Heat Shock Protein 70 Protein Research Articles

Heat shock protein 70 in Alzheimer's disease and other dementias: A possible alternative therapeutic

Alzheimer's disease (AD) is considered a global health issue with a high social burden due to the level of disability it causes in those who suffer from it. In the absence of a therapeutic alternative for this disease, we will follow one of the biochemical pathways involved in the development of AD, which is related to molecular chaperones. The molecules are responsible for eliminating toxins and misfolded proteins at the cerebral level. These chaperones are a set of proteins from the heat shock proteins (HSPs) family, which, among their functions, help maintain homeostasis and protect cells against stress. Various authors have described the activity of HSPs in different neurodegenerative diseases, highlighting the activity of heat shock protein 70 (HSP70) in the presence of aberrant proteins characteristic of neurodegeneration, such as amyloid-β (Aβ) and tau. The role of HSP70 in AD and other dementias lies in its mechanism, which, along with other proteins from the HSP family, has the capacity to eliminate Aβ aggregates by promoting catalytic pathways. In this review, we explore the biological role of the HSP70 protein in AD and other dementias and its potential therapeutic use

In Vivo Gastroprotective Upshots of the Novel Schiff Base CdCl2 (C14H21N3O2) Compound by Bax/HSP-70 Signaling and Inflammatory Cytokines.

Synthesis of the original Schiff base CdCl2 (C14H21N3O2) compound (Schiff base complex) displays an extensive range of bioactivities and was predictably utilized to treat several syndromes. The goal of the existing experiment is to evaluate the gastroprotective effects of a novel Schiff base CdCl₂ (C14H21N3O2) compound in alcohol-induced gastric ulcers in rats by examining its antioxidant activity, anti-inflammatory effects, and modulation of key molecular markers, including heat shock protein-70(HSP-70) and Bcl-2-associated X protein (Bax) proteins. Five groups of rats were utilized in the current study. Control and model groups were orally administered10% Tween 20. The treated groups were orally administered 20 mg/kg omeprazole or Schiff base compound (25 or 50 mg/kg). One hour later, only the control group received oral 10% Tween 20, and the treated groups received oral (5 ml/cage) absolute alcohol. During the second hour, all rats were sacrificed. All treatedrats presented considerable improvementin alcohol-induced gastric injury recognizedby decreasing ulcer index and raising % of ulcer inhibition. Increased mucus and gastric pH content and decreasedulcerated portion,reduced or non-appearanceof edema, and leucocytes penetrated the subcutaneous layer. In stomach epithelium homogenate, the Schiff base compound obtainable significant upsurge superoxide dismutase (SOD), catalase (CAT) activities, considerable declining malondialdehyde (MDA) quantity. Moreover, the Schiff base compound raised the intensity of periodic acid-Schiff (PAS) stains gastric epithelium. Furthermore, the Schiff base compound formed up-regulated HSP-70 and down-regulated Bax proteins gastric epithelium Schiff base compound, reduced the level of tumor necrosis factor-alpha (TNF-α), interleukin-6 (IL-6) and improved the quantity of IL-10.Administering a high dose of 500 mg/kg Schiff base compound revealed the nontoxic nature of the compound in rats. Schiff base compound exhibited gastroprotective effectsattributed to its antioxidant nature, its capability to enhance mucus excretion, SOD and CAT, reduce MDA amount, up-regulate HSP-70 protein, down-regulate Bax protein, andinflammatory cytokines.

Mechanism of Colquhounia Root Tablets in inhibiting osteoclast differentiation based on HSP90 target modulation

This study aimed to investigate the potential role of Colquhounia Root Tablets against bone destruction in rheumatoid arthritis(RA) and its molecular mechanism. The study used ultra-performance liquid chromatography-mass spectrometry to analyze the major components of Colquhounia Root Tablets and predicted its candidate target gene set based on the major components. The key targets of RA bone destruction were obtained through GeneCards and the Database of Genetics and Medical Literature(OMIM), protein-protein interaction(PPI) network was constructed, and the key targets were identified by topological analysis. The molecular mechanism of Colquhounia Root Tablets against RA bone destruction was further revealed using Gene Ontology(GO) and Kyoto Encyclopedia of Genes and Genomes(KEGG) enrichment analysis. The effects of Colquhounia Root Tablets on macrophage viability was assessed by MTS assay and screened for non-toxic concentrations. A model of receptor activator of nuclear factor-κB(RANKL) induced osteoclast differentiation in vitro was constructed. Colquhounia Root Tablets were used to observe the formation and differentiation of osteoclasts by tartrate-resistant acid phosphatase(TRAP) staining and fibrous actin(F-actin) staining, and the effects of Colquhounia Root Tablets on the changes of core target proteins in the osteoclast differentiation system were detected by immunofluorescence and Western blot. The results showed that the main components of Colquhounia Root Tablets included 14 compounds such as triptolide, celastrol, and triptophenolide. Further network analysis revealed that heat-shock protein 90(HSP90) was the key target gene of Colquhounia Root Tablets for anti-RA bone destruction. TRAP staining and F-actin staining showed that the number and area of TRAP-positive polymorphonuclear cells, as well as actin rings, were reduced in a dose-dependent manner after the intervention of Colquhounia Root Tablets(P<0.01). Western blot results showed that the expression of HSP90 protein was significantly reduced after intervention with Colquhounia Root Tablets at 20 and 40 μg·mL~(-1)(P<0.01); Colquhounia Root Tablets at 10 μg·mL~(-1) could significantly decrease the expression of necrosis factor receptor associated molecule 6(TRAF6) and nuclear factor of activated T cells 1(NFATc1) proteins(P<0.01); moreover, all doses of Colquhounia Root Tablets significantly reduced the expression of osteoclast differentiation marker proteins matrix metalloproteinase 9(MMP9) and cathepsin K(CTSK)(P<0.01).Immunofluorescence results further confirmed that Colquhounia Root Tablets significantly inhibited HSP90 and CTSK levels, as well as NFATc1 activation in osteoblasts. In conclusion, the present study confirmed that Colquhounia Root Tablets may inhibit RANKL-induced osteoclast differentiation by regulating the key target of HSP90, thus exerting an anti-RA bone destruction effect, which will provide a new idea for Colquhounia Root Tablets to prevent and treat bone destruction in rheumatoid arthritis.

The fertility recovering from heat stress and interactions of heat shock protein 20 with reproduction-related proteins in Monochamus alternatus.

Due to the rise in global temperatures with climate change, insects, as ectotherms, critically depend on their heat tolerance for survival and reproduction. Heat shock proteins (HSPs) are essential for heat tolerance by averting protein denaturation; however, whether HSPs contribute to reproduction-related heat tolerance remains largely unexplored. The study investigated the reproductive heat tolerance and recovery of Monochamus alternatus, a major forestry pest, in response to heat stress. Alongside impairing the development and viability of reproductive organs and sperm, heat stress was also found to reduce fecundity, fertility, mating, and oviposition behaviors. Remarkably, all reproductive parameters of M. alternatus recovered within 4 weeks postexposure. To investigate the recovery mechanisms, we identified 10 reproduction-related proteins as candidate substrate proteins of an HSP protein in M. alternatus using immunoprecipitation coupled with mass spectrometry analysis. Heat stress inhibited the transcription of these reproduction-related genes, thereby adversely affecting reproductive parameters. However, the induction of HSP20s transcription in response to heat stress appeared to facilitate the refolding of these critical reproduction-related proteins during the recovery phase, thus preventing lasting reproductive damage. Overall, this study suggests that while M. alternatus populations might be vulnerable to climate-induced temperature increases, their fertility can recover, mediated by the interaction of HSPs with reproduction-related genes. These findings offer profound insights into insect heat tolerance and recovery, expanding our understanding of HSP20 proteins' biological functions.

PU-H71 (NSC 750424): a molecular masterpiece that targets HSP90 in cancer and beyond.

Heat shock protein 90 (HSP90) is a pivotal molecular chaperone with multifaceted roles in cellular health and disease. Herein, we explore how HSP90 orchestrates cellular stress responses, particularly through its partnership with heat shock factor 1 (HSF-1). PU-H71, a selective inhibitor of HSP90, demonstrates significant potential in cancer therapy by targeting a wide array of oncogenic pathways. By inducing the degradation of multiple client proteins, PU-H71 disrupts critical signaling pathways such as MAPK, PI3K/Akt, JAK/STAT, EGFR, and mTOR, which are essential for cancer cell survival, proliferation, and metastasis. We examined its impact on combating triple-negative breast cancer and enhancing the effectiveness of carbon-ion beam therapy, offering new avenues for cancer treatment. Furthermore, the dual inhibition of HSP90A and HSP90B1 by PU-H71 proves highly effective in the context of myeloma, providing fresh hope for patients with this challenging malignancy. We delve into its potential to induce apoptosis in B-cell lymphomas that rely on Bcl6 for survival, highlighting its relevance in the realm of hematologic cancers. Shifting our focus to hepatocellular carcinoma, we explore innovative approaches to chemotherapy. Moreover, the current review elucidates the potential capacity of PU-H71 to suppress glial cell activation paving the way for developing novel therapeutic strategies for neuroinflammatory disorders. Additionally, the present report also suggests the promising role of PU-H71 in JAK2-dependent myeloproliferative neoplasms. Eventually, our report sheds more light on the multiple functions of HSP90 protein as well as the potential therapeutic benefit of its selective inhibitor PU-H71 in the context of an array of diseases, laying the foundations for the development of novel therapeutic approaches that could achieve better treatment outcomes.

Association between physiological responses and heat shock protein 70 (HSP70) expressions in the vulnerable populations of Kuala Lumpur

ABSTRACT Continued heat exposure can cause physiological and cellular responses. This study investigated the association between physiological responses and heat shock protein 70 (HSP70) expressions in Kuala Lumpur’s urban vulnerable population. We conducted a cross-sectional study involving 54 participants from four areas classified as experiencing moderate to strong heat stress. Physiological measurements included core body temperature, heart rate, and diastolic and systolic blood pressure. RT-qPCR and ELISA were also performed on blood samples to assess HSP70 gene and protein expressions. Despite indoor heat stress, participants maintained normal physiological parameters while there were significant indications of HSP70 expression at both the gene and protein levels. However, our study found no significant correlation (p > 0.05) between physiological responses and HSP70 expressions. This study shows no interaction between physiological responses and HSP70 expressions in the study population, revealing the complex mechanisms of indoor heat stress in vulnerable individuals.

Integrated stress response mediates HSP70 to inhibit testosterone synthesis in aging testicular Leydig cells

The integrated stress response (ISR) is implicated in age-related diseases, while the molecular chaperone heat shock protein 70 (HSP70) can facilitate proper protein folding. However, the regulatory mechanism of ISR in insufficient testosterone synthesis of aging Leydig cells (LCs) remains unclear. This study aims to elucidate the regulatory role of ISR in inadequate testosterone synthesis of aging LCs. We observed a positive correlation between testosterone and HSP70 levels, which were found to be decreased in elderly men. ISR was detected in testicular tissue from old mice. The expression of testosterone synthesis related protein and the content of testosterone decreased in testicular tissue of old mice. Conversely, inhibition of the integrated stress response in testicular tissue led to an increase in steroid synthase expression among old mice. Furthermore, inhibiting ISR specifically within aging LCs resulted in enhanced protein translation efficiency and increased expression levels of new HSP70 and steroidogenic acute regulatory protein (StAR). These findings suggest that ISR occurrence within aging LCs affects StAR protein expression through regulation of HSP70-mediated translation, consequently impairing testosterone synthesis.

Anti-Heat Shock Protein 70 Autoantibodies from Patients with Idiopathic Pulmonary Fibrosis Epigenetically Enhance Lung Fibroblast Apoptosis Resistance and Bcl-2 Expression.

IgG autoantibodies to heat shock protein 70 (HSP70) are found in many immune-mediated clinical syndromes, and their presence among patients with idiopathic pulmonary fibrosis (IPF) portends especially poor outcomes. However, pathological effects of IPF anti-HSP70 have not been studied extensively. IPF lung fibroblasts are apoptosis resistant, and this dysregulation contributes to the accumulation of fibroblasts that characterizes the disease. During stress, HSP70 protein is exported extracellularly, where it binds to cognate cell surface receptors that mediate a variety of functional effects, including apoptosis inhibition. We hypothesized anti-HSP70 could engage HSP70-receptor complexes on fibroblasts that alter their apoptosis susceptibility. We found HSP70 is ubiquitously expressed on primary human lung fibroblasts. Treatment with anti-HSP70 isolated from patients with IPF with acute exacerbations increased Bcl-2 expression in human lung fibroblasts and reduced their susceptibility to staurosporine-induced apoptosis. Chromatin immunoprecipitation assays showed Bcl-2 gene promoter regions are enriched with the active histone mark H4 lysine 16 acetylation, and this was increased in the autoantibody-treated fibroblasts. When H4 lysine 16 acetylation was decreased by knocking down its acetyltransferase, MOF (males absent on the first), the anti-HSP70 treatments failed to upregulate Bcl-2. This study describes a heretofore unknown, to our knowledge, pathogenic consequence of autoimmunity in which autoantibodies affect the epigenetic regulation of fibroblast apoptosis. In addition to IPF, this autoimmune process could also have relevance in other immunological syndromes characterized by anti-HSP70 autoimmunity. These findings lend credence to the importance of autoimmunity in IPF and illustrate pathways that could be targeted in innovative therapies for this morbid, medically refractory lung disease.

Modulation of the Prostate Cancer Resistance Factor Hsp27 by the Chemotherapeutic Drugs Abiraterone, Cabazitaxel, Docetaxel and Enzalutamide.

The cytoprotective heat shock protein 27 (HSP27) acts as a protein chaperone, antioxidant, and apoptosis regulator and is involved in cytoskeletal remodeling in prostate cancer. This study was designed to assess the effect of prostate cancer therapeutics on HSP27 to identify drugs that may benefit from an HSP27 inhibitor combination therapy. Cell counting was utilized to assess drug treatment efficiency. Changes in protein levels after drug treatment were assessed using western blot analysis. Abiraterone, cabazitaxel, docetaxel and enzalutamide significantly reduced cell proliferation in LNCaP and PC3 cells. Treatment with abiraterone and enzalutamide led to a significant reduction in HSP27 protein levels. In contrast, treatment with cabazitaxel and docetaxel did not change the HSP27 protein levels. Treatment with abiraterone and enzalutamide reduces HSP27 protein in an AR-independent manner and thus suppresses HSP27-correlated resistance mechanisms. However, docetaxel and cabazitaxel do not alter HSP27 protein levels, so that taxanes' efficacy may be enhanced by combining them with HSP27-inhibiting drugs.

Ultrashort wave diathermy inhibits pulmonary inflammation in mice with acute lung injury in a HSP70 independent way: a pilot study.

Acute lung injury (ALI) is a clinical syndrome characterized by pulmonary inflammation. Ultrashort wave diathermy (USWD) has been shown to be effective at in inhibiting ALI inflammation, although the underlying mechanism remains unclear. Previous studies have demonstrated that USWD generates a therapeutic thermal environment that aligns with the temperature required for heat shock protein 70 (HSP70), an endogenous protective substance. In this study, we examined the correlation between HSP70 and USWD in alleviating lung inflammation in ALI. Forty-eight male C57BL/6 mice were randomly divided into control, model, USWD intervention (LU) 1, 2, and 3, and USWD preintervention (UL) 1, 2, and 3 groups (n = 6 in each group). The mice were pretreated with LPS to induce ALI. The UL1, 2, and 3 groups received USWD treatment before LPS infusion, while the LU1, 2, and 3 groups received USWD treatment after LPS infusion. Lung function and structure, inflammatory factor levels and HSP70 protein expression levels were detected. USWD effectively improved lung structure and function, and significantly reduced IL-1β, IL-10, TGF-β1, and TNF-α levels in both the USWD preintervention and intervention groups. However, HSP70 expression did not significantly differ across the experimental groups although the expression of TLR4 was significantly decreased, suggesting that USWD may have anti-inflammatory effects through multiple signaling pathways or that the experimental conditions should be restricted. Both USWD intervention and preintervention effectively reduced the inflammatory response, alleviated lung injury symptoms, and played a protective role in LPS-pretreated ALI mice. HSP70 was potentially regulated by USWD in this process, but further studies are urgently needed to elucidate the correlation and mechanism.

Plant-Based HSP90 Inhibitors in Breast Cancer Models: A Systematic Review.

Breast cancer, the most invasive cancer in women globally, necessitates novel treatments due to prevailing limitations of therapeutics. Search of news anticancer targets is more necessary than ever to tackle this pathology. Heat-Shock Protein 90 (HSP90), a chaperone protein, is implicated in breast cancer pathogenesis, rendering it an appealing target. Looking for alternative approach such as Plant-based compounds and natural HSP90 inhibitors offer promising prospects for innovative therapeutic strategies. This study aims to identify plant-based compounds with anticancer effects on breast cancer models and elucidate their mechanism of action in inhibiting the HSP90 protein. A systematic review was conducted and completed in January 2024 and included in vitro, in vivo, and in silico studies that investigated the effectiveness of plant-based HSP90 inhibitors tested on breast cancer models. Eleven studies were included in the review. Six plants and 24 compounds from six different classes were identified and proved to be effective against HSP90 in breast cancer models. The studied plant extracts showed a dose- and time-dependent decrease in cell viability. Variable IC50 values showed antiproliferative effects, with the plant Tubocapsicum anomalum demonstrating the lowest value. Withanolides was the most studied class. Fennel, Trianthema portulacastrum, and Spatholobus suberectus extracts were shown to inhibit tumor growth and angiogenesis and modulate HSP90 expression as well as its cochaperone interactions in breast cancer mouse models. The identified plant extracts and compounds were proven effective against HSP90 in breast cancer models, and this inhibition showed promising effects on breast cancer biology. Collectively, these results urge the need of further studies to better understand the mechanism of action of HSP90 inhibitors using comparable methods for preclinical observations.

Heat shock protein 90 and prolyl hydroxylase 2 co-regulate hypoxia-inducible factor-1α expression in porcine small intestinal epithelial cells under heat stress

Heat stress (HS) poses a substantial threat to animal growth and development, resulting in declining performance and economic losses. The intestinal system is susceptible to HS and undergoes intestinal hyperthermia and pathological hypoxia. Hypoxia-inducible factor-1α (HIF-1α), a key player in cellular hypoxic adaptation, is influenced by prolyl-4-hydroxylase 2 (PHD2) and heat shock protein 90 (HSP90). However, the comprehensive regulation of HIF-1α in the HS intestine remains unclear. This study aims to explore the impact of HS on pig intestinal mucosa and the regulatory mechanism of HIF-1α. Twenty-four Congjiang Xiang pigs were divided into the control and five HS-treated groups (6, 12, 24, 48, and 72 h). Ambient temperature and humidity were maintained in a thermally-neutral state (temperature–humidity index (THI) < 74) in the control group, whereas the HS group experienced moderate HS (78 < THI <84). Histological examination revealed villus exfoliation after 12 h of HS in the duodenum, jejunum, and ileum, with increasing damage as HS duration extended. The villus height to crypt depth ratio (V/C) decreased and goblet cell number increased with prolonged HS. Quantitative real-time PCR, Western blot, and immunohistochemistry analysis indicated increased expression of HIF-1α and HSP90 in the small intestine with prolonged HS, whereas PHD2 expression decreased. Further investigation in IPEC-J2 cells subjected to HS revealed that overexpressing PHD2 increased PHD2 mRNA and protein expression, while it decreases HIF-1α. Conversely, interfering with HSP90 expression substantially decreased both HSP90 and HIF-1α mRNA and protein levels. These results suggest that HS induces intestinal hypoxia with concomitant small intestinal mucosal damage. The expression of HIF-1α in HS-treated intestinal epithelial cells may be co-regulated by HSP90 and PHD2 and is possibly linked to intestinal hyperthermia and hypoxia.

Pathogenicity of human CD91 SNPs

Abstract CD91, expressed by antigen presenting cells, is a necessary receptor for cancer immunosurveillance. It binds multiple ligands including immunogenic heat shock proteins (HSP) and functions as both an endocytic receptor for antigen capture and a signaling receptor to upregulate cytokines and costimulatory molecules. Due to its size, there are more than 3500 identified single nucleotide polymorphisms (SNPs) for human CD91, however the functional consequences for these SNPs have not been addressed. Thus, we sought to investigate if certain SNPs result in altered function of CD91 and if these SNPs are linked with cancer higher incidence. Using a cohort of sarcoma patients, we identified 11 SNPs that resulted in missense mutations of CD91. Correlations between these SNPs and the immunophenotype of the respective tumors has identified several SNPs which correlate with poor immune infiltration and increased tumor antigenicity. Alternatively, a small number of SNPs correlate with above average immune infiltration and reduced tumor antigenicity, potentially enhancing CD91 function. In addition to our patient data, predictive folding algorithms were used to assess the potential effects of individual SNPs on protein folding. In order to directly assess the function of these SNPs, we have generated an in vitro model system using THP1 cells. Cells carrying single CD91 SNPs will be assessed for protein expression levels, HSP binding and internalization as well as costimulatory function.

Environmentally friendly and efficient TBHP-mediated catalytic reaction for the synthesis of substituted benzimidazole-2-ones: In-silico approach to pharmaceutical applications

A novel method was used to synthesize benzimidazole-2-ones from the corresponding benzimidazolium salts. These salts were subsequently reacted with potassium tertiary butoxide (KOtBu), followed by oxidation using tertiary butyl hydrogen peroxide (TBHP) at room temperature in tetrahydrofuran (THF) to obtain the desired products in 1 h with excellent yields. After optimizing the reaction conditions, the study focused on preparing benzimidazole-2-ones with diverse substituents at N1 and N3 positions, including benzyl, 2′,4′,6′-trimethyl benzyl groups, and long-chain aliphatic substituents (hexyl, octyl, decyl, and dodecyl). The compounds were characterized by 1H and 13C NMR spectra, of which compound 2a is supported by single crystal XRD. Benzimidazole-2-one compounds exhibited promising anti-inflammatory and anti-cancer properties. The inhibition of mitochondrial Heat Shock Protein 60 (HSP60) of title compounds was also explored. Computational simulations were employed to assess anti-cancer properties of 19 benzimidazole-2-one derivatives (potential drugs). In-silico docking studies demonstrated promising binding interactions with HSP60, and these results were supported by molecular dynamics simulations. Notably, molecules 2b and 2d exhibited high affinity for HSP60 protein, highlighting their potential efficacy. The developed ligands were viable for the treatment of hepatocellular carcinoma (HCC). The findings provide valuable initial evidence supporting the efficacy of benzimidazole-2-ones as HSP60 inhibitors and lay the foundation for subsequent studies, including in-vitro assays.

Characterization and expression of heat shock protein 70s in Liposcelis bostrychophila: Insights into their roles in insecticidal stress response

Liposcelis bostrychophila is one of the most economically significant and important storage pests in the Psocoptera order. Heat shock proteins (HSPs) act as molecular chaperones and play an important role in insect responses to environmental stress. In this study, the genome-wide identification and characterization of 61 HSP proteins in the L. bostrychophila genome was conducted. These HSPs are classified into five different families, comprising 8 HSP70s, 3 HSP90s, 10 HSP60s, 35 HSP40s, and 5 sHSPs genes. Phylogenetic profiling of the HSP gene families disclosed unique inter-group connections for each HSP family. These families maintained relatively stable motif composition and gene structure. Particularly, the HSP40 family expanded substantially in L. bostrychophila. Furthermore, quantitative polymerase chain reaction (qPCR) revealed distinct expression profiles of the LbHSP genes during development of L. bostrychophila. Most LbHSP70 genes expression are induced by insecticide exposures, and differences in their mRNA abundance profiles may be associated with the type and concentration of the tested insecticides. Specifically, LbHSP70.4 and LbHSP70.5 were most significantly up-regulated after insecticide treatments. Silencing the expression of LbHSP70.4 and LbHSP70.5, respectively, resulted in significantly higher mortality upon both beta-cypermethrin and malathion (LC20) treatments. This study affirms the important roles played by specific LbHSP70 genes in responding to insecticide stresses. The findings of this study not only contribute to the database of insect heat shock protein genes but also enhance our understanding of the mechanism underlying resistance or tolerance formation in stored-product psocids.

Enhancing resistance and cell survival in Acipenser ruthenus liver, gill, and kidney cells: The potential of heat shock protein inducers against PAH-benzo[a]pyrene stress.

The Caspian Sea has faced many environmental challenges, such as oil pollution. Heat shock proteins (HSPs) play a critical role in stress conditions and physiological changes caused by disease or injury. By evaluating the effects of various HSP inducers (HSPi), including Pro-Tex® (NOP: 800 mM), amygdalin (AMG: 80 mM), and a novel synthetic compound derived from pirano piranazole (SZ: 80 µm) on isolated cells from Sterlet Sturgeon (Acipenser ruthenus) treated with 75% IC50 PAH-benzo[a]pyrene (BaP; B75). This study examines whether there is a correlation between exposure to the BaP pollutant and HSPs in fish. In vitro, after culturing cells from the liver, kidney, and gills, they were treated with HSPi compounds in the presence and absence of BaP. Western blotting was used to assess HSP27, HSP70, and HSP90 expression patterns. A variety of enzyme activities were measured before (without treatment) and after treatment with HSPis and HSPi + B75, including cytochrome P450 (CYP450) activity, specific enzyme activity for acetylcholinesterase (AChE), antioxidant capacity, liver indicator enzymes, cortisol levels, and immunity parameters. When compared to the control group, cells treated with B75 showed the lowest AChE enzyme activity (p < 0.0001). CYP450 activity was highest in group B75, while HSPi caused the opposite effect (p < 0.0001). HSPi + B75 increased HSP levels and antioxidant parameters while decreasing cortisol and liver indicator enzymes (p < 0.0001). HSPi may be a powerful and reliable method for enhancing the resistance of A. ruthenus to BaP stresses before exposure. Treating cells with HSP-inducing compounds, such as NOP, AMG, and SZ, can assist them in managing stress and increase HSP (27, 70, and 90) protein expression. Furthermore, the study findings suggest that HSPis can also mitigate the adverse effects of stress, ultimately increasing cell survival and resistance.

Clinicopathologic significance of heat shock protein 60 as a survival predictor in breast carcinoma.

While Heat Shock Protein 60 (HSP60) has been linked to human tumor, its clinic significance specifically in breast carcinoma is unclear. This investigation aims to retrospectively evaluate how HSP60 protein levels relate to survival outcomes among patients diagnosed with breast carcinoma. Evaluation of 206 patients diagnosed with breast carcinoma and receiving treatment from January 2012 to April 2018, carried out retrospectively. The protein level of HSP60 in breast carcinoma determined by immunohistochemical. The study provided evidence of a distinct upregulation of HSP60 expression in breast carcinoma tumor samples in contrast to adjacent normal tissue samples. Additionally, heightened HSP60 expression was linked to advanced T stage (P = 0.046), N stage (P = 0.034), tumor metastasis (P = 0.016), pathological grading (P = 0.012), and adjuvant therapy utilization (P = 0.004). Moreover, elevated levels of HSP60 proteins exhibited a significant inverse correlation with overall survival (OS) [hazard ratio (HR) 1.598, P = 0.018] and progression-free survival (PFS) (HR 1.600, P = 0.017) among breast carcinoma patients in univariate analyses. The results of multivariate analyses highlighted HSP60 may serve as an independent predictor for both OS and PFS in breast carcinoma patients (HR 1.525, P = 0.034; HR 1.528, P = 0.033, respectively). The involvement of HSP60 in breast carcinoma progression suggests its potential clinical relevance in treatment target validation and prognostic assessment of the disease.

Revealing Propolis Potential Activity on Inhibiting Estrogen Receptor and Heat Shock Protein 90 Overexpressed in Breast Cancer by Bioinformatics Approaches.

Breast cancer is the most commonly diagnosed cancer globally, with the highest incidence of breast cancer occurring in Asian countries including Indonesia. Among the types of breast cancer, the estrogen receptor (ER)-positive subtype which is prominent with estrogen receptor alpha (ERα) and heat shock protein 90 (HSP90) overexpression genes becomes the most prevalent than the others, approximately 75% of all breast cancer cases. ERα and HSP90 play a role in breast cancer activities including breast tumor growth, invasion, and metastasis mechanism. Propolis, a natural bee product, has been explored for its anticancer activity. However, there is lack of studies that evaluated the potential inhibitor from propolis compounds to the ERα and HSP90 proteins. Therefore, this article focuses on examining the correlation between ERα and HSP90's role in breast cancer and investigating the potential of 93 unique propolis compositions in inhibiting these genes in breast cancer using in silico approaches. This study revealed the positive correlation between ERα and HSP90 genes in breast cancer disease development. Furthermore, we also found novel potential bioactive compounds of propolis against breast cancer through binding with ERα and HSP90; they were 3',4',7-trihydroxyisoflavone and baicalein-7-O-β-D glucopyranoside, respectively. Further research on these compounds is needed to elucidate deeper mechanisms and activity in the real biological system to develop new breast cancer drug treatments.

Exploring variations in heat shock protein 70 expression among vulnerable populations across urban and rural areas in Klang Valley

As global temperatures rise due to climate change, the occurrence and intensity of heat waves are anticipated to increase. Despite this anticipation, there remains a gap in comprehending the underlying defense mechanisms against heat stress, particularly exhibited by Heat Shock Proteins (HSP) within vulnerable populations. Hence, this study aims to assess the expression of heat shock protein 70 (HSP70) in response to heat exposure among vulnerable populations residing in both urban and rural areas. A total of 108 respondents were recruited using multistage sampling. This study consists of three (3) methods: Part I: face-to-face questionnaire; Part II: indoor heat exposure monitoring using Universal Thermal Climate Index (UTCI) classification; and Part III: blood sample collection to determine HSP70 protein expression using HSP70 High Sensitivity Enzyme-linked Immunosorbent Assay (ELISA) kit. The results show that urban areas were exposed to strong UTCI thermal stress, whereas rural areas experienced moderate UTCI thermal stress. A higher level of HSP70 protein expression was observed in urban (2.524 ± 0.26) than in rural respondents (2.095 ± 0.27). This study concludes that both urban and rural vulnerable populations demonstrated different patterns of HSP70 protein expression in response to various levels of heat exposure.

Genome-Wide in Silico Analysis of the Heat Shock Protein (HSP) Family in Vigna Species: Insights into Molecular Mechanisms of Stress Response

Heat shock proteins, HSPs, are essential for plants to develop defense systems against various abiotic challenges. Vigna species are widely grown cash crops in the world. However, some unfavorable environmental conditions hinder the growth and production of these crops. It is therefore essential to investigate the factors influencing their growth, development, and tolerance to abiotic stress to develop stress-tolerant varieties. Consequently, a comprehensive genome-wide identification study was conducted to identify the Heat Shock Factor (HSF) genes in three Vigna species genomes employing computational tools. In the current study, 43 non-redundant HSP proteins were identified in three Vigna species including 17 in Vigna angularis, 22 in Vigna radiata, and 4 non-redundant in V. ungucuilata. Moreover, subcellular locations were predicted, and all HSPs were found in the nucleus. The theoretical isoelectric point predicted that most of the HSP proteins were acidic. The aliphatic index of the HSP proteins demonstrated that all proteins are highly thermostable. Moreover, the instability index revealed two proteins VangHSP_9 and VradHSP_9, considered stable while the rest of the HSP proteins were unstable. The phylogenetic analysis categorized HSP genes into two major clusters and gene structure analysis displayed that all HSP genes were intronless. This study gives novel insight into the functional characterization of HSPs in Vigna species for plant breeding programs.