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1.
Sphingomyelin phosphodiesterase (SMPD1) is a key enzyme in the sphingolipid metabolism. Genetic SMPD1 variants have been related to the Niemann-Pick lysosomal storage disorder, which has different degrees of phenotypic severity ranging from severe symptomatology involving the central nervous system (type A) to milder ones (type B). They have also been linked to neurodegenerative disorders such as Parkinson and Alzheimer. In this paper, we leveraged structural, evolutionary and stability information on SMPD1 to predict and analyze the impact of variants at the molecular level. We developed the SMPD1-ZooM algorithm, which is able to predict with good accuracy whether variants cause Niemann-Pick disease and its phenotypic severity; the predictor is freely available for download. We performed a large-scale analysis of all possible SMPD1 variants, which led us to identify protein regions that are either robust or fragile with respect to amino acid variations, and show the importance of aromatic-involving interactions in SMPD1 function and stability. Our study also revealed a good correlation between SMPD1-ZooM scores and in vitro loss of SMPD1 activity. The understanding of the molecular effects of SMPD1 variants is of crucial importance to improve genetic screening of SMPD1-related disorders and to develop personalized treatments that restore SMPD1 functionality.  相似文献   
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The potential use of stem cell-based therapies for the repair and regeneration of various tissues and organs is a major goal in repair medicine. Stem cells are classified by their potential to differentiate into functional cells. Compared with other sources, adipose-derived stem cells (ADSCs) have the advantage of being abundant and easy to obtain. ADSCs are considered to be tools for replacing, repairing, and regenerating dead or damaged cells. The capacity of ADSCs to maintain their properties depends on the balance of complex signals in their microenvironment. Their properties and the associated outcomes are in part regulated by reactive oxygen species, which mediate the oxidation-reduction state of cells as a secondary messenger. ADSC therapy has demonstrated beneficial effects, suggesting that secreted factors may provide protection. There is evidence that ADSCs secrete a number of cytokines, growth factors, and antioxidant factors into their microenvironment, thus regulating intracellular signaling pathways in neighboring cells. In this review, we introduce the roles of ADSCs in the protection of cells by modulating inflammation and immunity, and we develop their potential therapeutic properties.  相似文献   
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Peroxide crosslinking of unplasticized poly(vinyl chloride) with trimethylolpropane trimethacrylate was investigated. Formulations used in this work contained a nontoxic lead‐free stabilizer and showed good color and heat stability. The samples were examined by differential scanning calorimetry, and their tensile properties were measured at room temperature and at 130°C. Gel content or tetrahydrofuran‐insoluble material was measured as an indication of crosslinking. It was shown that premature crosslinking could be avoided during processing and that 190°C was the optimum processing temperature for maximum gel content. The residual unsaturation was monitored by using FTIR spectroscopy. J. VINYL ADDIT. TECHNOL., 2008. © 2008 Society of Plastics Engineers  相似文献   
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The effect and possible interactive influence of different dietary amounts of wheat bran, fat and calcium on the fecal excretion, concentration and composition of bile acids was studied in Fischer-344 rats. The fecal bile acids were analyzed using gas-liquid chromatography. Dietary wheat bran increased both total bile acid excretion and fecal weight without changes in fecal bile acid concentration. The proportion of fecal hyodeoxycholic acid decreased with increasing dietary fiber, whereas that of lithocholic and deoxycholic acids increased significantly with fiber intake. The percent content of fecal chenodeoxycholic acid did not change. Increasing dietary fat led to an increase in bile acid excretion without changes in either fecal weight or bile acid concentration. In contrast, the level of dietary calcium did not affect the total excretion of bile acids. However, since calcium increased the fecal weight, it consequently diluted bile acids and decreased their fecal concentration. Dietary fat and calcium had no influence on fecal bile acid composition. There were no interactive effects of wheat bran, fat and calcium on fecal bile acids. The finding in this study that dietary fiber, fat and calcium induce significant changes in fecal bile acids may be of relevance to the potential of bile acids to promote carcinogenesis.  相似文献   
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We investigated the effect of c-myb antisense phosphorothioate oligodeoxynucleotides [(S)ODNs] and cisplatin (CDDP) combination on the human colon carcinoma cell line LoVo Dx both in vitro and in nude mice bearing LoVo Dx solid tumour. We show that antisense (S)ODN treatment decreases c-myb mRNA and protein expression, induces growth arrest in the G1 phase of the cell cycle, and inhibits cell proliferation. In vivo treatment with c-myb antisense (S)ODNs results in a reduction in tumour growth. A greater inhibition of cell proliferation in vitro and a higher increase of tumour growth inhibition and growth delay in vivo were obtained with the combination of (S)ODNs and CDDP than when the two agents were administered separately. This comparative study, using the same tumour cell line in vitro and in vivo, suggests that c-myb antisense (S)ODNs might be useful in the therapy of colon cancer in combination with antineoplastic drugs.  相似文献   
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In this study, the effect of the chemical nature of different calcium (Ca)-based minerals as flame retardant additives in combination with ammonium polyphosphate (APP), in 1:1 proportions, on the flame retardancy behavior and performance of ethylene vinyl acetate copolymer was discussed. Combining APP with partly and completely hydrated calcium oxide led to superior flame-retardant function detected in mass loss calorimeter measurements with respect to the corresponding system containing carbonated calcium. This privileged character was attributed to the higher reactivity of hydrated Ca-based fillers toward APP in comparison with Ca carbonate, which induced the formation of an intumescent residue. The difference between reactivity potential of hydrated and dry Ca was demonstrated by the newly formed thermally stable species, and further evidenced by thermogravimetric analysis performed on APP/fillers blends. Moreover, the presence of more crystalline domains in the Ca/phosphorus-based compounds was evidenced by XRD analysis of the mass loss calorimeter test residues. The results of this work highlight the role of blend additive systems on the performance of flame retardancy of polymer materials.  相似文献   
10.
It has been studied the intrinsic viscosity ratios of cellulose solutions in different solvents and of the corresponding nitrates dissolved in aceton using cellulose samples from different origins and with different degrees of polymerization. The results demonstrate that with FeTNa and CdEn as solvents, molecular dispersed solutions are only produced with cellulose having a DP≤3000. FeTNa is limited to cotton cellulose only. Contrary to this, the intrinsic viscosity ratio [η]/[η] shows independence from the range of degree of polymerization and the origin of cellulose, confirming thus once more the polymeranalogous course of nitration. Its value referred to a degree of substitution S = 2.90±0.02, to absolute dry and pure cellulose and to standardized viscosity measurements amounts [η]Ac/[η]CuEn = 1.95±0.05. Determination of the intrinsic viscosity ratio permits, therefore, to obtain information in respect of the polymeranalogous and homogeneous character of the cellulose nitrate, and, in connection with determinations of yield of nitration, in respect of the purity of the corresponding unsubstituted cellulose. Basing on the constant value of the intrinsic viscosity ratio [η]Ac/[η]CuEn, and using the quotients [η]FeTNa/[η]CuEn and [η]CdEn/[η]CuEn, there has been derived the [η]-DP-relationships for unsubstituted cellulose in the respective solvents.  相似文献   
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