Role of gonadally synthesized steroid hormones in the colorectal cancer microenvironment.

Objective: To understand the relationship between steroid hormones synthesized by the gonads and colorectal cancer as well as its tumor microenvironment, in the expectation of providing new ideas in order to detect and treat colorectal cancer. Methods: Through reviewing the relevant literature at home and abroad, we summarized that androgens promote the growth of colorectal cancer, and estrogens and progesterone help prevent bowel cancer from developing; these three hormones also have a relevant role in the cellular and other non-cellular components of the tumor microenvironment of colorectal cancer. Conclusion: The current literature suggests that androgens, estrogens, and progesterone are valuable in diagnosing and treating colorectal cancer, and that androgens promote the growth of colorectal cancer whereas estrogens and progesterone inhibit colorectal cancer, and that, in addition, the receptors associated with them are implicated in the modulation of a variety of cellular components of the microenvironment of colorectal cancer.

Treated with interferon and the gene polymorphism of CGRP and its receptor.

OBJECTIVE: This case-control study aims to investigate the relationship of polymorphisms of four gene loci (CGRP rs155209 and rs3781719, RAMP1 rs3754701 and rs7590387) with the prognosis of interferon therapy for chronic hepatitis B (CHB). MATERIALS AND METHODS: A total of 317 CHB patients receiving interferon alone for the first time were recruited in northern China, and peripheral blood samples were obtained. The single-nucleotide polymorphisms (SNPs) in rs155209, rs3781719, rs3754701, and rs7590387 were genotyped using Matrix-Assisted Laser Desorption/Ionization Time-of-Flight Mass Spectrometry (MALDI-TOF MS). Univariate and multivariate logistic regression methods were employed to assess the correlation between CHB prognosis treated with interferon and polymorphisms of these gene loci. RESULTS: The study clearly demonstrated the relevance of polymorphisms of rs155209, rs3781719, rs3754701, and rs7590387 with DNA response and ALT response after interferon treatment. CHB patients with CGRP rs155209C had a lower risk of developing DNA response (CT vs. TT: OR = 0.159, 95% CI = 0.086-0.294, Padj < 0.001; CC vs. TT: OR = 0.131, 95% CI = 0.059-0.288, Padj < 0.001), as well as a lower risk of developing ALT response (CT vs. TT: OR = 0.530, 95% CI = 0.323-0.869, Padj < 0.05). Moreover, CHB patients with RAMP1 rs3754701T allele were more prone to develop DNA response (AT vs. AA: OR = 2.061, 95% CI = 1.237-3.435, Padj < 0.05; TT vs. AA: OR = 5.676, 95% CI =1.247-25.837, Padj < 0.05), and they also more likely to develop ALT response (AT vs. AA: OR = 1.766, 95% CI = 1.098-2.840, Padj < 0.05). We did not find a significant association between CGRP rs3781719 or RAMP1 rs7590387 and DNA response or ALT response. CONCLUSION: This study revealed that CGRP rs155209 and RAMP1 rs3754701 polymorphisms, but not CGRP rs3781719 and RAMP1 rs7590387, were correlated with interferon therapy prognosis for CHB in Han Chinese population, and RAMP1 rs3754701T was a protective factor for ALT response and DNA response, but CGRP rs155209C carriers were less prone to DNA and ALT responses.

The regulatory effects of a epoprostenol analog on the differentiation of CD4+ T cells to Treg cells and the possible mechanism / 中华微生物学和免疫学杂志

Objective To investigate the roles of a epoprostenol(PGI2) analog (Iloprost) in regulating the differentiation of CD4+ T cells to Treg cells and the possible mechanism.Methods Naǐve CD4+ T cells were isolated from human peripheral blood samples by using the magnetic-activated cell sorting (MACS) and then cultured under Treg-polarizing condition.The percentages of Treg cells and the expression of Foxp3 at mRNA level were respectively measured by using flow cytometry and RT-PCR for evaluation the effects of Iloprost on the differentiation of CD4+ T cells to Treg cells.The cAMP accumulation assay was used to detect the level of intracellular cAMP.Flow cytometry analysis was performed to detect the phosphorylation of signal transducer and activator of transcription 5 (STAT5).Results lloprost decreased the percentage of Treg cells and inhibited the expression of Foxp3 at mRNA level in a dose dependent manner (P＜0.05).However,the inhibitory effects of Iloprost were weakened when IP receptors were blocked by IP antagonist (CAY10449).A six-fold increase in the levels of intracellular cAMP in Treg cells was induced by Iloprost (P＜0.05) and a similar effect could be achieved by using a cAMP agonist,db-cAMP (P＞0.05).H-89,a protein kinase A inhibitor,inhibited the Iloprost-induced expression of cAMP in Treg cells.Moreover,Iloprost inhibited the IL-2 mediated phosphorylation of STAT5 (P＜0.05) and a similar effect could be achieved by using db-cAMP (P＞0.05).The Iloprost-mediated down-regulation of pSTAT5 was blocked by using H-89.Conclusion PGI2 could activate the cAMP-PKA signaling pathway by binding to the IP receptor,resulting in inhibited phosphorylation of STAT5 and suppressed differentiation of naǐve CD4+ T cells to Treg cells.

Association between HLA-DQ gene polymorphisms and different outcomes of hepatitis B virus infection / 中华流行病学杂志

Objective To understand the association between two single-nucleotide polymorphism (HLA-DQ rs28567185 and rs9275572) and different outcomes of hepatitis B virus (HBV) infection.Methods A total of 825 HBV infection related cases were enrolled,and peripheral blood samples were collected from them for DNA extraction.The single-nucleotide polymorphism in HLA-DQ region were genotyped by using matrix-assisted laser desorption/ionization time of flight mass spectrometry.Logistic regression analysis was conducted to evaluate the association between HLA-DQ gene polymorphism and different outcomes of hepatitis B virus infection.Results Our study indicated that cases with HLA-DQ rs2856718G (524 cases) and rs9275572A (369 cases) had reduced susceptibility to HBV infection (OR=0.702,95％CI:0.558-0.856,P=0.001;OR=0.548,95％C1:0.365-0.847,P=0.005) and higher HBV natural clearance (OR=0.589,95％ CI:0.478-0.892,P=8.81 × 10-3;OR=0.673,95％CI:0.457-0.860,P=0.014).Moreover,rs9275572A was also associated with the lower risk of the development of hepatocellular carcinoma (OR=0.759,95％CI:0.538-0.914,P=0.041).Conclusion Our study suggested that HLA-DQ loci might be associated with the different outcomes of HBV infection in Chinese in Han ethnic group in northern China,rs2856718G and rs9275572A might be protective factors for HBV infection,HBV natural clearance and HBV-related disease progress.

Construction of a eukaryotic expression system of IFN-λ and evaluation of bio-functions mediated by the system product / 军事医学

Objective To construct a eukaryotic expression system of IFN-λ,examine the expression of IFN-λand evaluate its bio-functions including anti-proliferation and anti-viral activity.Methods The genes of human IFN-λ1 /2 (hIFN-λ1 /2)were cloned from the mRNA of poly I∶C treated HuH-7 cells.The PCR product was examined with DNA sequencing.The genes of IFN-λ1 /2 were sub-cloned into pcDNA3 vector.The correct insertion of the gene IFN-λ1 /2 was identified with enzyme digestion.The constructed pcDNA3-IFN-λ1 /2 plasmids were transfected into COS-7 cells and IFN-λ1 /2 protein was checked in the supernatant and lysis of transfected cells using Western blotting analysis.The human esophageal carcinoma YES5 and T.Tn cells were treated with the IFN-λ1 /2 from the transfected cells and the proliferation of carcinoma cells were measured with CCK-8 kit.In the treated carcinoma cells,the apoptosis and antivirus related molecules such as caspase-3,ISG15 and MxA was analyzed with Western blotting or Quantitative real time PCR.Results The sequence of hIFN-λ1 /2 fragment matched that of the gene bank and the gene of the cytokines was inserted into pcDNA3 vector correctly.With Western blotting analysis,IFN-λ1 /2 protein was detected in the pcDNA3-IFN-λ1 /2 transfected COS-7 cells.The IFN-λ1 /2 from the transfected COS-7 cells inhibited the growth of YES5 and T.Tn cells, activated apoptosis related caspase-3,and up-regulated the anti-virus gene expression of ISG15 and MxA.Conclusion COS-7 cells can express IFN-λ1 /2 after transfection with pcDNA3-IFN-λ1 /2,suggesting that eukaryotic expression system of IFN-λis established.IFN-λ1 /2 from the system can perform bio-functions,such as proliferation inhibition,apoptosis induction and anti-viral gene up-regulation,which indicates that the system can contribute to further investigations of IFN-λbio-activity and its clinical application.