Search Results (352)

Background/Objectives: Clear cell renal cell carcinoma is the most common subtype of kidney cancer and exhibits marked biological heterogeneity, even among tumors of the same histological grade. Although tumor grade remains a key prognostic parameter, the molecular alterations associated with tumor differentiation are not fully understood. This study aimed to evaluate grade-dependent tissue-level expression patterns of proteins involved in cellular stress response, growth regulation, stemness, and apoptosis in clear cell renal cell carcinoma. Methods: Protein expression of heat shock protein 70, insulin-like growth factor 1, octamer-binding transcription factor 4, and apoptosis-inducing factor were analyzed in human clear cell renal cell carcinoma samples and normal renal cortex. Low-grade and high-grade tumors were compared using immunofluorescence staining combined with semi-quantitative and quantitative image analysis. The proportion of positive signals and the number of positive cells were assessed across tissue compartments. In addition, publicly available transcriptomic data from The Cancer Genome Atlas kidney renal clear cell carcinoma cohort were analyzed to explore associations between gene expression levels and overall survival. Results: Distinct grade-dependent expression patterns were observed for all investigated proteins. Heat shock protein 70, insulin-like growth factor 1, and octamer-binding transcription factor 4 showed a higher expression in normal renal tissue with a progressive reduction across tumor grades. In contrast, apoptosis-inducing factor exhibited increased expression in tumor tissue, particularly in low-grade tumors, with a relative decrease in high-grade carcinomas. Stromal compartments of tumor tissue showed minimal or no expression for most markers. Transcriptomic survival analysis did not reveal significant differences in overall survival between high- and low-expression groups for any of the investigated genes. Grade-stratified transcriptomic analysis of the TCGA KIRC cohort revealed consistent patterns for HSP70 family members and OCT4, with progressive grade-dependent mRNA reduction toward higher grades, while IGF1 showed an inverse mRNA trend and AIFM1 showed a uniform reduction across all tumor grades without a clear inter-grade pattern. Conclusions: The findings demonstrate that stress response, growth-related, stemness-associated, and apoptotic proteins display distinct grade-dependent tissue-level expression patterns in clear cell renal cell carcinoma, with the expression profiles of high-grade tumors being of particular translational interest given the aggressive clinical behavior and therapeutic resistance characteristic of this disease stage. These alterations appear to reflect tumor differentiation and biological behavior rather than independent prognostic value, highlighting the complexity of molecular regulation in renal tumorigenesis. Full article

Quercetagetin (QG), a principal flavonol from marigold (Tagetes erecta L.), is recognized for its potent antioxidant properties. However, its efficacy in mitigating intestinal injury under heat stress (HS) conditions remains unclear. We investigated the protective effects of QG using a mouse model of HS (41 °C, 70% humidity). Mice received oral QG (100 mg/kg/day) or saline for seven consecutive days before and during HS exposure. We assessed jejunal histopathology, oxidative stress markers, inflammatory cytokines, gene expression, and gut microbiota composition via 16S rRNA sequencing. QG supplementation significantly ameliorated HS-induced jejunal damage. It enhanced the activities of superoxide dismutase (SOD) and catalase (CAT) while reducing malondialdehyde (MDA) and pro-inflammatory cytokines (IL-1β, IL-6, TNF-α). QG downregulated the mRNA expression of heat shock proteins (Hsp70, Hsp90) and upregulated antioxidant-related genes (SOD1, GPX4, CAT, NQO1, Nrf2). Furthermore, QG preserved intestinal barrier integrity by upregulating tight junction proteins (Occludin, Zo-1, Claudin). 16S rRNA analysis revealed that QG significantly reshaped the gut microbiota, marked by an increased relative abundance of Lactobacillus and a decrease in potentially harmful taxa such as Allobaculum, Oscillibacter, and Colidextribacter. QG effectively alleviates HS-induced intestinal injury by enhancing antioxidant capacity, suppressing inflammation, and modulating the gut microbiota. These findings provide a scientific basis for the potential application of QG as a functional feed additive to improve animal health under heat stress conditions. Full article

Heat shock proteins 70 (HSP 70) are molecular chaperonins ubiquitously expressed in both prokaryotes and eukaryotes and are involved in the modulation and exacerbation of the immune response. The present study aimed to assess the immunohistochemical expression of HSP70 and apoptosis markers, such as TUNEL and Caspase-3, in 17 cases of cutaneous lupus erythematosus (CLE) in dogs to determine whether HSP70 expression correlates with cell apoptosis and to highlight possible involvement of HSP70 in the pathogenesis of CLE. The results revealed positive HSP70 expression in epidermal and inflammatory cells across all cases, with a significant correlation between HSP70 expression score and TUNEL-positive cells but not with Caspase-3-positive cells. This correlation could indicate a possible role for HSP70 in cell death via a caspase-independent apoptotic mechanism or other programmed cell death mechanisms, such as pyroptosis or necroptosis. The precise mechanisms by which HSP70 acts in this specific pathological context remain incompletely understood, but the results of this study provide important information for future investigations into autoimmune skin disease in dogs. Full article

Intensive aquaculture induces severe environmental stress and disease susceptibility in Pacific white shrimp (Litopenaeus vannamei). Cannabidiol (CBD) offers significant potential as a bioactive stress-mitigating additive. This study evaluated the effects of dietary CBD supplementation (0, 10, 20, 40, and 80 mg/kg) on the growth, intestinal microecology, and stress tolerance of juvenile L. vannamei over an 8-week feeding trial, followed by a combined chronic ammonia and acute hypoxia challenge. Moderate CBD supplementation (10–40 mg/kg) significantly promoted growth, minimized feed conversion ratios, and enriched muscle eicosapentaenoic (EPA) and docosahexaenoic acids (DHA). Furthermore, CBD restructured the intestinal microbiota by suppressing opportunistic pathogens and enriching beneficial taxa. Under combined stress, moderate CBD prolonged the median lethal time (LT₅₀) by up-regulating hypoxia-inducible factor 1-alpha (hif-1α) and heat shock protein 70 (hsp70) transcription and boosting systemic antioxidant capacity to neutralize lipid peroxidation. Conversely, the highest dose (80 mg/kg) induced metabolic exhaustion and hepatopancreatic toxicity, evidenced by drastically elevated serum transaminases and diminished stress tolerance. Conclusively, dietary CBD exerts a classic biphasic effect in L. vannamei. Inclusion at 10–40 mg/kg safely promotes the best comprehensive effects on growth, immune homeostasis, and environmental resilience within the concentration range tested in this study, whereas excessive administration provokes severe metabolic burden, highlighting the critical need for strict dosage regulation. Full article

Heat stress (HS) is one of the most challenging environmental conditions, responsible for impaired growth and reproduction in living systems. It also leads to altering the release of different biochemicals responsible for controlling the metabolic pathway. Five White Wistar rats were exposed at 42 ± 1 °C inside a closed chamber for the induction of hyperthermia. Their rectal temperature was recorded before and after heat exposure. The semi-digested food from the gut (colon) of sacrificed rats was collected under sterilized conditions for the isolation of gut bacteria on a nutrient agar plate at 50 °C, 60 °C, and 70 °C. The sample was incubated for 24 h and isolates were further purified. The proteolytic, amylolytic, cellulolytic, and xylanolytic activities were measured via plate assay and the enzymatic index was calculated. Total protein and estimation of heat shock protein 70 (HSP70) were also quantified. Initially, the rectal temperature of the animal was 37.1 ± 0.2 °C, but after exposure to heat, the temperature was 40.8 ± 0.2 °C. The number of purified isolates was recorded, i.e., at 50 °C (04), at 60 °C (01), and at 70 °C (03). Among eight isolates, Bacillus licheniformis (50 °C) showed all four enzymatic activities with a higher enzymatic index. Further, this novel isolate also exhibited a maximum concentration of HSP70. This preliminary study reveals the survival of a bacterium (B. licheniformis) capable of producing key metabolites, highlighting its significance in supporting host physiology and other pathophysiological conditions. As a probiotic, it may serve as a potential therapeutic bridge connecting HSP70, host physiological function, and gut health. Full article

Infertility affects a substantial proportion of women of reproductive age and is frequently associated with impaired endometrial receptivity. Successful implantation depends on tightly regulated hormonal, immune, apoptotic, and stress-response pathways within the endometrium. This pilot study aimed to evaluate the expression and distribution of granulocyte colony-stimulating factor (G-CSF), bone morphogenetic proteins 2/4 (BMP-2/4), heat shock protein 70 (HSP-70), apoptosis, progesterone, estrogen, and pentraxin-3 (PTX-3) in the endometrium of infertile women across different menstrual cycle days. A descriptive cross-sectional analysis was performed on endometrial tissue samples obtained from six infertile women aged 21–49 years at various menstrual cycle days. Routine histology, immunohistochemistry, TUNEL assay, and chromogenic in situ hybridization were used to assess tissue morphology, protein expression, apoptotic activity, and PTX-3 gene expression. Quantitative evaluation was applied to immunohistochemical markers and apoptosis, while PTX-3 expression was assessed semi-quantitatively. G-CSF expression showed low-to-moderate levels with a relative mid-cycle increase. BMP-2/4 demonstrated the highest overall positivity across most cycle days, with marked inter-sample variability. HSP-70 exhibited pronounced cycle-dependent variability. Apoptotic activity increased toward mid-to-late cycle days. Progesterone and estrogen positivity was heterogeneous and limited to selected cycle days. PTX-3 gene expression was highest during mid-cycle days and decreased toward later phases. No clear association with patient age was observed. Conclusions: The findings indicate distinct and cycle-dependent patterns of immune, morphogenetic, apoptotic, hormonal, and inflammatory markers in the endometrium of infertile women. These results highlight the dynamic nature of endometrial regulation and suggest that altered temporal coordination of these pathways may contribute to impaired endometrial receptivity. Full article

Metallothioneins (MTs) and heat shock protein 70 (HSP70) are key regulators of cellular stress response and metal homeostasis and play important roles in tumor biology. The aim of this study was to examine their expression patterns and potential prognostic significance in different molecular subtypes of breast cancer (BC), with special emphasis on triple-negative breast cancer (TNBC) and the Luminal A subtype, compared with benign breast lesions (fibroadenomas). A total of 90 tissue samples were included, and the expression of MTs in the cytoplasm and nucleus and HSP70 in the nucleus of tumor cells was analyzed immunohistochemically and correlated with clinicopathological features and treatment outcomes. Distinct expression patterns of HSP70 and MTs were observed between malignant and benign samples, as well as among the analyzed molecular subtypes of BC, suggesting their involvement in cellular adaptive mechanisms associated with malignant transformation. TNBC was characterized by less favorable clinicopathological features compared to the Luminal A subtype, including higher histological grade, increased proliferative activity, and a higher incidence of recurrence and metastatic disease. Survival analyses confirmed a worse outcome for patients with TNBC, while HSP70 and MTs expression did not show independent prognostic value in multivariate models. In conclusion, although HSP70 and MTs play important biological roles in the cellular response to stress and tumor adaptation, their expression in this study does not represent an independent prognostic indicator of clinical outcome. Nevertheless, the observed expression patterns provide insight into the complex mechanisms of tumor adaptation and emphasize the need for integrative approaches in BC biomarker research. Full article

Biofloc technology (BFT) is based on the reutilization of nitrogenous waste generated by cultured organisms through the biotransformation of these compounds primarily into microbial biomass, allowing a reduction in water exchange. The aim of this study was to evaluate BFT as a water-saving culture strategy, using two carbon sources (chancaca and molasses), and to assess its effects on water-use efficiency, growth performance, digestive enzyme activity, and physiological responses in juvenile northern river shrimp (Cryphiops caementarius). The experiment was conducted in triplicate using 400 L fiberglass tanks, with an initial stocking density of 75 shrimp m⁻² and an average individual weight of 0.85 ± 0.65 g, over a 157-day rearing period. Water quality parameters were maintained within suitable ranges throughout the study. Significant differences were observed in the composition of bacterial and plankton communities among the biofloc treatments, whereas no significant differences were detected in growth performance or digestive enzyme activities. Heat shock protein 70 (Hsp70), a stress-related biomarker indicative of physiological responses, exhibited higher levels in the biofloc treatment supplemented with molasses. Overall, BFT treatments reduced water exchange by 81.6% while maintaining comparable biological performance to the control, indicating that biofloc technology represents a water-efficient and environmentally sustainable culture approach for juvenile Cryphiops caementarius, an endemic freshwater shrimp species, particularly in water-limited regions of northern Chile. Full article

Background: The Qingyuan partridge chicken is a high-quality local chicken breed in China. Its weight gain directly affects breeding efficiency. This study used RNA sequencing to analyze gene expression dynamics in the breast muscle tissue of Qingyuan partridge chickens at 1, 35, 70, and 105 days of age. Methods: This study employed RNA-sequencing, integrated with differential expression analysis, weighted gene co-expression network analysis (WGCNA), and short time-series expression miner (STEM) analysis, to systematically investigate the transcriptomic dynamics in breast muscle tissue across four developmental stages. Results: Phenotypic analysis revealed a significant increase in both body weight (BW) and breast muscle weight with age (p < 0.05). Transcriptomic analysis identified 3521 genes specifically expressed at the age of one day compared with the other 3 ages. These were significantly enriched in pathways related to ribosomal biosynthesis, cytoskeletal regulation, and cell proliferation (p < 0.05). Turquoise and black modules were identified by WGCNA, containing 1563 hub genes, which significantly correlated with BW. Integration of differentially expressed genes and STEM analysis selected 26 BW-related key genes closely associated with muscle growth, including calmodulin 2 (CALM2), heat shock protein 90 alpha family class A member 1 (HSP90AA1), and cholinergic receptor nicotinic delta subunit (CHRND). Protein–protein interaction analysis revealed two functional networks centered around these genes. Enrichment analysis of the STEM profiles indicated that upregulated genes were significantly enriched in autophagy and the ErbB, FoxO, mTOR, and insulin signaling pathways, while genes related to the ribosome, cell cycle, and PPAR signaling pathways were downregulated. Conclusions: This study identified BW-related key genes and pathways, enriching our knowledge of the functional maintenance of chicken BW. Full article

L. infantum and L. donovani, distinct species in the L. donovani complex, show high phenotypic and genotypic polymorphism and share molecular traits. Therefore, genotyping by a single molecular target can give uncertain results. This study focuses on genotyping a set of L. donovani complex strains, including 18 zymodemes classified according to Montpellier nomenclature (ZMONs) and different clinical forms, by internal transcribed spacer (ITS), heat shock protein 70 (hsp70), and cysteine proteinase b (cpb) sequencing to evaluate their ability in species discrimination. We found an unexpected L. infantum hsp70 variability, with 8 sequence variants. Cpb-PCR could not distinguish L. donovani complex species, due to a L. infantum intraspecific allelic (cpbEF) polymorphism. By combining ITS-hsp70-cpb sequence variants, we obtained different genotypes. ITS(A)-hsp70inf(2)-cpbE identified 69.9% of L. infantum strains representing 12 ZMONs from Mediterranean visceral and cutaneous cases, ITS(A)-hsp70inf(2)-cpbF identified a non-ZMON-1 cluster. Four genotypes represented ZMON-24: ITS(A, B)-hsp70(Y)-cpbF identified a cutaneous cluster from Italy and North Africa, ITS(A, Lombardi)-hsp70(2)-cpbE identified cutaneous and visceral cases from Mediterranean areas. We believe this study contributes to an overview of L. infantum variant populations, and to the discussion on diagnostic targets, in single or multi -target-based approaches, to identify Leishmania populations in the Mediterranean area. Full article

In the filamentous fungus Neurospora crassa, a gene not having a pairing partner during meiosis is seen as a potential intruder and is targeted by a mechanism called meiotic silencing by unpaired DNA (MSUD). MSUD employs core RNA interference (RNAi) components such as the SMS-2 Argonaute, which uses small interfering RNAs (siRNAs) as guides to seek out mRNAs from unpaired genes for silencing. In Drosophila melanogaster, the heat shock protein 70 (Hsp70) chaperone system facilitates the conformational activation of an Argonaute and allows it to load siRNAs. Here, our results demonstrate that an Hsp70 protein in Neurospora interacts with SMS-2 and mediates the silencing of unpaired genes. Full article

Natural compounds, as honey-derived flavonoids and phenolic compounds, are increasingly investigated for their potential to mitigate skin aging and prevent oxidative stress-induced cellular damages. In this context, a dynamic cell culture model was employed to assess the protective influence of honey pre-treatment on stem cell–associated genes and the Wingless-related integration site (Wnt) signaling pathway following ultraviolet (UV)-induced aging. Using a bioreactor, skin stem cells (SSCs) derived from healthy skin biopsies and human skin fibroblasts (HFF1) were pre-treated with 1% honey for 48 h and then exposed to UV. Real-time quantitative polymerase chain reaction (RT-qPCR) analyses were performed on Wnt signaling and anti-aging molecular responses. Honey pre-treatment enhanced the expression of pluripotency markers (Octamer-binding transcription factor 4 (Oct4); SRY-box transcription factor 2 (Sox2)) and reduced senescence-related cell cycle regulators (cyclin-dependent kinase inhibitor 2A (p16); cyclin-dependent kinase inhibitor 1A (p21); tumor protein 53 (p53)) in SSCs. In UV-damaged SSCs, honey also significantly increased Wnt3a expression. In fibroblasts, honey pre-treatment upregulated Heat shock protein 70 (Hsp70) and Hyaluronan synthase 2 (HAS2) expression, while downregulating caspase-8 (CASP8), indicating a protective role against UV-mediated cellular stress. We also analyzed nitric oxide release and the total antioxidant capacity of cells after treatment. Collectively, these findings suggest that honey may safeguard skin stem cells from UV-induced aging by modulating pluripotency and senescence-associated genes and regulating differentiation through alterations in Wnt signaling. Furthermore, Hsp70 upregulation in fibroblasts appears to strengthen cellular stress responses and support homeostatic stability. Full article

Hylocereus undatus growth is limited by long-term heat stress, and heat shock protein 70 (Hsp70) is crucial in the plant’s heat stress (HS) response. In a previous study, transcriptomic data revealed that Hsp70 family members in pitaya seedlings respond to temperature changes. This study identified 27 HuHsp70 genes in pitaya, analyzed their physicochemical properties (such as molecular weight and isoelectric point), and divided them into five subfamilies with conserved gene structures, motifs (short conserved sequence patterns), and cis-acting elements (regulatory DNA sequences). The Ks value (synonymous substitution rate) ranged from 0.93~3.54, and gene duplication events occurred between 71.17 and 272.19 million years ago (Mya). Under HS, eight and nine differentially expressed genes (DEGs) were detected at 24 h and 48 h, respectively. Quantitative real-time PCR (qRT-PCR, a method for measuring gene expression) verified the expression trends, with HuHsp70-11 expression increasing with heat shock duration, indicating that HuHsp70-11 is a key candidate. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses revealed that HuHsp70s, especially HuHsp70-11, play key roles in responding to high temperatures (HT) in H. undatus seedlings. A potential model by which HuHsp70-11 removes excess reactive oxygen species (ROS) and enhances cell membrane permeability was constructed. These results provide new perspectives for exploring the HS response mechanisms and adaptability of H. undatus plants to heat stress. Full article

We present a computational study that precedes the potential interactions between SARS-CoV-2 helicase (NSP13) and selected host proteins implicated in chaperone-assisted folding and polyamine metabolism. Using structure-based modelling and protein–protein docking (BioLuminate v4.6), followed by all-atom molecular dynamics (MD) simulations (GROMACS v2018.6), and comparative MM-GBSA scoring (HawkDock v2), we evaluated the stability and interface properties of NSP13 complexes with cytosolic heat shock proteins; heat shock protein 40 (HSP40), heat shock protein 70 (HSP70), heat shock protein 90 (HSP90) and the polyamine biosynthesis enzyme ornithine decarboxylase (ODC). Docking, MD, and interface analyses indicate distinct complex behaviours: HSP70-NSP13 complexes sampled compact conformations, HSP90-NSP13 ensembles displayed greater conformational heterogeneity but more favourable comparative MM-GBSA estimates, and ODC-NSP13 interfaces were comparatively well packed. Per-residue contact mapping identified a small set of recurrent NSP13 residues, Lys22 and Asn51, as putative interaction hotspots. The reported findings herein generate testable hypotheses about NSP13 recruitment of host chaperones and modulation of polyamine metabolism that may inform downstream experimental studies. Full article

White Spot Syndrome Virus (WSSV) remains one of the most devastating pathogens in global shrimp aquaculture, causing massive economic losses annually. This study employed comparative transcriptomics to elucidate the molecular basis of the differential resistance to WSSV between the highly susceptible Pacific white shrimp (Litopenaeus vannamei) and the remarkably resistant oriental river prawn (Macrobrachium nipponense). Our analysis of gill, hepatopancreas, and muscle tissues at 24 h post-infection revealed fundamentally distinct defense strategies. The resistant M. nipponense employs a unique “proactive homeostatic reinforcement” strategy, characterized by significant enrichment of pathways central to cellular homeostasis, including signal transduction, cellular processes, and transport/catabolism. This approach, supported by coordinated up-regulation of heat shock proteins and structural genes, enables effective viral control without triggering excessive immune activation. In contrast, susceptible L. vannamei displays either widespread metabolic dysregulation leading to systemic collapse in moribund individuals or dependency on specific immune pathways (Toll-like receptor signaling and apoptosis) in survivors. Through comparative KEGG analysis, we identified heat shock protein 70 kDa (HSP70, K03283) as a key conserved gene and functionally validated its critical role in antiviral defense using RNA interference. Knockdown of HSP70 in M. nipponense significantly increased cumulative mortality and viral load, confirming its essential protective function. These findings provide novel insights into crustacean antiviral immunity and identify promising genetic targets for breeding WSSV-resistant shrimp strains, offering sustainable solutions for disease management in aquaculture. Full article