Search Results (11,810)

Background: Diffuse Large B-cell Lymphoma (DLBCL) is a biologically heterogeneous subtype of non-Hodgkin’s lymphoma (NHL), accounting for 30–40% of cases worldwide. Despite the incorporation of rituximab into standard chemo-immunotherapy regimen, approximately one-third of patients present with relapsed or refractory disease, implicating the need for improved prognostic markers and therapeutic targets. Gene expression profiling successfully classified DLBCL into Germinal Center B-cell-like (GCB) and non-GCB subtypes, which differ in genetic alterations, response to therapy, and clinical outcome. While intrinsic tumor biology has been extensively studied, the contribution of the tumor microenvironment (TME) to disease progression and therapeutic resistance still remains incompletely understood. Methods: In this study, we investigated the mutational landscape of stromal-related genes in DLBCL and evaluated their impact on gene expression, downstream signaling pathways, and tumor progression. Results: A total of 176 DLBCL patients were screened, of which 113 were enrolled based on availability of complete clinical data. The cohort demonstrated male predominance (male:female ratio: 2.1:1), advanced disease stage in 72.6% of patients, and elevated serum lactate dehydrogenase levels in 57.5%. Based on immunohistochemistry, 43.4% cases were classified as GCB-DLBCL and 56.6% as non-GCB DLBCL. Although the International Prognostic Index (IPI) retained prognostic significance for event-free survival (EFS) and overall survival (OS), considerable heterogeneity was observed within similar risk groups. Whole-exome sequencing (WES) uncovered recurrent somatic mutations in key oncogenic and epigenetic regulators, including TNFAIP3, NFIB, NOTCH1, TSC2, EZH2, EP300, KMT2D, and B2M, with subtype-specific distribution. Pathway enrichment analysis implicated role of Notch, Wnt, mTOR, JAK-STAT, TGF-β, and antigen-presentation pathways. Comprehensive WES analysis identified multiple novel mutations in genes associated with the stromal/extracellular matrix with distinct patterns in GCB and non-GCB DLBCL, accompanied by concordant alterations in gene expression profiles, suggesting functional relevance within the TME. Functional validation through primary cell culture demonstrated significantly elevated Th2 (IL-4, IL-6, IL-10) and Th17 (IL-17) cytokines in co-cultures containing both neoplastic cells and stromal components, underscoring the role of TME in DLBCL progression. Conclusions: Taken together, this study provides novel insights into stromal mutational signatures and cytokine-mediated tumor–stroma interactions, offering potential prognostic biomarkers and therapeutic targets for the improved management of DLBCL. Full article

Reactive astrocytes are a hallmark of several neurological diseases in multiple sclerosis and experimental demyelination models. Their morphological alterations are commonly assessed by qualitative histopathology, yet quantitative tools are required to better capture astrocytic heterogeneity and to allow correlations with imaging-derived biomarkers. Here, we present a workflow for the quantitative analysis of Glial Fibrillary Acidic Protein (GFAP) network remodeling in astrocytes in the cuprizone model of demyelination. C57BL/6 mice were intoxicated with cuprizone for 3 or 5 weeks to induce progressive demyelination, microglial activation, and reactive astrogliosis. Brain sections were processed for anti-GFAP immunohistochemistry, and individual astrocytes from the stratum oriens of the hippocampus were digitally reconstructed. Diverse parameters of GFAP topology, including soma size, process length, branching order, convex hull area, and ramification index, were extracted using either the commercial Neurolucida^® 360 software or the open-source Simple Neurite Tracer (SNT) plugin in ImageJ. Principal component analysis revealed clear differences between control astrocytes and astrocytes in cuprizone-intoxicated animals, with reactive astrocytes displaying increased numbers of primary processes, enhanced bifurcation, and process complexity. Comparative evaluation of Neurolucida^® 360 and SNT demonstrated that both tools are suitable for astrocyte reconstruction, although Neurolucida^® 360 enabled faster and more detailed tracing. This protocol provides a reproducible pipeline for the quantitative assessment of astrocyte morphology under control and pathological conditions, thereby supporting future efforts to link cellular remodeling to functional outcomes in neuroinflammatory disease models. Full article

Background: Immunosuppressed women are at increased risk of residual or recurrent high-grade cervical intraepithelial neoplasia (CIN 2–3) after excisional treatment, yet long-term comparative data remain limited. Previous studies are often small and heterogeneous, and they rarely compare outcomes directly with immunocompetent populations. This study evaluated the long-term incidence, timing and associated factors of CIN 2–3 recurrence after large loop excision of the transformation zone (LLETZ), stratified by immune status. Methods: We conducted a retrospective cohort study including 283 women treated with LLETZ for CIN 2–3 between 1996 and 2016 at Bellvitge University Hospital in Barcelona, Spain. Of these, 41 were immunosuppressed and 242 immunocompetent. Clinical, histopathological, virological, and immunological variables were extracted from hospital and pathology registries. Kaplan–Meier estimates and Cox proportional hazards models adjusted for immunosuppression status were used to evaluate time-to-recurrence and factors associated with recurrence. Results: At 36 months post-treatment, the probability of residual/recurrent CIN 2–3 was 44% in immunosuppressed women versus 5% in immunocompetent women (HR = 10.42, 95% CI 4.70–23.08, p < 0.001). Recurrence appeared earlier in immunosuppressed women (median 7 vs. 13 months). Persistent high-risk HPV infection at first follow-up (HR = 23.6, 95% CI 5.44–102, p < 0.001) and positive surgical margins (HR = 3.88, 95% CI 1.45–10.3, p = 0.007) were among the factors most strongly associated with recurrence, and advanced immunodeficiency (CD4+ < 200 cells/mm³ or detectable HIV viral load) was associated with earlier recurrences, though this association was not maintained after accounting for immunosuppression status in Cox models. Conclusions: Immunosuppressed women are at significantly higher and earlier risk of residual/recurrent CIN 2–3 after LLETZ. These findings support a risk-adapted, multidisciplinary follow-up integrating gynecologic, infectious disease, and immunologic care. Tailored surveillance and perioperative HPV vaccination may enhance secondary prevention in this high-risk population. Full article

This study aimed to evaluate the therapeutic effects of platelet-rich plasma (PRP) and Cervus and Cucumis polypeptide (CCP) injections in rats with post-traumatic osteoarthritis (OA). The model was established by transection of the anterior cruciate ligament, and the animals were subsequently treated with PRP and CCP. Articular cartilage degeneration was assessed through gross morphological observation, histopathological staining, and a standardized scoring system. Concurrently, pain-related behaviors, joint swelling, levels of inflammatory cytokines, and markers associated with extracellular matrix degradation were measured. The results demonstrated that, compared with the OA model group, PRP and CCP exhibited varying degrees of functional improvement, specifically, a reduction in pain-related behaviors and an alleviation of joint swelling. Furthermore, cartilage morphological damage was diminished, inflammatory marker levels decreased, and indicators of extracellular matrix degradation were attenuated. Histopathological examination of liver and kidney tissues revealed no apparent abnormalities. This study provides valuable experimental evidence for further treatment strategies for OA. Full article

Polysaccharides are important bioactive components of dried tangerine peel, exhibiting antioxidant, anti-inflammatory, and hypoglycemic activities. However, the ability of dried tangerine peel polysaccharides to alleviate gastric injury remains insufficiently understood. Therefore, the structure and alleviation of gastric injury induced by dried tangerine peel polysaccharides were explored in this study. Firstly, DTPP-4 was purified from dried tangerine peel. As shown in the HPLC chromatogram, DTPP-4 is a homogeneous polysaccharide with a mean molecular weight of 1.35 × 10³ kDa. DTPP-4 was mainly composed of L-Rha, L-Ara, D-Gal, and D-GalpA with percentages of 10.56%, 9.15%, 4.83%, and 75.45%, respectively. Methylation and NMR results suggested that DTPP-4 was a pectic polysaccharide with →4)-α-D-GalpA-6-OMe-(1→ and →4)-α-D-GalpA-(1→ as the backbone. The alleviation of gastric injury of dried tangerine peel polysaccharide was evaluated in ethanol-induced acute gastric injury mice. Based on the macroscopic images of gastric tissues and the area of gastric tissue injury in mice, the dried tangerine peel polysaccharide can reduce the mouse gastric lesion area and alleviate gastric tissue pathological damage. Histopathological analysis of H&E and PAS staining revealed that the dried tangerine peel polysaccharide could ameliorate the disordered arrangement and necrosis of epithelial cells, reduce inflammatory cell infiltration, and thus alleviate gastric injury. Dried tangerine peel polysaccharide confers gastroprotection by modulating MPO and PGE2 levels, reducing MDA accumulation, enhancing SOD and CAT antioxidant activities, suppressing IL-1β and TNF-α secretion, and upregulating IL-10 expression. These findings provide a theoretical foundation for subsequent structure–activity relationship investigations and provide empirical support for the subsequent development and practical application of this polysaccharide. Full article

SIRT2 (Sirtuin 2) is an NAD+-dependent deacetylase that exerts crucial regulatory effects on immune homeostasis and macrophage activation. While chronic cold exposure is a known predisposing factor for pulmonary dysfunction, the precise mechanisms by which SIRT2 potentially modulates lung macrophage polarization under cold stress remains poorly understood. In this study, we evaluated the protective capacity of SIRT2 using both wild-type (WT) and Sirt2-knockout (Sirt2−/−) murine models subjected to chronic cold exposure (4 °C for 3 h daily over 21 days). Our results demonstrated that Sirt2 deficiency significantly exacerbated cold-induced pulmonary histopathological damage and increased the secretion of pro-inflammatory cytokines (TNF-α, IL-1β, and IL-6) (p < 0.05). Furthermore, chronic cold stress triggered a macrophage-centered inflammatory response, a process wherein SIRT2 was found to curtail M1 pro-inflammatory polarization. To further investigate these mechanisms, in vitro experiments were conducted using the mouse alveolar macrophage cell line MH-S. While LPS was utilized as a canonical inflammatory stimulus to mimic the injury environment, SIRT2 overexpression was found to reverse the LPS-induced increase in M1 markers and attenuate inflammatory cytokine secretion. These findings suggest that SIRT2 maintains intracellular homeostasis by modulating macrophage plasticity and plays a protective role in the development of chronic cold stimulus-induced lung injury. Consequently, SIRT2 activation may represent a potential therapeutic pathway for the treatment of environment-related respiratory diseases. Full article

Background: Experimental animal models remain central to burn research and soft-tissue reconstruction/repair, but method heterogeneity compromises reproducibility, comparability, and translation for depth/area endpoints. Objective: We aimed to map burn-induction methods and examine reproducibility, intentional depth modulation, wound-area stability, validation, and operator-dependent variability. Methods: A PRISMA-ScR review, informed by JBI guidance, was conducted without registration but with predefined questions, criteria, and charting domains. PubMed/MEDLINE, Scopus, Web of Science, Embase, and Google Scholar were searched from inception to 30 January 2026. Eligible studies were English peer-reviewed full-text original in vivo animal studies. Two reviewers independently screened records; one charted data, another checked it. Evidence was mapped by modality, exposure-control architecture, validation, and operator-sensitive steps. Results: Studies varied by species, modality, device design, exposure settings, and severity verification. Modalities were contact, scald, steam, and radiant/infrared. Wound area was more reproducible than depth, which depended on temperature, duration, force/pressure, geometry, equilibration, anatomical site, and assessment timing. Histopathology was the main standard, sometimes complemented by morphometry, optical, or perfusion techniques. Operator-sensitive variability involved force, alignment, contact stability, template integrity, exposure geometry, source stability/environmental control. Conclusions: Burn induction is a measurement-system problem; constraining operator-sensitive variables, predefined validation timing, and quantitative variability reporting may improve validity, comparability, and translation. Full article

Background: Primary glomerular diseases (PGDs) are a leading cause of end-stage kidney disease (ESKD). While sex differences in chronic kidney disease progression have been reported, their role in PGDs remains unclear. Methods: We analyzed 2081 patients with biopsy-proven PGDs from the Turkish Society of Nephrology Glomerular Diseases Working Group (TSN-GOLD) registry. Baseline demographic, clinical, biochemical, and histopathological characteristics were compared between women and men. Outcomes were assessed as a composite of ESKD or death. Logistic and Cox regression models were applied to identify independent risk factors. Kaplan–Meier analyses evaluated survival differences. Results: At baseline, women and men had similar rates of hypertension (36.8% vs. 34.7%, p = 0.322). Women more frequently presented with leukocyturia (31.7% vs. 17.2%, p < 0.001) and hematuria (57.8% vs. 52.3%, p = 0.016), whereas men had higher proteinuria (5011 ± 4925 vs. 4388 ± 4529 mg/day, p = 0.003) and were more likely to be active smokers (20.7% vs. 7.4%, p < 0.001). Serum albumin (3.3 ± 0.8 vs. 3.2 ± 0.9 g/dL) and eGFR (79.7 ± 44.3 vs. 78.7 ± 45.5 mL/min/1.73 m²) were comparable between sexes (both NS). During a median follow-up of 24 months (IQR 7-60), 431 patients (20.7%) reached the composite outcome of ESKD or death (137 deaths [6.6%], 294 ESKD [14.1%]). In the multivariable Cox regression model, lower baseline eGFR (HR 0.98, 95% CI 0.98–0.98, p < 0.001), lower serum albumin (HR 0.65, 95% CI 0.55–0.77, p < 0.001), higher proteinuria (HR 1.03, 95% CI 1.00–1.05, p = 0.043), and biopsy diagnosis of RPGN (HR 3.78, 95% CI 1.37–10.45, p = 0.010) were independent predictors of poor prognosis. Sex was not an independent predictor of outcome (p = 0.48). Kaplan–Meier analysis demonstrated no significant survival difference between women and men (log-rank p = 0.052). Conclusions: In this nationwide PGD cohort, women and men differed significantly in baseline biochemical and clinical parameters, yet sex was not independently associated with progression to ESKD or death. Instead, disease severity at baseline and histopathological features were the main drivers of prognosis. Full article

Excessive glucocorticoids induced by stress trigger hepatic lipid metabolism disorder and oxidative stress in poultry, impairing growth performance and welfare. At the same time, resveratrol (RSV) has antioxidant and lipid-regulating properties, but the protective mechanisms in corticosterone (CORT)-challenged broilers remain unclear. This study investigated RSV’s effects on CORT-induced hepatic damage in AA broilers, with 240 one-day-old broilers randomized into three groups: control (basal diet), CORT (basal diet + 4 mg/kg BW CORT intraperitoneal injection), and RSV (400 mg/kg RSV-supplemented diet + CORT injection). Growth performance, hepatic redox status, serum biochemistry, liver histopathology, and gene/protein expression related to antioxidant/lipid metabolism were determined. The growth performance of AA broilers injected with CORT was significantly affected, showing reduced body weight gain (p < 0.05), increased abdominal fat content (p < 0.05), and hepatomegaly (p < 0.05). The addition of RSV in the diet significantly reduced abdominal fat accumulation and hepatomegaly (p < 0.05), improving the growth performance of broilers; Effects of RSV on liver function and lipid metabolism of CORT-treated AA broilers: After CORT injection, serum alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP) activity and total bile acid (TBA) content significantly increased (p < 0.05). Hepatic total cholesterol (TC) and triglycerides (TG) increased after CORT injection (p < 0.05), causing severe liver damage. RSV supplementation could reverse the increases in serum ALP, ALT, and AST activity (p < 0.05) and reduce TBA content in stressed broilers (p < 0.05). TC and TG levels in the liver decreased under the alleviation of RSV (p < 0.05), and serum TG levels declined (p < 0.05). Microscopic and ultrastructural observations showed that after CORT injection, hepatic tissue cells were swollen, scattered fat vacuoles were present, pores were enlarged, and intracellular lipid droplets appeared. The RSV group significantly alleviated hepatocyte damage, reduced vacuolation, showed uniform chromatin, and decreased lipid droplets. RSV significantly mitigated the CORT-induced increase in SREBP-1 mRNA and protein expression and the decrease in PPARα protein expression; CORT caused a decline in the antioxidant function of AA broiler livers, with significant decreases in SOD and GSH-PX (p < 0.05), and the expression of Nrf2 and its downstream genes also showed a decreasing trend. Compared to the CORT group, the RSV group exhibited significant increases in liver CAT, SOD, and GSH-PX (p < 0.05), and Nrf2 protein expression was elevated (p < 0.05). In summary, resveratrol can alleviate the decline in growth performance, liver steatosis, and hepatic oxidative stress in AA broilers induced by CORT, downregulate lipogenic genes such as SREBP-1c, regulate liver lipid metabolism, and mitigate CORT-induced hepatic oxidative stress in broilers by upregulating the Nrf2 pathway. Full article

Triplophysa siluroides, a unique species of plateau fish, holds significant economic value. However, its natural population has sharply declined due to overfishing and the construction of water conservancy projects. Investigating the various conditions necessary for its growth is a crucial prerequisite for successful artificial breeding. This study used Edwardsiella tarda as the pathogenic bacterium to determine the median lethal concentration following infection of T. siluroides, as well as to examine changes in tissues, organs, and gene expression. The study found that dead T. siluroides displayed symptoms such as abdominal distension, fluid accumulation, and a reddened anus, and the median lethal concentration of E. tarda for T. siluroides was calculated to be 1.00 × 10⁶ CFU/mL. Following infection with E. tarda, the liver, intestine, gills, spleen, and kidneys exhibited varying degrees of lesions. Transcriptome sequencing identified a total of 54,667 genes. Compared to the blank control group, 192 genes were downregulated and 125 genes were upregulated in T. siluroides infected with E. tarda. In contrast, after infection with the poly(I:C) viral mimic, 225 genes were downregulated and 436 genes were upregulated. This study determined the median lethal concentration of E. tarda for T. siluroides via intraperitoneal injection under laboratory conditions. The results may contribute to disease prevention and control in the breeding of T. siluroides, as well as inform future risk assessments of infection in aquaculture water bodies. Full article

Background: Persistent lymph node metastases after neoadjuvant radiochemotherapy (RCT) for locally advanced rectal cancer indicate poor response to treatment. This study evaluated the long-term prognosis of patients with residual nodal disease following neoadjuvant RCT and total mesorectal excision (TME) in comparison with patients who underwent upfront TME without adjuvant radiotherapy. Methods: Consecutive patients with rectal adenocarcinoma and histopathologically confirmed lymph node metastases after TME were identified from the prospectively maintained database of the colorectal unit at Dresden-Friedrichstadt General Hospital. Patients with distant metastases, in-hospital mortality, or postoperative radiotherapy were excluded. The two groups were comprehensively compared regarding patient-, tumor-, and treatment-related characteristics. Cumulative local recurrence, time to recurrence, cancer-specific survival, and overall survival were analyzed using the Kaplan–Meier method. Results: Between 1996 and 2021, 155 eligible patients were identified, including 101 patients in the RCT group and 54 in the upfront surgery group. Baseline characteristics were largely comparable, except for a higher median age (70.5 vs. 64 years, p < 0.001) and a higher proportion of lymphovascular invasion (36.0% vs. 15.2%, p = 0.004) in the upfront surgery group. Ten-year local recurrence rates were similar between groups (21.0% [95% CI: 10.4–31.6] vs. 20.8% [95% CI: 8.5–33.1], p = 0.609). No significant differences were observed in time to recurrence or cancer-specific survival. Overall survival was lower in the upfront surgery group, most likely reflecting the substantially higher age of these patients. Conclusions: Despite more intensive treatment, patients with a persistent ypN-positive category have outcomes no better than untreated patients with node-positive disease after TME, indicating a biologically high-risk subgroup. Non-response is therefore a sign of a negative selection. These patients may lose the opportunity for optimal local tumor control during prolonged neoadjuvant treatment, underscoring the urgent need for reliable predictive markers to identify non-responders and guide individualized treatment strategies. Full article

Agaricus subrufescens (AS) is a medicinal mushroom with notable bioactivity and the capacity to accumulate trace elements. In this study, selenium-enriched A. subrufescens (SAS) was cultivated, and its protective effects against alcoholic liver disease (ALD) were investigated, with an emphasis on clarifying the underlying mechanisms. The results showed that the yield and antioxidant capacity of mushrooms in a 10 mg·kg⁻¹ Se treatment group were increased. Nutritional analysis revealed that SAS contained considerable levels of crude protein (350.00 g·kg⁻¹), crude fiber (7.8%), free amino acids (250.20 g·kg⁻¹), and other bioactive constituents. Furthermore, the hepatoprotective effects of AS/SAS were studied in male Kunming mice with alcohol-induced liver injury. The body growth, liver index, serum and liver biochemical parameters, histopathological features of liver, hepatic mRNA levels and liver metabolomics were investigated. The results demonstrated that SAS significantly reduced hepatic lipid accumulation, enhanced antioxidant capacity, regulated the mRNA expression of key genes involved in lipid metabolism, oxidative stress, and inflammatory responses, and modulated liver metabolic characteristics. These findings provide theoretical evidence for the potential of SAS as a functional food against alcohol-induced liver injury. Full article

A 66-year-old woman was referred for evaluation of a large pelvic mass suspected to be ovarian cancer. Contrast-enhanced computed tomography (CECT) revealed a giant multiseptated cystic pelvic mass with enhancing solid components; although its superior aspect closely abutted the gastric serosa, its predominant pelvic location raised concern for an adnexal malignancy. Subsequent [¹⁸F]fluorodeoxyglucose positron emission tomography/computed tomography ([¹⁸F]FDG PET/CT) demonstrated mild uptake confined to the viable solid portion (SUVmax 2.72) without hypermetabolic nodal or distant metastases. Exploratory laparotomy revealed a giant pedunculated tumor arising from the gastric antrum and descending into the pelvis. Histopathology confirmed an epithelioid gastrointestinal stromal tumor positive for CD117, DOG1, and CD34. This case highlights an important diagnostic pitfall in which a giant exophytic gastric GIST may mimic ovarian cancer because of its pelvic location and cystic-solid appearance. Careful correlation of CECT, fused [¹⁸F]FDG PET/CT, and pathologic findings is essential for accurate assessment of the organ of origin in large abdominopelvic masses. Full article

Background and Clinical Significance: Primary cutaneous anaplastic large cell lymphoma (C-ALCL) is a CD30-positive T-cell lymphoproliferative disorder that can clinically resemble various non-melanoma skin cancers, making diagnosis challenging. Although histopathology remains the diagnostic gold standard, non-invasive imaging modalities such as dermoscopy and reflectance confocal microscopy (RCM) are increasingly used as complementary tools to support the differential diagnosis. To date, no data on RCM features of C-ALCL have been described. Case Presentation: We report the case of an 80-year-old man presenting with a rapidly enlarging nodule on the lateral aspect of his right eyelid, providing a detailed account of dermoscopic and RCM findings integrated with clinicopathological correlation. Dermoscopy revealed a red-orange homogeneous background with white streaks, and polymorphic vascular structures, while subsequent RCM (Vivascope 3000 probe) demonstrated marked architectural disarray of the epidermis and dermoepidemal junction, with prominent epidermal involvement characterized by aggregates of highly reflective cells. In the absence of alternative diagnostic patterns, these features raised suspicion for a cutaneous lymphoproliferative disorder, which was later confirmed by histopathological and immunohistochemical analyses. Conclusions: Our findings support the value of RCM as a practical tool in guiding differential diagnosis and biopsy, particularly for rapidly growing lesions located in anatomically sensitive areas. Full article

Background: Paclitaxel is a widely used chemotherapeutic agent whose clinical efficacy is limited by gonadotoxic side effects. Oxidative stress, apoptosis, and inflammation are key mechanisms underlying paclitaxel-induced testicular injury. This study aimed to comparatively evaluate the protective effects of melatonin and apigenin in a rat model. Methods: Adult male Sprague-Dawley rats were randomly assigned to seven groups: control, solvent control, melatonin, apigenin, paclitaxel, paclitaxel + melatonin, and paclitaxel + apigenin. Testicular malondialdehyde (MDA) and reduced glutathione (GSH) levels were measured, together with apoptotic activity (caspase-3), oxidative DNA damage (8-OHdG), inflammatory signaling (NF-κB/p65, immunoreactivity), and histopathological alterations (Johnsen score). Results: Paclitaxel significantly increased MDA levels and decreased GSH content, accompanied by elevated caspase-3, 8-OHdG, and NF-κB/p65 immunoreactivity, as well as marked degeneration of seminiferous tubules. Melatonin improved redox balance, suppressed apoptotic and inflammatory responses, and preserved testicular architecture. Apigenin reduced lipid peroxidation and improved antioxidant status in paclitaxel-treated rats while decreasing GSH levels under basal conditions without inducing histological damage, suggesting a context-dependent redox-modulating effect. Both agents significantly improved Johnsen scores compared with paclitaxel alone. Conclusions: Paclitaxel-induced testicular injury is mediated by a coordinated interplay of oxidative stress, apoptosis, inflammation, and structural degeneration. Melatonin and apigenin effectively mitigate these processes, with apigenin exhibiting context-dependent antioxidant activity. These findings suggest that melatonin and apigenin may serve as adjunctive strategies for preserving male reproductive function during chemotherapy. Full article