Rationale: Ferroptosis-driven loss of dopaminergic neurons plays a pivotal role in the pathogenesis of Parkinson\'s disease (PD). In PD patients, Hspb1 is commonly observed at abnormally high levels in the substantia nigra. The precise consequences of Hspb1 overexpression in PD, however, have yet to be fully elucidated. Methods: We used human iPSC-derived dopaminergic neurons and Coniferaldehyde (CFA)-an Nrf2 agonist known for its ability to cross the blood-brain barrier-to investigate the role of Hspb1 in PD. We examined the correlation between Hspb1 overexpression and Nrf2 activation and explored the transcriptional regulation of Hspb1 by Nrf2. Gene deletion techniques were employed to determine the necessity of Nrf2 and Hspb1 for CFA\'s neuroprotective effects. Results: Our research demonstrated that Nrf2 can upregulate the transcription of Hspb1 by directly binding to its promoter. Deletion of either Nrf2 or Hspb1 gene abolished the neuroprotective effects of CFA. The Nrf2-Hspb1 pathway, newly identified as a defense mechanism against ferroptosis, was shown to be essential for preventing neurodegeneration progression. Additionally, we discovered that prolonged overexpression of Hspb1 leads to neuronal death and that Hspb1 released from ruptured cells can trigger secondary cell death in neighboring cells, exacerbating neuroinflammatory responses. Conclusions: These findings highlight a biphasic role of Hspb1 in PD, where it initially provides neuroprotection through the Nrf2-Hspb1 pathway but ultimately contributes to neurodegeneration and inflammation when overexpressed. Understanding this dual role is crucial for developing therapeutic strategies targeting Hspb1 and Nrf2 in PD.

Acute lung injury (ALI) is a life-threatening condition characterized by respiratory failure. Rosuvastatin (RSV) is an antihypercholesterolemic agent with antioxidant properties. The current study aimed to investigate RSV novel therapeutic impact on ALI with emphasis on oxidative stress, inflammation, and heat shock protein B1 (HSPB1). Male albino rats (N = 30) were divided into five groups. Normal control (NC) group: rats received normal saline 2 mL/kg P.O daily. Lipopolysaccharides (LPS) group: rats received LPS (3 mg/kg intraperitoneally once). RSV group: rats received RSV (2 mg/kg P.O daily). LPS + RSV group: rats received RSV as in group 3 and on the 7th day rats received LPS as group 2. LPS + Dexamethasone (DX): rats received DX (2 mg/kg P.O, daily for one week) and on the 7th day rats received LPS as group 2. At the end of experiment (one week), lung tissue was used to determine HSPB1, high mobility group box 1 (HMGB1) using ELISA. IL-6, nuclear factor-2 (Nrf2), haem Oxygenase-1 (HO-1) protein levels were assessed using immunohistochemistry. GSH, catalase, MDA, NO, albumin and urea are assessed by colorimetry. The results revealed that RSV treatment resolved histopathological changes in lung tissue induced by LPS. Compared to LPS group, LPS + RSV group showed significant decrease in urea, NO, MDA, HMGB1, IL-6 and HO-1 level compared to LPS-treated rats. Conversely, RSV treatment significantly increased HSPB1, Nrf2, albumin, GSH, and CAT levels compared to LPS rats. RSV is effective for amelioration of ALI and thus can be used as adjuvant therapy for ALI.

Cardiovascular disease is one of the leading causes of mortality worldwide, primarily driven by atherosclerosis, a chronic inflammatory condition contributing significantly to fatalities. Various biological determinants affecting cardiovascular health across different age and sex groups have been identified. In this context, recent attention has focused on the potential therapeutic and preventive role of increasing circulating levels of heat shock protein 27 (plasma HSP27) in combating atherosclerosis. Plasma HSP27 is recognized for its protective function in inflammatory atherogenesis, offering promising avenues for intervention and management strategies against this prevalent cardiovascular ailment. Exercise has emerged as a pivotal strategy in preventing and managing cardiovascular disease, with literature indicating an increase in plasma HSP27 levels post-exercise. However, there is limited understanding of the impact of exercise on the release of HSP27 into circulation. Clarifying these aspects is crucial for understanding the role of exercise in modulating plasma HSP27 levels and its potential implications for cardiovascular health across diverse populations. Therefore, this review aims to establish a more comprehensive understanding of the relationship between plasma HSP27 and exercise.

The mortality rate of acute-on-chronic liver failure (ACLF) remains significantly elevated; hence, this study aimed to investigate the impact of heat shock protein family B (small) member 1 (HSPB1) on ACLF in vivo and in vitro and the underlying mechanism. This study used the ACLF mouse model, and liver damage extent was studied employing Masson trichrome, hematoxylin and eosin (H&E), Sirius red staining, and serum biochemical indices. Similarly, hepatocyte injury in lipopolysaccharide (LPS)-induced L02 cells was evaluated using cell counting kit-8 assay, enzymatic activity, flow cytometry, and TUNEL assay, while the underlying mechanism was investigated using western blot. Results showed that the morphology of liver tissue in ACLF mice was changed and was characterized by cirrhosis, fibrosis, collagen fiber deposition, inflammatory cell infiltration, and elevated liver injury indices. Moreover, HSPB1 was upregulated in both ACLF patients and mice, where overexpressing HSPB1 was found to inhibit ACLF-induced liver damage. Similarly, the HSPB1 expression in LPS-treated L02 cell lines was also increased, where overexpressing HSPB1 was found to promote cell viability, inhibit liver injury-related enzyme activity, and suppress apoptosis. Mechanistic investigations revealed that HSPB1 was responsible for inhibiting p-P53 and Bax protein levels, where activated P53 counteracted HSPB1\'s effects on cellular behaviors. In conclusion, HSPB1 attenuated ACLF-induced liver injury in vivo and inhibited LPS-induced hepatocyte damage in vitro, suggesting that HSPB1 may be a novel target for ACLF therapy.

OBJECTIVE: 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.
METHODS: Cell counting was utilized to assess drug treatment efficiency. Changes in protein levels after drug treatment were assessed using western blot analysis.
RESULTS: 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.
CONCLUSIONS: 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.

Introduction Oral cancer is a significant global health issue that is mainly caused by factors, such as smoking, alcohol consumption, poor oral hygiene, age, and the human papillomavirus. Unfortunately, delayed diagnosis contributes to high rates of illness and mortality. However, saliva shows promise as a potential source for early detection, prognosis, and treatment. By analyzing the proteins and their interactions in saliva, we can gain insights that can assist in early detection and prediction. In this study, we aim to identify and predict the key genes, known as hub genes, in the salivary transcriptomics data of oral cancer patients and healthy individuals. Methods The data used for the analysis were obtained from salivaryproteome.org (https://salivaryproteome.org/) . The retrieved data consisted of individuals with oral cancer who were assigned unique identification numbers (IDs) 1025, 1030, 1027, and 1029, while the healthy individuals were assigned IDs 4256, 4257, 4255, and 4258, respectively. Differential gene expression analysis was used to identify genes that showed significant differences between the two groups. Uniformity and clustering were assessed through heatmaps and principal component analysis. Protein-protein interactions were investigated using the STRING database and Cytoscape. In addition, machine learning algorithms were employed to identify key genes involved in the interatomic interactions by analyzing transcriptomics data generated from the differential gene expression analysis. Results The accuracy and class accuracy of the extra tree classifier showed 98% and 97% in predicting interactomic hub genes, and HSPB1 was identified as a hub gene using Cytohubba from Cytoscape. Conclusion The predictive extra tree classifier, with its high accuracy in analysing interactomic hub genes in oral cancer, can potentially improve diagnosis and treatment strategies.

Lung cancer is a common malignancy characterized by ferroptosis, an iron-dependent form of cell death caused by excessive lipid peroxidation. The disruption of the ubiquitination system plays a crucial role in tumor development and spread. In recent years, there has been increasing interest in utilizing ferroptosis for lung cancer treatment; however, the precise mechanism of how ubiquitination modulates ferroptosis remains unclear. We used databases to analyze STUB1 expression patterns in lung cancer tissues compared to normal tissues and performed immunohistochemistry. The functional role of STUB1 was investigated through gain-of-function and loss-of-function experiments both in vitro and in vivo. Malondialdehyde levels, Fe2+ content, and cell viability assays were employed to evaluate ferroptosis status. Downstream targets of STUB1 were identified through screening and validated using immunoprecipitation and ubiquitination assays. Our findings demonstrate that STUB1 is downregulated in lung cancer cells and functions as an inhibitor of their growth and metastasis both in vitro and in vivo while promoting ferroptosis. Mechanistically, STUB1 induces ferroptosis through E3 ligase-dependent degradation of the ferroptosis suppressor HSPB1. Furthermore, our study elucidated the specific types and sites of modification on HSPB1 mediated by STUB1. This research establishes STUB1 as a tumor suppressor influencing proliferation of lung cancer cells as well as the epithelial-mesenchymal transition process associated with it. Importantly, our work highlights the role of STUB1 in ubiquitination-mediated degradation of HSPB1, providing insights for potential treatments for lung cancer.

Acute pancreatitis (AP) is a common abdominal disease that typically resolves on its own, but the mortality rate dramatically increases when it progresses to severe acute pancreatitis (SAP). In this study, we investigated the molecular mechanism underlying the development of SAP from AP. We utilized two SAP models induced by pancreatic duct ligation and caerulein administration. Transcriptomic and proteomic analyses were subsequently performed to determine the mRNA and protein expression profiles of pancreatic samples from SAP and AP model and normal mice. To explore the role of Hspb1 in SAP, we used Hspb1 knockout (KO) mice, a genetically engineered chronic pancreatitis strain (T7D23A), Anxa2 KO mice, and acinar cell-specific Prdx1 knockout mice. Additionally, various in vivo and in vitro assays were performed to elucidate the molecular events and direct targets of Hspb1 in acinar cells. We found that Hspb1 expression was upregulated in AP samples but significantly reduced in acinar cells from SAP samples. KO or inhibition of Hspb1 worsened AP, while AAV8-Hspb1 administration mitigated the severity of SAP and reduced remote organ damage in mice. Furthermore, AAV8-Hspb1 treatment prevented the development of chronic pancreatitis. We found that KO or inhibition of Hspb1 promoted acinar cell death through apoptosis and ferroptosis but not necroptosis or autophagy by increasing reactive oxygen species (ROS) and lipid ROS levels. Mechanistically, Hspb1 directly interacted with Anxa2 to decrease its aggregation and phosphorylation, interact with the crucial antioxidant enzyme Prdx1, and maintain its antioxidative activity by decreasing Thr-90 phosphorylation. Notably, the overexpression of Hspb1 did not have a protective effect on acinar-specific Prdx1 knockout mice. In summary, our findings shed light on the role of Hspb1 in acinar cells. We showed that targeting Hspb1/Anxa2/Prdx1 could serve as a potential therapeutic strategy for SAP.

The clinical diagnosis and treatment of pituitary neuroendocrine tumors (PitNETs) that invade the cavernous sinus are fraught with difficulties and challenges. Exploring the biological characteristics involved in the occurrence and development of PitNETs that invade the cavernous sinus will help to elucidate the mechanism of cavernous sinus invasion. There are differences between intrasellar tumors (IST) and cavernous sinus-invasion tumors (CST) in ultramicrostructure, tumor microenvironment (TME), gene expression, and signaling pathways. The microvascular endothelial cell is increased in CST. The VEGFR signaling pathway, VEGF signaling pathway, and chemokine signaling pathway are activated in CST. HSPB1 is upregulated in CST and promotes cell proliferation, cell viability, and migration. HSPB1 promotes the release of VEGF from GT1-1 cells and activates the VEGF signaling pathway in bEnd.3 cells. HSPB1 promotes the migration of bEnd.3 cells to GT1-1 cells and promotes the formation of blood vessels of bEnd.3 cells. bEnd.3 cells can release CCL3 and CCL4 and promote the vitality, proliferation, and migration of GT1-1 cells. HSPB1 promotes the formation of blood vessels of bEnd.3 cells and ultimately leads to tumor growth in vivo. HSPB1 acts as a key gene for invasion of the cavernous sinus in PitNETs, remodeling TME by promoting the formation of blood vessels of brain microvascular endothelial cells. The synergistic effect of tumor cells and microvascular endothelial cells promotes tumor progression. The mechanism by which HSPB1 promotes tumor invasion by inducing angiogenesis in PitNETs may be a new target for the treatment of PitNETs invading the cavernous sinus.

Bladder cancer (BCa) stands as a significant malignancy within the genitourinary system. Notably, heat shock proteins (HSPs) exhibit elevated expression in cells subjected to environmental stresses and have been linked to the progression of many human malignancies. Among these, the functional implications and specific mechanism of HSPB8 in BCa have yet to be fully explored. In this study, we measured HSPB8 expression in both BCa tissues and various cell lines, further delving into its influence on cellular behaviors. Our observations pinpoint an upregulation of HSPB8 in BCa, a trend strongly associated with more advanced clinical manifestations. Suppressing HSPB8 exhibited marked reductions in cell proliferation and migration capabilities, while simultaneously amplifying apoptosis and inducing cell cycle arrest. Reinforcing these findings, our in vivo analyses using mouse models showed similar trends. Notably, upon HSPB8 knockdown, levels of specific proteins including eNOS (S1177), Hsp27 (S78/S82), PRAS40(T246), RSK1/2(S221/S227), and STAT3 (S727) decreased, with Hsp27 (S78/S82) and PRAS40(T246) experiencing the most profound drops. Furthermore, the application of an HSP27 inhibitor effectively reversed the phenotypes caused by increased HSPB8 expression. Collectively, our results suggest that elevated HSPB8 expression could act as a potential prognostic marker for BCa, and targeting HSPB8 might open new therapeutic avenues for treating this malignancy.