD=-0.22;95%CI:-0.32 to-0.12).The other HSP families were not associated with long-term survival.HSF1 was associated with a higher probability of lymph node metastasis(RD=-0.16;95%CI:-0.29 to-0.04).HSP40 was associated with a lower probability of lymph node dissemination(RD=0.18;95%CI:0.03-0.33).The expression of other HSP families was not significantly related to tumor depth and lymph node or distant metastasis.CONCLUSION The expression levels of certain families of HSP,such as HSP40 and 60 and HSF1,are associated with long-term survival and lymph node dissemination in patients with esophageal and esophagogastric cancer.

血清HSP60、HSP70水平与原发性免疫性血小板减少症患儿Th17/Treg细胞和预后的关系

目的分析血清热休克蛋白60(HSP60)、热休克蛋白70(HSP70)与原发性免疫性血小板减少症(ITP)患儿辅助性T细胞17/调节性T细胞(Th17/Treg)和预后的关系。方法选取2020年6月—2022年6月保山市人民医院儿科诊治的ITP患儿128例作为病例组,另选同期体检健康儿童60例作为健康对照组。检测并比较2组血清HSP60、HSP70与Th17/Treg细胞水平。Pearson法分析血清HSP60、HSP70与Th17/Treg细胞的相关性。ITP患儿出院后随访1年,根据不同预后情况分为预后良好亚组(107例)和预后不良亚组(21例)。收集ITP患儿的临床资料,采用单因素、多因素Logistic回归模型分析ITP患儿预后的影响因素,并构建风险预测列线图模型。建立受试者工作特征(ROC)曲线分析血清HSP60、HSP70与Th17/Treg细胞对ITP患儿预后的预测价值。结果病例组血清HSP60、HSP70水平及Th17/Treg细胞显著高于健康对照组(t/Z/P=20.445/<0.001、17.467/<0.001、5.823/<0.001)。Pearson相关分析显示,血清HSP60、HSP70与Th17/Treg细胞呈正相关(r/P=0.417/<0.001、0.348/<0.001)。多因素Logistic回归分析显示,HSP60高、HSP70高、Th17/Treg高为ITP患儿预后不良的独立危险因素[OR(95%CI)=1.177(1.041~1.331),1.181(1.038~1.343),9.895(2.171~68.177)],初诊时PLT计数偏高则为保护因素[OR(95%CI)=0.848(0.726~0.990)]。ROC曲线分析结果显示,初诊时PLT、HSP60、HSP70、Th17/Treg水平及列线图模型的曲线AUC分别为0.793、0.730、0.787、0.840、0.975;Bootstrap法(B=1000)对列线图模型进行内部验证显示,Bias-corrected预测曲线与Ideal线基本重合,该模型预测能力较好。决策曲线显示,该模型的阈值概率范围为0.01~0.98,其净收益率>0,高于两条无效线。结论IPT患儿血清HSP60、HSP70、Th17/Treg水平均明显升高,血清HSP60、HSP70与Th17/Treg呈显著正相关。初诊时PLT、HSP60、HSP70、Th17/Treg水平是ITP患儿预后不良的影响因素,且基于HSP60、HSP70等独立危险因素构建的列线图模型对ITP患儿预后不良具有较好的预测价值。

维持性腹膜透析患者血清CHI3L1、HSP60与钙磷代谢、冠状动脉钙化的关系

目的探讨维持性腹膜透析患者血清壳多糖酶3样蛋白1(CHI3L1)、热休克蛋白60(HSP60)与钙磷代谢、冠状动脉钙化的关系。方法选取2021年1月至2023年1月在周口市中心医院接受持续性非卧床腹膜透析或日间非卧床腹膜透析治疗>3个月的98例维持性腹膜透析患者作为研究对象,根据是否存在钙磷代谢异常分别分入钙磷正常组与钙磷异常组,根据多层螺旋CT结果参照Agatston评分法计算其冠状动脉钙化积分(CACS),将98例维持性腹膜透析患者再次分入未钙化组与钙化组,检测并对比两组患者的血清CHI3L1、血清HSP60水平。采用Pearson相关分析探讨血清CHI3L1、HSP60与钙磷代谢指标的关系,采用受试者工作特征(ROC)曲线评估血清CHI3L1、HSP60对维持性腹膜透析患者冠状动脉钙化的评估价值。通过多因素logistic逐步回归分析探讨维持性腹膜透析患者冠状动脉钙化的影响因素。结果98例维持性腹膜透析患者分为钙磷正常组(43例)、钙磷异常组(55例),钙磷代谢异常组患者血清CHI3L1、HSP60水平高于钙磷代谢正常组患者(P<0.05)。维持性腹膜透析患者血清CHI3L1、HSP60与钙磷乘积呈正相关(P<0.05)。根据多层螺旋CT结果参照Agatston评分法计算其CACS积分,将98例维持性腹膜透析患者分为未钙化组(37例)、钙化组(61例),钙化组患者血清CHI3L1、HSP60水平高于未钙化组患者(P<0.05)。血清CHI3L1、HSP60评估维持性腹膜透析患者预后的AUC分别为0.741、0.826,两者联合评估的AUC为0.915。钙化组患者低蛋白血症、高磷饮食人数及透析龄高于未钙化组(P<0.05)。多因素logistic回归分析显示:高磷饮食、透析龄、CHI3L1、HSP60是影响维持性腹膜透析患者冠状动脉钙化的危险因素(P<0.05)。结论血清CHI3L1、HSP60在钙磷代谢异常、发生冠状动脉钙化的维持性腹膜透析患者中均呈高表达,及早检测血清CHI3L1、HSP60水平有助于及时防治冠状动脉钙化。

Preparation and application of a novel monoclonal antibody specific for the heat shock protein 60 of Lawsonia intracellularis

Porcine proliferative enteropathy(PPE),an important infectious disease in pig production caused by an obligate intracellular bacterium Lawsonia intracellularis,is commonly associated with diarrhea and reduced weight gain in growing pigs widespread.An accurate method for detecting L.intracellularis is particularly important for preventing and controlling PPE.Heat shock protein 60(Hsp60)is an immunodominant bacterial antigen found in all eukaryotic and prokaryotic organisms.Thus,the purpose of the current investigation was to produce a novel L.intracellularis Hsp60 monoclonal antibody(mAb)useful for immunodiagnostics.Three hybridomas secreted anti-Hsp60 termed 3E5,4E2,and 9G6 were generated,and the titers of ascitic fluids of 3E5,4E2,9G6 were 1:1024000,1:2048000 and 1:2048000,respectively.The Western blotting analysis demonstrated that recombinant Hsp60(rHsp60)was recognized by mAbs 3E5,4E2 and 9G6.Subsequently,analyses of specificity showed all the mAbs were highly specific to L.intracellularis while could not significantly react with other enteric bacteria commonly found in the ileum of pigs,such as Escherichia coli,Salmonella Choleraesuis,Salmonella Typhimurium,and Brachyspira hyodysenteriae.Furthermore,the mAbs were useful for detecting L.intracellularis in the infected monolayer cells and histological sections of the ileum from PPE-affected pigs.Our research will provide a foundation for the development of immunological diagnostic tests.

Altered expression of nuclear matrix proteins in etoposide induced apoptosis in HL-60 cells

The events of cell death and the expression of nuclear matrix protein (NMP) have been investigated in a promyelocytic leukemic cell line HL-60 induced with etoposide. By means of TUNEL assay, the nuclei displayed a characteristic morphology change, and the amount of apoptotic cells increased early and reached maximun about 39% after treatment with etoposide for 2 h. Nucleosomal DNA fragmentation was observed after treatment for 4 h. The morphological change of HL-60 cells, thus, occurred earlier than the appearance of DNA ladder. Total nuclear matrix proteins were analyzed by 2-dimensional gel electrophoresis. Differential expression of 59 nuclear matrix proteins was found in 4 h etoposide treated cells. Western blotting was then performed on three nuclear matrix acssociated proteins, PML, HSC70 and NuMA. The expression of the suppressor PML protein and heat shock protein HSC70 were significantly upregulated after etoposide treatment, while NuMA, a nuclear mitotic apparatus protein, was down regulated. These results demonstrate that significant biochemical alterations in nuclear matrix proteins take place during the apoptotic process.

miR-186对HL-60细胞增殖、迁移的调控及机制研究

目的 探讨过表达微小RNA-186(miR-186)对人原髓细胞白血病HL-60细胞上皮间质转化(EMT)、增殖、迁移及磷脂酰肌醇3-激酶(PI3K)/丝苏氨酸蛋白激酶(AKT)信号通路的调控作用。方法 选取体外培养HL-60细胞,按照不同的转染方式分为对照组、mimic NC组、miR-186组、miR-186+抑制剂组、miR-186+激活剂组。采用实时荧光定量聚合酶链反应、5-乙炔基-2′脱氧尿嘧啶核苷(EdU)、Transwell小室法及蛋白免疫印迹法检测miR-186相对表达水平、增殖率、迁移率、EMT相关因子及其信使RNA(mRNA)相对表达水平并进行比较、分析。结果 与mimic NC组相比,miR-186组HL-60细胞miR-186相对表达水平、E-钙黏蛋白(E-cadherin)及其mRNA表达水平升高,差异均有统计学意义(P<0.05),而增殖率、迁移率、磷酸化(p)-PI3K、p-AKT、N-钙黏蛋白(N-cadherin)、波形蛋白(Vimentin)、纤维粘连蛋白(FN)及其mRNA表达水平降低,差异均有统计学意义(P<0.05)。与miR-186组相比,miR-186+抑制剂组HL-60细胞E-cadherin及其mRNA表达水平升高,差异均有统计学意义(P<0.05),而增殖率、迁移率、p-PI3K、p-AKT、N-cadherin、Vimentin、FN及其mRNA表达水平降低,差异均有统计学意义(P<0.05);与miR-186组相比,miR-186+激活剂组HL-60细胞E-cadherin及其mRNA表达水平下降,差异均有统计学意义(P<0.05),而增殖率、迁移率、p-PI3K、p-AKT、N-cadherin、Vimentin、FN及其mRNA表达水平升高,差异均有统计学意义(P<0.05)。结论 过表达miR-186通过阻遏PI3K/AKT信号通路抑制HL-60细胞EMT,进而抑制HL-60细胞增殖和迁移。

血清anti-HSP60、睾酮水平对多囊卵巢综合征合并不孕的预测价值

目的:探讨血清anti-热休克蛋白60(Heat shock protein 60,HSP60)、睾酮水平对多囊卵巢综合征(PCOS)合并不孕的预测价值。方法:2018年2月至2021年2月选择在本院诊治的多囊卵巢综合征合并不孕患者88例作为研究组,同期选择在本院体检中心进行孕前体检的88例健康妇女作为对照组。检测研究组与对照组血清anti-HSP60、睾酮水平并进行多因素与预测价值分析。结果:研究组与对照组的年龄、体重指数、初潮年龄、腰围、空腹血糖、低密度脂蛋白胆固醇、高密度脂蛋白胆固醇、总胆固醇、甘油三酯,对比无显著差异(P>0.05)。研究组的血清anti-HSP60、睾酮水平高于对照组(P<0.05)。多因素Logistic回归分析显示,血清anti-HSP60、睾酮是多囊卵巢综合征合并不孕发生的独立危险因素(P<0.05)。ROC曲线分析显示血清anti-HSP60、睾酮预测PCOS合并不孕症的曲线下面积分别为0.782、0.813,预测敏感性与特异性都超过了70.0%。结论:血清anti-HSP60、睾酮水平对多囊卵巢综合征合并不孕患者中呈现高表达水平,也是导致不孕发生的重要因素,对于多囊卵巢综合征合并不孕的预测也具有重要价值。

血清ESM-1、HSP60水平与胃癌根治术患者预后的相关性

目的:探讨血清内皮细胞特异性分子-1(ESM-1)、热休克蛋白60(HSP60)与胃癌根治术患者预后的关系。方法:选取2018年5月-2020年5月于信阳市中心医院确诊并行胃癌根治术治疗的136例胃癌患者作为研究对象。入院后次日,检测胃癌患者血清ESM-1、HSP60水平;术后对患者进行跟踪随访,随访时间截至2022年5月,评估患者预后情况,分析血清ESM-1、HSP60与胃癌根治术患者预后的相关性。结果:最终纳入130例患者进行研究;随访期间,130例胃癌患者中预后不良30例;预后不良组血清ESM-1、HSP60水平高于预后良好组,肿瘤分期为Ⅲ期、淋巴结转移占比高于预后良好组,差异有统计学意义(t=6.235、14.695;χ^(2)=2.742、10.566,P<0.05);经点二列相关性分析显示,血清ESM-1、HSP60与胃癌根治术患者预后呈正相关(r=0.632、0.675,P<0.05);血清ESM-1、HSP60二者联合预测的价值最佳(AUC=0.794)。结论:血清ESM-1、HSP-60水平与胃癌根治术患者预后有关,且血清ESM-1、HSP-60可作为预测患者预后的重要指标。

过表达miR-186对白血病HL-60细胞增殖和凋亡作用机制的研究

目的探究过表达miR-186对白血病细胞增殖、凋亡及磷脂酰肌醇3激酶(PI3K)/蛋白激酶B(AKT)信号通路的调控作用。方法选取人白血病HL-60细胞,通过实时荧光定量PCR(RT-qPCR)、细胞计数试剂-8(CCK-8)、Hoechst33258染色、酶联免疫吸附试验(ELISA)及蛋白质印迹法(WB)法分析细胞形态、miR-186相对表达量、增殖能力、凋亡情况、相关因子表达水平。结果转染24 h后,与mimic NC组相比,miR-186组细胞生长受到抑制,miR-186相对表达量、凋亡细胞数、超氧化物歧化酶(SOD)、caspase-3蛋白表达水平显著升高(P<0.05),而细胞增殖活力、丙二醛(MDA)、p-PI3K和p-AKT、Bcl-2蛋白表达水平均显著降低(P<0.05)。PI3K/AKT信号通路抑制剂的加入使各项指标差异更加显著(P<0.05)。结论过表达miR-186能够通过抑制PI3K/AKT信号通路抑制人白血病HL-60细胞的增殖并改善氧化应激水平,促进细胞凋亡。

Cryopreservation-induced decrease in heat-shock protein 90 in human spermatozoa and its mechanism

<abstract>Aim: To study the protein changes of spermatozoa associated with sperm motility during sperm cryopreservation and its mechanism. Methods: In 18 healthy men, the seminal sperm motility and HSP90 levels were studied before and after cryopreservation using SDS-PAGE, Western blotting and computerized image analysis. Results: The sperm motility declined significantly after cryopreservation (P<0.01). The average grey level and the integrated grey level of sperm HSP90 before cooling were 34.1±3.2 and 243.0±21.6, respectively, while those after thawing were 23.2±2.5 and 105.7±28.5, respectively. Both parameters were decreased significantly (P<0.01). No HSP90 was found in the seminal plasma before and after cryopreservation. Conclusion: HSP90 in human spermatozoa was decreased substantially after cryopreservation. This may result from protein degradation, rather than leakage into the seminal plasma.

H pylori infection and systemic antibodies to CagA and heat shock protein 60 in patients with coronary heart disease

AIM: To determine the overall prevalence of H pylori and CagA positive H pylori infection and the prevalence of other bacterial and viral causes of chronic infection in patients with coronary heart disease (CHD), and the potential role of anti-heat-shock protein 60 (Hsp60) anti- body response to these proteins in increasing the risk of CHD development. METHODS: Eighty patients with CHD and 160 controls were employed. We also compared the levels of anti- heat-shock protein 60 (Hsp60) antibodies in the two groups. The H pylori infection and the CagA status were determined serologically, using commercially available enzyme-linked immunosorbent assays (ELISA), and a Western blotting method developed in our laboratory. Systemic antibodies to Hsp60 were determined by a sandwich ELISA, using a polyclonal antibody to Hsp60 to sensitise polystyrene plates and a commercially available human Hsp60 as an antigen. RESULTS: The overall prevalence of H pylori infec- tion was 78.7% (n = 63) in patients and 76.2% (n = 122) in controls (P = 0.07). Patients infected by CagA- positive (CagA+) H pylori strains were 71.4% (n = 45) vs 52.4% of infected controls (P = 0.030, OR = 2.27). Sys-temic levels of IgG to Hsp60 were increased in H pylori- negative patients compared with uninfected controls (P < 0.001) and CagA-positive infected patients compared with CagA-positive infected controls (P = 0.007). CONCLUSION: CagA positive H pylori infection may concur to the development of CHD; high levels of anti- Hsp60 antibodies may constitute a marker and/or a con- comitant pathogenic factor of the disease.

Effects of moxibustion on heat-shock protein 70 expression in the spinal cord and colonic mucosa in a rat model of ulcerative colitis

Pathological changes in the colon are closely associated with the spinal cord, and innervation of spinal cord can regulate cellular functions. Our previous studies verified that moxibustion protects and restores the colonic mucosa, but the mechanisms of action remain unknown. The present study observed the effects of moxibustion and salicylazosulfapyridine on expression of heat-shock protein 70 （HSP70） and its mRNA in the spinal cord and colonic mucosa of ulcerative colitis rats. Results demonstrated that moxibustion and salicylazosulfapyridine increased HSP70 mRNA expression in the spinal cord and colonic mucosa of ulcerative colitis rats. The decreased transcriptional activity of HSP70 in the spinal cord and colonic mucosa might participate in damage to the colonic mucosa in ulcerative colitis rats. Moxibustion exerted protective effects on colonic mucosa by up-regulating HSP70 transcriptional activity in the spinal cord and colonic mucosa.

Modification of tooth development by heat shock protein 60

several heat shock proteins have been investigated in relation to tooth development, no available information is available about the spatial and temporal expression pattern of heat shock protein 60 （Hsp 60）. To characterize Hsp 60 expression in the structures of the developing tooth germ, we used Western blotting, immunohistochemistry and in situ hybridization. Hsp 60 was present in high amounts in the inner and outer enamel epithelia, enamel knot （EK） and stratum intermedium （SI）. Hsp 60 also appeared in odontoblasts beginning in the bell stage. To obtain data on the possible effect of Hsp 60 on isolated lower incisors from mice, we performed in vitro culturing. To investigate the effect of exogenous Hsp 60 on the cell cycle during culturing, we used the 5-bromo-2- deoxyuridine （BrdU） incorporation test on dental cells. Exogenously administered Hsp 60 caused bluntness at the apical part of the 16.5-day-old tooth germs, but it did not influence the proliferation rate of dental cells. We identified the expression of Hsp 60 in the developing tooth germ, which was present in high concentrations in the inner and outer enamel epithelia, EK, SI and odontoblasts. High concentration of exogenous Hsp 60 can cause abnormal morphology of the tooth germ, but it did not influence the proliferation rate of the dental cells. Our results suggest that increased levels of Hsp 60 may cause abnormalities in the morphological development of the tooth germ and support the data on the significance of Hsp during the developmental processes.

Heat shock and other apoptosis-related proteins as therapeutic targets in prostate cancer

Defects within apoptotic pathways have been implicated in prostate cancer （PCa） tumorigenesis, metastatic progression and treatment resistance. A hallmark of cancers is the ability to derail apoptosis by inhibiting the apoptotic signal, reducing the expression of apoptotic proteins and/or amplifying survival signals through increased production of antiapoptotic molecule. This review describes associations between heat shock proteins （HSPs） and the human androgen receptor （AR）, the role of HSPs and other stress-induced proteins in PCa development and emerging strategies in targeting these protective proteins to treat PCa.

Hepatitis C virus inhibitor synergism suggests multistepinteractions between heat-shock protein 90 and hepatitis Cvirus replication

AIM: To address the effect of heat-shock protein 90(HSP90) inhibitors on the release of the hepatitis C virus(HCV), a cell culture-derived HCV(JFH1/HCVcc) from Huh-7 cells was examined.METHODS: We quantified both the intracellular and extracellular(culture medium) levels of the components(RNA and core) of JFH-1/HCVcc. The intracellular HCV RNA and core levels were determined after the JFH1/HCVcc-infected Huh-7 cells were treated with radicicol for 36 h. The extracellular HCV RNA and core protein levels were determined from the medium of the last 24 h of radicicol treatment. To determine the possible role of the HSP90 inhibitor in HCV release, we examined the effect of a combined application of low doses of the HSP90 inhibitor radicicol and the RNA replication inhibitors cyclosporin A(Cs A) or interferon. Finally, we statistically examined the combined effect of radicicoland Cs A using the combination index(CI) and graphical representation proposed by Chou and Talalay.RESULTS: We found that the HSP90 inhibitors had greater inhibitory effects on the HCV RNA and core protein levels measured in the medium than inside the cells. This inhibitory effect was observed in the presence of a low level of a known RNA replication inhibitor(Cs A or interferon-α). Treating the cells with a combination of radicicol and cyclosporin A for 24 h resulted in significant synergy(CI < 1) that affected the release of both the viral RNA and the core protein. CONCLUSION: In addition to having an inhibitory effect on RNA replication, HSP90 inhibitors may interfere with an HCV replication step that occurs after the synthesis of viral RNA, such as assembly and release.

Genome-Wide Identification of heat shock protein 10/60 Genes in Japanese Flounder (Paralichthys olivaceus) and Their Regulated Expression After Bacterial Infection

Heat shock proteins 10/60(hsp10/60)are a family of conserved ubiquitously expressed heat shock proteins which are produced by cells in response to exposure to stressful conditions.Besides the chaperone and housekeeping functions,they are also known to be involved in immune response during bacterial infection.In this study,we identified and annotated 10 hsp10/60 genes through bioinformatic analysis in Japanese flounder(Paralichthys olivaceus).Among them one member of hsp10(hspe)family and nine members of hsp60(hspd)family were identified.Phylogenetic and selection pressure analysis showed that the hsp10/60 genes were evolutionarily constrained and their function was conserved.Besides,hsp10/60 genes were involved in different embryonic and larval stages and acted as the sentinel role in an unchallenged organism.In addition,we also observed the expression patterns of hsp10/60 genes after Edwardsiella tarda infection,for the first time in Japanese flounder.Eight out of 10 genes were differentially expressed after bacterial challenges,the significantly regulated expressions of flounder hsp10/60 genes after bacterial infections suggested their involvement in immune response in flounder.Our results provide valuable information for clarifying the evolutionary relationship,and early insights of the immune functions of hsp10/60 genes in Japanese flounder.

利拉鲁肽联合达格列净对老年2型糖尿病患者血糖波动、服药安全性及HSP60、Nesfatin-1水平的影响

目的探讨利拉鲁肽联合达格列净对老年2型糖尿病患者血糖波动、服药安全性及热休克蛋白60(HSP60)、Nesfatin-1水平的影响。方法选取我院2019年5月至2021年3月收治的96例老年2型糖尿病患者,根据入院顺序将其分为对照组和观察组,各48例。对照组采用达格列净治疗,观察组采用利拉鲁肽联合达格列净治疗。比较两组的治疗效果。结果治疗后,观察组的空腹血糖(FPG)、餐后2 h血糖(2 h PG)、总胆固醇(TC)及甘油三酯(TG)水平均低于对照组(P<0.05)。治疗后,观察组的平均血糖(MBG)、血糖水平标准差(SDBG)、最大血糖波动幅度(LAGE)及餐后血糖波动幅度(PPGE)水平均低于对照组(P<0.05)。治疗后,观察组的脂联素、一氧化氮(NO)水平高于对照组,内皮素(ET)水平低于对照组(P<0.05)。两组的胃肠道不适、头晕、低血糖、皮疹发生率及不良反应总发生率比较,差异无统计学意义(P>0.05)。治疗后,观察组的HSP60及Nesfatin-1水平均低于对照组(P<0.05)。结论采用利拉鲁肽联合达格列净治疗老年2型糖尿病患者有助于降低血糖和血脂水平,减轻血糖波动,改善脂联素和血管内皮功能指标水平,降低HSP60、Nesfatin-1水平,且不会增加不良反应的发生。

雄黄对NB4和HL-60细胞的形态,PML mRNA及蛋白的表达影响

本研究以NB4 ,HL 60细胞为研究对象 ,采用Wright′s染色法及荧光染色法、免疫荧光技术及RT PCR法 ,探讨雄黄对NB4 ,HL 60细胞的形态、PMLmRNA及蛋白的表达影响。结果发现 :①经雄黄处理后 ,各组均出现细胞凋亡的形态学上改变。②雄黄处理后NB4细胞内融合蛋白降解 ,PML蛋白聚积于POD结构 ,随后降解 ;在HL 60细胞中PML蛋白发生相似改变。③雄黄处理后各组细胞PMLmRNA表达均无显著影响。结论指出 ,在雄黄诱导下PML在蛋白水平参与诱导白血病细胞凋亡机制 ,雄黄能诱导NB4 ,HL 60细胞凋亡 。

HL-60/VCR多药耐药细胞株耐药机制的研究

背景与目的:白血病细胞对化疗药物的耐药是白血病治疗失败的主要原因,多药耐药细胞株为白血病多药耐药机制和逆转多药耐药性的研究提供了良好的模型。为探讨药物诱导产生多药耐药机制,我们对HL-60/VCR细胞的耐药机制进行了研究。方法:应用流式细胞术和一组抗体,对药物敏感细胞株HL-60和多药耐药细胞株HL-60/VCR细胞的耐药相关蛋白P-gp、MRP、LRP、BCRP、GST-π,以及凋亡调节蛋白bcl-2、bax、bcl-x、bad的表达进行分析。结果:在HL-60/VCR细胞株中,耐药相关蛋白P-gp、MRP、BCRP、GST-π分别是其在HL-60细胞株中的18.62、1.19、1.50、1.32倍,而LRP无变化。凋亡抑制蛋白bcl-2、bcl-x分别是其在HL-60细胞株中的2.48、1.25倍,凋亡调节蛋白bad是HL-60细胞株中的1.08倍;而凋亡诱导蛋白bax反而降低,是HL-60细胞株中的0.88倍。结论:多种机制参与HL-60/VCR的多药耐药,涉及耐药蛋白P-gp、MRP、BCRP和GST-π的表达增强,而且凋亡调节蛋白bcl-2、bax、bcl-x、bad均可能参与其耐药机制的形成。

两种真菌多糖对HL-60细胞酪氨酸蛋白磷酸化作用的影响

目的 :研究猪苓多糖和茯苓多糖对人早幼粒白血病细胞 (HL 6 0 )酪氨酸蛋白磷酸化作用的影响。方法 :用一定浓度的药物处理体外培养的HL 6 0细胞。用放射免疫法测定经过培养 12 ,2 4,48,72和 12 0h对照组和药物处理组细胞浆和膜部分的酪氨酸蛋白激酶 (TPK)和磷酸酪氨酸蛋白磷酸酶 (PTPP)的活力 ,比较酶活力变化情况。结果 :两种多糖对胞浆和膜部分TPK活力均有不同程度的抑制作用。而对两部分PTPP的活力均有不同程度的激活作用。结论 :两种真菌多糖均可使HL 6 0细胞酪氨酸蛋白磷酸化水平下降 ,提示两种多糖抗肿瘤作用的机制可能与酪氨酸蛋白磷酸化作用有关。