Methylenetetrahydrofolate Reductase C677T (rs1801133) Polymorphism Is Associated with Bladder Cancer in Asian Population: Epigenetic Meta-Analysis as Precision Medicine Approach.

The etiology of bladder cancer remains unclear. This study investigates the impact of gene polymorphisms, particularly methylenetetrahydrofolate reductase gene (MTHFR), on bladder cancer susceptibility, focusing on the rs1801133 single-nucleotide polymorphism (SNP). A meta-analysis was conducted after systematically reviewing the MTHFR gene literature, adhering to PRISMA guidelines and registering in PROSPERO (CRD42023423064). Seven studies were included, showing a significant association between the MTHFR C677T (rs1801133) polymorphism and bladder cancer susceptibility. Individuals with the T-allele or TT genotype had a higher likelihood of bladder cancer. In the Asian population, the overall analysis revealed an odds ratio (OR) of 1.15 (95% CI 1.03-1.30; p-value = 0.03) for T-allele versus C-allele and an OR of 1.34 (95% CI 1.04-1.72; p-value = 0.02) for TT genotype versus TC+CC genotype. The CC genotype, however, showed no significant association with bladder cancer. Notably, epigenetic findings displayed low sensitivity but high specificity, indicating reliable identified associations while potentially overlooking some epigenetic factors related to bladder cancer. In conclusion, the MTHFR T-allele and TT genotype were associated with increased bladder cancer risk in the Asian population. These insights into genetic factors influencing bladder cancer susceptibility could inform targeted prevention and treatment strategies. Further research is warranted to validate and expand these findings.

Association of Retinal Microangiopathy with Albuminuria in Patient with Chronic Kidney Disease: a Meta-analysis Study.

Background: Chronic kidney disease (CKD) patients suffer renal and cardiovascular problems and early death. In 2016, 13.4% of all ages globally had CKD. Kidney disease, diabetes, and hypertension have a microvascular component. Diabetic retinopathy (DR) and diabetic nephropathy (DN) commonly occur concurrently, indicating that the same mechanisms may be at action in the eyes and kidneys. Chronic kidney disease (CKD) has been a tough medical problem because of late signs and late treatment. Retinal vessels are a non-invasive technique to examine systemic microvasculature. Novel predictors may enhance microvascular disease risk categorization, leading to better therapy. Retinal vascular diameter and retinopathy are reported most often. Numerous investigations have linked this condition to kidney or other systemic disorders. The retinal microvasculature was linked with both the incidence and prevalence of renal illness in this investigation. We wanted to determine whether retinal microvasculature might be utilized to diagnose renal disease. Methods: Initial searching found 625 papers, of which 542 articles were rejected due to primary screening unrelated titles and/or abstracts. There were a total of 81 papers selected for full-text evaluation and due to insufficient data provided and duplication, we got 5 papers to enter the next step. Results: In five investigations, retinal microvascular symptoms correlated with albuminuria. All studies connected retinal vascular diameter with albuminuria. As a categorical variable, CRAE narrowed. There was a U-shaped relationship between CRAE and albuminuria in quintiles 1 and 5. There were relationship between albuminuria to a larger CRVE and a narrower CRAE. Studies relate AVR to albuminuria were associated as well. Conclusion: Our investigation demonstrated retinal vascular symptoms are linked to renal illness. Retinopathy correlates with CKD and ESRD in diabetic and nondiabetic individuals. Evidence linking retinal vascular width to early renal disease implies fundus photography might be a useful screening technique for CKD patients. Insufficient evidence links retinal vascular diameter to kidney-related morbidity and death. Future studies should stratify by age, gender, obesity, hypertension, ethnicity, and others.

Diabetes mellitus comorbidity in patients enrolled in tuberculosis drug efficacy trials around the world: A systematic review.

AIMS: With a prevalence of 16%, diabetes mellitus (DM) is one of the most frequent non-communicable comorbidities of tuberculosis (TB). DM is a major risk factor for adverse TB outcomes and may require personalized TB drug dosing regimens. However, information on the inclusion of DM in TB drug trials is lacking. We aimed to assess the percentage of recent TB drug efficacy trials that included DM patients. METHODS: A systematic review was performed and reported according to PRISMA guidelines. PubMed, Science Direct, and ClinicalTrials.gov databases were systematically searched for TB drug trials published between 1 January 2012 and 12 September 2017. Primary outcome was the percentage of TB drug trials performed around the world that included DM patients. RESULTS: Out of the included 41 TB drug trials, 12 (29.3%) reported DM comorbidity among the study participants. Nine trials (21.9%) excluded all patients with DM comorbidity, ten (24.4%) excluded only insulin-dependent or uncontrolled DM, and 10 (24.4%) did not mention whether DM was included or excluded. Of the 12 trials that included DM comorbidity, the majority did not report the diagnostic criteria for DM and none reported outcomes in the DM subpopulation. Inclusion of DM was higher in drug-resistant-TB trials (67%, P = .003, vs drug-susceptible) and trials performed in Asia (60%, P = .006, vs Africa). CONCLUSIONS: Fewer than 1/3 recent TB drug trials reported the inclusion of DM. To better reflect real-world DM prevalence and differential TB drug effectiveness, inclusion of DM patients requires increased attention for future TB drug trials.

Darapladib inhibits atherosclerosis development in type 2 diabetes mellitus Sprague-Dawley rat model.

OBJECTIVE: Increase in the low-density lipoprotein (LDL) level in diabetes mellitus and atherosclerosis is related to lipoprotein associated phospholipase A2 (Lp-PLA2). Lp-PLA2 is an enzyme that produces lysophosphatidylcholine (LysoPC) and oxidized nonesterified fatty acids (oxNEFA). LysoPC regulates inflammation mediators, including intra-cellular adhesion molecule-1 (ICAM-1). Darapladib is known as a Lp-PLA2 specific inhibitor. The aim of this study was to reveal the effect of darapladib on the foam cell number, inducible nitric oxide synthase (iNOS), and ICAM-1 expression in aorta at early stages of the atherosclerosis in type 2 diabetes mellitus Sprague-Dawley rat model. METHODS: Thirty Sprague-Dawley male rats were divided into 3 main groups: control, rats with type 2 diabetes mellitus (T2DM), and T2DM rats treated with darapladib (T2DM-DP). Each group was divided into 2 subgroups according the time of treatment: 8-week and 16-week treatment group. Fasting blood glucose, insulin resistance, and lipid profile were measured and analyzed to ensure T2DM model. The foam cells number were detected using hematoxylin-eosin (HE) staining and the expression of iNOS and ICAM-1 was analyzed using double immunofluorescence staining. RESULTS: Induction of T2DM in male Sprague-Dawley rats after high fat diet and streptozotocin injection was confirmed by elevated levels of total cholesterol and LDL and increased fasting glucose and insulin levels compared to controls after both times of treatment. Moreover, T2DM in rats induced a significant increase (p<0.05) in the foam cells number and iNOS and ICAM-1 expression in aorta compared to controls after both treatment times. Darapladib treatment significantly reduced (p<0.05) foam cells number as well as iNOS expression in aorta in rats with T2DM after both treatment times. A significant decrease (p<0.05) in ICAM-1 expression in aorta was observed after darapladib treatment in rats with T2DM only after 8 weeks of treatment. CONCLUSION: Our data indicate that darapladib can decrease the foam cells number, iNOS, and ICAM-1 expression in aorta at the early stages of atherosclerosis in T2DM rat model.