ABSTRACT
OBJECTIVE: To investigate the relationship of the function and gene polymorphism of insulin receptor substrate (IRS) with type 2 diabetes mellitus (T2DM), and to provide a new perspective for T2DM drug development. METHODS: Relevant literatures included in CNKI, Wanfang, VIP, PubMed, SpringerLink and other databases from Jan. 1991 to Nov. 2017 were retrieved by using "Insulin receptor substrate" "Type 2 diabetes" "Insulin resistance" "Polymorphism" as Chinese keywords, and "Insulin receptor substrate" "IRS" "Type 2 diabetes" "Insulin resistance" "Polymorphism" as English keywords. The relationship of the function and gene polymorphism of IRS family with T2DM was reviewed. RESULTS & CONCLUSIONS: A total of 328 literatures were retrieved, of which there were 38 valid literatures. At present, IRS family has six members (IRS-1 to IRS-6). The dysfunction of IRS-1 and IRS-2 will lead to insulin resistance and induce T2DM. The relationship of IRS-3 and IRS-4 with T2DM remains controversial. IRS-5 and IRS-6 were newly found and their functions are not clear. The Gly972Arg mutation of IRS-1 is positively correlated with the pathogenesis of T2DM. Gly1057Asp mutation of IRS-2 combined with obesity can induce insulin resistance, but there is controversy. The mutation types of IRS family other members include Ala94Thr, Ala512Pro and Ser892Gly mutation of IRS-1, ACC, Ala157Thr and Leu647Val mutation of IRS-2. The relationship between these types of mutation and T2DM has not yet been fully supported. Multiracial and large-scale studies are required. Some achievements have been made in the present study, but the study is not yet comprehensive. Relationship of IRS family members and their mutation sites with T2DM still needs to be further tested in the expanded population.
ABSTRACT
Objective To observe the expression of NOD-like receptor pyrin domain-3 (NLRP3) inflammasome and interleukin-1 beta (IL-1b) in pterygium and normal conjunctiva specimens,and clarify the role of NLRP3 in the development of pterygium.Methods Specimens from 20 cases of pterygium and 6 cases of normal eonjunctival were analyzed for establishing the expression of NLRP3 and IL-1b by immune-histochemistry.The level of caspase-1 and pro-caspase-1 protein were analyzed by Westernblot,gene expression of interleukin-18 (IL-18) was detected by RT-PCR.Results NLRP3 was not expressed in normal conjunctival epithelial cells,but was positive in the basal part of pterygium;IL-1was not expressed in normal conjunctival tissues,but was positive in pterygium.There was no significant difference about the expression of Procaspase-1 in normal conjunctiva and pterygium (P ＞ 0.05),However,caspase-1,also known as the active form of pro-caspase-1 expressed in pterygiun was higher than that in normal conjunctiva(P ＜ 0.05).The average level of IL-18 in 20 cases of pterygium was significantly higher than that in normal conjunctiva (P ＜ 0.05).Conclusion After NLRP3 signaling pathway activating in pterygium tissue,caspase-1,IL-1β and IL-18 are high expression abnormally,suggest that NLRP3 inflammasome and the related signaling pathways may play a role in the progression of pterygium.
ABSTRACT
OBJECTIVE: To investigate the expression of high mobility group protein B1 (HMGB1) and its receptor, receptor for advanced glycation end-product (RAGE), in renal cancer tissue and surrounding normal tissue and to analyze the relationship between the expression level of the protein and receptor as well as the clinical pathological characteristics and prognosis in renal cancer patients. METHODS: A total of 80 renal carcinoma patients who were surgically treated in our hospital from February 2004 to December 2012 were included in this study. Normal paratumoral tissues were collected as a control. All diagnoses were confirmed with a postoperative pathological examination. All patients had complete pathological data. The expression of HMGB1/RAGE proteins in renal cancer tissue and paratumoral tissue was examined using immunohistochemical methods. RESULTS: The positive expression rate of HMGB1 was 71% in renal cancer tissue, which was significantly higher than that in the paratumoral normal tissue (25%). The positive expression rate of RAGE was 72% in renal cancer tissue, which was significantly higher than that in the paratumoral normal tissue (27%). Further analysis did not indicate a correlation between the positive expression of HMGB1 and RAGE proteins and gender, age and tumor size (P > 0.05), whereas the expression patterns were shown to correlate with tumor differentiation, clinical stage and lymph node metastasis (P < 0.05). The expression of HMGB1 exhibited a significant positive correlation with RAGE level (P < 0.05), the expression of HMGB1/RAGE proteins exhibited a negative correlation with the prognosis of patients, and the five-year survival rate of patients with positive expression was significantly lower than that of patients with negative expression (P < 0.05). CONCLUSION: HMGB1/RAGE exhibited significantly elevated expression in renal cancer tissues that was closely related to the clinical prognosis of patients; thus, the expression levels may become a new target in the treatment of renal carcinoma.
