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Tumor-derived antioxidants suppress immunity by depriving T cells of reactive oxygen species.

Reactive oxygen species (ROS) promote genomic instability and fuel oncogenic signaling in cancer, but antioxidant therapies have so far failed to improve, or worsen, cancer outcomes. Emerging data suggest that T cells depend on ROS for signal transduction. In this study, we show that tumors exploit this dependency, releasing antioxidant enzymes into the tumor environment to suppress T cell-mediated antitumor immunity. The interstitial fluid of tumors possesses potent antioxidant activity, associated with enrichment of the antioxidant enzyme peroxiredoxin 1 (PRDX1). Extracellular PRDX1 deprives T cells of ROS, preventing oxidative inactivation of phosphatases required for T cell receptor-driven kinase signaling and effector function. Prdx1 is up-regulated upon cancer immunoediting, and loss of PRDX1 within tumors enhances antitumor immunity and immunotherapy responses. These findings define a redox-dependent mechanism of tumor immunosuppression that is potentially amenable to therapeutic intervention.

Animals

Discovery and characterisation of catedehas A-C, a new class of antioxidant α,β-dehydroamino acid derivatives.

Dehydroamino acids are a class of noncanonical unsaturated amino acids commonly found in various naturally occurring peptides and proteins. In this study, we successfully cloned and heterologously expressed the cda biosynthetic gene cluster from Streptomyces nitrosporeus ATCC 12769 in Streptomyces lividans TK24, leading to the identification of three α,β-dehydroamino acid derivatives, designated as catedehas A-C (1-3). Among these, compound 2, although previously reported, lacked any detailed characterisation data. Their structures were elucidated by high-resolution electrospray ionisation mass spectrometry, 1D and 2D nuclear magnetic resonance spectroscopy, along with other spectroscopic techniques. Compounds 1-3 exhibited remarkable antioxidant activity in DPPH· free radical scavenging assay, with IC50 values of 27.52, 12.51, and 8.32 μM, respectively.

Antioxidants

Comparative metabolomic and transcriptomic profiling of flavonoid diversity and antioxidant capacity in three Isatis species.

Flavonoids are key bioactive compounds in plants with significant health benefits. This study employs an integrated multi-omics approach to investigate flavonoid diversity and antioxidant capacity across three Isatis species: I. oblongata, I. tinctoria, and I. indigotica. Metabolomic profiling identified 200 flavonoids, with glycosides being the most abundant class. I. tinctoria exhibited the highest total flavonoid content and antioxidant activity, strongly correlated with the accumulation of 53 core differential flavonoid metabolites, most of which were glycosylated derivatives. Transcriptomic analysis revealed coordinated upregulation of phenylpropanoid pathway genes and specific UDP-glycosyltransferases (UGTs) in I. tinctoria, providing a genetic basis for its enhanced glycoside production. The study establishes a clear genotype-metabolite-phenotype linkage, highlighting glycosylation as a key mechanism underlying flavonoid-driven antioxidant superiority in Isatis. Although the current evidence is primarily correlative, the consistent and strong associations across independent transcriptomic, metabolomic, and antioxidant datasets provide a robust foundation for this conclusion. These findings offer new insights into the metabolic evolution and regulatory networks of flavonoids, with implications for breeding and metabolic engineering of high-value medicinal plants.

Flavonoids

Rhodococcus folensis sp. nov., an orange-red-pigmented bacterium from mining soil.

Mining-impacted environments represent chemically complex ecosystems that may harbor metabolically versatile and pigment-producing microorganisms. During a survey of pigment-producing bacteria from abandoned mining soil in Trabzon, Türkiye, a red-pigmented strain, designated FMA22T, was isolated and characterized using a polyphasic taxonomic approach. 16 S rRNA gene sequence analysis placed the strain within the genus Rhodococcus, showing the highest similarity to R. corynebacterioides DSM 20,151T (99.57%), R. kroppenstedtii DSM 44908ᵀ (99.06%) and R. trifolii T8T (98.96%). The strain was Gram-stain-positive, aerobic and non-motile, and grew at 4-40 °C. Polar lipids included phosphatidylethanolamine, diphosphatidylglycerol, phosphatidylinositol, phosphatidylinositol mannoside, phosphatidylcholine, five unidentified glycolipids, four unidentified lipids, one unidentified phospholipid and one unidentified phosphoglycolipid; MK-8(H2) was the major respiratory quinone. Major fatty acids were C18:1 ω9c, summed feature 3 (C16:1 ω7c/C16:1 ω6c) and C16:0. ANI and dDDH values with the closest relatives were below 76.8% and 20.5%, respectively. The draft genome (4.23 Mb; 67.2 mol% G + C; 4,106 CDSs) harbors a terpene-associated carotenoid cluster containing crtB, crtI and crtY. The orange-red pigment (λmax = 475 nm) showed antioxidant activity (DPPH SC₅₀ = 5.38 mg mL⁻¹; FRAP = 4.34 µmol TE g⁻¹) and weak but measurable HIV-1 reverse transcriptase inhibition (IC₅₀ = 22 mg mL⁻¹). These data support the proposal of Rhodococcus folensis sp. nov., with FMA22ᵀ (= LMG 34144ᵀ = DSM 120048ᵀ) as the type strain.

Soil Microbiology

Complete genome sequence of Streptomyces californicus ADR1, an anti-infective, anti-biofilm and anti-oxidant producing endophyte isolated from the medicinal plant Datura metel.

OBJECTIVE: Streptomyces californicus strain ADR1 is an endophytic actinobacterium isolated from Datura metel that produces secondary metabolites with potent antibacterial and anti-biofilm activities against WHO-listed high-priority Gram-positive pathogens. While anti-bacterial and antioxidant potential of the strain ADR1 has been extensively characterized, its complete genome sequence remains to be investigated for further insights into its biosynthetic potential. This study presents the complete genome sequence analysis of the strain ADR1 to provide a robust genomic foundation for understanding its metabolic versatility and biosynthesis of compounds with therapeutic significance. DATA DESCRIPTION: The ADR1 genome was sequenced using Illumina HiSeq. The assembly comprised 262 scaffolds with a total genome size of 8.4 Mb and G + C content of 72.5%, containing 7427 protein-coding genes. AntiSMASH and IIT-Hyderabad novelBGC analysis revealed 39 biosynthetic gene clusters, including non-ribosomal peptide synthetases, type I polyketide synthases, terpene and melanin clusters, correlating with the diverse therapeutic compounds previously identified through GC-MS analysis. This high-quality genome provides crucial insights into the biosynthetic potential underlying potent antimicrobial and antioxidant activities of the strain ADR1.

Streptomyces

Antioxidants in neoplastic cells: I. Changes in the antioxidative capacity of mouse neuroblastoma cells measured by a single-phase assay.

Cultured mouse neuroblastoma cells exhibit a striking increase in antioxidative capacity during the transition from logarithmically dividing cells to nondividing, neurite-bearing cells. Two physically separable phenomena are involved: (a) the membrane pellet of neurite-bearing cells is highly resistant to lipid peroxidation, and (b) the postmicrosomal supernatant of these cells inhibits peroxidation in rat liver mitochondria and other biological membranes. A precise, single-phase assay has been developed for assessing antioxidant levels in lipid extracts. By means of this assay, the increase in membrane resistance to lipid peroxidation has been correlated with a threefold increase in the antioxidant activity of the neuroblastoma neutral lipid fraction. This finding implies that generations of a neutral lipid antioxidant (or antioxidants) is involved in the profound increase in antioxidative capacity which occurs in differentiating neuroblastoma cells.

Animals

[Glutathione: dehydroascorbate-oxidoreductase activity in rat tissues].

Glutathione: dehydroascorbate reductase activity was studied in rat liver, heart, spleen, lungs as well as in Zajdela hepatoma. Correlation between the activities of glutathione reductase and glutathione: dehydroascorbate reductase was observed in all the tissues studied. Glutathione: dehydroascorbate reductase activity was higher in Zajdela hepatoma as compared with the rat liver. The role of glutathione: dehydroascorbate reductase in regulation of antioxidative activity and of cell division is discussed.

Animals

Broad-spectrum antibacterial and antibiofilm activity of dandelion endophytic bacteria against multidrug-resistant bacteria.

Microbial secondary metabolites have long served as a key source of natural product-based drugs. This study evaluates the antibacterial, antibiofilm, and antioxidant activities of endophytic bacteria derived from dandelion, focusing on their effects against multidrug-resistant (MDR) clinical isolates. In total, 33 endophytic bacteria strains were isolated from Taraxacum ohwianum, representing 15 genera. Among these, 13 exhibited antibacterial activity, with 6 demonstrating efficacy against MDR clinical isolates. The endogenous strain Bacillus velezensis DR8 showed strong antibacterial activity against all three MDR strains tested and exerted inhibitory effects on the biofilm formation and dispersal of methicillin-resistant Staphylococcus aureus. Genome sequencing and antibiotics and secondary metabolite analysis shell analysis revealed that this strain harbors 12 biosynthetic gene clusters (BGCs) associated with secondary metabolite production. Of these, seven BGCs exhibited ≥ 80% similarity to known clusters, suggesting the potential to synthesize surfactin, difficidin, fengycin, bacillaene, macrolactin H, bacilysin, and bacillibactin. Overall, these findings indicate that endophytic bacteria from dandelion are a potential source of antibacterial compounds and biofilm formation inhibitors.

Endophytes

Relationship between the antibacterial activity towards Escherichia coli NCTC 5933 and the physico-chemical properties of some esters of 3,4,5-trihydroxybenzoic acid (Gallic acid).

Aqueous solubilities, oleyl alcohol: water and octanol: water partition coefficients, RM values, reduction in surface tension of water, relative antioxidant activities and pKa values, were determined for gallic acid and a series of its alkyl esters. Correlations were sought between these physico-chemical measurements and MIC, MBC and killing-rate determinations against Escherichia coli. Variations in antibacterial activity generally correlated well with partition parameters, but these correlations did not accurately predict the cut-off point in antibacterial activity.

Chemical Phenomena

Screening, isolation, and identification of Latilactobacillus sakei strains from kimchi with potential probiotic properties.

UNLABELLED: The study aimed to screen 40 lactic acid bacterial isolates from kimchi types to isolate Latilactobacillus (L.) sakei strains for their probiotic potential. Based on random amplified polymorphic DNA-based initial screening, 16 S rRNA-based phylogeny, and species-specific PCR, three sakei strains (RKA, RKC, and TAB) were selected for evaluating their probiotic and functional attributes. The selected strains demonstrated probiotic characteristics, including acid tolerance (33-85%), bile salt tolerance (49-68%), cell surface hydrophobicity with ethyl acetate (11.5-25.6%) and hexane (21.0-47.4%), and auto-aggregation (12.6-44.0%). The safety of strains was assessed by γ-hemolytic activity and susceptibility to most tested antibiotics, including carbenicillin, clindamycin, chloramphenicol, ampicillin, erythromycin, and tetracycline, with resistance to cefoxitin and metronidazole. Both crude and cell-free supernatants (CFSs) of selected strains were tested for antimicrobial and antioxidant activities, as well as for cytotoxic effects against human colon adenocarcinoma (Caco-2) cells. CFSs displayed DPPH and ABTS radical scavenging activities of 34.1-37.9% and 41.6-43.1%, whereas the crude ranged from 3.9 to 8.7% and 11.0-17.3%, respectively, supported by the presence of the sod and katA genes. All strains showed good resistance to hydrogen peroxide at various concentrations. Notably, RKC showed superior antimicrobial activity against Escherichia coli, Bacillus subtilis, Pseudomonas aeruginosa, Staphylococcus aureus, and Candida albicans, compared to RKA and TAB. No significant cytotoxicity was observed in Caco-2 cells. In summary, these findings indicate the probiotic potential of L. sakei isolates and the preliminary functional properties of their CFSs; further genome-based characterization of selected strains is warranted. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at https://doi.org/10.1007/s13205-026-04978-7.

Antimicrobial

Oxidative stress and cancer: current insights and therapeutic implications.

OXIDATIVE STRESS: good or evil? Oxidative stress occurs when the balance between reactive oxygen species (ROS) and antioxidant defenses shifts toward an excess of ROS; while essential in physiological processes, it plays a context-dependent role in cancer, contributing to both the promotion and inhibition of tumorigenesis. Small to moderate amounts of ROS activate pathways supporting tumor progression and proliferation, while large amounts lead to genomic instability and cell death. ROS are generated endogenously and exogenously. In cancer, ROS activate pathways that prompt tumor development (KRAS, MYC, PI3K-Akt-mTOR) and block tumor suppressors (p53, BRCA1), allowing tumorigenesis and drug resistance. They also modulate the tumor microenvironment (TME) by altering tumor, stromal and immune cell interactions, which initiate angiogenesis, epithelial-mesenchymal transition (EMT), inflammation and metastasis. Myeloid-derived suppressor cells (MDSCs) and cancer-associated fibroblasts (CAFs) contribute to ROS-driven immunosuppression. Cancer cells mainly rely on glycolysis and oxidative phosphorylation (OXPHOS) to sustain their energetic and metabolic requirements. Generated ROS act as metabolic byproducts and signaling molecules supporting proliferation and tumorigenesis. Cancer stem cells (CSCs) produce low ROS levels by activating antioxidant pathways and mitochondria remodeling, ensuring recurrence and persistence. There is a redox duality that presents challenges and opportunities for therapies. Pro-oxidant approaches attempt to overwhelm the tumor's defenses, while antioxidants preserve healthy tissues. Advances in targeted redox modulation with immunotherapies improve therapy effectiveness. We propose a new "Adaptive Directed Redox Therapy" (ADRT), which involves a dynamic, feedback-controlled methodology that alternates pro- and antioxidant phases to selectively collapse tumor redox balance while preserving normal tissues.

Humans

Resurrection biology: Melatonin as a modulator of anastasis (Review).

Although apoptosis is regarded as an irreversible and terminal process, recent research has identified anastasis as a cellular mechanism that enables cell recovery even after the activation of executioner caspases. While important in supporting tissue homeostasis following mild or transient injury, anastasis presents significant challenges in oncology, as cancer cells may exploit this phenomenon to evade chemotherapy, subsequently acquiring aggressive traits such as genomic instability, stem‑like properties, and increased metastatic capacity. N‑acetyl‑5‑methoxytryptamine (melatonin), recognized for its antioxidant activity and role as a mitochondrial regulator, has been associated with several biological processes that overlap with pathways involved in anastasis, including mitochondrial bioenergetics, redox homeostasis, and DNA repair mechanisms. However, direct evidence supporting a role for melatonin in regulating anastasis remains limited. The present review consolidated current insights into the molecular regulation of anastasis, examining its biphasic transcriptional profile and oncogenic consequences, while exploring the mechanistic links between melatonin biology and pathways relevant to apoptotic recovery and evaluating the therapeutic prospects of melatonin in targeting anastasis as a strategy to mitigate tumor recurrence and improve clinical outcomes.

Melatonin

Whole-genome analysis of Brevibacterium sanguinis AZMABM HM27: a bacterial isolate from the sea anemone Radianthus magnifica and exhibiting promising multi-therapeutic properties.

BACKGROUND: The marine anemone Radianthus magnifica harbors symbiotic microbes with promising biomedical potential, yet their diversity and therapeutic properties remain underexplored. This study aimed to characterize a symbiotic bacterium isolated from R. magnifica collected from Samalona Island, Indonesia, and to evaluate its multi-therapeutic potential. METHODS: Strain AZMABM HM27 was characterized using whole-genome sequencing, functional annotation, biosynthetic gene cluster prediction, molecular docking, and in vitro bioactivity assays. RESULTS: Phylogenetic and genome-based analyses confirmed AZMABM HM27 as Brevibacterium sanguinis, with an OrthoANI value of 97.37% and a dDDH value of 76.50% against the type strain. The genome comprises a 3,834,082 bp chromosome encoding 3,362 protein-coding genes, including 95 genes involved in secondary metabolite biosynthesis. Five biosynthetic gene clusters were predicted, including those associated with ectoine, terpene, and siderophore production. The crude extract demonstrated antioxidant activity (IC₅₀ = 0.87 mg/mL), anti-inflammatory activity (up to 60% inhibition), antidiabetic activity through α-glucosidase inhibition (up to 40% inhibition), and dose-dependent antiproliferative activity against MCF-7 breast cancer cells (74.10% viability at 1 mg/mL). Molecular docking identified a lead compound, 8,9,9,10,10,11-hexafluoro-4,4-dimethyl-3,5-dioxatetracyclo [5.4.1.0(2,6)0.0(8,11)] dodecane, with strong binding affinities to selected therapeutic targets. CONCLUSIONS: B. sanguinis AZMABM HM27 represents a marine symbiotic strain associated with R. magnifica and a promising source of bioactive compounds with antioxidant, anti-inflammatory, antidiabetic, and antiproliferative potential. Further purification, structural elucidation, and in vivo studies are warranted to validate its therapeutic potential.

Animals

Protein isolation markedly enhances in vitro digestibility, nutritional quality, and bioactivity of fungal mycelial proteins.

Fungal mycelial proteins are promising sustainable protein sources, yet their nutritional utilization is often limited by structural constraints. This study systematically evaluated the effects of protein isolation on the proteomic composition, gastrointestinal digestion behavior, amino acid utilization, and bioactivity of Pleurotus citrinopileatus mycelial proteins. Quantitative proteomics identified 3591 proteins, of which 3374 were shared between mycelial flour (PCMF) and protein isolate (PCMPI), indicating that PCMPI primarily represents the soluble proteome fraction. In vitro digestion revealed that PCMPI exhibited significantly higher digestibility (93.98%) than PCMF (42.98%) (p&#xa0;<&#xa0;0.05), reaching levels comparable to whey protein isolate. Enhanced enzymatic accessibility in PCMPI promoted rapid peptide generation during the gastric phase and efficient amino acid release during the intestinal phase, resulting in higher peptide (634.76&#xa0;mg/g) and free amino acid levels (341.69&#xa0;mg/g) at the digestion endpoint. Consequently, PCMPI achieved a balanced amino acid profile with a PDCAAS of 1.0. Moreover, its digestion products exhibited stronger antioxidant activity (IC&#x2085;&#x2080;&#xa0;=&#xa0;8.36&#xa0;mg/mL) and ACE inhibitory activity (IC&#x2085;&#x2080;&#xa0;=&#xa0;15.65&#xa0;mg/mL) compared with PCMF. Mechanistically, protein isolation disrupted the cell wall matrix, shifting digestion from a structure-limited to an accessibility-driven regime. Collectively, these findings demonstrate that protein isolation markedly enhances the digestibility, nutritional quality, and functional potential of mycelial proteins, supporting their application as high-value sustainable protein ingredients.

Digestion

Pseudomonas gebzensis sp. nov., a Carotenoid-Producing Species Isolated from Solar Panels in T&#xfc;rkiye.

Strain RP23018ST was isolated from the solar panels in Gebze, T&#xfc;rkiye. According to the phylogenetic analysis of 16S rRNA gene sequences, strain RP23018ST was classified as a member of the genus Pseudomonas, being most closely related to Pseudomonas cremoricolorata DSM 17059T (99.3%). Strain RP23018ST was Gram-stain-negative, rod-shaped, aerobic, motile, growing between temperature range of 4&#x2013;35&#xa0;&#xb0;C. The polar lipids of strain RP23018ST consisted of phosphatidylethanolamine, di-phosphatidylglycerol, phosphatidylcholine, one unidentified phospholipid, and three unidentified aminolipids. It was determined that the main respiratory quinone of the RP23018ST strain was ubiquinone-9 (Q-9), which is a typical chemotaxonomic characteristic of the genus Pseudomonas. Major fatty acids were C16:0, summed feature 3 (C16:1 &#x3c9;6c and/or C16:1 &#x3c9;7c), summed feature 8 (C18:1 &#x3c9;6c and/or C18:1 &#x3c9;7c), and C17:0 cyclo. Strain RP23018ST had a genome size of 4,944,510&#xa0;bp and a G&#x2009;+&#x2009;C ratio of 63.0%. The average nucleotide identity (ANI) and digital DNA&#x2013;DNA hybridization (dDDH) values between RP23018&#x1d40; and related Pseudomonas species were below 86.4% and 26.7%, respectively, clearly falling below the thresholds for species delineation. Strain RP23018ST produced a deep yellow carotenoid pigment with absorption maxima at 455 and 482&#xa0;nm. Genome annotation revealed key carotenoid biosynthesis genes (crtX, crtY, crtI, crtZ), and the extracted pigment showed antioxidant activity in DPPH and FRAP assays. Polyphasic characterization, including the determination of overall genome relatedness indices, revealed that strain RP23018ST represents a novel species of the genus Pseudomonas, for which the name Pseudomonas gebzensis sp. nov. is proposed. The type strain is RP23018ST (=&#x2009;LMG 33436T&#x2009;=&#x2009;DSM 117295T).

Turkey

From bioactive compounds to volatile profiles: a multidimensional characterization of Indonesian stingless bee honeys.

BACKGROUND: Stingless bee honeys are drawing increasing attention as ingredients for functional foods and health-oriented products because of their distinctive sensory characteristics and bioactive potential. In this study, honeys collected from nine stingless bee species reared in West Sumatra, Indonesia, were comprehensively characterized using physicochemical indices, antioxidant assays [DPPH (i.e. 2,2-diphenyl-1-picrylhydrazyl) and ferric reducing antioxidant power], microbiological screening, volatile profiling [gas chromatography-mass spectrometry (GC-MS)] and Fourier transform infrared (FTIR) fingerprinting. RESULTS: Marked between-sample variability was observed across key quality attributes, including pH (2.80-3.68), Brix (49.83-61.25), viscosity (23.36-175.22&#x2009;cP) and color parameters. FTIR spectra were consistent with carbohydrate-rich matrices and exhibited carbonyl-related bands. GC-MS profiling identified linalool oxide isomers and junenol among the predominant volatiles. To the best of our knowledge, junenol has not previously been reported in stingless bee honey and may represent a potential regional chemical marker for Indonesian stingless bee honeys. Lactic acid bacteria were detected in selected samples, whereas yeast and mold were not detected. Antioxidant activities were comparatively low, which may reflect local environmental and ecosystem-related factors. CONCLUSION: The results provide a multi-parameter baseline for stingless bee honeys produced within a shared ecosystem in West Sumatra and demonstrate the value of integrating conventional chemical indices with FTIR and volatile fingerprints for quality assessment. This combined approach may also support future authentication and origin-tracing frameworks for Indonesian stingless bee honeys. &#xa9; 2026 Society of Chemical Industry.

Animals

Heterologous expression of DobHLH25 from Dendrobium officinale enhances drought tolerance in Arabidopsis.

Drought stress severely constrains the growth, yield, and accumulation of bioactive compounds in Dendrobium officinale (D. officinale), a valuable medicinal orchid, and this challenge is exacerbated under simulated wild cultivation where plants are inevitably exposed to recurring water deficits. Basic helix-loop-helix (bHLH) transcription factors are well-established regulators of plant abiotic stress responses. However, the molecular mechanisms by which bHLH transcription factors respond to drought stress in this species remain largely unknown. In this study, a bHLH transcription factor gene, DobHLH25, was cloned from D. officinale. Phylogenetic analysis revealed that DobHLH25 shares the highest sequence identity with its ortholog in Dendrobium nobile. Additionally, subcellular localization analysis indicated that DobHLH25 is targeted to the nucleus and possesses a functional transcriptional activation domain. Expression pattern analysis showed that DobHLH25 is most abundantly expressed in old leaves, and its expression in roots, stems, and leaves is induced by polyethylene glycol treatments. Heterologous expression of DobHLH25 in Arabidopsis thaliana resulted in higher seed germination rates and longer root lengths under mannitol-induced osmotic stress compared to wild-type plants. Under drought stress, DobHLH25 heterologous expression lines exhibited higher survival rates, reduced leaf water loss, lower malondialdehyde accumulation, and increased proline content. Moreover, the activities of antioxidant enzymes such as superoxide dismutase and peroxidase were significantly enhanced, and the expression levels of multiple drought-responsive genes were markedly upregulated. Collectively, these findings suggest a correlation between DobHLH25 expression and plant drought tolerance, as evidenced by reduced oxidative damage, increased osmolyte accumulation, enhanced antioxidant enzyme activities, and upregulation of drought-responsive genes. Together, these results suggest that DobHLH25 plays a positive role in drought tolerance, and provides a basis for future dissection of its regulatory network in D. officinale.

Drought Resistance

Integrated physiological and transcriptomic analyses reveal coordinated gill responses to heat stress in pikeperch (Sander lucioperca).

Climate change-driven warming of aquatic environments has made thermal stress an increasingly important factor influencing fish physiological homeostasis. Given their central roles in respiration and osmoregulation, gills are particularly responsive to variations in ambient temperature. Histological examination, physiological measurements, and transcriptome profiling were integrated to investigate the mechanisms associated with heat stress-induced gill injury in pikeperch (Sander lucioperca). Histological analysis revealed that exposure to 29&#xa0;&#xb0;C directly caused structural damage to the gills of pikeperch. Oxidative status was evaluated by measuring malondialdehyde (MDA) levels and the activities of antioxidant enzymes, including superoxide dismutase (SOD), peroxidase (POD), and catalase (CAT). MDA accumulation was significantly enhanced under heat stress, while antioxidant enzyme activities (SOD, POD, and CAT) displayed a transient increase followed by a subsequent decline. Transcriptome profiling showed marked enrichment of the protein processing in endoplasmic reticulum pathway after heat stress, suggesting activation of endoplasmic reticulum (ER) stress in pikeperch gills. With increasing stress duration, the unfolded protein response (UPR) appeared unable to re-establish ER homeostasis, shifting ire1 and atf6 toward a pro-apoptotic state. Protein-protein interaction (PPI) analysis further highlighted hub genes potentially involved in heat stress-induced ER stress and apoptosis. TUNEL staining and western blotting collectively confirmed that heat stress triggered apoptosis in pikeperch gill tissue. Overall, this study provides new insights into the physiological and molecular responses of pikeperch gills to heat stress and enhances our understanding of thermal stress adaptation in cold-water aquaculture species under climate change.

Animals