Search Results (10,030)

Nocardia, a rare but life-threatening pathogen, can invade multiple tissues and organs, such as lungs, brain, skin and soft tissue. In this study, we determined whether nitric oxide (NO) contributes to the severity of experimental pulmonary nocardiosis. BALB/c mice with or without aminoguanidine (AG) treatment were infected with N. farcinica through intranasal or intraperitoneal routes. Over experimental period, weight and mortality were monitored, and lung tissues were collected for NO production, cytokines detection, histopathological analysis, and bacterial load assessment. Next, alveolar MH-S macrophages were treated with various inhibitors to explore the impacts of NO, MAPK, and NF-κB against N. farcinica infection. AG treatment improved weight loss, lowered pulmonary bacterial load, and attenuated inflammatory response in infected mice. Similar effects were observed in alveolar MH-S macrophages. And all AG-treated mice survived infection. Furthermore, we suggest that NO is induced by N. farcinica through MAPK JNK and NF-κB signaling. Our study demonstrates the causative role of inducible NO on the severity of N. farcinica infection. Full article

Background/Objectives: To investigate the importance of ADC, SUVmax, and SUVmax/ADC values in the prognosis and biological behavior of prostate cancer. Methods: In this retrospective study, ADC measurements in diffusion MRI were made by two radiologists by correlating the lesions with the highest SUVmax value from Ga-68 PSMA PET/CT examinations of 81 patients with prostate cancer. The quantitative values were compared with histopathological grade, presence of perineural invasion, and lymph node and bone metastasis. Results: For D’Amico high-risk patients, a statistically significant difference among the ADC, SUVmax, and SUVmax/ADC measurements was reported (p < 0.001). Cut-off values were defined as 0.52 (×10⁻³ mm²/s) for ADC, 9.73 for SUVmax, and 20.28 for the SUVmax/ADC ratio (AUC = 0.887, 0.747, 0.817, respectively) for the high-risk categories. The Youden indices were 0.643, 0.405, and 0.437, respectively. In logistic regression, the SUVmax/ADC ratio was a significant predictor of the high-risk group (AUC = 0.844, p = 0.002), demonstrating superior performance to a model with individual ADC and SUVmax values (AUC = 0.796, p = 0.006). For the advanced-grade group, the SUVmax and SUVmax/ADC ratios differed significantly (p < 0.001). The CAPRA score showed significant correlations with all imaging biomarkers: negatively with ADC (rho = −0.456, p < 0.001) and positively with SUVmax (rho = 0.359, p = 0.001) and the SUVmax/ADC ratio (rho = 0.441, p < 0.001). The presence of perineural invasion had no significant correlation with any of the variables (p > 0.05). The presence of bone metastases and PSA and free PSA levels differed significantly (p = 0.003, p = 0.001, respectively). In the presence of lymph node metastasis, SUVmax and SUVmax/ADC ratios were found to be significant (p = 0.019, p = 0.01, respectively). In the survival (OS) analysis, a low ADC value was found to be associated with shorter survival (median OS: 61 vs. 106 months). Conclusions: Among advanced-grade and high-risk prostate cancer patients, ADC, SUVmax, and SUVmax/ADC values can be employed as alternative prognostic factors for predicting the biological behavior of the disease. Full article

Background/Objectives: High-frequency ultrasonography (HFUS) has gained increasing attention in dermatology as a non-invasive imaging technique capable of visualizing cutaneous structures with high resolution. In cutaneous T-cell lymphomas (CTCL), including mycosis fungoides (MF)/Sézary syndrome (SS), HFUS may provide an objective method for assessing disease activity and monitoring treatment response. This study aimed to evaluate the clinical utility of HFUS in detecting therapy-induced changes in subepidermal low-echogenic band (SLEB) thickness. Methods: We conducted a prospective, single-center study between May 2021 and May 2025. Thirty-three patients with histologically confirmed MF (n = 31) or SS (n = 2) underwent HFUS at baseline and after 4–8 weeks of treatment. SLEB thickness was measured before (E1) and after early treatment (E2). Patients received systemic agents, phototherapy, or topical regimens. Statistical analysis included mixed-model ANOVA with repeated measures to assess SLEB changes, and post hoc tests were applied to explore the influence of therapy type, age, and gender. Results: Among 31 evaluable patients with MF, HFUS revealed a significant reduction in SLEB thickness after treatment (0.90 ± 1.10 mm vs. 0.69 ± 0.89 mm; F(1,29) = 8.88, p = 0.006, η² = 0.23). The type of early therapy (systemic vs. topical) did not significantly affect outcomes (p = 0.452). Age emerged as a relevant factor: patients ≥ 66 years exhibited higher baseline SLEB values and a significant reduction post-treatment (p < 0.001), whereas no comparable effect was observed in younger patients. Gender did not significantly influence SLEB changes. Conclusions: HFUS is a sensitive and clinically applicable imaging tool for monitoring treatment response in MF/SS. Reductions in SLEB thickness were observed across therapeutic modalities and aligned with early clinical improvement. HFUS may serve as a valuable adjunct to standard clinical and histopathological evaluation in the routine management of MF/SS. Full article

Background: Deep infiltrating endometriosis (DIE) frequently affects the posterior pelvic compartment, where accurate non-invasive imaging is essential for diagnosis and surgical planning. Aim: This systematic review evaluates the diagnostic performance of transvaginal ultrasound (TVUS) in detecting posterior compartment DIE, specifically rectosigmoid lesions, uterosacral ligament involvement, and pouch of Douglas obliteration. Material and Methods: A comprehensive literature search of PubMed, Scopus, and Web of Science was performed for studies published between 2015 and 2025. Eligible studies assessed the accuracy of TVUS for posterior compartment DIE using laparoscopy and histology as reference standards. Data on sensitivity, specificity, and overall diagnostic accuracy were extracted or derived. The study’s quality was evaluated using the QUADAS-2 tool. Results: Thirty eligible studies were included. The mean sensitivities and specificities reported in the included studies reached 83.05% and 90.53% for rectosigmoid disease, 78.07% and 90.49% for uterosacral ligament involvement, and 79.58% and 89.75% for pouch of Douglas obliteration, respectively. Adjunctive techniques such as gel sonovaginography, rectal water contrast, or saline instillation into the pouch of Douglas were described, but their use was inconsistent. Marked heterogeneity in patient preparation, scanning protocols, and reporting limited comparability across studies. Despite this, TVUS demonstrated diagnostic performance within a similar range to that reported for MRI in prior systematic reviews, with the advantages of lower cost, accessibility, and integration into routine gynecological practice. Conclusions: TVUS is consistently reported as a reliable and cost-effective imaging modality and, in line with international guidelines, should be considered the first-line option for posterior compartment DIE, though further standardization of scanning and reporting protocols is needed to optimize reproducibility and clinical utility. Full article

Background/Objectives: MicroRNAs (miRNAs) regulate gene expression and are proposed as biomarkers in colorectal cancer (CRC). This study evaluated miR-185-5p, miR-141-5p, and miR-21-5p expression in CRC tissues; their association with tumor location, histopathology, and clinical outcomes; and the suitability of miR-16-5p and miR-151a-3p as housekeeping controls. Previous reports suggest tumor-suppressive roles for miR-185 and miR-141 and an oncogenic function for miR-21, though findings remain inconsistent. Methods: Paired tumor and adjacent normal tissues from 70 CRC patients were analyzed. RNA was extracted from FFPE samples, and miRNA expression quantified by RT-qPCR. Relative expression values were normalized to miR-151a-3p. Tumor–normal differences, localization effects, and associations with clinicopathological and outcome variables were assessed using repeated-measures ANOVA and non-parametric tests. Results: miR-185-5p and miR-141-5p were significantly reduced in tumors compared with normal mucosa while miR-21-5p was upregulated. miR-16-5p showed higher expression in normal tissue, indicating its instability and unsuitability as a housekeeping control. A modest but significant localization effect was observed for miR-185, while other miRNAs were minimally influenced by location. Baseline asymmetry between non-tumor samples, observed for miR-185-5p, further indicated sidedness effects. None of the miRNAs were associated with stage, histological type, grade, invasion, immune infiltration, progression, or five-year survival. Conclusions: miR-185-5p, miR-141-5p, and miR-21-5p show robust tumor–normal differences, supporting their diagnostic potential, while miR-16-5p is unsuitable as a housekeeper. Modest but significant localization effect was observed for miR-185 in right-sided tumors. None showed prognostic value in stage I–III CRC. Larger, location-stratified studies are warranted. Full article

Chronic sleep restriction (SR) impairs multiple organs. Although exogenous melatonin counteracts SR-induced gut microbiota disruption, its role in protecting renal function and the involvement of gut microbiota remain unclear. To this end, we subjected mice to a 28-day SR paradigm with exogenous melatonin treatment or antibiotic-induced microbiota depletion. SR mice demonstrated significant renal dysfunction evidenced by elevated serum creatinine, blood urea nitrogen, and uric acid levels compared to controls. Histopathological analysis revealed characteristic tubular abnormalities in SR mice, including epithelial degeneration and lumen dilation, with reduced expression of key renal filtration markers (Nephrin, Podocin, CD2-associated protein, and α-Actinin-4). All of these could be mitigated by melatonin treatment, and all changes were statistically significant (p < 0.05 or p < 0.01). Intriguingly, microbiota depletion significantly reversed the protective effect of exogenous melatonin on kidney injury in SR mice, while propionic acid supplementation mitigated SR-induced kidney injury. Furthermore, we found that gut microbiota and the metabolite propionic acid mediated the role of exogenous melatonin probably through attenuating SR-induced renal oxidative damage, including regulating renal superoxide dismutase (SOD) activity, total antioxidant capacity (T-AOC), and malondialdehyde (MDA) level. These findings collectively indicated that melatonin may ameliorate SR-associated kidney injury through gut microbiota-derived propionic acid. Our finding highlights a novel gut–kidney axis in SR-related pathophysiology. Full article

Background/Objectives: We aimed to evaluate the demographic characteristics, clinical findings, and survival outcomes of patients diagnosed with orbital metastasis, considering primary tumor type, age, and gender variables. Methods: In this observational study, demographic data, tumor localization, histopathological diagnoses, and survival times of 83 patients followed for secondary orbital metastasis at Çukurova University Ophthalmology Department between 2003 and 2023 were retrospectively reviewed. Subgroup analyses were performed according to age (<18 and ≥19), gender, and primary tumor groups. Results: The study included 83 patients (51 (61.4%) females and 32 (38.6%) males). The mean age at diagnosis was found to be 40.8 ± 24.6 years. A total of 24.1% of the cases were in the pediatric age group (mean age 5.9 years), and the most common tumor metastasizing to the orbit in this group was neuroblastoma (80%). In adult patients, the two most frequent tumors metastasizing to the orbit were breast cancer (33.3%) and lung cancer (14.3%). The most common clinical findings were proptosis (32.5%) and blurred vision (26.2%). Orbital metastases were observed more frequently in females than in males (61.4% vs. 38.6%). This ratio was similar in the pediatric age group (65.0% vs. 35.0%). The mean survival time after metastasis was calculated as 316.7 ± 68.6 days. Female patients had a significantly longer survival time after metastasis compared to males (mean 400.4 vs. 165.4 days; p = 0.037). The median survival after metastasis was 86 days for patients with breast cancer and 204 days for patients with neuroblastoma. Conclusions: The most common source of orbital metastases in females is breast cancer, while neuroblastoma is prominent in pediatric patients. Despite all available treatment options, the prognosis after orbital metastasis is poor; this highlights the importance of early diagnosis and a multidisciplinary approach. Full article

Herpes simplex virus type 1 (HSV-1) is a leading cause of infectious corneal blindness worldwide. Human donor corneal transplantation remains the primary treatment for scarred corneas resulting from herpes simplex keratitis (HSK), a severe inflammatory corneal disease caused by HSV-1 infection, despite a high risk of re-infection or immune rejection of the allografts. As possible alternatives to donor grafting for HSK, we developed cell-free, regeneration-stimulating corneal implants designed to work even under adverse inflammatory situations such as severe infections. The implants comprised short, fully synthetic collagen-like peptides conjugated to polyethylene glycol (CLP-PEG) and crosslinked using carbodiimide chemistry. Being cell-free, they lacked the cellular targets that an already activated immune system would encounter in these inflamed corneas. We tested the performance of these implants in guinea pig and rabbit models of HSK. Three different HSV-1 strains were used to create experimental HSK in rabbits and guinea pigs. There were no overall statistically significant species differences or species–strain differences in virus-induced mortality. At three months post-operation, all treated corneas showed tissue regeneration, but with haze or neovascularization. The initially cell-free CLP-PEG implants allowed for repopulation by ingrowing cells to regenerate neocorneal tissue, despite the inflammation. However, they did not prevent HSV-1 reactivation nor re-infection, as neovascularization and disorganization were observed within the neocorneas. A detailed histopathological examination revealed viral strain differences, but only KOS infection showed interspecies neovascularization differences. A more detailed examination with larger numbers of animals is merited to fully elucidate the effects of the different viral strains on rabbits versus guinea pigs. Full article

Background/Objectives: Innovative intranasal delivery systems have emerged as a strategy to overcome the limitations of conventional COVID-19 vaccines, including suboptimal mucosal immunity, limited antigen retention, and vaccine hesitancy. This study aimed to evaluate physicochemical properties and murine safety of a novel COVID-19 intranasal vaccine candidate based on CHIVAX 2.1 (CVX)-loaded chitosan nanoparticles (CNPs). Methods: The CVX recombinant protein was encapsulated into CNPs using the ionic gelation method. The nanoparticles were characterized by their physicochemical properties (mean size, zeta potential, morphology, and encapsulation efficiency) and spectroscopic profiles. Mucin adsorption and in vitro release profiles in simulated nasal fluid were also assessed. In vivo compatibility was evaluated through histopathological analysis of tissues in male C-57BL/6J mice following intranasal administration. Results: CNPs exhibited controlled size distribution (38.5–542.5 nm) and high encapsulation efficiency (65.4–92.2%). Zeta potential values supported colloidal stability. TEM analysis confirmed spherical morphology and successful CVX encapsulation, and immunogenic integrity was also demonstrated. Mucin adsorption analysis demonstrated effective nasal retention, particularly in particles ≈90 nm. In vitro release studies revealed a biphasic protein profile, where ≈80% of the recombinant protein was released within 2 h. Importantly, histopathological analyses and weight monitoring of intranasally immunized mice revealed no signs of adverse effects related to toxicity. Conclusions: The ionic gelation encapsulation process preserved the physical and immunological integrity of CVX antigen. Furthermore, the intranasal administration of the CVX-loaded CNPs demonstrated a favorable safety profile in vivo. These findings support the potential of the CVX intranasal vaccine formulation for further immunogenicity studies, with no apparent biosafety concerns. Full article

Background: Non-Hodgkin lymphomas (NHLs) are a heterogeneous group of indolent or aggressive lymphoproliferative neoplasms arising from lymph nodes or in extranodal locations. Computed tomography (CT) is the imaging modality of choice, while the definitive diagnosis is confirmed by analyzing tissue samples. The aim of this study was to determine the correlation between CT characteristics and histopathological types of abdominal lymphomas. Methods: A retrospective cross-sectional study included 119 patients with histopathologically confirmed abdominal lymphomas who underwent CT of the abdomen and pelvis prior to treatment. The following CT parameters were extracted: morphological presentation (enlarged lymph nodes/conglomerates, solid mass/masses, gastrointestinal wall thickening, abdominal organ involvement, intra- and extraperitoneal infiltrates), location, two-dimensional size, propagation if present, and postcontrast enhancement. Results: Enlarged lymph nodes were a slightly more common CT morphological appearance in the indolent B NHL group, while gastrointestinal (GI) wall thickening, solid masses, and infiltrates were more frequent in the aggressive B NHL group (p = 0.0256). Aggressive B-cell lymphomas had larger size at time of diagnosis compared to other types (p = 0.0436). CT postcontrast enhancement showed lymphomas originating from the gastrointestinal tract, which presented as wall thickening, had the highest enhancement (p = 0.0065 and p = 0.0485). Conclusions: Observed differences in abdominal lymphomas’ histopathological and imaging characteristics including location/origin, CT morphological appearance, and postcontrast enhancement revealed that extranodal lymphomas were more often of the aggressive B-cell type, aggressive B-cell types were larger, and GI tract lymphomas showed the most prominent enhancement. These findings can help in the diagnostic process and enable better management of lymphomas. Full article

Wild-type transthyretin amyloidosis is an underdiagnosed condition that significantly contributes to mortality in the elderly population. This histopathological study describes autopsy findings in patients with severe clinical course of COVID-19 and ATTR not identified during life. Autopsy findings in the myocardium were analyzed in 19 patients with pre-existing ATTR who died from severe COVID-19. RT PCR was used for pre- and post-mortem detection of SARS-CoV-2 RNA. Immunohistochemical typing was performed with a broad panel of antibodies against different amyloid types. Autopsy specimens from the myocardium and lungs were positive for SARS-CoV-2 RNA in 10 (53%) cases. Microscopic examination of the myocardium revealed focal cardiosclerosis and cardiomyocyte dissociation in 15 (68%) cases, hypertrophy and atrophy of cardiomyocytes in 17 (77%) and 7 (32%), respectively, and myocarditis in 4 (18%) cases. Immunohistochemical analysis determined ATTR amyloidosis in all cases. In patients with rapidly progressive heart failure, the postmortem examination revealed multiple sites of interstitial amyloid deposits and focal cardiosclerosis in the myocardium. Pre-existing cardiac amyloidosis contributes to the aggressive clinical course of COVID-19. Coupled with the toxic effect of the SARS-CoV-2 virus on the myocardium, the disease may lead to progressive heart failure and poor outcomes. Full article

Clostridium piliforme (Cp) is a pleomorphic spore-forming obligate intracellular bacterium and the causative agent of Tyzzer’s disease. The condition affects multiple species, including rabbits, in which the disease is sporadic in recently weaned animals. This report details a case of disease caused by Cp observed exclusively in breeding rabbits of a commercial farm. The clinical manifestations were a higher mortality rate in does and late-gestation abortions. We performed necropsy and further microbiological, parasitological and histopathological analyses. Anatomopathological lesions were suggestive of Tyzzer’s disease and the presence of Cp was confirmed by PCR. Parasitological analysis tested negative and standard bacteriological examination of intestines revealed a high load of Escherichia coli and Clostridium perfringens, which were considered secondary pathogens. Chlamydophila sp. and Toxoplasma gondii infections were excluded by PCR as causative agents of abortions. Moreover, in the months following the diagnosed outbreak, episodes of subcutaneous edema occurred in multiple does and young breeders born after the resolution of the epidemic. The constant reduction in the use of antimicrobials in recent years could make some neglected diseases emerge again. Therefore, it is crucial to suspect such uncommon pathologies in commercial rabbitries to properly manage them on farms. Full article

Psidium guajava L. (Myrtaceae) is a neotropical species whose leaf extracts demonstrate efficacy against cutaneous and mucosal inflammation and ulceration. This study aimed to prepare and characterize aqueous extracts of P. guajava leaves (EAPG) and incorporate them into chitosan nanoparticles for topical delivery to the oral mucosa. The extract was obtained by infusion, and its marker compound was quantified by a chromatographic method. EAPG exhibited antioxidant activity (IC₅₀: 6.35–7.01 µg/mL in DPPH^•; FRAP: 14.42–17.83 µg/mL ≈ 60 µM Fe²⁺) and anti-inflammatory potential by modulating the expression of IL-6. It also showed antifungal activity against Candida species. Nanoparticles loaded with EAPG had a mean diameter of 899.8 ± 10.8 nm, PdI 0.22 ± 0.03, Zeta potential +32.4 ± 2.3 mV, pH 5.0, and 62 ± 1% encapsulation efficiency. They remained stable for 30 days. In an ex vivo topical application, EAPG nanoparticles delivered 415.17 ± 71.7 µg/cm² of marker to the oral mucosa, eight times more than free EAPG (p < 0.05). These results suggest that chitosan-based EAPG nanoparticles are a promising strategy for topical treatment of mucosal disorders. Full article

Ocular melanoma is a rare but clinically significant malignancy, primarily comprising uveal and conjunctival subtypes. Although sharing some histopathological features with cutaneous melanoma, these tumours are characterized by distinct molecular and biological profiles with direct implications for prognosis and treatment. Uveal melanoma is predominantly driven by mutations in GNAQ and GNA11, along with alterations in BAP1, SF3B1, and EIF1AX, which are key prognostic determinants. Conversely, conjunctival and eyelid melanoma exhibits greater molecular similarity to cutaneous melanoma, commonly involving BRAF, NRAS, NF1, and TERT promoter mutations. Despite progress in the molecular characterization of these entities, metastatic disease continues to confer a poor prognosis, particularly in uveal melanoma. Ongoing research into the molecular basis of ocular melanoma is essential to advance targeted therapies and improve clinical outcomes. The aim of this review is to provide a comprehensive overview of ocular melanoma, with a particular focus on the molecular biology underlying its clinical behaviour and emerging therapeutic opportunities. Full article

Background/Objectives: Idiopathic pulmonary fibrosis (IPF) is a fatal lung disease characterized by progressive loss of lung function and poor prognosis. Cryptotanshinone (CTS), a small-molecule compound extracted from Salvia miltiorrhiza, possesses diverse pharmacological activities but suffers from poor oral bioavailability, which restricts its clinical development, particularly in pulmonary fibrosis. DST-3, a newly synthesized derivative of CTS, was designed to overcome these limitations. Methods: The antifibrotic effects of DST-3 were investigated in a bleomycin-induced pulmonary fibrosis model in C57BL/6 mice through lung function assessment, histopathological evaluation, hydroxyproline quantification, and cytokine profiling. In vitro, TGF-β1-stimulated MRC5 fibroblasts were employed to explore the mechanism of action, focusing on STAT3/Smad signaling via Western blotting and molecular binding assays. Furthermore, a validated HPLC–MS/MS method was developed for DST-3, and its pharmacokinetic profile was characterized in Sprague–Dawley rats and compared with that of CTS. Results: DST-3 markedly attenuated pulmonary fibrosis in vivo, as evidenced by improved lung function, reduced collagen deposition, and decreased proinflammatory cytokine levels. In vitro, DST-3 inhibited TGF-β1-induced fibroblast activation by directly binding to STAT3 and suppressing STAT3/Smad signaling. Pharmacokinetic analysis demonstrated that, compared with CTS, DST-3 exhibited more rapid absorption, a higher peak plasma concentration, a greater area under the curve (AUC), improved hepatic metabolic stability, and enhanced lung tissue exposure. Conclusions: Our study demonstrates that DST-3 exerts potent antifibrotic effects in vivo and in vitro, primarily through STAT3 pathway inhibition. Its improved pharmacokinetic characteristics further support its potential as a promising candidate for the treatment of pulmonary fibrosis. Full article