Association between CBS gene T833C, G919A and 844ins68 polymorphisms in the 8th exon region and coronary artery disease: a meta-analysis.

BACKGROUND: Several studies indicate that the cystathionine ß-synthase (CBS) gene T833C, G919A and 844ins68 polymorphisms in the 8th exon region may be correlated with coronary artery disease (CAD) susceptibility, but the results have been inconsistent and inconclusive. Thus, a meta-analysis was conducted to provide a comprehensive estimate of these associations. METHODS: On the basis of searches in the PubMed, EMBASE, Cochrane Library, Wanfang, VIP, and CNKI databases, we selected 14 case - control studies including 2123 cases and 2368 controls for this meta-analysis. Pooled odds ratios (ORs) with 95% confidence intervals (CIs) were calculated accordingly using a fixed-effect or random-effect model. RESULTS: The results indicated an increased risk between the CBS T833C gene polymorphisms and susceptibility to CAD under the dominant model (CC+CT vs. TT: OR = 1.92, 95% CI: 1.11 ~ 3.32), recessive model (CC vs. CT+TT: OR = 1.88, 95% CI: 1.17 ~ 3.03), and homozygous model (CC vs. TT: OR = 2.46, 95% CI: 1.04 ~ 5.83). In these three genetic models, no significant association was identified for CBS G919A (AA+AG vs. GG: OR = 1.48, 95% CI: 0.45 ~ 4.82),(AA vs. AG+GG: OR = 1.58, 95% CI: 0.93 ~ 2.70),(AA vs. GG: OR = 1.66, 95% CI: 0.40 ~ 6.92) or CBS 844ins68 (II+ID vs. DD: OR = 1.04, 95% CI: 0.80 ~ 1.35),(II vs. ID+DD: OR = 1.09, 95% CI: 0.51 ~ 2.36),(II vs. DD: OR = 1.10, 95% CI: 0.51 ~ 2.39). CONCLUSIONS: This meta-analysis suggests that the CBS T833C gene polymorphism is significantly associated with the risk of CAD and it shows a stronger association in Asian populations. Individuals with the C allele of the CBS gene T833C polymorphism might be particularly susceptible to CAD.

Distinctive microRNA expression in early stage nasopharyngeal carcinoma patients.

The goal of this study was to investigate microRNAs (miRs) expression at different stages of nasopharyngeal carcinoma (NPC). MiR expression profiling at various stages of NPC was performed by miR array and further verified using quantitative real-time RT-PCR. Pathway enrichment analysis was carried out to identify the functional pathways regulated by the miRs. The expression of a selected group of identified miRs was verified in stage I NPC by in situ hybridization (ISH). A total of 449 miRs were identified with significantly different expressions between NPC tissues and normal pharyngeal tissues. Eighty-four miRs were dysregulated only in stage I NPC, among which 45 miRs were up-regulated and the other 39 were down-regulated. Pathway enrichment assay revleaed that three significantly down-regulated and three significantly up-regulated miRs involved in 12 pathways associating with tumour formation and progression. Quantitative RT-PCR confirmed the miR array result. In addition, the low expression levels of hsa-miR-4324, hsa-miR-203a and hsa-miR-199b-5p were further validated in stage I NPC by ISH. This present study identifed the miR signature in stage I NPC, providing the basis for early detection and treatment of NPC.

[The role of Th9, Th17 and Treg cells on pathogenesis of nasal polyps].

OBJECTIVE: To investigate the expression levels of Th9, Th17 and Treg cells in peripheral blood of patients with chronic rhinosinusitis with nasal polyps (CRSwNP), and explore the role of Th9, Th17 and Treg cells in the progression of CRSwNP. METHOD: Forty-six cases with CRSwNP served as an experimental group, while 22 cases with simple nasal bleeding or nasal septum deviation served as a control group. The peripheral blood of patients in both groups was collected and analyzed. (1) Using flow cytometry (FCM) to detect the expression rates of Th9, Th17 and Treg cells in peripheral blood. (2) Using qRT-PCR to detect the expression of relevant transcription factor of Th9, Th17 and Treg cells (IL-9mRNA, PU. 1, IRF-4, RoRc, and Foxp3). (3) Using SPSS16.0 to analyse the differentiations and the revelance among these three cells. RESULT: (1) The expression rates of Th9 and Th17 cells in patients with CRSwNP (1.29% ± 0.18%, 4.03% ± 0.69%) was higher than the control group (0.45% ± 0.14%, 1.35% ± 0.26%). But the expression rates of Treg cells in the experimental group (2.98% ± 0.13%) was significantly lower than the control group (5.44% ± 0.57%). The differences were statistically significant (P < 0.05). (2) The expression of revelant transcription factor (IL-9mRNA, PU.1, IRF-4, RoRc) in NP group was also higher than the control group. The expression of Foxp3 in the control group was higher than NP, the differences both were statistically significant (P < 0.05). (3) The difference between Th9 and Th17 in patients with NP was not significant (P > 0.05), and the negative correlation was found between Th17 and Treg (r = -0.549, P < 0.05). CONCLUSION: The high expression level of Th9 and Th17 cells might promote the development of NP, whereas the low expression level of Treg cells might further aggravate the occurrence of NP. The main function of the imbalance of Th17/Treg cells may be immune regulation in the pathogenesis of nasal polys.

[The expression of IL-9, IL-17 and Foxp3 in nasal polyps].

OBJECTIVE: To observe the expression of IL-9, IL-17 and Foxp3 in nasal polyps,so that to explore the role of Th9, Th17/Treg cells imbalance in pathogenesis of nasal polyposis. METHOD: Forty cases of nasal polyps and 20 cases of normal middle turbinate mucosa (controls) were involved in this study. The expression patterns of IL-9, IL-17 and Foxp3 were detected by immunohistochemistry. RESULT: The positive rates of IL-9 and IL-17 in nasal polyps tissues were respectively 75.0% and 80.0%, which were both significantly higher than those in the controls (positive rates were 35.0% and 50.0%, respectively), but the Foxp3 expression was downregulated in nasal polyps tissues (37.5%) compared to the controls (80.0%), P < 0.05 respectively. CONCLUSION: The cytokines IL-9 and IL-17 are obviously involved in the occurrence and development of nasal polyposis, suggesting remarkable infiltration of Th9 and Th17/Treg imbalance exist in nasal polyps, both of which may play important roles in pathogenesis of nasal polyposis.

[The expression and correlation of inducible nitric oxide synthase, Bax and Bcl-2 in nasal polyps].

OBJECTIVE: To detect the expressions of inducible nitric oxide synthase (iNOS), apoptosis-related gene Bax, Bcl-2 in nasal polyps,and discuss the their relationship. METHOD: The apoptosis of 30 cases of nasal polyps was detected by TUNEL assay. The expressions of iNOS and Bax, Bcl-2 was detected by immunohistochemical SABC method. The expressions of iNOS and Bax, Bcl-2 was measured by western blot. RESULT: 1) The weakly positive stained apoptotic cells were detected at the surface epithelial cells and glandular epithelial cells of nasal polyps by TUNEL assay. 2) Immunohistochemical method revealed that positive stainings of iNOS, Bax, Bcl-2 located in the cytoplasm of epithelial cells, glandular epithelial cells, endothelial cells and infiltrating inflammatory cells in nasal polyps. The expression of Bax was weak, while the expressions of iNOS and Bcl-2 were strong. 3) iNOS, Bcl-2 and Bax was detected by western blot. The expressions of these proteins were significantly different (P<0.01). The expression of iNOS and Bcl-2 had a positive correlation (r=0.851, P<0.01), while the expression of iNOS and Bax had a negative correlation (r=-0.714, P<0.01). CONCLUSION: The pro-apoptotic and anti-apoptotic proteins are co-existed in the nasal polyps, iNOS may play an important role in the pathogens of nasal polyps through inhibition of apoptosis.

Sterol transfer by ABCG5 and ABCG8: in vitro assay and reconstitution.

ATP-binding cassette transporters G5 and G8 are half-transporters expressed on the apical membranes of enterocytes and hepatocytes that limit intestinal uptake and promote secretion of neutral sterols. Genetic defects that inactivate either half-transporter cause accumulation of cholesterol and plant sterols, resulting in premature coronary atherosclerosis. These observations suggest that G5 and G8 promote the translocation of sterols across membranes, but the primary transport substrate of the G5G8 complex has not been directly determined. Here we report the development of a sterol transfer assay using "inside-out" membrane vesicles from Sf9 cells expressing recombinant mouse G5 and G8. Radiolabeled cholesterol or sitosterol was transferred from donor liposomes to G5- and G8-containing membrane vesicles in an ATP-dependent and vanadate-sensitive manner; net transfer of cholesterol was associated with an increase in vesicular cholesterol mass. CTP, GTP, and UTP, as well as ATP, supported transfer but with lesser efficiency (ATP >> CTP > GTP > UTP). Transfer was specific for sterols and was stereoselective; minimal ATP-dependent and vanadate-sensitive transfer of cholesteryl oleate, phosphatidylcholine, or enantiomeric cholesterol was observed. These studies indicate that G5 and G8 are sufficient for reconstitution of sterol transfer activity in vitro and provide the first demonstration that sterols are direct transport substrates of the G5 and G8 heterodimer.