Progressive psychomotor regression for 2.5 years in a boy aged 5 years / 中国当代儿科杂志

A boy, aged 5 years, attended the hospital due to progressive psychomotor regression for 2.5 years. Motor function regression was the main manifestation in the early stage, and brain MRI and whole-exome sequencing (WES) of the family showed no abnormalities. After the age of 4 years and 9 months, the boy developed cognitive function regression, and brain MRI showed cerebellar atrophy. The reanalysis of WES results revealed a compound heterozygous mutation, [NM_000520, c.784C>T(p.His262Tyr]), c.1412C>T(p.Pro471Leu)], in the HEXA gene. The enzyme activity detection showed a significant reduction in the level of β-hexosaminidase encoded by this gene. The boy was diagnosed with juvenile Tay-Sachs disease (TSD). TSD has strong clinical heterogeneity, and cerebellar atrophy may be an important clue for the diagnosis of juvenile TSD. The reanalysis of genetic data when appropriate based on disease evolution may improve the positive rate of WES.

An association between diet quality index for Koreans (DQI-K) and total mortality in Health Examinees Gem (HEXA-G) study

BACKGROUND/OBJECTIVES: Diet quality scores or indices, based on dietary guidelines, are used to summarize dietary intake into a single numeric variable. The aim of this study was to examine the association between the modified diet quality index for Koreans (DQI-K) and mortality among Health Examinees-Gem (HEXA-G) study participants. SUBJECTS/METHODS: The DQI-K was modified from the original diet quality index. A total of 134,547 participants (45,207 men and 89,340 women) from the HEXA-G study (2004 and 2013) were included. The DQI-K is based on eight components: 1) daily protein intake, 2) percent of energy from fat, 3) percent of energy from saturated fat, 4) daily cholesterol intake, 5) daily whole-grain intake, 6) daily fruit intake, 7) daily vegetable intake, and 8) daily sodium intake. The association between all-cause mortality and the DQI-K was examined using Cox proportional hazard regression models. Hazard ratios and confidence intervals were estimated after adjusting for age, gender, income, smoking status, alcohol drinking, body mass index, and total energy intake. RESULTS: The total DQI-K score was calculated by summing the scores of the eight components (range 0–9). In the multivariable adjusted models, with good diet quality (score 0–4) as a reference, poor diet quality (score 5–9) was associated with an increased risk of all-cause mortality (hazard ratios = 1.23, 95% confidence intervals = 1.06–1.43). Moreover, a one-unit increase in DQI-K score resulted in a 6% higher mortality risk. CONCLUSIONS: A poor diet quality DQI-K score was associated with an increased risk of mortality. The DQI-K in the present study may be used to assess the diet quality of Korean adults.

Biodegradation of 2,4'-dichlorobiphenyl, a congener of polychlorinated biphenyl, by Pseudomonas isolates GSa and GSb.

Biodegradation of 2,4'-dichlorobiphenyl (2,4 CB), by two isolates of Pseudomonas (GSa and GSb) was compared using GC-MS. Transformer oil polluted soil was used for the isolation of 2,4 CB degrading bacteria. GC-MS analysis of the solvent extracts obtained from Pseudomonas sp. GSa spent culture indicated the presence of Phenol 2,6-bis (1,1-dimethyl)-4-methyl (C15H24O). Further, the enzyme analysis of the cell free extracts showed the presence of 2,4'-dichlorobiphenyl dehalogenase (CBD), 2,4'-dichlorobiphenyl-NADPH-oxido-reductase (2,4 CBOR) and 2,3-dihydro-xybiphenyl-NADPH-oxido-reductase (2,3 DHOR) with specific activity of 6.00, 0.4 and 0.22 μmol/min/mg of protein, suggesting that dechlorination as an important step during 2,4 CB catabolism. Further, the cell free extract of GSb showed only 2,4'-dichlorobiphenyl-NADPH-oxido-reductase (2,4 CBOR) and 2,3-dihydroxybiphenyl-NADPH-oxido-reductase (2,3 DHOR), with specific activity of 0.3 and 0.213 μmol/min/mg of protein, suggesting attack on non-chlorinated aromatic ring of 2,4 CB, releasing chlorinated intermediates which are toxic to the environment. Although, both the isolated bacteria (GSa and GSb) belong to Pseudomonas spp., they exhibited different metabolic potential.

Protection by Chrysanthemum zawadskii extract from liver damage of mice caused by carbon tetrachloride is maybe mediated by modulation of QR activity

Our previous study demonstrated that methanolic extract of Chrysanthemum zawadskii Herbich var. latilobum Kitamura (Compositae) has the potential to induce detoxifying enzymes such as NAD(P)H:(quinone acceptor) oxidoreductase 1 (EC 1.6.99.2) (NQO1, QR) and glutathione S-transferase (GST). In this study we further fractionated methanolic extract of Chrysanthemum zawadskii and investigated the detoxifying enzyme-inducing potential of each fraction. The fraction (CZ-6) shown the highest QR-inducing activity was found to contain (+)-(3S,4S,5R,8S)-(E)-8-acetoxy-4-hydroxy-3-isovaleroyloxy-2-(hexa-2,4-diynyliden)-1,6-dioxaspiro [4,5] decane and increased QR enzyme activity in a dose-dependent manner. Furthermore, CZ-6 fraction caused a dose-dependent enhancement of luciferase activity in HepG2-C8 cells generated by stably transfecting antioxidant response element-luciferase gene construct, suggesting that it induces antioxidant/detoxifying enzymes through antioxidant response element (ARE)-mediated transcriptional activation of the relevant genes. Although CZ-6 fraction failed to induce hepatic QR in mice over the control, it restored QR activity suppressed by CCl4 treatment to the control level. Hepatic injury induced by CCl4 was also slightly protected by pretreatment with CZ-6. In conclusion, although CZ-6 fractionated from methanolic extract of Chrysanthemum zawadskii did not cause a significant QR induction in mice organs such as liver, kidney, and stomach, it showed protective effect from liver damage caused by CCl4.

Molecular cloning, sequence identification and tissue expression profile of three novel sheep (Ovis aries) genes - BCKDHA, NAGA and HEXA

The complete coding sequences of three sheep genes- BCKDHA, NAGA and HEXA were amplified using the reverse transcriptase polymerase chain reaction (RT-PCR), based on the conserved sequence information of the mouse or other mammals. The nucleotide sequences of these three genes revealed that the sheep BCKDHA gene encodes a protein of 313 amino acids which has high homology with the BCKDHA gene that encodes a protein of 447 amino acids that has high homology with the Branched chain keto acid dehydrogenase El, alpha polypeptide (BCKDHA) of five species chimpanzee (93 percent), human (96 percent), crab-eating macaque (93 percent), bovine (98 percent) and mouse (91 percent). The sheep NAGA gene encodes a protein of 411 amino acids that has high homology with the alpha-N-acetylgalactosaminidase (NAGA) of five species human (85 percent), bovine (94 percent), mouse (91 percent), rat (83 percent) and chicken (74 percent). The sheep HEXA gene encodes a protein of 529 amino acids that has high homology with the hexosaminidase A(HEXA) of five species bovine (98 percent), human (84 percent), Bornean orangután (84 percent), rat (80 percent) and mouse (81 percent). Finally these three novel sheep genes were assigned to GenelDs: 100145857, 100145858 and 100145856. The phylogenetic tree analysis revealed that the sheep BCKDHA, NAGA, and HEXA all have closer genetic relationships to the BCKDHA, NAGA, and HEXA of bovine. Tissue expression profile analysis was also carried out and results revealed that sheep BCKDHA, NAGA and HEXA genes were differentially expressed in tissues including muscle, heart, liver, fat, kidney, lung, small and large intestine. Our experiment is the first to establish the primary foundation for further research on these three sheep genes.

A study on new cell-cycle inhibitors from the metabolites of marine-derived Streptomyces flavorectus / 中国海洋药物

Aim To explore the antitumor active metabolites of marine-derived Streptomyces flavorectus Z4-007. Methods The separation procedure was guided by a flow cytometric bioassay using tsFT210 cells to examine cell cycle inhibitory activity, and various column chromatography using silica gel, Sephadex LH-20, and ODS were employed for the isolation and purification of bioactive compounds. Chemical structures were investigated by spectroscopic methods and biological activities were evaluated by flow cytometry using mouse cancer tsFT210 cells. Results Four bioactive compounds were isolated from the fermentation broth of Streptomyces flavorectus Z4-007, one of them had been identified as 1-(2,4-Dihydroxy-3,5-dimethyl-phenyl)-hexa- (E,E)-2,4-dien-1-one (1) and the other three compounds were considered to be peptide, Compound Ⅰ inhibited the cell-cycle of tsFT210 cells at the G_0/G_1 phase at higher concentrations, while at the lower concentrations compound Ⅰ inhibited the cell-cycle mainly at the G_2/M phase, accompanied with induction of apoptosis in the tsFT210 cells.Conclusion Compound Ⅰ was isolated from the metabolites of the genus Streptomyces for the first time and provided as a new cell-cycle inhibitor.