BackgroundThe present study was designed to explore the association of angiotensin converting enzyme (ACE) gene insertion/deletion (I/D, rs4646994) polymorphism, plasma ACE activity, and circulating ACE mRNA expression with essential hypertension (EH) in a Chinese population. In addition, a new detection method for circulating ACE mRNA expression was explored.MethodsThe research was approved by the ethics committee of Zhejiang Provincial Center for Disease Prevention and Control. Written informed consent was obtained prior to the investigation. 221 hypertensives (cases) and 221 normotensives (controls) were interviewed, subjected to a physical examination, and provided blood for biochemical and genetic tests. The ACE mRNA expression was analyzed by real time fluorescent quantitative Reverse Transcription PCR (FQ-RT-PCR). We performed logistic regression to assess associations of ACE I/D genotypes, ACE activity, and ACE mRNA expression levels with hypertension.ResultsThe results of the multivariate logistic regression analysis showed that the additive model (ID, DD versus II) of the ACE genotype revealed an association with hypertension with adjusted OR of 1.43(95% CI: 1.04-1.97), and ACE ID genotype with adjusted OR of 1.72(95% CI: 1.01-2.92), DD genotype with adjusted OR of 1.94(95% CI: 1.01-3.73), respectively. In addition, our data also indicate that plasma ACE activity (adjusted OR was 1.13(95% CI: 1.08-1.18)) was significantly related to hypertension. However, the plasma ACE mRNA expressions were not different between the cases and controls.ConclusionACE I/D polymorphism and ACE activity revealed significant influence on hypertension, while circulating ACE mRNA expression was not important factors associated with hypertension in this Chinese population. The detection of circulating ACE mRNA expression by FQ-RT-PCR might be a useful method for early screening and monitoring of EH.

Axl is one of the TAM family members that downregulates activated immune responses to maintain immune homeostasis. We analyzed the expression and clinical relevance of Axl on the surface of CD14+ monocytes/macrophages (mAxl, membrane Axl) and in the plasma (sAxl, soluble Axl) from patients with systemic lupus erythematosus (SLE). Compared to healthy subjects, the concentrations of sAxl were significantly elevated in plasma from SLE patients, while the mAxl expression on CD14+ monocytes/macrophages from SLE patients was significantly downregulated. A series of severe disease clinical manifestations and laboratory features such as presence of autoantibodies, 24-hour proteinuria excretion or SLEDAI ≥10 were associated with decreased mAxl expression on monocytes/macrophages but elevated sAxl levels in plasma. The plasma level of Gas6, the main ligand of Axl, was slightly decreased in SLE patients, and was negatively correlated with anti-dsDNA antibodies and C-reactive protein. SLE patients with SLEDAI ≥10 showed significantly lower Gas6 levels. Our study suggests that abnormal mAxl and sAxl expression may be involved in the imbalance of immune regulation in SLE.

The metastasis-associated lung adenocarcinoma transcript 1 (MALAT1), a well-known long non-coding RNA, is involved in pathogenesis and progress of multiple tumors. However, no study has been performed to investigate the relationship between the genetic variants in promoter region of MALAT1 and colorectal cancer risk. In this study, we conducted a two-stage case-control study to evaluate whether MALAT1 genetic variants were associated with colorectal cancer risk. We identified that a single nucleotide polymorphism (SNP) rs1194338 was significantly associated with the decreased colorectal cancer risk with an odds ratio (OR) of 0.70 [95% confidence interval (CI) = 0.49-0.99] in the combined stage. The subsequently stratified analyses showed that the protective effect of rs1194338 was more pronounced in several subgroups. Furthermore, gene expression profiling analysis revealed overexpression of MALAT1 mRNA in colorectal cancer tissue compared with normal controls. Confirmation studies with large sample size and further mechanistic investigations into the function of MALAT1 and its genetic variants are warranted to advance our understanding of their roles in colorectal carcinogenesis, and to aid in the development of novel and targeted therapeutic strategies.

Ulcerative colitis (UC) is a chronic inflammatory bowel disease affecting the colon and rectum, in which the abnormality of B cells is involved in both its pathogenesis and progression. Follicular helper T cells (TFH) play an important role in assisting the immune function of human B cells in germinal centers, and follicular regulatory T cells (TFR) have the function of inhibiting TFH and germinal center B cell responses. The significance of circulating TFH and TFR in ulcerative colitis (UC) remains unclear. We analyzed peripheral blood of active and stable remission UC patients and found that circulating TFR was significantly decreased while TFH was increased in active UC patients. As to TFH subsets, TFH2 was elevated while TFH17 was decreased in active UC, with IL-4/IL-17A secretion enhanced. Helios + and CD45RA − FoxP3 high TFR cells were decreased while CD226 + and CD45RA + FoxP3 int TFR cells were increased in active UC patients. The levels of new memory B cells, plasmablasts and serum IgG were significantly increased in active UC patients, and were positively correlated with TFH and TFH2, and negatively correlated with TFR. Serum CRP and Mayo Clinic scores were positively correlated with TFH and TFH2 but negatively correlated with TFR. Serum IL-12 and IL-21 were up-regulated while IL-10 was down-regulated in active UC. To conclude, an imbalance of circulating TFH and TFR cells is associated with disease activity in UC patients. Our results suggest a new mechanism for TFH and TFR imbalance in the pathogenesis of UC, providing a new perspective for theoretical research and therapeutic strategies for UC.

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