Background Urothelial neoplasms are among the most common tumors affecting the urinary tract and are known for their high recurrence rates and variable clinical behavior. The prognosis and management of these tumors depend on histomorphological parameters like tumor grade and invasion into the muscularis propria mainly. However, assessment based only on morphology may be limited in certain cases. GATA3, a transcription factor expressed in urothelial cells has gained importance as an immunohistochemical marker. Studying its expression and its correlation with histomorphological parameters will help in better characterization of tumors and their prognostication. Materials and Methods This cross-sectional study was carried out in the Department of Pathology, Ramaiah Medical College, Bengaluru, over a period from March 2024 to February 2026. A total of 68 cases of urothelial neoplasms from cystoscopic biopsies, TURBT, and radical cystectomy specimens. Using light microscopy, the tumor morphology was examined. The evaluation of GATA3 expression was done by immunohistochemistry. The scoring was done using and immunoreactivity scoring system based on the intensity of staining and the proportion of positive tumor cells. Descriptive statistics and Chi-square test were used for statistical analysis and for the analysis of the association between GATA3 expression and histomorphological parameters respectively. Results A total of 68 cases of urothelial neoplasms were studied and evaluated, of which majority showed GATA3 positivity. The correlation between GATA3 expression and various histomorphological parameters was found to be statistically significant. Most low grade tumors with mild nuclear pleomorphism, low mitotic activity, no invasion, absence of necrosis and increased TILs showed strong expression of GATA3. The high grade tumors comparatively showed weak GATA3 expression. These findings indicate that GATA3 may serve not only as a diagnostic marker but also has prognostic significance. Conclusion The present study confirms that GATA3 is a highly sensitive immunohistochemical marker in urothelial neoplasms and demonstrates significant association with multiple histopathological prognostic parameters. The findings further strengthen the role of GATA3 as a marker of tumor differentiation and biological behavior. Importantly, the study expands the existing knowledge by demonstrating associations with mitotic activity, necrosis and TILs, suggesting a broader role of GATA3 in tumor biology.
Background: Oral cancer continues to be a significant health issue worldwide, and a late diagnosis is highly correlated with poorer treatment outcomes and shorter life expectancy. While these two steps (examining a patient and obtaining tissue cultures) are essential to this diagnosis (previously routine), they do not help to detect the patient in time at the population level. A minimally invasive, biological fluid such as saliva has many molecular components that may mirror pathological changes occurring in the oral cavity. Salivary omics domains could thereby yield a better assessment, through a combination of the domains, of the risk of oral cancer at an early stage. Artificial intelligence (AI) may further enhance the analysis of complex molecular patterns by integrating information from multiple salivary biomarker domains. Such approaches may support the identification of potential early indicators of oral cancer and improve the classification of individuals according to their estimated disease risk. Objective: This study aimed to evaluate the potential of multi-omics salivary biomarkers (genomic/transcriptomic, proteomic, metabolomic, and microbiome) for the early detection and risk classification of oral cancer. The study also highlights the potential application of AI-based analytical approaches to integrate multi-omics biomarker information and clinical characteristics for improved oral cancer risk classification. Methods: The approach applied was quantitative cross-sectional and analytical, and involved a number of respondents of 279 people. Demographic and behavioural risk factors and the perception of being assessed for these risk factors by biomarkers were investigated, along with oral symptoms, clinical findings, and salivary multi-omics classifications. Normality test and Cronbach's Alpha reliability test, Bartlett's Test of Sphericity, and KMO Test, Independent Samples t test, One-Way Analysis of Variance, Kruskal-Wallis, Chi-Square Test of Independence, Pearson correlation and regression analysis were used in statistical analysis. Results: The results showed a good level of reliability with an average Cronbach's Alpha of 0.901 - 0.938. Supporting construct validity is the value of kmo which is excellent (0.959), and the Bartlett's test result shows that the p-value is less than 0.001. Gender difference, differences in age groups, differences in category of areca use and cooked chew (areca/users, non-users), differences in Betel chewing (areca, non-users) were the significant differences. The overall multi-omics risk classification was well correlated with the clinical examination status, χ² (9) = 429.967, p < 0.001. Overall multi-omics risk revealed significant associations between domains of major biomarkers, with the highest between clinical examination and overall multi-omics risk. The regression analysis resulted in a highly significant predictive model of overall risk classification (R = 0.943, R² = 0.889, p < 0.001), which explained a great variance of risk predictors that were included in the model. Conclusion: Results showed that the multi-omics biomarkers of saliva were a prevalent candidate for use as a minimally invasive tool to aid early detection/classification of OCD. Combination of use of molecular biomarker domains with clinical examination may lead to improved identification of patients likely to show symptoms of a clinical disorder that would warrant early diagnosis referral. The disease diagnosis performance needs to be further tested in other populations before the wide-scale application of the system. Future studies should investigate the integration of salivary multi-omics biomarkers using appropriately validated AI models, with particular attention to early cancer detection, risk classification, model interpretability, and external validation across independent populations.
Nitrosamine impurities have become an important concern in the pharmaceutical industry because of their potential mutagenic and carcinogenic risks. The present study reports the synthesis, isolation, and structural characterization of three representative nitrosamine drug substance-related impurities (NDSRIs): N-nitroso tadalafil, N-nitroso ciprofloxacin, and N-nitroso ticagrelor. These impurities were synthesized through controlled nitrosation of the corresponding drug substances using sodium nitrite or tert-butyl nitrite under optimized reaction conditions. The crude products were purified by chromatographic techniques to obtain the desired nitrosamine impurities with suitable purity. Structural confirmation was carried out using high-performance liquid chromatography (HPLC), mass spectrometry (MS), and 1H nuclear magnetic resonance (1H NMR) spectroscopy. The analytical results verified the successful formation and identity of all three target compounds. The developed synthetic procedures and comprehensive characterization data provide valuable reference materials for impurity profiling, analytical method development, reference standard preparation, and toxicological evaluation. This work also contributes to regulatory investigations and risk assessment related to nitrosamine contamination in active pharmaceutical ingredients, supporting the development of safer pharmaceutical products.
Background: Metabolic dysfunction-associated steatotic liver disease (MASLD), formerly termed non-alcoholic fatty liver disease (NAFLD), is associated with metabolic dysfunction and progressive hepatic injury. Patatin-like phospholipase domain-containing protein 3 (PNPLA3) is involved in hepatic lipid metabolism, but the clinical significance of circulating PNPLA3 protein concentrations remains insufficiently characterized. Objective: To assess the association of serum PNPLA3 protein expression with insulin resistance, liver function parameters, fibrosis indices, and serum lipid profile in patients with fatty liver disease. Materials and Methods: This cross-sectional analytical study was conducted at ASIAN HOSPITAL, Hyderabad, Pakistan, from March to August 2025. A total of 120 patients with ultrasound-confirmed fatty liver disease were recruited using convenience sampling. Serum PNPLA3 concentrations were measured using enzyme-linked immunosorbent assay (ELISA). Participants were categorized into low, moderate, and high PNPLA3 expression groups. Insulin resistance was assessed using the homeostatic model assessment of insulin resistance (HOMA-IR), while fibrosis risk was evaluated using the fibrosis-4 (FIB-4) index. Statistical analysis was performed using IBM SPSS Statistics version 26.0. Results: Higher PNPLA3 expression was associated with increased HOMA-IR, alanine aminotransferase, aspartate aminotransferase, and FIB-4 values across expression groups. Spearman correlation analysis demonstrated positive associations between PNPLA3 concentrations and HOMA-IR (r=0.45), ALT (r=0.30), and FIB-4 (r=0.28). Associations with serum lipid parameters were not statistically significant. Conclusion: Serum PNPLA3 protein concentrations were associated with insulin resistance and biochemical indicators of hepatic injury and fibrosis risk. Further multicenter prospective studies using standardized assays and validated fibrosis assessments are needed to establish its clinical utility.
Background: Smokeless tobacco products are established carcinogens associated with oral squamous cell carcinoma (OSCC). However, evidence regarding the prognostic significance of naswar—the most widely used smokeless tobacco product in Central Asia—remains limited. Objective: To evaluate the impact of naswar use on clinicopathological characteristics, treatment outcomes, recurrence, and survival in patients with oral squamous cell carcinoma. Methods: This retrospective cohort study included 131 patients with morphologically confirmed stage III–IV OSCC treated at the Department of Head and Neck Tumors Surgery of RSSPMCOR between 2018 and 2025. Patients were stratified based on naswar use status. Kaplan–Meier analysis, Cox proportional hazards regression, and multivariable logistic regression were performed. Results: Naswar users exhibited a significantly higher frequency of leukoplakia, poorly differentiated tumors, cervical lymph node metastasis, and disease recurrence. Multivariable analyses confirmed naswar use as an independent adverse prognostic factor. Patients receiving cetuximab-based comprehensive therapy demonstrated better treatment responses; however, this benefit was attenuated in naswar users. Conclusions: Naswar use is independently associated with aggressive tumor biology, poor treatment response, and worse long-term survival in OSCC patients. Routine assessment of naswar use should be incorporated into risk stratification models.
