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1.
Article in Chinese | WPRIM | ID: wpr-1032150

ABSTRACT

Objective @# To explore the effects of microRNA-155 (miR-155) on apoptosis of chronic myeloid leukemia ( CML) cells,and the influence of miRNA-155 regulating the expression of heat shock proteins ( HSP) 27, HSP60,HSP70.@*Methods @#Reverse transcription-quantitative real-time PCR ( RT-qPCR) was used to detect the expression levels of miR-155 in CML-resistant imatinib (IM) cell line K562-G and CML cell line K562 .K562-G cells were infected with the lentivirus carrying miR-155 or the negative control lentivirus ,and they were named miR-155 group and control group.The effect of miR-155 on the proliferation of drug-resistant cells was detected by cell counting kit-8 ( CCK-8) method. RT-qPCR and Western blot were used to detect the effect of miR-155 on the expression of heat shock proteins HSP27,HSP60,HSP70.Flow cytometry was used to detect the percentage of cell apoptosis in miR-155 group and control group. @*Results @#ompared with K562 cells,miR-155 showed low expres- sion in K562-G cells (P <0. 05) .The proliferation of miR-155 group cells decreased significantly from the 36th hour (P<0. 05) .Compared with the control group,in the miR-155 group,HSP60 and HSP70 increased (P < 0. 05) ,while HSP27 decreased (P<0. 01) .The apoptosis rate of miR-155 group was higher than that of control group (P<0. 05) .@*Conclusion @#miR-155 promotes the apoptosis of chronic myeloid leukemia cells,increases the expression of HSP60 and HSP70,and decreases the expression of HSP27 .

2.
Braz. dent. j ; Braz. dent. j;34(5): 125-133, Sept.-Oct. 2023. tab, graf
Article in English | LILACS-Express | LILACS, BBO | ID: biblio-1528012

ABSTRACT

Abstract New methods of early detection and risk assessment have been studied aiming to predict the prognosis of patients and directing a specialized treatment of the oral tongue squamous cell carcinoma (OTSCC). In this context, several molecular biomarkers have been investigated for this purpose, and, among them, the heat shock protein 27 (HSP27) can be named. The study aimed to analyze whether heat shock protein 27 (HSP27) exerts any influence on OTSCC, correlating its immunoexpression with clinicopathological parameters, and patient survival. The sample comprised 55 OTSCC cases and 20 normal oral mucosa specimens. The malignancy grading systems proposed by the WHO in 2005, Brandwein-Gensler et al., and Almangush et al. were applied in a histomorphological study. HSP27 expressions were evaluated through the Immunoreactivity Score System (IRS). Significant values were considered at p <0.05 for all statistical tests. Higher IRS results were observed for normal oral mucosa specimens when compared to OTSCC cases (p <0.001). No significant associations between HSP27 immunostaining, the analyzed clinicopathological parameters and patient survival were observed. The results of the present study indicate lower HSP27 expression in OTSCC cases compared to normal oral mucosa specimens. Thus, HSP27 expression does not seem to influence patient prognosis.


Resumo Novos métodos de detecção precoce e avaliação de risco estão sendo estudados com o intuito de predizer o prognóstico dos pacientes e direcionar um tratamento diferenciado. Neste contexto, vários biomarcadores moleculares têm sido investigados com esta finalidade, dentre eles a heat shock protein 27 (HSP27). Esta pesquisa objetivou analisar se a HSP27 exerce alguma influência nos carcinomas de células escamosas de língua oral (CCELO), correlacionando a sua imunoexpressão com parâmetros clinicopatológicos e com a sobrevida dos pacientes. A amostra foi constituída por 55 casos de CCELO e 20 espécimes de mucosa oral normal. Os sistemas de gradação de malignidade propostos pela OMS em 2005, Brandwein-Gensler et al. e Almangush et al. foram aplicados em um estudo histomorfológico. A expressão da HSP27 foi avaliada através do Sistema de Escore de Imunorreatividade (IRS). Para todos os testes estatísticos foram considerados valores significativos com p<0,05. Foi observado um maior IRS para a mucosa oral normal quando comparado aos casos de CCELO (p<0,001). Não foram encontradas associações significativas entre a imunomarcação da HSP27 com os parâmetros clinicopatológicos analisados e com a sobrevida dos pacientes. Os resultados do presente estudo indicam uma menor expressão da HSP27 nos casos de CCELO quando comparados aos espécimes de mucosa oral normal. Assim, a expressão da HSP27 parece não influenciar o prognóstico dos pacientes.

3.
Journal of Clinical Hepatology ; (12): 2443-2447, 2023.
Article in Chinese | WPRIM | ID: wpr-998312

ABSTRACT

Hepatitis B virus (HBV) has the characteristics of wide transmission, a high chronic infection rate, and a low cure rate, and improving the cure rate of HBV may help to improve the long-term prognosis of patients. Heat shock protein 90 (Hsp90) is a chaperone protein widely present in organisms. In recent years, more and more studies have shown that Hsp90 is associated with HBV infection and plays an important role in HBV replication. It can not only interact with specific proteins of the virus to promote its replication, but also interact with the host’s own proteins to perform its function. This article reviews the role of Hsp90 in HBV replication in recent studies, so as to provide new theoretical guidance and directions for the development of new anti-HBV drugs targeting Hsp90 and the prevention and treatment of HBV infection in the future.

4.
Acta cir. bras ; Acta cir. bras;38: e385223, 2023. tab, graf, ilus
Article in English | LILACS, VETINDEX | ID: biblio-1527599

ABSTRACT

Purpose: Esophageal squamous cell carcinoma (ESCC) is characterized by early metastasis and late diagnosis. miR-29c-3p is confirmed to repress angiogenesis in multiple tumor types. Yet, the functions of miR-29c-3p in the mechanism of ESCC angiogenesis, which were not sufficiently explored previously, were exactly what we investigated here at the molecular level. Methods: The mRNA level of miR-29c-3p and Serpin peptidase inhibitor clade H member 1 (SERPINH1) in ESCC tissues were assessed via bioinformatics analysis. Thereafter, miR-29c-3p and SERPINH1 (HSP47) mRNA level in ESCC cell lines was evaluated via quantitative real-time polymerase chain reaction. The effects of abnormal miR-29c-3p and SERPINH1 expression on ESCC cell viability, proliferation, migration, invasion, and HUVEC angiogenesis were examined via CCK8, colony formation, transwell, and angiogenesis assays, respectively. The protein levels of SERPINH1, vascular endothelial growth factor-A (VEGFA), Wnt-1, ?-catenin, and p-?-catenin were evaluated via Western blot. Expression of VEGFA secreted by ESCC cells was measured via enzyme-linked immunosorbent assay. Treatment with the Wnt activator BML-284 further revealed the way miR-29c-3p mediated the Wnt signaling pathway and its effects on angiogenesis. Results: Herein, we revealed a decrease of miR-29c-3p expression in ESCC tissues and cells, while the overexpressed miR-29c-3p could remarkably suppress ESCC cell progression, as well as HUVEC angiogenesis. Meanwhile, overexpressed miR-29c-3p notably downregulated VEGFA and repressed the Wnt signaling pathway. Treatment with the Wnt activator BML-284 could reverse the inhibition of HUVEC angiogenesis caused by miR-29c-3p. SERPINH1 was a downstream target of miR-29c-3p. SERPINH1 knockdown suppressed the malignant phenotypes of ESCC cells and impeded the Wnt signaling activation, while such suppression was reversed through miR-29c-3p inhibitor. Conclusions: We confirmed the mechanism that miR-29c-3p targeted SERPINH1, thus regulating angiogenesis in ESCC through the Wnt signaling pathway. It improves the understanding of angiogenesis in ESCC and offers new ideas for the research of ESCC treatment strategies in the future.


Subject(s)
MicroRNAs , Angiogenic Proteins , Wnt Signaling Pathway , Esophageal Squamous Cell Carcinoma
5.
Rev. Assoc. Med. Bras. (1992, Impr.) ; Rev. Assoc. Med. Bras. (1992, Impr.);68(8): 1017-1022, Aug. 2022. tab, graf
Article in English | LILACS-Express | LILACS | ID: biblio-1406619

ABSTRACT

SUMMARY OBJECTIVE: We aimed to determine whether vitamin C has a protective effect on cisplatin-induced neuropathy in rats. METHODS: In total, 24 rats were included in the study of which 8 rats (no drug administered) were categorized as the control group. The remaining 16 rats were given a total dose of 20 mg/kg cisplatin to induce neuropathy. These drug-administered rats (16 rats) were randomly divided into two groups, namely, group-1 (n=8): cisplatin+saline and group-2 (n=8): cisplatin+vitamin C (500 mg/kg/day). All rats were tested for motor function and electromyographic activity 3 days after cisplatin. Motor performance was evaluated by an inclined-plane test. Compound muscle action potential was evaluated. Plasma malondialdehyde, glutathione, tumor necrosis factor-α, interleukin 6, and sciatic nerve HSP 70 levels were measured. Axon diameter and nerve growth factor expression levels were analyzed. RESULTS: Plasma malondialdehyde, tumor necrosis factor-α, and interleukin 6 levels were higher in the cisplatin+saline group than control group (p<0.001). But vitamin C significantly reduced malondialdehyde and inflammatory cytokine levels when compared with the cisplatin+saline group (p<0.001). Glutathione levels were lower in both cisplatin+saline and cisplatin+vitamin C groups than control group, but vitamin C significantly ameliorated the glutathione levels (p<0.05). Sciatic heat shock protein-70 levels were significantly higher in the cisplatin+vitamin C group than cisplatin+saline group. Compound muscle action potential amplitude and inclined plane test scores were significantly improved in the vitamin C group (p<0.05). Axon diameter and nerve growth factor expression ameliorated with vitamin C (p<0.05). CONCLUSIONS: We demonstrated the ameliorated effects of vitamin C on cisplatin-induced neuropathy through increased heat shock protein-70, nerve growth factor levels, and reduced inflammatory and oxidant effects. The results are promising to improve the neurotoxic effects of cisplatin in cancer patients.

6.
J Vector Borne Dis ; 2022 Apr; 59(2): 145-153
Article | IMSEAR | ID: sea-216875

ABSTRACT

We aimed to assess the effect of gamma radiation on the expression of heat shock proteins Hsc70 and Hsp83 in Aedes aegypti. Adult males were irradiated with 50Gy of gamma radiation, and changes in the expression of proteins in SDS-PAGE gel bands corresponding to molecular weights ~60–75kDa and ~80–95kDa were analyzed at two different time points 6 and 12-hour post-irradiation, using a temporal mass spectrometry based semi-quantitative analysis. A 2-3-fold increase was observed in both proteins Hsc70 and Hsp83, at both time points. In addition, the experiment also revealed the overexpression of several other molecules such as Arginine Kinase - known to be upregulated in certain insects during stress, Esterase B1- implicated in insecticide resistance, and also down-regulation of the 26S proteasome non-ATPase regulatory subunit 1 and ubiquitin-activating enzyme E1 - both known to be involved in ubiquitin-mediated protein degradation. The results taken together with existing data on Hsp83 and Hsc70, indicate that these proteins may enhance the survival of Ae. aegypti following gamma radiation and could serve as molecular markers for the detection of radiation-induced stress.

7.
Chinese Journal of Nephrology ; (12): 161-167, 2022.
Article in Chinese | WPRIM | ID: wpr-933851

ABSTRACT

Objective:To summarize and analyze the clinicopathological characteristics of patients with DNAJ heat shock protein family member B9 (DNAJB9)-positive fibrillary glomerulonephritis (FGN).Methods:The clinical and pathological data of 5 patients with DNAJB9-positive FGN diagnosed in Peking University First Hospital from January 2011 to January 2021 were retrospectively collected and analyzed.Results:Among the 5 patients, the female to male ratio was 4∶1, and the median age was 29 years old (24-71 years old). The clinical manifestations included 2 cases with nephrotic syndrome and 3 cases with proteinuria. One patient had gross hematuria, and 4 cases had mild microscopic hematuria. None of the 5 patients had evidence of monoclonal gammopathy. The renal pathological pattern of FGN showed mesangial-proliferative glomerulonephritis, mesangial nodular sclerosis, membranoproliferative glomerulonephritis, and atypical membranous nephropathy. Crescents formation could be accompanied. Immunofluorescence staining showed smudgy and granular IgG and C3 deposition in the mesangial region and capillary wall, and the subtypes of IgG were mainly IgG1 and IgG4. Under electron microscopy, fibrillary deposits with a diameter of 8-30 nm were observed in the mesangial and subendothelial area, accompanied by deposition in basement membrane and occasionally subepithelial area. The renal prognosis of FGN patients was poor. One patient entered end-stage renal disease within one week, and another patient entered end-stage renal disease within one year despite immunosuppressant therapy in 2 cases with nephrotic syndrome at onset. One patient had worsening proteinuria despite renin-angiotensin system (RAS) blocker treatment. Two patients achieved complete renal remission and stable renal function after RAS blocker treatment.Conclusions:Most FGN patients in China are young people. The main clinical manifestations are proteinuria or mild microscopic hematuria. The diagnosis depends on the discovery of fibrillary deposits in the mesangial area and subendothelial area with a diameter of about 10-30 nm under the electron microscope. DNAJB9 protein immunohistochemical staining can be used as an important marker for the diagnosis of FGN. The prognosis of FGN kidney is poor, and there is no effective targeted treatment option now.

8.
Article in Chinese | WPRIM | ID: wpr-935752

ABSTRACT

Objective: To study the effect of anti-fibrotic tetrapeptide N-acetyl-seryl-aspartyl-lysyl-proline (Ac-SDKP) on phosphorylated heat shock protein 27 (P-HSP27) and zinc finger family transcriptional repressor 1 (SNAI1) expression to explore the anti-silicosis fibrosis effect of Ac-SDKP. Methods: In December 2014, the rat silicosis animal model was prepared by one-time bronchial infusion of silicon dioxide (SiO(2)) dust. 80 SPF healthy adult Wistar rats were selected, and the rats were divided into 8 groups according to the random number table method, 10 in each group. Model control group for 4 weeks (feeding for 4 weeks) , model control group for 8 weeks (feeding for 8 weeks) : bronchial perfusion with normal saline 1.0 ml per animal. Silicosis model group for 4 weeks (feeding for 4 weeks) and silicosis model group for 8 weeks (feeding for 8 weeks) : bronchial perfusion of 50 mg/ml SiO(2) suspension 1.0 ml per animal. Ac-SDKP administration group for 4 weeks (feeding for 4 weeks) , Ac-SDKP administration group for 8 weeks (feeding for 8 weeks) : Ac-SDKP 800 μg·kg(-1)·d(-1) was administered by intraperitoneal pump. Ac-SDKP preventive treatment group: 48 h after Ac-SDKP 800 μg·kg(-1)·d(-1) administration, bronchial perfusion of SiO(2) suspension 1.0 ml per animal, raised for 8 weeks. Ac-SDKP anti-fibrosis treatment group: after bronchial perfusion of 1.0 ml of SiO(2) suspension for 4 weeks, Ac-SDKP 800 μg·kg(-1)·d(-1) was administered for 4 weeks. Western blotting was used to detect the expression of P-HSP27, SNAI1, α-smooth muscle actin (α-SMA) , and collage typeⅠ and Ⅲ in each group. The expression of P-HSP27 and SNAI1 was detected by immunohistochemistry, and the co-localized expression of P-HSP27 and α-SMA was detected by laser confocal microscopy. Results: Compared with the model control group, the expressions of P-HSP27, SNAI1, α-SMA, and collage typeⅠ and Ⅲ in the silicosis fibrosis area of the rats in the silicosis model group were enhanced, and the differences were statistically significant (P<0.05) . After Ac-SDKP intervention, compared with silicosis model group for 8 weeks, the expressions of P-HSP27, SNAI1 α-SMA, and collage typeⅠ and Ⅲ in the Ac-SDKP preventive and anti-fibrosis treatment groups were significantly decreased, and the differences were statistically significant (P<0.05) . However, the expressions of P-HSP27 SNAI1, and collage typeⅠ and Ⅲ between the Ac-SDKP administration group and the model control group did not change significantly, and the differences were not statistically significant (P>0.05) . Laser confocal results showed that the positive cells expressing P-HSP27 and α-SMA in the lung tissue of the silicosis model group were more than those in the model control group. Compared with the silicosis model group, the Ac-SDKP prevention and anti-fibrosis treatment groups expressing the positive cells of P-HSP27 and α-SMA decreased. Compared with the model control group for 8 weeks, there were some double-positive cells expressing P-HSP27 and α-SMA in the nodules of the silicosis model group for 8 weeks. Conclusion: Ac-SDKP may play an anti-silicic fibrosis effect by regulating the P-HSP27/SNAI1 pathway.


Subject(s)
Animals , Rats , HSP27 Heat-Shock Proteins , Oligopeptides , Rats, Wistar , Silicon Dioxide , Silicosis/metabolism
9.
Journal of Clinical Hepatology ; (12): 577-581, 2022.
Article in Chinese | WPRIM | ID: wpr-922957

ABSTRACT

Objective To investigate the influence of preoperative serum heat shock protein 90α (HSP90α) level on the survival time of patients with hepatocellular carcinoma treated by transarterial chemoembolization (TACE). Methods A retrospective analysis was performed for the clinical data of 97 patients with hepatocellular carcinoma who received TACE alone in Department of Hepatobiliary Surgery, The Affiliated Hospital of Southwest Medical University, from January 1, 2019 to June 1, 2020. With the median of serum HSP90α level as the cut-off value, the patients were divided into high-level group with 48 patients (HSP90α > 135 ng/L) and low-level group with 49 patients (HSP90α ≤135 ng/L). The chi-square test was used for comparison of categorical data between groups. The Kaplan-Meier method was used to calculate the median survival time, and the log-rank test was used for comparison between groups. The log-rank univariate analysis and multivariate Cox regression analysis were used to explore the influencing factors for the survival time of patients after surgery. Results There were significant differences between the high-level group and the low-level group in Child-Pugh class ( χ 2 =19.356, P <0.01), tumor necrosis ( χ 2 =9.964, P =0.002), BCLC staging ( χ 2 =22.356, P <0.01), and ECOG score ( χ 2 =6.644, P <0.05). The high-level group had a significantly shorter median survival time than the low-level group ( χ 2 =15.551, P <0.01). HSP90α level (hazard ratio [ HR ]=1.690, P <0.05) and BCLC staging ( HR =2.373, P <0.05) were independent influencing factors for the survival time of patients with hepatocellular carcinoma after TACE. Conclusion Preoperative serum HSP90α level is an independent influencing factor for the survival time of patients with hepatocellular carcinoma after TACE, and it is expected to become one of the potential indicators for evaluating the prognosis of patients with hepatocellular carcinoma treated by TACE.

10.
Article in Chinese | WPRIM | ID: wpr-930049

ABSTRACT

Tumor immunogenic cell death is a type of regulatory cell death, which is driven by stress including chemotherapy drugs, radiotherapy, oncolytic virus, nano carrier drugs and photodynamic force. It can induce specific immune response to tumor death cell antigen. The further study can provide theoretical basis and new ideas for anti-tumor immunity and clinical immunotherapy of tumor.

11.
Einstein (São Paulo, Online) ; 20: eRB6181, 2022. tab
Article in English | LILACS | ID: biblio-1364795

ABSTRACT

ABSTRACT Ischemia-reperfusion injury is a pathophysiological event occuring after abdominal organ transplantation, and has a significant influence on prognosis and survival of the graft. It is involved in delaying the primary function or non-functioning of the graft. The objective of this study was to provide information on heat shock protein mechanisms in ischemia-reperfusion injuries in abdominal organ transplantations, and to indicate the possible factors involved that may influence the graft outcome. Several classes of heat shock proteins are part of the ischemia and reperfusion process, both as inflammatory agonists and in protecting the process. Studies involving heat shock proteins enhance knowledge on ischemia-reperfusion injury mitigation processes and the mechanisms involved in the survival of abdominal grafts, and open space to support therapeutic future clinical studies, minimizing ischemia and reperfusion injuries in abdominal organ transplantations. Expression of heat shock proteins is associated with inflammatory manifestations and ischemia-reperfusion injuries in abdominal organ transplantations and may influence graft outcomes.


Subject(s)
Reperfusion Injury , Organ Transplantation , Heat-Shock Proteins/metabolism , Ischemia
12.
Colomb. med ; 52(1): e2024196, Jan.-Mar. 2021. tab, graf
Article in English | LILACS | ID: biblio-1249638

ABSTRACT

Abstract Background: Viruses are being used as alternative and complementary tools for treating cancers. Oncolytic viruses exhibit tumor tropism, ability to enhance anti-tumor immunity and ability to be used in combination with conventional chemotherapy and radiotherapy. We have recently selected some rotavirus isolates which are adapted to efficiently infect and kill tumor cell lines. Aim: We tested five tumor cell-adapted rotavirus isolates for their ability to infect the human adenocarcinoma cell line MCF-7. Methods: Cell surface membrane-associated proteins mediating virus particle attachment were characterized using ELISA, immunoprecipitation, FACS analysis, and antibody blocking. Results: It was found that heat shock proteins (HSPs) such as Hsp90, Hsp70, Hsp60, and Hsp40 are expressed on the cell surface forming complexes with protein disulfide isomerase (PDI), integrin β3, and heat shock cognate protein 70 (Hsc70) in lipid raft microdomains. Interaction of rotavirus isolates with these cellular proteins was further confirmed by a competition assay and an inhibition assay involving the HSPs tested. Conclusion: Our findings suggest that the tumor cell-adapted rotavirus isolates studied here offer a promising tool for killing tumor cells, thus encouraging further research into this topic, including animal models.


Resumen Antecedentes: Los virus se utilizan como herramientas alternativas y complementarias para el tratamiento del cáncer. Los virus oncolíticos exhiben tropismo por tumores, capacidad para intensificar la inmunidad antitumoral y la capacidad para utilizarse en combinación con quimioterapia y radioterapia convencionales. Recientemente, hemos seleccionado algunos aislamientos de rotavirus que están adaptados para infectar y eliminar de manera eficiente líneas de células tumorales. Objetivo: Se ensayaron cinco aislamientos de rotavirus adaptados a células tumorales para determinar su capacidad para infectar la línea celular de adenocarcinoma humano MCF-7. Métodos: Las proteínas asociadas a la membrana de la superficie celular que median la unión de partículas de virus se caracterizaron mediante ELISA, inmunoprecipitación, análisis FACS y bloqueo de anticuerpos. Resultados: Se encontró que las proteínas de choque térmico (HSPs) como Hsp90, Hsp70, Hsp60 y Hsp40 se expresan en la superficie celular formando complejos con la proteína disulfuro isomerasa (PDI), la integrina β3 y la proteína análoga de choque térmico 70 (Hsc70) en microdominios lipídicos (rafts). La interacción de los aislamientos de rotavirus con estas proteínas celulares se confirmó adicionalmente mediante un ensayo de competición y un ensayo de inhibición que incluía las HSP ensayadas. Conclusión: Nuestros hallazgos sugieren que los aislamientos de rotavirus adaptados a las células tumorales estudiados aquí ofrecen una herramienta prometedora para eliminar las células tumorales, lo que estimula más investigaciones sobre este tema, incluidos los modelos animales.


Subject(s)
Humans , Adenocarcinoma , Rotavirus , Oncolytic Viruses , Heat-Shock Proteins , Adenocarcinoma/therapy , HSC70 Heat-Shock Proteins , MCF-7 Cells
13.
Article in Chinese | WPRIM | ID: wpr-907527

ABSTRACT

Objective:To investigate the interaction between heat shock protein 90 (Hsp90) and silent mating-type information regulation 2 homolog 1 (SIRT1) and evaluate its effect on epithelial-mesenchymal transition (EMT) of lung cancer A549 cells.Methods:EMT model was established by treating lung cancer A549 cells with 5 μg/L transforming growth factor-β1 (TGF-β1), which was used as TGF-β1 group, and the normal lung cancer A549 cells were used as control group. The interaction between Hsp90 and SIRT1 in lung cancer A549 cells was detected by immunocoprecipitation method. The expression of Hsp90 gene was silenced by RNA interference technique, and the cells were divided into TGF-β1 group, TGF-β1+ siRNA-Hsp90-neg group and TGF-β1+ siRNA-Hsp90 group. Transwell invasion assay was used to investigate the effect of the interaction of Hsp90 and SIRT1 on the invasion ability of lung cancer A549 cells. The expressions of Hsp90, SIRT1, E-cadherin and vimentin were detected by Western blotting. The effect of inhibiting Hsp90 expression on the stability of SIRT1 protein and EMT of lung cancer A549 cells was observed.Results:After 48 h induction with TGF-β1, EMT characteristics of lung cancer A549 cells were induced successfully. The relative expression levels of Hsp90 protein in the control group and TGF-β1 group were 0.45±0.05 and 1.31±0.06, respectively, the relative expression levels of SIRT1 protein were 0.29±0.04 and 0.95±0.08, respectively, and there were statistically signigicant differences ( t=10.98, P=0.018; t=7.39, P=0.028). The results of immunocoprecipitation showed that there was an interaction between Hsp90 and SIRT1 protein in lung cancer A549 cells. The relative expression levels of Hsp90 in the TGF-β1 group, TGF-β1+ siRNA-Hsp90-neg group and TGF-β1+ siRNA-Hsp90 group were 0.75±0.07, 0.63±0.06 and 0.23±0.05, respectively, and there was a statistically significant difference ( F=18.85, P=0.012). The relative expression levels of SIRT1 in the above three groups were 0.99±0.08, 0.97±0.12 and 0.35±0.05, respectively, and there was a statistically significant difference ( F=16.52, P=0.014). The expression levels of Hsp90 and SIRT1 in the TGF-β1+ siRNA-Hsp90 group were significantly lower than those in the TGF-β1 group ( P=0.019, P=0.016). The numbers of cells passing Matrigel in the above three groups were 378.13±27.70, 323.52±19.82 and 142.51±22.54, respectively, and there was a statistically significant difference ( F=27.35, P=0.022). The number of cells passing Matrigel in the TGF-β1+ siRNA-Hsp90 group was significantly less than that in the TGF-β1 group ( P=0.028). The relative expression levels of E-cadherin in the above three groups were 0.31±0.02, 0.34±0.04 and 0.63±0.05, respectively, and there was a statistically significant difference ( F=19.39, P=0.031). The relative expression levels of vimentin in the above three groups were 0.33±0.02, 0.27±0.05 and 0.09±0.03, respectively, and there was a statistically significant difference ( F=12.58, P=0.012). The expression level of E-cadherin in the TGF-β1+ siRNA-Hsp90 group was significantly higher than that in the TGF-β1 group ( P=0.017), while the expression level of vimentin was significantly lower than that in the TGF-β1 group ( P=0.023). Conclusion:Hsp90 interacts with SIRT1, and Hsp90 inhibition can lead to the decrease of SIRT1 protein level. Hsp90 may play a role of molecular chaperone to maintain the conformation stability of SIRT1, and the interaction between Hsp90 and SIRT1 may be one of the molecular mechanisms for the occurrence of EMT and the enhancement of invasion ability of lung cancer A549 cells.

14.
Article in Chinese | WPRIM | ID: wpr-908721

ABSTRACT

Objective:To investigate the expression of serum heat shock protein 70 (HSP70), soluble programmed death protein 1 (sPD-1), and 25-hydroxy vitamin D 3 in hepatitis B associated liver cirrhosis (HBLC) combined with type 2 diabetes mellitus (T2DM) and their value in prognostic prediction. Methods:The clinical data of 97 patients with HBLC combined with T2DM (HBLC combined with T2DM group), 105 patients with HBLC (HBLC group) and 118 patients with T2DM (T2DM group) from June 2018 to November 2019 in Zhejiang Putuo Hospital were prospectively analyzed. The serum levels of HSP70, sPD-1 and 25-hydroxy vitamin D 3 were compared among 3 groups, and the correlation between above serum indexes and liver function indexes, blood sugar indexes were analyzed. The liver function indexes included alanine aminotransferase (ALT) and aspartate aminotransferase (AST), and the blood sugar indexes included fasting blood glucose (FBG) and glycosylated hemoglobin (HbA 1c). According to the prognosis 6 months later, the patients with HBLC combined with T2DM were divided into poor prognosis (28 cases) and good prognosis (69 cases), and the HSP70, sPD-1, 25-hydroxy vitamin D 3 and liver function Child-Pugh classification were compared. The predictive value of serum HSP70, sPD-1 and 25-hydroxy vitamin D 3 on prognosis in patients with HBLC combined with T2DM was analyzed by receiver operating characteristic (ROC) curve. Results:The HSP70 and sPD-1 in HBLC combined with T2DM group were significantly higher than those in HBLC group and T2DM group: (4.28 ± 1.19) μg/L vs. (2.27 ± 0.76) and (2.40 ± 0.84) μg/L, (7.86 ± 2.45) ng/L vs. (4.23 ± 1.62) and (3.85 ± 1.27) ng/L, the 25-hydroxy vitamin D 3 was significantly lower than that in HBLC group and T2DM group: (13.62 ± 3.96) μg/L vs. (18.63 ± 6.11) and (17.45 ± 4.36) μg/L, and there were statistical differences ( P<0.05); there were no statistical differences between HBLC group and T2DM group ( P>0.05). The Pearson correlation analysis result showeds that HSP70 and sPD-1 were positively correlated with ALT, AST, FBG and HbA 1c ( P<0.01), the 25-hydroxy vitamin D 3 was negatively correlated with ALT, AST, FBG and HbA 1c ( P<0.01) in patients with HBLC combined with T2DM. In patients with HBLC combined with T2DM, the HSP70, sPD-1 and rate of Child-Pugh classification B in patients with poor prognosis were significantly higher than those in patients with good prognosis: (6.03 ± 1.63) μg/L vs. (3.57 ± 1.02) μg/L, (9.86 ± 1.59) ng/L vs. (7.05 ± 2.62) ng/L and 71.43% (20/28) vs. 30.43% (21/69), the 25-hydroxy vitamin D 3 was significantly lower than that in patients with good prognosis: (9.26 ± 3.02) μg/L vs. (15.39 ± 5.84) μg/L, and there were statistical differences ( P<0.01 or <0.05). The ROC curve analysis result showed that the area under curve of HSP70, sPD-1 combined with 25-hydroxy vitamin D 3 in predicting prognosis was the highest in patients with HBLC combined with T2DM, which was 0.890, with a sensitivity of 89.29% and a specificity of 79.71%. Conclusions:The levels of serum HSP70 and sPD-1 in patients with HBLC combined with T2DM increase, and the level of 25-hydroxy vitamin D 3 decreases. There is a good linear relationship with liver function and blood glucose. Early combined detection of the above serum levels can provide new ideas for clinical implementation of symptomatic treatment and prognosis prediction.

15.
Int. j. morphol ; 38(5): 1455-1462, oct. 2020. tab, graf
Article in English | LILACS | ID: biblio-1134462

ABSTRACT

SUMMARY: This study aimed to investigate the changes in testis tissue of thioacetamide-induced rats and the effect of melatonin on these changes. Thirty-five male Wistar Albino rats were divided into five groups. Group I; Control (n=7), Group II; Melatonin (Mel) (10 mg/kg) a single dose (i.p)(n=7), Group III; Thioacetamide (TAA) (300 mg/kg) (i.p) 2 times with 24 hour intervals (n=7), Group IV; TAA (300 mg/kg) was administered at 24-hour intervals, afterwards of 10 mg/kg single dose of Mel (n=7), Group V; Mel was administered 10 mg/kg a single dose 24 hours before the administration of TAA (n=7). Testis was evaluated histologically, immunohistochemically (Heat Shock Proteins (HSP) 70 and 90), blood serum testosterone, total antioxidant status(TAS) and total oxidant status(TOS) in tissue. The tissue sections of Group III decreased seminiferous tubule diameters, and germinal epithelium spills were observed. HSP70 and HSP90 expressions were increased. There wasn't a statistically significant change in testosterone levels among the groups. While TAS levels decreased in Group III compared to control, TOS levels didn't change. HSP70 and HSP90 decreased in groups with Mel-treated. Mel was found to have both protective and therapeutic effects. According to our results, the therapeutic effect of Mel in thioacetamide-induced acute testicular injury is greater than its protective effect.


RESUMEN: Este estudio tuvo como objetivo investigar los cambios en el tejido testicular de ratas inducidas por tioacetamida y el efecto de la melatonina en estos cambios. Treinta y cinco ratas macho Wistar Albino se dividieron en cinco grupos. Grupo I; Control (n = 7), Grupo II; Melatonina (Mel) (10 mg / kg) una dosis única (i.p) (n = 7), Grupo III; Tioacetamida (TAA) (300 mg / kg) (i.p) 2 veces con intervalos de 24 horas (n = 7), Grupo IV; TAA (300 mg / kg) se administró a intervalos de 24 horas, luego de una dosis única de 10 mg / kg de Mel (n = 7), Grupo V; Mel recibió 10 mg / kg de una dosis única 24 horas antes de la administración de TAA (n = 7). Los testículos se evaluaron histológicamente, inmunohistoquímicamente (proteínas de choque térmico (PCT) 70 y 90), testosterona en suero sanguíneo, estado antioxidante total (EAT) y estado oxidante total (EOT) en el tejido. En secciones de tejido del Grupo III se observó disminución de los diámetros de los túbulos seminíferos y derrames en el epitelio germinal. Se aumentaron las expresiones HSP70 y HSP90. No hubo un cambio estadísticamente significativo en los niveles de testosterona entre los grupos. Mientras que los niveles de EAT disminuyeron en el Grupo III en comparación con el control, los niveles de EOT no cambiaron. HSP70 y HSP90 disminuyeron en los grupos tratados con Mel. Se descubrió que Mel tenía efectos protectores y terapéuticos. Según nuestros resultados, el efecto terapéutico de Mel en la lesión testicular aguda inducida por tioacetamida es mayor que su efecto protector.


Subject(s)
Animals , Male , Rats , Testis/drug effects , Thioacetamide/toxicity , Melatonin/pharmacology , Antioxidants/pharmacology , Enzyme-Linked Immunosorbent Assay , Immunohistochemistry , Rats, Wistar , Heat-Shock Proteins/drug effects , Heat-Shock Proteins/metabolism , Melatonin/administration & dosage , Antioxidants/administration & dosage
16.
Arq. bras. oftalmol ; Arq. bras. oftalmol;83(5): 378-382, Sept.-Oct. 2020. graf
Article in English | LILACS | ID: biblio-1131627

ABSTRACT

ABSTRACT Purpose: To measure humor heat-shock protein 70, periostin, and irisin levels in patients with pseudoexfoliation syndrome and cataract (without glaucoma), and compare them with those of patients with cataract but without pseudoexfoliation. Methods: We examined 31 eyes of 31 patients with pseudoexfoliation and cataract (without glaucoma) and 30 eyes of 30 patients with cataract. We collected aqueous humor samples from all patients at the time of cataract surgery through a limbal paracentesis via a 25-gauge cannula mounted on a tuberculin syringe that received 100 to 150 µL of aqueous humor. We measured levels of aqueous humor Heat shock protein 70, periostin, and irisin using enzyme-linked immunosorbent assay methods. Results: The age (p=0.221) and gender (p=0.530) means were similar between the pseudoexfoliation and control groups. The mean Heat shock protein 70 level (29.22 ± 9.46 ng/mL; 17.88-74.46) in the pseudoexfoliation group was significantly higher than that in the control group (19.03 ± 7.05 ng/mL; 9.93-35.52; p<0.0001). The mean periostin level was significantly higher (6017.32 ± 1271.79 pg/mL; 3787.50-10803.57) in the pseu doexfoliation group than that in the control group (4073.63 ± 1422.79 pg/mL; 2110.44-7490.64; p<0.0001). The mean irisin level (53.77 ± 10.19 ng/mL; 29.46-71.16) was significantly higher than that in the control group (39.29 ± 13.58 ng/mL; 19.41-70.56; p<0.0001). Conclusions: Heat shock protein 70, periostin, and irisin levels increase in the aqueous humor of patients with pseudoexfoliation without glaucoma.


RESUMO Objetivo: Comparar os níveis de proteína de choque térmico 70, de periostina e de irisina no humor aquoso de pacientes com pseudoexfoliação com catarata sem glaucoma e compará-los com pacientes com catarata sem pseudoexfoliação. Métodos: Trinta e um olhos de 31 pacientes com pseudoexfoliação com catarata sem glaucoma e 30 olhos de 30 indivíduos com catarata foram incluídos neste estudo. Amostras de humor aquoso foram coletadas de todos os pacientes no momento da cirurgia de catarata e obtidas através de uma paracentese límbica por meio de uma cânula de calibre 25 acoplada a uma seringa com tuberculina. Foram coletados 100 a 150 µL de humor aquoso. Os níveis de proteína de choque térmico 70, de periostina e de irisina no humor aquoso foram medidos usando o método de ensaio imunossorvente ligado a enzima. Resultados: A média da idade (p=0,221) e sexo (p=0,530) foram semelhantes entre os grupos pseudoexfoliação e controle. Os níveis médios de proteína de choque térmico 70 foram 29,22 ± 9,46 ng/mL (17,88-74,46) e 19,03 ± 7,05 ng/ mL (9,93-35,52) nos grupos pseudoexfoliação e controle, respectivamente. Os níveis de proteína de choque térmico 70 foram maiores no grupo pseudoexfoliação (p<0,0001). O nível médio de periostina foi de 6017,32 ± 1271,79 pg/mL (3787,50-10803,57) no grupo pseudoexfoliação e 4073,63 ± 1422,79 pg/mL (2110,44-7490,64) no grupo controle. O nível médio de periostina também foi maior no grupo pseudoexfoliação (p<0,0001). Os níveis médios de irisina foram 53,77 ± 10,19 ng/mL (29,46-71,16) e 39,29 ± 13,58 ng/mL (19,41-70,56) nos grupos pseudoexfoliação e controle, respectivamente. O nível médio de irisina foi maior no grupo pseudoexfoliação do que no grupo controle (p<0,0001). Conclusões: Os níveis de proteína de choque térmico 70, de periostina e de irisina aumentam no humor aquoso de pacientes com pseudoexfoliação sem glaucoma.


Subject(s)
Humans , Aqueous Humor , Cataract , Cell Adhesion Molecules , Glaucoma , Fibronectins , Exfoliation Syndrome , HSP70 Heat-Shock Proteins , Enzyme-Linked Immunosorbent Assay , Cell Adhesion Molecules/metabolism , Fibronectins/metabolism , Exfoliation Syndrome/metabolism , HSP70 Heat-Shock Proteins/metabolism
17.
Acta cir. bras ; Acta cir. bras;35(1): e202000105, 2020. tab, graf
Article in English | LILACS | ID: biblio-1088523

ABSTRACT

Abstract Purpose To investigate whether heat shock protein 90 (HSP90) is involved in complement regulation in ischemic postconditioning (IPC). Methods The left coronary artery of rats underwent 30 min of occlusion, followed by 120 min of reperfusion and treatment with IPC via 3 cycles of 30s reperfusion and 30s occlusion. The rats were injected intraperitoneally with 1 mg/kg HSP90 inhibitor geldanamycin (GA) after anesthesia. Eighty rats were randomly divided into four groups: sham, ischemia-reperfusion (I/R), IPC and IPC + GA. Myocardial infarct size, apoptosis index and the expression of HSP90, C3, C5a, tumor necrosis factor (TNF)-alpha, interleukin (IL)-1β and c-Jun N-terminal kinase (JNK) were assessed. Results Compared with the I/R injury, the IPC treatment significantly reduced infarct size, release of troponin T, creatine kinase-MB, and lactate dehydrogenase, and cardiomyocyte apoptosis. These beneficial effects were accompanied by a decrease in TNF-α, IL-1β, C3, C5a and JNK expression levels. However, all these effects were abrogated by administration of the HSP90 inhibitor GA. Conclusion HSP90 exerts a profound effect on IPC cardioprotection, and may be linked to the inhibition of the complement system and JNK, ultimately attenuating I/R-induced myocardial injury and apoptosis.


Subject(s)
Animals , Rats , Complement System Proteins/metabolism , Myocardial Reperfusion Injury/metabolism , Benzoquinones/pharmacology , HSP90 Heat-Shock Proteins/antagonists & inhibitors , Lactams, Macrocyclic/pharmacology , JNK Mitogen-Activated Protein Kinases/metabolism , Myocardial Infarction/metabolism , RNA, Messenger/metabolism , Random Allocation , Tumor Necrosis Factor-alpha/metabolism , Rats, Sprague-Dawley , Inflammation Mediators , Creatine Kinase, MB Form/metabolism , Ischemic Postconditioning/methods
18.
Rev. bras. cir. cardiovasc ; Rev. bras. cir. cardiovasc;34(2): 156-164, Mar.-Apr. 2019. tab, graf
Article in English | LILACS | ID: biblio-990568

ABSTRACT

Abstract Objetive: Coronary artery bypass grafting (CABG) with cardiopulmonary bypass (CPB) improved symptoms and increased survival and quality of life in patients with coronary artery disease. However, it should be the main cause of a complex organic systemic inflammatory response that greatly contributes to several postoperative adverse effects. Methods: We aimed to evaluate heat-shock protein 70 (HSP 70) expression as a morbimortality predictor in patients with preserved ventricular function undergoing coronary artery bypass grafting (CABG) with cardiopulmonary bypass (CPB) and to determine their association with the lactate as a marker of tissue hypoperfusion and the EuroSCORE risk score. This is a prospective, observational study including 46 patients and occurring between May and July 2016. Patients without ventricular dysfunction undergoing myocardial revascularization with extracorporeal circulation were included. They were divided into (1) complicated and (2) uncomplicated postoperative evolution groups. EuroSCORE, lactate levels, and HSP 70 expression and their correlations were determined. Results: Statistical analysis showed that the group with complicated evolution had higher EuroSCORE values than the other group. HSP 70 protein levels were significantly increased in the group with uncomplicated evolution and showed similar results. According to our results, HSP family proteins may be independent predictors of uncomplicated evolution in patients without ventricular dysfunction undergoing CABG with CPB. Conclusion: HSP 70 should be a good discriminator and protection marker for complications in cardiac surgery.


Subject(s)
Humans , Male , Female , Adult , Middle Aged , Aged , Aged, 80 and over , Cardiopulmonary Bypass/mortality , Coronary Artery Bypass/mortality , Risk Assessment/methods , HSP70 Heat-Shock Proteins/analysis , Lactic Acid/blood , Preoperative Period , Postoperative Complications/etiology , Biomarkers/analysis , Cardiopulmonary Bypass/methods , Logistic Models , Blotting, Western , Coronary Artery Bypass/methods , Sensitivity and Specificity , Statistics, Nonparametric , Myocardium/pathology
19.
Article in English | WPRIM | ID: wpr-761783

ABSTRACT

The present study was designed to examine the effect of heme oxygenase-1 (HO-1) induction by cobalt protoporphyrin (CoPP) on the cardiac functions and morphology, electrocardiogram (ECG) changes, myocardial antioxidants (superoxide dismutase [SOD] and glutathione [GSH]), and expression of heat shock protein (Hsp) 70 and connexin 43 (Cx-43) in myocardial muscles in isoproterenol (ISO) induced myocardial infarction (MI). Thirty two adult male Sprague Dawely rats were divided into 4 groups (each 8 rats): normal control (NC) group, ISO group: received ISO at dose of 150 mg/kg body weight intraperitoneally (i.p.) for 2 successive days; ISO + Trizma group: received (ISO) and Trizma (solvent of CoPP) at dose of 5 mg/kg i.p. injection 2 days before injection of ISO, with ISO at day 0 and at day 2 after ISO injections; and ISO + CoPP group: received ISO and CoPP at a dose of 5 mg/kg dissolved in Trizma i.p. injection as Trizma. We found that, administration of ISO caused significant increase in heart rate, corrected QT interval, ST segment, cardiac enzymes (lactate dehydrogenase, creatine kinase-muscle/brain), cardiac HO-1, Hsp70 with significant attenuation in myocardial GSH, SOD, and Cx-43. On the other hand, administration of CoPP caused significant improvement in ECG parameters, cardiac enzymes, cardiac morphology; antioxidants induced by ISO with significant increase in HO-1, Cx-43, and Hsp70 expression in myocardium. In conclusions, we concluded that induction of HO-1 by CoPP ameliorates ISO-induced myocardial injury, which might be due to up-regulation of Hsp70 and gap junction protein (Cx-43).


Subject(s)
Adult , Animals , Humans , Male , Rats , Antioxidants , Body Weight , Cobalt , Connexin 43 , Connexins , Creatine , Electrocardiography , Glutathione , Hand , Heart Rate , Heat-Shock Proteins , Heme Oxygenase-1 , Heme , HSP70 Heat-Shock Proteins , Isoproterenol , Muscles , Myocardial Infarction , Myocardium , Oxidoreductases , Tromethamine , Up-Regulation
20.
Article in Chinese | WPRIM | ID: wpr-745816

ABSTRACT

Objective To explore the mechanism of HSP70 on cell cycle regulation in hepatic IR (ischemia-reperfusion) injury.Methods SD rats were randomly divided into HSP70 inhibitor group (H-/P+),heat shock group (H+/P+),PARP-1 inhibitory group (H +/P-),IR group (PC) and negative control group (NC),respectively.After the IR model was induced,the liver specimen underwent IHC staining to observe the changes of the PARP-1 expression;Co-immunoprecipitation was used to detect the binding of HSPT0 with PARP-1.Results H +/P-was significantly different from H +/P +,H-/P +,PC,NC (P < 0.01);Immunoprecipitation suggested that HSP70 entered into the nucleus to bind PARP-1,and immunofluorescence imaging analysis demonstrated both HSP70 and CyclinD1 expressed at the same timeline.Conclusion Under reversible hepatic ischemia-reperfusion injury,HSP70 enters the nucleus and binds to PARP-1,negatively regulates G2/M phase,blocks cells for DNA replication and recombination,blocks its entry into mitosis,repairs damaged DNA chain;Liver ischemia-reperfusion positively regulates the G1/S phase,promoting hepatocyte regeneration and liver function compensation.

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