A Plant Kavalactone Desmethoxyyangonin PreventsInflammation and Fulminant Hepatitis in Mice

Alpinia pricei Hayata is a Formosan plant which has been popularly used as nutraceutical or folk medicine for inflammation and various disorders. An active compound of the plant rhizomes, desmethoxyyangonin (DMY), was identified in this study for its novel effect against endotoxin lipopolysaccharide (LPS)-stimulated inflammation in murine macrophages and LPS/D-galactosamine (LPS/D-GalN)-induced fulminant hepatitis in mice. DMY was observed to significantly inhibit proliferation and activation of T cells ex vivo and the activity of several pro-inflammatory mediators in vitro. DMY also protected LPS/D-GalN−induced acute hepatic damages in mice through inhibiting aminotransferases activities and infiltrations of inflammatory macrophages, neutrophils and pathogenic T cells into the liver tissues. In addition, pretreatment with DMY significantly improved the survival rate of LPS/D-GalN−treated mice to 90% (9/10), compared to LPS/D-GalN−treated group (40%, 4/10). UPLC/MS platform-based comparative metabolomics approach was used to explore the serum metabolic profile in fulminant hepatic failure (FHF) mice with or without the DMY pretreatment. The results showed that LPS/D-GalN−induced hepatic damage is likely through perturbing amino acid metabolism, which leads to decreased pyruvate formation via catalysis of aminotransferases, and DMY treatment can prevent to a certain degree of these alterations in metabolic network in mouse caused by LPS/D-GalN. Mechanistic investigation demonstrated that DMY protects LPS or LPS/D-GalN−induced damages in cell or liver tissues mainly through de-regulating IKK/NFκB and Jak2/STAT3 signaling pathways. This report provides evidence-based knowledge to support the rationale for the use of A. pricei root extract in anti-inflammation and also its new function as hepatoprotetive agent against fulminant hepatitis

Rare structural variants found in attention-deficit hyperactivity disorder are preferentially associated with neurodevelopmental genes

Attention-deficit/hyperactivity disorder (ADHD) is a common and highly heritable disorder, but specific genetic factors underlying risk remain elusive. To assess the role of structural variation in ADHD, we identified 222 inherited copy number variations (CNVs) within 335 ADHD patients and their parents that were not detected in 2026 unrelated healthy individuals. Although no excess CNVs, either deletions or duplications, were found in the ADHD cohort relative to controls, the inherited rare CNV-associated gene set was significantly enriched for genes reported as candidates in studies of autism, schizophrenia and Tourette syndrome, including A2BP1, AUTS2, CNTNAP2 and IMMP2L. The ADHD CNV gene set was also significantly enriched for genes known to be important for psychological and neurological functions, including learning, behavior, synaptic transmission and central nervous system development. Four independent deletions were located within the protein tyrosine phosphatase gene, PTPRD, recently implicated as a candidate gene for restless legs syndrome, which frequently presents with ADHD. A deletion within the glutamate receptor gene, GRM5, was found in an affected parent and all three affected offspring whose ADHD phenotypes closely resembled those of the GRM5 null mouse. Together, these results suggest that rare inherited structural variations play an important role in ADHD development and indicate a set of putative candidate genes for further study in the etiology of ADHD

Influence diagnostics for polyhazard models in the presence of covariates

Polyhazard model, Poly-Weibull distribution, Poly-log-logistic distribution, Influence diagnostics, Residual analysis,

Screening and comparative study of in vitro antioxidant and antimicrobial activities of ethanolic extracts of selected Vietnamese plants

This study aimed to screen the in vitro antioxidant and antimicrobial activities of ethanolic extracts from 20 plants and three herbal commercial products empirically used for aquaculture improvement in Vietnam. The results of 2,2-diphenyl-1-pycrylhydrazyl (DPPH) radical scavenging assays showed that Phyllanthus amarus extract was the strongest antioxidant, followed by four extracts in the subsequent order: Piper betle > Psidium guajava > Euphorbia hirta > Mimosa pudica. These five plant extracts were very active in a DPPH radical scavenging assay with concentrations needed to scavenge half of the DPPH (IC50) below 30 µg/mL. Seven plant extracts showed an IC50 ranging from 31.9 to 59.7 µg/mL, while eleven extracts showed an IC50 above 70 µg/mL. A positive association was found between phenolic content (expressed as gallic acid equivalents) and antioxidant activity of the plant extracts. Concerning in vitro antimicrobial activities, P. amarus extract showed the highest activity against two different strains of Aeromonas hydrophila as demonstrated by its low minimal inhibitory concentration (MIC) of 156 and 625 µg/mL, respectively; whereas, P. betle displayed a moderate activity against Edwardsiella ictaluri with a MIC value of 625 µg/mL. Tannins were observed as significant factors contributing to antioxidant and antimicrobial properties of the plant extracts tested