Search Results (235)

HIV infection and hypertensive disorders of pregnancy (HDP), particularly preeclampsia (PE) with severe features, are leading causes of maternal mortality worldwide. This study investigates the role of asymmetric dimethylarginine (ADMA) and prostacyclin (PGI2) concentrations in endothelial impairment in normotensive pregnant versus PE women within an HIV endemic setting in KwaZulu-Natal Province, South Africa. The study population (n = 84) was grouped according to pregnancy type, i.e., normotensive (n = 42) and PE (n = 42), and further stratified by HIV status. Clinical factors were maternal age, weight, blood pressure (both systolic and diastolic) levels, and gestational age. Plasma concentrations of ADMA and PGI2 were measured using the enzyme-linked immunoassay (ELISA). Differences in outcomes were analyzed using the Mann–Whitney U and Kruskal–Wallis test together with Dunn’s multiple-comparison post hoc test. The non-parametric data were presented as medians and interquartile ranges. Gravidity, gestational age, and systolic and diastolic blood pressures were significantly different across the study groups where p < 0.05 was deemed significant. Furthermore, the concentration of ADMA was significantly elevated in PE HIV-positive vs. PE HIV-negative (p = 0.0174) groups. PGI2 did not show a significant difference in PE compared to normotensive pregnancies (p = 0.8826) but was significantly different across all groups (p = 0.0212). An increase in plasma ADMA levels was observed in the preeclampsia HIV-negative group compared to the normotensive HIV-negative group. This is linked to the role played by ADMA in endothelial impairment, a characteristic of PE development. PGI2 levels were decreased in PE compared to the normotensive group regardless of HIV status. These findings draw attention to the importance of endothelial indicators in pathogenesis and possibly early prediction of PE development. Full article

Autism spectrum disorder (ASD) is increasingly associated with microbial and metabolic disturbances, including the altered production of gut-derived uremic toxins. We investigated urinary concentrations of five representative uremic toxins—indoxyl sulfate (IS), p-cresyl sulfate (PCS), trimethylamine N-oxide (TMAO), asymmetric dimethylarginine (ADMA), and symmetric dimethylarginine (SDMA)—in 161 children with ASD and 71 healthy controls. Toxins were measured using LC-MS/MS and were normalized to creatinine. Subgroup analyses were performed by sex, age group (2–5.9 vs. 6–17 years), and autism severity based on the Childhood Autism Rating Scale (CARS). In addition to individual concentrations, we calculated the total toxin burden, proportional contributions, and functional ratios (IS/PCS, PCS/TMAO, and IS/ADMA). While individual toxin levels did not differ significantly between groups, stratified analyses revealed that PCS was higher in girls and in severe cases of ASD, whereas IS and TMAO were reduced in younger and more severely affected children. The functional ratios shifted consistently with severity—IS/PCS declined from 1.69 in controls to 0.99 in severe cases of ASD, while PCS/TMAO increased from 12.2 to 20.5. These patterns suggest a phenolic-dominant microbial signature and an altered host–microbial metabolic balance in ASD. Functional toxin profiling may offer a more sensitive approach to characterizing metabolic disturbances in ASD than concentration analysis alone. Full article

Cardiovascular adaptation is vital for a healthy pregnancy but may be impaired in women at high risk for preeclampsia (PE), a condition marked by endothelial dysfunction. Smoking may lower the PE risk but harms vessels, and the effects of early cessation remain unclear. This prospective cohort study assessed vascular changes in high-risk pregnancies and the potential influence of early smoking cessation. Of 110 women screened for PE in the first trimester, 43 were classified as high-risk: 18 former smokers and 25 lifelong non-smokers. Vascular assessments were performed at 11–16, 24–28, and 34–37 weeks of gestation. Parameters included the carotid–femoral pulse wave velocity (cfPWV), asymmetric dimethylarginine (ADMA), mean arterial pressure (MAP), systolic and diastolic blood pressure (SBP, DBP), heart rate (HR), and retinal vessel calibers (central retinal arteriolar and venular equivalents (CRAE, CRVE)). Serum cotinine confirmed abstinence in former smokers. Across gestation, ADMA (p = 0.034), MAP (p = 0.001), SBP (p = 0.033), DBP (p = 0.004), and HR (p = 0.004) increased, while CRAE (p = 0.016) and CRVE (p = 0.004) narrowed in late pregnancy; cfPWV remained stable (p = 0.783). Non-smokers showed increases in their ADMA (p = 0.020), MAP (p = 0.001), and DBP (p = 0.0001) with no differences between groups. High-risk pregnancies showed vascular changes with similar profiles in former and non-smokers, underscoring the need for broader studies. Full article

It is hypothesized that growth hormone deficiency (GHD) is associated with increased oxidative stress (OS), contributing to elevated cardiovascular risk. This preliminary study evaluates changes in OS markers and cardiovascular biomarkers in 15 adult patients with severe GHD undergoing 12 months of recombinant human growth hormone (rhGH) therapy. IGF-1 concentrations increased significantly following 6 and 12 months of therapy (p = 0.0003 and p = 0.0001, respectively). These changes were accompanied by a significant decrease in endothelin-1 (ET-1) levels at 12 months (p = 0.007), as well as reductions in asymmetric dimethylarginine (ADMA) levels at both 6 and 12 months (p = 0.01 for each timepoint). Total oxidative capacity (TOC) decreased significantly after 6 months of therapy (p = 0.02), followed by a significant increase at 12 months (p = 0.04), whereas total antioxidant capacity (TAC) showed a significant increase at 12 months (p = 0.02). Tissue fat % showed significant reductions at 6 months (p = 0.006), suggesting early improvements in body composition. Correlation analyses indicated negative associations between IGF-1 and TOC (p < 0.006; R = −0.73), and positive associations with TAC (p < 0.001; R = 0.83). These findings suggest that rhGH therapy in adult patients with severe GHD reduces OS and cardiovascular risk through the modulation of biomarkers and improved body composition. This study explores the role of rhGH therapy in reducing cardiovascular risks in GHD, emphasizing the importance of individualized treatment approaches. Full article

Background and Objectives: Psoriasis vulgaris (PV) is a chronic inflammatory disease associated with oxidative stress. It has been reported that oxidative stress caused by disruption of redox signaling can cause molecular damage, activate dendritic cells, lymphocytes, and keratinocytes, and lead to angiogenesis, inflammation, cell necrosis, and apoptosis by increasing the levels of lipid peroxidation products. In this study, serum levels of asymmetric dimethylarginine (ADMA), malondialdehyde (MDA), and reduced glutathione (GSH) were analyzed to gain insight into the oxidative balance in patients with PV. Materials and Methods: This prospective study included 59 PV patients and 40 healthy volunteers as the healthy control group. Age, gender, body mass index (BMI), waist circumference, routine hematologic parameters [fasting blood glucose, C-reactive protein (CRP), erythrocyte sedimentation rate (ESR), blood lipid levels, hemogram parameters], disease duration, and disease severity were recorded on data forms. The levels of ADMA, MDA, and GSH were analyzed using the high-performance liquid chromatography (HPLC) method. Results: When analyzed in terms of demographic characteristics, no statistically significant difference was observed between the patient and control groups. When examined in terms of biochemical variables, white blood cell (WBC) values were found to be significantly higher in the patient group (t: 2.825; p < 0.05). Although waist circumference, BMI, glucose, CRP, ESR, lipids, platelet count, and systolic and diastolic blood pressure were higher in the patient group, this difference was not statistically significant (p > 0.05). ADMA (t: 4.532; p < 0.05) and MDA (t: 9.598; p < 0.05) values were found to be higher and GSH (t: −4.717; p < 0.05) values were found to be lower in the patient group compared to the control group. When correlation analysis was performed between the parameters, a significant relationship was found only between GSH values and ADMA values (r: −0.256; p < 0.05). Accordingly, as the patients’ GSH values increased, ADMA values decreased. Conclusions: Increased WBC, ADMA, and MDA levels, and decreased GSH levels in PV patients reveal the critical role of oxidative stress and inflammation in the disease process. Evaluation of these biomarkers may contribute to the identification of new targets for the treatment of PV and the development of more effective management strategies. Full article

Asymmetric dimethylarginine (ADMA), an endogenous methylated amino acid, has been implicated in tumor progression; however, its influence on tumor immunity, particularly dendritic cell (DC) function and antigen presentation, remains unclear. In this study, we examined the effects of ADMA on tumor antigen uptake, processing, and presentation in DCs using the murine dendritic cell line DC2.4 as a model. Our results reveal that ADMA treatment significantly reduces the phagocytic uptake of tumor antigens derived from EO771 and Py230 breast cancer cell lysates. Additionally, ADMA exposure leads to a marked downregulation of key genes involved in antigen processing and presentation, including MHC I, MHC II, TAP1, TAP2, ERp57, and CD80. This suppression at the transcriptional level corresponds with decreased surface protein expression of MHC I, MHC II, and CD80, as confirmed by flow cytometry. Furthermore, ADMA-treated DC2.4 cells exhibit impaired tumor antigen presentation on their surface. Consequently, these functional impairments result in a diminished capacity to activate CD4⁺ T cells, as evidenced by a 41.18% decrease in CD25 expression and a 30.28% reduction in IFN-γ secretion. Similarly, CD8⁺ T cell activation is compromised, as indicated by a 32.26% decrease in IFN-γ production, although CD25 expression remains unaffected. Collectively, our findings identify ADMA as a potential immunosuppressive factor that disrupts antigen uptake, processing, and presentation in DCs, thereby modulating T cell activation. These insights suggest a potential mechanism through which ADMA may contribute to immune evasion within the tumor microenvironment. Full article

Cardiovascular complications are a major concern in thalassemia patients, primarily driven by endothelial dysfunction. This systematic review and meta-analysis evaluated endothelial biomarkers as indicators of cardiovascular disease risk in thalassemia. A systematic search of PubMed, Scopus, and Embase identified 41 studies comparing biomarkers in thalassemia patients and healthy individuals. The biomarkers analyzed included ICAM-1, VCAM-1, E-selectin, P-selectin, von Willebrand factor (vWF), endothelial microparticles (EMPs), nitric oxide (NO), nitric oxide synthase (NOS), asymmetric dimethylarginine (ADMA), and endothelin-1 (ET-1). Using random effects modeling, pooled standardized mean differences (SMDs) and 95% confidence intervals (CIs) were calculated. The results showed significantly elevated levels of ICAM-1 (SMD 2.15, 95% CI: 1.09–3.22), VCAM-1 (SMD 2.50, 95% CI: 1.35–3.66), E-selectin (SMD 1.21, 95% CI: 0.92–1.50), P-selectin (SMD 1.62, 95% CI: 0.83–2.42), and ET-1 (SMD 1.23, 95% CI: 0.03–2.42) in thalassemia patients. However, NO, ADMA, and vWF showed no significant differences. No studies on NOS were identified, while only one study found significantly elevated EMPs in thalassemia patients. This review highlights ICAM-1, VCAM-1, E-selectin, P-selectin, and ET-1 as key biomarkers for cardiovascular complications in thalassemia. Further research on EMPs and NOS is essential to enhance the understanding of endothelial dysfunction in this population. Full article

Hyperhomocysteinemia (HHcy) influences the development and progression of neurodegenerative disorders in different ways. Homocysteine (Hcy) metabolism is related to that of asymmetric dimethylarginine (ADMA) and group B vitamins. The breakdown of the pathway involving nitric oxide (NO) and ADMA can be considered one of the causes of endothelial alteration that represents a crucial step in the development of several neurodegenerative disorders. Deficiencies of vitamins other than group B ones, such as D and A, have also been associated with central nervous system disorders. The aim of this narrative review is to describe the link between HHcy, ADMA, and vitamins in Parkinson’s disease (PD), Alzheimer’s disease (AD), and multiple sclerosis (MS) in terms of dysfunctional pathways and neuropathological processes, performing a literature search from 2015 to 2025 on PubMed. This review also provides an overview of the effects of vitamin supplementation on neurodegenerative diseases. The alteration of pathways involving NO production can lead to HHcy and elevated ADMA concentrations, causing neurodegeneration through various mechanisms, while vitamin supplementation has been shown to reduce Hcy levels, although with conflicting results about the improvement in clinical symptoms. Further studies are needed to develop optimal combined therapeutic strategies. Full article

Asymmetric dimethylarginine (ADMA) is an endogenous nitric oxide synthase (NOS) inhibitor associated with vascular disease, which is prevalent in human plasma. Two isoforms of the enzyme dimethylarginine dimethylaminohydrolase (DDAH), DDAH 1 and 2, degrade ADMA. This study investigates the association of DDAH 1 (rs669173, rs7521189) and DDAH 2 gene polymorphisms (rs805305, rs3131383) with the risk of preeclampsia (PE) comorbidity with human immunodeficiency virus (HIV) infection in pregnant women of African ancestry. A total of 405 women were enrolled in this study: 204 were PE, 201 were normotensive pregnant, and 202 were HIV positive. DNA was extracted from whole blood, and SNPs (rs669173, rs7521189, rs805305, and rs3131383) were amplified to detect single-nucleotide polymorphisms (SNPs). After PCR amplification, allelic discrimination was examined. Comparisons were conducted utilizing the Chi-squared test. Our findings indicated that preeclamptic women displayed a greater prevalence of the three variants compared to those with both PE and HIV infection. There is an association between the rs669173 and rs7521189 SNPs of the DDAH 1 gene and rs3131383 of the DDAH 2 gene, which could play a role in reducing the bioavailability of nitric oxide (NO), which affects endothelial function, leading to the development of PE in pregnant women of African ancestry. In contrast, the rs805305 variant of the DDAH 2 gene was not significantly associated with PE development. Interestingly, none of the SNPs investigated correlated with HIV infection or could be attributed to the human allelic variant influence on HIV infection outcome. Full article

Kidney disease and hypertension are interconnected, prevalent conditions that affect both pregnant women and children. Oxidative stress occurs when reactive oxygen species or reactive nitrogen species exceed the capacity of antioxidant systems. It plays a critical role in kidney development, resulting in kidney programming and increased risks for kidney disease and hypertension across the life course. Animal models have significantly advanced our understanding of oxidative stress-related kidney programming, the molecular mechanisms involved, and early-life antioxidant interventions to prevent kidney disease. This review critically examines the influence of perinatal oxidative stress on kidney development, highlighting its long-term effects on kidney outcomes and susceptibility to hypertension. It also explores the potential of antioxidant-based interventions in preventing kidney disease and hypertension. Furthermore, the review addresses the existing gap between insights gained from animal models and their translation into clinical practices, emphasizing the challenges and opportunities for future research in this area. Full article

The diagnosis of heart failure with preserved ejection fraction (HFpEF) remains challenging. The use of metabolomics approaches seems promising in speeding up and simplifying the diagnostic process in HFpEF patients, which can lead to earlier treatment initiation and better improvement of patient condition. The aim of this study was to develop a diagnostic panel of metabolites (metabolomic biomarkers) for the detection and diagnosis of HF with preserved ejection fraction. The study included 76 participants with hypertension, 36 of whom were diagnosed with HFpEF. The blood plasma metabolomic profile, including 72 metabolites, was detected using high-performance liquid chromatography combined with mass spectrometry. There were 18 statistically significant differences in concentrations of metabolites and 3 differences in their ratios between HFpEF and hypertension groups. The prognostic model for detecting the possibility of HFpEF included seven metabolites and two ratios: hexadecenoylcarnitine, arginine, trimethylamine-N-oxide, asymmetric dimethylarginine (ADMA), arginine/ADMA ratio, kynurenine, kynurenine/tryptophan, neopterin, and anthranilic acid. The area under the ROC curve was 0.981 ± 0.017. The resulting model was statistically significant (p < 0.001). The metabolomic panel could be considered as an addition to the present HFpEF laboratory diagnostic criteria for blood plasma analysis in clinical practice. Full article

Mastitis is one of the most frequent diseases in dairy farms and occurs in both clinical and subclinical forms, resulting in substantial economic losses. Asymmetrical dimethylarginine (ADMA) and symmetrical dimethylarginine (SDMA) are biomarkers that inhibit nitric oxide synthesis. Elevated ADMA levels are associated with an increased risk of mortality both in human medicine and in dogs and a potential need for intensive care, while SDMA correlates with poor prognoses in humans and the progression of renal disease in horses, though its impact varies depending on renal function. This study examines the plasma levels of ADMA and SDMA in healthy cows (H) and cows with subclinical mastitis (SCM) and clinical mastitis (CM). Cows were classified as having mastitis when CMT > 1 and SCC ≥ 250,000 cells/mL. The SCM group showed no clinical signs or milk alterations, whereas the CM group exhibited udder and/or milk changes. The study included 196 blood samples to determine ADMA and SDMA concentrations, with 96 from healthy cows and 100 from pathological cows (58 SCM and 42 CM). The descriptive statistics were reported as the median because the data were not normally distributed (Shapiro–Wilk test). Data were analyzed using the Kruskal–Wallis test with Bonferroni post hoc correction, and the cut-off and accuracy index were calculated using the gold-standard measurement, the SCC. Statistically significant differences in ADMA levels were observed between healthy cows (0.11 µmol/L) and cows with mastitis (SCM 0.26 µmol/L; CM 0.26 µmol/L), but no differences were found in their SDMA levels. The cut-off for ADMA was >0.164 µmol/L, with a sensitivity of 80.41% and specificity of 77.78%. This study suggests that the blood concentration of ADMA is statistically higher in cows with subclinical and clinical mastitis and could be further explored as a potential biomarker for diagnosing these diseases. Full article

Background/Objectives: Type 2 diabetes mellitus (T2DM) and its macro- and microvascular complications are major health concerns with multiple factors, like advanced end glycation products (AGEs), in the background. AGEs induce long-lasting functional modification of the proteins and collagen in the vascular wall and nerve tissue. We investigated the effect of alpha-lipoic acid (ALA) treatment on AGEs, soluble AGE receptor (sRAGE), the AGE/sRAGE ratio, and the parameters of endothelial dysfunction and their correlations. Methods: In our 6-month intervention study, 54 T2DM patients with neuropathy treated according to the actual therapeutic guidelines with unchanged oral antidiabetic drugs were included and treated by daily oral administration of 600 mg ALA. A total of 24 gender and age-matched T2DM patients without neuropathy served as controls. Results: In our work, we first demonstrated the attenuating effect of alpha lipoic acid therapy on AGEs in humans (11.89 (9.44–12.88) to 10.95 (9.81–12.82) AU/μg (p = 0.017)). sRAGE levels or the AGEs/sRAGE ratio were not affected by ALA treatment or by the presence of neuropathy. We found a correlation between the changes of AGEs and the improvement of current perception threshold and progranulin levels, and an inverse correlation with the change of asymmetric dimethylarginine. Conclusions: According to our results, ALA decreases AGEs, which may contribute to the clinically well-known beneficial effect in diabetic neuropathy and improvement of endothelial function. Full article

Background: Vascular calcification (VC) is a characteristic feature of atherosclerosis in patients with chronic kidney disease (CKD), and coronary artery calcification (CAC) significantly impacts future cardiovascular events and mortality. Although factors associated with CAC are well reported, only a few studies have evaluated the factors associated with the progression of CAC in pre-dialysis patients with CKD. Methods: We quantitatively evaluated CAC progression using the CAC score (CACS) measured using 16-row multi-detector computed tomography and assessed associated factors in 74 patients with CKD. Results: The median annual increase in CACS was 23.7 (IQR 2.0–73.0). CAC progression was associated with serum phosphate and plasma asymmetric dimethylarginine (ADMA) levels, an endogenous inhibitor of nitric-oxide synthase and a marker of endothelial dysfunction and atherosclerosis, in univariate analysis. Multivariate analysis revealed that ADMA is an independent risk factor for CAC progression in patients with CKD. The annual change in CACS was significantly different between patients with ADMA values <0.51 and those with ADMA values >0.51 (p < 0.05). Elevated ADMA levels were also significantly associated with estimated glomerular filtration rate (eGFR) decline in the univariate analysis. Conclusions: ADMA is a novel risk factor for CAC progression in patients with CKD. Vascular endothelial cell dysfunction, represented by elevated ADMA levels, may contribute to the progression of vascular calcification in patients with pre-dialysis CKD. Full article

Protein arginine methyltransferase 1 (PRMT1) is the main PRMT family member involved in the formation of monomethylarginine and asymmetric dimethylarginine on its protein substrates. Many protein substrates of PRMT1 are key mediators of cell proliferation and oncogenesis. As such, the function of PRMT1 has been most prominently investigated in the context of cancer development. However, recent in vitro and in vivo studies have highlighted that PRMT1 may also promote metabolic disorders. With the current review, we aim to present an in-depth overview of how PRMT1 influences epigenetic modulation, transcriptional regulation, DNA damage repair, and signal transduction in cancer. Furthermore, we summarize the current knowledge regarding the role of PRMT1 in metabolic reprogramming, lipid metabolism, and glucose metabolism and describe the association of PRMT1 with numerous metabolic pathologies such as obesity, liver disease, and type 2 diabetes. It has become apparent that inhibiting the function of PRMT1 will likely serve as the most beneficial therapeutic approach, since several PRMT1 inhibitors have already been shown to exert positive effects on both cancer and metabolic disease in preclinical settings. However, pharmacological PRMT1 inhibition has not yet been shown to be therapeutically effective in clinical studies. Full article