Search Results (217)

Background: Endothelial dysfunction is a key feature of diabetic vascular disease and is associated with high-glucose-induced changes in endothelial energy metabolism and redox balance. Transglutaminase-2 has been implicated in vascular stress responses, but its contribution to endothelial adaptation to high glucose remains incompletely defined. Methods: EA.hy926 endothelial cells were cultured under normoglycaemic (NG) or high-glucose conditions and treated with LDN-27219 at 20 µg/mL (48.9 µM). Cellular reducing capacity, total protein content, mitochondrial respiration, MitoSOX Red fluorescence, and selected cytokine and adhesion-marker secretion were assessed. Results: High glucose shifted cells toward a more glycolytic basal phenotype, increased MitoSOX Red fluorescence, and reduced glycolytic stress responsiveness compared with NG conditions. LDN-27219 had limited effects under NG conditions but, under high-glucose conditions, reduced basal respiration, maximal respiration, ATP-linked oxygen consumption, and spare respiratory capacity, while partially restoring stressed extracellular acidification. LDN-27219 also reduced high-glucose-induced MitoSOX Red fluorescence, although this cannot be interpreted as definitive evidence of reduced mitochondrial superoxide production because mitochondrial membrane potential was not measured. No statistically significant changes were detected in the selected inflammatory or adhesion markers. Conclusions: LDN-27219 modifies endothelial bioenergetic and oxidant-associated fluorescence responses under high-glucose conditions. Full article

Inflammation and oxidative stress induced by high glucose levels constitute essential factors impeding wound healing in diabetes, posing a significant threat to public health. Despite its notable anti-inflammatory and antioxidant potential, the clinical applicability of quercetin is hampered by its hydrophobicity and limited oral bioavailability. To address these issues, the thin-film hydration method was used to encapsulate quercetin into FQ micelles. Subsequently, 3-aminophenylboronic acid-modified oxidized alginate was crosslinked with polyvinyl alcohol, and simultaneously loaded with glucose oxidase (GOX) and FQ micelles, to construct a glucose-activated cascade acidification-triggered controlled-release hydrogel (OSSP@FQ&GOX). The phenylboronic ester bonds in the hydrogel are responsive to glucose and undergo cleavage. GOX-mediated oxidation of glucose produces gluconic acid, resulting in a lower local pH and subsequently triggering FQ micelle release. The released FQ micelles alleviate oxidative stress and exert immunomodulatory effects, while the hydrogel also provides self-healing, and biocompatible properties that facilitate cutaneous regeneration in diabetic mice. Thus, this study highlights the potential of combining GOX with natural products and multi-stimuli-responsive hydrogels for the treatment of chronic diabetic wounds, while also opening new avenues for the development of multifunctional wound dressings. Full article

Traditional monitoring frameworks heavily rely on static, total heavy metal concentrations and deterministic indices, failing to capture how climate-driven stressors and micro-interface interactions alter the stability, speciation, and bioavailability of toxic metals. This review synthesizes the state-of-the-art literature at the intersection of hydrology, geochemistry, microbial ecology, and toxicology to address this gap. We investigate how shifting redox (Eh-pH) gradients and climate-forced hydrological extremes—ranging from drought-induced sediment acidification to flood-driven shear stress—accelerate the reductive dissolution of iron/manganese oxyhydroxides. This process consequently triggers seasonal pulses of bioavailable metals. Furthermore, we evaluate how aged microplastics act as dynamic vector interfaces, altering competitive adsorption kinetics and biological uptake. Crucially, we highlight the heavy metal-microbiome-antibiotic resistance axis, demonstrating how sublethal metal exposure drives the co-selection and proliferation of antibiotic resistance genes (ARGs) via mobile genetic elements, revealing an indirect public health hazard. Finally, we critique deterministic assessments and advocate for probabilistic modeling via Monte Carlo simulations to capture exposure heterogeneity. By bridging macro-scale forcing with microscopic chemical and biological transformations, this review provides a comprehensive synthesis for shifting regulatory frameworks toward dynamic, bioavailability-based ecological governance. Full article

Heat stress impairs male reproductive function, but whether acute heat stress alters glutamine-derived carbon labeling in Sertoli cells and whether melatonin modulates this response remain unclear. This study aimed to determine whether acute heat stress alters glutamine-derived carbon labeling in primary goat Sertoli cells and to evaluate whether melatonin attenuates these heat stress-associated metabolic changes. Primary goat Sertoli cells were assigned to control, heat-stress, or heat-stress plus melatonin groups. Cells were labeled for 24 h with [U-¹³C₅] glutamine. Cells in the heat-stress and heat-stress plus melatonin groups were subsequently exposed to 42 °C for 0.5 h, whereas control cells were maintained at 37 °C. In the heat-stress plus melatonin group, melatonin (0.5 μM) was applied throughout labeling and heat exposure. GC–MS was used to measure mass isotopologue distributions, which were subsequently corrected for natural isotope abundance, and to calculate total ¹³C-labeled fractions of selected TCA cycle intermediates; extracellular acidification rate (ECAR)-derived parameters were measured as indirect indices of glycolysis-associated acidification. Heat stress increased the total ¹³C-labeled fraction of cis-aconitate and, as an exploratory combined readout, the unweighted average total ¹³C-labeled fraction of citrate and cis-aconitate; succinate and malate were unchanged, while fumarate decreased. Melatonin reduced the heat stress-associated total ¹³C-labeled fractions of citrate and cis-aconitate and decreased the relative abundance of cis-aconitate M + 5. Melatonin also attenuated heat stress-associated increases in ECAR-derived glycolysis, glycolytic capacity, and glycolytic reserve. These findings indicate that acute heat stress is associated with altered citrate/cis-aconitate ¹³C-labeling patterns that are potentially compatible with reductive carboxylation-related labeling but do not directly demonstrate altered pathway flux; these changes were attenuated by melatonin. Overall, the study objective was achieved by showing that acute heat stress altered citrate/cis-aconitate ¹³C-labeling patterns and increased ECAR-derived extracellular acidification in primary goat Sertoli cells, and that melatonin attenuated both responses. Further studies incorporating a melatonin-only group, dynamic isotope tracing, mitochondrial respiration measurements, redox analysis, and flux modeling are warranted to define the underlying metabolic routes more directly. Full article

Ocean acidification poses a critical threat to marine invertebrate survival and diversification, yet the post-transcriptional regulatory mechanisms underlying acid stress responses remain poorly understood. Here, we employed Oxford Nanopore long-read RNA sequencing to systematically characterize transcriptional and post-transcriptional responses to acidic pH stresses in the marine nematode Litoditis marina. Our analysis revealed 912 upregulated and 728 downregulated genes enriched in autophagy, fatty acid metabolism, and peroxisome activation, alongside 327 differential alternative splicing events and 1512 transcripts with significant usage changes under severe acidic pH stress. By integrating weighted gene co-expression network analysis with databases such as WormExp2, we found that acidic pH stress response exhibited resemblance to oxidative stress response. Specifically, we identified genes involved in the oxidative stress response, such as gpx-1, cyp-13A11, trxr-1, cyc-1, and key regulators, including hlh-30/TFEB. Genes such as gpx-1, trxr-1, and cyp-23A1 might protect L. marina from oxidative stress under acidic pH. Moreover, several ferroptosis-related genes, such as gpx-5, fat-2, and smf-1, might render L. marina vulnerable to acidic pH stress. Among the genes with splicing changes, we identified oxidative stress responding genes such as sod-4, prx-2, coq-2, coq-3, prx-10, ctl-2, gst-7, trx-1, mdt-15, and fat-2. Additionally, we discovered the preference for proximal 3′ UTR under acidic pH stress. Genes related to ferroptosis, including cyp-23A1, C07E3.9/PLA2G1B, and C53D5.5/GGT1, exhibited differential 3′ UTR usage under acidic pH stress. Our findings shift the focus from traditional gene-centric analyses to capturing the full breadth of post-transcriptional diversity, providing novel insights into post-transcriptional gene regulation in marine metazoans under environmental stress, as well as revealing that alleviating oxidative stress might increase resistance to acid pH stress. Full article

The skin microbiome plays a central role in maintaining cutaneous homeostasis, and its disruption has been implicated in a wide range of inflammatory and degenerative skin disorders. This review critically evaluates the current evidence on topical probiotics in dermatology, integrating microbiological mechanisms, formulation strategies, and translational and regulatory challenges within a single framework—an angle that remains insufficiently addressed in previous reviews. A targeted search of PubMed and ScienceDirect (2009–2025) was conducted to identify relevant original studies. The results suggest that topical probiotics may promote skin health through three broad, interconnected axes: (i) modulation of host responses (e.g., inflammation, immune signaling, and oxidative stress); (ii) microbial ecology and pathogen control (e.g., competition, acidification, and antimicrobial metabolite production); and (iii) support of barrier function and tissue repair (e.g., lipid metabolism, re-epithelialization, and extracellular matrix remodeling). Efficacy appears to depend strongly on strain specificity, formulation design, and microbial viability during storage and application. In addition to conventional dosage forms, advanced platforms—hydrogels, microgels, microparticles, and microneedle-based systems—have been investigated to improve stability and local delivery. Promising preclinical and clinical results have been reported for acne, wound healing, skin barrier repair, and anti-aging applications. Nevertheless, major translational challenges remain, including limited standardization, instability of live microorganisms, insufficiently representative experimental models, and regulatory uncertainty. Overall, topical probiotics represent a promising microbiome-based strategy in dermatology, but robust clinical validation and formulation optimization are still needed to support broader clinical implementation. Full article

The aim of this study was to isolate and molecularly identify lactic acid bacteria (LAB) associated with the epiphytic microflora and silage of wheatgrass (Agropyron spp.), as well as to evaluate their biotechnological potential as starter cultures for the ensiling of difficult-to-ensile forage crops under the climatic conditions of northern Kazakhstan. A total of 63 bacterial isolates were obtained and grown on MRS medium under different temperature conditions. Based on growth characteristics, pH values, and titratable acidity, 15 highly active strains were selected, demonstrating stable acidification (pH 3.99–4.75) and high metabolic activity. All isolates were catalase negative and capable of fermenting a wide range of carbohydrates and polyols, although pronounced strain-specific differences were observed. The selected strains exhibited proteolytic and antagonistic activity against test microorganisms and showed high tolerance to osmotic stress, maintaining growth at NaCl concentrations of up to 8–10%. Molecular identification based on 16S rRNA gene sequencing revealed that nine technologically significant strains belonged to the species Lactococcus garvieae, Pediococcus acidilactici, Lactiplantibacillus plantarum, Enterococcus faecalis and Enterococcus faecium. The results obtained in this study demonstrate the high environmental adaptability of the isolated strains and confirm their potential for the development of effective microbial inoculants aimed at improving fermentation processes and enhancing the preservation of difficult-to-ensile forage crops under cold-climate conditions. Full article

Global plastic production has led to widespread contamination by micro- and nanoplastics, with polystyrene nanoplastics (PSNPs) increasingly being detected in human biological samples, including blood and cardiac tissue. Given the critical role of mitochondria in cardiac energy metabolism, this study investigated whether 100 nm PSNPs interact with mitochondria and affect mitochondrial function in H9c2 cardiomyoblasts. Cellular uptake and intracellular distribution were examined, followed by an evaluation of mitochondrial ultrastructure, intracellular and mitochondrial reactive oxygen species (ROS) production, mitochondrial membrane potential, mitochondrial dynamics and mitophagy-related gene expression, mitochondrial DNA copy number, and metabolic function. PSNPs were internalized but did not directly localize to mitochondria within 24 h. No significant cytotoxicity, increase in intracellular or mitochondrial ROS production, or alteration in basal metabolic activity was observed. However, PSNP exposure resulted in intracellular accumulation, an altered mitochondrial ultrastructure characterized by crista loosening and vacuole-like structural changes. These changes were accompanied by reduced mitochondrial membrane potential; the upregulation of mitochondrial dynamics-related genes, including optic atrophy 1 (Opa1) and dynamin-related protein 1 (Drp1); the suppression of PTEN-induced kinase 1 (PINK1)/Parkin RBR E3 ubiquitin protein ligase (Parkin)-mediated mitophagy-related genes; and decreased maximal respiratory capacity. Lactate production and the extracellular acidification rate remained unchanged, suggesting that compensatory glycolysis was not activated. These findings indicate that PSNP exposure induces early mitochondrial structural and functional alterations without substantial cell damage, suggesting a potential reduction in cardiac adaptive capacity under PSNP-induced stress conditions. Full article

Autophagy-associated readouts in localized prostate cancer cannot be interpreted based on LC3, p62/SQSTM1, or LC3 puncta alone. In line with the concept of autophagy as a stress-response system, this review proposes a flux-aware, organelle-centered framework for assigning biological meaning to autophagy-related changes under disease-relevant stress. The framework integrates oxidative burden, lysosomal competence, selective autophagy, mitophagy, ferritinophagy, p62/SQSTM1-NRF2 signaling, ferroptosis-aware controls, and disease-stage context to distinguish four interpretive states: homeostatic quality control, adaptive tumor survival, blocked clearance, and stress-overload vulnerability. Flavonoid-associated responses are used as stress-test examples because they expose recurrent limitations in the field, including supraphysiologic exposures, limited metabolite realism, static-marker inflation, and insufficient assessment of lysosomal function. However, the framework is not restricted to dietary compounds; it applies to metabolic, pharmacological, inflammatory, androgen-related, radiation-associated, or therapy-induced perturbations in which autophagy-associated markers are altered without resolution of flux or organelle function. By linking autophagosome formation, cargo turnover, lysosomal acidification, redox buffering, and phenotype-level endpoints, this review defines a practical evidence hierarchy for interpreting autophagy in localized prostate cancer and for prioritizing translational vulnerabilities arising from organelle crosstalk. This contribution is primarily conceptual and is operationalized methodologically through flux-based evaluation criteria and translationally through disease-window-specific study-design recommendations. Full article

Soil acidification is a widespread consequence of intensive agriculture and represents a major abiotic stress affecting plant performance, nutrient availability, and ecosystem functioning. Long-term tea (Camellia sinensis) plantations provide model systems of chronic acidification, where sustained low pH imposes strong environmental filtering on soil microbial communities. Although microbial responses to acidification have been extensively studied, research has focused predominantly on bacteria and fungi, leaving other key functional groups, particularly protists, largely overlooked. Here, we synthesize current knowledge on microbial communities in acidified soils and highlight trophic interactions, especially protist-mediated regulation, as a potentially critical but underexplored dimension linking abiotic stress to plant–soil processes. We propose that soil acidification may not only filter microbial community composition but also reshape trophic interactions. Based on evidence from other soil systems, protist-mediated trophic interactions could influence nutrient cycling, pathogen suppression, and ultimately plant responses under stress conditions. Integrating environmental filtering with trophic perspectives provides a conceptual framework for understanding microbiome dynamics in acidified soils. However, direct evidence linking protist-mediated trophic regulation to ecosystem functioning and plant performance in tea plantation soils remains limited and requires experimental validation. We further suggest that these systems provide unique opportunities to investigate how abiotic constraints and biotic interactions jointly shape plant performance. Addressing this gap is essential for advancing predictive understanding of plant–microbiome interactions under ongoing environmental change. Full article

Plant growth-promoting rhizobacteria (PGPR) foster sustainable and environmentally friendly agriculture by promoting plant growth and development. PGPR colonize the root rhizosphere, rhizoplane and root tissues, where they drive organic matter turnover and nutrient cycling, thereby increasing the (phyto)availability of essential macro- (P, N, K, S, Ca, Mg) and micronutrients (Fe, Zn, Mn, Mo, Co, Ni, Cu, B). This process relies on various mechanisms, including acid secretion (rhizospheric acidification and metal chelation), siderophore production (binding Fe, Zn, and other metals) and hydrolytic enzyme-mediated catalysis (phosphatases, phytases). Some of these microorganisms can also modulate the phytohormonal balance, reshaping root architecture and enhancing nutrient uptake, and even can alleviate abiotic stress or serve as biocontrol agents, contributing to pathogen resistance. Even though plant cultivation practices relying solely on synthetic fertilizers rapidly increase crop yield and productivity, they eventually result in crops poor in essential micronutrients and trace elements. This may contribute to micronutrient malnutrition in the human population. On the contrary, PGPR enhance both crop yield and nutritional quality. Therefore, in utilization with other nutrient sources, PGPR provide a promising and scalable approach towards advancing environmentally sustainable agriculture systems. Full article

Nitrite is a key environmental challenge in intensive shrimp aquaculture, adversely affecting physiological regulation and survival. Although tolerant Penaeus vannamei families have been established by selective breeding, the basis of family-level variation in tolerance has yet to be clarified. In this study, nitrite-tolerant and nitrite-sensitive families were compared using survival analysis, transcriptomics, targeted qPCR validation, physiological assays, and RNA interference of representative transport-related genes. Under nitrite exposure, the tolerant family exhibited significantly higher survival and a distinct gill transcriptional response, characterized by stronger induction of acid–base and ion-transport genes, including carbonic anhydrase 2 (CA2), the Na⁺/K⁺-ATPase subunits ATP1A and ATP1B, as well as several V-type H⁺-ATPase-related genes. These transcriptional changes were accompanied by elevated ATP content and Na⁺/K⁺-ATPase activity, improved hemolymph pH stability, and reduced nitrite accumulation in both gill and hemolymph. RNAi-mediated knockdown of CA2 or ATP1B attenuated the nitrite-induced transport response, decreased ATP content and NKA activity, exacerbated hemolymph acidification, promoted internal nitrite accumulation, and ultimately reduced shrimp survival under nitrite stress. Family-based validation further showed that the tolerant family displayed higher survival than the sensitive family in the dsEGFP group, whereas this advantage was markedly reduced after CA2 or ATP1B knockdown under nitrite stress. These findings highlight that strengthened branchial ion transport and acid–base regulation represent key physiological mechanisms underlying nitrite tolerance in resistant shrimp families. Full article

Macrophage migration inhibitory factor (MIF) has been shown to induce M1 macrophage polarization with oxidative stress and associated metabolic reprogramming. Several tautomerase inhibitors were shown to selectively inhibit either MIF’s ketonase or enolase sub-activities. In this study, we aimed to investigate the role of enolase sub-activity in M1 polarization using the selective enolase inhibitor TE-91. We performed in silico molecular docking analysis and physicochemical characterization of TE-91. LPS + IFN-γ-induced RAW264.7 cells were applied as a model for M1 macrophage activation. We performed ROS and nitrite determinations, ELISA, qPCR, and immunoblot analysis, and measured mitochondrial oxygen consumption rate and extracellular acidification rate. Here, we reveal that TE-91 might directly bind to the MIF tautomerase active site. Furthermore, TE-91 reduces M1 activation by enhancing oxidative phosphorylation and reducing the glycolytic activity in LPS + IFN-γ-induced macrophage cells. In the same model, TE-91 reduces TNF-α, IL-6, CCL2, and iNOS mRNA transcription yet fails to modulate PARP1 and SOD2 mRNA transcription. It also decreases ROS, nitrite, and IL-6 production without influencing TNF-α and CCL2 protein production. TE-91 was unable to reduce either HIF-1α mRNA transcription or its protein expression. Finally, TE-91 reduced IL-1β cleavage, without affecting IL-1β protein expression. These results may highlight the importance of tautomerase sub-activities in M1 polarization. Full article

Background: Atherosclerosis preferentially develops at arterial regions exposed to low shear stress (LSS), highlighting the critical role of local hemodynamic forces in disease initiation and progression. Emerging evidence indicates that endothelial lipid metabolism is a key determinant of vascular homeostasis; however, whether LSS directly regulates endothelial lipid droplets’ (LDs) dynamics remains unclear. In particular, the mechano-transduction pathways linking shear stress to lysosome-mediated lipid processing within the endothelium have yet to be defined. Methods: Complementary in vitro flow systems and in vivo atheroprone models were employed to examine the effects of LSS on endothelial lipid metabolism. Endothelial LDs accumulation, lysosome-dependent lipophagy, and atherosclerotic lesion development were systematically assessed under LSS conditions. Mechanistically, molecular profiling and rapamycin-mediated functional rescue were conducted to delineate the role of the KLF4/TFEB/ATP1A1 signaling axis in LSS-induced impairment of lysosome-dependent lipophagy. Results: We found that LSS induced pathological accumulation of LDs in vascular endothelial cells, accompanied by a marked suppression of lysosome-dependent lipophagy. Elucidation of the mechanism showed that LSS downregulated the shear-responsive transcription factor KLF4, resulting in aberrant phosphorylation of transcription factor EB (TFEB) and impaired TFEB nuclear translocation. Consequently, the TFEB transcriptional program governing lysosomal function was disrupted, including reduced expression of the TFEB target ATP1A1, leading to defective lysosomal acidification and blockade of lipid autophagic flux. Restoration of the KLF4/TFEB/ATP1A1 axis reactivated lipophagy, alleviated endothelial lipid burden, and significantly attenuated atherosclerotic lesion development. Conclusions: Our findings demonstrate that disruption of the KLF4/TFEB/ATP1A1 signaling pathway mediates LSS-induced impairment of endothelial lipophagy, thereby driving pathological LDs accumulation. This highlights the potential of restoring this axis as a therapeutic strategy to attenuate atherosclerotic progression. Full article

Acetobacter cerevisiae KSO5 is an indigenous strain isolated from Korean fruit vinegar and is a potential starter candidate for vinegar fermentation. Here, we report the first complete circular genome of KSO5, comprising a 3.3 Mb chromosome and two plasmids encoding 2898 genes. Core-genome phylogeny clearly placed KSO5 within the A. cerevisiae clade, supported by ANI (97%) and dDDH (71%) values. Comparative analysis with seven draft A. cerevisiae genomes identified strain-specific genomic islands, mobile genetic elements, and plasmid-borne modules potentially related to genetic stability. Comparative COG profiling suggested enhanced potential for carbohydrate utilization, redox balancing, membrane transport, and stress adaptation within a conserved Acetobacter genomic background. The genome encoded a periplasmic oxidative fermentation system, including membrane-bound pyrroloquinoline quinone-dependent alcohol dehydrogenase and molybdopterin-dependent aldehyde dehydrogenase, together with predicted acetate-handling routes that may reduce intracellular acetate accumulation. Consistent with these features, KSO5 maintained growth and titratable acidity production up to 9% ethanol, with the strongest performance at 7–9% ethanol, whereas both traits declined markedly at 10% ethanol. In 5% ethanol medium, KSO5 also showed high ethanol consumption, comparable to that of A. pasteurianus LMG 1262 and higher than that of most reference strains. These findings link the genomic features of KSO5 to efficient ethanol oxidation, sustained acidification, and stable growth, supporting its potential as a starter strain for vinegar fermentation. Full article