Search Results (1,471)

Using light-emitting diodes (LEDs), we examined how different light wavelengths influence the hypersensitive response (HR) in tobacco plants infected with Pseudomonas syringae pv. tomato (Pst). Pst-infiltrated plants exhibited greater resistance to Pst infection under green and blue light compared to white and red light, as indicated by reduced HR-associated programmed cell death, lower H₂O₂ production, and up to 64% reduction in membrane damage. During the late stage of HR, catalase and ascorbate peroxidase activities peaked under green and blue LEDs, with 5- and 10-fold increases, respectively, while superoxide dismutase activity was higher under white and red LEDs. Defense-related genes CHS1, PALa, PR1, and PR2 were more strongly induced by white and red light. The plants treated with green or blue LEDs during Pst infection prompted faster degradation of phototoxic Mg-porphyrins and exhibited smaller declines in F_v/F_m, electron transport rate, chlorophyll content, and LHCB expression compared to those treated with white or red LEDs. By contrast, the induction of the chlorophyll catabolic gene SGR was 54% and 77% lower in green and blue LEDs, respectively, compared to white LEDs. This study demonstrates that light quality differentially affects Pst-mediated HR, with green and blue light more effectively suppressing HR progression, mainly by reducing oxidative stress through enhanced antioxidative capacity and mitigation of photosynthetic impairments. Full article

Fungi, from saprophytes to pathogens, face predictable daily fluctuations in light, temperature, humidity, and nutrient availability. To cope, they have evolved an internal circadian clock that confers a major adaptive advantage. This review critically synthesizes current knowledge on the molecular architecture and physiological relevance of fungal circadian systems, moving beyond the canonical Neurospora crassa model to explore the broader phylogenetic diversity of timekeeping mechanisms. We examine the core transcription-translation feedback loop (TTFL) centered on the FREQUENCY/WHITE COLLAR (FRQ/WCC) system and contrast it with divergent and non-canonical oscillators, including the metabolic rhythms of yeasts and the universally conserved peroxiredoxin (PRX) oxidation cycles. A central theme is the clock’s role in gating cellular defenses against oxidative, osmotic, and nutritional stress, enabling fungi to anticipate and withstand environmental insults through proactive regulation. We provide a detailed analysis of chrono-pathogenesis, where the circadian control of virulence factors aligns fungal attacks with windows of host vulnerability, with a focus on experimental evidence from pathogens like Botrytis cinerea, Fusarium oxysporum, and Magnaporthe oryzae. The review explores the downstream pathways—including transcriptional cascades, post-translational modifications, and epigenetic regulation—that translate temporal signals into physiological outputs such as developmental rhythms in conidiation and hyphal branching. Finally, we highlight critical knowledge gaps, particularly in understudied phyla like Basidiomycota, and discuss future research directions. This includes the exploration of novel clock architectures and the emerging, though speculative, hypothesis of “chrono-therapeutics”—interventions designed to disrupt fungal clocks—as a forward-looking concept for managing fungal infections. Full article

Poliovirus represents an oncolytic agent for human glioblastoma—one of the most aggressive types of cancer. Since interference of viruses with metabolic and redox pathways is often linked to their pathogenesis, drugs targeting metabolic enzymes are regarded as potential enhancers of oncolysis. Our goal was to reveal an imprint of poliovirus on the metabolism of glioblastoma cell lines and to assess the dependence of the virus on these pathways. Using GC-MS, HPLC, and Seahorse techniques, we show that poliovirus interferes with amino acid, purine and polyamine metabolism, mitochondrial respiration, and glycolysis. However, many of these changes are cell line- and culture medium-dependent. 2-Deoxyglucose, the pharmacologic inhibitor of glycolysis, was shown to enhance the cytopathic effect of poliovirus, pointing to its possible repurposing as an enhancer of oncolysis. Inhibitors of polyamine biosynthesis, pyruvate import into mitochondria, and fatty acid oxidation exhibited antiviral activity, albeit in a cell-dependent manner. We also demonstrate that poliovirus does not interfere with the production of superoxide anions or with levels of H₂O₂, showing an absence of oxidative stress during infection. Finally, we showed that a high rate of poliovirus replication is associated with fragmentation of the mitochondrial network, pointing to the significance of these organelles for the virus. Full article

Aging is associated with complex immune dysfunction that contributes to the onset and progression of the “geriatric giants”, including frailty, sarcopenia, cognitive decline, falls, and incontinence. Central to these conditions is immunosenescence, marked by thymic involution, the loss of naïve T cells, T-cell exhaustion, impaired B-cell class switch recombination, and increased autoreactivity. Concurrently, innate immunity deteriorates due to macrophage, neutrophil, and NK cell dysfunction, while chronic low-grade inflammation—or “inflammaging”—amplifies systemic decline. Key molecular pathways such as NF-κB, mTOR, and the NLRP3 inflammasome mediate immune aging, interacting with oxidative stress, mitochondrial dysfunction, and epigenetic modifications. These processes not only impair infection control and vaccine responsiveness but also promote tissue degeneration and multimorbidity. This review explores emerging interventions—ranging from senolytics and immunonutrition to microbiome-targeted therapies and exercise—that may restore immune homeostasis and extend healthspan. Despite advances, challenges remain in translating immunological insights into clinical strategies tailored to older adults. Standardization in microbiome trials and safety optimization in senolytic therapies are critical next steps. Integrating geroscience into clinical care could help to mitigate the burden of aging-related diseases by targeting fundamental drivers of immune dysfunction. Full article

The increasing threat of antimicrobial resistance (AMR), along with the limited availability of new lead compounds in the drug development pipeline, highlights the urgent need to discover antimicrobial agents with innovative mechanisms of action. In this regard, metal complexes offer a unique opportunity to access mechanisms distinct from those of conventional antibiotics. Although iron (Fe) is an essential element for all forms of life, including pathogenic bacteria, it also poses a serious risk of cytotoxicity due to its redox activity, which can trigger the production of reactive oxygen species (ROS) via the Fenton reaction. This review highlights recent advances in the development of iron-based antimicrobial agents that harness the toxicity resulting from dysregulated iron uptake, thereby inducing bacterial cell death through oxidative stress. These findings may guide the development of effective treatments for pathogenic infections and offer new perspectives on leveraging redox chemistry of iron to combat the growing threat of global bacterial resistance. Full article

Enterotoxigenic Escherichia coli (ETEC) leads to severe diarrhea in piglets. Naringenin (Nar), a natural flavonoid compound, is known for its antibacterial and anti-antioxidant properties. However, the protective effects of Nar against ETEC-induced diarrhea have not been reported yet. This study investigated the protective mechanisms of Nar against ETEC infection in porcine intestinal epithelial cells (IPEC-J2). ETEC infection induced oxidative stress and ferroptosis in IPEC-J2 cells by elevating intracellular iron content and ROS accumulation, increasing MDA levels, downregulating SOD activity and GPX4 expression, and upregulating the transcription of CHAC1 and SLC7A11. In contrast, Nar suppressed ETEC-induced ferroptosis of IPEC-J2 cells by inhibiting the SLC7A11/GPX4 pathway. Specifically, Nar mitigated mitochondrial damage, reduced intracellular iron levels and ROS accumulation, and ultimately reversed the oxidative stress. Network pharmacology and molecular docking identified heat-shock protein 90 (HSP90) as a potential target of Nar. Overexpression and knockdown experiments revealed that ETEC-induced ferroptosis was mediated by upregulation of HSP90, while the protective effects of Nar against ETEC-induced ferroptosis were dependent on the downregulation of HSP90. In conclusion, Nar targets host HSP90 to protect IPEC-J2 cells from ferroptosis caused by ETEC infection. This study demonstrates that Nar is a potent antioxidant natural compound with potential for preventing ETEC-induced intestinal damage. Full article

Although platelets have been traditionally thought of to be essential hemostasis mediators, new research shows how important they are for controlling cellular oxidative stress, inflammatory processes, and immunological responses—particularly during major surgery on the abdomen. Perioperative problems are largely caused by the continually changing interaction of inflammatory cytokines, the formation of reactive oxygen species (ROS), and platelet activation. The purpose of this review is to summarize the most recent data regarding the complex function of platelets in abdominal surgery, with an emphasis on how they interact with inflammation and oxidative stress, and to investigate the impact on postoperative therapy and subsequent studies. Recent study data on platelet biology, redox signals, surgical stress, and antiplatelet tactics was reviewed in a systematic manner. Novel tailored therapies, perioperative antiplatelet medication, oxidative biomarkers of interest, and platelet-derived microscopic particles are important themes. In surgical procedures, oxidative stress dramatically increases the reactive capacity of platelets, spurring thromboinflammatory processes that affect cardiac attacks, infection risk, and recovery. A number of biomarkers, including soluble CD40L, thromboxane B2, and sNOX2-derived peptide, showed potential in forecasting results and tailored treatment. Antiplatelet medications are still essential for controlling risk factors for cardiovascular disease, yet using them during surgery necessitates carefully weighing the risks of thrombosis and bleeding. Biomarker-guided therapies, antioxidant adjuncts, and specific platelet inhibitors are examples of evolving tactics. In abdominal procedures, platelets strategically operate at the nexus of oxidative stress, inflammatory processes, and clotting. Improved patient classification, fewer problems, and the creation of individualized surgical care strategies could result from an increased incorporation of platelet-focused tests and therapies into perioperative processes. To improve clinical recommendations, subsequent studies may want to focus on randomized studies, biomarker verification, and using translational approaches. Full article

Background/Objectives: The liver, the body’s primary detoxifying organ, is often affected by various inflammatory diseases, including hepatitis, cirrhosis, and non-alcoholic fatty liver disease (NAFLD), many of which can be exacerbated by secondary infections such as spontaneous bacterial peritonitis, bacteremia, and sepsis—particularly in patients with advanced liver dysfunction. The global rise in these conditions underscores the need for effective interventions. Natural products have attracted attention for their potential to support liver health, particularly through synergistic combinations of plant extracts. Epavin, a dietary supplement from Erbenobili S.r.l., formulated with plant extracts like Taraxacum officinale (L.), Silybum marianum (L.) Gaertn., and Cynara scolymus (L.), known for their liver-supporting properties, has been proposed as adjuvant for liver functions. The aim of this work was to evaluate of Epavin’s antioxidant, anti-inflammatory, and protective effects against heavy metal-induced toxicity. In addition, the antibacterial effect of Epavin against a panel of bacterial strains responsible for infections associated with liver injuries has been evaluated. Methods: The protection against oxidative stress induced by H₂O₂ was evaluated in HepG2 and BALB/3T3 cells using the dichlorofluorescein diacetate (DCFH-DA) assay. Its anti-inflammatory activity was investigated by measuring the reduction in nitric oxide (NO) production in LPS-stimulated RAW 264.7 macrophages using the Griess assay. Additionally, the cytoprotecting of Epavin against heavy metal-induced toxicity and oxidative stress were evaluated in HepG2 cells using the [3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-tetrazolium bromide] (MTT) and DCFH-DA assays. The antibacterial activity of Epavin was assessed by determining the minimum inhibitory concentration (MIC) and the minimum bactericidal concentration (MBC) against Gram-positive (Enterococcus faecalis ATCC 29212, and BS, Staphylococcus aureus 25923, 29213, 43300, and BS) and Gram-negative (Escherichia coli 25922, and BS, Klebsiella pneumoniae 13883, 70063, and BS) bacterial strains using the microdilution method in broth, following the Clinical and Laboratory Standards Institute’s (CLSI) guidelines. Results: Epavin effectively reduced oxidative stress in HepG2 and BALB/3T3 cells and decreased NO production in LPS-stimulated RAW 264.7 macrophages. Moreover, Epavin demonstrated a protective effect against heavy metal-induced toxicity and oxidative damage in HepG2 cells. Finally, it exhibited significant antibacterial activity against both Gram-positive and Gram-negative bacterial strains, with MIC values ranging from 1.5 to 6.0 mg/mL. Conclusions: The interesting results obtained suggest that Epavin may serve as a valuable natural adjuvant for liver health by enhancing detoxification processes, reducing inflammation, and exerting antibacterial effects that could be beneficial in the context of liver-associated infections. Full article

Penicillium expansum is an acidogenic fungal species that belongs to the phylum Ascomycota. During the infection and colonization of host fruits, P. expansum can efficiently express glucose oxidase (GOX) and oxidize β-D-glucose to generate gluconic acid (GLA). In this study, the bioinformatics analysis method was employed to predict and analyze the function of the GOX protein. In addition, a comprehensive assessment was conducted on the P. expansum GOX coding gene GOX2, and the expression response rules of GOX2 under different external stress environments were explored. The results show that GOX is an unstable hydrophilic protein. It is either an integrated membrane protein (such as a receptor or channel) that is directly anchored to the membrane through a transmembrane structure or a non-classical secreted protein that is secreted extracellularly. RNA-seq data analysis shows that the GOX2 gene is regulated by multiple environmental factors, including pH, temperature, carbon base, and chemical fungicides. The expression level of GOX2 reaches its maximum value under alkaline conditions (pH 8–10) and at approximately 10 °C. Using starch as the carbon source and adding sodium propionate or potassium sorbate has the effect of inhibiting the expression of the GOX2 gene. The analysis of the function of the GOX protein and the characteristics of the GOX2 gene in P. expansum provides new insights into the glucose oxidase-encoding gene GOX2. The research results provide significant value for the subsequent development of new disease resistance strategies by targeting the GOX2 gene and reducing post-harvest disease losses in fruits. Full article

Korean rockfish, Sebastes schlegeli, a coastal species, is vulnerable to pollutants such as microplastics and bacteria. While interactions between microplastics and other pollutants have been studied, little is known about microplastic and bacteria interactions. This study examined the effects of combined exposure to polystyrene microplastics in the form of microbeads (MB; 0.2 µm, 5 and 50 beads/L) and Streptococcus iniae (1 × 10⁵ and 1 × 10⁷ CFU/mL) for five days on oxidative stress and apoptosis in Korean rockfish. We assessed the mRNA expression and activity of oxidative stress markers (SOD, CAT, H₂O₂, NO, CYP1A1, GST), plasma LPO levels, and caspase-3 expression in liver tissue. Co-exposure to high MB and S. iniae concentrations significantly elevated oxidative stress and apoptosis markers, suggesting enhanced toxicity. This may result from MB facilitating pathogen transport into the fish, indicating microplastics can act as vectors for bacterial infection in aquatic environments. Full article

The distinctive nature of ferroptosis is that it is induced chemically and signifies a regulated cell death dependent on iron-dependent lipid peroxidation. The mechanism of ferroptosis involves oxidative damage to the membrane lipids. It differs from apoptosis and necroptosis, triggering metabolic changes in the iron-lipid homeostasis and antioxidant defense, such as glutathione (GSH) and glutathione peroxidase 4 (GPX4). Herein, the molecular mechanisms of ferroptosis and its role in the tumorigenesis process and infection-related diseases are presented. It also discusses metabolic reprogramming as a factor that modifies the levels of cell-sensitizing polyunsaturated fatty acids (PUFAs), iron dysregulation, and oxidative stress in aggressive cancers and inflammatory diseases such as sepsis, tuberculosis, and COVID-19. Particular attention is given to chemical modulators of ferroptosis, including synthetic inducers and inhibitors, as well as bioactive natural compounds. Our focus is on the significance of analytical tools, such as lipidomics and metabolomics, in understanding the phenomenon of ferroptosis. Finally, we explore novel therapeutic approaches targeting ferroptosis in cancer and infectious diseases, while navigating both the opportunities and challenges in drug development. The review then draws on chemical biology and disease pathology to propose promising areas of study for ferroptosis-related therapies. Full article

Diabetic foot ulcers (DFUs), which affect approximately 15% of individuals with diabetes mellitus (DM), result from complex molecular disturbances involving chronic hyperglycemia, immune dysfunction, and infection. At the molecular level, chronic hyperglycemia promotes the formation of advanced glycation end products (AGEs), activates the AGE-RAGE-NF-κB axis, increases oxidative stress, and impairs macrophage polarization from the pro-inflammatory M1 to the reparative M2 phenotype, collectively disrupting normal wound healing processes. The local wound environment is further worsened by antibiotic-resistant polymicrobial infections, which sustain inflammatory signaling and promote extracellular matrix degradation. The rising threat of antimicrobial resistance complicates infection management even further. Recent studies emphasize that optimal glycemic control using antihyperglycemic agents such as metformin, Glucagon-like Peptide 1 receptor agonists (GLP-1 receptor agonists), and Dipeptidyl Peptidase 4 enzyme inhibitors (DPP-4 inhibitors) improves overall metabolic balance. These agents also influence angiogenesis, inflammation, and tissue regeneration through pathways including AMP-activated protein kinase (AMPK), mechanistic target of rapamycin (mTOR), and vascular endothelial growth factor (VEGF) signaling. Evidence indicates that maintaining glycemic stability through continuous glucose monitoring (CGM) and adherence to antihyperglycemic treatment enhances antibiotic effectiveness by improving immune cell function and reducing bacterial virulence. This review consolidates current molecular evidence on the combined effects of glycemic and antibiotic therapies in DFUs. It advocates for an integrated approach that addresses both metabolic and microbial factors to restore wound homeostasis and minimize the risk of severe outcomes such as amputation. Full article

Respiratory infections caused by severe acute respiratory syndrome coronavirus 2, influenza virus, and respiratory syncytial virus pose significant global health challenges, leading to high morbidity and mortality, particularly in vulnerable populations. Despite their distinct virological characteristics, these viruses exploit host cellular metabolism to support replication, modulate immune responses, and promote disease progression. Emerging evidence shows that they induce metabolic reprogramming, shifting cellular energy production toward glycolysis to meet the bioenergetic demands of viral replication. Additionally, alterations in lipid metabolism, including enhanced fatty acid synthesis and disrupted cholesterol homeostasis, facilitate viral entry, replication, and immune evasion. The dysregulation of mitochondrial function and oxidative stress pathways also contributes to disease severity and long-term complications, such as persistent inflammation and immune exhaustion. Understanding these metabolic shifts is crucial for identifying new therapeutic targets and novel biomarkers for early disease detection, prognosis, and patient stratification. This review provides an overview of the metabolic alterations induced by severe acute respiratory syndrome coronavirus 2, influenza virus, and respiratory syncytial virus, highlighting shared and virus-specific mechanisms and potential therapeutic interventions. Full article

Background/Objectives: Inflammation is a crucial and complex mechanism that protects the body against infections. In our study, we propose to provide scientific evidence for the anti-inflammatory properties of 1,3,5-triazine derivatives. Methods: Initially, we ensured the safety of the three synthesized derivatives by administering graded doses of up to 2000 mg/kg intraperitoneally in Wistar rats. Thus, the three derivatives were considered generally safe. We also evaluated their ability to reduce carrageenan-induced rat paw edema. Results: Compounds 1, 2, and 3 demonstrated stronger anti-inflammatory activity than indomethacin (10 mg/kg), achieving maximum inhibition at the fourth hour with percentages of 96.31%, 72.08%, and 99.69%, respectively, at a dose of 200 mg/kg, compared to 57.66% for the standard drug. To explore the mechanism, levels of pro-inflammatory cytokines (TNF-α, IL-1α, IL-1β, IL-6, CRP) and oxidative stress markers were measured in paw tissue. All three compounds significantly reduced these markers more effectively than indomethacin and enhanced antioxidant levels (SOD and GSH) beyond those achieved by the standard treatment. Additionally, the compounds reduced COX-1 and COX-2 levels to values comparable to those in the normal (non-inflamed) control group. Conclusions: Compounds 1, 2, and 3 at doses of 200 mg/kg significantly (p  < 0.05) inhibited the heat-induced hemolysis of red blood cell (RBC) membranes by 94.6%, 93.9%, and 95.2%, respectively, compared to 94.5% produced by indomethacin. Consequently, we concluded that 1,3,5-triazine derivatives are a safe antioxidant agent with significant anti-inflammatory activity. Full article

The “milky disease” in Chinese mitten crabs (Eriocheir sinensis), caused by Metschnikowia bicuspidata, poses significant threats to aquaculture, though its pathogenic mechanisms remain poorly understood. This study employs transcriptomic sequencing to analyze gene expression changes in Metschnikowia bicuspidata under hemocyte challenge, iron overload (1 mmol/mL), and combined stress, with functional validation through Common in Fungal Extracellular Membrane (CFEMgene) overexpression strains. Key findings reveal that (1) hemocyte challenge activated base excision repair (−log₁₀[P] = 7.58) and ribosome biogenesis pathways, indicating fungal adaptation through DNA repair and enhanced protein synthesis to counter host immune attacks (e.g., ROS-mediated damage). (2) Iron overload induced glutathione metabolism and pentose phosphate pathway enrichment, demonstrating mitigation of ferroptosis through NADPH/GSH antioxidant systems and autophagy/proteasome coordination. (3) Under combined stress, ribosome biogenesis (−log₁₀[P] = 1.3) and non-homologous end-joining pathways coordinated DNA repair with stress protein synthesis, complemented by vacuolar V-ATPase-mediated iron compartmentalization. (4) CFEM genes showed significant upregulation under hemocyte stress, with overexpression strains exhibiting enhanced biofilm formation (35% increased MTT cytotoxicity) and infectivity (40% higher infection rate), confirming CFEM domains mediate pathogenesis through iron homeostasis and virulence factor production. This work elucidates how M. bicuspidata employs metabolic reprogramming, oxidative stress responses, and CFEM-mediated iron regulation to establish infection, providing critical insights for developing targeted control strategies against milky disease. Full article