Angiotensin-converting enzyme insertion/deletion (rs106180) and angiotensin type 1 receptor A1166C (rs106165) genotypes and psoriasis: Correlation with cellular immunity,lipid profile,and oxidative stress markers

Psoriasis is a chronic inflammatory skin condition and angiotensin-converting enzyme (ACE) is a key circulating enzyme converting angiotensin (Ang) I to the vasoactive peptide Ang II. The exact role of ACE insertion (I)/deletion (D) polymorphism (rs106180) in psoriasis is not clear. We aimed to examine whether the ACE I/D and Ang II type 1 receptor (AT1R) A₁₁₆₆C-polymorphisms (rs106165), lipid profile, and stress oxidative are associated with susceptibility to psoriasis. One hundred patients with psoriasis and 100 sex- and age-matched unrelated healthy controls were recruited for this case-control study. ACE I/D and AT1R A₁₁₆₆C polymorphisms were identified by the polymerase chain reaction (PCR) and PCR-restriction fragment length polymorphism, respectively, malondialdehyde (MDA) was detected by the high-performance liquid chromatography, serum arylesterase (ARE) activity of paraoxonase and catalase activities were detected by the spectrophotometry, superoxide dismutase (SOD) activity and vascular adhesion protein (VAP)-1 were measured by ELISA. The presence of C allele of AT1R A₁₁₆₆C and I allele of ACE considerably increased the risk of psoriasis by 6.42-fold (P < 0.001). The distribution of II-genotype of ACE was significantly higher in psoriasis patients than in control group and increased the risk of disease by 3.11-times (P = 0.023). The higher levels of MDA in patients and the higher activity of SOD, ARE, and CAT was observed in healthy controls with I/D+I/I-genotype of ACE I/D. This study for the first time demonstrated that the ACE I/D and AT1R A ₁₁₆₆C genes polymorphisms robustly increases the risk of developing psoriasis in population from west of Iran. In addition, these individuals had significantly higher VAP-1 and MDA concentration and lower enzymatic and nonenzymatic antioxidant-status, suggesting that psoriatic patients carrying C allele of AT1R₁₁₆₆ polymorphism may be more susceptible to cardiovascular disease and myocardial infarction compared with A allele.     

The enhancing effect of homocysteine thiolactone on insulin fibrillation and cytotoxicity of insulin fibril

In the current study both structural alteration and fibrillation of insulin were studied in the presence of homocysteine thiolactone (HCTL). The spectroscopic studies revealed that HCTL increases rate of insulin unfolding, giving rise to the appearance of solvent-exposed hydrophobic regions and induces a transition from α-helix into predominantly β-sheet structures. Thioflavin-T fluorescence studies revealed that HCTL markedly enhanced the quantity of insulin fibril formation in both agitating and non-agitating systems. Also gel electrophoresis results suggest that HCTL accelerates the process of formation of high molecular weight insulin aggregates. Moreover, insulin fibrils obtained in the presence of HCTL and those collected earlier in the pathway of insulin fibrillation displayed improved cytotoxicity against cancer cells. The enhancement of insulin fibril formation with elevated cytotoxic properties as occurred in the presence of HCTL, may suggest this homocysteine derivative as a possible contributing factor in the pathology of insulin fibrils.     

Resveratrol treatment reduces expression of MCP-1, IL-6, IL-8 and RANTES in endometriotic stromal cells

Endometriosis is an inflammatory disease affecting reproductive-aged women. Immunologic disturbance, as well as inflammation, have crucial roles in the pathogenesis of endometriosis. In this study, we evaluated the effects of resveratrol treatment on expression of monocyte chemotactic protein-1 (MCP-1), interleukin-6 (IL-6), IL-8, and regulated upon activation, normal T cell expressed and secreted (RANTES) in endometrial stromal cells from patients with endometriosis compared with non-endometriotic controls. Thirteen eutopic (EuESCs) and nine ectopic (EESCs) endometrial stromal cells from endometriotic patients as well as eleven endometrial stromal cells from non-endometriotic controls (CESCs) were treated with resveratrol (100 μmol/L) or ethanol, and gene and/or protein expression of MCP-1, IL-6, IL-8 and RANTES was examined at 6, 24 and 48 hours following treatment in the cells from all origins. Resveratrol treatment significantly reduced gene and protein expression of MCP-1, IL-6, and IL-8 in EuESCs and EESCs compared with CESCs (P < .05-.001, P < .05-.001 and P < .05-<.01, respectively), and this reduction was more noticeable in EESCs than EuESCs (P < .05-<.001). Besides, resveratrol treatment significantly reduced RANTES protein expression in EESCs in all time intervals (P < .05). Resveratrol treatment significantly reduced the expression of MCP-1, IL-6, IL-8 and RANTES in EESCs.