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Background: Over-expression of membranous CD154 and soluble CD154 (sCD154) in T lymphocytes is important in pathogenesis of autoimmune diseases. PKC pathway induces sCD154 production through promoting shedding of membranous CD154. Objectives: Hydroxychloroquine (HCQ) has been used in the treatment of autoimmune diseases for decades. We sought to identify the effects of HCQ on sCD154 and a possibly regulatory mechanism. Methods: CD4 +T cells were isolated from the blood of healthy donor. After stimulated with ionomycin +PMA and various concentrations of HCQ, concentration of sCD154 in the medium, expression of membranous CD154, Ca2+ pathway and PKC signalling pathway were assessed. Results: HCQ attenuated intracellular sustained calcium storage release and membranous CD154 synthesis in activated T cells. Besides, HCQ inhibited PKC activation and subsequently shedding of membranous CD154. Conclusions: HCQ inhibited production of sCD154 in activated T cells through suppressing Ca2+ and PKC signalling pathway. These findings provide one of the mechanistic insights into HCQ treatment. References [1] Alaaeddine N, Hassan GS, Yacoub D, Mourad W. CD154: an immunoinflammatory mediator in systemic lupus erythematosus and rheumatoid arthritis. Clin Dev Immunol. 2012:490148. [2] Goules A, Tzioufas AG, Manousakis MN, Kirou KA, Crow MK, Routsias JG. Elevated levels of soluble CD40 ligand (sCD40L) in serum of patients with systemic autoimmune diseases. J Autoimmun2006;26:165–71. [3] Matthies KM, Newman JL, Hodzic A, Wingett DG. Differential regulation of soluble and membrane CD40L proteins in T cells. Cell Immunol. 2006;241:47–58. [4] Wu SF, Chang CB, Hsu JM, Lu MC, Lai NS, Li C, Tung CH. Hydroxychloroquine inhibits CD154 expression in CD4+ T lymphocytes of systemic lupus erythematosus through NFAT, but not STAT5, signaling. Arthritis Res Ther2017Aug 9;19(1):183. Disclosure of Interest None declared

To study the effect of dietary docosahexaenoic acid (DHA) on the expression of adipocyte determination and differentiation-dependent factor 1 (ADD1) mRNA in pig tissues, weaned, crossbred pigs (30 d of age) were fed either 2% (as-fed basis) tallow or DHA oil for 18 d. Body weight of the pigs was not affected by different dietary fatty acid (FA) compositions. The plasma and liver FA composition reflected the composition of the diet. The adipose tissue and skeletal muscle FA composition only partially reflected the diet, indicating either a slower FA turnover or that a greater proportion of the FA in these tissues is from endogenous FA synthesis. The ADD1 is an important transcription factor that modulates transcription of FA synthase to regulate the endogenous FA synthesis in the liver and adipose tissue. The ADD1 mRNA was decreased (P < 0.05) in the liver of DHA-treated pigs compared with that of the tallow-treated pigs. The diets did not have an effect on the ADD1 mRNA in pig adipose tissue. The ADD1 transcript was not detected in pig skeletal muscle. These results indicate that significant enrichment of liver DHA content inhibits the expression of ADD1 mRNA. Such an effect is similar to that reported in porcine differentiating adipocytes cultured with DHA. The liver and muscle acyl CoA oxidase mRNA concentration was increased (P < 0.05) by DHA oil treatment, suggesting that DHA treatment may increase peroxisomal fatty acid oxidation in these two tissues. Our present observations demonstrate that dietary DHA enrichment not only affects tissue DHA concentration but also mildly modifies the expression of genes related to fatty acid metabolism in the porcine liver and skeletal muscle.

Polyunsaturated fatty acids (FA) regulate genes involved in lipid metabolism. The effects of polyunsaturated FA on the transcription factor adipocyte determination and differentiation-dependent factor (ADD) 1 and fatty acid synthase (FAS) mRNA in differentiating porcine adipocytes were measured using a stromal vascular cell culture system. Porcine stromal vascular cells were isolated from subcutaneous adi-pose tissues and plated in Dulbecco's modified Eagle's medium (DMEM)–nutrient mixture F-12 Ham (F-12) plus fetal bovine serum (100 ml/l) for 24 h. Then cells were differentiated in DMEM–F12 plus insulin, hydrocortisone and transferrin without or with polyunsaturated FA at 6·25, 25·00 or 100·00 μm. The ADD1 mRNA was decreased by 100·00 μm-arachidonic acid, 6·25 to 100·00 μm-docosahexaenoic acid orcis-9,trans-11-conjugated linoleic acid. The polyunsaturated FA reduced the transcription rate of FAS, but not of ADD1. All three polyunsaturated FA accelerated degradation of ADD1 and FAS mRNA to reduce the abundance of ADD1 and FAS mRNA. Results also showed that polyunsaturated FA inhibit the ADD1 expression, not only of mRNA concentration, but also of mature ADD1 protein concentration, suggesting an overall reduction of ADD1 function by polyunsaturated FA. Our present experiments demonstrate that polyunsaturated FA regulate the gene expression of ADD1 and enzymes involved in lipid metabolism in porcine adipocytes.

The effects of short-term and long-term ascorbic acid supplements on plasma alcohol clearance were studied in 13 clinically healthy male subjects. Two dose levels of alcohol, 0.5 and 0.8 g/kg body weight, were used. Blood samples were taken at zero time, 0.5 hours, then hourly up to 6 hours after alcohol consumption for the measurement of plasma alcohol and ascorbic acid levels, red-cell reduced glutathione level, and plasma alanine aminotransferase activity. At both dosages of alcohol, short-term as well as long-term pretreatment with ascorbic acid significantly enhanced the clearance of plasma alcohol. Although long-term ascorbic acid pretreatment resulted in better alcohol clearance, no significant difference in alcohol clearance was found between short-term and long-term ascorbic acid pretreatment. The two dose levels of alcohol had no significant effect on the red-cell reduced glutathione concentration or plasma alanine aminotransferase activity.

Two kinds of cecidomyiid galls induced by Daphnephila on Machilus thunbergii Sieb. & Zucc. leaves at various developmental stages, i.e., young, growing, and mature, were analyzed for their biochemical composition of photosynthetic pigment-protein complexes located in thylakoid membranes using the Thornber and MARS electrophoretic fractionation systems. Both kinds of galls were totally deficient in the pigment-protein complexes CP1, and A1, AB1, and AB2 through the whole period of gall formation. Immunoblotting of antibody against light-harvesting complex 2b (LHC2b) apoprotein confirmed this deficiency in gall’s lifetime, which never recovered under any condition. Electron microscopy demonstrated that already at the early developmental stage the gall chloroplasts had thylakoid morphology like that in a normal leaf.

A TD-SCDMA RF front-end receiver IC, which is fabricated in a 0.35 /spl mu/m SiGe BiCMOS technology, is presented in this paper. This IC contains two blocks, low-noise amplifier (LNA) and mixer, and operates at 2.7 V supply voltage with a current consumption of 14.7 mA. The measured NF and power gain of the IC are 2.7 dB and 31 dB, respectively. It is shown that RF front-end circuit which is implemented in a SiGe BiCMOS process has more advantages than CMOS circuits, such as power consumption and NF performance.

SummaryRats on a selenium-deficient torula yeast diet containing 100 mg Vitamin E/kg compared to a similar diet with 0.5 ppm selenium as sodium selenite do not show any decrease in protein, RNA and DNA synthesis in the pancreas or liver. The gross depression and change of pancreatic enzymes found in the chick on selenium-deficient diet were not apparent in the rat on a selenium-deficient diet.

Zinc has long been recognized as essential to normal growth and development in animals and in man. Its role in regulating metabolic events at the molecular level is becoming evident, but it is not yet possible to correlate biochemical function to the pathology of deficiency. Studies by a number of investigators have indicated that feeding animals with a diet low in zinc causes an abnormal condition on skin in addition to growth retardation. These include the rats (Todd et al., 1934), mice (Day and Skidmore, 1947), swine (Kernkam and Ferrin, 1953), cattle (Miller and Miller, 1962), lambs (Ott et al., 1964) goats (Miller et al., 1964), dogs (Robertson and Burns, 1963), rabbits (Graham and Telle, 1967), squirrel monkeys (Macapinlac et al., 1967), hamsters (Boquist and Lernmark, 1969), guinea pigs (McBean et al., 1972). In man (Prasad et al., 1963) the clinical aspects of zinc deficiency are remarkably similar to those described above for animals. They consisted of growth retardation and rough skin with hyperpigmentation. These observations indicate the importance of zinc in skin metabolism.