Urinary arginine methylation index associated with ambulatory blood pressure abnormalities in children with chronic kidney disease

Arginine (ARG) metabolites are interrelated and are involved in chronic kidney disease (CKD) and cardiovascular disease. Twenty-four-hour ambulatory blood pressure monitoring (ABPM) appears to correlate with cardiovascular outcomes. We investigated the relationship between ARG metabolites, and their combined ratios in urine, and the ABPM profiles of children and adolescents with CKD. This cross-sectional study included 45 children and adolescents (age, 5–18 years) with stage 1 to 4 CKD. Each child underwent office blood pressure (BP) measurements, 24-hour ABPM, and urinary ARG metabolite determinations. Seventy percent of children with CKD had abnormal 24-hour ABPM profiles, including nocturnal hypertension, increased BP load, and nondipping nocturnal BP. The urinary ARG-to-asymmetric dimethylarginine (ADMA) ratio was lower, and the ADMA-to-symmetric dimethylarginine (SDMA) ratio was higher in children with advanced CKD (stages 2–4) than those with stage 1 CKD. CKD patients with BP abnormalities also had reduced urinary ARG and dimethylamine (DMA) levels. The higher urinary (ADMA+SDMA)-to-ARG ratios were correlated to ABPM abnormalities, including increased systolic BP load and non-dipping nocturnal BP. ABPM abnormalities were significantly associated with a high urinary (ADMA+SDMA)-to-ARG ratio, suggesting the possible involvement of methylated ARG in the development of hypertension among children with CKD.     

Clinical phenotyping in selected national networks: demonstrating the need for high-throughput,portable, and computational methods

ObjectiveThe combination of phenomic data from electronic health records (EHR) and clinical data repositories with dense biological data has enabled genomic and pharmacogenomic discovery, a first step toward precision medicine. Computational methods for the identification of clinical phenotypes from EHR data will advance our understanding of disease risk and drug response, and support the practice of precision medicine on a national scale.MethodsBased on our experience within three national research networks, we summarize the broad approaches to clinical phenotyping and highlight the important role of these networks in the progression of high-throughput phenotyping and precision medicine. We provide supporting literature in the form of a non-systematic review.ResultsThe practice of clinical phenotyping is evolving to meet the growing demand for scalable, portable, and data driven methods and tools. The resources required for traditional phenotyping algorithms from expert defined rules are significant. In contrast, machine learning approaches that rely on data patterns will require fewer clinical domain experts and resources.ConclusionsMachine learning approaches that generate phenotype definitions from patient features and clinical profiles will result in truly computational phenotypes, derived from data rather than experts. Research networks and phenotype developers should cooperate to develop methods, collaboration platforms, and data standards that will enable computational phenotyping and truly modernize biomedical research and precision medicine.     

Rootstock effect on serotonin and nutritional quality of tomatoes produced under low temperature and light conditions

In this study, we explored the capacity of different tomato rootstocks to improve the nutritional value of tomatoes grown in a greenhouse during the winter–spring period under low temperature and light conditions. The results showed that relative to nongrafted plants, some grafted rootstocks either did not affect or had detrimental effects on the nutritional parameters measured. In addition, the amount of serotonin was significantly lower in tomatoes from all grafted rootstocks than in tomatoes from the nongrafted plants. Nevertheless, relative to the nongrafted plants, some grafted treatments increased total macroelements (by 1.16 times), total microelements (by 1.43 times), protein content (by 17%), free total and essential amino acids (by respectively 23% and 19%), total phenolic compounds (by 11%), vitamin C (by 13.8%), lycopene (by 48%), and also total hydrocinnamic acids (by 67%) and flavonoids (by 279%). As the grafted treatments did not increase the tomato yield, we hypothesize that these compounds accumulated in the tomatoes due to the lack of increased biomass, which prevented a dilution effect on the compounds of interest in the fruits.     

Daphnetin ameliorates 7,12-dimethylbenz[a]anthracene-induced mammary carcinogenesis through Nrf-2-Keap1 and NF-κB pathways

Cancer is a faction of disorders that conjugated primarily with oxidative imbalance. In mammary carcinoma, oxidative stress secondarily changes various gene expressions and signalling pathways that bring genomic instability and mutagenic alterations that fascinating carcinogenesis. Several coumarin compounds are active against various malignancies. Among them, daphnetin (DAP) exhibits valuable safety and bioactivity profile that contributes towards its efficacy against cancer. In this study, the antioxidative and chemotherapeutic potential of DAP against 7,12-dimethylbenz(a)anthracene (DMBA)- induced mammary carcinogenesis was evaluated in female Sprague-Dawley rats. Besides this, we have determined the effect of DAP on Keap1-Nrf-2, associated HO-1 and NF-κB expressions behind the antioxidative and anti-proliferating activity. In our findings, a protective effect of DAP was established against lipid peroxidation, enzymic (Total SOD, MnSOD, CuZnSOD, CAT, GPx) and non-enzymic (GSH) antioxidative markers in serum, liver, kidney and breast tissue of both control and experimental groups. An up-regulation of protective Nrf-2 & HO-1 with a synchronized suppression in Keap1 & NF-κB mRNA and protein expressions were observed. DAP revealed the inhibition of p-AKT which accountable for decrease in NF-κB expressions but shown to be ineffective on p-ERK1/2. This study revealed that DAP inhibits mammary carcinogenesis through multiple mechanisms. Dual efficacy of DAP on Nrf-2-Keap1 pathway and NF-κB expressions propose it as a potential chemotherapeutic agent in mammary cancer management.