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Understanding the molecular mechanisms of carcinogenesis, including disruptions in the homologous recombination system, is fundamental to understanding malignant transformation. Dysfunction of homologous recombination genes, such as BRCA1 and BRCA2, contributes to genomic instability and the development of more aggressive tumor clones. The use of chemical carcinogens enables the modeling of tumor formation and the monitoring of changes in molecular genetic parameters. This approach is important for understanding how tumor cells adapt to genotoxic stress and for advancing the development of personalized cancer therapies. The objective of this study was to evaluate the expression of key homologous recombination system genes in a model of chemically induced carcinogenesis in mice. Materials and Methods: Male outbred ICR (CD-1) laboratory mice (n = 40) were used to study chemically induced carcinogenesis. The animals were divided into four groups: two control groups and two experimental groups, which received 3-methylcholanthrene (MC) or trichloroacetic acid (TCA). Tumor cells were identified by histological analysis of autopsy material using light microscopy after standard hematoxylin and eosin staining. RNA and DNA were extracted from cell suspensions using the RNeasy Plus Mini Kit and QIAamp DNA Mini Kit (Qiagen, Hilden, Germany), respectively. The expression levels of homologous recombination genes were assessed by RT-PCR and microarray analysis. Digital PCR was performed to assess chromosomal aberrations in the Brca1 gene. Results: Tumor formations were identified in laboratory animals two months after 3-methylcholanthrene. Histological analysis revealed morphological changes in a pleomorphic cell tumor, forming diverse, multidirectional fascicular and swirling structures, as well as large solid foci composed of markedly polymorphic spindle-shaped and epithelioid cells. Analysis of copy number aberrations in the examined samples showed that the frequency of Brca1 deletions was 60%, while 40% of animals had normal gene copy number. To further characterize the molecular changes, we assessed gene expression levels through expression microarray analysis. A total of 14 genes were hypoexpressed in the tumor compared to the normal tissue, with p < 0.05. A high level of differential expression was characteristic for Rad50, Rad51, Brca1, Brca2, and Pold4. Two genes, Rad52 and Bard1, exhibited increased expression levels. It was shown that as the tumor mass increased, so did the frequency of homologous recombination genes with hypoexpression. Conclusions: Our findings confirm that MC and TCA influence tumor formation and reveal that suppression of homologous recombination genes may contribute to this process. In addition, it has been established that as tumors progress, the expression of DNA repair genes declines and aberrant gene states accumulate. These data emphasize the importance of studying the state of DNA repair genes for the development of more effective strategies for cancer diagnosis and therapy. Full article

Background: Etoricoxib, a selective cyclooxygenase-2 (COX-2) inhibitor, is widely prescribed for the management of inflammatory conditions. Despite its extensive clinical use, evidence regarding its hepatic safety profile remains limited and incompletely characterized. Aims: This study aimed to systematically evaluate the hepatic effects of etoricoxib in a murine model by integrating histopathological assessment with analysis of mRNA expression of key enzymes involved in arachidonic acid metabolism Methods: Male BALB/c mice (n = 7 per group) received either low or high doses of etoricoxib (10.5 or 21 mg/kg/day) or celecoxib (35 or 70 mg/kg/day) for 28 consecutive days. Liver tissues were examined histologically using hematoxylin and eosin staining, while molecular alterations were assessed by quantitative PCR targeting representative cyclooxygenase (COX), lipoxygenase (LOX), and cytochrome P450 (CYP450) isoforms involved in arachidonic acid metabolism. Results: High-dose etoricoxib exposure was associated with pronounced hepatic histopathological alterations, including hepatocellular necrosis, inflammatory cell infiltration, and sinusoidal congestion. In contrast, low-dose treatment resulted in only mild vascular and cellular changes. At the molecular level, etoricoxib administration was associated with marked downregulation of several arachidonic acid–metabolizing genes (including Cyp4a12 and Alox12), whereas Cox2 expression was significantly upregulated (p < 0.05), indicating a shift toward a pro-inflammatory transcriptional profile. Conclusions: Etoricoxib exposure is associated with dose-dependent hepatic injury in mice, accompanied by coordinated transcriptional alterations in arachidonic acid–metabolizing pathways. Notably, molecular changes were detectable even at low doses in the absence of overt histological damage, suggesting potential early indicators of hepatic stress. These findings underscore the importance of cautious dose optimization and further translational studies to clarify the long-term hepatic safety of etoricoxib in clinical settings. Full article

Transmissible viral proventriculitis (TVP) is an emerging disease in chickens, linked to chicken proventricular necrosis virus (CPNV), a recently identified birnavirus. Here, we provide the first molecular confirmation of TVP in Bangladesh from a coloured meat-type parent stock (PS) flock, while documenting a contemporaneous white layer flock with consistent clinical signs and characteristic gross lesions. Affected birds exhibited growth retardation, diarrhoea, and increased mortality, alongside hallmark gross changes in proventricular enlargement and wall thickening. From the meat-type PS, proventricular samples were collected for histopathology and molecular diagnostics. Histological analysis revealed severe glandular epithelial damage, necrosis, mononuclear infiltration, epithelial hyperplasia, and metaplasia. Using RT-PCR on nucleic acid extracted from FTA card samples, CPNV was detected. In addition, infectious bronchitis virus (IBV), infectious bursal disease virus (IBDV), and avian reovirus (ARV) nucleic acids were also identified. The amplified CPNV VP1 fragment was sequenced, and phylogenetic analysis placed the Bangladeshi strain within clades of previously reported CPNV isolates. This study represents the first molecularly confirmed report of CPNV associated with TVP in Bangladesh, highlighting the need for active surveillance in commercial and breeder poultry flocks to understand the virus’s epidemiology and support the development of control strategies. Full article

Limosilactobacillus fermentum MC1 is an exopolysaccharide (EPS)-producing strain with previously determined probiotic potential in vitro. This study aimed to investigate the in vivo capacity of the MC1 strain or its EPSs to modulate intestinal microbiota and assess its anti-inflammatory effects in both healthy and dysbiotic conditions. Therefore, Lb. fermentum MC1 and its EPSs were administered to a mouse model of dextran sulfate sodium (DSS)-induced colitis (DIC) and to a healthy group, and the effects were observed. Microbiome analysis was used to detect taxonomic differences between treatments. According to the results, administration of the MC1 strain and MC1-EPSs significantly altered gut microbiome composition at different taxonomic levels. The most notable effect was an increased relative abundance of Firmicutes and decreased levels of Candidatus saccharibacteria. Llb. fermentum MC1, and its EPS administration positively affected several disease parameters: reduced disease activity index (DAI), reduced mouse colitis histology index (MCHI), reduced expression of inflammation-related genes and levels of bleeding, and induced polarization of M1 macrophages to the M2-like macrophage phenotype in the DIC mice. These results, along with those related to the induction of antioxidant enzymes and changes in NF-κB-related gene expression, suggest that strain MC1 and MC1-EPSs could be further investigated for their capacity to alleviate DSS-induced histopathological changes and modulate pro-inflammatory cytokine gene expression in colon tissue, which positively correlates with the secretion of inflammatory cytokines, the delay of intestinal inflammation and the maintenance of intestinal barrier function. The obtained data provide a basis for further research into the potential application of intact or microencapsulated Llb. fermentum MC1 cells and its EPSs in colitis therapy. Full article

Background and Objectives: In real-world NSCLC management, prognostic assessment extends beyond tumour staging and molecular profiling, which represent a partial timeframe of disease biology. Routinely collected inflammatory and haematological markers may better reflect the dynamic host–tumour interactions during treatment. This study assessed the prognostic significance of baseline and longitudinal neutrophil-to-lymphocyte ratio (NLR) and haemoglobin levels on survival outcomes in a real-world NSCLC cohort. Materials and Methods: We conducted a retrospective observational cohort study of 615 patients with histologically confirmed NSCLC diagnosed between 1 May 2022 and 30 April 2024 at a tertiary referral centre in western Romania. Survival outcomes, including progression-free and overall survival, were analysed through Kaplan–Meier curves, complemented by 12-month restricted mean survival time estimates. High NLR was defined as ≥3 and low haemoglobin as <12 g/dL. Longitudinal changes were evaluated at 6 and 12 months, with 12-month analyses restricted to patients alive at that landmark. Results: The cohort had a median age of 66 years (IQR 60–72) and was predominantly male (66.3%). Most patients presented with advanced disease (60.3% stage IV, 23.6% stage III). At baseline, 57.1% (n = 351) exhibited high NLR and 39.8% (n = 245) had low haemoglobin. Median PFS was 9.0 months (IQR 4.5–15.5), and median OS was 16.5 months (IQR 8.5–27.0). Stage IV disease was associated with shorter PFS than stages I–II (7.0 vs. 20.8 months; log-rank p < 0.001). High-baseline NLR showed a borderline association with shorter PFS (adjusted HR 1.40; 95% CI 0.98–1.95). Among the 436 patients alive at 12 months, NLR increased in 56.7% of cases, and this increase showed a non-significant trend toward shorter PFS (HR 1.35; 95% CI 0.95–1.90; p = 0.09) in a 12-month landmark analysis. Conclusions: Baseline systemic inflammation and anaemia are highly prevalent in real-world NSCLC patients and cluster with advanced disease. Elevated NLR was associated with poorer survival outcomes, whereas low haemoglobin did not demonstrate a significant independent association in adjusted analyses. These haematological parameters are accessible tools for prognostic assessment in routine clinical practice. Full article

Background: Lupus nephritis (LN) is a severe manifestation of systemic lupus erythematosus (SLE), characterised by unpredictable outcomes due to the absence of reliable biomarkers. This hypothesis-generating study aimed to evaluate whether changes in the N-glycosylation of IgG, C3, AGP, and the serum proteins over one year of treatment correlate with clinical and histological features of LN and predict renal outcomes. Methods: Serum samples from 19 treatment-naïve patients with LN were collected at baseline and 12 months post-treatment, in conjunction with per-protocol repeat kidney biopsy. IgG (Fc, Fab, and total), C3, AGP, and total serum glycoproteins were isolated and analysed as either released N-glycans or N-glycopeptides using high-throughput glycomic approaches. Clinical and histological data were obtained at both time points, along with assessments of clinical and histological response at 12 months and long-term renal function. Results: In total, we identified 24/243 increased N-glycosylation traits (2 total IgG, 5 IgG Fc, 7 IgG Fab, 5 serum glycoproteins, 4 AGP, and 1 C3) and 10/243 decreased N-glycosylation traits (7 total IgG, 2 IgG Fc, 1 IgG Fab) following treatment. Baseline AGP IORMIF1N5H6S2F1 showed a positive correlation with eGFR both at baseline (r = 0.64, p = 0.005) and at 12 months (r = 0.51, p = 0.032). Among AGP N-glycosylation traits, IVORMI1N7H8S3 (r = 0.66, p = 0.002; r = 0.48, p = 0.041, respectively), VORMI1N8H9S4 (r = 0.51, p = 0.029; r = 0.49, p = 0.038, respectively), and VORMI1N8H9S4F1 (r = 0.48, p = 0.039; r = 0.49, p = 0.034, respectively) significantly correlated with activity index (AI) at baseline and at 12 months. Presence of cellular crescents at baseline positively correlated with three AGP N-glycosylation traits: IORMISORMIIA1N4H5S2 (r = 0.49, p = 0.036), VORMII1N5H6S3F1 (r = 0.63, p = 0.006), and VORMII1N4H5S2 (r = 0.48, p = 0.046). Total serum N-glycan (structure) N5H4F1 at 12 months was associated with both clinical and histological response to treatment. Delta of total serum N-glycan structure N5H5S1 was independently associated with poor long-term outcome. Conclusions: This study suggests that glycosylation changes over one year of treatment are associated with specific clinical and histological features and both short- and long-term renal outcomes in LN. Given the small cohort size, results should be considered hypothesis-generating warranting further investigation in independent cohorts. Full article

Background/Objectives: The human larynx exhibits marked sexual dimorphism and undergoes age-related structural remodeling, both of which influence voice characteristics and have important implications for diagnostic assessment. While sex-related differences in laryngeal size are well recognized, the extent to which aging contributes to dimensional versus qualitative structural changes remains incompletely defined. This study aimed to analyze sex- and age-related morphometric and histological characteristics of the human larynx, with a focus on features relevant to voice evaluation and diagnostic interpretation. Methods: A cross-sectional anatomical study was conducted on 80 cadaveric human larynges preserved in 10% buffered formalin. Specimens were stratified by sex and age (<30, 30–60, and ≥60 years). Direct morphometric measurements included anteroposterior laryngeal length, thyroid cartilage height, thyroid angle, and relative glottic area. Epiglottic morphology and the presence of laryngeal cartilage calcification/ossification (binary classification: present vs. absent) were recorded. Histological analysis of vocal fold tissue was performed on a stratified subset of specimens. Statistical analysis included t-tests, chi-square tests, two-way ANOVA, effect size estimation, and logistic regression. Results: Male specimens showed significantly greater anteroposterior length, thyroid cartilage height, and relative glottic area, along with a narrower thyroid angle, compared with females (all p < 0.001), with large effect sizes. Age did not significantly influence overall laryngeal dimensions. In contrast, cartilage calcification/ossification increased markedly after the age of 60. Logistic regression identified age ≥ 60 years as the only independent predictor of calcification (OR = 4.37, p = 0.039), while sex was not significant. Epiglottic morphology demonstrated a sex-dependent distribution. Histology revealed age-related muscle atrophy and reduced collagen and elastin density. Conclusions: Sex defines the baseline morphometric framework of the adult larynx, whereas aging, particularly beyond 60 years, drives qualitative structural degeneration. These findings provide a reproducible anatomical reference for distinguishing sex-related variation from age-related changes in diagnostic assessment. Full article

Background and Objectives: The biological state of anterior cruciate ligament (ACL) remnant tissue may influence postoperative healing, yet the molecular changes associated with injury chronicity remain poorly defined. This study evaluated MMP-13 and TGF-β1 expression in human ACL remnants to characterize their regenerative or fibrotic potential. Materials and Methods: ACL remnants from acute (<3 months) and chronic (>6 months) injuries were analyzed using histology, immunohistochemistry, and QuPath-based digital quantification. Clinical outcomes were correlated with marker expression. Protein–protein interaction and KEGG enrichment analyses were performed to identify extracellular matrix (ECM)-related pathways associated with MMP-13 and TGF-β1. Results: Chronic ACL remnants exhibited disorganized ECM structure with significantly higher MMP-13 and TGF-β1 expression across all digital metrics, including DAB-positive area, cell density, optical density, and H-score (p < 0.01). Higher expression of both markers correlated with lower IKDC and Lysholm scores and greater residual pivot-shift positivity. Bioinformatic analysis identified 39 shared proteins enriched in ECM-receptor interaction, TGF-β signaling, and fibrosis-related pathways, aligning with the degenerative phenotype observed in chronic tissue. Conclusions: ACL remnant biology evolves from a reparative profile in acute injuries to a fibrotic, matrix-degradative state in chronic injuries. MMP-13 and TGF-β1 serve as indicators of remnant quality and may help guide timing of surgery and future biologic strategies aimed at improving ACL reconstruction outcomes. Full article

Benzo(a)pyrene (B[a]P) is a pervasive freshwater pollutant, yet its toxicity to the fish gallbladder remains poorly understood. This study investigated the toxicological impacts of 2.5 and 25 μg/L B[a]P on common carp (Cyprinus carpio) using histological, transcriptomic, and single-cell RNA sequencing (scRNA-seq) analyses. Results showed that the gallbladder is a primary site for B[a]P accumulation. High B[a]P concentrations caused vacuolar degeneration of mucosal epithelial cells and nuclear deformities. Transcriptomic analysis revealed that B[a]P stress triggered autoimmune homeostasis imbalance and overinhibited apoptosis. scRNA-seq identified cellular heterogeneity changes, specifically T-cell impairment and epithelial cell (EC) proliferation. Mechanistically, T-cell reduction was linked to the T-cell 2 subset, while EC proliferation involved EC 0 and EC 4 subsets, all participating in the apoptosis pathway. These findings demonstrate that the apoptosis pathway is a key target of B[a]P toxicity in the gallbladder. This work provides a cellular-level framework for assessing environmental polycyclic aromatic hydrocarbon (PAH) risks in aquaculture. Full article

Liver disease represents a major global health issue, with limited availability of effective hepatoprotective treatments. Hojasé or hojasén or Flourensia cernua (Fc) is known for its antioxidant properties and high phenolic content and may exhibit a potential hepatoprotective effect. Additionally, natural products have been shown to restore gut microbiota and reduce liver inflammation. To evaluate the hepatoprotective activity of Fc and its impact on gut microbiota in a valproic acid (VPA)-induced injury model in Wistar rats. Seven groups of Wistar rats (n = 6) were treated as follows: Sham; Non-toxic Fc (NTox 200 and 400 mg/kg); VPA 500 mg/kg; VPA + Fc 200 and VPA + Fc 400; and silybinin 500 mg/kg (VPA + Slb). Liver function tests, malondialdehyde (MDA) and superoxide dismutase (SOD) markers, aerobic gut microbiota analysis, and histological analysis were conducted. No significant differences were observed in ALT and AST levels between NTox 200, NTox 400, and Sham. Only the 400 mg/kg dose of Fc significantly reduced ALT and AST versus VPA, similar to Slb. In VPA + Fc 200 and VPA + Fc 400, MDA and SOD decreased versus VPA, comparable to VPA + Slb. Only VPA + Fc 400 and VPA + Slb restored aerobic gut microbiota versus VPA. No histological changes were observed between groups. Fc extract demonstrated hepatoprotective effects at a dose of 400 mg/kg and impacted the restoration of aerobic gut microbiota against VPA-induced damage. Full article

Thymic malignancies are rare cancers arising from thymic epithelial cells and are characterized by a highly diverse clinical phenotype, substantial histologic and morphologic heterogeneity, and frequent associations with autoimmune syndromes. Although the clinical, immunological, and cytoarchitectural changes associated with thymomas have been increasingly elucidated in the contemporary literature, very few studies have interrogated the direct role of tumor staging and histological grading in shaping autoimmunity burden and infection risk. In this narrative review, we synthesize contemporary clinical, immunological, and morphologic evidence linking thymic architecture and selection defects to the spectrum of paraneoplastic autoimmunity (MG, pure red cell aplasia, Good’s syndrome) and to infectious vulnerability. We further appraise emerging therapeutic strategies, including immune checkpoint inhibition and adoptive cellular approaches, through a patient-stratified lens, emphasizing efficacy signals, immune-related adverse events, and practical considerations for selection and monitoring. We conclude by highlighting priorities for future investigation, including refining autoantibody signatures; mapping thymic microenvironments that drive tolerance failure, and prospectively evaluating stratified immunotherapeutic regimens that balance benefit with immune-mediated risk. Full article

Objectives: To evaluate the impact of non-invasive imaging techniques such as dermoscopy, reflectance confocal microscopy (RCM) and optical coherence tomography (OCT) to monitor the efficacy of risankizumab on plaque psoriasis of the legs by analyzing morpho-histological changes. Materials and Methods: Multicentre, real-world retrospective study involving 37 adults with moderate-to-severe plaque psoriasis. Assessments performed during routine visits at baseline, Week 4 and Week 12 included clinical response, dermoscopy, RCM and OCT. Results: Thirty-seven patients were included (mean age 52.1 years; 54% male; mean BMI 27.0 kg/m²). Dermoscopy showed progressive vascular normalization: at Week 12, 94.29% of lesions had minimal or no vascular pattern. White and yellow scales decreased significantly. On RCM, dilated vessels, inflammatory infiltrate, and papillomatosis progressively normalized. OCT showed reduction in epidermal and stratum corneum thickness and a decline in vascular intensity at multiple depths. Baseline haemorrhagic dots predicted early complete response: 44.8% of lesions with dots achieved complete clearance at Week 4 versus 0% without. Conclusions: Risankizumab induced rapid, significant regression of psoriatic changes, normalizing vascular patterns and skin architecture and reducing epidermal thickness. Findings support its efficacy and rapid onset of action in difficult-to-treat areas and highlight the value of non-invasive imaging for monitoring. Full article

Background/Aim: Fermented soybean-based products are known to influence gut microbial composition; however, the long-term effects of multicomponent soybean fermented preparations on gut microbiota and colonic mucosal features remain insufficiently characterized. This study examined the effects of a commercially available soybean fermented preparation (SFP), containing additional fermented plant and marine derived components, on gut microbial community structure and colonic histological features in BALB/c mice. Methods: BALB/c mice received oral SFP (1000 mg/kg) for 30 and 60 days. Gut microbial communities were analyzed using full-length rRNA operon sequencing. Colonic mucosal architecture and goblet cell density were evaluated via histological analysis (H&E). Results: SFP supplementation induced significant β-diversity separation at both 30 and 60 days (p < 0.05), indicating consistent restructuring of the gut microbial community. While alpha diversity (Observed OTUs) remained stable at 30 days, Shannon and Simpson indices were significantly reduced at 60 days (p = 0.001), indicating reduced community evenness driven by increased dominance of specific taxa, including Duncaniella. At the genus level, SFP administration was associated with increased relative abundances of Akkermansia, Lactobacillus, and Duncaniella, accompanied by reductions in several genera previously linked to dysbiosis. Histological analysis demonstrated a significant increase in goblet cell density (p < 0.01) in SFP-treated mice. Conclusions: Long-term SFP supplementation was associated with sustained alterations in gut microbial composition and measurable histological changes in the colonic mucosa. While these findings indicate that SFP intake influences microbial structure and goblet cell abundance, further studies are required to determine the functional and physiological implications of these changes, particularly in relation to epithelial barrier function and host health. Full article

The compatibility of economic efficiency and animal welfare is a major challenge given the increasing demand for animal-based foods. Various studies have shown that it is possible to promote the resistance and robustness of commercial poultry (primarily broilers) by modifying incubation temperatures. Focused on the histology of the Bursa fabricii, an important lymphatic organ in birds, the investigations in this paper aim to show whether short-term temperature changes during final incubation (+1 °C, 2 h/incubation day 17–20) could have an influence on the robustness of broilers compared to conventionally incubated ones. Overall, however, the temperature stimulation during final embryonic development did not result in any statistically significant morphological changes in the bursa or in the heterophil-to-lymphocyte ratio (HLR) that would clearly indicate improved immune function. However, there are obvious sex-specific differences. For instance, a sexual dimorphism could be seen in the parameters of follicle number, follicle density and in the HLR when looking at the absolute numbers. Calculation of the effect size using Cohen’s d showed that there was an effect on the relative weight of the Bursa fabricii (d = −0.28, d ♂ = −0.25, d ♀ = −0.35) cell density (d ♀ = −0.32), follicle density (d ♀ = 0.37) and the HLR (d = 0.24, d ♂ = 0.43), so that further investigations should be encouraged. Full article

Background: Developing an evidence base for physiotherapy programs for patients with Cerebral Palsy (CP) requires an understanding of the microscopic and metabolic processes in striated muscle. The gracilis muscle represents a logical object of study due to the significant morphological changes in individuals with cerebral palsy. This research aims to study morphological and biochemical alterations in the gracilis muscle depending on the severity of motor impairments in CP patients. Methods: The cross-sectional study included 24 patients stratified by the severity of motor impairment. Intraoperative gracilis muscle samples were obtained during tenomyotomies. Nutritional status of patients, morphometric, and biochemical parameters were evaluated. Results: Initial body mass and Quetelet index (p = 0.02) were lower in GMFCS V patients (p = 0.01) compared to GMFCS IV and GMFCS II-III. Muscle tissue predominated in histological samples of GMFCS II-III and GMFCS V patients (p = 0.79), while connective tissue content was higher in the GMFCS IV group (p = 0.03). Strong, fast-twitch, anaerobic fibers (p = 0.761) with reduced creatine phosphokinase activity (p = 0.012) were more frequently observed in the intraoperative samples of GMFCS V patients. Low creatine phosphokinase activity was revealed in children in the GMFCS V group (p = 0.012). Conclusions: The structural and metabolic abnormalities observed in gracilis muscle of patients with spastic cerebral palsy indicates profound functional muscular dysfunction, representing one of the factors limiting children’s motor ability. The morphological and biochemical alterations in the striated muscle of CP children correlate with severity of motor dysfunction conditioned by the primary upper motor neuron disorders. Less significant changes in muscles in ambulatory children reflect favorable basis for physical therapy. Full article