Search Results (2,496)

Far-infrared radiation (FIR) may influence vascular endothelial function, but its time-dependent molecular effects in adult arterial endothelial cells remain incompletely defined. We investigated FIR-induced responses in human femoral artery endothelial cells (HFAECs) using transcriptomic, proteomic, and phosphoproteomic analyses with three biological replicates per condition. Transcriptomic profiling 3 h after 30 min of FIR irradiation identified 424 differentially expressed genes (210 upregulated and 214 downregulated) among 16,081 genes, including endothelial-protective, nitric oxide-related, oxidative-stress, and heat-shock response genes. Proteomic analysis identified 13 differentially abundant proteins immediately after irradiation and 23, 75, and 61 proteins at 6, 12, and 24 h, respectively. These temporal changes involved mitogen-activated protein kinase kinase/extracellular signal-regulated kinase signaling, vascular maturation, cytoskeletal organization, cell polarity, calcium/nitric oxide regulation, and stress adaptation. Phosphoproteomic analysis identified 12, 10, and 53 phosphorylation-related changes at 6, 12, and 24 h, respectively, indicating progression from actin and adhesion remodeling to junctional reorganization, focal adhesion maturation, and mechanosensing. Network analysis identified caveolin-1, β-catenin, and lamin B1 as hubs in a Rho guanosine triphosphatase-related module. Collectively, FIR induced a coordinated endothelial adaptive molecular response in HFAECs; functional studies are required to determine whether these changes enhance vascular repair. Full article

Inflammation plays a pivotal role in the pathogenesis of myocardial ischemia/reperfusion (I/R) injury, highlighting inflammation suppression as a critical therapeutic strategy. The inflammatory response is largely mediated through Toll-like receptor 4 (TLR4), a transmembrane signal receptor whose expression is upregulated by Heat Shock Protein Family A Member 8 (HSPA8). Here, we investigated whether SEM1, a subunit of the 26S proteasome, interacts with HSPA8 and attenuates TLR4-mediated inflammation. Our results demonstrate that SEM1 expression is downregulated following myocardial I/R. Overexpression of SEM1 alleviated cardiac injury and dysfunction, inhibited myocardial inflammation, and downregulated HSPA8 expression in the I/R-injured heart. Co-IP assays confirmed a strong physical interaction between SEM1 and HSPA8, while the precise molecular mechanism responsible for SEM1-induced downregulation of HSPA8 remains to be fully elucidated. Mechanistically, SEM1 suppressed the activation of the TLR4/MyD88/NF-κB signaling pathway. Collectively, these findings identify SEM1 as a novel regulator that protects against myocardial I/R injury via its association with HSPA8 and inhibition of the TLR4-mediated inflammatory cascade, offering a promising therapeutic target for this condition. Full article

Heat stress severely hinders citrus yield and fruit quality. This study employed integrated physiological and transcriptomic analyses to investigate the effects of the exogenous application of abscisic acid (ABA) and brassinosteroid (BR) on heat stress responses in citrus. The results showed that the exogenous application of ABA and BR increased the contents of soluble sugar, proline, and ABA, and enhanced the activities of peroxidase and catalase under heat stress. Transcriptome trend analysis identified profiles 1, 6, and 7 as significantly enriched across exogenous ABA, BR, and control conditions. Profile 6 exhibited rapid upregulation followed by stabilization and showed a significantly higher gene count under both ABA and BR treatments than under the control. KEGG enrichment analysis revealed that genes in profile 6 were primarily enriched in amino sugar, nucleotide sugar, galactose, amino acids, 2-oxocarboxylic acid, glycerophospholipid, glucosinolate metabolism, MAPK signaling pathway, plant hormone signal transduction, protein processing in the endoplasmic reticulum, plant–pathogen interaction, and endocytosis. Furthermore, four genes encoding heat shock proteins (HSP), including HSP21A, HSP21B, HSP70-17, and HSP70A, were induced under heat stress and showed significant upregulation in response to exogenous ABA and BR treatments. In conclusion, these findings indicated that exogenous ABA and BR regulated ABA and osmoprotectant accumulation and antioxidant defense activation in response to heat stress. Full article

Heat shock protein 70 (HSP70) regulates the stress tolerance and reproductive ability of insects. In this study, the SfHSP70-7 gene was cloned and identified from the rice pest Sogatella furcifera. SfHSP70-7 encodes a typical cytoplasmic HSP70 protein that has a conserved functional domain and is highly similar to the HSP70 homologous protein of Laodelphax striatellus. SfHSP70-7 was found to be widely expressed across all developmental stages, with the highest levels in nymphs and female adults. In terms of tissue distribution, it was particularly abundant in the gut and ovaries. Its expression was strongly induced by high/low temperatures and three insecticides (triflumezopyrim, sulfoxaflor, and imidacloprid), with the maximum induction under heat and triflumezopyrim stress. RNA interference (RNAi) efficiently silenced SfHSP70-7 and significantly increased the susceptibility of S. furcifera to triflumezopyrim and sulfoxaflor, but it had no effect on susceptibility to imidacloprid. RNAi knockdown of SfHSP70-7 markedly reduced survival by 45.5% (30 °C) and 38.9% (35 °C) under heat stress. In addition, gene knockdown can damage the reproductive performance of females by reducing oviposition and egg hatchability. These results indicate that SfHSP70-7 is involved in regulating the heat tolerance, insecticide adaptability, and reproductive regulation mechanism of S. furcifera, providing a potential target for pest control. Full article

Heat shock proteins (HSPs) are a family of conserved molecular chaperons present in both prokaryotic and eukaryotic species, playing a crucial role in maintaining cellular proteostasis and enhancing stress resilience. HSPs have a multitude of roles in regulating cell signaling transduction, antioxidant defenses, apoptosis, and protein folding, thereby contributing to overall cellular homeostasis. Insulin resistance is characterized by elevated oxidative stress, dysregulated pro-inflammatory signaling, and impaired cellular stress response, ultimately leading to deficient glucose uptake in skeletal muscle. Many studies have illustrated the benefits of exercise in improving insulin resistance and reducing the risk of metabolic disorders, such as type 2 diabetes. Habitual exercise and lifestyle modifications have been shown to activate heat shock response, enhancing HSP70 expression and promoting cellular adaptations that protect against metabolic dysfunction. However, the link between HSPs, particularly HSP70, and skeletal muscle insulin resistance remains complex and not fully elucidated. In this review, we discuss the mechanistic pathways by which HSP70 modulates insulin resistance, mitochondrial function, and inflammatory responses in skeletal muscle. Additionally, we discuss the protective effects of exercise-induced HSP70 expression and its potential as a therapeutic target for improving insulin sensitivity and metabolic health. Full article

Stress-associated transcriptional programs are common in single-cell perturbation data, but they are often treated as technical or experimental nuisance signals. Whether rare high-stress populations arise stochastically after perturbation or reflect outcomes associated with pre-existing cellular heterogeneity remains unclear. Herein, we build a cross-dataset stress-program prediction framework spanning 146,321 single cells and 926 perturbation–cell-line tasks. Untreated baseline heterogeneity, together with perturbation identity, predicted future rare integrated-stress burden across held-out cell-line–drug pairs ($R^2=0.742$, Pearson $r=0.862$). Single-cell stress-program prediction generalized across leave-task-out, leave-cell-line-out and leave-perturbation-out splits; retained signal in leave-dataset-out evaluation; and collapsed to near-null performance under within-task label permutation. Independent validation datasets provided external support for the inferred stress axes: tunicamycin and thapsigargin activated unfolded protein response/integrated stress response (UPR/ISR) modules in bulk RNA sequencing (RNA-seq), thapsigargin expanded populations with high X-box binding protein 1 (XBP1) UPR or activating transcription factor 4 (ATF4) ISR activity in donor-paired single-cell data, and an independent protocol-stress dataset indicated heat shock/proteostasis structure beyond cell type and quality control (QC). The resulting resource summarizes perturbation responses as activator protein 1 (AP1) immediate, UPR/ATF4, heat shock, replication-coupled and low/mixed dominant stress-program patterns. These findings suggest that stress variation should not be viewed solely as a nuisance covariate but may represent a predictable and biologically structured dimension of perturbation response space. Full article

The multistress concept is a recent approach developed to better understand the effects of environmental stress in animals under real-world conditions. In nature, animals are exposed to simultaneous environmental fluctuations on daily and seasonal time scales, and interactions among stressors can produce antagonistic, additive, or synergistic physiological responses. Consequently, studies examining only one stressor under controlled laboratory conditions may fail to reflect responses in natural habitats. This review discusses the effects of multiple stressors on redox metabolism and heat shock protein (HSP) responses, focusing on aquatic environments. We discuss the multistress approach in laboratory and field studies, highlighting major abiotic stressors such as salinity changes, solar radiation, temperature, and low oxygen availability, including hypoxia and aerial exposure. The effects of multiple stressors on HSPs and antioxidants are summarized using examples from the literature. Finally, the role of social stress and life history stage in shaping responses to multiple abiotic stressors is considered. Overall, the review highlights the application of the multistress approach in laboratory and field experiments, emphasizing key stress responses involving endogenous antioxidants and HSPs, both initiated by reactive oxygen species (ROS). Full article

Intervertebral disc degeneration is a major pathological contributor to low back pain and functional impairment, yet its complex molecular mechanisms have not been fully elucidated. Heat shock proteins, as important molecular chaperones and core regulators of cellular stress responses, exhibit dual protective and pathogenic roles in the process of intervertebral disc degeneration. This review summarizes the expression changes and related regulatory networks of heat shock protein family members such as HSP70, HSP90, HSP27 and GRP78 in nucleus pulposus and annulus fibrosus cells, comprehensively discussing their involvement in the molecular mechanisms of intervertebral disc degeneration by influencing key processes such as cellular homeostasis, inflammatory responses, apoptosis, autophagy, and the synthesis and degradation of the extracellular matrix. Furthermore, this review highlights HSP-centered proteostasis regulation as an emerging therapeutic framework for IVDD and discusses how HSP modulation may be integrated with biomaterials, physical stimulation, and regenerative strategies. However, direct IVDD-specific evidence for certain HSP members remains limited, and this review also highlights current knowledge gaps and future research directions for HSP-centered proteostasis regulation. Full article

Heat shock proteins (HSPs), particularly HSP70 and HSP90, are highly conserved molecular chaperones that protect cells from a wide range of stressors and maintain proteome homeostasis. In cancer, tumor cells frequently overexpress and actively release HSPs into the extracellular space and circulation in response to metabolic alterations, hypoxia, oxidative stress, and therapeutic interventions. Consequently, circulating HSP levels are often elevated in patients with malignancies compared with healthy individuals. This review summarizes current evidence on the diagnostic, prognostic, and predictive value of circulating HSPs in both solid and hematological cancers. Clinical studies indicate that circulating HSP concentrations are associated with tumor type, disease stage, lymph node involvement, metastatic burden, treatment response, and risk of recurrence. Importantly, membrane-associated and extracellular vesicle-associated forms of HSP70 appear to exhibit greater tumor specificity than freely circulating proteins, highlighting the importance of selecting appropriate analytical approaches for biomarker assessment. Beyond their utility as biomarkers, extracellular HSPs actively participate in tumor biology and anti-tumor immunity. Depending on the cellular and immunological context, they can either support tumor progression or stimulate immune responses through activation of natural killer cells, antigen-presenting cells, and cross-presentation of tumor-derived antigens. These immunomodulatory properties have provided the foundation for the development of HSP-based vaccines and adoptive immunotherapeutic strategies, several of which have demonstrated encouraging results in clinical trials. We further discuss the relationship between extracellular chaperone biology and responses to major anticancer treatments, including radiotherapy, chemotherapy, HSP90-targeted therapies, and immune checkpoint blockade. In conclusion, the available evidence supports circulating extracellular HSPs as promising non-invasive biomarkers and potential pharmacodynamic indicators that may improve patient stratification, treatment monitoring, and prediction of therapeutic efficacy in clinical oncology. Full article

Backgrounds/Objectives: Probiotics confer health-promoting and immunomodulatory effects on the host. However, a lot remains to be understood regarding their safety profile, characteristics and functional mechanisms. This study was conducted to comprehend the functional mechanisms of Limosilactobacillus reuteri isolated from chickens and characterize some of its uncharacterized proteins (hypothetical proteins). Methods: The chicken-isolated Limosilactobacillus reuteri genome, sequenced using Illumina MiSeq sequencing technology, was explored for proteome comparison analyses, comprehensive antibiotic resistance analysis, interleukin-4 (IL-4) expression across various conditions as well as IL-4-inducing potential. Results: Five antibiotic resistance-associated genes were found. Hypothetical proteins labeled QHPv.2.1, QHPv.2.12 and QHPv.2.16 induced IL-4, but QHPv.2.12 was not immunogenic. Immunogenic IL-4-inducing mutants from QHPv.2.1 (0.7013) and QHPv.2.16 (0.7040) had the best support vector machine (SVM) values, which were significantly (p < 0.05) higher than the rest of the group, followed by those from QHPv.2.12 (0.4587). QHPv.2.5 (0.0560) had the lowest value. QHPv.2.1 (5484.71) and QHPv.2.16 (5491.05) had significantly (p < 0.05) larger molecular weights (MWs), followed by QHPv.2.12 (5302.05). The lowest value was obtained for QHPv.2.7 (3386.74). Conclusions: This explorative study revealed the IL-4 inducing capacity of the hypothetical proteins of L. reuteri and their mutants, as well as identified heat and cold shock proteins associated with L. reuteri. Full article

Repeated exposure to subinhibitory concentrations of antiseptics may lead to reduced susceptibility or resistance and potentially promote cross-resistance to antibiotics. However, the underlying molecular mechanisms remain incompletely understood. This study investigated whether antiseptic-adapted Escherichia coli strains exhibit altered protein expression profiles compared with wild-type (WT) E. coli. Protein expression was analysed in E. coli strains previously adapted over ten passages to subinhibitory concentrations of chlorhexidine (CHX), cetylpyridinium chloride (CPC), and benzalkonium chloride (BAC). WT bacteria were exposed to sub-minimum inhibitory concentrations (sub-MICs) of antiseptics for 3 h to induce stress. Untreated WT and heat-shocked WT E. coli (42 °C, 2 h) served as controls. Protein expression profiles were assessed using SDS-PAGE and Western blotting targeting stress-associated proteins. SDS-PAGE demonstrated altered protein expression patterns in antiseptic-adapted strains, including differences in band intensities and additional protein bands. Western blot analysis showed increased DnaK and GroEL expression with reduced LexA levels in heat-shocked WT bacteria, whereas RecA remained largely unchanged. Antiseptic-adapted strains exhibited increased DnaK, GroEL, and OmpF expression together with reduced LexA and RecA expression. These findings indicate that adaptation to antiseptics involves complex mechanisms among multiple proteins rather than a single adaptive mechanism. Full article

Assessment of the stability of inflammatory parameters in bovine blood samples is important because it enables evaluation of the impact of preanalytical factors on biomarker preservation, standardization of sample processing and storage conditions, as well as reliable and consistent interpretation of results in diagnostic and research studies. The aim of the work was to evaluate the stability of the most common inflammatory markers in the blood of cows in early lactation. The influence of the serum–clot contacts duration and the storage of the separated serum in 24 cows, at 25 °C and 4 °C, in intervals of 0–24 h, was examined. Concentrations of interleukin 1 and 6 (IL-1, IL-6), tumor necrosis factor α (TNF-α), interferon γ (IFN-γ), haptoglobin (Hp), serum amyloid A (SAA) and extracellular heat shock protein 70 (eHsp70) were determined by ELISA method, stability was assessed by ANOVA analysis and maximum permissible instability method. Stability was determined over a range of 2–15 h for IL-1, 8–24 h for IL-6, 9–13 h for TNF-α, 10–20 h for IFN-γ, 20–24 h for Hp, 15–24 h for SAA, and 9–12 h for eHsp70. The stability was strongly dependent on temperature and sample type, with storage at 4 °C providing the highest stability in most cases, while differences between serum and serum–clot samples were analyte-specific and less consistent compared to the effect of temperature. Full article

Osteoradionecrosis of the jaw (ORNJ) remains one of the most severe late complications of head and neck radiotherapy. Current evidence suggests that ORNJ is a progressive and biologically heterogeneous disorder driven by microvascular injury, chronic hypoxia, oxidative stress, fibro-atrophic remodeling, impaired bone turnover, immune dysregulation, and systemic susceptibility factors. Within this complex pathogenic network, heat shock protein 27 (HSP27) emerges as a biologically plausible but unexplored mediator. HSP27 regulates multiple stress-response pathways, including redox homeostasis, cytoskeletal stabilization, endothelial protection, apoptosis control, fibroblast activation, and osteoblast–osteoclast function, all of which overlap with key mechanisms implicated in ORNJ. However, no studies have directly investigated HSP27 expression, activation, or functional significance in irradiated mandibular tissues or ORNJ-specific cohorts. This review summarizes current knowledge of ORNJ pathobiology, examines potential mechanistic links with HSP27, and outlines future research priorities involving biomarker development, tissue-level characterization, preclinical modeling, and therapeutic targeting. Integrating HSP27 into ORNJ research may improve understanding of pathogenesis, risk stratification, and the development of novel preventive and therapeutic strategies. Full article

Global warming is associated with an increased frequency and intensity of heat waves, which severely threaten crop production and sustainable agriculture. As sessile organisms, plants evolved complex heat stress memory mechanisms to cope with recurring heat waves. Heat shock transcription factors (HSFs) are at the core of plant heat stress responses and memory. They regulate basal thermotolerance, acquired thermotolerance, and the maintenance of acquired thermotolerance. These processes involve multiple mechanisms, including temperature perception, activation of heat shock protein expression, and integration of hormonal and epigenetic signals. Here, we review the pivotal role HSFs play in the formation of heat stress memory, their structural characteristics, functional differentiation, and signal perception and transcriptional regulatory mechanisms. We further discuss the functional conservation and the diversity of HSFs across multiple species—for instance, HSFA2 acts as a conserved regulator of heat stress memory in Arabidopsis, tomato, wheat, and barley—and outline future research directions, including the functional characterization of heat shock transcription factor (HSF) subfamilies, investigation of their roles under stress combination, and strategies to balance stress tolerance with growth and development. We hope that our review will provide a theoretical foundation for the genetic improvement of crop thermotolerance as well as contribute to efforts directed at ensuring food security in the face of climate change. Full article

The small heat shock protein HSPB1 is a ubiquitously expressed mechanoresponsive chaperone essential for cytoskeletal remodeling under mechanical load. Mutations in HSPB1, including S135F, cause Charcot-Marie-Tooth (CMT) peripheral neuropathy, yet the mechanisms underlying the selective vulnerability of peripheral nerves remain enigmatic. Here we demonstrate that substrate stiffness is a critical determinant of HSPB1^S135F-mediated neurodegeneration. Using stiffness-tunable polydimethylsiloxane (PDMS) substrates (1 kPa, 10 kPa, 2 MPa) and uniaxial cyclic stretch, we show that primary dorsal root ganglia (DRG) neurons and SH-SY5Y cells expressing HSPB1^S135F exhibit profound deficits in mechanoadaptation. On compliant substrates (10 kPa), HSPB1^S135F causes stretch-induced axon fragmentation and neuronal death, whereas HSPB1^WT confers robust neuroprotection. HSPB1^S135F also disrupts stiffness-directed neuritogenesis in differentiated SH-SY5Y cells: HSPB1^WT-expressing cells show optimal axonal outgrowth and βIII-tubulin expression on 10 kPa substrates mimicking muscle tissue stiffness, while HSPB1^S135F mutants display disorganized focal adhesions and complete differentiation failure. Mechanistically, we uncover that HSPB1^S135F dysregulates stage-specific transglutaminase (TGase) expression—insufficient TGase during early neuritogenesis impairs filopodia stabilization, whereas aberrant TGase persistence at late stages constrains axon extension. Our findings establish HSPB1 as a biomechanical sensor that integrates ECM stiffness signals to coordinate peripheral nerve regeneration, and identify defective mechanoadaptation as a previously unrecognized pathomechanism in CMT. These results open new avenues for stiffness-targeted therapeutic strategies in peripheral neuropathy. Full article