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Background: Diabetic peripheral neuropathy (DPN) in children and adolescents with type 1 diabetes mellitus (T1DM) is a growing issue, with controversial data in the terms of prevalence and evaluation timelines. Currently, there are no clear standards for its early detection. Therefore, our aim was to assess the contribution of the Michigan neuropathy screening instrument (MNSI), lipid profile, serum neuron specific enolase (NSE), and serum heat shock protein 27 (HSP 27) to the prediction of DPN in children and adolescents with T1DM. Methods: In this case-control study, fifty children diagnosed with T1DM for at least five years were enrolled and evaluated through complete neurological examination, MNSI, and nerve conduction study (NCS). Additionally, HbA1c, lipid profile, serum NSE, and serum HSP 27 levels were measured for patients and controls. Results: The prevalence of DPN in our study was 24% by NCS, and electrophysiological changes showed a statistically significant lower conduction velocity for the posterior tibial and sural nerves, as well as a prolonged latency period for the common peroneal and sural nerves in neuropathic patients. In these patients, older age, earlier age of diabetes onset, longer disease duration, higher total cholesterol, triglycerides, low density lipoprotein cholesterol, HbA1c, serum NSE, and HSP27 levels were observed. The MNSI examination score ≥ 1.5 cutoff point had an area under the curve (AUC) of 0.955, with 75% sensitivity and 94.74% specificity, according to receiver operating characteristic curve analysis. However, the questionnaire's cutoff point of ≥ 5 had an AUC of 0.720, 75% sensitivity, and 63% specificity, with improved overall instrument performance when combining both scores. Regarding blood biomarkers, serum NSE had greater sensitivity and specificity in discriminating neuropathic patients than HSP27 (92% and 74% versus 75% and 71%, respectively). Regression analysis revealed a substantial dependency for MNSI and serum NSE in predicting DPN in patients. Conclusions: Despite limited research in pediatrics, MNSI and serum NSE are promising predictive tools for DPN in children and adolescents with T1DM, even when they are asymptomatic. Poor glycemic control and lipid profile changes may play a critical role in the development of DPN in these patients, despite conflicting results in various studies. [ABSTRACT FROM AUTHOR]

Abstract Background Diabetic peripheral neuropathy (DPN) in children and adolescents with type 1 diabetes mellitus (T1DM) is a growing issue, with controversial data in the terms of prevalence and evaluation timelines. Currently, there are no clear standards for its early detection. Therefore, our aim was to assess the contribution of the Michigan neuropathy screening instrument (MNSI), lipid profile, serum neuron specific enolase (NSE), and serum heat shock protein 27 (HSP 27) to the prediction of DPN in children and adolescents with T1DM. Methods In this case-control study, fifty children diagnosed with T1DM for at least five years were enrolled and evaluated through complete neurological examination, MNSI, and nerve conduction study (NCS). Additionally, HbA1c, lipid profile, serum NSE, and serum HSP 27 levels were measured for patients and controls. Results The prevalence of DPN in our study was 24% by NCS, and electrophysiological changes showed a statistically significant lower conduction velocity for the posterior tibial and sural nerves, as well as a prolonged latency period for the common peroneal and sural nerves in neuropathic patients. In these patients, older age, earlier age of diabetes onset, longer disease duration, higher total cholesterol, triglycerides, low density lipoprotein cholesterol, HbA1c, serum NSE, and HSP27 levels were observed. The MNSI examination score ≥ 1.5 cutoff point had an area under the curve (AUC) of 0.955, with 75% sensitivity and 94.74% specificity, according to receiver operating characteristic curve analysis. However, the questionnaire’s cutoff point of ≥ 5 had an AUC of 0.720, 75% sensitivity, and 63% specificity, with improved overall instrument performance when combining both scores. Regarding blood biomarkers, serum NSE had greater sensitivity and specificity in discriminating neuropathic patients than HSP27 (92% and 74% versus 75% and 71%, respectively). Regression analysis revealed a substantial dependency for MNSI and serum NSE in predicting DPN in patients. Conclusions Despite limited research in pediatrics, MNSI and serum NSE are promising predictive tools for DPN in children and adolescents with T1DM, even when they are asymptomatic. Poor glycemic control and lipid profile changes may play a critical role in the development of DPN in these patients, despite conflicting results in various studies.

Introduction: Many biomarkers are used to assess the severity of sepsis and septic shock (SS), but none are highly sensitive in predicting outcome. Aim of the research: To estimate the value of serum changes of C-reactive protein, procalcitonin, presepsin, heat shock protein 27 (HSP27) and neutrophil to lymphocyte ratio in assessing the prognosis in patients with SS treated in an intensive care unit. Material and methods: Thirty-seven selected adult patients with SS were included. Serum concentrations of biomarkers were measured at admission and daily for 4 consecutive days (time points T0, T1, T2, T3 and T4 respectively). The mortality rate was determined 28 days after admission. Patients were divided into survivor and non-survivor groups according to their mortality. The differences between the levels of biomarkers at the time points T0 and T4 were analyzed. Results: The mean value of the SOFA score on admission was 11.7 ±2.7, and the APACHE II scale 29.9 ±6.85. Nine patients died. Univariate logistic analysis revealed that changes between T0 and T4 of presepsin, procalcitonin, and HSP27 were associated with prognosis. A multivariate Cox analysis showed that an increase in HSP27 at T4 was the only independent predictor of good prognosis in SS patients. The area under the receiver operating characteristics curve for HSP27 was 0.785. Kaplan-Meier analysis showed that the mortality was lower (p = 0.014) in patients who had an increase in HSP27 at T4 compared to those whose serum HSP27 did not increase at T4. Conclusions: The increase of HSP27 level on the 4th day predicts a favorable outcome in SS patients. [ABSTRACT FROM AUTHOR]

We studied the effect of the HSP27 inhibitor, 5-(5-ethyl-2-hydroxy-4-methoxyphenyl)-4-(4-methoxyphenyl)-isoxazole, at a final concentration of 0.1 μM and/or the apoptosis inducer dexamethasone at a final concentration of 10 μM on the content of hydroxyl radical, reduced and oxidized glutathione, HSP27, activity of glutathione reductase, glutathione peroxidase, caspase-3, and the number of Annexin+ Jurkat tumor cells. The involvement of HSP27 in apoptosis of Jurkat tumor cells was demonstrated. Simultaneous exposure to the HSP27 inhibitor and dexamethasone resulted in an increase in the level of HSP27 against the background of developing oxidative stress (increase in the concentration of hydroxyl radicals and changes in the state of the glutathione system). [ABSTRACT FROM AUTHOR]

Background: Adolescent idiopathic scoliosis (AIS) is a scoliotic deformity of unknown etiology that occurs during adolescent development. Abnormal bone metabolism is closely related to AIS, but the cause is uncertain. Recent studies have shown that heat shock protein 27 (HSP27) and its phosphorylation (pHSP27) play important roles in bone metabolism. However, whether HSP27 and pHSP27 are involved in abnormal bone metabolism in AIS is unclear. Methods: Osteoblasts (OBs) and bone marrow stem cells (BMSCs) were extracted from the facet joints and bone marrow of AIS patients and controls who underwent posterior spinal fusion surgery. The expression levels of HSP27 and pHSP27, as well as the expression levels of bone formation markers in OBs from AIS patients and controls, were examined by quantitative real‐time PCR (qRT–PCR) and Western blotting. The mineralization ability of OBs from AIS patients and controls was analyzed by alizarin red staining after osteogenic differentiation. Heat shock and thiolutin were used to increase the levels of pHSP27 in OBs, and the levels of bone formation markers were also investigated. In addition, the levels of pHSP27 and the bone formation ability of BMSCs from AIS patients and controls were investigated after heat shock treatment. Results: Lower pHSP27 levels and impaired osteogenic differentiation abilities were observed in the OBs of AIS patients than in those of controls. Thiolutin increased HSP27 phosphorylation and increased the mRNA levels of SPP1 and ALPL in OBs from AIS patients. Heat shock treatment increased SPP1 and HSP27 mRNA expression, pHSP27 levels, OCN expression, and mineralization ability of both OBs and BMSCs from AIS patients. Conclusion: Heat shock treatment and thiolutin can increase the levels of pHSP27 and further promote the bone formation of OBs and BMSCs from AIS patients. Therefore, decreased pHSP27 levels may be associated with abnormal bone metabolism in AIS patients. [ABSTRACT FROM AUTHOR]

Abstract Background Adolescent idiopathic scoliosis (AIS) is a scoliotic deformity of unknown etiology that occurs during adolescent development. Abnormal bone metabolism is closely related to AIS, but the cause is uncertain. Recent studies have shown that heat shock protein 27 (HSP27) and its phosphorylation (pHSP27) play important roles in bone metabolism. However, whether HSP27 and pHSP27 are involved in abnormal bone metabolism in AIS is unclear. Methods Osteoblasts (OBs) and bone marrow stem cells (BMSCs) were extracted from the facet joints and bone marrow of AIS patients and controls who underwent posterior spinal fusion surgery. The expression levels of HSP27 and pHSP27, as well as the expression levels of bone formation markers in OBs from AIS patients and controls, were examined by quantitative real‐time PCR (qRT–PCR) and Western blotting. The mineralization ability of OBs from AIS patients and controls was analyzed by alizarin red staining after osteogenic differentiation. Heat shock and thiolutin were used to increase the levels of pHSP27 in OBs, and the levels of bone formation markers were also investigated. In addition, the levels of pHSP27 and the bone formation ability of BMSCs from AIS patients and controls were investigated after heat shock treatment. Results Lower pHSP27 levels and impaired osteogenic differentiation abilities were observed in the OBs of AIS patients than in those of controls. Thiolutin increased HSP27 phosphorylation and increased the mRNA levels of SPP1 and ALPL in OBs from AIS patients. Heat shock treatment increased SPP1 and HSP27 mRNA expression, pHSP27 levels, OCN expression, and mineralization ability of both OBs and BMSCs from AIS patients. Conclusion Heat shock treatment and thiolutin can increase the levels of pHSP27 and further promote the bone formation of OBs and BMSCs from AIS patients. Therefore, decreased pHSP27 levels may be associated with abnormal bone metabolism in AIS patients.

BACKGROUND: The intestinal epithelium acts as a barrier against harmful luminal materials, thus preventing intestinal diseases and maintaining intestinal health. Heat shock protein 27 (HSP27) promotes intestinal epithelial integrity under both physiological and stressed conditions. The effects of partially hydrolyzed guar gum (PHGG) on HSP27 expression in intestinal Caco‐2 cells and mouse intestines were investigated. RESULTS: The present study showed that PHGG upregulated HSP27 expression in Caco‐2 cells without upregulating Hspb1, the gene encoding HSP27. Feeding PHGG increased HSP25 expression in epithelial cells of the small intestine of mice. Inhibition of protein translation using cycloheximide suppressed PHGG‐mediated HSP27 expression, indicating that PHGG upregulated HSP27 via translational modulation. Signaling inhibition of the mechanistic target of rapamycin (mTOR) and phosphatidyl 3‐inositol kinase reduced PHGG‐mediated HSP27 expression, whereas mitogen‐activated protein kinase kinase inhibition by U0126 increased HSP27 expression, irrespective of PHGG administration. PHGG increases mTOR phosphorylation and reduces extracellular signal‐regulated protein kinase (ERK) phosphorylation. CONCLUSION: PHGG‐mediated translation of HSP27 in intestinal Caco‐2 cells and mouse intestine via the mTOR and ERK signaling pathways may promote intestinal epithelial integrity. These findings help us better understand how dietary fibers regulate the physiological function of the intestines. © 2023 Society of Chemical Industry. [ABSTRACT FROM AUTHOR]

Background: Pulmonary fibrosis (PF) is a progressive lung disease characterized by fibroblast accumulation and collagen deposition, resulting in lung scarring and impaired gas exchange. Current treatments for idiopathic pulmonary fibrosis (IPF) have limited efficacy and significant side effects. Heat shock protein 27 (HSP27) has emerged as a potential therapeutic target for PF due to its involvement in fibrotic processes. However, effective HSP27 inhibitors for PF treatment are still lacking. Methods: To assess the anti-fibrotic effects of NA49, we utilized murine PF models induced by radiation (IR) or bleomycin (BLM). We administered NA49 to the PF mice and evaluated its impact on lung fibrosis progression. We also investigated the molecular mechanisms underlying NA49's effects, focusing on its inhibition of EMT-related signaling pathways. Results: In our study, we evaluated the potential of a novel HSP27 inhibitor, NA49, in preclinical models of PF. NA49 effectively suppressed PF development in radiation and bleomycin-induced PF models. It reduced fibrosis, inhibited NFkB signaling, and downregulated EMT-related molecules. Importantly, we evaluated the safety profile of NA49 by assessing its impact on DNA strand breakage. Compared to previous HSP27 inhibitors, NA49 showed lower levels of DNA damage in human lung epithelial cells, and suggests that NA49 may have reduced toxicity compared to other HSP27 inhibitors. Overall, our results demonstrate that NA49 effectively inhibits PF development in preclinical models. It reduces lung fibrosis, inhibits EMT-related signaling pathways, and exhibits improved safety profiles. These findings highlight the potential of NA49 as a promising candidate for the treatment of PF. Conclusion: NA49 exhibited significant anti-fibrotic effects, inhibiting fibrosis development and EMT-related signaling pathways. Moreover, NA49 showed improved safety profiles compared to previous HSP27 inhibitors. [ABSTRACT FROM AUTHOR]

Objective: To explore the relationship between serum tumor abnormal protein(TAP), trefoil factor 3(TFF3) and the sensitivity and prognosis of containing oxaliplatin chemotherapy regimen in patients with advanced gastric cancer. Methods: 115 patients with advanced gastric cancer who were admitted to Affiliated Hospital of Hebei University from January 2017 to January 2020 were selected. All patients received containing oxaliplatin chemotherapy regimen treatment, and they were divided into sensitive group(47 cases)and drug-resistant group(68 cases) according to the efficacy. Serum TAP and TFF3 levels were detected before chemotherapy, and the value of TAP and TFF3 in predicting the efficacy of oxaliplatin chemotherapy in patients with advanced gastric cancer was analyzed by receiver operating characteristic(ROC) curve. After treatment of follow-up, Wilcoxon analysis was used to analyze the difference in the median OS survival time of patients with advanced gastric cancer with different serum TAP and TFF3 expression. Results: Serum TAP and TFF3 levels in the drug-resistant group were higher than those in the sensitive group(P＜0.05). TAP and TFF3 predicted the area under curve of containing oxaliplatin chemotherapy resistance of patients with advanced gastric cancer were 0.717 and 0.690, respectively,combined TAP and TFF3 predicted the area under curve of containing oxaliplatin chemotherapy resistance of patients with advanced gastric cancer was 0.801, which was higher than TAP and TFF3 alone detection. During follow-up, 2 cases were lost to follow-up, and 54cases died, the median OS survival time of patients with high level of TAP and high level of TFF3 and advanced gastric cancer were lower than those of patients with low level of TAP and low level of TFF3 and advanced gastric cancer(P＜0.05). Conclusion: Serum TAP and TFF3 levels were significantly higher in advanced gastric cancer patients who were resistant to containing oxaliplatin chemotherapy, and high levels of TAP and TFF3 were associated with a shorter median OS survival time in advanced gastric cancer patients, and the combined detection of serum TAP and TFF3 may predict chemotherapeutic responsiveness and prognosis in advanced gastric cancer patients. [ABSTRACT FROM AUTHOR]

Purpose: Heat shock proteins (HSP-27) are reported to be involved in the pathophysiology of diabetes complications. The purpose of the current study is to assess the effects of eicosapentaenoic acid (EPA) supplementation on serum HSP-27, glycemic status and anthropometric indices in type 2 diabetes mellitus (T2DM) patients. Methods: Thirty-six patients with T2DM were randomly allocated to obtain 2 g per day EPA (n = 18) or placebo (n = 18) for 8 weeks in a randomized, double-blind, placebo-controlled clinical trial. Fasting serum levels of HSP 27, fasting blood sugar, hemoglobin A1C, as well as anthropometric indices were measured. Results: EPA supplementation reduces the serum level of HSP 27 in the EPA group compared with the placebo (P < 0.03). Although waist circumference (WC) decreased significantly in the EPA group at the end of the trial (P < 0.02), there was no significant difference in weight, WC, body mass index (BMI), and glycemic markers in both groups after intervention (P > 0.05). Conclusions: We found that EPA supplementation reduces HSP 27 serum level in T2DM patients. However, future large-scale trials are needed. [ABSTRACT FROM AUTHOR]

Heat shock protein 27 (HSP27) is a small chaperone protein that is overexpressed in a variety of cellular stress states. It is involved in regulating proteostasis and protecting cells from multiple sources of stress injury by stabilizing protein conformation and promoting the refolding of misfolded proteins. Previous studies have confirmed that HSP27 is involved in the development of cardiovascular diseases and plays an important regulatory role in this process. Herein, we comprehensively and systematically summarize the involvement of HSP27 and its phosphorylated form in pathophysiological processes, including oxidative stress, inflammatory responses, and apoptosis, and further explore the potential mechanisms and possible roles of HSP27 in the diagnosis and treatment of cardiovascular diseases. Targeting HSP27 is a promising future strategy for the treatment of cardiovascular diseases.

In cancer, antigen-presenting cells (APC), including dendritic cells (DCs), take up and process proteins to mount adaptive antitumor immune responses. This often happens in the context of inflamed cancer, where reactive oxygen species (ROS) are ubiquitous to modify proteins. However, the inflammatory consequences of oxidized protein uptake in DCs are understudied. To this end, we investigated human monocyte-derived cell surface marker expression and cytokine release profiles when exposed to oxidized and native proteins. Seventeen proteins were analyzed, including viral proteins (e.g., CMV and HBV), inflammation-related proteins (e.g., HO1 and HMGB1), matrix proteins (e.g., Vim and Coll), and vastly in the laboratory used proteins (e.g., BSA and Ova). The multifaceted nature of inflammation-associated ROS was mimicked using gas plasma technology, generating reactive species cocktails for protein oxidation. Fourteen oxidized proteins led to elevated surface marker expression levels of CD25, CD40, CD80, CD86, and MHC-II as well as strongly modified release of IL6, IL8, IL10, IL12, IL23, MCP-1, and TNFα compared to their native counterparts. Especially IL8, heme oxygenase 2, and vimentin oxidation gave pronounced effects. Furthermore, protein kinase phospho-array studies in monocyte-derived cells pulsed with native vs. oxidized IL8 and insulin showed enhanced AKT and RSK2 phosphorylation. In summary, our data provide for the first time an overview of the functional consequences of oxidized protein uptake by human monocyte-derived cells and could therefore be a starting point for exploiting such principle in anticancer therapy in the future. [ABSTRACT FROM AUTHOR]

Pseudorabies (PR) is a domestic and wild animal infectious disease caused by the pseudorabies virus (PRV) and is one of the major infectious diseases that endanger the global swine industry. Studies have reported that PRV may achieve cross-species transmission from pigs to humans in recent years. Therefore, in-depth exploration of the relationship between PRV and host proteins is of great significance for elucidating the pathogenic mechanism of PRV and anti-PRV infection. Here, we report that heat shock protein 27 (HSP27) ubiquitinates and degrades cyclic GMP-AMP synthase (cGAS) and attenuates cGAS-mediated antiviral responses, thereby promoting PRV infection. Overexpression of HSP27 promoted PRV proliferation in vitro, while knockdown of HSP27 inhibited PRV infection. Importantly, we found that HSP27 inhibited PRV infection or poly(dA:dT)-activated IFN-β expression. Further studies found that HSP27 may inhibit cGAS-STING-mediated IFN-β expression through targeting cGAS. In addition, we found that HSP27 can suppress the expression of endogenous cGAS in different cells at both gene transcription and protein expression levels, and that HSP27 interacts with and ubiquitinates cGAS. In conclusion, we reveal for the first time that HSP27 is a novel negative regulator of the cGAS-STING signaling pathway induced by PRV infection or poly(dA:dT) activation and demonstrate that HSP27 plays a crucial role in PRV infection. [ABSTRACT FROM AUTHOR]

Heart failure (HF), an end-stage clinical syndrome secondary to cardiac impairment, significantly affects patients' quality of life and long-term prognosis. Myocardial fibrosis leads to systolic and diastolic dysfunction, and promotes the progression of HF. Several studies involving the modulation of myocardial fibrosis have been conducted in an effort to improve cardiac function. Heat shock protein 27 (HSP27) is a small chaperone protein that is overexpressed in cellular stress states. HSP27 modulates epithelial-mesenchymal transition, playing a crucial role in the pathology of several fibrotic diseases. However, its association with myocardial fibrosis regulation is unknown. This study aimed to investigate the mechanisms by which HSP27 regulates myocardial fibrosis. We created cardiac-specific HSP25 (the murine ortholog of human HSP27) knockout mice and found that HSP25 knockdown inhibited endothelial-mesenchymal transition (EndMT), attenuated myocardial fibrosis, and ameliorated diastolic dysfunction in isoproterenol-induced HF mice via echocardiography, histology, and western bloting. In vitro, HSP27 knockdown attenuated transforming growth factor beta-induced EndMT, whereas HSP27 overexpression promoted EndMT. Furthermore, the SMAD3/SNAIL1 pathway was found to be crucial for HSP27-mediated EndMT regulation. As an essential molecule in EndMT regulation and myocardial fibrosis modulation, HSP27 may hold promise as a therapeutic target for patients with HF., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024. Published by Elsevier Inc.)

Simple Summary: Schizothorax prenanti is a valuable cold-water fish that is commercially farmed in southwest China. Numerous aquaculture farmers have recently adopted high-density farming to achieve greater economic benefits, but this has rendered S. prenanti more susceptible to microbial pathogens and resulted in economic losses. Hence, the immune mechanisms of S. prenanti against pathogens should be investigated. Heat shock proteins (Hsps) comprise a family of molecular chaperones that are involved in immune pathways. Here, we identified and cloned the cDNA encoding SpHsp27 gene and detected its tissue distribution and using polyinosinic-polycytidylic acid [Poly (I:C)] as a viral analog to challenge the fish. We also explored the expression of SpHsp27, SpHsp60, SpHsp70, and SpHsp90 in four immune organs from fish that were injected with Poly (I:C). We found that Poly (I:C) induced SpHsp27 expression in all of these tissues, and significantly up-regulated most SpHsps genes compared with controls that were injected with phosphate-buffered saline. However, temporal expression and tissues were organ-specific. The present findings will help to further clarify the roles of Hsp genes in the mechanisms of antiviral immunity in fish. We identified and cloned cDNA encoding the heat shock protein (Hsp) 27 gene from Schizothorax prenanti (SpHsp27), and compared its expression with that of SpHsp60, SpHsp70, and SpHsp90 in the liver, head kidney, hindgut, and spleen of S. prenanti that were injected with polyinosinic-polycytidylic acid [Poly (I:C)]. The SpHsp27 partial cDNA (sequence length, 653 bp; estimated molecular mass, 5.31 kDa; theoretical isoelectric point, 5.09) contained an open reading frame of 636 bp and a gene encoding 211 amino acids. The SpHsp27 amino acid sequence shared 61.0–92.89% identity with Hsp27 sequences from other vertebrates and SpHsp27 was expressed in seven S. prenanti tissues. Poly (I:C) significantly upregulated most SpHsps genes in the tissues at 12 or 24 h (p < 0.05) compared with control fish that were injected with phosphate-buffered saline. However, the intensity of responses of the four SpHsps was organ-specifically increased. The expression of SpHsp27 was increased 163-fold in the head kidney and 26.6-fold SpHsp27 in the liver at 24 h after Poly (I:C) injection. In contrast, SpHsp60 was increased 0.97–1.46-fold in four tissues and SpHsp90 was increased 1.21- and 1.16-fold in the liver and spleen at 12 h after Poly (I:C) injection. Our findings indicated that Poly (I:C) induced SpHsp27, SpHsp60, SpHsp70, and SpHsp90 expression and these organ-specific SpHsps are potentially involved in S. prenanti antiviral immunity or mediate pathological process. [ABSTRACT FROM AUTHOR]

The deposition of β-amyloid peptides and of α-synuclein proteins is a neuropathological hallmark in the brains of Alzheimer's disease (AD) and Parkinson's disease (PD) subjects, respectively. However, there is accumulative evidence that both proteins are not exclusive for their clinical entity but instead co-exist and interact with each other. Here, we investigated the presence of a newly identified, pyroglutamate79-modified α-synuclein variant (pGlu79-aSyn)—along with the enzyme matrix metalloproteinase-3 (MMP-3) and glutaminyl cyclase (QC) implicated in its formation—in AD and in the transgenic Tg2576 AD mouse model. In the human brain, pGlu79-aSyn was detected in cortical pyramidal neurons, with more distinct labeling in AD compared to control brain tissue. Using immunohistochemical double and triple labelings and confocal laser scanning microscopy, we demonstrate an association of pGlu79-aSyn, MMP-3 and QC with β-amyloid plaques. In addition, pGlu79-aSyn and QC were present in amyloid plaque-associated reactive astrocytes that were also immunoreactive for the chaperone heat shock protein 27 (HSP27). Our data are consistent for the transgenic mouse model and the human clinical condition. We conclude that pGlu79-aSyn can be generated extracellularly or within reactive astrocytes, accumulates in proximity to β-amyloid plaques and induces an astrocytic protein unfolding mechanism involving HSP27. [ABSTRACT FROM AUTHOR]

Heat shock proteins (HSPs) are stress-induced proteins that are important constituents of the cell's defense system. The activity of HSPs enhances when the cell undergoes undesirable environmental conditions like stress. The protective roles of HSPs are due to their molecular chaperone and anti-apoptotic functions. HSPs have a central role in the eye, and their malfunction has been associated with the manifestation of ocular diseases. Heat shock protein 27 (HSP27, HSPB1) is present in various ocular tissues, and it has been found to protect the eye from disease states such as retinoblastoma, uveal melanoma, glaucoma, and cataract. But some recent studies have shown the destructive role of HSP27 on retinal ganglionic cells. Thus, this article summarizes the role of heat shock protein 27 in eye and ocular diseases and will focus on the expression, regulation, and function of HSP27 in ocular complications. [ABSTRACT FROM AUTHOR]

Objective To investigate the effects of targeting fusion peptide MAP2K6-FP combined with paclitaxel on the proliferation, invasion, and metastasis in human ovarian cancer cells HO8910 and their mechanism. Methods HO8910 cells were separately treated with different concentrations of MAP2K6-FP (0, 0. 3, 0. 6, and 1. 0 μg/mL)and paclitaxel (0, 5, 10, 15, 20, and 25 μmol/L), and the cell proliferation rate was measured by CCK-8 to screen out the optimal concentration for invasion and migration assays. HO8910 cells were randomly divided into the following four groups：the control group (with culture medium and cells), MAP2K6-FP group (0. 3 μg/mL MAP2K6-FP), paclitaxel group (15μmol/L paclitaxel), and combination group (0. 3 μg/mL MAP2K6-FP+15 μmol/L paclitaxel). The ability of cell invasion was detected by Scratch assay, the migration ability of cells was detected by Transwell assay, and the proteins of JNK, Beclin-1, LC3, and HSP27 in cells were detected by Western blotting. The four groups were divided into inhibitor subgroups (pretreated with SP600125 for 1 h)and control subgroups (unpretreated), and the expression levels of JNK, Beclin-1, LC3 of each group were detected by Western blotting. Results The proliferation rate of HO8910 cell decreased with the increased doses of MAP2K6-FP and paclitaxel. The combination group had less transmembrane cells and lower wound healing rate than the MAP2K6-FP group, paclitaxel group and control group (all P<0. 05). The protein ex⁃ pression levels of JNK, Beclin-1 and LC3 were higher in the combination group, MAP2K6-FP group, and paclitaxel group than in the control group, but the protein expression of HSP27 was lower (all P<0. 05). The protein expression levels of JNK, Beclin-1, and LC3 in the cells of the combination group were higher than those in the MAP2K6-FP group and the pa⁃ clitaxel group, and the protein expression of HSP27 was lower than those in the MAP2K6-FP group and the paclitaxel group (all P<0. 05). After the cells in each group were given JNK inhibitor, the protein expression levels of JNK, Beclin- 1 and LC3 in the inhibitor subgroups were lower than those in the control subgroups (all P<0. 05). Conclusion MAP2K6-FP combined paclitaxel may significantly inhibit the proliferation, invasion, and migration of ovarian cancer cells through promoting the expression of JNK signaling pathway-related proteins and HSP protein and increasing the cell autophagy. [ABSTRACT FROM AUTHOR]

Hepatocellular carcinoma is one of the most common malignances worldwide. Sorafenib, a multikinase inhibitor, is the standard therapy for patients with advanced-stage hepatocellular carcinoma. Therefore, it is essential to develop more effective therapeutic strategies to overcome resistance and improve the efficacy of sorafenib in treating hepatocellular carcinoma patients. In this study, we demonstrate that sorafenib chemotherapy combined with gene therapy, which expressed short hairpin ribonucleic acid against heat shock protein 27, effectively overcomes the sorafenib resistance of hepatocellular carcinoma cells and improves the anti-tumor effect of sorafenib. This combinational therapy will be a new hope for hepatocellular carcinoma patients who have sorafenib resistance, can be a better therapeutic strategy to control the malignant liver cancer. Our study provides a new therapeutic strategy for hepatocellular carcinoma that not only overcomes the resistance of hepatocellular carcinoma to sorafenib, but also utilizes cutting edge of gene therapies. [ABSTRACT FROM AUTHOR]

Stem cell-based therapy has been evaluated in many different clinical trials for various diseases. This capability was applied in various neurodegenerative diseases, such as multiple sclerosis, which is characterized by demyelination, axonal injury, and neuronal loss. Dental pulp stem cells (DPSCs) are mesenchymal stem cells from the oral cavity that have been studied with potential application for the regeneration of different tissues. Heat shock protein 27 (HSP27) regulates neurogenesis in the process of neural differentiation of placenta multipotent stem cells. Here, we hypothesize that HSP27 expression is also critical for the neural differentiation of DPSCs. An evaluation of the possible role of HSP27 in the differentiation of DPSCs was performed using gene knockdown and neural immunofluorescent staining. We found that HSP27 played a role in the differentiation of DPSCs and that knockdown of HSP27 in DPSCs rendered cells to oligodendrocyte progenitors; i.e., small hairpin specific for HSP27 DPSCs exhibited NG2-positive immunoreactivity and gave rise to oligodendrocytes or type-2 astrocytes. This neural differentiation of DPSCs may have clinical significance in the treatment of patients with neurodegenerative diseases. In conclusion, our data provide an example of the oligodendrocyte differentiation of a DPSC model, which may be applied in human regenerative medicine. [ABSTRACT FROM AUTHOR]

Amyloid β protein deposition in cerebral vessels, a characteristic of Alzheimer's disease, is a risk factor for intracerebral hemorrhage. Amyloid β protein directly modulates human platelet function; however, the exact mechanism of action is unclear. Therefore, we investigated the effects of amyloid β protein on human platelet activation using an aggregometer with laser scattering. Amyloid β protein decreased platelet aggregation induced by thrombin receptor-activating protein, but not by collagen and ADP. Amyloid β protein also suppressed platelet aggregation induced by SCP0237 and A3227. Platelet-derived growth factor-AB secretion and phosphorylated-heat shock protein 27 release by thrombin receptor-activating protein were inhibited by amyloid β protein. Additionally, thrombin receptor-activating protein-induced phosphorylation of JNK and p38 MAP kinase was reduced by amyloid β protein. Collectively, our results strongly suggest that amyloid β protein negatively regulates protease-activated receptor-elicited human platelet activation. These findings may indicate a cause of intracerebral hemorrhage due to amyloid β protein. [ABSTRACT FROM AUTHOR]

AIM: To investigate the relationships between the changes of heat shock protein 27 antibody (anti-HSP27) in serum/cerebrospinal fluid (CSF), intraocular pressure (IOP), retinal ganglion cell (RGC) apoptosis in a rat glaucoma model and disclose the underlying pathogenesis of glaucoma. METHODS: A total of 115 Wistar rats were randomly divided into 4 groups. Group 1 was the ocular hypertension group by condensing 3 episcleral & limbal veins or episcleral area of right eye (HP group, n=25) and sham operation group with conjunctiva incision without coagulation (n=25). Group 2: HSP27 or dose-matched PBS was injected into the vitreous (V-HSP27 group, n=15; V-PBS group, n=15). Group 3: HSP27 and complete Freund’s adjuvant or dose-matched PBS was injected subcutaneously into the hind limb accompanied intraperitoneal injection of pertussis toxin [sensitized group (I-HSP27 group), n=15; I-PBS group, n=15)]. Group 4 was normal group without any treatment (n=5). IOPs of the rats were measured before, day 3, weeks 1, 2, 4, 6, and 8 after treatment. Paraffin-embedded sections were prepared for HE staining and RGCs apoptosis were detected by TUNEL. Anti-HSP27 level in serum and CSF were examined by ELISA. RESULTS: IOPs were elevated significantly in HP and V-HSP27, V-PBS groups (P

ABSTRACT: This study compared the meat quality traits, histochemical characteristics, and heat shock protein (HSP) 27 expression levels of the broiler Pectoralis major (PM) muscles in groups classified by pale, soft, and exudative (PSE)-like and fast-glycolyzing conditions using the lightness and muscle pH change values. Chicken PM muscles showing higher pH change value and paler meat surface (as HP group) could be associated with the PSE-like condition, and exhibited a lower pH24 h value and higher cooking loss compared to PM muscles showing lower pH change value and normal color (as LN group) (P < 0.05). Greater PM muscle weight and fiber area were observed in the HP group compared to the other groups (P < 0.05); meanwhile, the PM muscles showing higher pH change value with normal color (as HN group) and the PM muscles showing lower pH change value with paler color (as LP group) did not differ in the water holding capacity, Warner-Bratzler shear force, and muscle fiber characteristics (P > 0.05). Muscle samples showing a higher pH change value exhibited a greater level of HSP27 compared to muscle samples showing a lower pH change value (P < 0.05). Therefore, the current findings suggested that the expression level of HSP27 can be a useful indicator for explaining variations in the glycolytic rate of chicken breast muscle.

In cancer, antigen-presenting cells (APC), including dendritic cells (DCs), take up and process proteins to mount adaptive antitumor immune responses. This often happens in the context of inflamed cancer, where reactive oxygen species (ROS) are ubiquitous to modify proteins. However, the inflammatory consequences of oxidized protein uptake in DCs are understudied. To this end, we investigated human monocyte-derived cell surface marker expression and cytokine release profiles when exposed to oxidized and native proteins. Seventeen proteins were analyzed, including viral proteins (e.g., CMV and HBV), inflammation-related proteins (e.g., HO1 and HMGB1), matrix proteins (e.g., Vim and Coll), and vastly in the laboratory used proteins (e.g., BSA and Ova). The multifaceted nature of inflammation-associated ROS was mimicked using gas plasma technology, generating reactive species cocktails for protein oxidation. Fourteen oxidized proteins led to elevated surface marker expression levels of CD25, CD40, CD80, CD86, and MHC-II as well as strongly modified release of IL6, IL8, IL10, IL12, IL23, MCP-1, and TNFα compared to their native counterparts. Especially IL8, heme oxygenase 2, and vimentin oxidation gave pronounced effects. Furthermore, protein kinase phospho-array studies in monocyte-derived cells pulsed with native vs. oxidized IL8 and insulin showed enhanced AKT and RSK2 phosphorylation. In summary, our data provide for the first time an overview of the functional consequences of oxidized protein uptake by human monocyte-derived cells and could therefore be a starting point for exploiting such principle in anticancer therapy in the future.

Human papillomavirus (HPV) infections are highly prevalent globally. While preventive HPV vaccines exist, therapeutic vaccines are needed to treat existing HPV lesions and malignancies. This study evaluated the immunostimulatory and anti-tumor effects of three therapeutic vaccine candidates based on the recombinant protein, tumor cell lysate (TCL), and engineered exosome (Exo) harboring the heat shock protein 27 (Hsp27)-E7 fusion construct in mouse model. At first, the recombinant Hsp27-E7 protein was generated in E. coli expression system. Then, tumor cell lysates-based and engineered exosomes-based vaccine constructs harboring green fluorescent protein (GFP) and Hsp27-E7 were produced using lentiviral system. Finally, their immunological and antitumor effects were investigated in both prophylactic and therapeutic experiments. Our data showed that the recombinant Hsp27-E7 protein, TCL-Hsp27-E7 and Exo-Hsp27-E7 regimens can induce the highest level of IFN-γ, TNF-α and Granzyme B, respectively. The percentage of tumor-free mice was identical for three vaccine strategies (survival rate: 75 %) in both prophylactic and therapeutic experiments. Generally, the TCL-Hsp27-E7, Exo-Hsp27-E7 and recombinant Hsp27-E7 protein regimens induced effective immune responses toward Th1 and CTL activity, and subsequently antitumor effects in mouse model. Regarding to higher Granzyme B secretion, lower tumor growth and more safety, the Exo-Hsp27-E7 regimen can be considered as the most promising HPV vaccination strategy. Schematic model of design, construction, and in vitro and in vivo functional effects of three vaccine candidates. [Display omitted] [ABSTRACT FROM AUTHOR]

Pseudorabies (PR) is a domestic and wild animal infectious disease caused by the pseudorabies virus (PRV) and is one of the major infectious diseases that endanger the global swine industry. Studies have reported that PRV may achieve cross-species transmission from pigs to humans in recent years. Therefore, in-depth exploration of the relationship between PRV and host proteins is of great significance for elucidating the pathogenic mechanism of PRV and anti-PRV infection. Here, we report that heat shock protein 27 (HSP27) ubiquitinates and degrades cyclic GMP-AMP synthase (cGAS) and attenuates cGAS-mediated antiviral responses, thereby promoting PRV infection. Overexpression of HSP27 promoted PRV proliferation in vitro, while knockdown of HSP27 inhibited PRV infection. Importantly, we found that HSP27 inhibited PRV infection or poly(dA:dT)-activated IFN-β expression. Further studies found that HSP27 may inhibit cGAS-STING-mediated IFN-β expression through targeting cGAS. In addition, we found that HSP27 can suppress the expression of endogenous cGAS in different cells at both gene transcription and protein expression levels, and that HSP27 interacts with and ubiquitinates cGAS. In conclusion, we reveal for the first time that HSP27 is a novel negative regulator of the cGAS-STING signaling pathway induced by PRV infection or poly(dA:dT) activation and demonstrate that HSP27 plays a crucial role in PRV infection.

We identified and cloned cDNA encoding the heat shock protein (Hsp) 27 gene from Schizothorax prenanti (SpHsp27), and compared its expression with that of SpHsp60, SpHsp70, and SpHsp90 in the liver, head kidney, hindgut, and spleen of S. prenanti that were injected with polyinosinic-polycytidylic acid [Poly (I:C)]. The SpHsp27 partial cDNA (sequence length, 653 bp; estimated molecular mass, 5.31 kDa; theoretical isoelectric point, 5.09) contained an open reading frame of 636 bp and a gene encoding 211 amino acids. The SpHsp27 amino acid sequence shared 61.0–92.89% identity with Hsp27 sequences from other vertebrates and SpHsp27 was expressed in seven S. prenanti tissues. Poly (I:C) significantly upregulated most SpHsps genes in the tissues at 12 or 24 h (p < 0.05) compared with control fish that were injected with phosphate-buffered saline. However, the intensity of responses of the four SpHsps was organ-specifically increased. The expression of SpHsp27 was increased 163-fold in the head kidney and 26.6-fold SpHsp27 in the liver at 24 h after Poly (I:C) injection. In contrast, SpHsp60 was increased 0.97–1.46-fold in four tissues and SpHsp90 was increased 1.21- and 1.16-fold in the liver and spleen at 12 h after Poly (I:C) injection. Our findings indicated that Poly (I:C) induced SpHsp27, SpHsp60, SpHsp70, and SpHsp90 expression and these organ-specific SpHsps are potentially involved in S. prenanti antiviral immunity or mediate pathological process.

The deposition of β-amyloid peptides and of α-synuclein proteins is a neuropathological hallmark in the brains of Alzheimer’s disease (AD) and Parkinson’s disease (PD) subjects, respectively. However, there is accumulative evidence that both proteins are not exclusive for their clinical entity but instead co-exist and interact with each other. Here, we investigated the presence of a newly identified, pyroglutamate79-modified α-synuclein variant (pGlu79-aSyn)—along with the enzyme matrix metalloproteinase-3 (MMP-3) and glutaminyl cyclase (QC) implicated in its formation—in AD and in the transgenic Tg2576 AD mouse model. In the human brain, pGlu79-aSyn was detected in cortical pyramidal neurons, with more distinct labeling in AD compared to control brain tissue. Using immunohistochemical double and triple labelings and confocal laser scanning microscopy, we demonstrate an association of pGlu79-aSyn, MMP-3 and QC with β-amyloid plaques. In addition, pGlu79-aSyn and QC were present in amyloid plaque-associated reactive astrocytes that were also immunoreactive for the chaperone heat shock protein 27 (HSP27). Our data are consistent for the transgenic mouse model and the human clinical condition. We conclude that pGlu79-aSyn can be generated extracellularly or within reactive astrocytes, accumulates in proximity to β-amyloid plaques and induces an astrocytic protein unfolding mechanism involving HSP27.

Atherosclerosis is the primary cause of heart attacks, and while efforts to prevent its development or progression have historically focused largely on reducing cholesterol levels, there is now important proof-of-principle data that supports the role that inflammation plays in atherogenesis. Heat shock protein 27 (HSP27) is a novel biomarker of atherosclerosis that is also atheroprotective. Through a series of murine and in vitro experiments, an iterative narrative is emerging that demonstrates how HSP27 can act as an extracellular mediator that reduces plaque inflammation—either directly via transcriptional pathways, or indirectly via important effects on macrophage biology. While there is much more to learn about the biology of HSP27, we now review the strong foundation of knowledge that highlights the potential anti-inflammatory role of HSP27 as a novel therapeutic for not only atherosclerosis but potentially other inflammatory disorders. [ABSTRACT FROM AUTHOR]

• Hsp27 accelerates sensory functional recovery and prevents motor deficit in GBS. • Hsp27 promotes axon regeneration and formation of neuromuscular junction in GBS. • Hsp27 extends critical period of functional recovery after severe PNI. • Hsp27 preserves axonal and mitochondrial integrity after prolonged muscle denervation. • Hsp27 initiates efficient innate-immune response of Wallerian degeneration and cytokine expression. Guillain-Barré syndrome (GBS) is an autoimmune peripheral neuropathy and a common cause of neuromuscular paralysis. Preceding infection induces the production of anti-ganglioside (GD) antibodies attacking its own peripheral nerves. In severe proximal peripheral nerve injuries that require long-distance axon regeneration, motor functional recovery is virtually nonexistent. Damaged axons fail to regrow and reinnervate target muscles. In mice, regenerating axons must reach the target muscle within 35 days (critical period) to reform functional neuromuscular junctions and regain motor function. Successful functional recovery depends on the rate of axon regeneration and debris removal (Wallerian degeneration) after nerve injury. The innate-immune response of the peripheral nervous system to nerve injury such as timing and magnitude of cytokine production is crucial for Wallerian degeneration. In the current study, forced expression of human heat shock protein (hHsp) 27 completely reversed anti-GD-induced inhibitory effects on nerve repair assessed by animal behavioral assays, electrophysiology and histology studies, and the beneficial effect was validated in a second mouse line of hHsp27. The protective effect of hHsp27 on prolonged muscle denervation was examined by performing repeated sciatic nerve crushes to delay regenerating axons from reaching distal muscle from 37 days up to 55 days. Strikingly, hHsp27 was able to extend the critical period of motor functional recovery for up to 55 days and preserve the integrity of axons and mitochondria in distal nerves. Cytokine array analysis demonstrated that a number of key cytokines which are heavily involved in the early phase of innate-immune response of Wallerian degeneration, were found to be upregulated in the sciatic nerve lysates of hHsp27 Tg mice at 1 day postinjury. However, persistent hyperinflammatory mediator changes were found after chronic denervation in sciatic nerves of littermate mice, but remained unchanged in hHsp27 Tg mice. Taken together, the current study provides insight into the development of therapeutic strategies to enhance muscle receptiveness (reinnervation) by accelerating axon regeneration and Wallerian degeneration. [ABSTRACT FROM AUTHOR]

Aim: Assessment of the effect of nonsurgical periodontal therapy on haematological parameters in patients with grades B (BP) and C periodontitis (CP). Methods: Eight BP and 46 CP patients received full-mouth periodontal debridement within 48 h, if positive for Aggregatibacter actinomycetemcomitans with adjunctive systemic antibiotics (4 BP, 17 CP). Clinical data were collected prior and 12 weeks after periodontal therapy. Blood was sampled prior to and 1 day as well as 6 and 12 weeks after the first SD visit. Erythrocyte count, haemoglobin value, haematocrit (HCT), mean erythrocyte volume (MCV), mean corpuscular haemoglobin (MCH), MCH concentration (MCHC), platelets (PLT) and heat shock protein 27 (Hsp27) were assessed. Results: Both groups showed significant clinical improvement (p < 0.05). Using univariate analysis, MCV was noticeably lower in CP than BP at all examinations, HCT only at baseline. For CP, MCHC was noticeably higher 12 weeks after SD than at baseline and 1 day (p ≤ 0.005) and Hsp27 increased noticeably at 1 day (p < 0.05). Repeated measures analysis of variance revealed African origin to be associated with lower MCV and female sex with lower MCHC. Conclusion: Based on multivariate analysis, periodontal diagnosis (BP/CP) was not associated with haematological parameters measured in this study or serum Hsp27. In CP, nonsurgical periodontal therapy improved MCHC 12 weeks after SD. Also in CP Hsp27 was increased 1 day after SD. [ABSTRACT FROM AUTHOR]

Objectives This study set out to analyze the difference of heat shock protein 27 (HSP27) and its phosphorylation in patients with lower extremity arteriosclerosis obliterans (LEASO) at different stages. This research also examined their clinical significance in this disease. Methods Blood samples from 60 patients with LEASO were collected and divided into two groups according to ankle-brachial index (ABI): group A (ABI ≤ 0.43) and group B (ABI > 0.43). The expression of HSP27 in each stage of Fontaine was measured by ELISA, and the difference of HSP27 concentration and ABI between the two groups was analyzed. Meanwhile, three normal femoral artery specimens (normal group) and three atherosclerotic femoral artery specimens (lesion group) were collected, and HSP27 and its Phospho-HSP27 (Ser15), Phospho-HSP27 (Ser78) and Phospho-HSP27 (Ser82) were detected by western blotting. The data of the protein level between the normal group and the lesion group was made a statistical analysis. Results HSP27 concentration in group A was (40.73 ± 15.99) ng/ml, and ABI was 0.26 ± 0.20. HSP27 concentration in group B was (66.30 ± 24.70) ng/ml, and ABI was 0.64 ± 0.20. The protein expression of HSP27 and its phosphorylation in the normal group was 0.82 ± 0.13, 0.66 ± 0.12, 0.91 ± 0.24 and 0.90 ± 0.16, respectively; the protein expression of the lesion group was 0.45 ± 0.08, 0.42 ± 0.09, 0.39 ± 0.12 and 0.58 ± 0.11. Conclusion Patients with higher LEASO Fontaine stage and lower ABI had a lower HSP27 concentration. Serum HSP27 concentration was negatively correlated with the severity of LEASO, while HSP27 concentration was positively correlated with ABI value. The content of HSP27 and its phosphorylation of lesion group is significantly lower than that of normal group, which may be closely related to the occurrence and development of atherosclerosis.

Patients with obstructive jaundice are prone to develop cardiovascular complications during surgery. However, the underlying mechanisms remain largely unknown. The present study was aimed to investigate the role of p38 MAPK-pHsp27 pathway in vascular hyporesponsiveness induced by obstructive jaundice. Firstly, an experimental rat obstructive jaundice model was established by bile duct ligation (BDL). We found that the thoracic aorta rings isolated from BDL rats showed decreased response to norepinephrine and acetylcholine, while continuous intraperitoneal injection with SB203580, a selective P38 MAPK inhibitor, could significantly prevented BDL-induced hyporeactivity. Also, the immunohistochemistry and Western blot assays revealed that the up-regulation of pHsp27 and F-actin in thoracic aorta rings from BDL rats and bilirubin-treated vascular smooth muscle cells (VSMCs) were also inhibited by SB203580. Moreover, we identified that bilirubin could induced decreased cell proliferation of VSMCs by using CCK8 assay and which was also prevented by SB203580. All these data demonstrated that p38 MAPK-pHsp27 mediates vascular hyporesponsiveness in rats with obstructive jaundice by modulating the expression level of pHsp27 and F-actin, and that inhibition of p38 MAPK signaling could remodel the vascular activity.

Background/Aims: Thrombin induces the activation of human platelets through protease-activated receptor (PAR) 1 and PAR4, and Rac, a member of the Rho family of small GTPases, is implicated in PAR activation. We previously reported that phosphorylated-heat shock protein 27 (HSP27) is released from the thrombin receptor-activating peptide (TRAP)-stimulated platelets of diabetic patients. In the present study, we investigated the role of Rac in the TRAP-elicited release of phosphorylated-HSP27 from human platelets. Methods: Platelet aggregation was measured using an aggregometer with laser scattering. Protein phosphorylation was analyzed by Western blotting. The levels of phosphorylated-HSP27 and platelet-derived growth factor-AB (PDGF-AB) were measured by enzyme-linked immunosorbent assays. Results: NSC23766, an inhibitor of Rac-guanine nucleotide exchange factor interaction, suppressed the TRAP-elicited release of phosphorylated-HSP27 as well as platelet aggregation. The TRAP-induced phosphorylation of HSP27, p38 mitogen-activated protein kinase (MAPK) and c-Jun N-terminal kinase (JNK) was attenuated by NSC23766. SB203580, a p38 MAPK inhibitor, but not SP600125, a JNK inhibitor, suppressed the release of phosphorylated-HSP27 in addition to HSP27 phosphorylation. On the other hand, both SB203580 and SP600125 reduced the TRAP-stimulated secretion of PDGF-AB. Conclusion: Our results strongly suggest that Rac acts as a positive regulator of the PAR-elicited release of phosphorylated-HSP27 from human platelets via p38 MAPK but not JNK.

Abstract Background Some women with genetic risk of breast and/or ovarian cancer (e.g., BRCA1/2) opt to undergo prophylactic salpingo-oophorectomy (PSO, or surgical removal of the ovaries & fallopian tubes) in order to reduce their risk of cancer. As a consequence, these women experience “surgical menopause” – accompanied by more severe climacteric symptoms that occur in a much shorter time frame. While the risk of coronary artery disease (CAD) rises with menopause, little is known about how the sudden loss of ovarian function from PSO alters the whole-body physiology, and whether it predisposes women to premature CAD. Methods/Design To manage CAD risk there is a prerequisite for reliable biomarkers that can help guide risk assessment and therapeutic interventions. To address these needs, this prospective, observational cohort study will evaluate surrogate markers reflective of CAD health in women experiencing surgical menopause after PSO. Twenty women representing each of the following groups will be enrolled over 3 years (total participants = 240): (i) pre-menopausal PSO, (ii) post-menopausal PSO, (iii) pre-menopausal women undergoing other pelvic surgery, and (iv) pre-menopausal controls (no surgery). All participants will provide blood plasma samples pre- and 1, 3, 6, & 12 months post-operatively, with serial samples collectively assessed for measurements of the study’s primary endpoints of interest. These include a hormone profile (estradiol, follicle stimulating hormone (FSH), luteinizing hormone (LH), and progesterone) and both conventional (lipid profile) and novel biomarkers (Heat Shock Protein 27 (HSP27), HSP27-antibodies (HSP27 Ab), proprotein convertase subtilisin/kexin 9 (PCSK9), inflammatory cytokines) of CAD. Another aspect of this study is the measurement and analysis of retinal vessel diameters – an emerging physiological parameter reflective of CAD risk. Finally, a patient engagement exercise will result in the drafting of patient-generated questionnaires that address the well-being and health concerns of these women as they transition through premature menopause and work with our research team to identify and discuss their health priorities. Discussion The protocol of our planned study investigating the effects of PSO on CAD is described herein. Characterization of novel CAD markers in women experiencing surgical menopause will yield new insights into the role of the functional ovary in modulating lipid parameters and other CAD risk factors such as HSP27 and HSP27 Ab.

Abstract Background The most striking feature of molecular apocrine breast cancer (MABC) is the expression of androgen receptor (AR). We report here the mechanism of the AR in regulating the behavior of MABC. Methods The MABC cell line, MDA-MB-453, and the nonMABC cell line, MCF7, were used in this study. The effect of dihydrotestosterone (DHT) and heat shock protein 27 (HSP27) on cell proliferation was quantified using the cell counter kit-8 (CCK8) and clonogenic assays in vitro and by a xenograft tumor model in vivo. The expression of the AR and HSP27 was analyzed using western blot, qPCR, and immunofluorescence assays. Complexes of the AR and HSP27 were detected by co-immunoprecipitation (Co-IP). Results In MDA-MB-453 cells, DHT promoted cell proliferation and stimulated AR and HSP27 translocation from the cytoplasm to the nucleus, whereas, it inhibited MCF7 cell growth, and only the AR translocated into the nucleus. HSP27 knock-down decreased the proliferative ability of MDA-MB-453 cells, which could be rescued by DHT, while HSP27 and DHT had synergistic effects on MCF7 cells. HSP27 phosphorylation was a prerequisite for AR translocation into the nucleus, especially phosphorylation on serine 82. In addition, DHT stimulated the tumorigenic and metastatic capacities of MDA-MB-453 cells, while HSP27 knock-down decreased the rate of tumor formation and induced apoptosis in cells. Conclusions The results suggest that HSP27 assists the AR in regulating the malignant behavior of MABC, and these findings might be helpful in the treatment of MABC.

Blood levels of heat shock protein (HSP27) and natural IgG auto‐antibodies to HSP27 (AAbs) are higher in healthy controls compared to cardiovascular disease patients. Vaccination of mice with recombinant HSP25 (rHSP25, murine ortholog of human rHSP27) increased AAb levels, attenuated atherogenesis and reduced plaque inflammation and cholesterol content. We sought to determine if the HSP27 immune complex (IC) altered MΦ inflammation signaling (Toll Like Receptor 4; TLR4), and scavenger receptors involved in cholesterol uptake (SR‐AI, CD‐36). Combining a validated polyclonal IgG anti‐HSP27 antibody (PAb) with rHSP27 enhanced binding to THP‐1 MΦ cell membranes and activation of NF‐κB signaling via TLR4, competing away LPS and effecting an anti‐inflammatory cytokine profile. Similarly, adding the PAb with rHSP27 enhanced binding to SR‐AI and CD‐36, as well as lowered oxLDL binding in HEK293 cells separately transfected with SR‐AI and CD‐36, or THP‐1 MΦ. Finally, the PAb enhanced the uptake and internalization of rHSP27 in THP‐1 MΦ. Thus, the HSP27 IC potentiates HSP27 cell membrane signaling with receptors involved in modulating inflammation and cholesterol uptake, as well as HSP27 internalization. Going forward, we are focusing on the development of HSP27 Immune Complex Altered Signaling and Transport (ICAST) as a means of modulating inflammation. [ABSTRACT FROM AUTHOR]

Heat shock proteins (HSPs) are a class of proteins with highly conserved sequences produced under heat shock or other stress states. Heat shock proteins 27 (HSP27) is the most researched member of its protein family. It plays an important role as an ATP-independent molecular chaperones in protein folding. It also participates in the pathological processes of many diseases, including cancer. A large amount of research has proved that protein phosphorylation is closely related to tumorigenesis. The Phosphorylation of HSP27 in tumorigenesis is one of the recenthot topics. This article reviews the relationship between phosphorylated HSP27 and tumorigenesis of malignant tumors as well as its possibility to become a tumor treatment target. It providesa new idea for the prevention and treatment for malignant tumors. [ABSTRACT FROM AUTHOR]

The long noncoding RNA (lncRNA) LINC00520 is an important modulator of the oncogenicity of multiple human cancers. However, whether LINC00520 is involved in the malignant characteristics of colorectal cancer (CRC) has not been extensively studied until recently. Therefore, the present study aimed to detect LINC00520 expression in CRC and evaluate its clinical significance in patients with CRC. Functional experiments were conducted to test the biological roles and underlying mechanisms of LINC00520 in CRC progression. In this study, high-LINC00520 expression was verified in CRC tissues and cell lines, and this high expression was associated with patients' unfavorable clinicopathological parameters and shorter overall survival and disease-free survival. Functionally, interference of LINC00520 resulted in a significant decrease of CRC cell proliferation, migration, colony forming ability, and invasion. Mechanistically, LINC00520 functioned as a competing endogenous RNA by sponging microRNA-577 (miR-577) and thereby increasing heat shock protein 27 (HSP27) expression. Rescue experiments revealed that inhibiting miR-577 or restoring HSP27 could abrogate the effects of LINC00520 silencing on malignant phenotypes of CRC. LINC00520 functioned as an oncogenic lncRNA in CRC, and it facilitated CRC progression by regulating the miR-577/HSP27 axis, suggesting that the LINC00520/miR-577/HSP27 axis is an effective target in anticancer management. [ABSTRACT FROM AUTHOR]

Tumor cells overexpress low-density lipoprotein (LDL) receptors (LDL-r). Hence, LDL is proposed as a targeting shuttle of anticancer drugs. Therefore, the objective of this study was to synthesize a dual inhibitor of heat shock protein 27 (HSP27) and human epidermal growth factor receptor 2 (HER2) conjugated with cholesterol and encapsulated into LDL for selective targeting of ovarian cancer cells. In the present study, the anticancer agent and its cholesterol conjugate were successfully prepared and characterized physically for color, shape, and melting point. Moreover, the compounds were chemically characterized for 1H NMR and 13C NMR spectra using FTIR and LCMS/MS. Our results revealed that the prepared anticancer agent and its cholesterol conjugate elicited dual HSP27 and HER2 inhibition, as confirmed using western blotting. The anticancer agent (compound D) entered cells and targeted the HSP27 function, thereby reducing HER2 expression. However, a cholesterol-conjugated anticancer agent (compound F) had high cellular uptake and inhibited the growth of SKOV3 cells after encapsulation into LDL. The obtained results concluded that the design of an LDL-encapsulated cholesterol-conjugated HSP27-HER2 dual inhibitor may be a promising approach to realize specific targeted achieve killing of ovarian cancer. [ABSTRACT FROM AUTHOR]

Copyright of West China Journal of Stomatology is the property of Sichuan University, West China College of Stomatology and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Patients with metastatic melanoma have a poorer prognosis. Prion protein (PrP) in melanoma is known to play an important role in cancer cell migration and invasion by interacting with filamin A (FLNa), a cytolinker protein. To investigate if PrP may contribute to cancer cell mobility independent of its binding to FLNa, we knocked out PRNP in M2 melanoma cell, which lacked FLNa expression. We found that deletion of PRNP in M2 significantly reduced its motility. When PRNP was deleted, the level of Akt was decreased. As a consequence, phosphorylation of small heat shock protein (hsp27) was also reduced, which resulted in polymerization of F-actin rendering the cells less migratory. Accordingly, when PrP was re-expressed in PRNP null M2 cells, the mobility of the recurred cells was rescued, so were the expression levels of Akt and phosphorylated hsp27, resulting in a decrease in the polymerization of F-actin. These results revealed that PrP can play a FLNa independent role in cytoskeletal organization and tumor cell migration by modulating Akt-hsp27-F-actin axis. • Filamin A (FLNa) independent cell migration has not been thoroughly studied. • Prion protein (PrP) modulates actin polymerization and mediates M2 melanoma cell migration independent of FLNa. • Expression of PrP stabilizes protein kinase B (Akt), enhances interaction between Akt and heat shock protein 27 (hsp27). • Akt phosphorylates hsp27 to reduce polymerization of F-actin, which in turn to enhance cancer cell migration. [ABSTRACT FROM AUTHOR]

Copyright of Shipin Kexue/ Food Science is the property of Food Science Editorial Department and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Background: Heat shock proteins (HSPs) are a class of highly conserved proteins responsible for various functions critical to cell survival. Pharmacological induction of HSPs has been implicated in the regulation of neuronal loss and functional deficits in peripheral and central nervous system injuries. Accordingly, the present study was conducted to investigate the effect of trehalose on spinal expression of HSP27, HSP70 and caspase-3 genes following traumatic spinal cord injury (SCI) in rats. Methods: Male rats weighing 250-300 g underwent laminectomy and were divided into four groups including sham, SCI (received SCI), vehicle (received SCI and phosphate buffer saline intrathecally) and trehalose (received 10 mM trehalose intrathecally following SCI). On days 1, 3 and 7 after injury, HSP27, HSP70 and caspase-3 genes transcripts were quantified in spinal cord tissues via a real-time PCR technique. In addition, locomotor function was assessed using the Basso, Beattie and Bresnahan (BBB) rating scale. Results: SCI induced the expression of HSP27, HSP70 and caspase-3 genes and BBB score at all time points. Trehalose treatment upregulated HSP27, HSP70 genes expression at 1 day after SCI. Interestingly, a significant reduction in the expression of HSP27 and HSP70 genes was observed on days 3 and 7 following trauma compared with the vehicle group (p < 0.01). Caspase-3 gene showed a decrease in expression in the trehalose-treated group at all times. In addition, neurological function revealed an improvement after treatment with trehalose. Conclusion: This study suggests that the neuroprotective effect of trehalose is mediated via regulation of HSP27 and HSP70, which are involved in cytoprotection and functional recovery following SCI. [ABSTRACT FROM AUTHOR]

Chemotherapy resistance of breast cancer cells is one of the major factors affecting patient survival rate. Heat shock protein 27 (Hsp27) is a member of the small heat shock protein family that has been reported to be associated with chemotherapy resistance in tumor cells, but the exact mechanism is not fully understood. Here, we explored the regulation of Hsp27 in adriamycin-resistant pathological conditions of breast cancer in vitro and in vivo. We found that overexpression of Hsp27 in MCF-7 breast cancer cells reversed DNA damage induced by adriamycin, and thereby reduced subsequent cell apoptosis. Non-phosphorylated Hsp27 accelerated ubiquitin-mediated degradation of c-Myc under normal physiological conditions. After stimulation with adriamycin, Hsp27 was phosphorylated and translocated from the cytoplasm into the nucleus, where phosphorylated Hsp27 upregulated c-Myc and Nijmegen breakage syndrome 1 (NBS1) protein levels thus leading to ATM activation. We further showed that phosphorylated Hsp27 promoted c-Myc nuclear import and stabilization by regulating T58/S62 phosphorylation of c-Myc through a protein phosphatase 2A (PP2A)-dependent mechanism. Collectively, the data presented in this study demonstrate that Hsp27, in its phosphorylation state, plays a critical role in adriamycin-resistant pathological conditions of breast cancer cells. [Display omitted] • Phosphorylated Hsp27 (p-Hsp27) contributed to ADR resistance. • p-Hsp27 facilitated ADR resistance by the c-Myc-NBS1-ATM signaling pathway. • p-Hsp27 promoted c-Myc translocation by increasing Ser62 phosphorylation of c-Myc. • p-Hsp27 maintained c-Myc stabilization by reducing Thr58 phosphorylation of c-Myc. • p-Hsp27 regulated T58/S62 phosphorylation of c-Myc through PP2A-dependent mechanism. [ABSTRACT FROM AUTHOR]

Purpose: It is known that the low-power irradiation of a high-output laser accelerates wound healing. However, there is little fundamental research on it, especially for cultured osteoblasts. The purpose of this study was to evaluate the effect of low-level irradiation of a hard laser on cultured osteoblasts, Materials and Methods: Osteoblasts cultured in collagen gel were irradiated using either a CO2 or a semiconductor laser. Expressions of OC, BSP, and HSP27 were examined at 3 days after irradiation and calcium volumes were measured after 1 week. Results: In the CO2 laser group, a significant difference was only observed with 2.6-W laser irradiation. There was no promoting effect of semiconductor laser irradiation. Additionally, the highest expression of HSP27 was shown with 2.6 W of CO2 laser irradiation. Conclusion: The CO2 laser at 2.6 W can increase the calcification of osteoblasts in three-dimensional cultures. The mechanism seems to be related to the cascade of HSP27. [ABSTRACT FROM AUTHOR]