IRS-2 Partially Compensates for the Insulin Signal Defects in IRS-1^-/- Mice Mediated by miR-33

Tang, Chen-Yi,Man, Xiao-Fei,Guo, Yue,Tang, Hao-Neng,Tang, Jun,Zhou, Ci-La,Tan, Shu-Wen,Wang, Min,Zhou, Hou-De Korean Society for Molecular and Cellular Biology 2017 Molecules and cells Vol.40 No.2

Insulin signaling is coordinated by insulin receptor substrates (IRSs). Many insulin responses, especially for blood glucose metabolism, are mediated primarily through Irs-1 and Irs-2. Irs-1 knockout mice show growth retardation and insulin signaling defects, which can be compensated by other IRSs in vivo; however, the underlying mechanism is not clear. Here, we presented an Irs-1 truncated mutated mouse ($Irs-1^{-/-}$) with growth retardation and subcutaneous adipocyte atrophy. $Irs-1^{-/-}$ mice exhibited mild insulin resistance, as demonstrated by the insulin tolerance test. Phosphatidylinositol 3-kinase (PI3K) activity and phosphorylated Protein Kinase B (PKB/AKT) expression were elevated in liver, skeletal muscle, and subcutaneous adipocytes in Irs-1 deficiency. In addition, the expression of IRS-2 and its phosphorylated version were clearly elevated in liver and skeletal muscle. With miRNA microarray analysis, we found miR-33 was down-regulated in bone marrow stromal cells (BMSCs) of $Irs-1^{-/-}$ mice, while its target gene Irs-2 was up-regulated in vitro studies. In addition, miR-33 was down-regulated in the presence of Irs-1 and which was up-regulated in fasting status. What's more, miR-33 restored its expression in re-feeding status. Meanwhile, miR-33 levels decreased and Irs-2 levels increased in liver, skeletal muscle, and subcutaneous adipocytes of $Irs-1^{-/-}$ mice. In primary cultured liver cells transfected with an miR-33 inhibitor, the expression of IRS-2, PI3K, and phosphorylated-AKT (p-AKT) increased while the opposite results were observed in the presence of an miR-33 mimic. Therefore, decreased miR-33 levels can up-regulate IRS-2 expression, which appears to compensate for the defects of the insulin signaling pathway in Irs-1 deficient mice.

Temperature-dependent development of Lista haraldusalis (Walker) (Lepidoptera: Pyralidae) on Platycarya strobilacea

Jian-Feng Liu,Man Liu,Mao-Fa Yang,Dimitris C. Kontodimas,Xiao-Fei Yu,Qi-Xian Lian 한국응용곤충학회 2014 Journal of Asia-Pacific Entomology Vol.17 No.4

The effect of constant temperatures on development and survival of Lista haraldusalis (Walker) (Lepidoptera:Pyralidae), a newly reported insect species used to produce insect tea in Guizhou province (China), was studiedin laboratory conditions at seven temperatures (19 °C, 22 °C, 25 °C, 28 °C, 31 °C, 34 °C, and 37 °C) on Platycaryastrobilacea. Increasing the temperature from 19 °C to 31 °C led to a significant decrease in the developmentaltime from egg to adult emergence, and then the total developmental time increased at 34 °C. Egg incubationwas the stage where L. haraldusalis experienced the highest mortality at all temperatures. The survival ofL. haraldusalis was significantly higher at 25 °C and 28 °C, whereas none of the eggs hatched at 37 °C. Commonand Ikemoto linear models were used to describe the relationship between the temperature and the developmentalrate for each immature stage of L. haraldusalis. The estimated values of the lower temperature thresholdand thermal constant of the total immature stages using Common and Ikemoto linear models were 11.34 °C and11.20 °C, and 939.85 and 950.41 degree-days, respectively. Seven nonlinear models were used to fit the experimentaldata to estimate the developmental rate of L. haraldusalis. Based on the biological significance for modelevaluation, Ikemoto linear, Logan-6, and SSI were the best models that fitted each immature stage ofL. haraldusalis and they were used to estimate the temperature thresholds. These thermal requirements and temperaturethresholds are crucial for facilitating the development of factory-based mass rearing of L. haraldusalis.

IRS-2 Partially Compensates for the Insulin Signal Defects in IRS-1−/−Mice Mediated by miR-33

Chen-Yi Tang,Xiao-Fei Man,Yue Guo,Hao-Neng Tang,Jun Tang,Ci-La Zhou,Shu-Wen Tan,Min Wang,Hou-De Zhou 한국분자세포생물학회 2017 Molecules and cells Vol.40 No.2

Insulin signaling is coordinated by insulin receptor substrates (IRSs). Many insulin responses, especially for blood glucose metabolism, are mediated primarily through Irs-1 and Irs-2. Irs-1 knockout mice show growth retardation and insulin signaling defects, which can be compensated by other IRSs in vivo; however, the underlying mechanism is not clear. Here, we presented an Irs-1 truncated mutated mouse (Irs-1−/−) with growth retardation and subcutaneous adipocyte atrophy. Irs-1−/− mice exhibited mild insulin resistance, as demonstrat-ed by the insulin tolerance test. Phosphatidylino-sitol 3-kinase (PI3K) activity and phosphorylated Protein Kinase B (PKB/AKT) expression were elevated in liver, skeletal muscle, and subcu-taneous adipocytes in Irs-1 deficiency. In addition, the expression of IRS-2 and its phosphorylated version were clearly elevated in liver and skeletal muscle. With miRNA microarray analysis, we found miR-33 was down-regulated in bone marrow stromal cells (BMSCs) of Irs-1−/− mice, while its target gene Irs-2 was up-regulated in vitro studies. In addition, miR-33 was down-regulated in the presence of Irs-1 and which was up-regulated in fasting status. What’s more, miR-33 restored its expression in re-feeding status. Meanwhile, miR-33 levels decreased and Irs-2 levels increased in liver, skeletal muscle, and subcutaneous adipocytes of Irs-1−/− mice. In primary cultured liver cells transfected with an miR-33 inhibitor, the expression of IRS-2, PI3K, and phosphorylated-AKT (p-AKT) increased while the opposite results were observed in the presence of an miR-33 mimic. Therefore, decreased miR-33 levels can up-regulate IRS-2 expression, which appears to compensate for the defects of the insulin signaling pathway in Irs-1 deficient mice.

Human Papillomavirus Vaccine Awareness, Acceptability, and Decision-Making Factors among Chinese College Students

Wang, Shao-Ming,Zhang, Shao-Kai,Pan, Xiong-Fei,Ren, Ze-Fang,Yang, Chun-Xia,Wang, Zeng-Zhen,Gao, Xiao-Hong,Li, Man,Zheng, Quan-Qing,Ma, Wei,Zhao, Fang-Hui,Qiao, You-Lin,Sivasubramaniam, Priya Asian Pacific Journal of Cancer Prevention 2014 Asian Pacific journal of cancer prevention Vol.15 No.7

Background: College students are recommended as the target groups for catch-up human papillomavirus (HPV) vaccination. Systematical exploration of awareness, acceptability, and decision-making factors of HPV vaccination among Chinese college students has been limited. Materials and Methods: A multi-center survey was conducted in mainland China between November 2011 and May 2012. College students aged 18-22 years were stratified by their grade, gender, and major for sampling. Socio-demographic and HPV-related information such as knowledge, perceptions, acceptability, and attitudes were collected through a questionnaire. Results: A total of 3,497 undergraduates completed the questionnaire, among which 1,686 were males. The acceptability of the HPV vaccine was high (70.8%). Undergraduates from high-level universities, at lower grade, or with greater prior knowledge of HPV vaccines showed higher acceptability of HPV vaccination ($p_{trend}$ <0.001). Additionally, undergraduates with vaccination experience outside the National Expanded Program on Immunization (OR=1.29; 95%CI: 1.10-1.51) or fear of HPV-related diseases (OR=2.79; 95%CI: 2.28-3.41) were more willing to accept HPV vaccination. General knowledge of HPV vaccine was low among undergraduates, and safety was a major concern (71.05%). The majority of students wished to pay less than 300RMB for HPV vaccine and chose the Chinese Center for Disease Control and Prevention as the most appropriate venue for vaccination. Conclusions: Although most undergraduates demonstrate positive attitudes towards HPV vaccination, challenges pertaining to introduction exist in China. Corresponding proactive education and governmental subsidy to do so are urgently needed by this age-group population. Suggestions and potential strategies indicated may help shape the future HPV vaccination program in China.

Efficacy and Safety of Sorafenib for Advanced Non-Small Cell Lung Cancer: a Meta-analysis of Randomized Controlled Trials

Wang, Wei-Lan,Tang, Zhi-Hui,Xie, Ting-Ting,Xiao, Bing-Kun,Zhang, Xin-Yu,Guo, Dai-Hong,Wang, Dong-Xiao,Pei, Fei,Si, Hai-Yan,Zhu, Man Asian Pacific Journal of Cancer Prevention 2014 Asian Pacific journal of cancer prevention Vol.15 No.14

Background: Many clinical trials have been conducted to evaluate sorafenib for the treatment of advanced NSCLC, but the results for efficacy have been inconsistent. The aim of this study was to evaluate the efficacy and safety of sorafenib in patients with advanced NSCLC in more detail by meta-analysis. Methods: This meta-analysis of randomized controlled trials (RCTs) was performed after searching PubMed, EMBASE, ASCO Abstracts, ESMO Abstracts, and the proceedings of major conferences for relevant clinical trials. Two reviewers independently assessed the quality of the trials. Outcomes analysis were disease control rate (DCR), progression- free survival (PFS), overall survival (OS) with 95% confidence intervals (CI) and major toxicity. Subgroup analysis was conducted according to sorafenib monotherapy, in combination with chemotherapy or EGFR-TKI to investigate the preferred therapy strategy. Results: Results reported from 6 RCTs involving 2, 748 patients were included in the analysis. Compared to sorafenib-free group, SBT was not associated with higher DCR (RR 1.31 (0.96- 1.79), p=0.09), PFS (HR 0.82 (0.66-1.02), p=0.07) and OS (HR 1.01 (0.92-1.12), p=0.77). In terms of subgroup results, sorafenib monotherapy was associated with significant superior DCR and longer PFS, but failed to show advantage with regard to OS. Grade 3 or greater sorafenib-related adverse events included fatigue, hypertension, diarrhea, oral mucositis, rash and HFSR. Conclusions: SBT was revealed to yield no improvement in DCR, PFS and OS. However, sorafenib as monotherapy showed some activity in NSCLC. Further evaluation may be considered in subsets of patients who may benefit from this treatment. Sorafenib combined inhibition therapy should be limited unless the choice of platinum-doublet regimen, administration sequence or identification of predictive biomarkers are considered to receive better anti-tumor activity and prevention of resistance mechanisms.