Ectopic Over-expression of Oncogene Pim-2 Induce Malignant Transformation of Nontumorous Human Liver Cell Line L02

Ke Ren,Wentao Duan,Yujun Shi,Bo Li,Zuojin Liu,Jiangping Gong 대한의학회 2010 Journal of Korean medical science Vol.25 No.7

In order to prove that ectopic over-expression of Pim-2 could induce malignant transformation of human liver cell line L02, three groups of cells were set up including human liver cell line L02 (L02), L02 cells transfected with Pim-2 gene (L02/Pim-2) and L02cells transfected with empty-vector (L02/Vector). Pim-2 expression levels were detected. The morphology, proliferation level, apoptosis rate and migration ability of the cells were detected respectively. Then the cells were subcutaneously inoculated into athymic mice and the microstructures of the neoplasm were observed. Compared with the controls, Pim-2expression levels were significantly higher in L02/Pim-2 cells (P<0.05), and their morphology had obvious malignant changes. They also showed a significantly increased proliferation rate (P<0.05) and migration capacity (P<0.05), as well as a significantly decreased apoptosis rate (P<0.05). Only the athymic mice inoculated with L02/Pim-2 cells could generate neoplasm, and the morphology of the neoplasm coincided with that of the hepatoma. The results manifest that ectopic Pim-2 gene could be stably expressed in L02/Pim-2 cells. Both the morphological and biological changes of L02/Pim-2 cells demonstrate the trend of malignant transformation. L02/Pim-2 cells could generate hepatoma in athymic mice. In conclusion, Pim-2 could induce malignant transformation of human liver cell line L02.

Invasive versus Conservative Treatment Approach among Older Adult Patients Admitted with Acute ST-Segment Elevation Myocardial Infarction

Keren-Lee Rozenfeld,Lior Lupu,Ilan Merdler,Samuel Morgan,Shmuel Banai,Yacov Shacham 대한노인병학회 2022 Annals of geriatric medicine and research Vol.26 No.4

Background: Primary percutaneous coronary intervention (PCI) is the preferred treatment strategy for patients with ST-elevation myocardial infarction (STEMI); however, its efficacy remains unclear in very older adult patients with STEMI. Methods: This retrospective single-center observational study included 530 patients aged >75 years admitted to Tel Aviv Sourasky Medical Center with a diagnosis of acute STEMI. Primary PCI was performed for patients with symptoms ≤12 hours in duration, while the other patients were conservatively treated. We evaluated 30-day mortality and complications occurring during hospitalization based on data from patient records. Results: Among the study patients, only 28/530 (5%) were conservatively treated. In-hospital complications, including the use of inotropes or intra-aortic balloon counterpulsation and the need for mechanical ventilation, did not differ significantly between the groups. The only parameter that showed a trend toward significance was the incidence of heart failure during hospitalization (p=0.042). The risk for 30-day mortality was substantially higher in the conservative treatment group than in the invasive treatment group (27% vs. 10%; p = 0.02). Conclusion: Our data suggested that despite concerns regarding the safety of the primary PCI strategy in the older adult STEMI population, this treatment strategy was associated with a survival benefit.

Eradication of Food Deserts through Public Policy : Case of Durham, North Carolina

Keren R. Campbell,Terri Lawson,Dohyeong Kim 위기관리 이론과 실천 2011 Journal of Safety and Crisis Management Vol.1 No.2

Typically in many urban cities and neighborhoods across the U.S., low-wealth citizens in low-income communities have had limited access to healthy foods and food sources and thus their food intake are forced to depend heavily on low-quality food suppliers like convenient stores and fast food restaurants. Notably, such food insecurity concerns are especially prevalent in minority communities. The lack of access to healthy and affordable foods is not a natural and accidental phenomenon but the result of policy decisions made at multiple levels by multiple actors. Although a growing number of scholars and practitioners are involved in this “food desserts” issue, there is still a need of more academic research not just on identifying communities with no or distant grocery stores, but also assessing the impact of the lack of food security on health disparity at the local and community levels. In this paper, we examine how people in communities have been affected by inadequate access to healthy foods using cases from Durham, North Carolina which has been plagued by food deserts. We also examine how this unequal distribution of food access has aggravated health disparity status regarding various health-related outcomes at the individual and community levels. Based on the review of the current policy actions to eradicating food deserts, specifically in the city of Durham, North Carolina, we suggest several public policy recommendations for providing better access to healthier foods while developing stable food environments, particularly thorough a public-private partnership as a more efficient and equitable delivery mechanism of healthy and affordable foods to such underserved communities.

Study on the role of gga-miRNA-200a in regulating cell differentiation and proliferation of chicken breast muscle by targeting Grb2

Keren Jiang,Fengbin Yan,Meng Zhang,Fang Li,Donghua Li,Guirong Sun,Xiaojun Liu,Hong Li,Ruili Han,Ruirui Jiang,Zhuanjian Li,Xiangtao Kang 한국통합생물학회 2017 Animal cells and systems Vol.21 No.6

Growth factor receptor-bound protein 2 (Grb2) have been proved by a lot of studies playing a major role in cell proliferation and cell differentiation. However, the regulation of Grb2 expression by microRNAs (miRNAs) in chicken breast muscle still remains unknown. The expression profile of Grb2 was checked based on our previous RNA sequencing data and the Grb2 relative expression level in breast muscle of aged hens (55-week-old) was validated significantly higher than juvenile hens (20-week-old) using qRT-PCR. miRNAs that interact with Grb2 have been predicted in chicken and the relationship between the potential miRNA and Grb2 was verified using dual luciferase reporter assay in chicken DF1 cells. Dual-luciferase reporter assays results demonstrated that the expression of luciferase reporter gene linked with part sequence of the 3′UTR of chicken Grb2 gene was down-regulated by the overexpression of gga (Gallus Gallus)- miR-200a-3p in the DF1 cells, and the down-regulation behavior was abolished when the ggamiR- 200a-3p binding site in 3′UTR of Grb2 was mutated, indicating that gga-miR-200a can suppress the expression level of its target gene Grb2. Therefore, we concluded that the significantly increased expression level of Grb2 in the breast muscle of aged chicken can (at least partly can) be explained by the decreased expression of miR-200a, which reduced the inhibitory effect on Grb2. Taken together, these findings suggest that gga-miR-200a can suppress the expression level of its target gene Grb2 and might be involved in the cell differentiation and proliferation of chicken breast muscle through binding with the 3’UTR of Grb2.

Effect of Vitamin D Status on Von Willebrand Factor and ADAMTS13 in Diabetic Patients on Chronic Hemodialysis

Keren Cohen-Hagai,Gloria Rashid,Yael Einbinder,Meital Ohana,Sydney Benchetrit,Tali Zitman-Gal 대한진단검사의학회 2017 Annals of Laboratory Medicine Vol.37 No.2

Von Willebrand factor (vWF) is a glycoprotein with a crucial role in the formation of platelet thrombi, and ADAMTS13 is the main enzyme responsible for vWF cleavage. Both are important in the relationship between diabetic nephropathy, hypercoagulability, and cardiovascular disease. This study evaluated a potential relationship between vitamin D (vitD) levels, vWF, ADAMTS13 activity, and inflammation in diabetic patients on chronic hemodialysis (HD). Blood samples from 52 diabetic patients on chronic HD were obtained to determine vitD levels, vWF, and ADAMTS13 activity, and inflammatory markers. HD patients were grouped according to 25-hydroxyvitamin D [25(OH) VitD]<25 nmol/L (n=16) or >25 nmol/L (n=36). vWF antigen and vWF activity were elevated in both groups, with an average of 214.3±82.6% and 175.8±72.6%, respectively. Average ADAMTS13 activity was within the normal range in both groups. Blood samples from the vitD <25 nmol/L group showed a positive correlation between c-reactive protein (CRP) and vWF levels (P=0.023; r=0.564; 95% confidence interval=0.095-0.828), with a negative correlation between HbA1c and 25(OH) VitD (P=0.015; r=-0.337; 95% confidence interval=-0.337-0.19). Diabetic patients on chronic HD had elevated vWF levels and activity with no significant change in ADAMTS13 activity. The correlation between CRP and vWF levels in the 25(OH) VitD<25 nmol/L group suggests inflammatory-related endothelial dysfunction in these patients.

The Ubiquitin E3/E4 Ligase UBE4A Adjusts Protein Ubiquitylation and Accumulation at Sites of DNA Damage, Facilitating Double-Strand Break Repair

Baranes-Bachar, Keren,Levy-Barda, Adva,Oehler, Judith,Reid, Dylan A.,Soria-Bretones, Isabel,Voss, Ty C.,Chung, Dudley,Park, Yoon,Liu, Chao,Yoon, Jong-Bok,Li, Wei,Dellaire, Graham,Misteli, Tom,Huertas, Elsevier 2018 Molecular cell Vol.69 No.5

<P><B>Summary</B></P> <P>Double-strand breaks (DSBs) are critical DNA lesions that robustly activate the elaborate DNA damage response (DDR) network. We identified a critical player in DDR fine-tuning: the E3/E4 ubiquitin ligase UBE4A. UBE4A’s recruitment to sites of DNA damage is dependent on primary E3 ligases in the DDR and promotes enhancement and sustainment of K48- and K63-linked ubiquitin chains at these sites. This step is required for timely recruitment of the RAP80 and BRCA1 proteins and proper organization of RAP80- and BRCA1-associated protein complexes at DSB sites. This pathway is essential for optimal end resection at DSBs, and its abrogation leads to upregulation of the highly mutagenic alternative end-joining repair at the expense of error-free homologous recombination repair. Our data uncover a critical regulatory level in the DSB response and underscore the importance of fine-tuning the complex DDR network for accurate and balanced execution of DSB repair.</P> <P><B>Highlights</B></P> <P> <UL> <LI> The E3/E4 ubiquitin ligase UBE4A is a new player in the DNA damage response </LI> <LI> UBE4A is required for optimal repair of DNA double-strand breaks </LI> <LI> After initial action of E3 ubiquitin ligases, UBE4A modulates ubiquitylation extent </LI> <LI> UBE4A’s activity is required for appropriate balance of repair pathways </LI> </UL> </P> <P><B>Graphical Abstract</B></P> <P>[DISPLAY OMISSION]</P>

Coupling analysis and optimization of commercial vehicles cab comfort with multi-platform integrated calculation

Shuilong He,Keren Chen,Enyong Xu,Mingsong Ye,Yanxue Wang 대한기계학회 2021 JOURNAL OF MECHANICAL SCIENCE AND TECHNOLOGY Vol.35 No.10

This article introduces a rigid-flexible coupling calculation model based on a multi-platform integrated method to analyze and optimize the cab comfort of commercial vehicles. A 12 degree-of-freedom (DOF) vibration model is first derived by Lagrange's equations. Further, a refined cab with flexible body, bushing, and nonlinear damping is constructed and connected with the vibration model to form a novel dynamics model. Next, the coupled suspend parameters on cab vibration are explored with a Latin hypercube method, which concluded that the front suspend is the most significant component for cab comfort. The multi-objective genetic algorithm (MOGA) and multiverse optimizer (MVO) is then applied to obtain the optimal suspend parameters for ideal cab comfort. Finally, the optimization is verified via simulation and experiment, illustrating that the coupling calculation model and multi-platform integrated method can provide an effective approach to excavate the optimal solution for the optimization of high-complexity engineering problems.

Is There a "Trial Effect" on Outcome of Patients with Metastatic Renal Cell Carcinoma Treated with Sunitinib?

Daniel Keizman,Keren Rouvinov,Avishay Sella,Maya Gottfried,Natalie Maimon,Jenny J. Kim,Mario A. Eisenberger,Victoria Sinibaldi,Avivit Peer,Michael A. Carducci,Wilmosh Mermershtain,Raya Leibowitz-amit 대한암학회 2016 Cancer Research and Treatment Vol.48 No.1

Purpose Studies suggested the existence of a ‘trial effect,’ in which for a given treatment, participa- tion in a clinical trial is associated with a better outcome. Sunitinib is a standard treatment for metastatic renal cell carcinoma (mRCC). We aimed to study the effect of clinical trial participation on the outcome of mRCC patients treated with sunitinib, which at present, is poorly defined. Materials and Methods The records of mRCC patients treated with sunitinib between 2004-2013 in 7 centers across 2 countries were reviewed. We compared the response rate (RR), progression free survival (PFS), and overall survival (OS), between clinical trial participants (n=49) and a matched cohort of non-participants (n=49) who received standard therapy. Each clinical trial participant was individually matched with a non-participant by clinicopathologic factors. PFS and OS were determined by Cox regression. Results The groups were matched by age (median, 64), sex (male, 67%), Heng risk (favorable, 25%; intermediate, 59%; poor, 16%), prior nephrectomy (92%), RCC histology (clear cell 86%), pre-treatment neutrophil to lymphocyte ratio (> 3 in 55%, n=27), sunitinib induced hyper- tension (45%), and sunitinib dose reduction/treatment interruption (41%). In clinical trial participants versus non-participants, RR was partial response/stable disease 80% (n=39) versus 74% (n=36), and progressive disease 20% (n=10) versus 26% (n=13) (p=0.63; odds ratio, 1.2). The median PFS was 10 versus 11 months (hazard ratio [HR], 0.96; p=0.84), and the median OS 23 versus 24 months (HR, 0.97; p=0.89). Conclusion In mRCC patients treated with sunitinib, the outcome of clinical trial participants was similar to that of non-participants who received standard therapy.

Provincial Development in China: Lessons from EU Regional Policy Experience

Phillip J. Bryson,Keren Sun 연세대학교 동서문제연구원 2007 Global economic review Vol.36 No.3

This article evaluates and compares regional development in the Chinese provinces and in the regions of the European Union (EU) countries. Development efforts in southern Italy, northeast England and eastern Germany are reviewed along with EU, Community-wide regional development programmes. Equity concerns suggest promotion of regional policy, but the pursuit of maximum national economic growth would avoid it, since it sacrifices some economic growth. The impact of foreign direct investment (FDI) and domestic investments on individual Chinese provinces is compared with their impact in Europe. There is an implicit contrast between public sector regional development programs and more effective private foreign direct investments.

Direct-current triboelectricity generation by a sliding Schottky nanocontact on MoS₂ multilayers

Liu, Jun,Goswami, Ankur,Jiang, Keren,Khan, Faheem,Kim, Seokbeom,McGee, Ryan,Li, Zhi,Hu, Zhiyu,Lee, Jungchul,Thundat, Thomas Nature Publishing Group UK 2018 Nature nanotechnology Vol.13 No.2

<P>The direct conversion of mechanical energy into electricity by nanomaterial-based devices offers potential for green energy harvesting(1-3). A conventional triboelectric nanogenerator converts frictional energy into electricity by producing alternating current (a.c.) triboelectricity. However, this approach is limited by low current density and the need for rectification(2). Here, we show that continuous direct-current (d.c.) with a maximum density of 10(6) A m(-2) can be directly generated by a sliding Schottky nanocontact without the application of an external voltage. We demonstrate this by sliding a conductive-atomic force microscope tip on a thin film of molybdenum disulfide (MoS2). Finite element simulation reveals that the anomalously high current density can be attributed to the non-equilibrium carrier transport phenomenon enhanced by the strong local electrical field (105-106 V m(-2)) at the conductive nanoscale tip(4). We hypothesize that the charge transport may be induced by electronic excitation under friction, and the nanoscale current-voltage spectra analysis indicates that the rectifying Schottky barrier at the tip-sample interface plays a critical role in efficient d.c. energy harvesting. This concept is scalable when combined with microfabricated or contact surface modified electrodes, which makes it promising for efficient d.c. triboelectricity generation.</P>