The transcription factors signal transducer and activator of transcription 5A (STAT5A) and STAT5B negatively regulate cell proliferation through the activation of cyclin‐dependent kinase inhibitor 2b (<i>Cdkn2b</i>) and <i>Cdkn1a</i> expression

Yu, Ji Hoon,Zhu, Bing‐,Mei,Wickre, Mark,Riedlinger, Gregory,Chen, Weiping,Hosui, Atsushi,Robinson, Gertraud W.,Hennighausen, Lothar Wiley Subscription Services, Inc., A Wiley Company 2010 Hepatology Vol.52 No.5

<P><B>Abstract</B></P><P>Although the cytokine‐inducible transcription factor signal transducer and activator of transcription 5 (STAT5) promotes proliferation of a wide range of cell types, there are cell‐specific and context‐specific cases in which loss of STAT5 results in enhanced cell proliferation. Here, we report that loss of STAT5 from mouse embryonic fibroblasts (MEFs) leads to enhanced proliferation, which was linked to reduced levels of the cell cycle inhibitors p15<SUP>INK4B</SUP> and p21<SUP>CIP1</SUP>. We further demonstrate that growth hormone, through the transcription factor STAT5, enhances expression of the <I>Cdkn2b</I> (cyclin‐dependent kinase inhibitor 2B) gene and that STAT5A binds to interferon‐gamma–activated sequence sites within the promoter. We recently demonstrated that ablation of STAT5 from liver results in hepatocellular carcinoma upon CCl<SUB>4</SUB> treatment. We now establish that STAT5, like in MEFs, activates expression of the <I>Cdkn2b</I> gene in liver tissue. Loss of STAT5 led to diminished p15<SUP>INK4B</SUP> and increased hepatocyte proliferation. <I>Conclusion:</I> This study for the first time demonstrates that cytokines, through STAT5, induce the expression of a key cell cycle inhibitor. These experiments therefore shed mechanistic light on the context‐specific role of STAT5 as tumor suppressor. (HEPATOLOGY 2010;52:1808‐1818)</P>

Asymptotic ruin probabilities for proportional investment under interest force with dominatedly-varying-tailed claims

Yu Chen,,Yin Huang,Weiping Zhang 한국통계학회 2012 Journal of the Korean Statistical Society Vol.41 No.1

We study the asymptotic behavior of the ruin probabilities in the renewal risk model, in which the insurance company is allowed to invest a constant fraction of its wealth in a stock market which is described by a geometric Brownian motion and the remaining wealth in a bond with nonnegative interest force. We give the expression of the wealth process by the Itô formula, and finally we derive the asymptotic behavior of finite-time and infinite-time ruin probabilities in the presence of pairwise quasi-asymptotically independent claims with dominant varying tails for this model. In the particular case of compound Poisson model, explicit asymptotic expressions for the ruin probabilities are given with tails of regular variation, where the relation of the infinite-time ruin probability is the same as Gaier and Grandits (2004). For this case, we give some numerical results to assess the qualities of the asymptotic relations.

Inhibition of miRNA-222-3p Relieves Staphylococcal Enterotoxin B-Induced Liver Inflammatory Injury by Upregulating Suppressors of Cytokine Signaling 1

Peng Zhang,Jingda Yu,Yifang Gui,Cui Sun,Weiping Han 연세대학교의과대학 2019 Yonsei medical journal Vol.60 No.11

Purpose: Staphylococcal enterotoxin B (SEB) has been well-documented to induce liver injury. miRNA-222-3p (miR-222-3p) wasimplicated in SEB-induced lung injury and several liver injuries. This study aimed to explore the role of miR-222-3p in SEB-inducedliver injury. Materials and Methods: Expression of miR-222-3p and suppressors of cytokine signaling 1 (SOCS1) was detected using real-timequantitative PCR and western blot. Liver injury was determined by levels of aspartate aminotransferase (AST), alanine aminotransferase(ALT), and inflammatory cytokines, numbers of infiltrating mononuclear cells using AST/ALT assay kit, enzyme-linked immunosorbentassay (ELISA), and hematoxylin-eosin staining, respectively. Target binding between miR-222-3p and SOCS1 waspredicted on targetScan software, and confirmed by luciferase reporter assay. Results: SEB induced liver injury in D-galactosamine (D-gal)-sensitized mice, as demonstrated by increased serum levels of ASTand ALT, elevated release of interferon-gamma (INF-γ), tumor necrosis factor-alpha (TNF-α), interleukin-6 (IL-6), and IL-2, andpromoted infiltrating immune cells into liver. Expression of miR-222-3p was dramatically upregulated, and SOCS1 was downregulatedin SEB-induced liver injury both in mice and splenocytes. Moreover, miR-222-3p knockout (KO) mice exhibited alleviatedliver injury accompanied with SOCS1 upregulation. Besides, splenocytes under SEB challenge released less INF-γ, TNF-α, IL-6,and IL-2 during miR-222-3p knockdown. Mechanically, SOCS1 was targeted and downregulated by miR-222-3p. Upregulation ofSOCS1 attenuated INF-γ, TNF-α, IL-6, and IL-2 release in SEB-induced splenocytes; downregulation of SOCS1 could block thesuppressive role of miR-222-3p knockdown in SEB-induced splenocytes. Conclusion: Inhibition of miR-222-3p relieves SEB-induced liver inflammatory injury by upregulating SOCS1, thereby providingthe first evidence of miR-222-3p in SEB-induced liver injury.

Efficient Mean-Shift Tracking Using an Improved Weighted Histogram Scheme

( Dejun Wang ),( Kai Chen ),( Weiping Sun ),( Shengsheng Yu ),( Hanbing Wang ) 한국인터넷정보학회 2014 KSII Transactions on Internet and Information Syst Vol.8 No.6

An improved Mean-Shift (MS) tracker called joint CB-LBWH, which uses a combined weighted-histogram scheme of CBWH (Corrected Background-Weighted Histogram) and LBWH (likelihood-based Background-Weighted Histogram), is presented. Joint CB-LBWH is based on the notion that target representation employs both feature saliency and confidence to form a compound weighted histogram criterion. As the more prominent and confident features mean more significant for tracking the target, the tuned histogram by joint CB-LBWH can reduce the interference of background in target localization effectively. Comparative experimental results show that the proposed joint CB-LBWH scheme can significantly improve the efficiency and robustness of MS tracker when heavy occlusions and complex scenes exist.

Genome-wide analyses reveal the extent of opportunistic STAT5 binding that does not yield transcriptional activation of neighboring genes

Zhu, Bing-Mei,Kang, Keunsoo,Yu, Ji Hoon,Chen, Weiping,Smith, Harold E.,Lee, Daeyoup,Sun, Hong-Wei,Wei, Lai,Hennighausen, Lothar Oxford University Press 2012 Nucleic acids research Vol.40 No.10

<P>Signal Transducers and Activators of Transcription (STAT) 5A/B regulate cytokine-inducible genes upon binding to GAS motifs. It is not known what percentage of genes with GAS motifs bind to and are regulated by STAT5. Moreover, it is not clear whether genome-wide STAT5 binding is modulated by its concentration. To clarify these issues we established genome-wide STAT5 binding upon growth hormone (GH) stimulation of wild-type (WT) mouse embryonic fibroblasts (MEFs) and MEFs overexpressing STAT5A more than 20-fold. Upon GH stimulation, 23 827 and 111 939 STAT5A binding sites were detected in WT and STAT5A overexpressing MEFs, respectively. 13 278 and 71 561 peaks contained at least one GAS motif. 1586 and 8613 binding sites were located within 2.5 kb of promoter sequences, respectively. Stringent filtering revealed 78 genes in which the promoter/upstream region (−10 kb to +0.5 kb) was recognized by STAT5 both in WT and STAT5 overexpressing MEFs and 347 genes that bound STAT5 only in overexpressing cells. Genome-wide expression analyses identified that the majority of STAT5-bound genes was not under GH control. Up to 40% of STAT5-bound genes were not expressed. For the first time we demonstrate the magnitude of opportunistic genomic STAT5 binding that does not translate into transcriptional activation of neighboring genes.</P>

fects of Dietary Soy Intake on Maternal Thyroid Functions and Serum Anti-Thyroperoxidase Antibody Level During Early Pregnancy

Jing Li,Xiaochun Teng,Weiwei Wang,Yanyan Chen,Xiaohui Yu,Shen Wang,Jianxin Li,Lin Zhu,Chenyan Li,Chenling Fan,Hong Wang,Hongmei Zhang,Weiping Teng,Zhongyan Shan 한국식품영양과학회 2011 Journal of medicinal food Vol.14 No.5

Soy and its isoflavones have been suggested to suppress thyroperoxidase (TPO), induce goiter, inhibit deiodinase, and modulate immune functions. This study initially investigated the effects of dietary soy consumption on maternal thyroid functions and anti-TPO antibody (TPOAb) production during early pregnancy. Data were collected through questionnaire from 505 women enrolled during early pregnancy by random sampling in Shenyang, China. Based on soy intake frequency, the subjects were divided into three groups (frequent [three or more times per week], conventional [more than twice per month but less than three times per week], and occasional [two or fewer times per month]). Serum thyrotropin (TSH), free thyroxine (FT_4), and TPOAb were measured by chemiluminescence immunoassay. Additionally, the concentrations of two primary isoflavones (daidzein and genistein) and creatinine were assessed in the spot urine samples from representative subjects (about 20%) randomly selected from the three groups. The percentages of frequent, conventional, and occasional consumers were 18.6%, 62.6%, and 18.8%, respectively. No difference was found in age, medical records, family history of thyroid diseases, serum FT_4, TSH, and TPOAb levels, TPOAb-positive percentages, or prevalence of thyroid dysfunctions among the groups. Both urinary daidzein and genistein levels were significantly higher in the frequent consumers compared with the other two groups. No correlations were found between urinary isoflavone levels and serum FT_4 or TSH. Urinary isoflavone levels were not significantly different between TPOAb-positive and -negative women among the randomly selected representative subjects. On the whole, our findings suggest dietary soy consumption during early pregnancy is not associated with the development of thyroid dysfunction or autoimmunity.

Impeller inlet geometry effect on performance improvement for centrifugal pumps

Xianwu Luo,Yao Zhang,Junqi Peng,Hongyuan Xu,Weiping Yu 대한기계학회 2008 JOURNAL OF MECHANICAL SCIENCE AND TECHNOLOGY Vol.22 No.10

This research treats the effect of impeller inlet geometry on performance improvement for a boiler feed pump, who is a centrifugal pump having specific speed of 183 m⋅m3min-1⋅min-1 and close type impeller with exit diameter of 450 mm. The hydraulic performance and cavitation performance of the pump have been tested experimentally. In order to improve the pump, five impellers have been considered by extending the blade leading edge or applying much larger blade angle at impeller inlet compared with the original impeller. The 3-D turbulent flow inside those pumps has been analyzed basing on RNG k-ε turbulence model and VOF cavitation model. It is noted that the numerical results are fairly good compared with the experiments. Based on the experimental test and numerical simulation, the following conclusions can be drawn: (1) Impeller inlet geometry has important influence on performance improvement in the case of centrifugal pump. Favorite effects on performance improvement have been achieved by both extending the blade leading edge and applying much larger blade angle at impeller inlet; (2) It is suspected that the extended leading edge have favorite effect for improving hydraulic performance, and the much larger blade angle at impeller inlet have favorite effect for improving cavitation performance for the test pump; (3) Uniform flow upstream of impeller inlet is helpful for improving cavitation performance of the pump.

Cross‐sectional survey of biosimilar insulin utilization in Asia: The Joint Asia Diabetes Evaluation Program

Gani, Linsey,Lau, Eric,Luk, Andrea,Sobrepena, Leorino,Tran, Quang Khanh,Kesavadev, Jothydev,Jia, Weiping,Yu, Weinan,Tsang, Chiu Chi,Mukhopadhyay, Monojitketan,Jha, Sujeet,Sheu, Wayne,Ho, Yoon Kun,Nguy John Wiley and Sons Inc. 2018 Journal of diabetes investigation Vol.9 No.6

<P><B>Abstract</B></P><P><B>Aims/Introduction</B></P><P>Biosimilar insulin can reduce treatment costs, although the extent of its use is largely unknown. We examined biosimilar insulin use and its associations with the quality of glycemic control using the Joint Asia Diabetes Evaluation register.</P><P><B>Materials and Methods</B></P><P>We carried out a cross‐sectional analysis in 81,531 patients with type 1 and type 2 diabetes enrolled into the Joint Asia Diabetes Evaluation Program from 2007 to 2014. All insulin related terms are extracted from the Joint Asia Diabetes Evaluation portal, and compared clinical profiles between biosimilar and originator insulin users. Multivariate analysis was performed to assess the association of biosimilar insulin compared with originator insulin with dosage, glycated hemoglobin and hypoglycemia events.</P><P><B>Results</B></P><P>Amongst 81,531 patients, 20.5% (<I>n</I> = 16,738) were insulin‐treated. In four countries with high use of biosimilar insulin, 4.7% (<I>n</I> = 719) of insulin users (<I>n</I> = 10,197) were treated with biosimilar insulin (India <I>n</I> = 507, 70.3%; the Philippines <I>n</I> = 90, 12.5%; China <I>n</I> = 62, 8.6%; Vietnam <I>n</I> = 60, 8.3%). Biosimilar insulin users were younger and had higher body mass index, glycated hemoglobin, insulin dosage and more frequent hypoglycemia than originator insulin users. These associations were non‐significant after adjustment for confounders. Only age, college education, diabetes education, lipid control, physical activity and history of cardiovascular complications were independently associated with these quality measures.</P><P><B>Conclusions</B></P><P>Biosimilar insulin use is not uncommon in Asia. Data exclusion due to incomplete capturing of brand names suggests possibly higher use. The multiple determinants of the quality of glycemic control call for establishment of prospective cohorts and diabetes registers to monitor the safety and efficacy of different brands of biosimilar insulin and their impacts on clinical outcomes.</P>

Chinese Society of Allergy Guidelines for Diagnosis and Treatment of Allergic Rhinitis

Lei Cheng,Jianjun Chen,Qingling Fu,Shaoheng He,Huabin Li,Zheng Liu,Guolin Tan,Zezhang Tao,Dehui Wang,Weiping Wen,Rui Xu,Yu Xu,Qintai Yang,Chonghua Zhang,Gehua Zhang,Ruxin Zhang,Yuan Zhang,Bing Zhou,Do 대한천식알레르기학회 2018 Allergy, Asthma & Immunology Research Vol.10 No.4

Allergic rhinitis (AR) is a global health problem that causes major illnesses and disabilities worldwide. Epidemiologic studies have demonstrated that the prevalence of AR has increased progressively over the last few decades in more developed countries and currently affects up to 40% of the population worldwide. Likewise, a rising trend of AR has also been observed over the last 2-3 decades in developing countries including China, with the prevalence of AR varying widely in these countries. A survey of self-reported AR over a 6-year period in the general Chinese adult population reported that the standardized prevalence of adult AR increased from 11.1% in 2005 to 17.6% in 2011. An increasing number of original articles and imporclinical trials on the epidemiology, pathophysiologic mechanisms, diagnosis, management and comorbidities of AR in Chinese subjects have been published in international peer-reviewed journals over the past 2 decades, and substantially added to our understanding of this disease as a global problem. Although guidelines for the diagnosis and treatment of AR in Chinese subjects have also been published, they have not been translated into English and therefore not generally accessible for reference to non-Chinese speaking international medical communities. Moreover, methods for the diagnosis and treatment of AR in China have not been standardized entirely and some patients are still treated according to regional preferences. Thus, the present guidelines have been developed by the Chinese Society of Allergy to be accessible to both national and international medical communities involved in the management of AR patients. These guidelines have been prepared in line with existing international guidelines to provide evidence-based recommendations for the diagnosis and management of AR in China.

The Correlation between Thyrotropin and Dyslipidemia in a Population-based Study

Li Lu,Beibei Wang,Zhongyan Shan,Fengwei Jiang,Xiaochun Teng,Yanyan Chen,Yaxin Lai,Jiani Wang,Haibo Xue,Sen Wang,Chenyan Li,He Liu,Ningna Li,Jiashu Yu,Liangfeng Shi,Xin Hou,Qian Xing,Xue Bai,Weiping Te 대한의학회 2011 Journal of Korean medical science Vol.26 No.2

This study investigated the relationship between serum thyrotrophin levels and dyslipidemia in subclinical hypothyroid and euthyroid subjects. A total of 110 subjects with subclinical hypothyroidism and 1,240 euthyroid subjects enrolled in this study. Patients with subclinical hypothyroidism had significantly lower high density lipoprotein cholesterol (HDL-C) levels than those who were euthyroid. The lipid profiles were each categorized and mean thyrotrophin levels were higher in subjects in the dyslipidemia subclasses than subjects in the normal subclasses. Thyrotrophin was positively associated with serum triglyceride and negatively associated with serum HDL-C in women. Thyrotrophin was also positively associated with total cholesterol (TC) in the overweight population along with TC and LDL-C in overweight women. In the euthyroid population, thyrotrophin was positively associated with TC in the overweight population. In conclusion, serum thyrotrophin was correlated with dyslipidemia in subclinical hypothyroid and euthyroid subjects; the correlation was independent of insulin sensitivity.