雏鸡的氧缺乏症

育雏鸡氧缺乏症是临床诊疗中的常见病，多发于严寒的冬季。发病原因是养殖户在育雏过程中没有解决好保温与通风之间的矛盾，为保温而将育雏室用塑料薄膜封闭得严严实实，不注意通风换气。数量很多的苗鸡，在很小的空间内呼吸消耗掉大量的氧气。此外，用煤炉加温，煤炭在燃烧过程中也消耗掉不少的氧气，造成氧气缺乏、二氧化碳蓄积过多，从而导致发病（单纯用电热管加温的鸡群亦可发生该病）。

Injections of Substances Inducing Apoptosis to Cancer Cells but Stimulation of Normal Cells May Prevent Cancer

Selenium（Se） compounds have prevented and Se-deficiency has induced the initiation of cancer. Se（0）-forming compounds and hydroxy-xanthones have killed cancer ceils but shown beneficial effects to normal cells. They may together be effective in the treatment of cancer. Many enzymes which contain selenocysteine （Secys） can catalyze reactions with reducible oxygen （O2~ 02 or H202）. Experiments strongly support that Se-enzymes are activated by Se（0）, from e.g. selenite, selenodiglutathione, binding to Se（-II） in Secys, forming an electron conducting Se-link to reducible oxygen as a protection against oxidations. Cancer cells, which are energy supported only from fermentation, are not dependent on Se which is why they are more sensitive to toxic effects of Se than normal cells. The energy from fermentation is insufficient for normal cell functions. High doses of Se（0）-containing compounds are toxic in that they form links with thiols （R-S-Se） reducing their reaction rate. The reaction of an SH-enzyme, necessary in fermentation, is impaired. Mangostins （hydroxy-xanthones） induce apoptosis in human cancer ceils but stimulate respiration. The OH-groups are responsible for the effects and the reduction of NADP＋ into NADPH. Fermentation is inhibited as NADP＋ is necessary for the process. Cancer may be treated by injections of Se（0）-forming compounds and hydroxy-xanthones into cancer cells in doses causing apoptosis. However, in diluted form, when meting normal cells, the substances promote the yield of energy by stimulating the electron transference to reducible oxygen. Se（0）-activated Se-links and hydrogen from hydroxy-xanthones hopefully prevent the initiation of cancer.

Constitutive androstane receptor agonist, TCPOBOP,attenuates steatohepatitis in the methionine choline-deficientdiet-fed mouse

AIM： To ascertain whether constitutive androstane receptor （CAR） activation by 1,4-bis-[2-（3,5,- dichloropyridyloxy）] benzene （TCPOBOP） modulates steatohepatitis in the methionine choline-deficient （MCD） diet-fed animal.METHODS： C57/BL6 wild-type mice were fed the MCD or standard diet for 2 wk and were treated with either the CAR agonist, TCPOBOP, or the CAR inverse agonist, androstanol.RESULTS： Expression of CYP2B10 and CYP3A11, known CAR target genes, increased 30-fold and 45-fold, respectively, in TCPOBOP-treated mice fed the MCD diet. TCPOBOP treatment reduced hepatic steatosis （44.6 ＋ 5.4% vs 30.4 ＋ 4.5%, P 〈 0.05） and serum triglyceride levels （48 ＋ 8 vs 20 ＋ 1 mg/dL, P 〈 0.05） in MCD diet- fed mice as compared with the standard diet-fed mice. This reduction in hepatic steatosis was accompanied by an increase in enzymes involved in fatty acid microsomal co-oxidation and peroxisomal p-oxidation, namely CYP4A10, LPBE, and 3-ketoacyI-CoA thiolase. The reduction in steatosis was also accompanied by a reduction in liver cell apoptosis and inflammation. In contrast, androstanol was without effect on any of the above parameters.CONCLUSION： CAR activation stimulates induction of genes involved in fatty acid oxidation, and ameliorates hepatic steatosis, apoptosis and inflammation.

Novel ACADVL variants resulting in mitochondrial defects in long-chain acyl-CoA dehydrogenase deficiency

The pathogenesis of very-long-chain acyl-CoA dehydrogenase(VLCAD)deficiency is highly heterogeneous and still unclear.Additional novel variants have been recently detected in the population.The molecular and cellular effects of these previously unreported variants are still poorly understood and require further characterization.To address this problem,we have evaluated the various functions and biochemical consequences of six novel missense variants that lead to mild VLCAD deficiency.Marked deficiencies in fatty acid oxidation(FAO)and other mitochondrial defects were observed in cells carrying one of these six variants(c.541 C>T,c.863 T>G,c.895 A>G,c.1238 T>C,c.1276 G>A,and c.1505 T>A),including reductions in mitochondrial respiratory-chain function and adenosine teriphosphate(ATP)production,and increased levels of mitochondrial reactive oxygen species(ROS).Intriguingly,higher apoptosis levels were found in cells carrying the mutant VLCAD under glucose-limited stress.Moreover,the stability of the mutant homodimer was disturbed,and major conformational changes in each mutant VLCAD structure were predicted by molecular dynamics(MD)simulation.The data presented here may provide valuable information for improving management of diagnosis and treatment of VLCAD deficiency and for a better understanding of the general molecular bases of disease variability.