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Heat shock protein 70 dampens the inflammatory response of human PDL cells to mechanical loading in vitro.

Previously, we demonstrated an inflammatory response of human PDL (hPDL) cells to mechanical loading. The cellular reaction was dampened by heat pre-treatment suggesting a protective role for heat shock proteins (HSP) during stress-induced ischemia. Here we explored if HSP70, which has already been documented in the pressure zone of tooth movement, might be regulatorily involved in the attenuation of the inflammatory response.

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Heat Shock 70kDa Protein Human Macrophage Inflamma Human Macrophage Inflamma Human Macrophage Inflamma Human Macrophage Inflamma Human Macrophage Inflamma Human Gro g Macrophage In Heat Shock Protein 20, hu Heat Shock Protein 22, hu Heat Shock Protein 27, hu Heat Shock Protein 90, hu Heat Shock Protein 70, hu

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Hydrogen peroxide-mediated oxidative stress induces inflammasome activation in term human placental explants.

The placenta is a multifunctional organ that can suffer with imbalances between pro- and antioxidant molecules, contributing for inflammatory imbalance. The inflammation generated by oxidative stress may induce inflammasome activation, an essential complex for pro-inflammatory cytokine production.

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Curcumin inhibits liver cancer by inhibiting DAMP molecule HSP70 and TLR4 signaling.

Curcumin has been revealed to inhibit liver cancer, however, no studies have reported that the mechanism of curcumin's action on liver cancer is related to damage-associated molecular pattern (DAMP) molecules heat shock protein 70 (HSP70) and the toll-like receptor 4 (TLR4) signaling. This study aimed to investigate whether the activation of TLR4 signaling by HSP70 could be inhibited by curcumin, thus investigating the possible mechanism of curcumin in the inhibition of liver cancer. Western blotting was used to evaluate the expression of the HSP70 and TLR4 in HepG2 cells and ELISA was used to detect the concentration of HSP70 in cell culture medium. A thermal tolerance HepG2 (HepG2TT) cell model was established to simulate HSP70 accumulation in the microenvironment. A certain concentration of curcumin was co-cultured with HepG2 and HepG2TT cells to observe the changes of HSP70 and TLR4. Our results revealed that heat stress significantly increased the expression of extracellular HSP70 (eHSP70) and TLR4 (P<0.01), but significantly reduced the expression of intracellular HSP70 (P<0.01). Curcumin inhibited proliferation, invasion, and metastasis of HepG2 cells, caused cells to remain in the DNA S phase, promoted apoptosis, and significantly reduced intracellular HSP70, eHSP70 and TLR4 levels of HepG2TT cells. Following the removal of curcumin, eHSP70 increased again. In summary, our results demonstrated that the antitumor effect of curcumin was related to the inhibition HSP70-TLR4 signaling.

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Colon cancer, metastasize GI cancer (esophageal, ga Cancer Samples: Liver Ca Cancer samples: Liver Ca Liver cancer antibody scr Liver cancer tissue array Liver cancer tissue array Liver cancer tissue array High density liver cancer Liver cancer (hepatocellu Hepatic disease spectrum Liver cancer survey tissu

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T-helper 2 cytokine-induced heat shock protein 70 secretion and its potential association with allergic rhinitis.

Various inflammatory mediators have been found to be involved in the pathogenesis of allergic disease (AR). The role of heat shock proteins in AR has not been studied. The aim of this study was to investigate the levels of heat shock protein 70 (Hsp70) in the nasal lavage fluids of AR patients and controls to elucidate the role of Hsp70 in the pathogenesis of AR.

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Heat Shock 70kDa Protein Heat Shock Protein 70 (H Heat Shock Protein 70 (H Heat Shock Protein 20, hu Heat Shock Protein 22, hu Heat Shock Protein 27, hu Heat Shock Protein 65, my Heat Shock Protein 90, hu Heat Shock Protein 70, hu Heat Shock Protein 70, hu Heat Shock Protein 70, hu HSP90C | alfa HSP90C, hea

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Primary Human and Rat β-Cells Release the Intracellular Autoantigens GAD65, IA-2, and Proinsulin in Exosomes Together With Cytokine-Induced Enhancers of Immunity.

The target autoantigens in several organ-specific autoimmune diseases, including type 1 diabetes (T1D), are intracellular membrane proteins, whose initial encounter with the immune system is poorly understood. Here we propose a new model for how these proteins can initiate autoimmunity. We found that rat and human pancreatic islets release the intracellular β-cell autoantigens in human T1D, GAD65, IA-2, and proinsulin in exosomes, which are taken up by and activate dendritic cells. Accordingly, the anchoring of GAD65 to exosome-mimetic liposomes strongly boosted antigen presentation and T-cell activation in the context of the human T1D susceptibility haplotype HLA-DR4. Cytokine-induced endoplasmic reticulum stress enhanced exosome secretion by β-cells; induced exosomal release of the immunostimulatory chaperones calreticulin, Gp96, and ORP150; and increased exosomal stimulation of antigen-presenting cells. We propose that stress-induced exosomal release of intracellular autoantigens and immunostimulatory chaperones may play a role in the initiation of autoimmune responses in T1D.

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Urine heat shock protein 70 levels as a marker of urinary tract infection in children.

Heat shock proteins (HSPs) are a multi-family group of proteins which are upregulated by the cell in response to exposure to hazardous (stress) factors, including infectious agents, to prevent changes in protein structure. The aim of our study was to assess whether urine levels of the 70-kDa family of HSPs (HSP70s) increase in children with urinary tract infection (UTI) and to determine the optimal urine (u) HSP70 cut-off level to predict UTI in children.

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Characterization of calcium oxalate crystal-induced changes in the secretome of U937 human monocytes.

In kidney stone disease, migratory monocytes have been found to mediate progressive renal inflammation through the secretion of numerous inflammatory mediators. However, whether calcium oxalate monohydrate (COM), which is the major crystalline compound of kidney stones, has any effects on proteins secreted from monocytes remained largely unknown. The present study aimed to characterize changes in the secretome of U937 human monocytes induced by COM crystals. The viability of cells in serum/protein-free medium was serially evaluated and the data revealed that an exposure time of 16 h was optimal for this study, whereas prolonged incubation for 24 h resulted in declined cell viability. Using this optimal time-point, the secreted proteins recovered from serum/protein-free culture supernatants of controlled and COM-treated cells were resolved in 2-DE and stained with Deep Purple fluorescent dye. Quantitative intensity analysis revealed statistically significant changes in levels of 18 secreted proteins (14 increased and 4 decreased) from COM-treated cells. These significantly altered secreted proteins were then identified by Q-TOF MS and/or MS/MS analyses. Among these, the increased levels of secreted heat shock protein 90 (HSP90), HSP70 and β-actin were confirmed by Western blot analysis. The increased level of extracellular HSP90 was confirmed on the COM-treated cell surface by the immunofluorescence study, whereas the increased secretion of IFN-α was validated by ELISA. Global protein network analysis, literature search and bioinformatics revealed that these significantly altered secreted proteins were involved mainly in immune response and cell survival. Therefore, changes in the secretome of monocytes induced by COM crystals may be related, at least in part, to progressive renal inflammation found in kidney stone disease.

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Effects of oxygen on the antigenic landscape of prostate cancer cells.

Use of allogeneic cancer cells-based immunotherapy for treatment of established prostate cancer (PCa) has only been marginally effective. One reason for failure could stem from the mismatch of antigenic signatures of vaccine cells and cancer in situ. Hence, it is possible that vaccine cells expressed antigens differently than tumor cells in situ. We hypothesized that cells grown in vitro at low oxygen tension (pO2) provide a better antigen match to tumors in situ and could reveal a more relevant antigenic landscape than cells grown in atmospheric pO2.

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Preclinical Study of AUY922, a Novel Hsp90 Inhibitor, in the Treatment of Esophageal Adenocarcinoma.

To assess the efficacy of heat-shock protein 90 (Hsp90) inhibitor, NVP-AUY922-AG (AUY922), in the treatment of esophageal adenocarcinoma (EAC) in vitro and in vivo.

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Identification and analysis of exosomes secreted from macrophages extracted by different methods.

Exosomes were small vesicles secreted by many cells, and they can play an important role in cell signal transductions. Because the diameter of exosomes is about 30-100 nm, it is so difficult to collection them. In this paper, three kinds of exosomes purifying methods (density gradient ultracentrifugation method, the ultracentrifugation and ultrafiltration method, ExoQuick™ Extraction kit method) were used to collected exosomes in culture supernatants of macrophages. The morphologies of three kinds of exosomes were analyzed by transmission electron microscopy (TEM), and the characteristic molecules such as CD86, LAMP-1, HSP-70 on exosomes were analyzed with Western blot. In addition, the biological activities of exosomes purified by three kinds of methods in vitro were analyzed by ELISA and flow cytometry methods. All experimental results show that the purity and quality of exosomes collected by ExoQuick™ extraction kit and ultracentrifugation and ultrafiltration method were better, and they could enhance the expression of MHC-I in macrophages and promote cells to secrete more TNF-α to cause inflammatory response of macrophages. The analysis pointed out that the advantages and disadvantages of the three methods by biological activities or components of exosomes. Therefore, the ultracentrifugation and ultrafiltration method or the ExoQuick™ Extraction kit method were more suitable to be applied in the scientific research.

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