Subcellular Targeting Domains of Sphingomyelin Synthase 1 and 2

Sphingomyelin synthase (SMS) sits at the crossroads of sphingomyelin (SM), ceramide, diacylglycerol (DAG) metabolism. It utilizes ceramide and phosphatidylcholine as substrates to produce SM and DAG, thereby regulating lipid messengers which play a role in cell survival and apoptosis. Furthermore, its product SM has been implicated in atherogenic processes such as retention of lipoproteins in the blood vessel intima. There are two mammalian sphingomyelin synthases: SMS1 and SMS2. SMS1 is found exclusively in the Golgi at steady state, whereas SMS2 exists in the Golgi and plasma membrane. Conventional motifs responsible for protein targeting to the plasma membrane or Golgi are either not present in, or unique to, SMS1 and SMS2. In this study, we examined how SMS1 and SMS2 achieve their respective subcellular localization patterns. Brefeldin A treatment prevented SMS1 and SMS2 from exiting the ER, demonstrating that they transit through the classical secretory pathway. We created truncations and chimeras of SMS1 and SMS2 to define their targeting signals. We found that SMS1 contains a C-terminal Golgi targeting signal and that SMS2 contains a C-terminal plasma membrane targeting signal

Diagnostic value of two dimensional shear wave elastography combined with texture analysis in early liver fibrosis.

BACKGROUND: Staging diagnosis of liver fibrosis is a prerequisite for timely diagnosis and therapy in patients with chronic hepatitis B. In recent years, ultrasound elastography has become an important method for clinical noninvasive assessment of liver fibrosis stage, but its diagnostic value for early liver fibrosis still needs to be further improved. In this study, the texture analysis was carried out on the basis of two dimensional shear wave elastography (2D-SWE), and the feasibility of 2D-SWE plus texture analysis in the diagnosis of early liver fibrosis was discussed. AIM: To assess the diagnostic value of 2D-SWE combined with textural analysis in liver fibrosis staging. METHODS: This study recruited 46 patients with chronic hepatitis B. Patients underwent 2D-SWE and texture analysis; Young\u27s modulus values and textural patterns were obtained, respectively. Textural pattern was analyzed with regard to contrast, correlation, angular second moment (ASM), and homogeneity. Pathological results of biopsy specimens were the gold standard; comparison and assessment of the diagnosis efficiency were conducted for 2D-SWE, texture analysis and their combination. RESULTS: 2D-SWE displayed diagnosis efficiency in early fibrosis, significant fibrosis, severe fibrosis, and early cirrhosis (AUC \u3e 0.7, P \u3c 0.05) with respective AUC values of 0.823 (0.678-0.921), 0.808 (0.662-0.911), 0.920 (0.798-0.980), and 0.855 (0.716-0.943). Contrast and homogeneity displayed independent diagnosis efficiency in liver fibrosis stage (AUC \u3e 0.7, P \u3c 0.05), whereas correlation and ASM showed limited values. AUC of contrast and homogeneity were respectively 0.906 (0.779-0.973), 0.835 (0.693-0.930), 0.807 (0.660-0.910) and 0.925 (0.805-0.983), 0.789 (0.639-0.897), 0.736 (0.582-0.858), 0.705 (0.549-0.883) and 0.798 (0.650-0.904) in four liver fibrosis stages, which exhibited equivalence to 2D-SWE in diagnostic efficiency (P \u3e 0.05). Combined diagnosis (PRE) displayed diagnostic efficiency (AUC \u3e 0.7, P \u3c 0.01) for all fibrosis stages with respective AUC of 0.952 (0.841-0.994), 0.896 (0.766-0.967), 0.978 (0.881-0.999), 0.947 (0.835-0.992). The combined diagnosis showed higher diagnosis efficiency over 2D-SWE in early liver fibrosis (P \u3c 0.05), whereas no significant differences were observed in other comparisons (P \u3e 0.05). CONCLUSION: Texture analysis was capable of diagnosing liver fibrosis stage, combined diagnosis had obvious advantages in early liver fibrosis, liver fibrosis stage might be related to the hepatic tissue hardness distribution

Impact of sphingomyelin levels on coronary heart disease and left ventricular systolic function in humans

Sphingomyelin (SM) is an abundant phospholipid in cell membranes and in lipoproteins. In human plasma, SM is mainly found in atherogenic lipoproteins; therefore, higher levels of SM may promote atherogenesis. We investigated the relations between plasma SM levels and the presence of angiographic coronary heart disease (CHD) and left ventricular systolic dysfunction. We studied 732 patients referred for coronary angiography. Median SM levels were higher among patients with CHD and in those with LV systolic dysfunction (LVEF<50%) than in patients without CHD or LV dysfunction. SM levels were significantly correlated with fibrinogen levels, diabetes, apoB, and triglyceride levels. On multivariate analyses, higher median SM levels were associated with a higher risk of CHD and lower LV ejection fraction. The pro-atherogenic property of plasma SM might be related to 1) CHD; 2) LV systolic dysfunction; and 3) metabolism of apoB-containing or triglyceride-rich lipoproteins

Mycobacterial Interspersed Repetitive Unit Can Predict Drug Resistance of Mycobacterium tuberculosis in China

BackgroundRecently, Mycobacterial Interspersed Repetitive Unit (MIRU) was supposed to be associated with drug resistance in M.tuberculosis (MTB). However, whether the MIRU was related to drug resistance actually was still unknown. This research was conducted to explore that association.MethodsDrug susceptibility testing was used to evaluate the drug resistance of five anti-tuberculosis drug (isoniazid, INH; rifampicin, RFP; streptomycin, SM; ethambutol, EMB; and Paminosalicylicacid, PAS.). We tested the number of the repeat unite of MIRU (Mycobacterial Interspersed Repetitive Unit) locus based on PCR of miru-vntr genotyping. Then, through logistic regression, we evaluated the association between fifteen MIRU and the resistance. In addition, we explored the most suitable MIRU locus of identified MIRU loci for drug resistance through multivariate logistic regression.ResultsAmong these fifteen MIRU, we found several MIRU loci could predict the drug resistance well. For example ,ETRB and ETRC could predict INH resistance; MIRU20 was associated with EMB resistance; and QUB11a was a predictive factor of PSA. ConclusionOur results may provide candidate regions for future genetic studies and aid in the prediction for drug resistance of MTB

Antioxidant phenolics from Broussonetia papyrifera fruits

Fractionation of the EtOH extract from the fruits of Broussonetia papyrifera led to the isolation of 15 phenolic compounds (1–15). Their structures were identified using spectroscopic methods. Among these compounds, 1 and 2 are new and 3–15 were isolated from this plant for the first time. Antioxidant activities of compounds 2–15 against H2O2-induced injury in SY5Y cells and 1,1-diphenyl-2-picrylhydrazyl radical scavenging activities were evaluated

Plasma PLTP activity is inversely associated with HDL-C levels

Phospholipid transfer protein (PLTP) is an important modulator of lipoprotein metabolism, including interparticle phospholipid transfer, remodeling of HDL, cholesterol and phospholipid efflux from peripheral tissues, and the production of hepatic VLDL. PLTP also plays an important role in inflammation and oxidative stress. Accordingly, PLTP has been implicated in the development of atherosclerosis. In this study, we evaluated the association between PLTP activity and lipoprotein metabolism in a Chinese patients cohort with or without coronary heart disease (CHD group n = 407, control group n = 215), the PLTP activity was measured and PLTP genotyping was screened for sequence anomalies by PCR. We found that human plasma PLTP activity was negatively associated with plasma HDL and apoA-I levels, and positively associated with plasma TG, apoB and apoE levels. We also found that PLTP rs2294213 polymorphism was tended to be associated with increased plasma PLTP activity