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https://www.readbyqxmd.com/read/28100269/a-spleen-tyrosine-kinase-inhibitor-attenuates-the-proliferation-and-migration-of-vascular-smooth-muscle-cells
#1
Hyang-Hee Seo, Sang Woo Kim, Chang Youn Lee, Kyu Hee Lim, Jiyun Lee, Eunhyun Choi, Soyeon Lim, Seahyoung Lee, Ki-Chul Hwang
BACKGROUND: Pathologic vascular smooth muscle cell (VSMC) proliferation and migration after vascular injury promotes the development of occlusive vascular disease. Therefore, an effective chemical agent to suppress aberrant proliferation and migration of VSMCs can be a potential therapeutic modality for occlusive vascular disease such as atherosclerosis and restenosis. To find an anti-proliferative chemical agent for VSMCs, we screened an in-house small molecule library, and the selected small molecule was further validated for its anti-proliferative effect on VSMCs using multiple approaches, such as cell proliferation assays, wound healing assays, transwell migration assays, and ex vivo aortic ring assay...
January 18, 2017: Biological Research
https://www.readbyqxmd.com/read/28076854/open-angle-glaucoma-drug-development-pipeline-during-the-last-20-years-1995-2015
#2
André Vicente, Sylvie Prud'homme, Joana Ferreira, Luís Abegão Pinto, Ingeborg Stalmans
OBJECTIVES: To analyse drug development for open-angle glaucoma during the last 20 years. METHODS: Research was performed by referring to clinical trials registered at the International Clinical Trials Registry Platform (ICTRP). A search for the condition "open-angle glaucoma" with the intervention "drug" was performed. We included trials registered from 01/01/1995 to 01/01/2015, only involving studies in phases 1, 2, and 3. Only studies resorting to novel treatment strategies (either novel drugs or yet-untested fixed associations of approved medication) were considered...
January 12, 2017: Ophthalmic Research
https://www.readbyqxmd.com/read/28069903/improvement-of-in-vitro-produced-bovine-embryo-treated-with-coa-a-under-heat-stressed-condition
#3
Imran Khan, Kyeong-Lim Lee, Lianguang Xu, Ayman Mesalam, Mmr Chowdhury, Myeong-Don Joo, Ihsan-Ul- Haq, Bushra Mirza, Il-Keun Kong
Heat stress has large effects on reproduction including conception rate in cattle. In this study, we examined the effects of coagulansin-A (coa-A), a steroidal lactone, on acquired thermo tolerance during in vitro production of bovine embryos. Oocytes were incubated in in vitro maturation (IVM) media with or without coa-A at two different temperatures, 40.5 °C and 42 °C, for 20 h. The treatment of coa-A significantly improved blastocyst development only at 40.5 °C (P < 0.05). Interestingly, immunofluorescence analysis demonstrated that coa-A induced heat shock protein 70 (HSP70) and phosphatidylinositol-3-kinase (PI3K), but significantly attenuated nuclear factor kappa B (NF-kB) and cyclooxygenase-2 (COX2)...
January 9, 2017: Reproduction: the Official Journal of the Society for the Study of Fertility
https://www.readbyqxmd.com/read/28069000/long-non-coding-rna-tug1-is-involved-in-cell-growth-and-chemoresistance-of-small-cell-lung-cancer-by-regulating-limk2b-via-ezh2
#4
Yuchun Niu, Feng Ma, Weimei Huang, Shun Fang, Man Li, Ting Wei, Linlang Guo
BACKGROUND: Taurine upregulated gene1 (TUG1) as a 7.1-kb lncRNA, has been shown to play an oncogenic role in various cancers. However, the biological functions of lncRNA TUG1 in small cell lung cancer (SCLC) remain unknown. The aim of this study is to explore the roles of TUG1 in cell growth and chemoresistance of SCLC and its possible molecular mechanism. METHODS: The expression of TUG1 in thirty-three cases of SCLC tissues and SCLC cell line were examined by quantitative RT-PCR (qRT-PCR)...
January 9, 2017: Molecular Cancer
https://www.readbyqxmd.com/read/28053047/structural-analysis-of-pathogenic-mutations-in-the-dyrk1a-gene-in-patients-with-developmental-disorders
#5
Jochem M G Evers, Roman A Laskowski, Marta Bertolli, Jill Clayton-Smith, Charu Deshpande, Jacqueline Eason, Frances Elmslie, Frances Flinter, Carol Gardiner, Jane A Hurst, Helen Kingston, Usha Kini, Anne K Lampe, Derek Lim, Alison Male, Swati Naik, Michael J Parker, Sue Price, Leema Robert, Ajoy Sarkar, Volker Straub, Geoff Woods, Janet M Thornton, Caroline F Wright
Haploinsufficiency in DYRK1A is associated with a recognizable developmental syndrome, though the mechanism of action of pathogenic missense mutations is currently unclear. Here we present 19 de novo mutations in this gene, including five missense mutations, identified by the Deciphering Developmental Disorder study. Protein structural analysis reveals that the missense mutations are either close to the ATP or peptide binding-sites within the kinase domain, or are important for protein stability, suggesting they lead to a loss of the protein's function mechanism...
January 4, 2017: Human Molecular Genetics
https://www.readbyqxmd.com/read/28045574/autophagy-and-krt8-keratin-8-protect-degeneration-of-retinal-pigment-epithelium-under-oxidative-stress
#6
Ahruem Baek, Soojin Yoon, Jean Kim, Yu Mi Baek, Hanna Park, Daehan Lim, Hyewon Chung, Dong-Eun Kim
Contribution of autophagy and regulation of related proteins to the degeneration of retinal pigment epithelium (RPE) in age-related macular degeneration (AMD) remain unknown. We report that upregulation of KRT8 (keratin 8) as well as its phosphorylation are accompanied with autophagy and attenuated with the inhibition of autophagy in RPE cells under oxidative stress. KRT8 appears to have a dual role in RPE pathophysiology. While increased expression of KRT8 following autophagy provides a cytoprotective role in RPE, phosphorylation of KRT8 induces pathologic epithelial-mesenchymal transition (EMT) of RPE cells under oxidative stress, which is mediated by MAPK1/ERK2 (mitogen-activated protein kinase 1) and MAPK3/ERK1...
January 3, 2017: Autophagy
https://www.readbyqxmd.com/read/28035396/anticancer-effect-of-luteolin-is-mediated-by-downregulation-of-tam-receptor-tyrosine-kinases-but-not-interleukin-8-in-non-small-cell-lung-cancer-cells
#7
Youn Ju Lee, Taeho Lim, Min Su Han, Sun-Hwa Lee, Suk-Hwan Baek, Hong-Yan Nan, Chuhee Lee
TAM receptor tyrosine kinases (RTKs), Tyro3, Axl and MerTK, transduce diverse signals responsible for cell survival, growth, proliferation and anti-apoptosis. In the present study, we demonstrated the effect of luteolin, a flavonoid with antioxidant, anti-inflammatory and anticancer activities, on the expression and activation of TAM RTKs and the association with its cytotoxicity in non-small cell lung cancer (NSCLC) cells. We observed the cytotoxic effect of luteolin in parental A549 and H460 cells as well as in cisplatin-resistant A549/CisR and H460/CisR cells...
February 2017: Oncology Reports
https://www.readbyqxmd.com/read/28028053/mrtf-potentiates-tead-yap-transcriptional-activity-causing-metastasis
#8
Tackhoon Kim, Daehee Hwang, Dahye Lee, Jeong-Hwan Kim, Seon-Young Kim, Dae-Sik Lim
Yes-associated protein (YAP) and myocardin-related transcription factor (MRTF) play similar roles and exhibit significant crosstalk in directing transcriptional responses to chemical and physical extracellular cues. The mechanism underlying this crosstalk, however, remains unclear. Here, we show MRTF family proteins bind YAP via a conserved PPXY motif that interacts with the YAP WW domain. This interaction allows MRTF to recruit NcoA3 to the TEAD-YAP transcriptional complex and potentiate its transcriptional activity...
December 27, 2016: EMBO Journal
https://www.readbyqxmd.com/read/28028034/rapamycin-insensitive-companion-of-mtor-rictor-amplification-defines-a-subset-of-advanced-gastric-cancer-and-is-sensitive-to-azd2014-mediated-mtorc1-2-inhibition
#9
S T Kim, S Y Kim, S J Klempner, J Yoon, N Kim, S Ahn, H Bang, K-M Kim, W Park, S H Park, J O Park, Y S Park, H Y Lim, S H Lee, K Park, W K Kang, J Lee
PURPOSE: Targeting oncogenic genomic aberrations is an established therapeutic strategy in multiple tumor types. Molecular classification has uncovered a number of novel targets, and rapamycin-insensitive companion of mTOR (RICTOR) amplification has been identified in lung cancer. Further investigation assessing the therapeutic potential of RICTOR amplification as a novel target across advanced cancers is needed. PATIENTS AND METHODS: Tumor samples from 640 patients with metastatic solid tumors, primarily gastrointestinal and lung cancers were prospectively subjected to a next-generation sequencing (NGS) assay to identify molecular targets...
December 27, 2016: Annals of Oncology: Official Journal of the European Society for Medical Oncology
https://www.readbyqxmd.com/read/28013532/aurora-kinase-a-is-a-prognostic-marker-in-colorectal-adenocarcinoma
#10
Hyun Min Koh, Bo Geun Jang, Chang Lim Hyun, Young Sill Kim, Jin Won Hyun, Weon Young Chang, Young Hee Maeng
Background: Aurora kinase A (AURKA), or STK15/BTAK, is a member of the serine/threonine kinase family and plays important roles in mitosis and chromosome stability. This study investigated the clinical significance of AURKA expression in colorectal cancer patients in Korea. Materials and Methods: AURKA protein expression was evaluated by immunohistochemistry in 151 patients with colorectal adenocarcinoma using tissue microarray blocks. We analyzed the relationship between clinicopathological characteristics and AURKA expression...
December 25, 2016: Journal of Pathology and Translational Medicine
https://www.readbyqxmd.com/read/28008317/chrysophanic-acid-suppresses-adipogenesis-and-induces-thermogenesis-by-activating-amp-activated-protein-kinase-alpha-in-vivo-and-in-vitro
#11
Hara Lim, Jinbong Park, Hye-Lin Kim, JongWook Kang, Mi-Young Jeong, Dong-Hyun Youn, Yunu Jung, Yong-Il Kim, Hyun-Ju Kim, Kwang Seok Ahn, Su-Jin Kim, Seong-Kyu Choe, Seung-Heon Hong, Jae-Young Um
Chrysophanic acid (CA) is a member of the anthraquinone family abundant in rhubarb, a widely used herb for obesity treatment in Traditional Korean Medicine. Though several studies have indicated numerous features of CA, no study has yet reported the effect of CA on obesity. In this study, we tried to identify the anti-obesity effects of CA. By using 3T3-L1 adipocytes and primary cultured brown adipocytes as in vitro models, high-fat diet (HFD)-induced obese mice, and zebrafish as in vivo models, we determined the anti-obesity effects of CA...
2016: Frontiers in Pharmacology
https://www.readbyqxmd.com/read/28003232/anaplastic-large-cell-lymphoma-masquerading-as-osteomyelitis-of-the-shoulder-an-uncommon-presentation
#12
Matthew Tuck, Jane Lim, Jose Lucar, Debra Benator
The presentation of anaplastic lymphoma kinase protein (ALK)-negative anaplastic large cell lymphoma (ALCL) in bone is rare. We describe a patient with ALK-negative ALCL presenting with clinical and radiographic findings suggesting osteomyelitis 6 months after left rotator cuff repair surgery. A review of the characteristics of ALK-negative ALCL with primary bone involvement is presented. ALCL should be considered in patients not responding to therapies for osteomyelitis.
December 21, 2016: BMJ Case Reports
https://www.readbyqxmd.com/read/27997117/engineering-high-affinity-protein-protein-interactions-using-a-high-throughput-microcapillary-array-platform
#13
Sungwon Lim, Bob Chen, Mihalis S Kariolis, Ivan K Dimov, Thomas M Baer, Jennifer R Cochran
Affinity maturation of protein-protein interactions requires iterative rounds of protein library generation and high-throughput screening to identify variants that bind with increased affinity to a target of interest. We recently developed a multipurpose protein engineering platform, termed μSCALE (Microcapillary Single Cell Analysis and Laser Extraction). This technology enables high-throughput screening of libraries of millions of cell-expressing protein variants based on their binding properties or functional activity...
December 20, 2016: ACS Chemical Biology
https://www.readbyqxmd.com/read/27994054/trp-asp-wd-repeat-domain-1-is-essential-for-mouse-peri-implantation-development-and-regulates-cofilin-phosphorylation
#14
Yi Xiao, Haixia Ma, Ping Wan, Dandan Qin, Xiaoxiao Wang, Xiaoxin Zhang, Yunlong Xiang, Wenbo Liu, Jiong Chen, Zhaohong Yi, Lei Li
Trp-Asp (WD) repeat domain 1 (WDR1) is a highly conserved actin binding protein across all eukaryotes and is involved in numerous actin-based processes by accelerating Cofilin severing actin filament. However, the function and the mechanism of WDR1 in mammalian early development are still largely unclear. We now report that WDR1 is essential for mouse peri-implantation development and regulates Cofilin phosphorylation in mouse cells. The disruption of maternal WDR1 does not obviously affect ovulation and female fertility...
December 19, 2016: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/27986089/the-anti-inflammatory-role-of-extranuclear-apurinic-apyrimidinic-endonuclease-1-redox-effector-factor-1-in-reactive-astrocytes
#15
Hyunjung Baek, Chae Seong Lim, Hee Sun Byun, Hyun Sil Cho, Yu Ran Lee, Yong Sup Shin, Hyun-Woo Kim, Byeong Hwa Jeon, Dong Woon Kim, Jinpyo Hong, Gang Min Hur, Jin Bong Park
Apurinic/apyrimidinic endonuclease 1 (APE1), a ubiquitous multipurpose protein, is also known as redox effector factor-1 (Ref-1). It is involved in DNA repair and redox signaling and, in turn, oxidative stress-induced neurodegeneration. Although previous studies have demonstrated that APE1/Ref-1 functions as a negative regulator of inflammatory response via several mechanisms in neuronal cells, little is known about the roles of APE1/Ref-1 in glial cells. In this study, we found that cytoplasmic APE1/Ref-1 expression was upregulated in reactive astrocytes of the kainic acid- or lipopolysaccharide (LPS)-injected hippocampus...
December 16, 2016: Molecular Brain
https://www.readbyqxmd.com/read/27965942/attenuation-of-rankl-induced-osteoclast-formation-via-p38-mediated-nfatc1-signaling-pathways-by-extract-of-euphorbia-lathyris-l
#16
Ju-Hee Kang, Hyojung Lim, Ji-Eun Jeong, Mijung Yim
BACKGROUND: Osteoclasts are the only cell type capable of breaking down bone matrix, and its excessive activation is responsible for the development of bone-destructive diseases. Euphorbia lathyris L. (ELL) is an herbal plant that belongs to the Euphorbiaceae family. This study investigated the effects of the methanol extract of the aerial part of ELL on receptor activator of nuclear factor-kappa B ligand (RANKL)-induced osteoclast formation and signaling pathways. METHODS: Osteoclasts were formed by co-culturing mouse bone marrow with osteoblasts or by culturing mouse bone marrow-derived macrophages (BMMs) with macrophage colony-stimulating factor (M-CSF) and RANKL...
November 2016: Journal of Bone Metabolism
https://www.readbyqxmd.com/read/27956716/therapeutic-potential-of-medicinal-plants-and-their-constituents-on-lung-inflammatory-disorders
#17
REVIEW
Hyun Pyo Kim, Hyun Lim, Yong Soo Kwon
Acute bronchitis and chronic obstructive pulmonary diseases (COPD) are essentially lung inflammatory disorders. Various plant extracts and their constituents showed therapeutic effects on several animal models of lung inflammation. These include coumarins, flavonoids, phenolics, iridoids, monoterpenes, diterpenes and triterpenoids. Some of them exerted inhibitory action mainly by inhibiting the mitogen-activated protein kinase pathway and nuclear transcription factor-κB activation. Especially, many flavonoid derivatives distinctly showed effectiveness on lung inflammation...
December 16, 2016: Biomolecules & Therapeutics
https://www.readbyqxmd.com/read/27955743/protective-effects-of-a-polymethoxy-flavonoids-rich-citrus-aurantium-peel-extract-on-liver-fibrosis-induced-by-bile-duct-ligation-in-mice
#18
Seol-Wa Lim, Dong-Ryung Lee, Bong-Keun Choi, Hong-Suk Kim, Seung Hwan Yang, Joo-Won Suh, Kyung Soo Kim
OBJECTIVE: To evaluate the possible protective effect of Citrus aurantium peel extract (CAE) against apoptosis in cholestatic liver fibrosis induced by bile duct ligation in mice. METHODS: Male ICR mice were divided to 5 groups: 1) Control group (Sham-operated mice), 2) Cholestatic liver injury group induced by bile duct ligation (BDL), 3) BDL mice treated with silymarin (200 mg/kg) for 4 weeks, 4) BDL mice treated with 50 mg/kg CAE for 4 weeks, 5) BDL mice treated with 200 mg/kg CAE for 4 weeks...
December 2016: Asian Pacific Journal of Tropical Medicine
https://www.readbyqxmd.com/read/27939697/genetic-and-functional-analysis-of-tbk1-variants-in-korean-patients-with-sporadic-amyotrophic-lateral-sclerosis
#19
Young-Eun Kim, Ki-Wook Oh, Min-Young Noh, Minyeop Nahm, Jinseok Park, Su Min Lim, Ja-Hyun Jang, Eun-Hae Cho, Chang-Seok Ki, Seungbok Lee, Seung Hyun Kim
The TANK-binding kinase 1 (TBK1) gene has recently been identified as a novel causative gene of amyotrophic lateral sclerosis (ALS). This study aims to determine the frequency and spectrum of TBK1 variants and their functional implications in Korean patients with sporadic ALS (sALS). TBK1 sequences were analyzed in 129 consecutive patients with sALS using either multigene panel or exome sequencing. One frameshift (c.1414delA) and 3 missense variants of uncertain significance in TBK1 were found in 4 patients each...
February 2017: Neurobiology of Aging
https://www.readbyqxmd.com/read/27938392/ulk1-mediated-phosphorylation-of-atg14-promotes-autophagy-and-is-impaired-in-huntington-s-disease-models
#20
Mitchell S Wold, Junghyun Lim, Véronik Lachance, Zhiqiang Deng, Zhenyu Yue
BACKGROUND: Autophagy is a bulk degradation pathway for long-lived proteins, protein aggregates, and damaged organelles. ULK1 protein kinase and Vps34 lipid kinase are two key autophagy regulators that are critical for autophagosome biogenesis. However, it isn't fully understood how ULK1 regulates Vps34, especially in the context of disease. Polyglutamine expansion in huntingtin (Htt) causes aberrant accumulation of the aggregated protein and disrupts various cellular pathways including autophagy, a lysosomal degradation pathway, underlying the pathogenesis of Huntington's disease (HD)...
December 9, 2016: Molecular Neurodegeneration
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