Discoveries (Craiova, Romania)最新文献

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.

While the recurrence rates of inguinal hernia have been significantly reduced by the use of mesh in laparoscopic hernia repair, it has also introduced rare complications, including the uncommon erosion of the mesh into adjacent viscera. We report a 36-year-old male, who following left-sided hernia repair in 2014, presented with persistent dysuria, increased urinary frequency and chronic discomfort at the surgical site. Initially, his symptoms were intermittent but gradually progressed to recurrent urinary tract infections unresponsive to prolonged antibiotic therapy. On further investigation, ultrasound revealed an echogenic linear structure extending from the left inguinal region into the urinary bladder, and contrast-enhanced CT confirmed mesh migration, along with a pseudo-diverticular outpouching from the bladder wall. The imaging was corroborated by surgical findings, and the mesh was removed. This case adds to the limited existing literature and emphasizes the importance of considering mesh-related complications in patients with persistent urinary symptoms after hernia repair. Additionally, it highlights the key role of imaging in diagnosis and in guiding management.

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.

Preliminary data for the Cellular Therapy for In Utero Repair of Myelomeningocele (CuRe) Trial have recently been published. These data showcase innovation in fetal surgery but introduce ethical questions regarding tissue sourcing. The CuRe Trial utilizes early gestational placental mesenchymal stromal/stem cells (PMSCs) in the repair technique. The ethical implications of this approach vary depending on whether they are sourced from miscarriage or elective abortion. The specific source of the PMSCs is unclear, but evidence suggesting that they might be sourced from elective abortion is presented, along with an overview of ethical implications if this is the case. Key questions considered include 1) whether research such as this is impacted by the recent decision by the National Institutes of Health (NIH) to cease funding of research using fetal tissue from elective abortion; 2) what ethical alternatives currently or may plausibly exist; and 3) whether scientific justifications exist for the use of tissue sourced from elective abortion over more ethical alternatives.

Metformin-associated lactic acidosis (MALA) is a rare but life-threatening complication of metformin therapy that most commonly occurs in the setting of acute kidney injury (AKI) and impaired drug clearance. Given the widespread use of metformin for type 2 diabetes mellitus, recognition of precipitating factors for MALA remains critically important. We report a case of severe euglycemic diabetic ketoacidosis (DKA) with refractory lactic acidosis in a patient with previously unrecognized obstructive uropathy due to recurrent nephrolithiasis causing bilateral hydronephrosis and severe AKI while on metformin therapy. The patient developed profound metabolic derangements that were unresponsive to conventional medical therapy, with resolution only after emergent hemodialysis. This case highlights the importance of early recognition of AKI from obstructive uropathy as a reversible precipitant of metformin accumulation and emphasizes the role of prompt renal replacement therapy in patients with severe MALA and refractory metabolic acidosis.

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.

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.

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.

Diuretic resistance is a major therapeutic challenge in acute decompensated heart failure (ADHF). Acetazolamide, a carbonic anhydrase inhibitor, has emerged as a potential adjunct to conventional loop diuretics, as demonstrated in the ADVOR trial. We present a 74-year-old woman with acute coronary syndrome complicated by cardiogenic shock and refractory pulmonary edema despite inotropic support and guideline-directed therapy. The patient received intravenous acetazolamide 500 mg daily for three days, resulting in marked diuresis and radiographic resolution of pulmonary edema within 72 hours. The patient improved clinically. This case supports the potential utility of acetazolamide as an adjunctive strategy for overcoming diuretic resistance in ADHF.

Spina bifida is a neural tube defect (NTD) that arises when the neural tube fails to close properly during early development. This review focuses on myelomeningocele (MMC), the most common severe form of spina bifida, which often leads to motor and sensory impairments, including lower limb weakness or paralysis, as well as renal, urological, orthopedic, developmental, and psychosocial challenges. We explore the etiology, pathogenesis, prevention, diagnosis, and management of spina bifida, with a special emphasis on in-utero surgical repair. Over the past several decades, researchers and clinicians have made remarkable strides across all stages of care from prevention to postnatal outcomes. Widespread use of folic acid supplementation has significantly reduced the number of new cases. Advances in prenatal imaging and diagnostics now allow for earlier and more accurate detection, enabling timely intervention. In-utero surgical techniques continue to evolve, with innovative hybrid approaches that combine the strengths of open and minimally invasive methods. The momentum in this field shows no sign of slowing. Promising developments in stem cell therapy, biomaterials, robotic-assisted surgery, 3D printing, and enhanced imaging are redefining treatment goals in spina bifida. With each advance, clinicians gain better tools to improve outcomes for both mother and child, minimizing risks and maximizing long-term health and quality of life for both patients.