Shujin Guo

Increased Serum ox-LDL Levels Correlated with Lung Function, Inflammation, and Oxidative Stress in COPD

Chronic obstructive pulmonary disease (COPD) is associated with abnormal inflammation and high oxidative stress. Studies suggest that oxidized low density lipoprotein (ox-LDL) is involved in diseases associated with oxidative stress and inflammation. However, no data on the possible relationship between COPD and ox-LDL are available. This study compared serum levels of ox-LDL in 48 COPD patients and 32 health controls and correlated them with lung function, systematic inflammation, and oxidative stress. Serum levels of ox-LDL, C-reactive protein (CRP), and oxidative stress (measured by reactive oxygen species, ROS) were analyzed using commercial kits. Mean levels of serum ox-LDL were significantly higher in COPD patients than in controls (18.62 ± 7.56 versus 12.57 ± 5.90 mU/L, P < 0.05). Serum levels of CRP and ROS were also significantly higher in COPD patients. Serum levels of ox-LDL in COPD patients correlated inversely with FEV1% predicted, an index of lung function (r = −0.347, P = 0.016), while they correlated positively with CRP and ROS levels. These results suggest that serum levels of ox-LDL are increased in COPD patients and that these levels are associated with lung function, inflammation, and oxidative stress in COPD. Future studies are needed to determine whether and how ox-LDL plays a role in COPD.

Silymarin Attenuates Airway Inflammation Induced by Cigarette Smoke in Mice

Cigarette smoke (CS), which increases inflammation and oxidative stress, is a major risk factor for the development of COPD. In this study, we investigated the effects of silymarin, a polyphenolic flavonoid isolated from the seeds and fruits of milk thistle, on CS-induced airway inflammation and oxidative stress in mice and the possible mechanisms. BALB/c mice were exposed to CS for 2 h twice daily, 6 days per week for 4 weeks. Silymarin (25, 50 mg/kg · day) was administered intraperitoneally 1 h before CS exposure. Bronchoalveolar lavage fluid (BALF) was acquired for cell counting and the detection of pro-inflammatory cytokine levels. Lung tissue was collected for histological examination, myeloperoxidase (MPO) activity assay, superoxide dismutase (SOD) activities, and malondialdehyde (MDA) levels. The phosphorylation of ERK and p38 was evaluated by Western blotting. Pretreatment with silymarin significantly attenuated CS-induced thickening of the airway epithelium, peribronchial inflammatory cell infiltration, and lumen obstruction. The numbers of total cells, macrophages, and neutrophils, along with the MPO activity (a marker of neutrophil accumulation) in BALF, were remarkably decreased by silymarin in CS-exposed mice (all p < 0.05). In addition, silymarin pretreatment dampened the secretion of TNF-α, IL-1β, and IL-8 in BALF. High-dose silymarin (50 mg/kg · day) administration also prevented CS-induced elevation in MDA levels and decrease in SOD activities (p < 0.05). Furthermore, the CS-induced phosphorylation of ERK and p38 was also attenuated by silymarin (p < 0.05). These results suggest that silymarin attenuated inflammation and oxidative stress induced by cigarette smoke. The anti-inflammatory effect might partly act through the mitogen-activated protein kinases (MAPK) pathway.

The -173 G/C polymorphism of the MIF gene and inflammatory bowel disease risk: a meta-analysis.

The -173 G/C polymorphism in the macrophage migration inhibitory factor (MIF) gene has been implicated in susceptibility to inflammatory bowel disease (IBD), but the results are inconclusive. The present meta-analysis aimed to investigate the overall association between the -173 G/C polymorphism and IBD risk. We searched in Pubmed, and Embase for studies evaluating the association between the -173G/C gene polymorphism and IBD risk. Data were extracted and statistical analysis was performed using Revman 5.1 and STATA 12.0 software. A total of seven publications involving 4729 subjects (2282 IBD cases and 2447 controls) were included in this meta-analysis. Combined analysis revealed a clear association between this polymorphism and IBD susceptibility (OR = 1.48, 95% CI: 1.10–2.00, p = 0.009 for CC vs. CG + GG). Subgroup analysis by ethnicity showed that the IBD risk associated with the -173G/C gene polymorphism was significantly elevated among Asians (OR = 1.79, 95% CI: 1.08–2.96, p = 0.02), but not among Caucasians. Subgroup analysis by disease suggested that the -173G/C gene polymorphism is a risk factor for ulcerative colitis (OR = 1.62, 95% CI: 1.10–2.37, p = 0.01), but that it was not associated with Crohn’s disease. This meta-analysis suggests that the -173 G/C polymorphism in the macrophage MIF gene contributes to IBD susceptibility, specifically in Asian populations. Further studies are needed to validate these findings.

The 2518 A/G polymorphism in the MCP-1 gene and cancer risk: a meta-analysis.

BACKGROUND The 2518 A/G polymorphism in the MCP-1 gene has been extensively studied for associations with cancer; however, results from replication studies have been inconsistent. The aim of this investigation was to determine links with risk of cancer by meta-analysis. METHODS We searched Pubmed, Embase, CNKI, Weipu and Wanfang databases, covering all case-control studies until March, 2013. Statistical analyses were performed using the Revman 5.0 software. RESULTS A total of 11 case-control studies met our inclusion criteria, including 1,422 cases and 2,237 controls. The results indicated that the MCP-1 2518 gene polymorphism had no association with cancer risk overall (GG vs.GA+ AA: OR = 0.89, 95%CI = 0.61-1.28, P = 0.52). However, in the subgroup analysis by ethnicity, a decrease of cancer risk was found in Asian populations (GG vs.GA+ AA: OR = 0.79, 95%CI = 0.63-0.99, P = 0.04). CONCLUSION This meta-analysis suggested that the 2518A/G polymorphism of MCP-1 gene is associated with risk of cancer among Asian, but not in Caucasian populations.

The -159C/T polymorphism in the CD14 gene and cancer risk: a meta-analysis.

Purpose The -159C/T polymorphism in the cluster of differentiation (CD)14 gene has been extensively studied for an association with cancer; however, results from replication studies have been inconclusive. The aim of this study was to perform a comprehensive assessment of the possible association between the -159C/T polymorphism in the CD14 gene and cancer risk, by meta-analysis. Methods We searched in PubMed, Embase, and other databases, covering all case-control studies on the possible association between CD14 -159C/T gene polymorphism and cancer risk. Data were extracted and statistical analyses were performed using RevMan 5.0 and STATA 12.0 software. Results A total of 12 case-control studies met our inclusion criteria, including 2,498 cases and 2,696 controls. The combined analysis indicated that the CD14 -159C/T gene polymorphism didn’t confer risk for cancer – the recessive model (TT versus (vs) CT + CC), showed odds ratio (OR) =1.01, 95% confidence interval (CI) =0.82–1.23 (P=0.94), while the dominant model (TT + TC vs CC) showed OR =0.81, 95% CI =0.66–1.00 (P=0.05). A subgroup analysis by ethnicity showed that the cancer risk associated with CD14 -159C/T gene polymorphism was significantly decreased among Caucasians for the TC + TT vs CC comparison (OR =0.83, 95% CI =0.70–0.98 [P=0.03]). The subgroup analysis by cancer type suggested that the CD14 -159C/T gene polymorphism was not associated with gastric cancer risk. Conclusion The evidence from the present meta-analysis did not support the CD14 -159C/T gene polymorphism as a genetic risk factor for cancer. Further studies on different cancer types and ethnicities are needed to validate our findings.

Tumor necrosis factor-α −308 G/A polymorphism and risk of sepsis, septic shock, and mortality: an updated meta-analysis

Background The -308G/A polymorphism in the gene encoding tumor necrosis factor-α (TNF-α) has been implicated in sepsis risk in many studies but with variable results. This study aimed to comprehensively assess the evidence of association between this polymorphism and risk of sepsis and sepsis-related mortality. Materials and Methods PubMed, EMBASE and other databases were searched to identify relevant studies, and data were analyzed using Review Manager 5.0 and STATA 12.0. Results Data from 34 publications involving 12,284 subjects were meta-analyzed. Combined analysis revealed an association between TNF-α -308G/A gene polymorphism and risk of sepsis (AA+GA vs. GG, OR 1.35, 95% CI 1.10–1.67, P = 0.005). This association was observed in the Caucasian subgroup (OR 1.50, 95% CI 1.13–2.00, P = 0.006), but not in the Asian subgroup. Across the entire study population, the polymorphism was also significantly related to septic shock risk (OR 1.52, 95% CI 1.18–1.95, P = 0.001) but not to sepsis-related mortality (OR 0.99, 95% CI 0.71–1.40, P = 0.97). Conclusions This meta-analysis suggests that the -308G/A gene polymorphism in the TNF-α gene may contribute to risk of sepsis and septic shock, but not risk of mortality.

Involvement of Ca2+-activated K+ channel 3.1 in hypoxia-induced pulmonary arterial hypertension and therapeutic effects of TRAM-34 in rats

Pulmonary artery hypertension (PAH) is an incurable disease associated with the proliferation of pulmonary artery smooth muscle cells (PASMCs) and vascular remodeling. The present study examined whether TRAM-34, a highly selective blocker of calcium-activated potassium channel 3.1 (Kca3.1), can help prevent such hypertension by reducing proliferation in PASMCs. Rats were exposed to hypoxia (10% O2) for 3 weeks and treated daily with TRAM-34 intraperitoneally from the first day of hypoxia. Animals were killed and examined for vascular hypertrophy, Kca3.1 expression, and downstream signaling pathways. In addition, primary cultures of rat PASMCs were exposed to hypoxia (3% O2) or normoxia (21% O2) for 24 h in the presence of TRAM-34 or siRNA against Kca3.1. Activation of cell signaling pathways was examined using Western blot analysis. In animal experiments, hypoxia triggered significant medial hypertrophy of pulmonary arterioles and right ventricular hypertrophy, and it significantly increased pulmonary artery pressure, Kca3.1 mRNA levels and ERK/p38 MAP kinase signaling. These effects were attenuated in the presence of TRAM-34. In cell culture experiments, blocking Kca3.1 using TRAM-34 or siRNA inhibited hypoxia-induced ERK/p38 signaling. Kca3.1 may play a role in the development of PAH by activating ERK/p38 MAP kinase signaling, which may then contribute to hypoxia-induced pulmonary vascular remodeling. TRAM-34 may protect against hypoxia-induced PAH.