Search Results (5,782)

Myocardial ischemia–reperfusion injury (MIRI) remains a major complication in acute coronary syndrome and cardiac surgery, with oxidative stress and metabolic dysregulation serving as central pathogenic drivers. This study aimed to clarify whether the novel MyD88 inhibitor TJ-M2010-5 confers cardioprotection against MIRI by remodeling immune–metabolic homeostasis, particularly through regulating NADPH oxidase (NOX)-derived reactive oxygen species (ROS) overproduction and endothelial nitric oxide synthase (eNOS) functional activity. In this study, male C57BL/6 mice were subjected to 30 min myocardial ischemia followed by 24 h reperfusion, with or without TJ-M2010-5 pretreatment (50 mg/kg, i.p.), and mouse cardiac vascular endothelial cells (H5V) were exposed to hypoxia–reoxygenation (H/R) with or without TJ-M2010-5 intervention. We systematically evaluated myocardial infarct size, ROS production, cell apoptosis, NF-κB activation, NOX expression and activity, NADPH redox homeostasis, NO production, and eNOS phosphorylation levels. The results showed that TJ-M2010-5 significantly reduced myocardial infarct size and inhibited IKKβ/NF-κB activation in I/R-treated mice, and functionally disrupted MyD88 homodimerization in ischemic myocardium. In H/R-challenged H5V cells, TJ-M2010-5 decreased ROS generation and cell apoptosis, suppressed NOX2/NOX4 expression and activity, restored NADPH levels and NADP⁺/NADPH redox balance, preserved tissue NO content, and maintained eNOS Ser1177 phosphorylation. In conclusion, pharmacologic blockade of MyD88 by TJ-M2010-5 alleviates NOX-dependent oxidative stress, stabilizes NADPH redox homeostasis, preserves NO bioavailability, and maintains eNOS functional activity, thereby exerting potent cardioprotective effects against MIRI via regulating redox homeostasis. The TLR/MyD88–NOX/ROS–eNOS signaling axis represents a novel and promising redox-regulatory therapeutic target for the clinical prevention and treatment of MIRI. Full article

Algal biofilms contribute to the biodeterioration of building materials (BMs), while restrictions on conventional algicides stimulate the search for sustainable protection strategies. This study evaluated the antialgal potential of selected essential oils and active compounds, with particular emphasis on lemongrass essential oil (LGC), for the control of microalgal biofilms on brick and render surfaces. Three essential oils (Lavandula angustifolia, Melaleuca alternifolia, and Cymbopogon citratus) and two active compounds, eugenol (EU) and geraniol, were screened against terrestrial microalgal strains associated with biodeterioration. Antialgal activity was assessed based on minimum inhibitory and algicidal concentrations. LGC and EU inhibited microalgal growth, reducing photosynthetic activity, chlorophyll a content, and inducing cellular alterations. Metabolomic analysis revealed a strong stress response involving membrane lipid remodeling, oxidative stress, and disruption of photosynthetic metabolism. LGC and EU caused cellular damage, with LGC inducing faster degradation and EU enabling partial adaptation. LGC effectively reduced microalgal biofilms on brick and render, decreased photosynthetic activity, and partially restored surface coloration, without causing significant changes in substrate pH or water absorptivity. Effectiveness depended on biofilm maturity and substrate characteristics. The integrated microbiological, physiological, metabolomic, and material-based approach confirmed the potential of LGC as a sustainable component of future protective coatings for mineral BMs. Full article

Glucosylglycerol (GG) is a compatible solute with excellent moisturizing capacity and macromolecule stability, exhibiting broad application potential in cosmetics, food, and pharmaceutical industries. The halophilic cyanobacterium Cyanobacterium aponinum SCSIO-45682 can synthesize GG under salt stress and represents a promising strain for photoautotrophic GG production. In this study, the GG product extracted from SCSIO-45682 was structurally identified as 2-O-α-D-GG by high-performance liquid chromatography (HPLC) and nuclear magnetic resonance (NMR) analysis. The effects of salinity, initial pH, light intensity, and carbon, nitrogen, and phosphorus concentrations on biomass and GG accumulation were systematically investigated using single-factor experiments, and response surface methodology (RSM) was subsequently applied to optimize intracellular GG content as a percentage of dry weight (% DW). The results showed that salinity was the primary factor driving GG accumulation in SCSIO-45682. As salinity increased from 30 ppt to 120 ppt, GG content increased by 3.41-fold. Light intensity was another key factor affecting GG accumulation, with moderate irradiance of 2000–5000 lux being more favorable for GG accumulation. Among the nutritional factors, nitrogen and phosphorus had relatively weak effects, whereas increasing carbon concentration enhanced GG yield by promoting biomass accumulation. The RSM results showed that salinity × light intensity exhibited a synergistic enhancement pattern, whereas the pH × carbon concentration interaction displayed an inverse regulatory effect. Under the optimal conditions of 96 ppt salinity, pH 5.0, 5000 lux light intensity, and 7.0 mM NaHCO₃, GG content and yield reached 16.30% DW and 366.75 mg/L, respectively, representing a 3.29-fold increase compared with the control. In addition, the GG-containing crude extract exhibited concentration-dependent 2,2-diphenyl-1-picrylhydrazyl (DPPH) and 2,2′-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid, ABTS) radical-scavenging activities. Overall, this study achieved a high level of natural 2-O-α-D-GG accumulation in a wild-type cyanobacterial photoautotrophic cultivation system through multi-factor synergistic optimization, providing a foundation for the green biomanufacturing of GG using wild-type C. aponinum. Full article

Bacterial infection and persistent oxidative stress can impair wound healing and limit the efficacy of conventional antibacterial therapies. Here, we developed a pH- and near-infrared (NIR) light-responsive polymer hydrogel microneedle (PHMN) system by incorporating curcumin-loaded polydopamine particles (PDA@CUR) into photo-crosslinked methacrylated hyaluronic acid (HAMA) microneedles with a poly(vinyl alcohol) (PVA) backing layer. The synthesized CUR-loaded PDA nanoparticles (PDA@CUR) exhibited uniform spherical morphology, efficient CUR loading, and pH- and NIR light-responsive drug release. The fabricated PHMN/PDA@CUR patch displayed a well-defined array, sufficient mechanical strength, and efficient photothermal conversion under NIR irradiation. The patch could effectively inhibit both E. coli and S. aureus, with NIR irradiation further enhancing antibacterial activity. This PHMN-based system also exhibited favorable cytocompatibility and significantly alleviated H₂O₂-induced cellular oxidative injury. Overall, the PHMN/PDA@CUR patch integrate localized drug delivery, NIR-enhanced photothermal antibacterial activity, and cellular protection, providing an in vitro proof-of-concept platform for localized management relevant to infected wounds. Full article

Background: Type 2 diabetes mellitus (T2DM) is a multifactorial metabolic disorder characterized by hyperglycemia, insulin resistance, hepatic steatosis, chronic inflammation, and oxidative damage. Echinatin (ECH), a naturally occurring chalcone compound, has shown potential metabolic regulatory activities, but its effects and underlying mechanisms in T2DM remain unclear. This study aimed to investigate the effects of ECH and its underlying mechanisms in db/db mice. Methods: Male db/db mice were orally administered ECH at low and high doses for 8 weeks. Glucose metabolism was evaluated by fasting blood glucose measurement and oral glucose tolerance test (OGTT). Insulin sensitivity was assessed by serum insulin levels and hepatic AKT phosphorylation. Pancreatic β-cell integrity was examined by insulin immunohistochemistry. Hepatic glucose metabolism-related genes, including Pck1, G6pc, Gys1, Gys2, Gck, and Slc2a2, were analyzed by quantitative PCR. Serum and hepatic lipid profiles, hepatic steatosis, inflammatory cytokines, and oxidative stress markers were also evaluated. Results: ECH treatment significantly reduced fasting blood glucose levels and improved glucose tolerance, as indicated by ECH-preserved pancreatic β-cell integrity and increased serum insulin levels. Furthermore, ECH enhanced hepatic insulin signaling, as demonstrated by an increased p-AKT/AKT ratio. At the transcriptional level, high-dose ECH significantly suppressed the expression of gluconeogenic genes Pck1 and G6pc, while upregulating the glucose transporter gene Slc2a2 without significantly altering Gys1, Gys2, or Gck expression. In addition, ECH reduced serum and hepatic triglyceride and total cholesterol levels, alleviated hepatic lipid accumulation by H&E and Oil Red O staining, and decreased circulating inflammatory cytokines (TNF-α and IL-1β) and oxidative markers (4-HNE and 8-OHdG). Conclusions: ECH treatment was associated with improvements in multiple metabolic parameters in db/db mice, including glucose homeostasis, insulin sensitivity, hepatic steatosis, and systemic inflammation and oxidative stress. These observations may provide a basis for further studies on the effects of ECH on T2DM-related glucose and lipid metabolism. Full article

Salt stress severely restricts the growth and development of pear trees, and DNA methylation may potentially modulate the salt tolerance of Pyrus betulaefolia by regulating ion transporter genes. Cyclic nucleotide-gated channel (CNGC) family genes are essential for plant ion transport and salt stress adaptation; however, the epigenetic regulatory relationship between DNA methylation and CNGC genes underlying pear salt tolerance remains unclear. In this study, 26 PbCNGC genes were systematically identified from P. betulaefolia, which possess the conserved motifs characteristic of the CNGC family and can be classified into five subclades. PbCNGC members exhibit distinct spatiotemporal expression patterns in ordinary and salt-tolerant genotypes. Under salt stress, core members PbCNGC3, PbCNGC4, PbCNGC10, and PbCNGC14 displayed typical fluctuating up-and-down expression patterns across roots, stems, and leaves, with distinct spatiotemporal specificity in their expression peaks. In contrast, PbCNGC19 and PbCNGC20;1 were exclusively induced in roots under salt stress. Quantitative results showed marked genotypic differences in salt responsiveness. At 4 h of salt treatment, the root transcript levels of PbCNGC4 and PbCNGC14 were upregulated by 8.27-fold and 6.76-fold in the salt-tolerant genotype, respectively, which were considerably higher than those in the ordinary genotype (2.08-fold and 4.50-fold). Obvious genotypic differences in mCHH methylation modifications of PbCNGC4 and PbCNGC14 were detected after salt treatment, and pharmacological experiments confirmed that DNA methylation negatively modulates the transcription of these two genes. Yeast functional complementation assays further demonstrated that PbCNGC4 and PbCNGC14 act as functional Na⁺ and K⁺ permeable cation influx channels. Combined with methylation analysis results, this study reveals a potential regulatory cascade in which DNA methylation may inhibit the transcription of PbCNGC4 and PbCNGC14, modulating their ion-transport capacity, effectively reduces Na⁺ overaccumulation, sustains cellular K⁺ retention to alleviate salt-induced ionic toxicity, and may ultimately shape the salt tolerance of P. betulaefolia. These findings enrich the understanding of epigenetic regulation of plant salt tolerance and provide valuable candidate genes and theoretical references for salt-tolerant molecular breeding in pear trees. Full article

Chemoresistance in breast cancer remains a major clinical challenge, fueled by robust antioxidant defenses that neutralize cisplatin-induced oxidative stress through the NRF2/SLC7A11/GPX4 pathway in luminal breast cancer cells. This study examined camel milk whey protein (CMP), a bioactive fraction rich in lactoferrin and antioxidant peptides, as a redox-modulating chemosensitizer to boost cisplatin efficacy in MCF-7 cells while simultaneously assessing treatment selectivity in non-tumorigenic MCF-12A mammary epithelial cells. Cells were treated for 24 h with CMP (at 200 and 600 ng/mL, designated as P1 and P2) and cisplatin (25 µM), both individually and in combination. Cell viability was evaluated via the MTT assay, and the mRNA expression levels of NRF2, GPX4, and SLC7A11 were quantified using RT-qPCR. Bliss independence synergy analysis was applied to the MTT datasets, and a protein–protein interaction network was constructed via STRING (v12.0). Furthermore, the clinical significance of the NRF2/SLC7A11/GPX4 axis was explored through Kaplan–Meier survival analysis (using KM Plotter), alongside genomic profiling via cBioPortal (TCGA PanCancer Atlas). Co-treatment with CMP and cisplatin significantly diminished MCF-7 cell viability compared to single-agent treatments, driven by the coordinated downregulation of NRF2, SLC7A11, and GPX4. Bliss independence modeling confirmed synergistic cytotoxicity for both the P1 + Cis and P2 + Cis combinations. Conversely, MCF-12A cells showed no intrinsic cytotoxicity (CC₅₀ > 600 ng/mL) and displayed a distinct transcriptional profile following cisplatin exposure, marked by the upregulation of GPX4 and SLC7A11. In silico evaluations further reinforced the clinical relevance of this axis, revealing that elevated NRF2 and SLC7A11 expression correlates with poor relapse-free survival and recurrent genomic alterations across breast cancer cohorts. Ultimately, these results demonstrate that CMP disrupts the NRF2/SLC7A11/GPX4 antioxidant axis in cancer cells, offering a promising, selective strategy to enhance cisplatin sensitivity while safeguarding healthy tissues. Full article

Background/Objectives: Oxidative stress is a key contributor to breast cancer (BC) progression and therapeutic response. Although carboplatin is widely used in BC treatment, the effects of combining carboplatin with metformin and boric acid (BA) on cellular redox homeostasis remain poorly understood. This study investigated the effects of these agents on cell viability, migration, and oxidative stress in BC and normal mammary epithelial cells. Methods: Human BC MCF-7 cells and normal mammary epithelial CRL-4010 cells were treated with carboplatin, metformin, BA, and selected combination regimens. Cell viability was assessed using the Cell Counting Kit-8 (CCK-8) assay following 24, 48, and 72 h of treatment. Cell migration was evaluated using a scratch wound-healing assay, and intracellular oxidative stress responses were assessed by measuring superoxide dismutase (SOD) activity. Statistical analyses were performed using one-way ANOVA followed by Fisher’s least significant difference (LSD) post hoc test. Results: Treatment responses were both time- and treatment-dependent in MCF-7 and CRL-4010 cells. Combination regimens significantly reduced cell viability after 48 and 72 h (all p < 0.0001) and generally exhibited greater inhibitory effects than single-agent treatments. Metformin- and BA-containing combinations also produced more pronounced inhibition of cell migration. Significant treatment-related alterations in SOD activity were observed in both cell lines, indicating treatment-associated changes in antioxidant enzyme activity. While several combination regimens decreased SOD activity, others induced increased SOD activity, suggesting differential oxidative stress responses between malignant and non-malignant cells. Conclusions: Carboplatin, metformin, and BA significantly modulated cell viability, migration, and antioxidant responses in both BC and normal mammary epithelial cells. Combination treatments generally produced greater inhibitory effects on cell viability and migration than selected single-agent treatments, particularly in MCF-7 cells. These findings demonstrate treatment-dependent changes in cell viability, migration, and SOD activity and provide a basis for further investigation of the molecular mechanisms underlying carboplatin-based combination treatments. Full article

Background: Oxidative stress-mediated neuronal injury is critically involved in the pathogenesis of neurodegenerative disorders, including Alzheimer’s disease and Parkinson’s disease. Manganese dioxide (MnO₂), owing to its intrinsic reactive oxygen species (ROS)-scavenging capacity, has emerged as a promising neuroprotective candidate; however, the underlying molecular mechanisms remain insufficiently defined. Methods: Bovine serum albumin-templated MnO₂ nanoparticles (BSA-MnO₂ NPs) were synthesized, and their protective effects were evaluated in H₂O₂-treated PC12 cells. Results: BSA-MnO₂ NPs significantly inhibited H₂O₂-induced reductions in cell viability, ROS overproduction, and mitochondrial membrane potential disruption. Mechanistically, H₂O₂ increased both LC3-II and p62 levels, indicating impaired autophagic flux. Activation of autophagy by serum starvation alleviated H₂O₂-induced injury, whereas chloroquine exacerbated cellular damage and abolished the protective effects of BSA-MnO₂ NPs, suggesting that the restoration of autophagy contributes to BSA-MnO₂ NPs-mediated neuroprotection. Further analysis showed that BSA-MnO₂ NPs enhanced Akt phosphorylation, while LY294002, a PI3K inhibitor, suppressed Akt activation, disrupted autophagy regulation, and eliminated their neuroprotective effects. In contrast, chloroquine did not affect Akt phosphorylation, indicating that PI3K/Akt signaling acts upstream of autophagy regulation. Conclusions: Collectively, these findings demonstrate that BSA-MnO₂ NPs protect PC12 cells against H₂O₂-induced oxidative injury by restoring autophagy through the PI3K/Akt signaling pathway, highlighting a potential role of BSA-MnO₂ NPs in the treatment of oxidative-stress-related neurodegenerative disorders. Full article

Oxidative stress is a major physiological constraint on industrial lager yeast, compromising fermentation efficiency and flavor quality. Unsaturated fatty acids are known to influence membrane fluidity, but whether exogenous fatty acid supplementation can actively reprogram the yeast defense system, beyond serving as a passive membrane component, remains unclear. Here, we compared the effects of four fatty acids (palmitic, palmitoleic, oleic, and linoleic acid) on oxidative stress tolerance and fermentation performance in industrial lager yeast, under a defined chemical oxidative challenge (2.0 mM H₂O₂) in 15 °P wort, combining physiological assays with targeted gene-expression and untargeted metabolomic analyses; the dose was selected from a 0–2.0 mM gradient, with an ethanol-vehicle control included throughout. Among the fatty acids tested, palmitoleic acid (POA) most markedly enhanced oxidative stress tolerance, maintaining 91% cell viability, restoring intracellular pH to 6.1 by 24 h after transient acidification, and reducing ROS accumulation by 41.2%. Mechanistically, POA upregulated the antioxidant system, increasing catalase and glutathione peroxidase activities by 35.6% and 85.5%, respectively, and restoring glutathione levels by 35.5%. Metabolic profiling revealed a global reconfiguration, including a 2.6-fold increase in the stress-protectant proline and elevated pantothenate and coenzyme A levels, accompanied by a shift in the volatile profile toward esters, which rose from 26.1% to 60.3% of the total pool, alongside a 52.1% increase in total volatiles that did not reach significance after correction for multiple testing (q = 0.070); sensory evaluation confirmed higher fruity-estery intensity and lower soapy and staling notes in the POA beer. These findings identify POA as an active metabolic modulator, not merely a passive structural lipid, pointing to a non-transgenic nutritional strategy whose industrial value now requires validation under high-gravity, pilot-scale, and serial-repatching conditions. Full article

Pulmonary hypertension (PH) is a well-recognized complication of chronic hemolytic anemias such as sickle cell disease and thalassemia, yet the relative contributions of hypoxia and cell-free hemoglobin (Hb) to disease progression remain incompletely understood. Patients with hemolytic anemia experience a lifelong cycle of chronic and inter bitten hypoxia that compounds vascular injury driven by extracellular Hb and its degradation products, heme and iron. While the effects of hypoxia and Hb exposure have historically been studied in isolation, the combined impact of sustained, low-level plasma Hb together with chronic hypoxia—more representative of steady-state hemolysis—has been largely overlooked. A rat model incorporating chronic hypoxia with continuous low-dose Hb infusion via an implanted pump demonstrates that even modest plasma Hb concentrations (10–20 µM heme) exert an additive effect on hypoxia-induced PH. This effect is associated with increased adventitial macrophage accumulation, oxidative stress, and inflammation, driving more severe pulmonary vascular remodeling. Building on this model, therapeutic strategies targeting Hb-mediated vascular injury are evaluated, with particular focus on repeated-dose haptoglobin (Hp) therapy, given that Hp is often severely depleted in sickle cell disease. Restoring circulating Hp sequesters plasma Hb into a non-reactive, compartmentalized Hb–Hp complex, limiting NO scavenging and oxidative damage. These mechanistic findings are further linked to functional outcomes through studies of skeletal muscle microvascular oxygen tension and exercise capacity in Berkeley sickle cell disease mice. This review synthesizes findings across these studies to clarify the interplay between hypoxia, macrophage biology, and extracellular Hb in driving pulmonary vascular remodeling and to highlight emerging Hb-targeted therapeutic strategies for hemolysis-associated PH. Full article

Background: Aortic dissection (AD) is a life-threatening vascular disease with high mortality, yet its molecular pathogenesis remains incompletely understood. This study investigated the role of regulated in development and DNA damage responses 1 (REDD1) in vascular smooth muscle cells (VSMCs) apoptosis and the underlying mechanisms. Methods: Single-cell RNA sequencing data from GSE222318 were analyzed to investigate the expression levels of REDD1 in VSMCs and its role in inducing apoptosis and autophagy. The target gene was silenced in C57BL/6J mice via tail-vein injection of Adeno-associated virus.β-aminopropionitrile (BAPN) was used for AD induction. Western blotting was used to assess REDD1, LC3B, p62, BAX, BCL-2 in aortic tissues. Aortic histopathological alterations were examined by hematoxylin and eosin (H&E), Elastica van Gieson (EVG), and Masson’s trichrome staining. Immunofluorescence was performed to examine REDD1 expression and its localization in α-SMA-positive vascular smooth muscle cells. REDD1, LC3B, p62, BAX, BCL-2, mTOR, and p-mTOR were also examined by Western blotting in cultured cells. Mitochondrial membrane potential was evaluated by JC-1 staining, and apoptosis was assessed by flow cytometry. Results: REDD1 expression levels were significantly increased in human AD tissues and localized predominantly to medial VSMCs. REDD1 levels were positively correlated with BAX and LC3B and negatively correlated with BCL-2 and p62. Knockdown of REDD1 in AD mice was associated with increased levels of BAX and p62 and decreased levels of BCL-2 and LC3B in aortic tissues, accompanied by more severe pathological manifestations. REDD1 silencing in VSMCs increased BAX, p62 and p-mTOR while reducing BCL-2 and LC3B, accompanied by increased apoptosis and loss of mitochondrial membrane potential, whereas rapamycin reduced apoptosis and alleviated mitochondrial injury. Conclusions: REDD1 appears to play a protective, compensatory role in AD. Increased REDD1 expression may help preserve mitochondrial membrane potential and attenuate VSMC apoptosis under pathological stress, accompanied by changes in static autophagy-related markers that suggest a possible association with increased autophagic activity. Loss of REDD1 activity promotes mitochondrial injury and VSMC apoptosis, thereby aggravating AD. Targeting REDD1 may therefore represent a potential therapeutic strategy for AD. Full article

Sclerotinia sclerotiorum is a notoriously destructive, broad-host-range necrotrophic fungus responsible for devastating crop losses worldwide. Although genes encoding oxygenases are ubiquitous in fungal genomes, and the encoded enzymes play instrumental roles in driving diverse biochemical cascades, their specific functional repertoire in S. sclerotiorum pathogenesis remains poorly defined. Here, we characterize a contiguous pair of early-infection-induced oxygenase genes: SsOxy1 (encoding a 2-oxoglutarate-dependent oxygenase) and SsOxy2 (encoding a non-heme iron-dependent oxygenase). Targeted gene disruption demonstrated distinct developmental roles: ΔSsOxy1 mutants exhibited compromised vegetative growth (colony diameter reduced by approximately 18% to 27% at 24 h) and significantly diminished sclerotial biomass (ranging from approximately 8% to 28% reduction), whereas the absence of SsOxy2 selectively uncoupled the spatial regulation of sclerotial biogenesis without restricting radial growth. Importantly, both mutants displayed a severe decline in virulence across multiple hosts, with lesion diameters reduced by approximately 30% to 67% in ΔSsOxy1 and 62% to 66% in ΔSsOxy2 (p < 0.01).This attenuation was fundamentally linked to their inability to elaborate mature infection cushions, compounded by hypersensitivity to exogenous oxidative (H₂O₂) and hyperosmotic (NaCl) stresses. Untargeted metabolomics uncovered a profound metabolic reprogramming shared by both mutants, characterized by severe depletion of purine metabolism intermediates, including hypoxanthine (4.6–4.9-fold), xanthine (6.1–8.1-fold), and guanine (2.5–3.7-fold), alongside a disrupted glutathione redox pool (elevated GSSG: 3.0-fold in ΔSsOxy1 and 5.7-fold in ΔSsOxy2). Genomic colocalization combined with these metabolomic shifts suggests that SsOxy1 and SsOxy2 may function in a coordinated manner within a putative secondary metabolite biosynthetic gene cluster, although direct evidence for co-transcription and a shared product is currently lacking. Our findings provide novel mechanistic insights into how these paired oxygenases govern redox homeostasis, energy allocation, and the critical morphological transitions required for successful host colonization in S. sclerotiorum. Full article

Diabetes constitutes one of the major prevailing diseases worldwide, with cardiovascular pathologies as the primary cause of the morbidity and mortality rates reported. Hyperglycemia, the principal hallmark of diabetes, results from accumulated glucose levels. Although molecular mechanisms induced by high glucose (HG) have been extensively investigated, their complex interconnections and immediately activated signaling pathways remain unresolved. Hence, in the present study, we tried to identify effectors directly responsive to HG, focusing on the early activated signal transduction routes in H9c2 cardiac cells. MTT analysis illustrated the apoptosis- and oxidative-stress-mediated detrimental effect of 25 mM glucose on H9c2 viability. Initiation of oxidative-stress-related mechanisms was corroborated via detection of POR and HOX-1 augmented expression levels. Additionally, western blot analysis demonstrated activation of p38-MAPK and ERK1/2, along with autophagy- and ER-stress-related markers. Of note, involvement of biomechanical signaling players was also revealed, with Piezo1, connexin 43 and GJA1-20k expression being gradually enhanced. Intriguingly, ERK1/2 and ER-stress-associated effectors were observed to mediate connexin 43 and GJA1-20k upregulation. With connexins playing a nodal biological role in diabetes-driven cardiovascular pathologies, exploring potential modulatory effectors may provide insight into development of promising therapeutic interventions, favoring preservation of cell function and systems homeostasis under hyperglycemic conditions. Full article

Background/Objectives: Second-degree burns require strategies that address microbial contamination, oxidative stress, exudate, and tissue repair. This study aimed to develop and evaluate a marine-derived chitosan hydrogel incorporating ethanolic extract of propolis (EEP) from Chihuahua, Mexico, for second-degree burn management. Methods: EEP was characterized using parameters established in NOM-003-SAG/GAN-2017 and complementary biological assays. Chitosan hydrogels containing 1%, 3%, and 5% (w/w) EEP were evaluated for physicochemical properties, swelling, mass loss, flavonoid release, antioxidant activity, antimicrobial performance, and cell viability. The 1% EEP hydrogel was further evaluated in a murine second-degree burn model. Results: Chihuahua propolis exhibited high phenolic (27.42 ± 2.53%) and flavonoid (9.23 ± 0.314%) contents. EEP incorporation modified the chitosan matrix, providing high swelling capacity, increased structural persistence, sustained flavonoid release for 72 h, and radical-scavenging activity for 96 h. Antimicrobial activity was concentration-dependent, with the 5% EEP hydrogel reducing recoverable Escherichia coli counts below the detection limit (<10² CFU/mL). However, EEP-containing hydrogels reduced NIH-3T3 viability below the 70% ISO 10993-5 threshold under static extraction conditions. At 144 h, the 1% EEP hydrogel produced greater wound contraction than silver sulfadiazine (p = 0.021), although it did not differ significantly from the propolis-free chitosan hydrogel or untreated control. Qualitative histological assessment showed features consistent with early tissue repair, with cutaneous appendages observed in several sections from the 1% EEP group. Conclusions: Chihuahua propolis-loaded chitosan hydrogels showed promising physico-chemical, release, antioxidant, antimicrobial, and short-term in vivo findings. The in vitro reduction in metabolic activity observed under static extraction conditions warrants further evaluation using physiologically relevant exposure models, extended follow-up, and comprehensive safety assessment. Full article