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Objective:To investigate the relationships between the expression levels of chemokines CCL19 and CCL21 in serum of patients with RA and interstitial lung disease,as well as the correlation between the chemokines and the clinical parameters.Methods:Patients hospitalized in the First Hospital of China Medical University from May 2016 to March 2017 were enrolled.Serum levels of CCL21 and CCL19 in the 62 patients with RA,among them,34 cases without pulmonary interstitial lesions while 28 cases with lung interstitial diseases,18 cases ⅡP and 20 health control were detected with enzyme-linked immunosorbent assay (ELISA).One-way ANOVA,LSD-t test,Kruskal-Wallis test,Pearson and Spearman correlation analysis were used for statistical analysis.Results:The levels of CCL21 and CCL19 were both higher in the RA patients than the health controls(P＜0.05;P＜0.01),The concentrations of CCL21 in serum of the RA patients with ILD were higher than thoes without ILD,higher than the health controls (P＜0.05;P＜0.01),serum levels of CCL21 in the ⅡP patients were higher than the health controls (P＜0.01),too.The serum levels of CCL21 in men were higher than women(P＜0.05).Serum CCL21 levels were negatively correlated with albumin and BMI(r=-0.280,P＜0.05;r =-0.605,P＜0.05).Levels of CCL19 were negatively correlated with the levels of C4 (r =-0.326,P＜0.05),and positively correlated with the levels of D-Dimer(r =0.592,P＜0.05).Conclusion:Chemokines CCL21 and CCL19 are highly expressed in serum of patients with RA,they may be involved in the pathogenesis of RA.Furthermore,CCL21 may has a correlation with the lung interstitial lesion in RA.
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To explore the effects and mechanism of aqueous extracts of gecko on cancer stem cells properties of hepatocellular carcinoma. In vitro, MTT assay was used to detect the cells growth in Huh7 and Hep3B. Spheroid-forming assay and flow cytometry were performed to observe the the stemness of Huh7 and Hep3B cells. The protein expressions of β-catenin, CD44, c-Myc, CCND1, Sox2, Oct4, Nanog and ABCG2 were detected by Western blot. Interacting proteins were detected by co-immunoprecipitation; and a subcutaneous xenograft model was used to detect the stemness of hepatoma carcinoma cells. The results indicated that aqueous extracts of gecko induced cell growth inhibition in a dose- and time-dependent manner, with the IC₅₀ of (0.750±0.112) g•mL⁻¹ for Huh7 and (0.454±0.039) g•mL⁻¹ for Hep3B, respectively. The number and size of tumor spheres formed by hepatoma carcinoma cells were decreased after treatment by aqueous extracts of gecko(P<0.05); the proportions of cells staining with putative markers for cancer stem cells, such as CD133 and CD44, were decreased(P<0.05). After treatment with aqueous extracts of gecko, the expression levels of β-catenin, CD44, c-Myc, CCND1, Sox2, Oct4, Nanog and ABCG2 were decreased. Co-immunoprecipitation results showed that the aqueous extracts of gecko could inhibit the interaction between LRP6 and Frizzled6, indicating that the aqueous extracts of gecko could inhibit the proliferation of hepatoma cells, the formation of tumor spheres and the proportion of tumor stem cells, and inhibit the Wnt signaling pathway by targeting LRP6 to prevent the formation of LRP6 and Frizzled6 complexes.
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<p><b>OBJECTIVE</b>To explore the relationship between genetic polymorphism of quinone oxidoreductase 1 (NQO1), glutathione S-transferase theta 1 (GSTT1), glutathiones S-transferase mu 1 (GSTM1) and susceptibility to chronic benzene poisoning (BP).</p><p><b>METHODS</b>The genotypes of NQO1, GSTT1, GSTM1 for 100 patients with benzene poisoning and 90 workers exposed to benzene who were engaged in the same working time and job title as patients with benzene poisoning were detected by PCR-RFLP and multi-PCR.</p><p><b>RESULTS</b>There was a 2.82-fold (95% CI: 1.42 approximately 5.58, P < 0.05) increased risk of BP in the subjects with NQO1 C609T mutation genotype (T/T) compared with those carrying heterozygous (C/T) and wild type (C/C), and there was a 2.94-fold (95% CI: 1.25 approximately 6.90, P < 0.05) increased risk of BP in the subjects with NQO1 C609T T/T genotype compared with those carrying C/C genotype. The subjects with GSTT1 null genotype had a 1.91-fold (95% CI: 1.05 approximately 3.45, P < 0.05) increased risk of BP compared with those with GSTT1 non-null genotype. The interaction of two genes showed that there was a increased risk of BP in subjects with any two genotypes of NQO1 C609T T/T genotype and GSTT1 null genotype and GSTM1 null genotype, compared to the individual with any two genotypes of NQO1 C609T C/C genotype and GSTT1 non-null genotype and GSTM1 non-null genotype. The interaction of three genes showed that there was a 20.41-fold (95% CI: 3.79 approximately 111.11, P < 0.01) increased risk of BP in subjects with NQO1 C609T T/T genotype and GSTT1 null genotype and GSTM1 null genotype compared with those carrying NQO1 C609T C/T genotype and C/C genotype and GSTT1 non-null genotype and GSTM1 non-null genotype.</p><p><b>CONCLUSIONS</b>The interaction of multi-genes may be an important role to BP. The genetic polymorphisms of 3 genes (NQO1, GSTT1 and GSTM1) led to declining of detoxifying ability in benzene metabolism, so the individual with NQO1 C609T T/T genotype, GSTT1 null genotype and GSTM1 null genotype is most susceptive to benzene. The results were consistent with that of the theoretic presumption. It could be suggested as a biomarker to assess the risk of benzene poisoning for individuals.</p>
Subject(s)
Adult , Aged , Female , Humans , Male , Middle Aged , Benzene , Poisoning , Case-Control Studies , Chronic Disease , Genetic Predisposition to Disease , Glutathione Transferase , Genetics , NAD(P)H Dehydrogenase (Quinone) , Genetics , Polymorphism, GeneticABSTRACT
<p><b>OBJECTIVE</b>To study the relationship between the polymorphism myeloperoxidase (MPO) gene and the genetic susceptibility to benzene toxicity in workers exposed to benzene and in patients with benzene poisoning.</p><p><b>METHODS</b>Using polymerase chain reaction-restriction fragment length polymorphisms (PCR-RFLP) techniques, the genotypes' polymorphism of MPO gene in 35 patients with chronic benzene poisoning, 46 workers exposed to benzene from the same workplace (as exposed control) and 26 controls were analyzed.</p><p><b>RESULT</b>There were three (G/G, G/A and A/A) genotypes in the region of 463 bp upstream of MPO gene. The distribution frequency in G/G wild-type genotype in patients was 27.4% more than that in the exposed workers. The risk of benzene-hematotoxicity in those with G/G genotype was 2.8-fold higher than G/A + A/A genotype (OR = 2.835, 95% CI: 1.065 - 7.549, P < 0.05). The polymorphism of myeloperoxidase was not associated with gender specific.</p><p><b>CONCLUSION</b>In the same benzene-exposed environment, the subjects with MPO-463 G/G genotype may be more susceptible to benzene toxicity.</p>