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John H. Zhang

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https://www.readbyqxmd.com/read/28930954/acute-procedural-interventions-after-pediatric-blunt-abdominal-trauma-a-prospective-multicenter-evaluation
#1
Chase A Arbra, Adam M Vogel, Jingwen Zhang, Patrick D Mauldin, Eunice Y Huang, Kate B Savoie, Matthew T Santore, KuoJen Tsao, Tiffany G Ostovar-Kermani, Richard A Falcone, M Sidney Dassinger, John Recicar, Jeffrey H Haynes, Martin L Blakely, Robert T Russell, Bindi J Naik-Mathuria, Shawn D St Peter, David P Mooney, Chinwendu Onwubiko, Jeffrey S Upperman, Christian J Streck
BACKGROUND: Pediatric intra-abdominal injuries (IAI) from blunt abdominal trauma (BAT) rarely require emergent intervention. For those children undergoing procedural intervention, our aim was to understand the timing and indications for operation and angiographic embolization. METHODS: We prospectively enrolled children younger than 16 years after BAT at 14 Level I Pediatric Trauma Centers over a 1-year period. Patients with IAI who received an intervention (IAI-I) were compared with those who did not receive an intervention using descriptive statistics and univariate analysis; p less than 0...
October 2017: Journal of Trauma and Acute Care Surgery
https://www.readbyqxmd.com/read/28929521/safety-tolerability-and-pharmacokinetics-of-radavirsen-avi-7100-an-antisense-oligonucleotide-targeting-influenza-a-m1-m2-translation
#2
John H Beigel, Jocelyn Voell, Paula Muñoz, Parag Kumar, Kristina M Brooks, Jianbo Zhang, Patrick Iversen, Alison Heald, Michael Wong, Richard T Davey
AIMS: To assess the safety, tolerability, and pharmacokinetics (PK) of radavirsen following single ascending doses and multiple doses given as IV infusions in healthy adults. METHODS: A Phase 1 safety and pharmacokinetic (PK) study of radavirsen was performed in healthy volunteers. The study was divided into 2 parts. The first was a single-ascending dose study of 5 cohorts of 8 subjects each, randomized 6:2 to receive single intravenous doses of radavirsen ranging from 0...
September 20, 2017: British Journal of Clinical Pharmacology
https://www.readbyqxmd.com/read/28928391/interaction-between-karst-terrain-and-bauxites-evidence-from-quaternary-orebody-distribution-in-guangxi-sw-china
#3
Lin Yang, Qingfei Wang, Qizuan Zhang, Emmanuel John M Carranza, Huan Liu, Xuefei Liu, Jun Deng
Most bauxite in China is located upon the karst surface, yet the relation between karstification process and bauxite formation is barely known. Here we discuss how the relation affects the karst and bauxite evolution through analyzing distributions of orebody parameters from 9,007 exploration wells (434 orebodies) in western Guangxi, South China block. In high-elevation karst terrain dominated by peaks, orebodies have greater average thickness, lower Al2O3 and higher Fe2O3(T) than those in low-elevation region dominated by depressions...
September 19, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28925323/recanalization-reperfusion-and-recirculation-in-stroke
#4
John H Zhang, Andre Obenaus, David S Liebeskind, Jiping Tang, Richard Hartman, William J Pearce
Recirculation, from arterial inflow routes through venous outflow pathways, was conceptualized in stroke research 50 years ago. As new technologies were developed, blocked arteries could be reopened, capillaries could be reperfused, and the use of recanalization and reperfusion grew to dominate therapeutic strategies. These approaches overwhelmingly focused on restoration of arterial and capillary inflow, but not on veins even though venous disorders may initiate or exacerbate brain injury. In this commentary, we advance the term "recirculation" after "recanalization" and "reperfusion" as a primary concept of stroke pathophysiology that targets the restoration of both the arterial and venous cerebral circulations...
January 1, 2017: Journal of Cerebral Blood Flow and Metabolism
https://www.readbyqxmd.com/read/28919040/heme-binding-biguanides-target-cytochrome-p450-dependent-cancer-cell-mitochondria
#5
Zhijun Guo, Irina F Sevrioukova, Ilia G Denisov, Xia Zhang, Ting-Lan Chiu, Dafydd G Thomas, Eric A Hanse, Rebecca A D Cuellar, Yelena V Grinkova, Vanessa Wankhede Langenfeld, Daniel S Swedien, Justin D Stamschror, Juan Alvarez, Fernando Luna, Adela Galván, Young Kyung Bae, Julia D Wulfkuhle, Rosa I Gallagher, Emanuel F Petricoin, Beverly Norris, Craig M Flory, Robert J Schumacher, M Gerard O'Sullivan, Qing Cao, Haitao Chu, John D Lipscomb, William M Atkins, Kalpna Gupta, Ameeta Kelekar, Ian A Blair, Jorge H Capdevila, John R Falck, Stephen G Sligar, Thomas L Poulos, Gunda I Georg, Elizabeth Ambrose, David A Potter
The mechanisms by which cancer cell-intrinsic CYP monooxygenases promote tumor progression are largely unknown. CYP3A4 was unexpectedly associated with breast cancer mitochondria and synthesized arachidonic acid (AA)-derived epoxyeicosatrienoic acids (EETs), which promoted the electron transport chain/respiration and inhibited AMPKα. CYP3A4 knockdown activated AMPKα, promoted autophagy, and prevented mammary tumor formation. The diabetes drug metformin inhibited CYP3A4-mediated EET biosynthesis and depleted cancer cell-intrinsic EETs...
August 29, 2017: Cell Chemical Biology
https://www.readbyqxmd.com/read/28912017/indoleamine-2-3-dioxygenase-1-increased-in-human-gastric-pre-neoplasia-promotes-inflammation-and-metaplasia-in-mice-and-is-associated-with-type-ii-hypersensitivity-autoimmunity
#6
Mohamad El-Zaatari, Adam J Bass, Reanne Bowlby, Min Zhang, Li-Jyun Syu, Yitian Yang, Helmut Grasberger, Andrew Shreiner, Bei Tan, Shrinivas Bishu, Wai K Leung, Andrea Todisco, Nobuhiko Kamada, Marilia Cascalho, Andrzej A Dlugosz, John Y Kao
BACKGROUND & AIMS: Chronic gastrointestinal inflammation increases the risk of cancer by mechanisms that are not well understood. Indoleamine-2,3-dioxygenase 1 (IDO1) is a heme-binding enzyme that regulates the immune response via catabolization and regulation of tryptophan availability for immune cell uptake. IDO1 expression is increased during the transition from chronic inflammation to gastric metaplasia. We investigated whether IDO1 contributes to the inflammatory response that mediates loss of parietal cells leading to metaplasia...
September 11, 2017: Gastroenterology
https://www.readbyqxmd.com/read/28906433/effect-of-environmental-factors-on-intra-specific-inhibitory-activity-of-carnobacterium-maltaromaticum
#7
Peipei Zhang, Mandeep Kaur, John P Bowman, David A Ratkowsky, Mark Tamplin
Carnobacterium maltaromaticum is frequently associated with foods having extended shelf-life due to its inhibitory activity to other bacteria. The quantification of such inhibition interactions affected by various environmental factors is limited. This study investigated the effect of environmental factors relevant to vacuum-packaged beef on inhibition between two model isolates of C. maltaromaticum, D0h and D8c, specifically D8c sensitivity to D0h inhibition and D0h inhibitor production. The effects of temperature (-1, 7, 15, 25 °C), atmosphere (aerobic and anaerobic), pH (5...
September 14, 2017: Microorganisms
https://www.readbyqxmd.com/read/28898252/impact-of-common-genetic-determinants-of-hemoglobin-a1c-on-type-2-diabetes-risk-and-diagnosis-in-ancestrally-diverse-populations-a-transethnic-genome-wide-meta-analysis
#8
Eleanor Wheeler, Aaron Leong, Ching-Ti Liu, Marie-France Hivert, Rona J Strawbridge, Clara Podmore, Man Li, Jie Yao, Xueling Sim, Jaeyoung Hong, Audrey Y Chu, Weihua Zhang, Xu Wang, Peng Chen, Nisa M Maruthur, Bianca C Porneala, Stephen J Sharp, Yucheng Jia, Edmond K Kabagambe, Li-Ching Chang, Wei-Min Chen, Cathy E Elks, Daniel S Evans, Qiao Fan, Franco Giulianini, Min Jin Go, Jouke-Jan Hottenga, Yao Hu, Anne U Jackson, Stavroula Kanoni, Young Jin Kim, Marcus E Kleber, Claes Ladenvall, Cecile Lecoeur, Sing-Hui Lim, Yingchang Lu, Anubha Mahajan, Carola Marzi, Mike A Nalls, Pau Navarro, Ilja M Nolte, Lynda M Rose, Denis V Rybin, Serena Sanna, Yuan Shi, Daniel O Stram, Fumihiko Takeuchi, Shu Pei Tan, Peter J van der Most, Jana V Van Vliet-Ostaptchouk, Andrew Wong, Loic Yengo, Wanting Zhao, Anuj Goel, Maria Teresa Martinez Larrad, Dörte Radke, Perttu Salo, Toshiko Tanaka, Erik P A van Iperen, Goncalo Abecasis, Saima Afaq, Behrooz Z Alizadeh, Alain G Bertoni, Amelie Bonnefond, Yvonne Böttcher, Erwin P Bottinger, Harry Campbell, Olga D Carlson, Chien-Hsiun Chen, Yoon Shin Cho, W Timothy Garvey, Christian Gieger, Mark O Goodarzi, Harald Grallert, Anders Hamsten, Catharina A Hartman, Christian Herder, Chao Agnes Hsiung, Jie Huang, Michiya Igase, Masato Isono, Tomohiro Katsuya, Chiea-Chuen Khor, Wieland Kiess, Katsuhiko Kohara, Peter Kovacs, Juyoung Lee, Wen-Jane Lee, Benjamin Lehne, Huaixing Li, Jianjun Liu, Stephane Lobbens, Jian'an Luan, Valeriya Lyssenko, Thomas Meitinger, Tetsuro Miki, Iva Miljkovic, Sanghoon Moon, Antonella Mulas, Gabriele Müller, Martina Müller-Nurasyid, Ramaiah Nagaraja, Matthias Nauck, James S Pankow, Ozren Polasek, Inga Prokopenko, Paula S Ramos, Laura Rasmussen-Torvik, Wolfgang Rathmann, Stephen S Rich, Neil R Robertson, Michael Roden, Ronan Roussel, Igor Rudan, Robert A Scott, William R Scott, Bengt Sennblad, David S Siscovick, Konstantin Strauch, Liang Sun, Morris Swertz, Salman M Tajuddin, Kent D Taylor, Yik-Ying Teo, Yih Chung Tham, Anke Tönjes, Nicholas J Wareham, Gonneke Willemsen, Tom Wilsgaard, Aroon D Hingorani, Josephine Egan, Luigi Ferrucci, G Kees Hovingh, Antti Jula, Mika Kivimaki, Meena Kumari, Inger Njølstad, Colin N A Palmer, Manuel Serrano Ríos, Michael Stumvoll, Hugh Watkins, Tin Aung, Matthias Blüher, Michael Boehnke, Dorret I Boomsma, Stefan R Bornstein, John C Chambers, Daniel I Chasman, Yii-Der Ida Chen, Yduan-Tsong Chen, Ching-Yu Cheng, Francesco Cucca, Eco J C de Geus, Panos Deloukas, Michele K Evans, Myriam Fornage, Yechiel Friedlander, Philippe Froguel, Leif Groop, Myron D Gross, Tamara B Harris, Caroline Hayward, Chew-Kiat Heng, Erik Ingelsson, Norihiro Kato, Bong-Jo Kim, Woon-Puay Koh, Jaspal S Kooner, Antje Körner, Diana Kuh, Johanna Kuusisto, Markku Laakso, Xu Lin, Yongmei Liu, Ruth J F Loos, Patrik K E Magnusson, Winfried März, Mark I McCarthy, Albertine J Oldehinkel, Ken K Ong, Nancy L Pedersen, Mark A Pereira, Annette Peters, Paul M Ridker, Charumathi Sabanayagam, Michele Sale, Danish Saleheen, Juha Saltevo, Peter Eh Schwarz, Wayne H H Sheu, Harold Snieder, Timothy D Spector, Yasuharu Tabara, Jaakko Tuomilehto, Rob M van Dam, James G Wilson, James F Wilson, Bruce H R Wolffenbuttel, Tien Yin Wong, Jer-Yuarn Wu, Jian-Min Yuan, Alan B Zonderman, Nicole Soranzo, Xiuqing Guo, David J Roberts, Jose C Florez, Robert Sladek, Josée Dupuis, Andrew P Morris, E-Shyong Tai, Elizabeth Selvin, Jerome I Rotter, Claudia Langenberg, Inês Barroso, James B Meigs
BACKGROUND: Glycated hemoglobin (HbA1c) is used to diagnose type 2 diabetes (T2D) and assess glycemic control in patients with diabetes. Previous genome-wide association studies (GWAS) have identified 18 HbA1c-associated genetic variants. These variants proved to be classifiable by their likely biological action as erythrocytic (also associated with erythrocyte traits) or glycemic (associated with other glucose-related traits). In this study, we tested the hypotheses that, in a very large scale GWAS, we would identify more genetic variants associated with HbA1c and that HbA1c variants implicated in erythrocytic biology would affect the diagnostic accuracy of HbA1c...
September 2017: PLoS Medicine
https://www.readbyqxmd.com/read/28892626/biomimetic-virulomics-for-capture-and-identification-of-cell-type-specific-effector-proteins
#9
John D Lapek, Ronnie H Fang, Xiaoli Wei, Pengyang Li, Bo Wang, Liangfang Zhang, David J Gonzalez
An unmet challenge in the study of disease is to accurately streamline the identification of important virulence factors. Traditional, genetically driven approaches miss biologically relevant markers due to discordance between the genome and proteome. Here, we developed a nanotechnology-enabled affinity enrichment strategy coupled with multiplexed quantitative proteomics, namely Biomimetic Virulomics, for successful identification of cell-type specific effector proteins of both prokaryotic and eukaryotic pathogens...
September 20, 2017: ACS Nano
https://www.readbyqxmd.com/read/28892296/tailored-approaches-in-drug-development-and-diagnostics-from-molecular-design-to-biological-model-systems
#10
REVIEW
Cecilia Sahlgren, Annika Meinander, Hongbo Zhang, Fang Cheng, Maren Preis, Chunlin Xu, Tiina A Salminen, Diana Toivola, Daniel Abankwa, Ari Rosling, Didem Şen Karaman, Outi M H Salo-Ahen, Ronald Österbacka, John E Eriksson, Stefan Willför, Ion Petre, Jouko Peltonen, Reko Leino, Mark Johnson, Jessica Rosenholm, Niklas Sandler
Approaches to increase the efficiency in developing drugs and diagnostics tools, including new drug delivery and diagnostic technologies, are needed for improved diagnosis and treatment of major diseases and health problems such as cancer, inflammatory diseases, chronic wounds, and antibiotic resistance. Development within several areas of research ranging from computational sciences, material sciences, bioengineering to biomedical sciences and bioimaging is needed to realize innovative drug development and diagnostic (DDD) approaches...
September 11, 2017: Advanced Healthcare Materials
https://www.readbyqxmd.com/read/28888602/properties-of-acid-gels-made-from-sodium-caseinate-maltodextrin-conjugates-prepared-by-a-wet-heating-method
#11
Shuwen Zhang, Yuansheng Gong, Som Khanal, Yanjie Lu, John A Lucey
Covalent attachment of polysaccharides to proteins (conjugation) via the Maillard reaction has been extensively studied. Conjugation can lead to a significant improvement in protein functionality (e.g., solubility, emulsification, and heat stability). Caseins have previously been successfully conjugated with maltodextrin (Md), but the effect on the detailed acid gelation properties has not been examined. We studied the effect of conjugating sodium caseinate (NaCN) with 3 different sized Md samples via the Maillard reaction in aqueous solutions...
September 6, 2017: Journal of Dairy Science
https://www.readbyqxmd.com/read/28882870/crispr-cas9-mediated-gene-editing-in-human-ipsc-derived-macrophage-reveals-lysosomal-acid-lipase-function-in-human-macrophages
#12
Hanrui Zhang, Jianting Shi, Melanie A Hachet, Chenyi Xue, Robert C Bauer, Hongfeng Jiang, Wenjun Li, Junichiro Tohyama, John Millar, Jeffrey Billheimer, Michael C Phillips, Babak Razani, Daniel J Rader, Muredach P Reilly
OBJECTIVE: To gain mechanistic insights into the role of LIPA(lipase A), the gene encoding LAL (lysosomal acid lipase) protein, in human macrophages. APPROACH AND RESULTS: We used CRISPR (clustered regularly interspaced short palindromic repeats )/Cas9 (CRISPR-associated protein 9) technology to knock out LIPA in human induced pluripotent stem cells and then differentiate to macrophage (human-induced pluripotent stem cells-derived macrophage [IPSDM]) to explore the human macrophage LIPA loss-of-function phenotypes...
September 7, 2017: Arteriosclerosis, Thrombosis, and Vascular Biology
https://www.readbyqxmd.com/read/28881090/an-activity-transition-from-nadh-dehydrogenase-to-nadh-oxidase-during-protein-denaturation
#13
Scott Huston, John Collins, Fangfang Sun, Ting Zhang, Timothy D Vaden, Y-H Percival Zhang, Jinglin Fu
A decrease in the specific activity of an enzyme is commonly observed when the enzyme is inappropriately handled or is stored over extended period. Here, we reported a functional transition of a FMN-bound diaphorase (FMN-DI) that happened during the long-term storage process. It was found that FMN-DI did not simply lose its NADH dehydrogenase activity after a long-time storage, but obtained a new enzyme activity of NADH oxidase. Further mechanistic studies suggested that the alteration of the binding strength of a FMN cofactor with a DI protein could be responsible for this functional switch of the enzyme...
September 7, 2017: Biotechnology and Applied Biochemistry
https://www.readbyqxmd.com/read/28878011/nondestructive-tissue-analysis-for-ex-vivo-and-in-vivo-cancer-diagnosis-using-a-handheld-mass-spectrometry-system
#14
Jialing Zhang, John Rector, John Q Lin, Jonathan H Young, Marta Sans, Nitesh Katta, Noah Giese, Wendong Yu, Chandandeep Nagi, James Suliburk, Jinsong Liu, Alena Bensussan, Rachel J DeHoog, Kyana Y Garza, Benjamin Ludolph, Anna G Sorace, Anum Syed, Aydin Zahedivash, Thomas E Milner, Livia S Eberlin
Conventional methods for histopathologic tissue diagnosis are labor- and time-intensive and can delay decision-making during diagnostic and therapeutic procedures. We report the development of an automated and biocompatible handheld mass spectrometry device for rapid and nondestructive diagnosis of human cancer tissues. The device, named MasSpec Pen, enables controlled and automated delivery of a discrete water droplet to a tissue surface for efficient extraction of biomolecules. We used the MasSpec Pen for ex vivo molecular analysis of 20 human cancer thin tissue sections and 253 human patient tissue samples including normal and cancerous tissues from breast, lung, thyroid, and ovary...
September 6, 2017: Science Translational Medicine
https://www.readbyqxmd.com/read/28869590/identification-of-new-susceptibility-loci-for-type-2-diabetes-and-shared-etiological-pathways-with-coronary-heart-disease
#15
Wei Zhao, Asif Rasheed, Emmi Tikkanen, Jung-Jin Lee, Adam S Butterworth, Joanna M M Howson, Themistocles L Assimes, Rajiv Chowdhury, Marju Orho-Melander, Scott Damrauer, Aeron Small, Senay Asma, Minako Imamura, Toshimasa Yamauch, John C Chambers, Peng Chen, Bishwa R Sapkota, Nabi Shah, Sehrish Jabeen, Praveen Surendran, Yingchang Lu, Weihua Zhang, Atif Imran, Shahid Abbas, Faisal Majeed, Kevin Trindade, Nadeem Qamar, Nadeem Hayyat Mallick, Zia Yaqoob, Tahir Saghir, Syed Nadeem Hasan Rizvi, Anis Memon, Syed Zahed Rasheed, Fazal-Ur-Rehman Memon, Khalid Mehmood, Naveeduddin Ahmed, Irshad Hussain Qureshi, Tanveer-Us-Salam, Wasim Iqbal, Uzma Malik, Narinder Mehra, Jane Z Kuo, Wayne H-H Sheu, Xiuqing Guo, Chao A Hsiung, Jyh-Ming J Juang, Kent D Taylor, Yi-Jen Hung, Wen-Jane Lee, Thomas Quertermous, I-Te Lee, Chih-Cheng Hsu, Erwin P Bottinger, Sarju Ralhan, Yik Ying Teo, Tzung-Dau Wang, Dewan S Alam, Emanuele Di Angelantonio, Steve Epstein, Sune F Nielsen, Børge G Nordestgaard, Anne Tybjaerg-Hansen, Robin Young, Marianne Benn, Ruth Frikke-Schmidt, Pia R Kamstrup, J Wouter Jukema, Naveed Sattar, Roelof Smit, Ren-Hua Chung, Kae-Woei Liang, Sonia Anand, Dharambir K Sanghera, Samuli Ripatti, Ruth J F Loos, Jaspal S Kooner, E Shyong Tai, Jerome I Rotter, Yii-Der Ida Chen, Philippe Frossard, Shiro Maeda, Takashi Kadowaki, Muredach Reilly, Guillaume Pare, Olle Melander, Veikko Salomaa, Daniel J Rader, John Danesh, Benjamin F Voight, Danish Saleheen
To evaluate the shared genetic etiology of type 2 diabetes (T2D) and coronary heart disease (CHD), we conducted a genome-wide, multi-ancestry study of genetic variation for both diseases in up to 265,678 subjects for T2D and 260,365 subjects for CHD. We identify 16 previously unreported loci for T2D and 1 locus for CHD, including a new T2D association at a missense variant in HLA-DRB5 (odds ratio (OR) = 1.29). We show that genetically mediated increase in T2D risk also confers higher CHD risk. Joint T2D-CHD analysis identified eight variants-two of which are coding-where T2D and CHD associations appear to colocalize, including a new joint T2D-CHD association at the CCDC92 locus that also replicated for T2D...
September 4, 2017: Nature Genetics
https://www.readbyqxmd.com/read/28867147/lmo1-synergizes-with-mycn-to-promote-neuroblastoma-initiation-and-metastasis
#16
Shizhen Zhu, Xiaoling Zhang, Nina Weichert-Leahey, Zhiwei Dong, Cheng Zhang, Gonzalo Lopez, Ting Tao, Shuning He, Andrew C Wood, Derek Oldridge, Choong Yong Ung, Janine H van Ree, Amish Khan, Brittany M Salazar, Edroaldo Lummertz da Rocha, Mark W Zimmerman, Feng Guo, Hong Cao, Xiaonan Hou, S John Weroha, Antonio R Perez-Atayde, Donna S Neuberg, Alexander Meves, Mark A McNiven, Jan M van Deursen, Hu Li, John M Maris, A Thomas Look
A genome-wide association study identified LMO1, which encodes an LIM-domain-only transcriptional cofactor, as a neuroblastoma susceptibility gene that functions as an oncogene in high-risk neuroblastoma. Here we show that dβh promoter-mediated expression of LMO1 in zebrafish synergizes with MYCN to increase the proliferation of hyperplastic sympathoadrenal precursor cells, leading to a reduced latency and increased penetrance of neuroblastomagenesis. The transgenic expression of LMO1 also promoted hematogenous dissemination and distant metastasis, which was linked to neuroblastoma cell invasion and migration, and elevated expression levels of genes affecting tumor cell-extracellular matrix interaction, including loxl3, itga2b, itga3, and itga5...
September 11, 2017: Cancer Cell
https://www.readbyqxmd.com/read/28860188/discovery-of-a-highly-selective-chemical-inhibitor-of-matrix-metalloproteinase-9-mmp-9-that-allosterically-inhibits-zymogen-activation
#17
Robert H Scannevin, Richard Alexander, Tara Mezzasalma Haarlander, Sharon L Burke, Monica Singer, Cuifen Hou, Yue-Mei Zhang, Diane Maguire, John Spurlino, Ingrid Deckman, Karen I Carroll, Frank Lewandowski, Eric Devine, Keli Dzordzorme, Brett Tounge, Cindy Milligan, Shariff Bayoumy, Robyn Williams, Celine Schalk-Hihi, Kristi Leonard, Paul Jackson, Matthew Todd, Lawrence C Kuo, Kenneth J Rhodes
Aberrant activation of matrix metalloproteinases (MMPs) is a common feature of pathological cascades observed in diverse disorders such as cancer, fibrosis, immune dysregulation and neurodegenerative diseases. MMP-9, in particular, is highly dynamically regulated in several pathological processes. Development of MMP inhibitors has therefore been an attractive strategy for therapeutic intervention. However, a long history of failed clinical trials has demonstrated that broad-spectrum MMP inhibitors have limited clinical utility, which has spurred the development of inhibitors selective for individual MMPs...
August 31, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28859059/phase-1-safety-pharmacokinetic-and-pharmacodynamic-study-of-the-cyclin-dependent-kinase-inhibitor-dinaciclib-administered-every-three-weeks-in-patients-with-advanced-malignancies
#18
Monica M Mita, Alain C Mita, Jennifer L Moseley, Jennifer Poon, Karen A Small, Ying-Ming Jou, Paul Kirschmeier, Da Zhang, Yali Zhu, Paul Statkevich, Kamelesh K Sankhala, John Sarantopoulos, James M Cleary, Lucian R Chirieac, Scott J Rodig, Rajat Bannerji, Geoffrey I Shapiro
BACKGROUND: Dinaciclib is a potent inhibitor of cell cycle and transcriptional cyclin-dependent kinases. This Phase 1 study evaluated the safety, tolerability and pharmacokinetics of various dosing schedules of dinaciclib in advanced solid tumour patients and assessed Pharmacodynamic and preliminary anti-tumour activity. METHODS: In part 1, patients were enrolled in escalating cohorts of 2-h infusions administered once every 3 weeks, utilising an accelerated titration design until a recommended phase 2 dose (RP2D) was defined...
August 31, 2017: British Journal of Cancer
https://www.readbyqxmd.com/read/28852909/effects-of-rifampin-itraconazole-and-esomeprazole-on-the-pharmacokinetics-of-alisertib-an-investigational-aurora-a-kinase-inhibitor-in-patients-with-advanced-malignancies
#19
Xiaofei Zhou, Shubham Pant, John Nemunaitis, A Craig Lockhart, Gerald Falchook, Todd M Bauer, Manish Patel, John Sarantopoulos, Michael Bargfrede, Andreas Muehler, Lakshmi Rangachari, Bin Zhang, Karthik Venkatakrishnan
Aim Two studies investigated the effect of gastric acid reducing agents and strong inducers/inhibitors of CYP3A4 on the pharmacokinetics of alisertib, an investigational Aurora A kinase inhibitor, in patients with advanced malignancies. Methods In Study 1, patients received single doses of alisertib (50 mg) in the presence and absence of either esomeprazole (40 mg once daily [QD]) or rifampin (600 mg QD). In Study 2, patients received single doses of alisertib (30 mg) in the presence and absence of itraconazole (200 mg QD)...
August 30, 2017: Investigational New Drugs
https://www.readbyqxmd.com/read/28852409/traumatic-brain-injury-and-stem-cell-pathophysiology-and-update-on-recent-treatment-modalities
#20
REVIEW
Cesar Reis, Vadim Gospodarev, Haley Reis, Michael Wilkinson, Josileide Gaio, Camila Araujo, Sheng Chen, John H Zhang
Traumatic brain injury (TBI) is a complex condition that presents with a wide spectrum of clinical symptoms caused by an initial insult to the brain through an external mechanical force to the skull. In the United States alone, TBI accounts for more than 50,000 deaths per year and is one of the leading causes of mortality among young adults in the developed world. Pathophysiology of TBI is complex and consists of acute and delayed injury. In the acute phase, brain tissue destroyed upon impact includes neurons, glia, and endothelial cells, the latter of which makes up the blood-brain barrier...
2017: Stem Cells International
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