Asymmetric and symmetric dimethylarginine (ADMA and SDMA, respectively) are toxic, non‐proteinogenic amino acids formed by post‐translational modification and are uremic toxins that inhibit nitric oxide (NO) production and play multifunctional roles in many human diseases. Both ADMA and SDMA have emerged as strong predictors of cardiovascular events and death in a range of illnesses. Major progress has been made in research on ADMA‐lowering therapies in animal studies; however, further studies are required to fill the translational gap between animal models and clinical trials in order to treat human diseases related to elevated ADMA/SDMA levels. Here, we review the reported impacts of ADMA and SDMA on human health and disease, focusing on the synthesis and metabolism of ADMA and SDMA; the pathophysiological roles of these dimethylarginines; clinical conditions and animal models associated with elevated ADMA and SDMA levels; and potential therapies against ADMA and SDMA. There is currently no specific pharmacological therapy for lowering the levels and counteracting the deleterious effects of ADMA and SDMA. A better understanding of the mechanisms underlying the impact of ADMA and SDMA on a wide range of human diseases is essential to the development of specific therapies against diseases related to ADMA and SDMA.

Congenital anomalies of the kidney and urinary tract (CAKUT) are 1 of the major factors in young adults needing renal replacement therapy, but there is little extensive assessment of their incidence and risk factors. This study aimed to evaluate trends in the incidence of and risk factors for CAKUT among all births in Taiwan. This population-based case–control study design was conducted using the Taiwan national births registry, which contains detailed information about maternal health and characteristics of newborns, supplied by health professionals. Of 1,603,794 newborns registered between 2004 and 2014, 668 infants were reported to have CAKUT. Newborns without congenital anomalies were matched with CAKUT cases by birth year, month, and Apgar score in a ratio of 5:1. Odds ratio (OR) and 95% confidence interval (CI) for developing CAKUT were calculated using a conditional multivariate logistic regression model. The incidence of CAKUT was approximately 4.2 per 10,000 births. The adjusted ORs for CAKUT in newborns associated with maternal age of 20 to 29 (OR, 2.18; 95% CI, 1.11–4.28), or 30 to 39 (OR, 2.29; 95% CI, 1.17–4.51), maternal gestational diabetes (OR, 2.22, 95% CI, 1.06–4.67), maternal thalassemia/hemochromatosis (OR, 2.67; 95% CI, 1.35–5.27), polyhydramnios or oligohydramnios (OR, 9.16; 95% CI, 5.46–15.37), birth parity >1 (OR, 0.27; 95% CI, 0.15–0.50), having a gestational age <37 weeks (OR, 1.48; 95% CI, 1.23–1.78), and being a boy (OR, 1.83; 95% CI, 1.53–2.19). Infants of mother with gestational diabetes were more likely to have congenital anomalies, small gestational age (<37 weeks) and low birth weight. CAKUT are associated with several maternal health risk factors. As Taiwan has the highest prevalence and incidence rates of end-stage renal disease in the world, these findings strongly support the need to develop professional guidelines for prenatal counseling and management of women at risk of adverse birth outcomes, to prevent kidney disease progression and reduce complications.

Resveratrol, also known as 3,5,4′-trihydroxystilbene, is a natural polyphenol that occurs as a phytoalexin. It is produced by plant sources such as grapes, apples, blueberries, plums, peanuts, and other oilseeds. This compound has a variety of effects on human health and diseases. This review summarizes the mounting evidence that resveratrol is helpful in treating metabolic syndrome and related disorders. Resveratrol can be provided either early as a reprogramming agent or later as part of treatment. A few of the main mechanisms underlying the beneficial effects of resveratrol on metabolic syndrome are outlined. This review also discusses the potential of resveratrol derivatives as a complementary or alternative medicine. In conclusion, resveratrol could be a useful regimen for the prevention and treatment of metabolic syndrome and its related conditions.

One of the leading global public-health burdens is metabolic syndrome (MetS), despite the many advances in pharmacotherapies. MetS, now known as “developmental origins of health and disease” (DOHaD), can have its origins in early life. Offspring MetS can be programmed by various adverse early-life conditions, such as nutrition imbalance, maternal conditions or diseases, maternal chemical exposure, and medication use. Conversely, early interventions have shown potential to revoke programming processes to prevent MetS of developmental origins, namely reprogramming. In this review, we summarize what is currently known about adverse environmental insults implicated in MetS of developmental origins, including the fundamental underlying mechanisms. We also describe animal models that have been developed to study the developmental programming of MetS. This review extends previous research reviews by addressing implementation of reprogramming strategies to prevent the programming of MetS. These mechanism-targeted strategies include antioxidants, melatonin, resveratrol, probiotics/prebiotics, and amino acids. Much work remains to be accomplished to determine the insults that could induce MetS, to identify the mechanisms behind MetS programming, and to develop potential reprogramming strategies for clinical translation.

Excessive intake of fructose is associated with hypertension. Gut microbiota and their metabolites are thought to be associated with the development of hypertension. We examined whether maternal high-fructose (HF) diet-induced programmed hypertension via altering gut microbiota, regulating short-chain fatty acids (SCFAs) and their receptors, and mediating nutrient-sensing signals in adult male offspring. Next, we aimed to determine whether early gut microbiota-targeted therapies with probiotic Lactobacillus casei and prebiotic inulin can prevent maternal HF-induced programmed hypertension. Pregnant rats received 60% high-fructose (HF) diet, with 2 × 10⁸ CFU/day Lactobacillus casei via oral gavage (HF+Probiotic), or with 5% w/w long chain inulin (HF+prebiotic) during pregnancy and lactation. Male offspring (n = 7–8/group) were assigned to four groups: control, HF, HF+Probiotic, and HF+Prebiotic. Rats were sacrificed at 12 weeks of age. Maternal probiotic Lactobacillus casei and prebiotic inulin therapies protect against hypertension in male adult offspring born to fructose-fed mothers. Probiotic treatment prevents HF-induced hypertension is associated with reduced plasma acetate level and decreased renal mRNA expression of Olfr78. While prebiotic treatment increased plasma propionate level and restored HF-induced reduction of Frar2 expression. Maternal HF diet has long-term programming effects on the adult offspring’s gut microbiota. Probiotic and prebiotic therapies exerted similar protective effects on blood pressure but they showed different mechanisms on modulation of gut microbiota. Maternal HF diet induced developmental programming of hypertension, which probiotic Lactobacillus casei or prebiotic inulin therapy prevented. Maternal gut microbiota-targeted therapies could be reprogramming strategies to prevent the development of hypertension caused by maternal consumption of fructose-rich diet.