Search Results (10,377)

Radiation-induced chronic wounds remain a major clinical challenge owing to persistent non-healing and progressive tissue degeneration. Rather than simply representing delayed wound repair, they arise from a self-perpetuating pathological cascade involving DNA damage, oxidative stress, chronic inflammation, microvascular dysfunction, cellular senescence, stem cell impairment, and fibrosis. Current clinical management remains largely supportive and symptomatic, with limited efficacy and no standardized therapeutic regimens targeting the core pathological mechanisms. Emerging strategies—antioxidant, antifibrotic, senolytic, stem cell/exosome-based, and functional biomaterial approaches—show promise. This review critically summarizes recent advances in pathogenic mechanisms and mechanism-based therapeutic strategies, highlighting current translational challenges and future directions for microenvironment-oriented regenerative therapies. Full article

Non-alcoholic fatty liver disease (NAFLD) induces renal injury via the liver–kidney axis, with oxidative stress as the core pathological mechanism. Apigenin (API) and aerobic exercise (AE) exhibit antioxidant and metabolic regulatory properties, but their combined renoprotective effect in NAFLD and the underlying mechanism remain poorly characterized. This study aimed to explore the protective efficacy of API combined with AE against NAFLD-associated renal damage and its association with the AMP-activated protein kinase (AMPK)/sirtuin 1 (SIRT1)/peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PGC-1α) pathway. A NAFLD mouse model was established via 12-week high-fat-diet feeding, followed by 8-week API intraperitoneal injection and/or treadmill AE intervention. Renal histology, biochemical parameters, inflammatory cytokines, tubular injury markers, and pathway molecules were examined. Combined intervention significantly reduced serum creatinine (SCr) and blood urea nitrogen (BUN), alleviated renal lipid accumulation, and attenuated oxidative stress and inflammation. It significantly downregulated the tubular injury marker KIM-1, and induced a downward trend in NGAL and L-FABP without statistical significance. The combined intervention also enhanced AMPK phosphorylation and upregulated SIRT1 and PGC-1α protein expression, with greater effects than single interventions and significant statistical interactions between the two interventions on these pathway molecules. These results suggest that API combined with AE attenuates NAFLD-related renal injury, and that this protective effect is associated with the upregulation of AMPK phosphorylation and SIRT1/PGC-1α protein expression, the significant statistical interaction between the two interventions suggests the potential involvement of this pathway in mediating renoprotection. These findings provide preliminary evidence for the association between the AMPK/SIRT1/PGC-1α pathway and the renoprotective effect of this combined intervention strategy. Full article

Background: Proton radiation is both a core component of the space radiation environment and a pivotal modality for precision clinical tumor radiotherapy. Proton exposure can impair cognitive, learning and memory functions, representing a common concern in the fields of deep space aerospace medicine and clinical radiotherapy. Nevertheless, the cellular and molecular regulatory mechanisms underlying proton-induced cognitive impairment remain incompletely elucidated. Methods: In vivo and in vitro injury models were established via 100 MeV proton radiation. Specifically, an in vivo model of proton radiation-induced cognitive injury was constructed using C57BL/6J mice (male), and an in vitro radiation injury model was established with HT22 hippocampal neuronal cells to systematically investigate the molecular mechanism of cognitive impairment caused by proton radiation. Results: Proton radiation induced a persistent decline in learning and memory capacity in mice, triggered systemic oxidative stress, caused metabolic disturbances of multiple neurotransmitters in the hippocampus, and induced structural mitochondrial damage and decreased mitochondrial membrane potential in hippocampal neurons, suggesting that mitochondria are the key subcellular target of its neurotoxicity. Proton radiation induced oxidative stress in hippocampal neurons. Hyperactivation of mTORC1 inhibited the kinase activity of ULK1 by phosphorylating its Ser757 residue and downregulated ULK1 protein levels, resulting in mitophagy dysfunction and mitophagic flux blockade. Persistent severe oxidative stress prevented damaged mitochondria from being cleared via mitophagy and activated the apoptotic cascade, ultimately leading to hippocampal neuronal death and cognitive impairment. Conclusions: This study reveals the molecular mechanism by which proton radiation induces mitophagy dysfunction and hippocampal neuronal apoptosis and subsequently triggers cognitive impairment, providing a new theoretical basis and potential intervention targets for the prevention and treatment of neurocognitive complications associated with space radiation exposure and clinical radiotherapy. Full article

Exogenous gonadotropin-based estrus synchronization is widely used in livestock reproduction. However, this hormonal treatment has been associated with adverse reproductive outcomes, suggesting that it may alter the uterine environment and endometrial receptivity, although the underlying molecular mechanism remains poorly understood. Here, we investigated the endometrial responses to gonadotropin-induced estrus synchronization using both in vivo and in vitro models. We found that gonadotropin treatment caused structural and inflammatory changes in the endometrium of both pigs and mice, accompanied by elevated circulating estradiol (E₂) levels and enhanced NLRP3 inflammasome-related signaling. In mice, gonadotropin treatment also altered the expression of MUC1, Hand2, and HoxA11, indicating disruption of molecular features associated with endometrial receptivity. In porcine endometrial epithelial cells, supraphysiological E₂ exposure induced mitochondrial oxidative stress, characterized by increased mitochondrial reactive oxygen species production, loss of mitochondrial membrane potential, increased cellular mtDNA abundance, and oxidative DNA damage. E₂ treatment further promoted NLRP3 inflammasome-associated signaling and ASC speck formation, whereas antioxidant N-acetyl-L-cysteine treatment attenuated ASC speck formation. Collectively, these findings support a link between high E₂ exposure, mitochondrial oxidative stress, and enhanced NLRP3 inflammasome signaling in endometrial epithelial cells. Our results suggest that an E₂–mitochondrial oxidative stress–NLRP3 axis may contribute to gonadotropin-associated endometrial dysfunction and provide a basis for further investigation of antioxidant and inflammasome-targeted strategies in livestock reproduction. Full article

Inflammation is a complex protective biological response triggered by harmful stimuli such as pathogens, chemical agents, or physical injury, and is closely associated with the development of pain and various chronic diseases. It involves a coordinated cascade of cellular and molecular events, including activation of pattern recognition receptors, release of pro-inflammatory cytokines, production of reactive oxygen species, and recruitment of immune cells. Acute inflammation is essential for host defense and tissue repair. However, persistent or dysregulated inflammation may lead to chronic inflammation, oxidative stress, and tissue damage. Inflammatory pain, a subtype of nociceptive pain, arises from the sensitization of peripheral and central nociceptive pathways by inflammatory mediators such as cytokines, prostaglandins, and nitric oxide. Herbal products have been traditionally used to manage inflammatory diseases due to their bioactive compounds, which modulate inflammatory pathways and alleviate symptoms, and gaining increasing attention due to their multi-targeted mechanisms and lower adverse effects. Polygonum minus (PM), a medicinal herb widely used in Southeast Asia, is rich in bioactive compounds including flavonoids, phenolics, polygodial and essential oils. Phytochemical studies have identified compounds such as qsiuercetin and myricetin, which exhibit strong antioxidant and anti-inflammatory properties. Experimental evidence suggested that PM exerts its anti-inflammatory effects through the inhibition of key inflammatory pathways, including cyclooxygenase (COX) and lipoxygenase (5-LOX), suppression of pro-inflammatory cytokines, and modulation of nuclear factor-kappa B (NF-κB) signaling. Additionally, its antioxidant activity contributes to the reduction in oxidative stress, thereby limiting inflammation-induced tissue damage. This review highlights the mechanisms the potential therapeutic role of PM in modulating underlying inflammation and inflammatory pain. The evidence suggested that PM may serve as a potential promising natural agent for the management of inflammation and pain. Further studies are warranted to elucidate its molecular mechanisms and to validate its efficacy and safety in clinical settings. Full article

Inflammation is a central pathological process in many chronic diseases and is closely linked to tissue injury and organ dysfunction. Although anti-inflammatory drugs are widely used in clinical practice, their long-term application can be limited by adverse effects and inadequate efficacy, creating a need for safer and more effective therapeutic approaches. Allicin, the principal bioactive organosulfur compound derived from garlic, has attracted increasing research interest because of its anti-inflammatory and antioxidant activities. Preclinical evidence indicates that allicin can attenuate inflammatory responses, inhibit inflammatory cell activation, reduce oxidative stress, and limit tissue damage in various disease models. Protective effects have been reported in models involving the digestive, respiratory, cardiovascular, urinary, and nervous systems. This review summarizes the preclinical evidence for the anti-inflammatory effects of allicin across these organ systems, focusing on the underlying molecular mechanisms, shared signaling pathways, and organ-associated features. The chemical instability, rapid metabolism, and poor oral bioavailability of allicin remain important barriers to clinical translation, while high-quality clinical evidence from studies of purified allicin in humans remains limited. These challenges, together with potential strategies for overcoming them, are also discussed. Full article

Background/Objectives: A chronic neurological disorder known as epilepsy results in neurodegeneration, oxidative stress, and damage to the retina and the central nervous system’s structure. The main objective of this research was to examine the neuroprotective benefits of Resveratrol (RES) on the retina in a model using Pentylenetetrazol (PTZ) in rats to induce kindling and to investigate the underlying molecular and biochemical mechanisms (SIRT1, GFAP, VEGF, apoptotic pathways, and oxidative stress markers [malondialdehyde (MDA) and reduced glutathione (GSH)] of this protective effect. Methods: A total of thirty-two male Wistar albino rats were randomly assigned to four distinct groups: Sham, RES (5 mg/kg/day), PTZ (35 mg/kg), and PTZ + RES (n = 8 per group). Electrocorticography (ECoG) recordings were used to assess seizure severity. Retinal expression of GFAP, VEGF, SIRT1, Bax, Bcl-2, Caspase-3, and Caspase-9 was evaluated via qPCR and immunofluorescence, while tissue lipid peroxidation (MDA) and reduced glutathione (GSH) levels were quantified spectrophotometrically to directly evaluate retinal redox status. Results: Substantial increases in seizure scores and electrocorticogram spike counts were noted in the PTZ group, whereas RES treatment significantly reduced the total ECoG spike count by 49.6% (from 702.87 ± 145.82 in PTZ to 354.25 ± 31.22 in PTZ + RES, p < 0.0001) and lowered the average seizure stage from 4.25 ± 0.27 to 2.43 ± 0.49 (p < 0.05), while lengthening the initial myoclonic jerk latency (from 162 ± 29.62 s to 219.37 ± 32.12 s, p < 0.01). Molecular and histopathological analyses revealed that RES treatment was associated with enhanced localized retinal cell survival and a significant increase in the nuclear SIRT1 immunofluorescence area fraction in the retina, which more than doubled the nuclear SIRT1 immunofluorescence area fraction in the retina (from 4.2 ± 0.9% in PTZ to 8.4 ± 0.8% in PTZ + RES, p < 0.05) despite a physiological transcription-level feedback reduction in SIRT1 mRNA. Furthermore, RES treatment significantly suppressed PTZ-induced retinal apoptosis (Caspase-3 area fraction decreased from 10.6 ± 0.9% to 5.6 ± 0.8%, p < 0.001) and attenuated reactive gliosis (GFAP area fraction decreased from 14.1 ± 1.2% to 9.1 ± 1.4%, p < 0.01). Biochemically, PTZ kindling induced a profound increase in retinal lipid peroxidation (MDA) and a severe depletion of reduced glutathione (GSH) reserves, both of which were robustly reversed by RES treatment back toward physiological Sham levels (p < 0.01). Conclusions: Chronic epilepsy causes glial activation, oxidative damage, and apoptosis in the retina, with RES-associated retinal protection involving the restoration of redox homeostasis and the upregulation of the SIRT1 signaling pathway. These preclinical findings suggest that RES represents a promising protective strategy against epilepsy-associated retinal damage, though further clinical validation is warranted to establish its therapeutic safety and efficacy in human patients. Full article

Nasopharyngeal carcinoma (NPC) is a geographically distinct malignancy closely associated with Epstein–Barr virus (EBV) infection and characterized by extensive epigenetic reprogramming within a highly immunosuppressive tumor microenvironment (TME). High-mobility group box 1 (HMGB1), a multifunctional chromatin-binding protein that can also act as an extracellular damage-associated molecular pattern (DAMP), has emerged as an important regulator of genome organization, transcriptional control, cellular stress responses, and immune signaling. Increased HMGB1 expression has been reported in NPC and is associated with adverse clinicopathological features and poor patient outcomes. Emerging evidence suggests that the diverse biological functions of HMGB1 are influenced by post-translational modifications (PTMs), which affect its subcellular localization, molecular interactions, and extracellular signaling functions. Through these regulatory mechanisms, HMGB1 may transition from a nuclear chromatin-associated protein to an extracellular mediator of immune and inflammatory responses. PTMs including acetylation, phosphorylation, glycosylation, oxidation, methylation, and lactylation have been implicated in regulating HMGB1 trafficking and function, although the specific roles of many of these modifications in NPC remain incompletely characterized. In this review, we summarize current evidence regarding HMGB1 PTMs and discuss their potential implications for EBV-associated NPC, with emphasis on nuclear regulation, immune crosstalk, and therapeutic response. We explicitly distinguish findings directly demonstrated in NPC from mechanistic insights derived from other malignancies and related disease models, and identify areas where proposed mechanisms remain hypothesis-generating rather than experimentally validated in NPC. By integrating current evidence with emerging mechanistic concepts, we highlight key knowledge gaps, unresolved questions, and priorities for future research. A better understanding of PTM-dependent HMGB1 regulation may facilitate the development of novel biomarker and therapeutic strategies for EBV-associated NPC. 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

Salinity disrupts plant redox balance, ion homeostasis, and water relations, and exogenous polyamines have been widely investigated as potential mitigators of these effects. However, it remains unclear which polyamine-mediated responses are reproducible across independent studies and whether redox protection consistently translates into downstream physiological recovery. We therefore conducted an integrated systematic review, evidence map, and publication-family-aware quantitative synthesis to evaluate the effects of exogenous putrescine, spermidine, and spermine in salt-stressed plants. We systematically searched Scopus and Web of Science through 9 August 2026, and eligible studies compared exogenous-polyamine-treated plants with corresponding salt-stressed controls. The review was not prospectively registered. Of 1093 records, 647 unique records were screened, and 179 reports were assessed in full text, yielding 34 retained reports and 444 complete quantitative contrasts. Multilevel random-effects models estimated reductions of 19.2% in malondialdehyde (95% confidence interval [CI], 12.9–25.1%) and 25.6% in hydrogen peroxide (H₂O₂; 95% CI, 15.5–34.6%). Superoxide showed a protective mean response but remained uncertain because its 95% CI included the null. In contrast, antioxidant-enzyme responses varied widely across studies, with no consistent cross-family increase in superoxide dismutase (SOD), catalase (CAT), ascorbate peroxidase (APX), or peroxidase (POD/POX) activity. Conservative independent-family syntheses supported favorable ion balance, modestly higher relative water content, and greater dry biomass, whereas total chlorophyll remained uncertain and net photosynthesis was highly heterogeneous. No clear superiority of putrescine, spermidine, or spermine was detected. Overall, exogenous polyamines most consistently reduced oxidative damage and stabilized ion–water homeostasis, whereas antioxidant–enzyme activity and photosynthetic recovery were more context-dependent. Interpretation is limited by small independent-family counts, incomplete reporting in some studies, and the absence of a formal study-level risk-of-bias assessment. By integrating systematic review, evidence mapping, and family-aware quantitative synthesis, this review provides an evidence-based hierarchy that distinguishes reproducible polyamine-mediated responses from context-dependent outcomes and helps define priorities for future salinity-tolerance research. Full article

The functions of most proteins encoded by the African swine fever virus (ASFV) remain largely unknown, although several have been reported to possess immunomodulatory properties. Among these, we identified that the DP71L protein exerts an inhibitory effect on inflammatory bowel disease. To investigate its protective role in murine colitis, we constructed and expressed a recombinant DP71L protein. Colitis was induced in mice using DSS, and the effects of DP71L treatment were evaluated by assessing histopathological changes, inflammatory cytokine profiles, oxidative stress markers, colonic tissue pathology, and the expression of tight-junction proteins (claudin-1, occludin, and ZO-1). Our results showed that DP71L intervention significantly attenuated body weight loss and organ damage and ameliorated DSS-induced colonic histopathological injury. Moreover, DP71L treatment markedly increased superoxide dismutase (SOD) activity and reduced malondialdehyde (MDA) content in colonic tissues. Mechanistically, DP71L suppressed both DSS-induced NF-κB and JAK-STAT activation and concurrently inhibited DSS-induced epithelial cell apoptosis. These events likely underlie the observed reduction in pro-inflammatory cytokines (IL-1β, IL-6, IFN-γ, and TNF-α) and the restoration of tight-junction protein expression, as DP71L treatment effectively prevented DSS-induced downregulation of claudin-1, occludin, and ZO-1, while also promoting the anti-inflammatory cytokines IL-10 and TGF-β. Collectively, our findings demonstrate that DP71L effectively inhibits the progression of murine colitis through coordinated anti-inflammatory and anti-apoptotic mechanisms. This study suggests that DP71L may function as a potential immunosuppressant, opening new avenues for the application of viral proteins in the treatment of immune-related disorders. Full article

Oral lichen planus (OLP) is a chronic T cell-mediated inflammatory disorder characterized by recurrent epithelial injury and incomplete inflammatory resolution. Cellular senescence and the senescence-associated secretory phenotype may help explain how stromal cells sustain this inflammatory circuit. This narrative review critically evaluates direct and indirect evidence linking senescence to OLP. A focused search of PubMed/MEDLINE, Scopus, and Web of Science through 31 July 2026 identified evidence localizing senescence-associated signatures predominantly to PDGFRα-positive mesenchymal cells. The available multimodal study also reported enhanced CXCL12–CXCR4 and extracellular matrix–CD44 communication toward CD8-positive T cells and showed that conditioned medium from experimentally induced senescent fibroblasts increased lymphoid-cell activation and keratinocyte injury in non-oral and immortalized cell models. Earlier studies of p16, p21, p53, altered cyclin-dependent kinases, oxidative/nitrative DNA damage, and SASP-compatible cytokines provide supportive evidence but are insufficient to establish cellular senescence. We hypothesize a feed-forward model in which persistent oxidative and cytokine stress induces senescence in mesenchymal and possibly epithelial cells. A context-dependent SASP may recruit and activate cytotoxic lymphocytes, promote basal keratinocyte damage, and propagate further cellular stress. Further progress will require spatially resolved multi-marker validation and functional testing in primary oral-cell models before biomarker-guided clinical trials can be considered. These advances may ultimately support the development of novel targeted therapies for OLP. Full article

Obesity is recognized as a pathological condition that induces chronic low-grade systemic inflammation capable of affecting multiple organs, including the central nervous system, thereby promoting neuroinflammation. Although adipose and neural tissues differ in their structural and functional characteristics, they share common inflammatory mechanisms involving the TLR4/NF-κB/MAPK signaling pathways, the ROS/NRF2 axis, and the NLRP3 inflammasome. This review summarizes current evidence demonstrating the ability of berberine (BBR) to modulate these shared molecular pathways across different experimental models and pathophysiological conditions, with particular emphasis on obesity-induced neuroinflammation. A narrative literature search was conducted using academic search and indexing resources, including PubMed, Scopus, Web of Science, and Google Scholar, with the literature updated through 24 August 2026. The available evidence indicates that BBR modulates these signaling pathways, reduces the production of pro-inflammatory cytokines, attenuates oxidative stress, and limits glial activation. Furthermore, several studies suggest that BBR may help preserve the functional integrity of the blood–brain barrier and reduce neuronal damage associated with neuroinflammatory processes. Available evidence suggests that BBR may modulate inflammatory and oxidative pathways involved in obesity-associated neuroinflammation; however, current findings derive mainly from preclinical studies and indirect models. Future studies are needed to determine the bioavailability, central nervous system penetration, and clinical relevance of BBR. 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

Chronic administration of L-methionine (L-met) induces hyperhomocysteinemia, which triggers oxidative stress, impairs hippocampal neurogenesis and ultimately causes cognitive decline. Caffeic acid (CA) has been reported to exert neuroprotective effects through its antioxidant properties, attenuating oxidative damage in the brain, promoting hippocampal neurogenesis, and improving cognitive function. This study evaluated the neuroprotective efficacy of CA against L-met-mediated hyperhomocysteinemia and associated hippocampal neurotoxicity in a rat model. Twenty-four male Sprague-Dawley rats were randomly divided into four groups (n = 6/group): Vehicle, L-met (1.7 g/kg), CA (40 mg/kg), and CA + L-met. Treatments were administered orally once daily for 28 days. Immunofluorescence analysis revealed that CA effectively prevented L-met-induced depletion of nestin-positive cells. Structural assessments further confirmed that CA counteracted tissue atrophy, preserving the anatomical volumes of both the dentate gyrus (DG) and granule cell layer (GCL). Furthermore, CA attenuated the L-met-induced downregulation of the neurogenesis-related proteins nestin and Notch-1 in the hippocampus. Notably, CA also modulated apoptosis-related protein expression by reducing Bax and Caspase-3 levels while upregulating Bcl-2 expression. In conclusion, CA was associated with protection against L-met-induced alterations in hippocampal neurogenesis- and apoptosis-related protein expression, as well as preservation of hippocampal architecture, in this experimental model. Full article