Search Results (10,713)

Background/Objectives: Iron deficiency anemia (IDA) is a widespread nutritional disorder characterized by impaired iron absorption, inflammation-associated iron restriction, and disrupted iron homeostasis. Increasing evidence suggests that gut microbiota play an important role in iron metabolism; however, the mechanisms underlying probiotic-assisted iron supplementation remain unclear. Our research group previously conducted in vitro fermentation screening experiments and obtained a bacterial strain, B. lactis Ca360, which possesses iron absorption-enhancing activity. Methods: In this study, an IDA mouse model induced by a low-iron diet was used to investigate whether B. lactis Ca360 could synergistically improve iron metabolism when combined with iron supplementation. Mice were treated with FeSO₄ alone or FeSO₄ combined with B. lactis Ca360, and hematological parameters, organ indices, serum iron-related markers, histopathological changes, duodenal iron metabolism-related gene expression, hepatic inflammatory responses, gut microbiota composition, short-chain fatty acid (SCFA) levels, and correlation networks were analyzed. Results: Iron deficiency induced typical anemia phenotypes, multi-organ dysfunction, intestinal iron absorption dysregulation, hepatic inflammation, and gut microbiota dysbiosis. Compared with FeSO₄ alone, the combined intervention more effectively improved hematological parameters, reduced organ indices, restored liver and spleen histological integrity, normalized intestinal iron metabolism-related gene expression, and alleviated hepatic inflammation. In addition, B. lactis Ca360 markedly reshaped gut microbiota composition, enriching SCFA-producing anaerobic genera, including Ruminococcus, Roseburia, Acetatifactor, Intestinimonas, Eubacterium_coprostanoligenes_group_unclassified, and Oscillibacter, accompanied by increased acetate, propionate, and butyrate levels. Spearman correlation analysis further revealed close associations between gut microbiota remodeling, improved iron metabolism, reduced inflammatory status, and recovery of anemia-related phenotypes. Conclusions: Overall, these findings demonstrate that B. lactis Ca360 enhances the efficacy of iron supplementation by modulating SCFA-producing and anti-inflammatory gut microbiota, thereby coordinately regulating intestinal iron absorption, inflammation, and systemic iron homeostasis, supporting probiotic-assisted iron supplementation as a promising nutritional strategy for IDA management. Full article

Background/Objectives: The limited targeting efficiency and systemic toxicity of conventional medicine present significant challenges in the treatment of skeletal disorders, such as bone tuberculosis. To address these limitations, we developed a bone-targeting nanomicelle delivery system functionalized with alendronate (ALN), designated ALN-PLGA-mPEG@RPT, to improve the targeted delivery and therapeutic efficacy of rifapentine (RPT) in bone tissue. Methods: The ALN-PLGA-mPEG blank micelles, prepared in accordance with our research group’s optimized protocol, were loaded with RPT and subjected to systematic formulation optimization. The resulting nanomicellar system was comprehensively characterized in terms of its physicochemical properties, including particle size and polydispersity index (PDI). Additionally, drug-loading capacity, encapsulation efficiency, and in vitro release curve were evaluated. Bone-targeting efficacy was assessed using in vivo imaging techniques, while biodistribution and safety profiles were determined through in vivo distribution studies and histopathological examination. Results: The optimized ALN-PLGA-mPEG@RPT nanomicelles exhibited a mean particle size of 101.90 ± 4.17 nm, and a PDI of 0.242 ± 0.021. The formulation achieved a drug loading of 16.74 ± 0.51% with an encapsulation efficiency of 50.27 ± 1.91%. In vitro release studies confirmed a sustained-release profile, with only 25% of RPT released within 12 h. In vivo imaging revealed significantly enhanced bone-targeting capability in the ALN-modified group, showing a 1.93-fold higher drug accumulation in bone tissue compared to blood. Histopathological analysis indicated no observable pathological alterations in major organs. Conclusions: The ALN-PLGA-mPEG@RPT nanomicelle system exhibits favorable bone-targeting efficiency, sustained-release properties, and biocompatibility, representing a promising strategy for the precise treatment of bone tuberculosis and other skeletal diseases. Full article

Autoantibodies targeting α6β4 integrin have been identified in individual patients with mucous membrane pemphigoid (MMP). Reactivity against α6 integrin has been associated with oral lesions, while anti-β4 integrin reactivity has been linked to ocular involvement. However, the pathogenic effects of these antibodies have not been fully elucidated. Here, we investigated the pathogenic potential of anti-α6 and anti-β4 integrin IgG both in vitro and in vivo. Immune complexes of anti-α6 and anti-β4 integrin induced the release of reactive oxygen species from normal human leukocytes and stimulated CXCL2 secretion in cultured murine C5N keratinocytes. In vivo, repeated injections of IgG against a recombinant fragment of β4 integrin into C57BL/6 mice led to palpebral conjunctival swelling and mild oral lesions. The latter was observed following injection of IgG against a recombinant fragment of α6 integrin. Histopathological analysis revealed subepithelial inflammatory infiltrates without evidence of split formation. Direct immunofluorescence microscopy showed linear deposits of IgG at the basement membrane zone in most tissues, whereas C3 deposition was largely absent. This lack of complement activation was corroborated by a complement fixation assay, which confirmed that IgG against α6 and β4 integrin failed to induce C3 deposition in normal murine conjunctivae, buccal mucosa, or skin. Collectively, these findings indicate that IgG autoantibodies against α6 and β4 integrin exhibit pathogenic activity in vitro and induce mild disease in vivo, possibly due in part to relatively inefficient complement activation in this model. Full article

Background: Autophagy is a conserved intracellular degradation pathway essential for maintaining cellular homeostasis by recycling damaged organelles and proteins. Dysregulation of autophagy has been implicated in pregnancy-related complications such as preeclampsia and fetal growth restriction, underscoring its importance in maternal and fetal health. However, the autophagy status in the placental tissue of COVID-19-infected pregnant women remains unknown. Objective: To investigate autophagy activity in term placentas from pregnant women infected with COVID-19 compared to those from uninfected control pregnant women. Methods: In this prospective cross-sectional single-center study, 15 COVID-19-positive and 15 COVID-19-negative term pregnant women who delivered at Sultan Qaboos University Hospital between January 2020 and December 2022 were included. Immediately after delivery, the placental tissue samples were collected and assessed for autophagy activity using immunohistochemistry for LC3B and p62 markers, histopathological examination, and transmission electron microscopy. The proportion and intensity of LC3B and p62 staining were quantified. Statistical analysis was performed using the Mann–Whitney U test. Results: There was a significant reduction in p62 and LC3B expression in both the proportion and intensity in COVID-19 placentas compared to the control group. The proportion of p62 (p = 0.001) and LC3B (U = 46.000, p = 0.003) was significantly reduced in infected placentas. Similarly, intensity levels of both markers showed significant differences (p < 0.05), supporting the evidence of reduced LC3B/p62, suggesting autophagy modulation in COVID-19 patients’ placentas. Additionally, abnormal ultrastructural changes were observed in COVID-19–positive placentas, including mitochondrial injury, endoplasmic reticulum stress, microvillus loss, and basement membrane thickening. Conclusion: The study results from a limited sample size demonstrate a significantly altered autophagy flux in the placental tissues of term pregnant women with COVID-19 infection. These findings highlight the potential impact of COVID-19 infection on placental function and fetal development and underscore the need for further investigation into autophagy-modulating strategies to improve maternal–fetal health. Full article

Background: While smoking is the dominant global driver of lung cancer, less than a quarter of Ethiopian patients have ever smoked, pointing to locally relevant risk factors. Evidence to guide prevention and early detection in resource-limited settings is scanty. Methods: To address this gap, this study conducted a multicenter matched case–control study including 351 histopathologically confirmed primary lung cancer cases and 702 hospital-based controls matched by sex, age (±5 years), and residence. Directed acyclic graphs informed the selection of variables, and multivariable hierarchical conditional logistic regression was used to identify risk factors beyond smoking. Results: The analysis shows that lung cancer was independently associated with low education, wealth, solid-fuel use, occupational exposure, insufficient physical activity, meat-based and processed food dietary patterns, secondhand smoke (SHS), prior tuberculosis, and family history of cancer. Subgroup analysis by sex revealed consistent associations across males and females, but exposure distributions explained sex-specific patterns: smoking, occupational exposure, meat-based diets, and family history were more common among males, whereas SHS, the use of solid fuels, and processed food dietary patterns predominated in females. Conclusions: Lung cancer in Ethiopia appears to be associated with several factors in addition to smoking. Gender-sensitive public health interventions targeting these locally relevant risk factors are essential for effective prevention and early detection. Full article

Introduction: Immune checkpoint inhibitors (ICIs) have transformed the treatment of metastatic melanoma; however, predictive markers of therapeutic response remain poorly defined. This study systematically assesses clinical, histological, and molecular predictors associated with survival outcomes in melanoma patients treated with ICIs. Methods: Following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) and the Meta-Analysis of Observational Studies in Epidemiology (MOOSE) guidelines, a systematic search was conducted in MEDLINE, Web of Science, and the Cochrane Central Register of Controlled Trials (CENTRAL) for studies published between January 2018 and October 2025. Eligible studies reported associations between predictive factors and overall survival (OS) or progression-free survival (PFS) in adult melanoma patients receiving ICIs. Pooled hazard ratios (HRs) with corresponding 95% confidence intervals (CIs) from univariate (UVA) and multivariate analyses (MVA) were synthesized using random-effects meta-analyses. Results: Sex was not a consistent predictor (contradictory effects; PFS heterogeneity I² ≈ 90%), whereas older age predicted worse OS (MVA continuous: HR 1.05, 95% CI 1.02–1.08; UVA ≥ 65 vs. <65: HR 1.70, 95% CI 1.36–2.12). Poor performance status, assessed using the Eastern Cooperative Oncology Group (ECOG) scale, strongly predicted inferior outcomes (ECOG ≥ 1 vs. 0: MVA OS HR 2.01, 95% CI 1.61–2.51; MVA PFS HR 1.49, 95% CI 1.18–1.88; ECOG ≥ 2 vs. <2: MVA OS HR 2.24, 95% CI 1.79–2.81). Elevated lactate dehydrogenase (LDH) was consistently associated with poorer survival (MVA OS HR 1.71, 95% CI 1.53–1.91; MVA PFS HR 1.61, 95% CI 1.41–1.85), whereas body mass index (BMI) > 25 kg/m² was associated with improved OS (HR 0.82, 95% CI 0.68–0.98). Higher disease burden predicted worse prognosis (Stage IV vs. III: MVA OS HR 1.57, 95% CI 1.16–2.13; >2 metastatic sites vs. ≤2: MVA OS HR 2.38, 95% CI 1.40–4.07; brain metastases: MVA OS HR 1.69, 95% CI 1.30–2.20; MVA PFS HR 1.52, 95% CI 1.00–2.33). Histologic and molecular factors showed prognostic value: ulceration worsened OS (UVA HR 2.08, 95% CI 1.25–3.44) and PFS (UVA HR 2.97, 95% CI 1.39–6.32); acral subtype had poorer OS than cutaneous melanoma (MVA HR 2.99, 95% CI 1.63–5.48); high tumor mutational burden (TMB) improved PFS (UVA HR 0.47, 95% CI 0.33–0.70); and cutaneous immune-related adverse events (irAEs) were associated with favorable outcomes (skin disorders: UVA OS HR 0.26, 95% CI 0.14–0.47; UVA PFS HR 0.50, 95% CI 0.34–0.74). In contrast, detectable circulating tumor DNA (ctDNA) predicted markedly worse PFS (MVA HR 4.72, 95% CI 2.31–9.65) and a non-significant trend toward worse OS (MVA HR 3.34, 95% CI 0.96–11.67). Liver metastases and programmed death-ligand 1 (PD-L1) expression were not significantly associated with survival. Discussion: This meta-analysis synthesizes evidence on clinicopathologic, laboratory, and histopathologic predictors of immunotherapy outcomes in metastatic melanoma. Performance status, age, LDH, BMI, and metastatic burden consistently correlated with prognosis, while ulceration, disease stage, and TMB emerged as key histologic determinants. Conversely, PD-L1 and gender showed no consistent predictive value, whereas cutaneous immune-related adverse events and ctDNA reflected favorable and poor outcomes, respectively. These findings highlight the multifactorial nature of immunotherapy response and support the further development of integrated prognostic models to refine patient stratification and optimize treatment outcomes. Full article

Background/Objectives: Dementia remains one of the major global health challenges of the modern era. Researchers worldwide continue to seek effective therapeutic strategies to combat this neurodegenerative condition. Silymarin is a natural compound with strong neuroprotective and antioxidant properties that holds great potential for dementia management; however, its poor aqueous solubility and limited ability to cross the blood–brain barrier (BBB) have restricted its clinical application. This study focused on the formulation and evaluation of a heparin–pullulan silymarin liposomal (HPSL) nano-gel to enhance the neuroprotective efficacy of silymarin, with potential for improved brain targeting effects. Methods: The HPSL nano-gel was synthesized using the thin-film hydration technique and optimized based on entrapment efficiency, particle size distribution, zeta potential, and in vitro release kinetics. The neuroprotective efficacy of the HPSL nano-gel was evaluated in mice using behavioral evaluations, biochemical quantification of oxidative stress markers, evaluation of cholinergic enzyme activity and detailed histopathological examination of brain tissues. Results: Morphological characterization using scanning electron microscopy (SEM) confirmed a uniform nano-scale structure. The optimized formulation (HPSL-3) exhibited a particle size of 406.07 ± 19.33 nm, zeta potential of −23.72 ± 7.64 mV and an entrapment efficiency of 73.53 ± 12.05%, indicating good colloidal stability and efficient drug loading. The in vitro release profile followed non-Fickian diffusion kinetics, suggesting sustained drug release behavior. Behavioral studies in scopolamine-induced amnesic mice (elevated plus maze, hole board, and light/dark paradigms) demonstrated significant (p ≤ 0.001) improvements in learning and memory retention. Biochemical analyses showed increased levels of ChAT, SOD, CAT, and GSH, along with decreased AChE and MDA levels, supporting the neuroprotective potential of the formulation. Histopathological evaluation revealed marked attenuation of neuronal degeneration, inflammation, and edema (HAI = 4) compared to the scopolamine-treated group (HAI = 11). Conclusions: Overall, the HPSL-2 formulation effectively enhanced silymarin delivery across the BBB, demonstrating potent antioxidant, neuroprotective, and cholinergic modulatory effects. These findings suggest that HPSL-2 represents a promising nano-carrier system for the management of dementia and other oxidative-stress-related neurological disorders. Full article

Background/Objectives: Solitary rectal ulcer syndrome (SRUS) is a rare benign disorder presenting with rectal bleeding, straining, and mucosal discharge. Its pathogenesis likely involves pelvic floor dysfunction, particularly dyssynergic defecation. Although studied in adults, pediatric data—specifically anorectal manometry (ARM) findings—remain limited. We aimed to evaluate dyssynergic defecation in pediatric SRUS using ARM and analyze associated clinical, endoscopic, histopathological, and treatment data. Methods: A retrospective study of 24 children with biopsy-proven SRUS diagnosed between 2016 and 2024 was conducted. Clinical symptoms, colonoscopic, histopathological, treatment, and outcome data were reviewed. ARM was performed in 20 patients unresponsive to conservative treatment to assess anal pressures, rectal sensation, rectoanal inhibitory reflex, and balloon expulsion. Results: The median age was 13 years, with male predominance. Rectal bleeding was the most common symptom (95.8%). Colonoscopy revealed predominantly solitary ulcerative lesions 5–10 cm from the anal verge. Dyssynergic defecation was detected in 60% of patients, and only 25% could expel the balloon. Resting anal pressures were lower than reference values. Treatments included diet, laxatives, and topical agents, with partial or complete clinical response in approximately 60% of patients after 12 months. Conclusions: Pediatric SRUS is strongly associated with dyssynergic defecation. More pediatric-specific manometric studies are needed to optimize diagnosis and guide targeted therapies. Full article

Purpose: Accurate preoperative risk stratification in endometrial cancer (EC) is essential for guiding surgical and therapeutic decisions. This study aimed to evaluate the discriminative performance of [18F]-FDG PET/CT-derived radiomic features combined with machine learning models for differentiating low-risk (LRH-EC) and high-risk histology (HRH-EC) subtypes. Methods: A total of 159 patients with histopathologically confirmed EC who underwent preoperative [18F]-FDG PET/CT were retrospectively analyzed. Radiomic features were extracted using LIFEx version 7.4.0 software following IBSI guidelines. After FDR correction and Pearson correlation–based redundancy reduction (|r| > 0.80), 16 radiomic features were retained for modeling. Three feature configurations (Conventional PET parameters, Radiomics16, and Combined) were evaluated. Machine learning models were developed using stratified 5-fold cross-validation. Model performance was assessed using AUC, accuracy, sensitivity, specificity, F1-score, Wilson confidence intervals, DeLong’s test, and McNemar’s test. Results: Artificial Neural Network (ANN) (AUC = 0.709) and Random Forest (RF) (AUC = 0.686) achieved the highest discriminative performance within the Radiomics16 feature set. No statistically significant superiority between algorithms or feature configurations was observed by DeLong analysis. However, McNemar’s test demonstrated significant patient-level classification differences for the Combined ANN model (p < 0.001). NGTDM_Coarseness and SUVmin emerged as the most influential features, reflecting tumor heterogeneity and metabolic activity. Conclusions: [18F]-FDG PET/CT-based radiomics combined with machine learning provides moderate yet consistent discrimination between LRH-EC and HRH-EC. While external validation is required, this approach may support noninvasive preoperative risk stratification in endometrial cancer. Full article

Background/Objectives: 18F-fluorodeoxyglucose (FDG) positron emission tomography/computed tomography (PET/CT) is used in oncology but has limited specificity due to uptake in infectious and inflammatory conditions. This study evaluated the diagnostic value of 18F-FDG PET/CT in patients with infectious, inflammatory, and malignant lesions and its role in guiding histopathological biopsy decisions in an infectious disease setting. Methods: A retrospective cohort study included 186 adult patients who underwent 18F-FDG PET/CT between 2018 and 2023 for diagnostic evaluation at a tertiary care hospital. Clinical indications were fever of unknown origin (FUO), inflammation of unknown origin (IUO), lymphadenopathy of unknown origin, and suspected solid mass. Diagnostic yield, biopsy decisions, and factors associated with biopsy were analyzed. Results: The diagnostic yield of 18F-FDG PET/CT was 58.6%, with higher in malignant conditions (hematologic malignancy 85.7%, solid organ malignancy 88.9%) and lower in autoimmune/inflammatory diseases (20.8%) and mycobacterial infections. PET/CT showed moderate sensitivity (59.8%) and high specificity (98.7%) for infection detection, improving to 67.8% sensitivity after excluding mycobacterial infections. Biopsy was performed more in patients with lymphadenopathy, higher SUVmax (>7.4), and PET/CT findings not suggestive of infection. Analysis identified lymphadenopathy (aOR = 2.77), PET/CT not suggestive of infection (aOR = 4.73), and SUVmax > 7.4 (aOR = 4.98) as predictors of biopsy. Conclusions: 18F-FDG PET/CT provides moderate diagnostic value across infectious, inflammatory, and malignant diseases and guides biopsies effectively, particularly in patients with lymphadenopathy, elevated SUVmax, and non-infectious findings. Its limited performance in mycobacterial and autoimmune diseases requires cautious interpretation. Overall, 18F-FDG PET/CT supports clinical decisions in complex diagnostic scenarios. Full article

Rumenitis is an inflammatory condition of the rumen, typically seen in adult cattle managed on high-energy diets. In calves, it is uncommon and often linked to ruminal drinking due to esophageal groove dysfunction. Early diagnosis is challenging due to nonspecific clinical signs. A one-month-old male Limousin calf was presented with persistent non-fetid fluid regurgitation, rhythmic mastication, inappetence, and progressive neurological signs. Clinical examination revealed signs of dehydration and neurological dysfunction. Laboratory evaluation demonstrated metabolic acidosis (pH 7.16), hyperkalemia, and elevated serum urea. Endoscopy identified diffuse mucosal hyperemia, erosions, and fluid accumulation in the rumen. Symptomatic and supportive therapy was initiated; however, the calf died spontaneously. Necropsy was therefore performed, and rumen samples were collected for histological and microbiological investigations. Histopathological analysis confirmed acute suppurative rumenitis. The microbiological culture of rumen and reticulum samples yielded mixed bacterial flora, including Escherichia coli and Proteus mirabilis. The fungal culture isolated Penicillium spp., Mucoraceae, Geotrichium spp., and Aspergillus fumigatus. This case details the value of integrating clinical examination, blood gas analysis, endoscopy, histopathology, and microbiology in diagnosing rumenitis in young calves. Although Limousin calves are not considered predisposed, management and feeding practices may play a critical role in disease onset. Rumenitis should be considered in calves presenting persistent regurgitation and neurological signs. Early, minimally invasive diagnostics such as endoscopy can improve diagnostic accuracy and inform timely clinical decision-making. Full article

Background/Objectives: Xu Chunfu’s Modified Xianglian Pill (XXLP) has been used for centuries in Chinese medicine to treat “diarrhea” and “dysentery,” conditions analogous to modern ulcerative colitis (UC). However, the scientific basis for its efficacy and mechanisms remains unclear. Methods: The chemical composition of XXLP was analyzed via UPLC-ESI-MS/MS. A colitis mouse model was established using DSS, and the therapeutic effects were assessed based on body weight, disease activity index (DAI), colon length, and histopathology. Inflammatory cytokines were measured using ELISA. Proteomic analysis and molecular docking identified key targets, which were validated using LPS-induced HT-29 cells via Western blot (WB), qRT-PCR, immunofluorescence (IF), and transmission electron microscopy (TEM). Gut microbiota composition was analyzed using 16S rRNA gene sequencing. Results: Analysis of XXLP led to the detection of 373 compounds. XXLP significantly improved colitis symptoms, including weight loss and colon shortening, and reduced the concentrations of inflammatory markers IL-1β, IL-18, TNF-α, and IL-6. Proteomics and molecular docking identified NADPH oxidase 2 (NOX2) as a key target of XXLP intervention in mice with colitis. qRT-PCR, WB, IF, and TEM results further confirmed that XXLP effectively suppressed the expression of NOX2 and its associated protein levels. Sequencing analysis of 16S rRNA showed that XXLP significantly increased the relative abundance of beneficial bacterial genera (Muribaculaceae and Ruminococcaceae) while markedly reducing the levels of harmful bacteria (Enterobacteriaceae). Correlation analysis revealed that specific microorganisms were correlated with NOX2-related protein expression and severity of colonic inflammation. Conclusions: XXLP effectively alleviates colitis by suppressing inflammatory responses. Its mechanism involves regulating the NOX2/ROS/mitochondria/NLRP3 axis and altering gut microbiota composition, providing novel insights for colitis treatment. Full article

Neoplasia of the cornea is overall rare, with corneal squamous-cell carcinoma (c-SCC) being most commonly reported in all species. C-SCC pathogenesis has been related to UV exposure in humans and horses, and to papillomavirus infection in humans. In dogs, brachycephalic conformation and chronic keratitis were associated with c-SCC. Corneal vascular tumors have also been exceptionally reported in humans, and rarely in animals. In dogs, they have been suggested to be UV-related. Except for equine c-SCCs, most studies on corneal neoplasms are case reports. The present study aimed to review the literature on epithelial and vascular corneal tumors in dogs, cats, and horses, adding new cases from our archives. Pubmed and Web of Science were searched (1980–2025) using the following keywords: cornea, neoplasia, carcinoma, hemangioma, hemangiosarcoma, dog, cat, and horse. Additionally, 94 new cases of corneal neoplasia were retrieved: 47 dogs (40 epithelial and seven vascular); 29 cats (14 epithelial and 15 vascular) and 18 horses. Signalment, clinical history, and histopathological characteristics were analyzed and compared with the literature. The combined results supported a strong association between brachycephalic dogs and c-SCC occurrence and highlighted the frequent coexistence in the feline species of symblepharon and corneal perforation, with corneal tumors. Full article

Objective: The therapeutic efficacy of the classic antibiotic combination trimethoprim/sulfamethoxazole (TMP/SMZ) is often limited by the significant pharmacokinetic mismatch. In this study, a polyethylene glycol-polylactic-co-glycolic acid (PEG-PLGA) nanodelivery system was employed to improve the pharmacokinetic matching of TMP and SMZ. The investigation also evaluated the enhanced in vivo antibacterial efficacy of this formulation. Methods: Ultra-High Performance Liquid Chromatography–Tandem Mass Spectrometry (UPLC-MS/MS) was employed to systematically characterize the absorption, distribution, and excretion profiles of PEG-PLGA-loaded TMP nanoparticles (NPs) in rats. In vitro antibacterial activity was assessed against Escherichia coli (E. coli) and Staphylococcus aureus (S. aureus). In vivo efficacy and biosafety of the TMP NPs/SMZ regimen were evaluated using a murine E. coli infection model via survival monitoring, biochemical assays, and histopathology. Results: Pharmacokinetic analysis revealed that TMP NPs achieved a relative bioavailability of 193.05% and extended the elimination half-life by 3.37-fold compared to free TMP. Tissue distribution showed significantly increased drug accumulation in the liver, spleen, and kidneys, with renal clearance as the primary excretion pathway (73.89%). In vitro, the nano-formulation reduced the minimum inhibitory concentration (MIC) by 2-4-fold and shortened the bactericidal duration from 12 to 8 h. In vivo, the TMP NPs/SMZ combination significantly improved survival rates, accelerated recovery, and alleviated infection-induced organ damage without systemic toxicity. Conclusions: This nanotechnology-based strategy effectively aligns the pharmacokinetics of TMP and SMZ, prolongs their synergistic window, and enhances biosafety, offering a viable approach to revitalize classic antibiotic combinations. Full article

Foreign material is an uncommon finding in routine gastrointestinal histopathology, but may occasionally contribute to disease pathogenesis or create diagnostic pitfalls. We report two illustrative cases highlighting the diverse clinical and histologic implications of ingested plant material. The first case involves a 10-year-old boy who presented with clinical features consistent with acute appendicitis and underwent appendectomy. Although gross examination revealed a macroscopically unremarkable appendix, histological evaluation demonstrated mucosal ulceration associated with an impacted plant seed within the appendiceal lumen, supporting a diagnosis of obstructive acute appendicitis. The second case describes a 60-year-old woman undergoing a screening colonoscopy, during which a small sessile lesion in the transverse colon was resected. Histologic examination revealed no colonic mucosa; instead, the specimen consisted entirely of plant material, morphologically consistent with a tomato seed, representing an incidental finding mimicking a colonic polyp. These cases underscore that plant seeds, while rare, may act as obstructive agents in appendicitis or simulate true pathological lesions during endoscopic and histologic evaluation. Awareness of the characteristic microscopic features of plant material is essential to avoid misdiagnosis and to recognise their potential clinical and forensic relevance. Full article