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https://www.readbyqxmd.com/read/28438897/downregulation-of-mir-200a-3p-targeting-ctbp2-is-involved-in-the-hypoproduction-of-il-2-in-systemic-lupus-erythematosus-derived-t-cells
#1
Eri Katsuyama, Minglu Yan, Katsue Sunahori Watanabe, Syun Matsushima, Yuriko Yamamura, Sumie Hiramatsu, Keiji Ohashi, Haruki Watanabe, Takayuki Katsuyama, Sonia Zeggar, Nobuya Yoshida, Vaishali R Moulton, George C Tsokos, Ken-Ei Sada, Jun Wada
Systemic lupus erythematosus (SLE) damages multiple organs by producing various autoantibodies. In this study, we report that decreased microRNA (miR)-200a-3p causes IL-2 hypoproduction through zinc finger E-box binding homeobox (ZEB)1 and C-terminal binding protein 2 (CtBP2) in a lupus-prone mouse. First, we performed RNA sequencing to identify candidate microRNAs and mRNAs involved in the pathogenesis of SLE. We found that miR-200a-3p was significantly downregulated, whereas its putative targets, ZEB2 and CtBP2, were upregulated in CD4(+) T cells from MRL/lpr-Tnfrsf6(lpr) mice compared with C57BL/6J mice...
April 24, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/28406939/role-of-neurod1-on-the-negative-regulation-of-pomc-expression-by-glucocorticoid
#2
Rehana Parvin, Akiko Saito-Hakoda, Hiroki Shimada, Kyoko Shimizu, Erika Noro, Yasumasa Iwasaki, Ken Fujiwara, Atsushi Yokoyama, Akira Sugawara
The mechanism of the negative regulation of proopiomelanocortin gene (Pomc) by glucocorticoids (Gcs) is still unclear in many points. Here, we demonstrated the involvement of neurogenic differentiation factor 1 (NeuroD1) in the Gc-mediated negative regulation of Pomc. Murine pituitary adrenocorticotropic hormone (ACTH) producing corticotroph tumor-derived AtT20 cells were treated with dexamethasone (DEX) (1-100 nM) and cultured for 24 hrs. Thereafter, Pomc mRNA expression was studied by quantitative real-time PCR and rat Pomc promoter (-703/+58) activity was examined by luciferase assay...
2017: PloS One
https://www.readbyqxmd.com/read/28404726/regulation-of-strigolactone-biosynthesis-by-gibberellin-signaling
#3
Shinsaku Ito, Daichi Yamagami, Mikihisa Umehara, Atsushi Hanada, Satoko Yoshida, Yasuyuki Sasaki, Shunsuke Yajima, Junko Kyozuka, Miyako Ueguchi-Tanaka, Makoto Matsuoka, Ken Shirasu, Shinjiro Yamaguchi, Tadao Asami
Strigolactones (SLs) are a class of plant hormones that regulate diverse physiological processes, including shoot branching and root development. They also act as rhizosphere signaling molecules to stimulate the germination of root parasitic weeds and the branching of arbuscular mycorrhizal fungi. Although various types of cross talk between SLs and other hormones have been reported in physiological analyses, the cross talk between gibberellin (GA) and SLs is poorly understood. We screened for chemicals that regulate the level of SLs in rice (Oryza sativa) and identified GA as, to our knowledge, a novel SL-regulating molecule...
June 2017: Plant Physiology
https://www.readbyqxmd.com/read/28366744/fission-yeast-apc15-stabilizes-mcc-cdc20-apc-c-complexes-ensuring-efficient-cdc20-ubiquitination-and-checkpoint-arrest
#4
Karen M May, Flora Paldi, Kevin G Hardwick
During mitosis, cells must segregate the replicated copies of their genome to their daughter cells with extremely high fidelity. Segregation errors lead to an abnormal chromosome number (aneuploidy), which typically results in disease or cell death [1]. Chromosome segregation and anaphase onset are initiated through the action of the multi-subunit E3 ubiquitin ligase known as the anaphase-promoting complex or cyclosome (APC/C [2]). The APC/C is inhibited by the spindle checkpoint in the presence of kinetochore attachment defects [3, 4]...
April 24, 2017: Current Biology: CB
https://www.readbyqxmd.com/read/28341363/a-gene-regulatory-program-controlling-early-xenopus-mesendoderm-formation-network-conservation-and-motifs
#5
REVIEW
Rebekah M Charney, Kitt D Paraiso, Ira L Blitz, Ken W Y Cho
Germ layer formation is among the earliest differentiation events in metazoan embryos. In triploblasts, three germ layers are formed, among which the endoderm gives rise to the epithelial lining of the gut tube and associated organs including the liver, pancreas and lungs. In frogs (Xenopus), where early germ layer formation has been studied extensively, the process of endoderm specification involves the interplay of dozens of transcription factors. Here, we review the interactions between these factors, summarized in a transcriptional gene regulatory network (GRN)...
June 2017: Seminars in Cell & Developmental Biology
https://www.readbyqxmd.com/read/28302118/ybx1-gene-silencing-inhibits-migratory-and-invasive-potential-via-coro1c-in-breast-cancer-in-vitro
#6
Jia Pei Lim, Sukanya Shyamasundar, Jayantha Gunaratne, Olivia Jane Scully, Ken Matsumoto, Boon Huat Bay
BACKGROUND: Y-box binding protein-1 is an evolutionary conserved transcription and translation regulating protein that is overexpressed in various human malignancies, including breast cancer. Despite reports of YB-1 and its association with distant spread of breast cancer, the intrinsic mechanism underlying this observation remains elusive. This study investigates the role of YB-1 in mediating metastasis in highly invasive breast cancer cell lines. METHODS: Silencing the YBX1 gene (which encodes the YB-1 protein) by small interfering RNA (siRNA) was performed in MDA-MB-231 and Hs578T breast cancer cell lines, followed by phenotypic assays including cell migration and invasion assays...
March 16, 2017: BMC Cancer
https://www.readbyqxmd.com/read/28278289/toyocamycin-attenuates-free-fatty-acid-induced-hepatic-steatosis-and-apoptosis-in-cultured-hepatocytes-and-ameliorates-nonalcoholic-fatty-liver-disease-in-mice
#7
Ikuko Takahara, Yuko Akazawa, Maiko Tabuchi, Katsuya Matsuda, Hisamitsu Miyaaki, Youko Kido, Yasuko Kanda, Naota Taura, Ken Ohnita, Fuminao Takeshima, Yusuke Sakai, Susumu Eguchi, Masahiro Nakashima, Kazuhiko Nakao
BACKGROUND AND AIMS: A high serum level of saturated free fatty acids (FFAs) is associated with the development of nonalcoholic fatty liver disease (NAFLD). X-box binding protein-1 (XBP-1) is activated by FFA treatment upon splicing. XBP-1 is a transcription factor induced by the endoplasmic reticulum (ER) stress sensor endoribonuclease inositol-requiring enzyme 1 alpha (IRE1α). However, the role of XBP-1 in NAFLD remains relatively unexplored. Toyocamycin was recently reported to attenuate the activation of XBP-1, possibly by inducing a conformational change in IRE1α...
2017: PloS One
https://www.readbyqxmd.com/read/28228263/reciprocal-regulation-between-53bp1-and-the-anaphase-promoting-complex-cyclosome-is-required-for-genomic-stability-during-mitotic-stress
#8
Thomas J Kucharski, Paul E Minshall, Mohamed Moustafa-Kamal, Andrew S Turnell, Jose G Teodoro
The anaphase-promoting complex/cyclosome (APC/C) is an E3 ubiquitin ligase that targets substrates for degradation to promote mitotic progression. Here, we show that the DNA damage response protein 53BP1 contains conserved KEN boxes that are required for APC/C-dependent degradation in early mitosis. Mutation of the 53BP1 KEN boxes stabilized the protein and extended mitotic duration, whereas 53BP1 knockdown resulted in a shorter and delayed mitosis. Loss of 53BP1 increased APC/C activity, and we show that 53BP1 is a direct APC/C inhibitor...
February 21, 2017: Cell Reports
https://www.readbyqxmd.com/read/28178520/identification-of-a-sgo2-dependent-but-mad2-independent-pathway-controlling-anaphase-onset-in-fission-yeast
#9
John C Meadows, Theresa C Lancaster, Graham J Buttrick, Alicja M Sochaj, Liam J Messin, Maria Del Mar Mora-Santos, Kevin G Hardwick, Jonathan B A Millar
The onset of anaphase is triggered by activation of the anaphase-promoting complex/cyclosome (APC/C) following silencing of the spindle assembly checkpoint (SAC). APC/C triggers ubiquitination of Securin and Cyclin B, which leads to loss of sister chromatid cohesion and inactivation of Cyclin B/Cdk1, respectively. This promotes relocalization of Aurora B kinase and other components of the chromosome passenger complex (CPC) from centromeres to the spindle midzone. In fission yeast, this is mediated by Clp1 phosphatase-dependent interaction of CPC with Klp9/MKLP2 (kinesin-6)...
February 7, 2017: Cell Reports
https://www.readbyqxmd.com/read/27939943/the-mitotic-checkpoint-complex-requires-an-evolutionary-conserved-cassette-to-bind-and-inhibit-active-apc-c
#10
Barbara Di Fiore, Claudia Wurzenberger, Norman E Davey, Jonathon Pines
The Spindle Assembly Checkpoint (SAC) ensures genomic stability by preventing sister chromatid separation until all chromosomes are attached to the spindle. It catalyzes the production of the Mitotic Checkpoint Complex (MCC), which inhibits Cdc20 to inactivate the Anaphase Promoting Complex/Cyclosome (APC/C). Here we show that two Cdc20-binding motifs in BubR1 of the recently identified ABBA motif class are crucial for the MCC to recognize active APC/C-Cdc20. Mutating these motifs eliminates MCC binding to the APC/C, thereby abolishing the SAC and preventing cells from arresting in response to microtubule poisons...
December 15, 2016: Molecular Cell
https://www.readbyqxmd.com/read/27935476/assessing-the-mechanism-and-therapeutic-potential-of-modulators-of-the-human-mediator-complex-associated-protein-kinases
#11
Paul A Clarke, Maria-Jesus Ortiz-Ruiz, Robert TePoele, Olajumoke Adeniji-Popoola, Gary Box, Will Court, Stephanie Czasch, Samer El Bawab, Christina Esdar, Ken Ewan, Sharon Gowan, Alexis De Haven Brandon, Phillip Hewitt, Stephen M Hobbs, Wolfgang Kaufmann, Aurélie Mallinger, Florence Raynaud, Toby Roe, Felix Rohdich, Kai Schiemann, Stephanie Simon, Richard Schneider, Melanie Valenti, Stefan Weigt, Julian Blagg, Andree Blaukat, Trevor C Dale, Suzanne A Eccles, Stefan Hecht, Klaus Urbahns, Paul Workman, Dirk Wienke
Mediator-associated kinases CDK8/19 are context-dependent drivers or suppressors of tumorigenesis. Their inhibition is predicted to have pleiotropic effects, but it is unclear whether this will impact on the clinical utility of CDK8/19 inhibitors. We discovered two series of potent chemical probes with high selectivity for CDK8/19. Despite pharmacodynamic evidence for robust on-target activity, the compounds exhibited modest, though significant, efficacy against human tumor lines and patient-derived xenografts...
December 9, 2016: ELife
https://www.readbyqxmd.com/read/27899582/the-zebrafish-model-organism-database-new-support-for-human-disease-models-mutation-details-gene-expression-phenotypes-and-searching
#12
Douglas G Howe, Yvonne M Bradford, Anne Eagle, David Fashena, Ken Frazer, Patrick Kalita, Prita Mani, Ryan Martin, Sierra Taylor Moxon, Holly Paddock, Christian Pich, Sridhar Ramachandran, Leyla Ruzicka, Kevin Schaper, Xiang Shao, Amy Singer, Sabrina Toro, Ceri Van Slyke, Monte Westerfield
The Zebrafish Model Organism Database (ZFIN; http://zfin.org) is the central resource for zebrafish (Danio rerio) genetic, genomic, phenotypic and developmental data. ZFIN curators provide expert manual curation and integration of comprehensive data involving zebrafish genes, mutants, transgenic constructs and lines, phenotypes, genotypes, gene expressions, morpholinos, TALENs, CRISPRs, antibodies, anatomical structures, models of human disease and publications. We integrate curated, directly submitted, and collaboratively generated data, making these available to zebrafish research community...
January 4, 2017: Nucleic Acids Research
https://www.readbyqxmd.com/read/27799366/hmgb2-orchestrates-the-chromatin-landscape-of-senescence-associated-secretory-phenotype-gene-loci
#13
Katherine M Aird, Osamu Iwasaki, Andrew V Kossenkov, Hideki Tanizawa, Nail Fatkhutdinov, Benjamin G Bitler, Linh Le, Gretchen Alicea, Ting-Lin Yang, F Brad Johnson, Ken-Ichi Noma, Rugang Zhang
Cellular senescence is a stable cell growth arrest that is characterized by the silencing of proliferation-promoting genes through compaction of chromosomes into senescence-associated heterochromatin foci (SAHF). Paradoxically, senescence is also accompanied by increased transcription of certain genes encoding for secreted factors such as cytokines and chemokines, known as the senescence-associated secretory phenotype (SASP). How SASP genes are excluded from SAHF-mediated global gene silencing remains unclear...
November 7, 2016: Journal of Cell Biology
https://www.readbyqxmd.com/read/27765767/uvb-exposure-prevents-atherosclerosis-by-regulating-immunoinflammatory-responses
#14
Naoto Sasaki, Tomoya Yamashita, Kazuyuki Kasahara, Atsushi Fukunaga, Tomoyuki Yamaguchi, Takuo Emoto, Keiko Yodoi, Takuya Matsumoto, Kenji Nakajima, Tomoyuki Kita, Masafumi Takeda, Taiji Mizoguchi, Tomohiro Hayashi, Yoshihiro Sasaki, Mayumi Hatakeyama, Kumiko Taguchi, Ken Washio, Shimon Sakaguchi, Bernard Malissen, Chikako Nishigori, Ken-Ichi Hirata
OBJECTIVE: UVB irradiation is an established treatment for immunoinflammatory cutaneous disorders and has been shown to suppress cutaneous and systemic inflammatory diseases through modulation of the adaptive immune response. However, it remains unknown whether UVB irradiation prevents an immunoinflammatory disease of arteries such as atherosclerosis. APPROACH AND RESULTS: Here, we show that UVB exposure inhibits the development and progression of atherosclerosis in atherosclerosis-prone mice by expanding and enhancing the functional capacity of CD4(+) forkhead box P3(+) regulatory T cells and regulating proatherogenic T-cell responses...
January 2017: Arteriosclerosis, Thrombosis, and Vascular Biology
https://www.readbyqxmd.com/read/27660208/expression-and-localization-of-forkhead-box-protein-foxj1-in-s100%C3%AE-positive-multiciliated-cells-of-the-rat-pituitary
#15
Takashi Nakakura, Takeshi Suzuki, Kotaro Horiguchi, Ken Fujiwara, Takehiro Tsukada, Anshin Asano-Hoshino, Hideyuki Tanaka, Kenjiro Arisawa, Yoshimi Nishijima, Yoko Nekooki-Machida, Yoshiko Kiuchi, Haruo Hagiwara
S100β-positive cells exist in the marginal cell layer (MCL) of the adenohypophysis and follicle structure in the parenchyma of anterior lobe (ALFS) in pituitary. They have multiple functions as phagocytes or cells that regulate hormone secretion. Majority of S100β-positive cells in the adenohypophysis express sex determining region Y-box 2 protein (SOX2), a stem cell marker; therefore, S100β/SOX2 double positive cells are also considered as one type of stem/progenitor cells. MCL and ALFS are consisting of morphologically two types of cells, i...
September 22, 2016: Medical Molecular Morphology
https://www.readbyqxmd.com/read/27590588/protective-and-therapeutic-effects-of-fucoxanthin-against-sunburn-caused-by-uv-irradiation
#16
Mio Matsui, Kosuke Tanaka, Naoki Higashiguchi, Hisato Okawa, Yoichi Yamada, Ken Tanaka, Soichiro Taira, Tomoko Aoyama, Misaki Takanishi, Chika Natsume, Yuuki Takakura, Norihisa Fujita, Takeshi Hashimoto, Takashi Fujita
Mild exposure to ultraviolet (UV) radiation is also harmful and hazardous to the skin and often causes a photosensitivity disorder accompanied by sunburn. To understand the action of UV on the skin we performed a microarray analysis to isolate UV-sensitive genes. We show here that UV irradiation promoted sunburn and downregulated filaggrin (Flg); fucoxanthin (FX) exerted a protective effect. In vitro analysis showed that UV irradiation of human dermal fibroblasts caused production of intracellular reactive oxygen species (ROS) without cellular toxicity...
September 2016: Journal of Pharmacological Sciences
https://www.readbyqxmd.com/read/27565207/cullin1-p-is-an-essential-component-of-non-self-recognition-system-in-self-incompatibility-in-petunia
#17
Ken-Ichi Kubo, Mai Tsukahara, Sota Fujii, Kohji Murase, Yuko Wada, Tetsuyuki Entani, Megumi Iwano, Seiji Takayama
Self-incompatibility (SI) in flowering plants is a genetic reproductive barrier to distinguish self- and non-self pollen to promote outbreeding. In Solanaceae, self-pollen is rejected by the ribonucleases expressed in the styles (S-RNases), via its cytotoxic function. On the other side, the male-determinant is the S-locus F-box proteins (SLFs) expressed in pollen. Multiple SLFs collaboratively detoxify non-self S-RNases, therefore, non-self recognition is the mode of self-/non-self discrimination in Solanaceae...
November 2016: Plant & Cell Physiology
https://www.readbyqxmd.com/read/27467575/open-source-drug-discovery-with-the-malaria-box-compound-collection-for-neglected-diseases-and-beyond
#18
Wesley C Van Voorhis, John H Adams, Roberto Adelfio, Vida Ahyong, Myles H Akabas, Pietro Alano, Aintzane Alday, Yesmalie Alemán Resto, Aishah Alsibaee, Ainhoa Alzualde, Katherine T Andrews, Simon V Avery, Vicky M Avery, Lawrence Ayong, Mark Baker, Stephen Baker, Choukri Ben Mamoun, Sangeeta Bhatia, Quentin Bickle, Lotfi Bounaadja, Tana Bowling, Jürgen Bosch, Lauren E Boucher, Fabrice F Boyom, Jose Brea, Marian Brennan, Audrey Burton, Conor R Caffrey, Grazia Camarda, Manuela Carrasquilla, Dee Carter, Maria Belen Cassera, Ken Chih-Chien Cheng, Worathad Chindaudomsate, Anthony Chubb, Beatrice L Colon, Daisy D Colón-López, Yolanda Corbett, Gregory J Crowther, Noemi Cowan, Sarah D'Alessandro, Na Le Dang, Michael Delves, Joseph L DeRisi, Alan Y Du, Sandra Duffy, Shimaa Abd El-Salam El-Sayed, Michael T Ferdig, José A Fernández Robledo, David A Fidock, Isabelle Florent, Patrick V T Fokou, Ani Galstian, Francisco Javier Gamo, Suzanne Gokool, Ben Gold, Todd Golub, Gregory M Goldgof, Rajarshi Guha, W Armand Guiguemde, Nil Gural, R Kiplin Guy, Michael A E Hansen, Kirsten K Hanson, Andrew Hemphill, Rob Hooft van Huijsduijnen, Takaaki Horii, Paul Horrocks, Tyler B Hughes, Christopher Huston, Ikuo Igarashi, Katrin Ingram-Sieber, Maurice A Itoe, Ajit Jadhav, Amornrat Naranuntarat Jensen, Laran T Jensen, Rays H Y Jiang, Annette Kaiser, Jennifer Keiser, Thomas Ketas, Sebastien Kicka, Sunyoung Kim, Kiaran Kirk, Vidya P Kumar, Dennis E Kyle, Maria Jose Lafuente, Scott Landfear, Nathan Lee, Sukjun Lee, Adele M Lehane, Fengwu Li, David Little, Liqiong Liu, Manuel Llinás, Maria I Loza, Aristea Lubar, Leonardo Lucantoni, Isabelle Lucet, Louis Maes, Dalu Mancama, Nuha R Mansour, Sandra March, Sheena McGowan, Iset Medina Vera, Stephan Meister, Luke Mercer, Jordi Mestres, Alvine N Mfopa, Raj N Misra, Seunghyun Moon, John P Moore, Francielly Morais Rodrigues da Costa, Joachim Müller, Arantza Muriana, Stephen Nakazawa Hewitt, Bakela Nare, Carl Nathan, Nathalie Narraidoo, Sujeevi Nawaratna, Kayode K Ojo, Diana Ortiz, Gordana Panic, George Papadatos, Silvia Parapini, Kailash Patra, Ngoc Pham, Sarah Prats, David M Plouffe, Sally-Ann Poulsen, Anupam Pradhan, Celia Quevedo, Ronald J Quinn, Christopher A Rice, Mohamed Abdo Rizk, Andrea Ruecker, Robert St Onge, Rafaela Salgado Ferreira, Jasmeet Samra, Natalie G Robinett, Ulrich Schlecht, Marjorie Schmitt, Filipe Silva Villela, Francesco Silvestrini, Robert Sinden, Dennis A Smith, Thierry Soldati, Andreas Spitzmüller, Serge Maximilian Stamm, David J Sullivan, William Sullivan, Sundari Suresh, Brian M Suzuki, Yo Suzuki, S Joshua Swamidass, Donatella Taramelli, Lauve R Y Tchokouaha, Anjo Theron, David Thomas, Kathryn F Tonissen, Simon Townson, Abhai K Tripathi, Valentin Trofimov, Kenneth O Udenze, Imran Ullah, Cindy Vallieres, Edgar Vigil, Joseph M Vinetz, Phat Voong Vinh, Hoan Vu, Nao-Aki Watanabe, Kate Weatherby, Pamela M White, Andrew F Wilks, Elizabeth A Winzeler, Edward Wojcik, Melanie Wree, Wesley Wu, Naoaki Yokoyama, Paul H A Zollo, Nada Abla, Benjamin Blasco, Jeremy Burrows, Benoît Laleu, Didier Leroy, Thomas Spangenberg, Timothy Wells, Paul A Willis
A major cause of the paucity of new starting points for drug discovery is the lack of interaction between academia and industry. Much of the global resource in biology is present in universities, whereas the focus of medicinal chemistry is still largely within industry. Open source drug discovery, with sharing of information, is clearly a first step towards overcoming this gap. But the interface could especially be bridged through a scale-up of open sharing of physical compounds, which would accelerate the finding of new starting points for drug discovery...
July 2016: PLoS Pathogens
https://www.readbyqxmd.com/read/27457505/sox9-is-a-novel-cancer-stem-cell-marker-surrogated-by-osteopontin-in-human-hepatocellular-carcinoma
#19
Takayuki Kawai, Kentaro Yasuchika, Takamichi Ishii, Yuya Miyauchi, Hidenobu Kojima, Ryoya Yamaoka, Hokahiro Katayama, Elena Yukie Yoshitoshi, Satoshi Ogiso, Sadahiko Kita, Katsutaro Yasuda, Ken Fukumitsu, Junji Komori, Etsuro Hatano, Yoshiya Kawaguchi, Shinji Uemoto
The current lack of cancer stem cell (CSC) markers that are easily evaluated by blood samples prevents the establishment of new therapeutic strategies in hepatocellular carcinoma (HCC). Herein, we examined whether sex determining region Y-box 9 (SOX9) represents a new CSC marker, and whether osteopontin (OPN) can be used as a surrogate marker of SOX9 in HCC. In HCC cell lines transfected with a SOX9 promoter-driven enhanced green fluorescence protein gene, FACS-isolated SOX9(+) cells were capable of self-renewal and differentiation into SOX9(-) cells, and displayed high proliferation capacity in vitro...
2016: Scientific Reports
https://www.readbyqxmd.com/read/27277165/optimization-of-pancreatic-lipase-inhibitory-and-antioxidant-activities-of-ilex-paraguariensis-by-using-response-surface-methodology
#20
Kyung-Eon Oh, Hyeji Shin, Young Ho Jeon, Yang Hee Jo, Mi Kyeong Lee, Ken S Lee, Byoungduck Park, Ki Yong Lee
Response surface methodology (RSM) using a Box-Behnken design was used to optimize the extraction conditions for obtaining pancreatic lipase inhibitory and antioxidant principles from Ilex paraguariensis leaves. Three influencing factors: extraction time (min), the liquid-solid ratio, and ethanol concentration (%, v/v) were investigated in the ultrasonic extraction process. Optimization of the extraction conditions to obtain a product with minimum PL activity, maximum antioxidant activity, and maximum yield was performed using RSM by focusing on the three target influencing factors...
July 2016: Archives of Pharmacal Research
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