Search Results (2,443)

Histiocytic sarcoma (HS) is an aggressive hematological malignancy whose transformed cells exhibit morphological and immunophenotypic characteristics similar to macrophages, and arises de novo or as part of a clonal ‘evolution’ of other pre-existing hematological neoplasms. This study investigates the potential use of the J774A.1 cell line (a cell line derived from murine tumor cells, commonly used in macrophage research) as a research model to study the role of polydisperse extracellular vesicles (PEVs) secreted by the HS cells, considering that bacterial infections are common in patients with cancer, including HS. The influences of bacterial components on tumor progression are still not fully understood. We stimulated the J774A.1 cell line in vitro with a fraction of E. coli, and our results show that the bacterial stimulation increases the secretion of PEVs by these cells. Comparative results of J774A.1 cells with PEVs using confocal and scanning electron microscopy with micrographic reports of HS histological slides (from several cited mammal species, including humans) suggest a possible relationship of large PEVs with marks, footprints, or traces of possible large PEVs disrupted in the HS of these reports. A subsequent proteomic analysis of these PEVs revealed a diverse subcellular origin of their components, such as proteins including: Triosephosphate isomerase (TPI), Heat shock cognate 71 kDa, Apolipoprotein A-1, Rho GDP-dissociation inhibitor 1, GAPDH, Galectin, Moesin, globular Actin, and Annexin. These results highlight the importance of studying the interplay between HS, other hematological cancers, and bacterial infections to better understand the progression of this cancer, identify new therapeutic targets, and emphasize the importance of preventing bacterial infections in cancer patients. Furthermore, the results demonstrate the potential use of the stimulated J774A.1 cell line for research on HS-related PEVs. Full article

Honeybee (Apis mellifera) health is governed by the integrated action of detoxification, immunity, and microbiota within complex environmental contexts. The coordinated detoxification system (DETOXome), primarily active in the midgut, fat body, and Malpighian tubules, includes cytochrome P450s, glutathione S transferases, carboxylesterases, and ABC transporters, and functions in concert with innate immune pathways such as Toll, Imd, Jak/STAT, JNK, antimicrobial peptides, and RNA interference. Cellular maintenance mechanisms, including heat shock proteins, proteostasis, and antioxidant defenses, support these systems under chemical, thermal, and pathogen-induced stress. Multi-stressor exposures encompassing pesticides, pathogens, nutritional limitations, and climate variations interact to affect physiological resilience, behavior, and colony function. This review synthesizes molecular, organ-specific, and colony-level evidence to provide a mechanistic framework connecting environmental stressors to detoxification and immune responses. Predictive markers derived from transcriptomic, proteomic, and microbiome analyses offer early detection of sublethal stress, while genomic and selective breeding strategies hold the potential to enhance honeybee resilience. By integrating stress pathways across biological scales, this review advances a unified model of honeybee health that moves beyond descriptive lists to highlight cross-system interactions driving colony survival. Full article

The rumen epithelium of Tibetan sheep plays a critical role in energy metabolism and immune defense; however, its post-transcriptional regulatory mechanisms under high-altitude hypoxia stress remain unclear. In this study, we employed integrated mRNA and miRNA transcriptome sequencing to analyze the adaptive strategies of the rumen epithelium in Tibetan sheep at different altitudes. A total of 2183 differentially expressed genes (DEGs) and 135 differentially expressed miRNAs (DEmiRNAs) were identified. Functional enrichment analysis revealed that DEGs and their target genes were significantly enriched in immune-related pathways such as the NF-κB signaling pathway and cytokine–cytokine receptor interaction, as well as metabolic pathways including oxidative phosphorylation and branched-chain amino acid degradation. Integrated network analysis highlighted key regulatory pairs, including oar-miR-370-3p targeting PCK2 and IL1R2, and novel-miR-781 regulating PIK3R5, suggesting coordinated modulation between mitochondrial homeostasis and immune responses. Specifically, the upregulation of immune genes (CCL19, MADCAM1) and heat shock proteins at TS4500m indicates enhanced mucosal immunity and stress tolerance, while altered expression of metabolic genes reflects a shift in energy substrate utilization. These findings elucidate a complex mRNA-miRNA regulatory network that enables Tibetan sheep to maintain rumen epithelial integrity and energy balance under extreme high-altitude conditions, providing novel insights into the molecular basis of hypoxia adaptation in ruminants. Full article

Background: Heat shock protein 100 (HSP100) is a key molecular chaperone that maintains intracellular proteostasis and enhances plant tolerance. However, the HSP100 gene family in soybean (Glycine max) has not been systematically characterized. Methods: In this study, we performed genome-wide identification and comprehensive analysis of the GmHSP100 gene family and analyzed their phylogeny, genomic distribution, synteny, protein structures, subcellular localization, promoter cis-elements, and expression patterns under heat and salt stresses via bioinformatics approaches and quantitative real-time PCR (qRT-PCR) validation. Results: Thirteen GmHSP100 members were identified, which were classified into CLPB, CLPC and CLPD subfamilies. Segmental and whole-genome duplications primarily drove the expansion of this gene family. All encoded proteins possessed conserved AAA+ ATPase domains, with distinct motifs across subfamilies. Most proteins localized to the cytoplasm, while CLPC and CLPD targeted chloroplasts and GmCLPB4 localized to mitochondria. Promoter analysis identified numerous elements associated with light, hormone and stress responses. Expression profiling showed strong tissue specificity and time-dependent stress-treatment induction. Heat stress triggered rapid and strong upregulation of the GmHSP100s, whereas salt stress salt stress induced their relatively delayed and sustained expression. Conclusion: These findings reveal the evolutionary conservation and diversification of the GmHSP100 gene family in soybean, providing a foundational framework for understanding the functions of GmHSP100 in stress adaptation. Full article

Fetal growth restriction (FGR) is frequently defined as the failure of the fetus to reach its genetically predetermined growth potential. Heat shock proteins (HSPs) are extreme-temperature-resistant molecules that help proteostasis. The aim of this prospective case–control immunohistochemistry study is to evaluate the expression of HSP90 and HSP70 in the placentas of pregnancies complicated with FGR and compare their levels with the control placentas of normal-growth pregnancies. A prospective case–control study was conducted including people undergoing singleton pregnancies who gave birth in a tertiary university hospital in Central Greece. Participants were divided into two equal groups: an FGR pregnancy group and a control group with normal growth. Immunohistochemistry of placental samples was assessed using anti-HSP90 alpha/beta antibody (clone F-8, Santa Cruz Biotechnology, Dallas, TX, USA) and anti-HSC70/HSP70 antibody (clone W27, sc-24, Santa Cruz Biotechnology, Dallas, TX, USA). A scoring system was created to quantify the expression of HSP90 and HSP70 in each sample, and the grade of staining was measured at four points. A total of 80 pregnant people were prospectively enrolled in our study, with 40 in each group. Both constitutive (HSP90β and HSC70/HSPA8) and stress-inducible (HSP90α and HSP70/HSPA1A/B) isoforms were analyzed. When comparing the total score of HSP expression, a statistically significant difference was observed for both HSP90 and HSP70. For HSP90 expression, only the Hofbauer cell’s stain was identified as a statistically significant independent factor, meaning that its positive expression was observed in Hofbauer cells. For HSP70 expression, only the staining of syncytiotrophoblasts was identified as an independent factor. FGR is a common pregnancy complication and a leading cause of stillbirth, neonatal mortality, and short- and long-term neonatal morbidity worldwide. Based on our findings, the lower expression levels of both HSP90 and HSP70 are associated with FGR, revealing a possible association with stress response in FGR pathophysiology. However, more robust data from larger-scale prospective studies are needed to elucidate the possible role of HSPs as potential FGR biomarkers. Full article

Plant diseases remain a major constraint to crop productivity and global food security. Conventional breeding has long been used to develop resistant cultivars through the introgression of resistance traits from wild relatives and the selection of favorable phenotypes. However, this process is often slow and limited by linkage drag, known genetic diversity, intrinsic genetic limitations, and the rapid evolution of pathogen populations. Molecular breeding strategies, including marker-assisted selection and genomic selection, have improved the precision of resistance breeding but still rely on existing genetic variation. Recent advances in genome editing technologies are transforming plant breeding by enabling precise modification of gene targets. CRISPR-based systems allow targeted gene knockouts, promoter editing, allelic replacement, and multiplex editing to rapidly generate resistance traits. Many studies have demonstrated that editing susceptibility genes or regulatory regions can enhance resistance to diverse pathogens. Recent research shows that resistance can also be improved by targeting non-classical genes involved in plant immunity, including transcription factors, membrane transporters, heat shock proteins, cell wall-related genes, metabolic enzymes, and epigenetic regulators. Emerging tools such as base editing, prime editing, regulatory tools, and transposon-associated genome engineering systems are further expanding the precision and versatility of plant genome editing. Despite these advances, challenges related to delivery systems, editing efficiency, regulatory frameworks, and field validation remain. Continued technological progress and improved knowledge of plant immune networks will be essential to fully integrate genome editing into crop improvement programs. Full article

Unexplained infertility affects up to 30% of couples and has been associated with heat shock proteins (HSP) and endometrial stress. HSPs and their co-chaperones are part of a complex network of proteins responsible for maintaining protein homeostasis and cell survival. This exploratory hypothesis-generating study investigated the possible relationship between HSPs and unexplained infertility. Twenty-five women were recruited from an IVF clinic. Eleven were confirmed for unexplained infertility (UI), while fourteen were age- and body mass index (BMI)-matched couples with confirmed male factor infertility (MFI), acting as controls. Blood samples were obtained at day 21 of the luteal phase, and plasma measurement of 19 HSPs and co-chaperones undertaken using the slow off-rate modified aptamer (SomaScan) platform. Welch’s t-test and a permutation test were used to compare group means, and Pearson’s correlations to examine relationships with HSPs. Of the 19 proteins measured, plasma HSP70 was decreased (permutation p = 0.002) in cases with unexplained infertility, while HSC70 and STIP1 were increased (permutation p = 0.017 and p = 0.001, respectively) when compared to MFI control. HSP70 was negatively correlated to both HSC70 and STIP 1 in UI (r = −0.77, permutation p = 0.017; −0.80, permutation p = 0.003, respectively), but not in MFI, whilst HSC70 and STIP1 were positively correlated in both UI and MFI (r = 0.93, permutation p = 0.001; r = 0.65, permutation p = 0.035, respectively). The HSP70-HSC70-STIP1 axis showed HSC70-STIP1 coupling with an inverse relationship with inducible HSP70, findings that may suggest dysregulation of constitutive and stress-inducible chaperone systems in UI. Full article

Background: Fibrolamellar carcinoma (FLC) is a rare liver malignancy affecting adolescents. FLCs harbor a DNAJB1–PRKACA gene fusion that combines heat shock protein DNAJB1 with the catalytic subunit of protein kinase A. Surgery with systemic therapy provides 5-year survivals of 30–50%, but advanced disease remains largely incurable. Three-dimensional explants from 41 FLC patients were interrogated for drug sensitivity, resistance, and synergy against cytotoxics, targeted agents, and signal transduction inhibitors. Methods: Sterile specimens from histologically confirmed FLC patients were analyzed by Ex Vivo Analysis of Programmed Cell Death (EVA/PCD™) in a CLIA-licensed laboratory. Following mechanical and enzymatic disaggregation, explants underwent 72 h drug exposure. LC₅₀ values were derived from five-point dose–response curves and compared with a database of over 10,000 human tumor analyses. Synergy was assessed by combination index. In parallel, targeted metabolomic profiling was performed in five FLC patients using tandem MS/MS. Results: Forty-one samples were analyzed. Of 24 drugs selected, tumor-cell yields were adequate for testing in 18 (75%). Single-agent activity favored vorinostat, followed by phenformin and 6-diazo-5-oxo-L-norleucine. Combinations favored gemcitabine plus oxaliplatin (GEMOX) and 5-FU plus interferon. Metabolomic analysis identified distinct signature consistent with mitochondrial dysfunction and altered polyamine metabolism. Conclusions: The present findings are exploratory, and hypothesis-generating and should not be interpreted as evidence of clinical efficacy. Prospective clinical validation and mechanistic studies will be required to further define the therapeutic relevance of these observations in fibrolamellar carcinoma. Full article

Global warming-induced extreme heatwaves present a severe threat to global tomato yield and production stability. To elucidate the molecular regulatory mechanisms underlying heat stress tolerance in tomato (Solanum lycopersicum), this study utilized label-free quantitative proteomics to profile alterations in protein abundance in tomato leaves in response to heat stress. A total of 294 differentially expressed proteins (DEPs) were identified, with function enrichment in the systematic activation of core stress-responsive biological processes, including the mitogen-activated protein kinase (MAPK) signaling cascade, the endoplasmic reticulum protein processing, and glutathione metabolism. Among them, heat shock protein (HSP) family members exhibited the most significant changes, particularly two small heat shock proteins (sHSPs), designated as SlsHSP1 and SlHSP17.4. Functional validation showed that silencing either SlsHSP1 or SlHSP17.4 drastically impaired heat tolerance in tomato plants. Specifically, silenced lines displayed excessive reactive oxygen species (ROS) accumulation and reduced antioxidant enzyme activities, with SlsHSP1-silenced plants showing more severe heat-induced phenotypic damage. Subcellular localization assays further demonstrated SlsHSP1 was located in the ER and SlHSP17.4 in the nucleus. Collectively, this study unravels multiple heat defense regulatory networks in tomato, in which organelle-specific sHSPs like SlsHSP1 and SlHSP17.4 synergistically maintain protein homeostasis and cellular redox balance, conferring broad-spectrum stress resistance in plants under high-temperature stress. Full article

Heat stress (HS) is among the most economically consequential environmental challenges to global dairy production, causing progressive declines in milk yield, compositional quality, and mammary cellular integrity. The temperature–humidity index (THI) is the primary thermal load metric, with performance-impairment thresholds typically beginning at THI 68 in Holstein cattle, with severe impacts manifesting beyond THI 72; breed-specific thresholds for Jersey, Brown Swiss, and Simmental cows differ owing to their lower metabolic heat load and greater inherent thermotolerance. At the molecular level, HS activates heat shock protein networks—notably HSPA1A, HSP90B1, and HSPH1—through HSF1/HSF4 transcriptional activation, while simultaneously suppressing casein genes (CSN1S1, CSN2, CSN3), lipogenic genes (FASN, SCD, CD36), amino acid transporters (SLC7A5, SLC38A2), and mTOR-AKT-STAT5 translational machinery, collectively impairing milk biosynthetic capacity. Pro-apoptotic signaling (BAX, CASP3 upregulation; BCL2 downregulation) and mitochondrial dysfunction further compromise mammary epithelial viability. Post-transcriptional regulation through miRNA, circRNA, and lncRNA competing endogenous RNA networks, alongside epitranscriptomic m6A modifications, adds further regulatory complexity. Genome-wide association studies have identified SNPs in HSP70A1A, HSPA4, TLR4, and PRLR as thermotolerance candidates compatible with sustained milk production. Nutritional supplementation with methionine, arginine, and taurine partially restores cellular synthetic capacity. Integrating multi-trait genomic selection with Bos indicus introgression, precision cooling, and targeted nutrition offers the most viable path toward climate-resilient, high-producing dairy cattle. Full article

Celiac disease (CD) is a chronic immune-mediated enteropathy triggered by the ingestion of gluten in genetically predisposed individuals. While the adaptive immune response to deamidated gliadin peptides represents a central pathogenic mechanism, growing evidence suggests that epithelial stress and innate immune activation play a fundamental role in the onset and persistence of the disease. Heat shock proteins (Hsps), central regulators of cellular proteostasis, have emerged as potential mediators at the interface between epithelial distress and immune signaling. This review discusses the involvement of major Hsp families, including Hsp27, Hsp60, Hsp70, and Hsp90, in the pathophysiology of CD. The altered expression of Hsp27 and Hsp70 in the intestinal mucosa reflects a persistent state of epithelial stress that often persists despite a strict gluten-free diet (GFD). We focus specifically on Hsp60, whose extracellular release under stress conditions may allow it to function as a damage-associated molecular pattern (DAMP), engaging Toll-like receptors and promoting NF-κB- and inflammasome-dependent inflammatory pathways. Although direct mechanistic evidence linking Hsp60 to CD remains limited, the convergence of epithelial stress signs, Toll-like receptor (TLR) upregulation, and prolonged innate immune activation supports the hypothesis of a stress-induced inflammatory amplification circuit in the coeliac mucosa. Further studies are essential to clarify the pathogenic relevance and potential therapeutic implications of this proposed axis. Full article

The increasing fragmentation of plastic debris into nanosized particles represents a threat to freshwater ecosystems, yet the biological effects of nanoplastics (NPs) on freshwater invertebrates remain poorly understood. This study investigated tissue distribution, cellular effects and immune responses following acute exposure to polyethylene terephthalate nanoplastics (PET-NPs) in the freshwater gastropod Pomacea canaliculata, a species of high ecological relevance and physiological resilience. Adult snails were injected with PET-NPs at 5 or 10 mg/L and sampled after 24 and 72 h. PET-NPs accumulation in the anterior and posterior kidneys was assessed by fluorescence imaging and tissue morphology was evaluated. Stress- and inflammation-related genes (Pc-Heat Shock Protein (HSP)70, Pc-HSP90 and Pc-Allograft inflammatory factor 1) expression was quantified by RT-qPCR. PET-NPs uptake and phagocytic activity were analyzed in circulating hemocytes in vivo and ex vivo. PET-NPs were accumulated in renal tissues, persisting up to 72 h without histopathological alterations. Gene expression analyses revealed non-linear and dose/time-dependent responses. Hemocytes of different morphologies internalized PET-NPs in a dose-dependent manner and showed intercellular particle transfer. Overall, acute PET-NP exposure determines rapid immune handling and tissue sequestration with limited short-term physiological impact, underscoring the potential involvement of immune processes in NPs fate and highlighting the need for chronic exposure studies. Full article

In this report, we describe systemic granulomatous mycobacteriosis in an orbiculate batfish from an aquarium in South Korea. Gross examination of the deceased fish showed multifocal nodular lesions in multiple internal organs including the gills, spleen, and kidney. Histopathological analysis demonstrated severe chronic systemic granulomatous inflammation, and Ziehl–Neelsen staining highlighted abundant intralesional acid-fast bacilli. Molecular analysis based on partial sequencing of the 16S ribosomal RNA (rRNA) and heat shock protein 65 (hsp65) genes showed that the detected organism was most closely related to Mycobacterium marinum. Because the molecular analysis was performed using partial sequences obtained from formalin-fixed, paraffin-embedded tissues, definitive species-level identification was not possible. This case represents systemic granulomatous mycobacteriosis associated with a Mycobacterium marinum-like organism in orbiculate batfish in an aquarium in South Korea and emphasizes the need for continuous disease surveillance and improved diagnostic awareness of non-tuberculous mycobacterial infections in ornamental and public aquarium fish. Full article

This study is a narrative review of natural killer (NK) cells in Behcet disease (BD). BD is an inflammatory disorder with manifestations in mucosal tissues. Unlike autoimmune diseases that generate autoantibodies, BD is believed to be an autoinflammatory disease triggered by innate immune cells rather than adaptive cells. Hyperactivation of neutrophils causes vasculitis and thrombosis, and they migrate into cutaneous and ocular lesions. Dominance of M1 macrophages promotes the differentiation of Th1 cells. Moreover, the cross-reaction of bacterial heat shock proteins induces production of cytokines such as IL-4 and IFN-γ in γδT cells, which alters the balance between Th1 and Th2 phenotypes. Nevertheless, NK cells play more critical roles in BD pathogenesis than other innate immune cells because not only is their activity precisely controlled by the interaction between ligands and receptors, but NK1 shift also elicits Th1 dominance. The genetic factors associated with BD are HLA-B51 and major histocompatibility complex class I-related chain A (MICA), which stimulate NK receptors as ligands. Improperly processed peptides dysregulate their interaction with NK receptors, triggering the inflammatory response. NK1 and NK2 subsets represent cytokine production in relapse and remission periods; however, the cytotoxicity of NK cells in relapse is lower than that in remission periods. It still remains unclear how NK cells are activated recurrently and expand cytokine production. This review highlights the regulation of gene expression encoding NK receptors, tissue-resident NK cells, and adaptive NK cells to discuss their potential for relapse. Splicing variants and readthrough genes encoding NK receptors easily alter cytokine production. Moreover, tissue-resident NK cells in mucosal tissues and adaptive NK cells that memorize the virus infection have the potential to trigger hyperactivation in relapse. Full article

Heat shock proteins (HSPs) fulfil protective tasks in the whole organism; in pregnant dogs, they are expressed in the ovary, placenta and preimplantation embryo. Our objective was to compare the expression of HSP60 and -70, along with indicators of proliferation and apoptosis, in the non-pregnant and pregnant uterus/placenta and ovaries. Tissues were obtained after ovariohysterectomy and examined by means of immunohistochemistry. There were differences between pregnant and non-pregnant tissues: the expression level of HSP70 during preimplantation in superficial cells was significantly lower than that in early diestrus, with similar results observed for Ki67. The immunosignal for HSP70 was significantly decreased during the postimplantation stage in almost all cell types, whilst the number of HSP60-positive cells did not change. In pregnant animals, the number of Ki67-positive cells significantly increased until the postimplantation stage. In the placenta and trophoblast, the expression of HSP60 and -70 was strong, while no HSP70 signal was detected in endometrial epithelial cells. The caspase 3 immunosignal in the uterus and placenta was generally weak. In the corpora lutea, HSP60, HSP70 and caspase 3 were mainly detected in theca lutein cells, while no signal for KI67 was seen. In follicles, caspase 3 and KI67 expression was low, except in granulosa cells of tertiary follicles and oocytes. We conclude that the different expression of HSPs in pregnant and non-pregnant animals may point towards different regulatory and/or protective tasks. Full article