Search Results (1,050)

Oral squamous cell carcinoma (OSCC) frequently develops within chronically injured oral mucosa and may be preceded by clinically recognizable oral potentially malignant disorders (OPMDs), which provide an important window for cancer interception. This review examines how etiological exposures, persistent inflammation, and lesion-specific epithelial–stromal–immune interactions cooperate during the transition from mucosal injury to dysplasia, carcinoma in situ, and invasive OSCC. Major carcinogenic exposures, including tobacco, alcohol, and areca nut, are considered together with context-dependent contributors such as microbial dysbiosis, viral infection, and immune-mediated epithelial injury. At the molecular level, inflammation-driven oral carcinogenesis involves cytokine and chemokine amplification, oxidative and nitrosative stress, NF-κB and STAT3 activation, the COX-2/PGE₂ axis, genomic instability, field cancerization, epithelial–stromal crosstalk, angiogenesis, immune dysregulation, and epigenetic and non-coding RNA-mediated reprogramming. Emerging tools such as molecular risk assessment, liquid biopsy, optical imaging, spatially resolved profiling, and artificial intelligence-assisted models may improve identification of high-risk lesions, although most biomarkers require further prospective validation. Prevention should therefore integrate exposure control, biopsy-based diagnosis, local treatment when indicated, long-term surveillance, and trial-based precision strategies according to lesion risk, intervention window, and safety profile. This review supports a shift from lesion-centered management toward risk-adapted precision prevention in inflammation-driven oral carcinogenesis. Full article

Aquatic organisms are exposed to multiple stressors, including microplastic pollution and rising temperatures. Bioplastics like Poly(3-hydroxybutyrate-co-3-hydroxyvalerate) (PHBV) are considered sustainable alternatives to conventional plastics, although their biological effects remain poorly understood. This study evaluated the effects of PHBV microplastics on Artemia franciscana under different temperature and exposure conditions. Organisms were exposed to 25 and 100 mg·L⁻¹ PHBV for 7, 14, and 21 days at 25 °C and for 14 days at 29 °C. Growth, development, antioxidant enzyme (CAT, GST) and esterase activities (ChE, CbE), lipid peroxidation (LPO), gut histology, fatty acid profiles and polymer particle length distributions were assessed. Growth and development increased with PHBV concentration, exposure time, and temperature. Enzymatic activities and LPO were significantly affected by these factors, although no evidence of oxidative damage was detected. Marked gut lesions were observed at 100 mg·L⁻¹ PHBV at 29 °C after 14 days. Fatty acid profiles were mainly influenced by time and temperature, while high PHBV levels were associated with additional, more subtle changes in long-chain polyunsaturated fatty acids. PHBV particle length distributions also varied depending on exposure conditions. These findings suggest that PHBV induces physiological responses distinct from those typically reported for conventional microplastics and highlight the importance of considering multiple stressors in ecotoxicological studies. Full article

Background/Objectives: Tordylium trachycarpum Boiss. (Apiaceae) is traditionally used in Kurdish ethnomedicine for the management of gastrointestinal disorders; however, its pharmacological efficacy and safety profile remain insufficiently investigated. This study evaluated, for the first time, the gastroprotective activity and associated antioxidant, inflammatory, and apoptotic responses of the methanolic extract of T. trachycarpum using an ethanol-induced gastric ulcer model in Sprague–Dawley rats. Methods: Preliminary phytochemical screening revealed the presence of phenolics, flavonoids, terpenoids, tannins, coumarins, and glycosides. Acute oral toxicity testing demonstrated no signs of toxicity at doses up to 5 g/kg. Gastric ulceration was induced by absolute ethanol, and animals were pretreated with the extract (250 and 500 mg/kg) or omeprazole (20 mg/kg). Results: The extract significantly decreased the gastric lesion area from 258.50 ± 6.38 mm² in the ulcer control group to 143.70 ± 0.76 mm² and 115.50 ± 0.76 mm², corresponding to ulcer inhibition rates of 44.41% and 55.31%. Additionally, the extract increased mucus production, maintained mucosal structure, and raised stomach pH. Biochemical analysis showed a significant increase in antioxidant enzymes [superoxide dismutase (SOD) and catalase (CAT)] and a reduction in malondialdehyde (MDA) levels, indicating attenuation of oxidative stress. In addition, the extract modulated pro-inflammatory cytokines (TNF-α, IL-1β, IL-6, and IL-10). Blood-based ELISA analysis demonstrated increased expression of heat shock protein 70 (HSP70) and reduced Bax levels, suggesting anti-apoptotic activity. Conclusions: These findings indicate that T. trachycarpum exerts significant gastroprotective activity through antioxidant, anti-inflammatory, and anti-apoptotic mechanisms, supporting its traditional use and highlighting its potential as a natural therapeutic candidate for the management of gastric ulcers. Full article

Background: Obesity is a chronic endocrine–metabolic disorder. The risk of comorbidities increases with a higher body mass index (BMI), particularly when BMI ≥ 35.0 kg/m². Common complications include insulin resistance, type 2 diabetes, dyslipidemia, and chronic low-grade inflammation, which collectively impair DNA stability by promoting the formation of genotoxic species. Methods: This non-randomised, quasi-experimental clinical intervention study included 53 participants (both sexes) with a BMI ≥ 35.0 kg/m², who were assigned to parallel experimental or control streams based on clinical needs and institutional eligibility. During a three-week intervention, the experimental group received a hospital-supervised very-low-calorie diet (VLCD; ~600 kcal/day) under continuous medical monitoring. Conversely, the control group followed a standard reduced-calorie diet (SRD) of 1500 kcal/day in a free-living home environment. Before and after the intervention, primary, oxidative, and permanent DNA damage were measured using alkaline, FPG-modified comet (peripheral blood mononuclear cells), and cytokinesis-block micronucleus cytome assays (phytohaemagglutinin-stimulated binucleated lymphocytes), alongside anthropometric and biochemical tracking. Results: Within-group evaluations revealed that both dietary regimens improved several metabolic health indicators, notably modulating insulin resistance, lipid profiles, and leukocyte counts. However, participants in the VLCD stream experienced significantly greater downward changes in body weight, BMI, and absolute lipid values. Crucially, the VLCD intervention was associated with a highly significant within-group reduction in parameters of permanent chromosomal damage, effectively halving the frequencies of micronuclei and nuclear buds, independent of baseline variations, in adjusted multivariate regression models. Conversely, the home-based SRD regimen demonstrated no measurable impact on permanent genomic damage. Neither diet induced a significant change in repairable primary or oxidative DNA lesions over this short timeframe. Conclusions: These exploratory findings suggest that strict calorie restriction can rapidly stabilise genome stability in advanced clinical settings, warranting future randomised controlled trials with long-term longitudinal follow-up to assess permanent risk reductions. Due to structural baseline variations in age, chronic comorbidities, and compliance environments between the cohorts, direct comparative superiority cannot be definitively established. Full article

Ischemic stroke triggers a severe redox disequilibrium that critically shapes cell survival within the penumbra. Although oxidative DNA damage arises from excessive ROS production, the capacity to repair such lesions is tightly constrained by cellular metabolic status. Growing evidence indicates that astrocytes, key metabolic regulators of the neurovascular unit, modulate neuronal susceptibility to genomic injury through redox buffering, NAD⁺ maintenance, and metabolic support. In the metabolically impaired yet structurally preserved penumbra, astrocytic control of glutathione turnover, mitochondrial function, and lactate shuttling may determine whether oxidative DNA lesions are efficiently repaired or progress toward energetic collapse. Poly(ADP-ribose) polymerase 1 activation following DNA strand breaks couples genomic stress to NAD⁺ depletion and bioenergetic failure, forming a critical interface between redox biology and metabolism. This framework posits that astrocytes preserve genomic integrity not by directly altering DNA repair pathways but by sustaining the energetic capacity required for an effective DNA damage response. Elucidating this astrocyte-centered redox–metabolic axis may reveal therapeutic strategies to stabilize penumbral tissue and improve stroke outcomes. Full article

Background: Cervical cancer is primarily caused by the human papillomavirus (HPV), with persistent infections progressing to low- (LGSIL) and high-grade (HGSIL) lesions. Emerging evidence indicates that the cervicovaginal microbiota influences HPV persistence and disease progression, although the underlying metabolic mechanisms remain unclear. Therefore, we assessed the relationship between the cervicovaginal microbiota and the metabolic milieu in women with cervical dysplasia and HPV infections. Methods: We recruited 36 non-menopausal, non-pregnant women who were classified as negative, LGSIL, or HGSIL based on pathology and HPV results. Cervical swabs were collected for genomic DNA extraction to characterize bacterial communities using 16S rRNA sequencing and to perform HPV genotyping. Cervical lavages were collected for untargeted metabolomic profiling using Gas Chromatography-Mass Spectrometry. Integrative multiomic analysis was performed using the MIMOSA2 pipeline. Results: Although bacterial community structure was not different between groups, women with HGSIL had higher richness and exhibited a higher abundance of Prevotella bivia, Prevotella buccalis, and Lachnospiraceae G-9 oral taxon 924. Lesion-positive samples had shifts in tyramine and putrescine, biogenic amines linked to cancer development. Specifically, Pseudomonas was identified as a potential contributor to tyramine oxidation. Conclusions: Cervical lesions and HPV risk are associated with shifts in the cervicovaginal microbial metabolic milieu, highlighting the role of low-abundant anaerobic bacteria. Despite the small sample size, biogenic amines were associated with anaerobic taxa and microbial dysbiosis. These findings warrant further assessment of microbial-derived metabolites and their potential to promote tumor progression by driving a pro-inflammatory, metabolically altered microenvironment. Full article

Necrotic enteritis (NE), primarily associated with Clostridium perfringens, remains a major enteric disease in poultry production, particularly under reduced-antibiotic and antibiotic-free systems. Natural adsorbents, including biochar, clay minerals, and graphite-based materials, have attracted interest because of their capacity to interact with toxins, microbial metabolites, pathogens, and the intestinal environment. This conceptual review synthesizes current evidence on the physicochemical and biological properties of these materials and evaluates their potential relevance to NE mitigation. Biochar and clay minerals have stronger poultry-related evidence, particularly for mycotoxin adsorption, gut microbial modulation, and performance responses, whereas graphite remains an emerging candidate supported mainly by in vitro, non-poultry, and graphite-derivative literature. Across all three adsorbent classes, direct evidence for NetB-specific adsorption is currently absent, making this a central research gap rather than an established mechanism. Therefore, this review proposes a structured evaluation pipeline integrating material characterization, in vitro toxin-binding and epithelial response assays, and in vivo poultry NE outcomes such as lesion scores, CP burden, barrier integrity, inflammation, oxidative stress, microbiome shifts, and growth performance. Overall, natural adsorbents should be viewed as promising but incompletely validated candidates requiring standardized, NE-specific testing before therapeutic or commercial application. Full article

Acute cardiovascular events driven by atherosclerosis primarily originate from thrombosis triggered by vulnerable plaque rupture or endothelial erosion. Endothelial barrier destabilization—characterized by glycocalyx impairment, intercellular junction disassembly, and abnormal cytoskeletal tension—is a core upstream pathological stage that promotes atherogenic lipoprotein leakage, inflammatory cell infiltration, and matrix degradation. Hemodynamics, primarily through wall shear stress (WSS), shape the spatial distribution and plaque phenotypes of atherosclerosis; notably, low or oscillatory shear stress is associated with, and in experimental systems can promote, pro-inflammatory, pro-oxidant and pro-permeability endothelial phenotypes that contribute to plaque initiation and vulnerability. Conversely, regular exercise training, as an intervention that modulates hemodynamics, is widely suggested to promote anti-inflammatory, antioxidant, and antithrombotic endothelial phenotypes by significantly increasing antegrade shear stress and reducing detrimental retrograde/oscillatory shear stress. With a central focus on the axis of “exercise-shear stress-glycocalyx-cytoskeleton/junction-permeability-plaque stability,” this review integrates evidence from in vitro flow chambers, animal models and human studies to critically discuss: (1) the spatiotemporal heterogeneity of WSS and its relationship with plaque vulnerability; (2) the composition, barrier function, and plasticity of the glycocalyx as the primary interface for shear stress; (3) the mechanosensory complexes at the glycocalyx and junctions that transduce shear stimuli to protective pathways such as Phosphoinositide 3-kinase (PI3K)-Akt-endothelial nitric oxide synthase (eNOS) and Krüppel-like factor 2 (KLF2), thereby stabilizing adherens/tight junctions; (4) how improved barrier homeostasis promotes the maintenance of the fibrous cap collagen scaffold by reducing lipoprotein leakage and dampening the inflammation–matrix metalloproteinase (MMP) axis. Finally, this review highlights the boundary conditions of the biological effects of shear stress: low/oscillatory shear stress is primarily associated with plaque initiation and susceptible sites, whereas focal, extremely high WSS in established stenotic lesions may contribute to late-stage high-risk remodeling. Therefore, the protective hemodynamic adaptations induced by exercise should not be simply equated with the pathologically high WSS found at stenotic sites. Full article

Colorectal cancer (CRC) is a major global health burden characterized by progressive genetic and metabolic alterations, with iron metabolism being increasingly recognized as a key contributor to tumorigenesis. This review provides an integrated synthesis of current evidence on iron metabolism across the continuum of colorectal cancer development, from preneoplastic lesions to advanced disease. We analyzed data from epidemiological, experimental, and mechanistic studies addressing systemic and cellular iron homeostasis, including the hepcidin–ferroportin axis, as well as iron handling within tumor cells and the tumor microenvironment. Available data indicate that colorectal epithelial cells progressively develop an iron-retentive phenotype, characterized by increased iron uptake and reduced export, leading to expansion of the intracellular labile iron pool. This imbalance contributes to oxidative stress, DNA damage, metabolic adaptation, and activation of oncogenic signaling pathways while also influencing immune responses. However, epidemiological findings on dietary iron and CRC risk remain inconsistent, highlighting the context-dependent nature of iron-related effects. In conclusion, iron metabolism represents a dynamic regulator of CRC progression and a mechanistic framework for understanding stage-specific tumor evolution, although further studies are needed to clarify how iron-dependent pathways differ across colorectal tumor subtypes and microenvironmental contexts. Full article

Background: Actinic keratoses are common keratinocytic precursor lesions arising within chronically ultraviolet-damaged skin and are associated with an increased risk of progression to cutaneous squamous cell carcinoma. The concept of field cancerization has shifted therapeutic strategies from the treatment of isolated visible lesions toward broader field-directed approaches targeting both clinical and subclinical disease. Methods: This narrative review summarizes the rationale, mechanisms of action, efficacy profile, tolerability, and practical limitations of currently available field-directed therapies for actinic keratosis, including 5-fluorouracil, imiquimod, diclofenac, photodynamic therapy, and tirbanibulin. Based on their distinct biological targets, we propose a mechanism-based framework for sequential treatment strategies. Results: Available therapies act through partially non-overlapping mechanisms, including cytotoxic activity, immune activation, cyclooxygenase-2 inhibition, photodynamic oxidative damage, and tubulin/Src pathway inhibition. These complementary effects provide a biological rationale for sequential regimens aimed at addressing the heterogeneity of field cancerization. However, direct clinical evidence supporting specific treatment sequences remains limited, and proposed regimens should be interpreted as hypothesis-generating rather than as validated therapeutic protocols. Conclusions: Mechanism-based sequential field therapy may represent a rational strategy to optimize long-term control of actinic keratosis and field cancerization. Prospective comparative studies are needed to define optimal sequences, treatment intervals, patient selection criteria, and clinically meaningful endpoints, including sustained field clearance, recurrence reduction, tolerability, adherence, and prevention of progression to invasive cutaneous squamous cell carcinoma. Full article

Aging-associated dyslipidemia and chronic low-grade inflammation contribute to atherosclerosis and cardiovascular risk. As a blend of long-chain aliphatic alcohols, policosanol from insect wax (PIW) has been documented to regulate lipid metabolism. However, the effects of PIW on atherosclerosis remain insufficiently characterized. In this study, ApoE^−/− mice fed a high-fat diet were concurrently administered PIW (75 and 150 mg/kg) for eight weeks. PIW was associated with weight gain reduction and improvement in lipid profile, particularly a decrease in triglycerides and total cholesterol. PIW also lowered circulating inflammatory biomarkers (IL-6, TNF-α, and C-reactive protein). Histopathological analyses revealed attenuated hepatic injury and reduced aortic lipid deposition and lesion features. In parallel, PIW reduced serum endothelin-1 and oxidized LDL levels and modulated aortic ET-1, MMP-9/TIMP-1 balance, and LOX-1/NF-κB-related protein signals. Notably, as PIW was administered concurrently with high-fat diet induction, these findings should be interpreted within a preventive intervention framework. Collectively, PIW help attenuate HFD-associated atherosclerotic features and hold promise as a functional food ingredient for cardiovascular health and healthy aging. Full article

Tomato is susceptible to various fungal pathogens, including Alternaria alternata and Curvularia spicifera, which can cause extensive post-harvest losses. Chemical fungicides have limited effectiveness in controlling post-harvest fungal pathogens and pose risk to human health and the environment. Therefore, this study assessed indigenous isolates of three species of Trichoderma (Tr1: T. longibrachiatum; Tr2: T. harzianum; and Tr3: T. asperellum) as biocontrol agents against two fungal pathogens in vitro and in vivo and determined their physicochemical analysis and plant-growth-promoting traits. The three species of Trichoderma exhibited catalase production in vitro, while T. longibrachiatum and T. asperellum showed the highest potential for plant-growth promotion by producing indole-3-acetic acid and phosphate solubilization but not nitrogen-fixing capability. T. harzianum showed lower potential in these traits. Mycelial growth was found to be maximum (5.77–12.27 cm) at 30 °C and a pH of 7–9, but inhibition (2.60–5.13 cm) was recorded at the highest temperature (45 °C) and pH (11). In vivo, studies on tomato fruits indicated that T. longibrachiatum and T. asperellum significantly (p < 0.05) reduced lesion diameters of A. alternata by 53.60% and 48.71%, respectively, and C. spicifera by 55.58% and 56.19%, respectively, relative to the infected control. Besides their antifungal efficacy, the three species of Trichoderma enhanced tomato seedling growth, particularly at 1/10 filtrate dilution, and improved fruit quality parameters by increasing firmness and nitrate content, while reducing oxidative stress. Physicochemical analysis indicated that Trichoderma-treated fruits had better firmness, pH, and nitrate value coupled with a reduction in oxidative stress (reduced malondialdehyde content) compared to pathogen-infected controls. The indigenous isolates of the three species of Trichoderma provided high efficacy as biocontrol agents of the two fungal pathogens that cause post-harvest losses of tomato, suggesting that biological control can replace synthetic chemicals in preserving tomato under storage conditions and contribute to agricultural sustainability. Full article

Garlic (Allium sativum) contains organosulfur compounds capable of inducing oxidative damage to erythrocytes in dogs, leading to hemolytic anemia and methemoglobinemia. Although Allium toxicosis is relatively common, fatal cases with detailed histopathological characterization are rarely reported. This case report describes a fatal episode of garlic toxicosis in a 3-year-old female mixed-breed dog. At necropsy, gastric contents included food material and raw garlic cloves (16 g). Gross findings included pulmonary hyperemia and thoracic hemorrhagic effusion. Histopathological examination revealed multifocal myocardial hemorrhages, diffuse pulmonary capillary congestion, hepatic sinusoidal dilation with hemorrhagic areas, splenic hemorrhage, and renal glomerular capillary dilation. These lesions were consistent with systemic hypoxic and vascular injury secondary to oxidative erythrocyte damage. The lower quantity of garlic recovered compared with reported toxic doses suggests possible individual susceptibility or incomplete recovery of ingested material. This case highlights the diagnostic value of histopathology in suspected Allium fatal toxicosis and contributes to increasing the limited literature describing these outcomes in dogs. Full article

Resistance training (RT) can help with injury recovery and the healing process. Still, high-intensity exercise can cause ischemia and reperfusion, resulting in exacerbated production of reactive oxygen species and oxidative stress. This study aimed to evaluate the effects of RT with progressive loads on markers of tissue damage and oxidative stress in rats subjected to skin lesions. Forty male Wistar rats were used, divided into four groups (n = 10): Control (CG): no intervention; Sedentary Injury (SHAM): subjected to injury, no training; Training + Injury 1 (G1): injury after one week of training; Training + Injury 2 (G2): injury followed by training. The protocol consisted of climbing a vertical ladder three times a week, 48 h apart, using progressive loads (50%, 65%, and 80%). After euthanasia, markers of tissue damage (CK, LDH, ALT, AST), oxidative stress (MDA/TBARS, SH, uric acid), and histological analysis of collagen deposition in the injured tissue were assessed. Groups G1 and G2 showed a significant increase (p < 0.0001) in CK, LDH, ALT, and AST levels compared to GC and SHAM. Oxidative stress markers, such as MDA and SH, were also elevated in the G1 and G2 groups (p < 0.0001). Uric acid concentrations increased significantly in the exercised groups compared to the controls (p < 0.0001). Histology revealed an inflammatory infiltrate and disorganized collagen fibers in the SHAM group, while G1 and G2 showed tissue with greater cellular maturity and organization. Although RT induced muscle damage and an increase in pro-oxidant markers, it also favored cellular organization and scar tissue quality. Full article

Cryptocaryon irritans, a ciliated protozoan parasite, is the causative agent of marine white spot disease and results in significant economic losses in mariculture. In this study, golden pompano (Trachinotus ovatus) were challenged with C. irritans at different infection doses (2000, 4000, and 8000 theronts per fish) for 48 h to evaluate histopathological, oxidative stress, immune, and intestinal microbiota responses. Histopathological analysis revealed pronounced tissue damage in the gills, skin, intestine, and liver, with severity positively correlated with infection intensity. Typical lesions included intestinal mucosal damage, hepatic vacuolation, gill epithelial hyperplasia, and skin epidermal thickening. Hepatic malondialdehyde (MDA) levels increased significantly with infection intensity, while superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px) showed non-linear activation patterns. Catalase (CAT), alkaline phosphatase (AKP), and acid phosphatase (ACP) activities were consistently suppressed. Immune-related gene expression exhibited tissue-specific regulation, with myd88 downregulated in gills but upregulated in skin, while pro-inflammatory cytokines (il-1β and il-8) and il-10 were significantly elevated. Infection also altered intestinal microbiota composition, reducing beneficial bacteria (e.g., Photobacterium) and increasing opportunistic pathogens such as Vibrio. These findings provide insights into host–parasite–microbiota interactions in T. ovatus and improve our understanding of the physiological and immune responses of fish to C. irritans infection. Full article