Relationship between vascular endothelial growth factor -2578C > a gene polymorphism and lung cancer risk: a meta-analysis.

BACKGROUND: Several reports were published on the relationship between the vascular endothelial growth factor (VEGF) -2578C > A gene polymorphism and lung cancer risk; however, the results are debatable. This meta-analysis was conducted to assess the relationship between VEGF -2578C > A gene polymorphism and lung cancer risk. METHODS: The associated literatures were identified on the 1st of September 2018 from CBM-disc (China Biological Medicine Database) and PubMed. RESULT: A total of 14 reports were recruited into our meta-analysis to assess the association between VEGF -2578C > A gene polymorphism and lung cancer susceptibility. There was a marked association between VEGF -2578C > A A allele / CC genotype and lung cancer risk in overall and Asian populations (overall populations: A allele: OR = 1.26, 95% CI: 1.08-1.46, P = 0.003; CC genotype: OR = 0.72, 95% CI: 0.54-0.95, P = 0.02; Asians: A allele: OR = 1.33, 95% CI: 1.15-1.55, P = 0.0002; CC genotype: OR = 0.68, 95% CI: 0.50-0.93, P = 0.01). However, VEGF -2578C > A gene polymorphism was not associated with the risk of lung cancer in Caucasians. CONCLUSION: VEGF -2578C > A A allele / CC genotype is associated with the lung cancer susceptibility in Asians and in overall populations.

Association of glutathione S-transferase P1 gene polymorphism with the risk of small-cell carcinoma of lung cancer.

The conclusions of the published reports on the relationship between glutathione S-transferase P1 (GSTP1) gene polymorphism and the risk of small-cell carcinoma of lung cancer are still debated. GSTP1 is one of the important mutant sites reported at present. This meta-analysis was performed to evaluate the association between GSTP1 and the risk of small-cell carcinoma of lung cancer. The association investigations were identified from PubMed and Cochrane Library, and eligible studies were included and synthesized using meta-analysis method. Ten reports were included into this meta-analysis for the association of GSTP1 A/G gene polymorphism and small-cell carcinoma of lung cancer. The G allele and GG genotype were not associated with the susceptibility of risk of small-cell carcinoma in overall populations, East-Asians and Turkish population. However, there was an association between GG genotype with the risk of small-cell carcinoma in Caucasians. In conclusion, GG genotype was associated with the risk of small-cell carcinoma in Caucasian patients with lung cancer. However, GSTP1 A/G gene polymorphism is not associated with the susceptibility of small-cell carcinoma in overall populations, East-Asians and Turkish population.

Association of vitamin D receptor BsmI gene polymorphism with the risk of type 2 diabetes mellitus.

Relationship between vitamin D receptor (VDR) BsmI (rs1544410) gene polymorphism and the type 2 diabetes mellitus (T2DM) susceptibility is still conflicting at present. This meta-analysis was conducted to assess the association between VDR BsmI gene polymorphism and the risk of T2DM. The association studies were identified from PubMed, and Cochrane Library on 1 January 2014, and eligible investigations were included and synthesized using meta-analysis method. Eleven reports were recruited into this meta-analysis for the association of VDR BsmI gene polymorphism with T2DM susceptibility. In overall populations, B allele, BB genotype and bb genotype were not associated with T2DM risk. VDR BsmI gene polymorphism was also not associated with the T2DM risk in Asians and Caucasians. In conclusion, VDR BsmI gene polymorphism was also not associated with T2DM risk in overall populations, Asians and Caucasians. However, more studies should be conducted to confirm it.

Association of vitamin D receptor gene polymorphism with the risk of renal cell carcinoma: a meta-analysis.

Relationship between vitamin D receptor (VDR) gene polymorphism and the risk of renal cell carcinoma from the published reports are still conflicting. This study was conducted to evaluate the relationship between VDR ApaI (rs7975232), BsmI (rs1544410), TaqI (rs731236), and Fok1 (rs2228570) gene polymorphism and the risk of renal cell carcinoma using meta-analysis method. The association studies were identified from PubMed, and Cochrane Library on 1 March 2014, and eligible investigations were included and synthesized using meta-analysis method. Five reports were recruited into this meta-analysis for the association of VDR gene polymorphism with renal cell carcinoma susceptibility. In this meta-analysis, the ApaI AA genotype, BsmI BB genotype, Fok1 f allele, and Fok1 FF genotype were associated with the risk of renal cell carcinoma in Asians. However, VDR ApaI, BsmI, TaqI, and Fok1 gene polymorphism were not associated with the risk of renal cell carcinoma in overall populations and in Caucasians. In conclusion, the ApaI AA genotype, BsmI BB genotype, Fok1 f allele, and Fok1 FF genotype were associated with the risk of renal cell carcinoma in Asians. However, more studies should be conducted to confirm it.

Novel Compound Heterozygous Pathogenic Mutations of SLC5A5 in a Chinese Patient With Congenital Hypothyroidism.

Background and Objectives: Defects in the human sodium/iodide symporter (SLC5A5) gene have been reported to be one of the causes of congenital hypothyroidism (CH). We aimed to identify SLC5A5 mutations in Chinese patients with CH and to evaluate the function of the mutation. Methods: Two hundred and seventy-three patients with primary CH were screened for mutations in SLC5A5 using next-generation sequencing. We investigated the expression and cellular localization of the novel compound heterozygous mutation in SLC5A5. The functional activity of the mutants was further examined in vitro. Results: In 273 patients with CH, two previously undescribed pathogenic mutations p.Gly51AlafsTer45 (G51fs) and p.Gly421Arg (G421R) in a compound heterozygous state in SLC5A5 were identified in a pediatric patient. G51fs was located in the first intercellular loop connecting transmembrane segment I and II, whereas G421R was in the transmembrane segment (TMS) XI. G51fs and G421R resulted in a truncated NIS and reduced protein expression, respectively. In vitro experiments further showed that the normal function of iodine transport of sodium-iodide symporter (NIS) mutants was markedly impaired. Conclusion: The undescribed compound heterozygous mutation of SLC5A5 was discovered in a Chinese CH patient. The mutation led to significantly reduced NIS expression and impaired iodide transport function accompanied by the impaired location of the NIS on the plasma membrane. Our study thus provides further insights into the roles of SLC5A5 in CH pathogenesis.

[Mechanism of cardioprotection induced by noninvasive limb ischemic preconditioning].

OBJECTIVE: To verify the inhibitory effect of mitochondrial calcium uniporter in remote preconditioning-induced cardioprotection. METHODS: By occlusion and reperfusion of left anterior descending artery, the rat hearts were subjected to 30 min regional ischemia and 120 min reperfusion in vivo. Thus the ischemic reperfusion model was established. The rats were randomly assigned to undergo one of the following maneuvers: (1) remote preconditioning; (2) ruthenium red (an inhibitor of mitochondrial calcium uniporter); (3) spermine or SB202190 (an opener of mitochondrial calcium uniporter). Remote preconditioning was elicited by three cycles of 5 min of right femoral artery occlusion interspersed with 5 min of reperfusion. The mean arterial blood pressure, heart rate and lactate dehydrogenase released in plasma were measured during reperfusion but the infarct size was measured after reperfusion. RESULTS: In comparison with I/R group, remote preconditioning limited infarct size [(20.4 +/- 2.5)% vs (51.0 +/- 6.0)%] and lactate dehydrogenase release [(271 +/- 9) U/L vs (339 +/- 39)U/L] during reperfusion. On the contrary, spermine or SB202190 attenuated the reduction of infarct size and lactate dehydrogenase release induced by remote preconditioning. The group of spermine was [(40.8 +/- 9.2)% vs (20.4 +/- 2.5)%] and [(383 +/- 43) U/L vs (271 +/- 9) U/L] while the group of SB202190 was [(44.3 +/- 6.8)% vs (20.4 +/- 2.5)%] and [(356 +/- 26) U/L vs (271 +/- 9) U/L]. CONCLUSION: Inhibition of mitochondrial calcium uniporter opening is involved in the remote preconditioning-induced cardioprotection.

[Changes of serum hepatocyte growth factor before and after percutaneous coronary intervention in patients with unstable angina pectoris and significance there].

OBJECTIVE: To investigate the effect of unfitrate heparin (UFH) and low molecular weight heparin (LMWH) on the expression of serum hepatocyte growth factor (HGF) during percutaneous coronary intervention (PCI). METHODS: Seventy patients with chronic unstable angina pectoris were divided into 2 groups: PCI group (n = 49, with at least one main coronary artery branch with stenosis > or = 70%) and non-PCI group (n = 21, with the main coronary artery branch with stenosis < 70%). UFH was used at the beginning of coronary angiography in both groups and LMWH was used after PCI only in the PCI group. The serum level of HGF was measured before, during, and 1 and 7 days after PCI; and cardiac troponin 1 (cTnI) was measured before and 1 day after PCI in all 70 patients. RESULTS: The serum level of HGF of the PCI group increased during and immediately after PCI (12 322 +/- 3723 ng/L and 13 566 +/- 3767 ng/L respectively), both significantly higher than that before the procedure (1736 +/- 604 ng/L, both P < 0.0001), The serum level of HGF of the non-PCI group increased during and immediately after the procedure (10 928 +/- 2196 ng/L and 11 457 +/- 2298 ng/L respectively), both significantly higher than that before the procedure (967 +/- 349 ng/L, both P < 0.01). However, there were no significant differences in the HGF levels during and after the procedure between the PCI and non-PCI groups. The serum HGF returned to the normal level 24 h after the procedure in both groups. The serum GHF 7 days after the procedure of the cTnI (-) PCI group was significantly lower than that before the procedure (P < 0.01), however, the serum GHF 7 days after the procedure of the cTnI (+) PCI group remained relatively high, not significantly different from that before the procedure. CONCLUSION: There is an enhanced secretion of cardiac HGF in the patients with severe coronary artery disease. UFH promotes the release of serum HGF in the patients with chronic unstable angina pectoris undergoing PCI, which indicates some other biological effects in addition to its anticoagulant property. The delayed fall of serum HGF after PCI has relationship with minor myocardial infarction.

Relationship between hs-CRP, proMMP-1, TIMP-1 and coronary plaque morphology: intravascular ultrasound study.

BACKGROUND: Rupture of unstable plaque with subsequent thrombus formation is the common pathophysiological substrate of the acute coronary syndrome (ACS). It is of potential significance to explore the blood indexes predicting plaque characteristics. Little studies have focused on this field. Therefore we investigated the relationship between hypersensitive C-reactive protein (hs-CRP), pro-matrix metalloproteinase-1 (proMMP-1), tissue inhibitors of matrix metalloproteinase-1 (TIMP-1) and coronary plaque morphology. METHODS: Intravascular ultrasound (IVUS) examination was done in 152 patients with confirmed coronary heart disease before percutaneous coronary intervention from February 2003 to July 2005. Plasma samples of arterial blood were collected prior to the procedure. The level of hs-CRP, proMMP-1 and TIMP-1 were respectively measured by enzyme-linked immunosorbent assay (ELISA). RESULTS: Unstable and ruptured plaque were found more frequently in patients with acute myocardial infarction and unstable angina. External elastic membrane cross-sectional area (EEM CSA), plaque area, lipid pool area and plaque burden were significantly larger in ruptured and unstable plaque group. Positive remolding, thinner fabric-cap, smaller minimal lumen cross-sectional area (MLA), dissection and thrombus were significantly more frequent in ruptured and unstable plaque group. The levels of plasma hs-CRP, proMMP-1 and TIMP-1 were higher in ruptured plaque group. hs-CRP > 8.94 mg/L was used to predict ruptured plaque with a ROC curve area of 0.76 [95% confidence interval (CI), 67.0% - 85.8%], sensitivity of 71.8%, specificity of 77.0% and accuracy of 69.2% (P < 0.01), similarly for proMMP-1 > 0.12 ng/ml with a ROC curve area of 0.69 [95% CI, 58.2% - 80.2%], sensitivity of 69.2%, specificity of 75.2% and accuracy of 66.2% (P < 0.01), and TIMP-1 > 83.45 ng/ml with a ROC curve area of 0.67 [95% CI, 56.2% - 78.3%], sensitivity of 66.7%, specificity of 61.9% and accuracy of 66.2% (P < 0.01). CONCLUSION: The plaque characteristics correlate with the clinical presentation. The elevation of hs-CRP, proMMP-1 and TIMP-1 are related to the plaque instability and rupture.

[Effects of puerarin on proliferation of vascular smooth muscle cells induced by thrombin].

OBJECTIVE: To investigate the effects of puerarin on the proliferation of vascular smooth muscle cells (VSMC) induced by thrombin and the mechanism thereof. METHODS: VSMCs were isolated from the thoracic aorta of a SD rat and cultured, then co-cultured with thrombin of the concentration 0.1, 0.3, 1.0, 3.0, and 10 U/L for 24 h, thrombin of the concentration of 1 U/L for 0, 6, 12, 24, 36, and 48 h respectively, or thrombin of the concentration of 1 U/L combined with puerarin of the concentrations of 1.5 x 10(-5), 1.5 x 10(-4), or 1.5 x 10(-3) mol/L for 24 h. Flow cytometry was used to detect the cell number and cell cycle. Western blotting was used to indicate the protein expression of the oncogenes c-fos and bcl-2 RT-PCR was used to evaluate the thrombin receptor (TR) mRNA expression. RESULTS: he numbers of the groups of VSMCs stimulated by 0.1, 0.3, 1.0, 3.0, and 10 U/L thrombin for 24 hours were 4.82 x 10(4)/ml +/- 0.11 x 10(4)/ml, 6.37 x 10(4)/ml +/- 0.09 x 10(4)/ml, 8.78 x 10(4)/ml +/- 0.08 x 10(4)/ml, 7.37 x 10(4)/ml +/- 0.07 x 10(4)/ml, and 5.28 x 10(4)/ml +/- 0.12 x 10(4)/ml respectively, all significantly higher than that of the control group (4.08 +/- 0.054 x 10(4)/ml, all P < 0.05). The effect of thrombin was in a dose-dependent manner within a concentration range of 0.1 - 1.0 U/L. The suppression rates of VSMC proliferation in the combination groups with puerarin of the concentrations of 1.5 x 10(-5), 1.5 x 10(-4), and 1.5 x 10(-3) mol/L were 10.9% +/- 1.6%, 32.1% +/- 3.3%, and 42.6% +/- 5.2% respectively in comparison with the thrombin group (all P < 0.05). The c-fos protein expression of the VSMCs after thrombin stimulation for 24 h increased by 156.0% +/- 11.3% (P < 0.05), and the bcl-2 protein expression of the VSMCs pretreated with puerarin of the concentrations of 1.5 x 10(-5), 1.5 x 10(-4), and 1.5 x 10(-3) mol/L, and then stimulated by thrombin was significantly lower than that of the VSMCs only stimulated by thrombin with the suppression rates of 20.7% +/- 2.1%, 31.6% +/- 5.2%, and 44.5% +/- 7.5% respectively (all P < 0.05). The bcl-2 protein expression of the VSMCs after thrombin stimulation for 24 h increased by 96.7% +/- 8.3% (P < 0.05), and the bcl-2 protein expression of the VSMCs pretreated with puerarin of the concentrations of 1.5 x 10(-5), 1.5 x 10(-4), and 1.5 x 10(-3) mol/L, and then stimulated by thrombin was significantly lower than that of the VSMCs only stimulated by thrombin with the suppression rates of 7.1% +/- 0.8%, 18.8% +/- 1.2%, and 39.6% +/- 6.4% respectively (all P < 0.05). The stimulation of thrombin increased the TR mRNA expression by 183.9% +/- 9.4%. The puerarin of the concentrations of 1.5 x 10(-5) mol/L and 1.5 x 10(-4) mol/L decreased the increase of TR mRNA expression induced by thrombin, however, without significant differences (both P > 0.05), and puerarin of the concentration of 1.5 x 10(-3) mol/L significantly suppressed the increase of TR mRNA expression induced by thrombin by 17.6% +/- 1.7% (P < 0.05). CONCLUSION: Puerarin suppresses the proliferation and DNA synthesis of VSMC induced by thrombin. The inhibitory effect of puerarin is closely related with the suppression of the protein expression of c-fos and bcl-2n, and partly related with the suppression of the TR mRNA expression.

[C-reactive protein induced human endothelium cells apoptosis is associated with Bcl-2/Bax gene expression changes].

OBJECTIVE: In the present study, we examined the expression changes of Bcl-2/Bax in C-reactive protein (CRP) treated human endothelium cells in vitro. METHODS: The human umbilical vein endothelial cells (HUVEC) were cultured by digest method for 2 - 3 posterities and incubated with human CRP (0, 1, 5, 25 mg/L for 24 hours) and analyzed by flow cytometer for apoptosis ratio. The effects of CRP in various concentrations on Bcl-2/Bax mRNA and protein expression were examined by RT-PCR and Western Blotting. RESULTS: Apoptosis ratio increased, downregulated Bcl-2 (gene promoting cell survival) and upregulated Bax (gene promoting apoptosis) at mRNA and protein levels in proportion to increased CRP concentrations. CONCLUSION: These results demonstrate that Bcl-2/Bax could be regulated by CRP in human HUVECs and might play a causal role in CRP-induced apoptosis.

[Puerarin suppresses the proliferation of vscular smooth muscule cells and c-fos and bcl-2 protein expression].

OBJECTIVE: To observe the role of puerarin on the proliferation of vascular smooth muscle cells(VSMC) induced by thrombin (T) and the effect of puerarin on the c-fos and bcl-2 protein expression. METHOD: Cell number and cell cycle analysis using flow cytometry were adopted as two different indicators of effects on proliferation of VSMC. Western blot was used to indicate the changes of c-fos and bcl-2 protein after 24 h of treatment of T and puerarin. RESULT: 1.5 x 10(-5) - 1.5 x 10(-3) mol x L(-1) puerarin could significantly suppress this stimulation of VSMC proliferation and DNA synthesis induced by T. Western blot demonstrated that after 24 hour of treatment with T and puerarin, T could significantly increase c-fos and bcl-2 protein and 1.5 x 10(-5) - 1.5 x 10(-3) mol x L(-1) puerain could significantly suppress this increase. CONCLUSION: puerarin can suppress the proliferation and DNA synthesis of VSMC promoted by T. This inhibitory effects of puerarin are closely related with the suppression of c-fos and bcl-2 protein.