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Role of OAS-1 and MxA Gene Polymorphisms in Susceptibility and Treatment of HCV Patients
Hosam Zaghloul, prof. of clinical pathology,Mansoura faculty of medicine,Egypt, -----
Response to IFN therapy in HCV infected patients differs among individuals, suggesting a role of host genetic factors. IFN stimulates the expression of a number of enzymes with antiviral activities, including OAS-1 gene and MxA gene. OAS1 gene was found to have a SNP at exon 7-SAS that affect the expression of OAS-1 protein. MxA gene also was found to possess a SNP at nt -88 in the promotor region that affect the expression of Mx 1 protein. The two SNPs was genotyped by RFLP analysis in 60 interferon treatment-naïve Egyptian patients who were treated with PEG-IFN and ribavirin and 20 healthy control volunteers. Correlations of SNP genotypes with susceptibility to HCV infection and with response to interferon and clinical status of patients were statistically analyzed. AG genotype of OAS-1 gene was significantly higher in control group representing a protective gene against HCV infection. Also, AG genotype of OAS-1 gene and TT genotype of MxA gene was found to be non-significantly higher in chronic HCV patients. Subsequently, it was concluded that OAS-1 gene gene polymorphisms might be considered as biological markers to identify susceptibility to HCV infection
Borderline-to-moderate hypertriglyceridemia associated alteration in plasma lysophosphatidylcholines and amides in nonobese and nondiabetic subjects
Mi-Hyang Lee, Doctoral Course, Yonsei University
Hypertriglyceridemia (HTG) is a risk factor for atherosclerotic cardiovascular disease. We investigated alterations in plasma metabolites that are associated with borderline-to-moderate HTG (TG 150-500 mg/dL). A group of 111 nondiabetic and nonobese individuals was identified who remained within the range of borderline-to-moderate HTG during repeated measurements in a 3-month period. This HTG group was compared with the control group of 111 normotriglyceridemia (NTG, TG <150mg/dL) subjects who were matched for age and gender. Metabolomic profiles were analyzed with UPLC-LTQ-Orbitrap mass spectrometry. The HTG group showed higher plasma levels of lysophosphatidylcholines (lysoPCs) containing C14:0 (q=0.001) and C16:0 (q=1.8E-05), amides including N-ethyldodecamide (q=3.0E-05), N-propyldodecamide (q=3.5E-05), palmitoleamide (q=2.9E-06), and palmitic amide (q=0.019); whereas the HTG group showed lower levels of cis-4-octenedioic acid (q<1.00E-9) and docosanamide (q=0.002). LysoPC (16:0) and palmitoleamide were the most important plasma lysoPC and amide metabolites for evaluating the difference between NTG and HTG groups, with a variable important in the protection (VIP) values of 18.6318 and 7.1228, respectively, and these two metabolites showed positive associations with fasting triglyceride concentration. These data elucidated borderline-to-moderate HTG associated alterations in lysoPCs, amides, and cis-4-octenedioic acid in nondiabetic and nonobese individuals and suggest novel insights into the metabolic alterations occurring in the early metabolic changes of HTG, thereby permitting early intervention designed to prevent disease progression.
The triglyceride-lowering effect of supplementation with dual probiotic strains, Lactobacillus curvatus HY7601 and Lactobacillus plantarum KY 1032, reduced fasting plasma lysophosphatidylcholines in nondiabetic and hypertriglyceridemic subjects
Young Ju Lee, Doctoral Course, Yonsei University
The objective was to evaluate the triglyceride-lowering effect of the consumption of dual probiotic strains containing Lactobacillus curvatus (L. curvatus) HY7601 and Lactobacillus plantarum (L. plantarum) KY 1032 on fasting plasma metabolomes. A randomized, double-blind, placebo-controlled study was conducted on 92 nondiabetic and hypertriglyceridemic subjects. Over a 12 week test period, the probiotic group consumed a daily 2 g powder of a dual probiotic strains containing 0.5 x 1010 colony-forming units (cfu) of L. curvatus HY7601 and 0.5 x 1010 cfu L. plantarum KY1032, while the placebo group consumed the same product without probiotics for 12 weeks. Fasting plasma metabolomes were profiled using UPLC-LTQ-Orbitrap MS. After 12 weeks of treatment, the probiotic group presented a reduction of 20% (P=0.001) in serum triglyceride and increases of 25% (P=0.001) in apolipoprotein A-V (apoA-V). At the 12-week follow-up, the probiotic group showed the following 12 plasma metabolites showed greater reductions compared to the placebo group - palmitoleamide, palmitic amide, oleamide, lysophosphatidylcholine (lysoPC) containing C14:0, C16:1, C16:0, C17:0, C18:3, C18:2, C18:1, and C20:3. In the probiotic group, changes (?) triglyceride negatively correlated with ? apoA-V, which positively correlated with ? FFA. Additionally, ? FFA strongly and positively correlated with ? lysoPCs in the probiotic group but not in the placebo group. The triglyceride-lowering effects of probiotic supplementation partly through elevated apoA-V in borderline to moderate hypertriglyceridemic subjects showed reductions in plasma metabolites; fatty acid primary amides and lysoPCs.
Nerve growth factor as a biomarker for diabetic neuropathy and its correlation with mechanical and thermal nociception
Salim Alrejaie, , King Saud University
Studying diabetic rodents responses to thermal and mechanical hyper- and hypoalgesia has led to identification of a number of mechanisms of abnormal sensation and pain in diabetes. Moreover, diabetic neuropathy (DN) is characterized by neuronal degeneration and marked alterations in neural growth factors such as Nerve growth factor (NGF). Thus, the aim of the current study was to correlate the behavioral response associated with DN and the expression of NGF and to assess NGF as a biomarker for DN. Peripheral DN was induced by single IP injection of streptozotocin (STZ; 55 mg/kg) in Wistar rats. Seven weeks later mechanical and thermal nociceptive thresholds were determined. Sciatic expression of NGF was determined biochemically and molecularly using ELISA and western blot; respectively. Histopathological changes were estimated in sciatic nerve. Histopathological evaluation showed obvious nerve degeneration confirming DN in the diabetic group. There was a significant reduction in mechanical and thermal nociceptive thresholds in diabetic animals. The diabetic animals also revealed a significant decrease in sciatic NGF expression. The present findings demonstrated that the degree of DN expressed as mechanical and thermal nociception is in positive correlation with sciatic NGF expression, which may suggest NGF as potential biomarker for DN.
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