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https://www.readbyqxmd.com/read/28199362/flowtaxis-of-osteoblast-migration-under-fluid-shear-and-the-effect-of-rhoa-kinase-silencing
#1
Brandon D Riehl, Jeong Soon Lee, Ligyeom Ha, Il Keun Kwon, Jung Yul Lim
Despite the important role of mechanical signals in bone remodeling, relatively little is known about how fluid shear affects osteoblastic cell migration behavior. Here we demonstrated that MC3T3-E1 osteoblast migration could be activated by physiologically-relevant levels of fluid shear in a shear stress-dependent manner. Interestingly, shear-sensitive osteoblast migration behavior was prominent only during the initial period after the onset of the steady flow (for about 30 min), exhibiting shear stress-dependent migration speed, displacement, arrest coefficient, and motility coefficient...
2017: PloS One
https://www.readbyqxmd.com/read/28185954/wip1-directly-dephosphorylates-nlk-and-increases-wnt-activity-during-germ-cell-development
#2
Seung-Ju Cho, Bok-Sik Cha, Ok-Seon Kwon, Jisun Lim, Dong-Myung Shin, Dong Wook Han, Tohru Ishitani, Eek-Hoon Jho, Albert J Fornace, Hyuk-Jin Cha
Mice null for wild-type p53-induced phosphatase 1 (WIP1) display defects in testis development and spermatogenesis, resulting in reduced fertility. However, the molecular mechanism underlying these abnormalities in the testis remains uncharacterized. We report that the phosphatase activity of WIP1 increases Wnt activity through Nemo-like kinase (NLK). WIP1 directly interacted with NLK, which is highly homologous to p38 MAPK, a WIP1 substrate, and dephosphorylated its activation site. The WIP1-mediated inhibition of NLK activity markedly decreased the phosphorylation of lymphoid enhancer-binding factor 1 (LEF1), disrupting its interaction with β-catenin...
February 6, 2017: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/28185804/7-cyclopentyl-5-4-phenoxyphenyl-7h-pyrrolo-2-3-d-pyrimidin-4-ylamine-inhibits-the-proliferation-and-migration-of-vascular-smooth-muscle-cells-by-suppressing-erk-and-akt-pathways
#3
Hyang-Hee Seo, Sang Woo Kim, Chang Youn Lee, Kyu Hee Lim, Jiyun Lee, Soyeon Lim, Seahyoung Lee, Ki-Chul Hwang
Excessive vascular smooth muscle cell (VSMC) proliferation and migration after vascular injury significantly contributes to the development of occlusive vascular disease. Therefore, inhibiting the proliferation and migration of VSMCs is a validated therapeutic modality for occlusive vascular disease such as atherosclerosis and restenosis. In the present study, we screened chemical compounds for their anti-proliferative effects on VSMCs using multiple approaches, such as MTT assays, wound healing assays, and trans-well migration assays...
February 6, 2017: European Journal of Pharmacology
https://www.readbyqxmd.com/read/28167507/parp-inhibitor-upregulates-pd-l1-expression-and-enhances-cancer-associated-immunosuppression
#4
Shiping Jiao, Weiya Xia, Hirohito Yamaguchi, Yongkun Wei, Mei-Kuang Chen, Jung-Mao Hsu, Jennifer L Hsu, Wen-Hsuan Yu, Yi Du, Heng-Huan Lee, Chia-Wei Li, Chao-Kai Chou, Seung-Oe Lim, Shih-Shin Chang, Jennifer K Litton, Banu Arun, Gabriel N Hortobagyi, Mien-Chie Hung
PURPOSE: To explore whether a crosstalk exists between PARP inhibition and PD-L1/ PD-1 immune checkpoint axis, and determine if blockade of PD-L1/ PD-1 potentiates PARP inhibitor (PARPi) in tumor suppression. EXPERIMENTAL DESIGN: Breast cancer cell lines, xenograft tumors and syngeneic tumors treated with PARPi were assessed for PD-L1 expression by immunoblotting, immunohistochemistry and FACS analyses. The phospho-kinase antibody array screen was used to explore the underlying mechanism of PARPi-induced PD-L1 upregulation...
February 6, 2017: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/28162947/fty720-supplementation-partially-improves-erectile-dysfunction-in-rats-with-streptozotocin-induced-type-1-diabetes-through-inhibition-of-endothelial-dysfunction-and-corporal-fibrosis
#5
Kai Cui, Yajun Ruan, Tao Wang, Ke Rao, Zhong Chen, Shaogang Wang, Jihong Liu
INTRODUCTION: Erectile dysfunction (ED) in patients with diabetes mellitus (DM) seriously affects their quality of life. However, these patients show a poor effect rate for oral phosphodiesterase type 5 inhibitors. Thus, new treatment methods are urgently needed. Fingolimod hydrochloride (FTY720) was approved in 2010 for the treatment of patients with the relapsing-remitting form of multiple sclerosis. AIM: To investigate whether FTY720 supplementation could ameliorate ED induced by DM (DMED)...
February 2, 2017: Journal of Sexual Medicine
https://www.readbyqxmd.com/read/28161468/capillarisin-augments-anti-oxidative-and-anti-inflammatory-responses-by-activating-nrf2-ho-1-signaling
#6
Jinhee Kim, Juhee Lim, Bok Yun Kang, Kiwon Jung, Hyun Jin Choi
Capillarisin is a naturally isolated chromone, which is one of the major bioactive constituents of Artemisia capillaries. Capillarisin has antioxidant, anti-inflammatory, and anti-tumor potential, but the underlying molecular mechanisms remain largely unclear. In the present study, we demonstrate that the transcription factor nuclear factor E2-related factor-2 (Nrf2) is activated by capillarisin in neuroblastoma SH-SY5Y cells and microglial BV2 cells. Capillarisin leads to Nrf2 phosphorylation, subsequent activation of antioxidant response element (ARE)-mediated transcription, and up-regulation of downstream molecules, such as heme oxygenase-1 (HO-1) and NAD(P)H:quinone oxidoreductase 1...
February 1, 2017: Neurochemistry International
https://www.readbyqxmd.com/read/28150859/brain-derived-neurotrophic-factor-improves-proliferation-of-endometrial-epithelial-cells-by-inhibition-of-endoplasmic-reticulum-stress-during-early-pregnancy
#7
Whasun Lim, Hyocheol Bae, Fuller W Bazer, Gwonhwa Song
Brain-derived neurotrophic factor (BDNF) is a member of the neurotrophin family binds to two transmembrane receptors; neurotrophic receptor tyrosine kinase 2 (NTRK2) with high affinity and p75 with low affinity. Although BDNF-NTRK2 signaling in the central nervous system is known, signaling in the female reproductive system is unknown. Therefore, we determined effects of BDNF on porcine endometrial luminal epithelial (pLE) cells isolated from Day 12 of pregnancy, as well as expression of BDNF and NTRK2 in endometria of cyclic and pregnant pigs...
February 2, 2017: Journal of Cellular Physiology
https://www.readbyqxmd.com/read/28147342/inhibition-of-cdk8-mediator-kinase-suppresses-estrogen-dependent-transcription-and-the-growth-of-estrogen-receptor-positive-breast-cancer
#8
Martina S J McDermott, Alexander A Chumanevich, Chang-Uk Lim, Jiaxin Liang, Mengqian Chen, Serena Altilia, David Oliver, James M Rae, Michael Shtutman, Hippokratis Kiaris, Balázs Győrffy, Igor B Roninson, Eugenia V Broude
Hormone therapy targeting estrogen receptor (ER) is the principal treatment for ER-positive breast cancers. However, many cancers develop resistance to hormone therapy while retaining ER expression. Identifying new druggable mediators of ER function can help to increase the efficacy of ER-targeting drugs. Cyclin-dependent kinase 8 (CDK8) is a Mediator complex-associated transcriptional regulator with oncogenic activities. Expression of CDK8, its paralog CDK19 and their binding partner Cyclin C are negative prognostic markers in breast cancer...
January 29, 2017: Oncotarget
https://www.readbyqxmd.com/read/28146407/immunostimulatory-activity-of-opuntia-ficus-indica-var-saboten-cladodes-fermented-by-lactobacillus-plantarum-and-bacillus-subtilis-in-raw-264-7-macrophages
#9
Joon-Ho Hwang, Sang-Bin Lim
To increase the functionality of Opuntia ficus-indica var. saboten cladodes, it was fermented by Lactobacillus plantarum and Bacillus subtilis. Eighty percent methanol extracts were investigated for their effects on nitric oxide (NO) production, cytokine secretion, nuclear factor-κB (NF-κB) activity, and mitogen-activated protein kinase (MAPK) phosphorylation in RAW 264.7 cells. Methanol extracts of L. plantarum culture medium (LPCME) and B. subtilis culture medium (BSCME) did not affect lipopolysaccharide (LPS)-induced NO production but, at 500 μg/mL, increased interferon (IFN)-γ-induced NO production by 55...
February 2017: Journal of Medicinal Food
https://www.readbyqxmd.com/read/28142230/compound-k-attenuates-glucose-intolerance-and-hepatic-steatosis-through-ampk-dependent-pathways-in-type-2-diabetic-oletf-rats
#10
Yoo-Cheol Hwang, Da-Hee Oh, Moon Chan Choi, Sang Yeoul Lee, Kyu-Jeong Ahn, Ho-Yeon Chung, Sung-Jig Lim, Sung Hyun Chung, In-Kyung Jeong
Background/Aims: Non-alcoholic fatty liver disease is associated with insulin resistance. Compound K (CK) is the final metabolite of panaxadiol ginsenosides that have been shown to exert antidiabetic effects. However, the molecular mechanism of the antidiabetic effects in the liver have not been elucidated; further, whether CK has beneficial effects in hepatosteatosis remains unclear. Therefore, we evaluated the effect of CK on hepatosteatosis as well as its mechanism in high-fat diet (HFD)-fed type 2 diabetic Otsuka Long-Evans Tokushima Fatty (OLETF) rats...
February 1, 2017: Korean Journal of Internal Medicine
https://www.readbyqxmd.com/read/28137909/ndr1-dependent-regulation-of-kindlin-3-controls-high-affinity-lfa-1-binding-and-immune-synapse-organization
#11
Naoyuki Kondo, Yoshihiro Ueda, Toshiyuki Kita, Madoka Ozawa, Takashi Tomiyama, Kaneki Yasuda, Dae-Sik Lim, Tatsuo Kinashi
Antigen-specific adhesion between T cells and antigen-presenting cells (APC) during the formation of the immunological synapse (IS) is mediated by LFA-1 and ICAM-1. Herein, LFA-1/ICAM-1 interactions were measured at the single-molecule level on supported lipid bilayers. High-affinity binding was detected at low frequencies in the inner peripheral supramolecular activation cluster (SMAC) zone that contained high levels of activated Rap1 and kindlin-3. Rap1 was essential for T cell attachment, whereas deficiencies of ste20-like kinases, Mst1/Mst2 diminished high-affinity binding, and abrogated central SMAC formation with mislocalized kindlin-3 and vesicle transport regulators involved in TCR recycling/releasing machineries, resulting in impaired T-APC interactions...
January 30, 2017: Molecular and Cellular Biology
https://www.readbyqxmd.com/read/28137596/ew-7197-a-activin-like-kinase-5-inhibitor-suppresses-granulation-tissue-after-stent-placement-in-rat-esophagus
#12
Eun Jung Jun, Jung-Hoon Park, Jiaywei Tsauo, Su-Geun Yang, Dae-Kee Kim, Kun Yung Kim, Min Tae Kim, Sung Hwan Yoon, Young Je Lim, Ho-Young Song
BACKGROUND & AIMS: Self-expanding metallic stent (SEMS) placement is a well-established method for treating malignant esophageal strictures; however, this procedure has not gained widespread acceptance for treating benign esophageal strictures because of the granulation tissue formation. The aim of the present study was to investigate if EW-7197, a novel per-oral transforming growth factor-β type I receptor kinase inhibitor, suppressed granulation tissue formation after SEMS placement in the rat esophagus...
January 27, 2017: Gastrointestinal Endoscopy
https://www.readbyqxmd.com/read/28134270/signal-mingle-micropatterns-of-bmp-2-and-fibronectin-on-soft-biopolymeric-films-regulate-myoblast-shape-and-smad-signaling
#13
Vincent Fitzpatrick, Laure Fourel, Olivier Destaing, Flora Gilde, Corinne Albigès-Rizo, Catherine Picart, Thomas Boudou
In vivo, bone morphogenetic protein 2 (BMP-2) exists both in solution and bound to the extracellular matrix (ECM). While these two modes of presentation are known to influence cell behavior distinctly, their role in the niche microenvironment and their functional relevance in the genesis of a biological response has sparsely been investigated at a cellular level. Here we used the natural affinity of BMP-2 for fibronectin (FN) to engineer cell-sized micropatterns of BMP-2. This technique allowed the simultaneous control of the spatial presentation of fibronectin-bound BMP-2 and cell spreading...
January 30, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28130275/modulation-of-mtor-signaling-as-a-strategy-for-the-treatment-of-pompe-disease
#14
Jeong-A Lim, Lishu Li, Orian S Shirihai, Kyle M Trudeau, Rosa Puertollano, Nina Raben
Mechanistic target of rapamycin (mTOR) coordinates biosynthetic and catabolic processes in response to multiple extracellular and intracellular signals including growth factors and nutrients. This serine/threonine kinase has long been known as a critical regulator of muscle mass. The recent finding that the decision regarding its activation/inactivation takes place at the lysosome undeniably brings mTOR into the field of lysosomal storage diseases. In this study, we have examined the involvement of the mTOR pathway in the pathophysiology of a severe muscle wasting condition, Pompe disease, caused by excessive accumulation of lysosomal glycogen...
January 27, 2017: EMBO Molecular Medicine
https://www.readbyqxmd.com/read/28126323/mutations-of-the-lim-protein-ajuba-mediate-sensitivity-of-head-and-neck-squamous-cell-carcinoma-to-treatment-with-cell-cycle-inhibitors
#15
Ming Zhang, Ratnakar Singh, Shaohua Peng, Tuhina Mazumdar, Vaishnavi Sambandam, Li Shen, Pan Tong, Lerong Li, Nene Kalu, Curtis R Pickering, Mitchell Frederick, Jeffrey N Myers, Jing Wang, Faye M Johnson
The genomic alterations identified in head and neck squamous cell carcinoma (HNSCC) tumors have not resulted in any changes in clinical care, making the development of biomarker-driven targeted therapy for HNSCC a major translational gap in knowledge. To fill this gap, we used 59 molecularly characterized HNSCC cell lines and found that mutations of AJUBA, SMAD4 and RAS predicted sensitivity and resistance to treatment with inhibitors of polo-like kinase 1 (PLK1), checkpoint kinases 1 and 2, and WEE1. Inhibition or knockdown of PLK1 led to cell-cycle arrest at the G2/M transition and apoptosis in sensitive cell lines and decreased tumor growth in an orthotopic AJUBA-mutant HNSCC mouse model...
January 23, 2017: Cancer Letters
https://www.readbyqxmd.com/read/28117756/talin-modulation-by-a-synthetic-n-acylurea-derivative-reduces-angiogenesis-in-human-endothelial-cells
#16
I-Rang Lim, Hyung Joon Joo, Minseon Jeong, Jong-Ho Kim, Seung-Cheol Choi, Chungho Kim, Jong-Wha Jung, Soon Jun Hong
Talin is a focal adhesion protein that activates integrins and recruits other focal adhesion proteins. Talin regulates the interactions between integrins and the extracellular matrix, which are critical for endothelial cells during angiogenesis. In this study, we successfully synthesized a novel talin modulator, N-((2-(1H-indol-3-yl)ethyl)carbamoyl)-2-(benzo[d][1,3]dioxol-5-yloxy)acetamide, referred to as KCH-1521. KCH-1521 was determined to bind talin and modulate downstream signaling molecules of talin. After 24 h of treatment, KCH-1521 changed the cell morphology of human umbilical vein endothelial cells (HUVECs) and reduced focal adhesion protein expression including vinculin and paxillin...
January 22, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28116173/electroacupuncture-regulates-hippocampal-synaptic-plasticity-via-mir-134-mediated-limk1-function-in-rats-with-ischemic-stroke
#17
Weilin Liu, Jie Wu, Jia Huang, Peiyuan Zhuo, Yunjiao Lin, Lulu Wang, Ruhui Lin, Lidian Chen, Jing Tao
MircoRNAs (miRs) have been implicated in learning and memory, by regulating LIM domain kinase (LIMK1) to induce synaptic-dendritic plasticity. The study aimed to investigate whether miRNAs/LIMK1 signaling was involved in electroacupuncture- (EA-) mediated synaptic-dendritic plasticity in a rat model of middle cerebral artery occlusion induced cognitive deficit (MICD). Compared to untreatment or non-acupoint-EA treatment, EA at DU20 and DU24 acupoints could shorten escape latency and increase the frequency of crossing platform in Morris water maze test...
2017: Neural Plasticity
https://www.readbyqxmd.com/read/28112737/pediatric-non-down-syndrome-acute-megakaryoblastic-leukemia-is-characterized-by-distinct-genomic-subsets-with-varying-outcomes
#18
Jasmijn D E de Rooij, Cristyn Branstetter, Jing Ma, Yongjin Li, Michael P Walsh, Jinjun Cheng, Askar Obulkasim, Jinjun Dang, John Easton, Lonneke J Verboon, Heather L Mulder, Martin Zimmermann, Cary Koss, Pankaj Gupta, Michael Edmonson, Michael Rusch, Joshua Yew Suang Lim, Katarina Reinhardt, Martina Pigazzi, Guangchun Song, Allen Eng Juh Yeoh, Lee-Yung Shih, Der-Cherng Liang, Stephanie Halene, Diane S Krause, Jinghui Zhang, James R Downing, Franco Locatelli, Dirk Reinhardt, Marry M van den Heuvel-Eibrink, C Michel Zwaan, Maarten Fornerod, Tanja A Gruber
Acute megakaryoblastic leukemia (AMKL) is a subtype of acute myeloid leukemia (AML) in which cells morphologically resemble abnormal megakaryoblasts. While rare in adults, AMKL accounts for 4-15% of newly diagnosed childhood AML cases. AMKL in individuals without Down syndrome (non-DS-AMKL) is frequently associated with poor clinical outcomes. Previous efforts have identified chimeric oncogenes in a substantial number of non-DS-AMKL cases, including RBM15-MKL1, CBFA2T3-GLIS2, KMT2A gene rearrangements, and NUP98-KDM5A...
January 23, 2017: Nature Genetics
https://www.readbyqxmd.com/read/28107519/cudraflavone-c-induces-tumor-specific-apoptosis-in-colorectal-cancer-cells-through-inhibition-of-the-phosphoinositide-3-kinase-pi3k-akt-pathway
#19
Hsien-Chuen Soo, Felicia Fei-Lei Chung, Kuan-Hon Lim, Veronica Alicia Yap, Tracey D Bradshaw, Ling-Wei Hii, Si-Hoey Tan, Sze-Jia See, Yuen-Fen Tan, Chee-Onn Leong, Chun-Wai Mai
Cudraflavone C (Cud C) is a naturally-occurring flavonol with reported anti-proliferative activities. However, the mechanisms by which Cud C induced cytotoxicity have yet to be fully elucidated. Here, we investigated the effects of Cud C on cell proliferation, caspase activation andapoptosis induction in colorectal cancer cells (CRC). We show that Cud C inhibits cell proliferation in KM12, Caco-2, HT29, HCC2998, HCT116 and SW48 CRC but not in the non-transformed colorectal epithelial cells, CCD CoN 841. Cud C induces tumor-selective apoptosis via mitochondrial depolarization and activation of the intrinsic caspase pathway...
2017: PloS One
https://www.readbyqxmd.com/read/28106783/extract-of-polygala-tenuifolia-alleviates-stress-exacerbated-atopy-like-skin-dermatitis-through-the-modulation-of-protein-kinase-a-and-p38-mitogen-activated-protein-kinase-signaling-pathway
#20
Bongjun Sur, Bombi Lee, Ye Seul Yoon, Pooreum Lim, Riwon Hong, Mijung Yeom, Hyang Sook Lee, Hijoon Park, Insop Shim, Hyejung Lee, Young Pyo Jang, Dae-Hyun Hahm
Atopic dermatitis (AD) and stress create a vicious cycle: stress exacerbates atopic symptoms, and atopic disease elicits stress and anxiety. Targeting multiple pathways including stress and allergic inflammation is, therefore, important for treating AD. In this study, we investigated the remedial value of Polygala tenuifolia Willd. (PTW) for treating immobilization (IMO) stress-exacerbated atopy-like skin dermatitis and its underlying mechanism. Trimellitic anhydride (TMA) was applied to dorsal skin for sensitization and subsequently both ears for eliciting T-cell-dependent contact hypersensitivity in mice, which underwent 2 h-IMO stress and PTW administration for the latter 6 and 9 days in the ear exposure period of TMA, respectively...
January 18, 2017: International Journal of Molecular Sciences
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