Uric acid is the end product of purine metabolism and plays a dichotomous role in the human body. On one hand, it exerts antioxidant and neuroprotective effects; on the other hand, chronic hyperuricemia has been strongly associated with diseases beyond gout, affecting the cardiovascular, renal, metabolic, autoimmune, and central nervous systems (CNS). Excess uric acid promotes oxidative stress, endothelial damage, neurodegeneration, inflammasome activation, and impairs energy metabolism. It exacerbates autoimmune diseases, such as Systemic Lupus Erythematosus (SLE) and antiphospholipid syndrome (APS), by increasing inflammatory and oxidative damage, leading to greater end-organ damage. The British Society for Rheumatology, European League Against Rheumatism, American College of Rheumatology, and National Institute for Health and Care Excellence (NICE) have all established a “treat-to-target” approach for hyperuricemia with serum urate levels below 6 mg/dL and below 5 mg/dL in severe cases. Allopurinol and Febuxostat, xanthine oxidase inhibitors, are used as first-line pharmacological therapies for the treatment of hyperuricemia, whereas uricosurics and Interleukin-1 (IL-1) inhibitors are preferred in cases of refractory hyperuricemia. Lifestyle modifications, such as the Dietary Approaches to Stop Hypertension (DASH) diet, weight reduction, and smoking cessation, are also recommended for the long-term management of the disease. Sodium-Glucose Cotransporter 2 (SGLT2) inhibitors, selective urate transport inhibitors, and plant-derived anti-inflammatory compounds have emerged as new treatments with promising responses. This review synthesizes the current literature on the multifaceted role of uric acid and emphasizes its systemic implications in chronic diseases. It also outlines the already established management options and new innovative therapies for managing this disease. Understanding this dichotomous role is essential for adopting a precise management approach that balances the protective and pathological effects of uric acid.
Epigenetic modifications, particularly aberrant DNA methylation, play an important role in the pathogenesis of both solid and hematologic malignancies. Global hypomethylation and promoter hypermethylation can silence numerous tumor suppressor genes identified in acute myeloid leukemia (AML) and myelodysplastic neoplasm (MDS). Among stemness-associated transcription factors, OCT-4 and SOX-2 are key regulators of pluripotency and stem cell maintenance and have been implicated in cancer stem cell biology and tumor progression. Although their abnormal expression and epigenetic regulation have been reported in various malignancies, limited data are available regarding their promoter methylation status specifically in AML and MDS. Therefore, this study aimed to evaluate the methylation patterns of the transcription factors, specifically OCT-4 and SOX-2, in patients with AML and MDS. The study involved 84 newly diagnosed AML and MDS patients and 16 age, and sex-matched healthy controls. DNA was extracted from blood or bone marrow using a QIAGEN RDNA extraction kit. The SOX-2 and OCT-4 genes were studied using PCR-specific primers for methylated and unmethylated targets. SOX-2 gene methylation was observed in a significantly higher proportion of AML (n=48/77) and MDS (n=4/7) as compared to Controls (n=3/16) (p<0.001). OCT-4 methylation was also observed in a significantly higher proportion of AML (n=44/77) as compared to MDS (n=3/7) and Controls (n=1/16) (p<0.001). Only a few cases in the AML group had both SOX-2 and OCT-4 gene methylation (n=25/77), compared with MDS (n=0/7) and Controls (n=0/16) (p<0.007). This study indicates that SOX-2 and OCT-4 gene methylation is significantly more prevalent in AML and MDS patients than healthy controls, suggesting their potential involvement in leukemogenesis. These findings highlight the potential role of methylation of stemness-associated transcription factors as a biomarker for disease characterization and identification of epigenetic therapeutic targets in AML and MDS.
Teledentistry has evolved from asynchronous communication to real-time consultations, with adoption accelerating during and post-COVID. Concurrently, AI has been leveraged to enhance diagnostic accuracy, efficiency, and accessibility using machine learning, GANs, and connected devices. This scoping review, conducted using Arksey and O'Malley framework and Joanna Briggs Institute guidance, explores the ethical, legal, and economic considerations of AI-driven teledentistry. Following a PRISMA-ScR compliant screening process by two independent reviewers, 137 studies published between 2018 and 2025 were included. Unlike previous reviews that have primarily focused on clinical applications or the general use of AI in healthcare, this review addresses the ethical, legal, and economic considerations of AI in teledentistry in a single paper. It underscores the importance of explainable AI, explores cross-border regulatory challenges, and discusses possible cost models for adoption in smaller practices. This review indicates that AI-powered teledentistry could enhance diagnostic accuracy, facilitate early detection, improve monitoring, and increase accessibility. Nonetheless, these advantages come with critical concerns including data privacy, potential biases, patient autonomy, accountability, and cost. Addressing these issues through governance, oversight, transparency, and economic viability is essential. AI-enabled teledentistry has the potential to transform dental care delivery, but its integration must be approached with careful consideration of its associated challenges.
CD36 functions as both a lipid transporter and scavenger receptor, integrating metabolic and inflammatory signaling pathways. It plays a critical role in maintaining cellular homeostasis and influencing disease progression. This review summarizes the structure, ligands, functions, regulation, and clinical implications of CD36 in renal and bladder cancer. Increased CD36 expression promotes enhanced fatty acid uptake, which supports tumor cell proliferation, migration and survival, by mediating metabolic reprogramming and interacting with the tumor microenvironment. In renal cancer, most frequently clear cell renal carcinoma (ccRCC), which has a typical metabolic phenotype, CD36 is involved in lipid accumulation and oxidative stress pathways. Pathogenic mechanisms include hypoxia-inducible factor (HIF)-driven pathways and carnitine palmitoyl transferase 1A (CPT1A) via the PPARα/CD36 axis, which phosphorylate Akt. By using fatty acid oxidation, CD36 lead to the production of reactive oxygen species and to transcription of genes mediating a pro-tumor function, inducing tumor-associated macrophages (TAM). In bladder cancer, CD36 is implicated in tumoral cells proliferation, survival, and adaptation to metabolic stress, epithelial-mesenchymal transition (EMT) and influences the tumor microenvironment, through interactions with tumor-associated macrophages and inflammatory signaling pathways. Although multiple studies propose CD36 as a prognostic biomarker, inconsistencies across cohorts limit its clinical translation. Notably, advances have revealed the regulatory networks governing distinct physiological properties of CD36, thereby identifying targeting CD36 as a potential strategy for cancer treatment. Inhibition of CD36-mediated lipid metabolism and signaling pathways may reduce tumor growth and metastatic potential. However, further research is necessary to clarify its context-dependent functions and to develop effective CD36-targeted therapies. To our knowledge, this is the first review to systematically examine the role of CD36 across both renal and bladder cancer. It could be the first step toward identifying new mechanisms mediated by CD36 in these malignancies.
Ischemic heart disease (IHD) remains the leading cause of cardiovascular mortality worldwide. Although age standardized death rates have declined over the past two decades, the absolute number of deaths continues to rise due to population growth and demographic aging. This Perspective examines the resulting paradox of progress, in which improving mortality rates coexist with an expanding global burden. Emerging evidence from recent global analyses highlights widening disparities across regions, sexes, and age groups. Global Burden of Disease (GBD) studies suggest an increasing burden of early onset IHD among adults aged 15 to 49 years, associated with rising incidence and prevalence, with notable regional variability and links to metabolic and dietary risks. While high income settings continue to achieve sustained mortality reductions, low- and middle-income regions face persistent gaps in prevention and care. These disparities reflect differences in health system capacity, including limited screening, delayed access to acute cardiac care, and suboptimal use of secondary prevention. Scalable strategies such as task-sharing and simplified treatment approaches offer practical solutions but remain underused. A strategic shift toward implementation, life-course prevention, and equity-focused policy reform is essential. Importantly, this perspective bridges the gap between epidemiological trends and health policy, linking epidemiologic trends to scalable implementation strategies for clinicians and policymakers to address the global burden of IHD.
