Search Results (1,672)

Ofloxacin (OFL) and sulfamethoxazole (SMX) are common co-occurring antibiotic contaminants in aquatic environments, yet their long-term combined toxicity to freshwater fish remains poorly elucidated. In this study, adult mosquitofish (Gambusia affinis) were used as a model to investigate histopathological alterations, oxidative stress responses, gene expression, and gut microbiota changes after 30 days of exposure to environmentally relevant concentrations of OFL and SMX (0 ng/L, 50 ng/L, 1 μg/L, and 20 μg/L), either individually or in combination. The results showed that both single and combined exposures induced liver and intestinal damage. Oxidative stress responses exhibited clear tissue specificity, with activation of antioxidant defenses in the liver, whereas the intestine was mainly characterized by decreased SOD and GST activities, as well as reduced MDA content. Changes in gene expression were relatively limited, with significant alterations observed only in hepatic sod2 and hsp90 and intestinal hsp70 in certain treatment groups. Gut microbiota analysis showed that OFL exerted a stronger disruptive effect than SMX, as reflected by increased alpha diversity, reduced abundance of core genera, and functional remodeling, whereas combined exposure triggered weaker microbial community restructuring relative to single exposures. Overall, OFL and SMX induced tissue-specific toxicity in mosquitofish by causing tissue injury, oxidative stress imbalance, and gut microbiota dysbiosis, with OFL showing the stronger overall effect. 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

Soybean (Glycine max (L.) Merr.) is a globally crucial food crop and a model plant for studying symbiotic nitrogen fixation in legumes. Triacontanol (TRIA) is a natural plant growth regulator that enhances photosynthetic efficiency, stress tolerance, antioxidant enzyme activities and yield in crops. However, its regulatory role in nodulation and nitrogen fixation in legumes remains unclear. In this study, soybean seedlings inoculated with Bradyrhizobium japonicum strain USDA110 were treated with different concentrations of TRIA (0, 0.33, 0.5, 1 and 2 μg/mL). Then, oxidative stress indicators and comparative transcriptomic analysis were performed to check the oxidative status and screen the candidate genes under TRIA treatment. Our results showed that the 0.5 μg/mL TRIA treatment produced the greatest nodule number. TRIA treatment significantly induced antioxidant responses in soybean roots. Comparative transcriptome identified 867 differentially expressed genes (DEGs), Gene Ontology and Kyoto Encyclopedia of Genes and Genomes enrichment analyses of DEGs revealed that a large number of genes were enriched in pathways related to oxidative activity. Combined with the expression pattern, we identified a Glutathione S-Transferase family gene, GmHSP26 (Glyma.07G139700), whose expression was induced by both TRIA and rhizobial infection, with its promoter activity was activated throughout the entire process of nodule development. Further function study using overexpression and gene editing proved that GmHSP26 was a positive regulator of soybean nodulation. Collectively, this study identifies the optimal TRIA concentration for promoting soybean nodulation, reveals the function and mechanism of GmHSP26 in response to TRIA-regulated nodulation, and provides a theoretical basis and genetic resource for enhancing nodulation and nitrogen fixation in leguminous crops through exogenous growth regulators. Full article

Caffeine (CAF) is a widely consumed psychostimulant known to modulate adenosine receptors and neurotransmitter systems, although its effects in invertebrates remain poorly understood. Environmentally relevant concentrations (5, 30, and 50 µg/L) are associated with altered behavior, including locomotion, exploration, and feeding, in the freshwater gastropod Physella acuta. This study examined molecular responses underlying these effects. Adult snails were exposed to CAF for 24 h and 7 days. Gene expression related to the nervous system and stress pathways was analyzed by RT-PCR, including A1AR, ADORA2B, AChE, GLRA2, DRD2, RYR, HSD11β, HSP70, SLC6A2, and SLC6A1. After 24 h, exposure to 50 µg/L CAF altered A1AR expression and caused downregulation of AChE, GLRA2, and DRD2, associated with observed behavioral changes. A1AR upregulation may indicate compensatory adjustment in adenosine signaling. After 7 days, A1AR remained upregulated, while genes linked to inhibitory neurotransmission showed partial recovery. Increased expression of genes involved in dopamine regulation and steroid metabolism suggested physiological adaptation. Overall, CAF induced dose- and time-dependent molecular responses in P. acuta, linking neurochemical disruption with behavioral changes and highlighting its ecological risk as an emerging freshwater contaminant. 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

Background: This study aimed to investigate the anti-aging mechanisms of Alpinia oxyphylla polysaccharides (AOFs) through integrated in vivo experiments, network pharmacology, and molecular docking. Methods: Three purified fractions (AOF1, AOF2, and AOF3) were structurally characterized for monosaccharide composition and molecular weight. Anti-aging and antioxidant activities were evaluated using Caenorhabditis elegans, followed by gene expression analysis, network pharmacology target identification, and molecular docking validation. Results: All AOFs significantly extended lifespan, enhanced resistance to oxidative and heat stress, reduced reactive oxygen species and lipid peroxidation, and upregulated superoxide dismutase and catalase activities. Gene expression analysis revealed activation of the insulin/insulin-like growth factor signaling pathway through upregulation of daf 16, skn 1, sod 3, ctl 1, and hsp 16.2. Network pharmacology identified 254, 85, and 119 core targets for AOF1, AOF2, and AOF3 respectively, enriched in PI3K/AKT, MAPK, hypoxia, and xenobiotic response pathways. KEGG analysis further implicated lipid and atherosclerosis, HIF 1, FoxO, and PI3K Akt signaling. Molecular docking showed that critical monosaccharides and metformin formed stable hydrogen-bonded complexes with AKT1, INS, SRC, and STAT3. Among the fractions, AOF1 and AOF3 exhibited superior activities. Conclusions: These findings demonstrate the multi-target, multi-pathway anti-aging actions of AOFs and support their potential as natural antioxidants and functional food ingredients for anti-aging therapeutics. 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

This study evaluated the effects of scallion white and ginger extracts on stress indicators, gene expression, tissue structure, and muscle quality in crucian carp during transportation. Compared with the control group, ginger extract effectively alleviated long-term transportation stress (48 h), as evidenced by lower levels of glucose and lactate dehydrogenase activity, along with reduced pathological damage in gill, liver, and muscle tissues. Consequently, muscle quality parameters including shear force, glycogen content, and inosine monophosphate levels were notably improved. These improvements were associated with the suppression of heat shock responses, inflammation, and apoptosis, supported by the downregulation of hsp70, il-6, caspase 3, caspase 8 and bax gene expression. Similar trends were observed in the scallion white extract group, though its anti-stress effects and muscle quality enhancement were comparatively weaker. The findings suggest that natural extracts offer a promising approach to mitigating stress and improving muscle quality during live fish transportation. Full article

Infestation by boring sponges poses a serious problem for Pacific oyster Magallana gigas (Thunberg, 1793) aquaculture. This study aimed to assess the effect of Pione vastifica sponge infestation on the oysters’ capacity for shell repair, antioxidant defence status, and hemocyte functional state. We analysed the expression of VEGF pathway genes and biomineralisation enzymes, molecular chaperones (Hsp70, Hsp90), growth arrest and DNA damage gene (Gadd45α), antioxidant enzyme activity and lipid peroxidation levels in the hemolymph and various mantle parts (central and outer-edge). Intracellular reactive oxygen species (ROS) levels and mitochondrial membrane potential in hemocytes were evaluated. The results showed that infection significantly increases intracellular ROS levels in hemocytes without changing mitochondrial membrane potential. Oxidative damage was localised primarily in the central mantle contacting the damaged shell. In the outer-edge mantle responsible for shell growth, marked upregulation of SodMn, Cat, and Gadd45α was observed, coupled with suppression of VEGF-R receptor expression and organic matrix genes. Heat shock protein expression decreased in all examined tissues of infected molluscs. Our results demonstrate that shell damage induced by boring sponges triggers a tissue-specific reorganisation of physiological priorities, manifesting as a bioenergetic trade-off where limited energy resources are reallocated from the ATP-demanding process of biomineralisation to sustain antioxidant defence and cell survival. Full article

Background: Breast cancer remains a leading cause of cancer-related mortality in women, largely due to metastasis and treatment resistance. ELF3, an ETS transcription factor, has been linked to cancer progression; however, the mechanisms regulating its activity remain incompletely understood. Methods: ELF3 expression and its association with patient survival were analyzed using GEO datasets and the Kaplan–Meier Plotter platform. Functional studies were performed using ELF3 knockdown in breast cancer cell lines, followed by WST-1 assays and crystal violet staining. Protein–protein interactions were evaluated using co-expression analysis, immunofluorescence, split luciferase complementation, GST pull-down, and yeast two-hybrid assays. Cycloheximide chase assays were conducted to assess ELF3 protein stability. A panel of small molecules was screened to identify inhibitors of the ELF3-HSP27 interaction, and a lead compound was further validated using biochemical and functional assays. Antitumor activity was evaluated in a xenograft mouse model. Results: High ELF3 expression was associated with poorer overall survival in breast cancer patients. HSP27 was identified as a binding partner that stabilizes ELF3 protein, thereby promoting breast cancer cell proliferation. A novel small-molecule inhibitor disrupting the ELF3-HSP27 interaction suppressed cancer cell growth in vitro and reduced tumor growth in vivo. Conclusions: The ELF3-HSP27 interaction represents a previously unrecognized contributor to breast cancer progression, and its disruption provides a promising therapeutic strategy. Full article

This study aimed to investigate the effects of supplementing with an essential oil blend and ascorbic acid on performance, semen characteristics, antioxidant status, gut microbiota, immunity, and gene expression in heat-stressed male rabbits. One hundred and forty male New Zealand White rabbits, aged 6 months, were randomly distributed into four dietary groups: the control group receiving basal feed (CON), the group receiving an essential oil blend (EOB, 200 mg/kg), the group receiving ascorbic acid (ASA, 1000 mg/kg), and the group receiving an essential oil blend and ascorbic acid (MAO). The experimental period lasted for eight weeks. The MAO mixture supported rabbits’ tolerance to heat stress by enhancing stress markers, as demonstrated by decreased glucose and HSP70 and increased triiodothyronine (T3). In addition, increased body weight, carcass weight, and nutrient digestibility, but reduced mortality rate, were observed in rabbits fed the MAO mixture. Additionally, semen density and volume, as well as sperm progressive motility and normality, were enhanced in rabbits fed the MAO mixture. Furthermore, MAO mixture supplementation decreases plasma cholesterol, triglycerides, AST, urea, and creatinine levels, while raising HDL and total protein levels. Adding MAO mixture contributed to an increase in plasma SOD and GPx levels, as well as seminal fluid TAC and GSH levels. Additionally, the incorporation of MAO increases IgA, IgG, and IL-10 levels while decreasing IL-6 and TNF-α levels. Adding the MAO mixture reduced C. perfringens and E. coli, as well as increased the expression of the MUC-2, CAT-1, and CLDN-1 genes. Combining an essential oil blend and ascorbic acid may contribute to improvements in performance, semen quality, immune response, antioxidant capacity, and gut health in heat-stressed male rabbits. Full article

Background: Chlorophyll (Chl), widespread in fruits and vegetables, has been shown to have numerous nutritional functions, including beneficial effects on obesity. However, whether Chl has an anti-aging effect remains unclear. Methods: Here, we studied the beneficial effects and mechanism of Chl on delaying aging using a Drosophila model. Results: The results showed that dietary supplementation of Chl in an appropriate dose (3.925 mg/L) significantly extended the lifespan (7.66–13.94%), improved climbing ability, increased CAT activity, reduced MDA content, enhanced stress resistance to starvation, heat stress, and cold shock in Drosophila. Notably, lifespan extension was not associated with dietary restriction, reproductive sacrifice, or circadian rhythm regulation. RNA-Seq analysis showed that Chl supplementation led to differential expression of 723 genes in female flies and 435 genes in male flies. KEGG analysis revealed that these differentially expressed genes were significantly enriched in the xenobiotic metabolism (XM) pathway. Within this pathway, phase II detoxifying enzyme genes associated with the CncC (Nrf2) signaling pathway (GstD10, GstE7, Ugt37A3, and AOX2) were significantly downregulated in both sexes. In contrast, protective target genes from the same pathway (cat, Mrp4, Hsp68) were significantly upregulated, as confirmed by qPCR. Conclusions: Taken together, our data indicate that Chl supplementation delays aging in Drosophila melanogaster via enhanced stress resistance and remodeling of the detoxification network. Full article

Prion diseases are caused by self-propagating and transmissible alternative conformations of certain proteins, which induce neurotoxicity and lead to transmissible spongiform encephalopathy (TSE) in mammalian. Prions were also found in fungi, and in particular, the yeast Saccharomyces cerevisiae. Manganese (Mn) is an essential nutrient and plays crucial roles in central nervous system. However, high concentration of manganese is regarded as an environmental neuronal stressor which would induce striatal neurotoxicity. Long-term exposure to high concentration of manganese would increase the proportion of the infectiously pathogenic isoform (PrPSc) of prion protein. Additionally, increase of manganese levels was found to be age-related in human brain. Here, we studied the effect of manganese on prion using budding yeast prion [URE3] as model organism. We found the exposure to manganese can enhance the de novo generation and propagation of yeast prion [URE3], as well as the expression levels of chaperones Hsp104p and Hsp70p, in a dose-dependent manner. Full article

Sheng Mai San (SMS), a traditional Chinese medicine formula for treating qi and yin deficiency, is widely used in the management of conditions such as cardiovascular diseases and heatstroke. However, its role in mitigating heat stress (HS)-induced liver injury remains underexplored. In this study, a rat model of HS was established under high-temperature and high-humidity conditions, and SMS was administered as an intervention. The pharmacodynamic effects of SMS were comprehensively evaluated through histopathological examination, detection of heat shock protein 70 (HSP70) and heat shock protein 90(HSP90) expression, and analysis of liver function biomarkers (AST, ALT). Meanwhile, oxidative stress indicators were measured using biochemical assay kits (GSH, SOD, CAT, MDA, T-AOC), and transmission electron microscopy was employed to observe mitochondrial ultrastructure, thereby assessing the protective effects of SMS on hepatic oxidative stress and mitochondrial damage induced by HS. In vitro, BRL-3A cells were cultured, subjected to HS, and treated with SMS. Cell viability was assessed using the CCK-8 assay, and changes in mitochondrial reactive oxygen species (ROS) levels, mitochondrial permeability transition pore (MPTP) opening, and mitochondrial membrane potential (MMP) were evaluated using fluorescent probes. The results showed that SMS effectively restored HS-induced histopathological damage in rat liver tissues, reduced serum AST and ALT levels, and downregulated the mRNA expression of HSP70 and HSP90 in liver tissues. Meanwhile, SMS strengthened the hepatic antioxidant system by increasing the levels of GSH, SOD, T-AOC, and CAT, while decreasing MDA content. In vitro experiments confirmed that SMS increased the viability of BRL-3A cells, reduced ROS production, improved MPTP opening/closing regulation, and stabilized MMP. This study provides a clinical reference for its application in treating HS-related conditions in humans and animals. Full article