Activity

Primary cultured rat and human hepatocytes were considered to be useful for the evaluation of effects of the benzimidazole compounds on their inducibility and inhibitory activities of cytochrome P450 forms.Quercetin and gallic acid are phytochemicals with interesting pharmacological properties. We herein investigated the protective effect of quercetin (QUE) in comparison with gallic acid (GAL) against exogenously-induced oxidative damage in rats’ kidney and human embryonic kidney (HEK-293) cell lines. Adult Wistar rats were treated with QUE and GAL (50 mg/kg) separately or in combination with di-n-butylphthalate (DnBP) for 14 days; and HEK-293 cells were treated with different concentrations of GAL (25-294 μM) or QUE (2-17 μM or 28-165.43 μM) singly or in combination with H2O2 (200 μM). After treatment, the kidney and cell extracts were processed for biochemical analysis and histopathology. We found that GAL but not QUE prevented DnBP-induced increase in lipid peroxidation (2.603 ± 0.25 vs. 3.65 ± 0.21 μmol/mL). Treatment with QUE but not GAL was associated with increased plasma creatinine (729.09 ± 55.68 vs. 344.25 ± 50.78 μmol/l) and tissue malondialdehyde (3.72 ± 0.62 vs. 1.67 ± 0.47 μmol/mL) concentrations, along with histo-pathological changes such as glomerular and tubular degenerations. However, QUE exhibited wider therapeutic concentration ranges than GAL at which it inhibits lipid peroxidation in HEK-293 cells, and was found to inhibit H2O2-induced lipid peroxidation even at the lowest concentration (2 μM) that was tested (0.607 ± 0.074 vs. learn more 0.927 ± 0.106 μmol/l). These suggest that the in vivo dosages required for the antioxidant protective effects of QUE in renal tissues are low.

Phenylketonuria (PKU) can be effectively treated with the use of a low-phenylalanine diet. However, some patients become overweight despite proper dietary treatment. We hypothesized that this phenomenon could be explained by the presence of specific variants within the genes involved in phenylalanine transport or in the phenylalanine transamination/oxygenation pathway.

We selected a clinically homogenous group of 100 infants with PKU and assessed their growth patterns in the context of dietary phenylalanine tolerance. Next, within the sample, we performed exome sequencing and assessed a potential relationship between the observed phenotypical variability and the presence of structural variants in a priori selected genes of interest.

We detected a highly significant association between overweight and carriership of the rs113883650/rs2287120 haplotype of the

(

) gene, which encodes the main transmembrane transporter of large neutral amino acids and of thyroid hormones.

Our findings suggest a pharmacogenetic effect of the relatively common rs113883650/rs2287120 haplotype of the

gene. This can have practical implications for patients with PKU, since treatment protocols need to be reassessed to better prevent overweight in the carriers of the above variant.

Our findings suggest a pharmacogenetic effect of the relatively common rs113883650/rs2287120 haplotype of the SLC7A5 gene. This can have practical implications for patients with PKU, since treatment protocols need to be reassessed to better prevent overweight in the carriers of the above variant.Asymptomatic aminotransferase elevation has a broad differential in the pediatric population. We report an 11-year old male with a history of urine discoloration found to have persistently elevated aminotransferases. Biochemical evaluation was notable for elevated uroporphyrin, consistent with porphyria cutanea tarda (PCT). Genetic testing revealed biallelic pathogenic variants in HFE and a pathogenic variant in UROD, consistent with a diagnosis of hereditary hemochromatosis (HHC) and PCT, respectively. Dual diagnosis likely explains the pediatric onset of these typically adult-onset conditions.Congenital Disorders of Glycosylation (CDG) are scarcely reported from Latin America. We here report on a Mexican mestizo with a multi-systemic syndrome including neurological involvement and a type I transferrin (Tf) isoelectric focusing (IEF) pattern. Clinical exome sequencing (CES) showed known compound missense variants in PMM2 c.422G > A (p.R141H) and c.395 T > C (p.I132T), coding for the phosphomanomutase 2 (PMM2). PMM2 catalyzes the conversion of mannose-6-P to mannose-1-P required for the synthesis of GDP-Man and Dol-P-Man, donor substrates for glycosylation reactions. This is the third reported Mexican CDG patient and the first with PMM2-CDG. PMM2 has been recently identified as one of the top 10 genes carrying pathogenic variants in a Mexican population cohort.Bacillus subtilis is a model Gram-positive bacterium, which has been widely used as industrially important chassis in synthetic biology and metabolic engineering. Rapid growth of chassis is beneficial for shortening the fermentation period and enhancing production of target product. However, engineered B. subtilis with faster growth phenotype is lacking. Here, fast-growing B. subtilis were constructed through rational gene knockout and adaptive laboratory evolution using wild type strain B. subtilis 168 (BS168) as starting strain. Specifically, strains BS01, BS02, and BS03 were obtained through gene knockout of oppD, hag, and flgD genes, respectively, resulting 15.37%, 24.18% and 36.46% increases of specific growth rate compared with BS168. Next, strains A28 and A40 were obtained through adaptive laboratory evolution, whose specific growth rates increased by 39.88% and 43.53% compared to BS168, respectively. Then these two methods were combined via deleting oppD, hag, and flgD genes respectively on the basis of evolved strain A40, yielding strain A4003 with further 7.76% increase of specific growth rate, reaching 0.75 h-1 in chemical defined M9 medium. Finally, bioproduction efficiency of intracellular product (ribonucleic acid, RNA), extracellular product (acetoin), and recombinant proteins (green fluorescent protein (GFP) and ovalbumin) by fast-growing strain A4003 was tested. And the production of RNA, acetoin, GFP, and ovalbumin increased 38.09%, 5.40%, 9.47% and 19.79% using fast-growing strain A4003 as chassis compared with BS168, respectively. The developed fast-growing B. subtilis strains and strategies used for developing these strains should be useful for improving bioproduction efficiency and constructing other industrially important bacterium with faster growth phenotype.