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https://www.readbyqxmd.com/read/29150987/therapeutic-effect-of-curcumin-and-methylprednisolone-in-the-rat-spinal-cord-injury
#1
Xuehong Liu, Yong Zhang, Yang Yang, Jingquan Lin, Xue Huo, Xiaoxue Du, Benson O A Botchway, Marong Fang
In addition to imperiling an individual's daily life, spinal cord injury (SCI), a catastrophic medical damage, can permanently impair an individual's body function. Methylprednisolone (MP), a medically accepted therapeutic drug for SCI, is highly controversial for the lack of consensus on its true therapeutic effect. In recent years, curcumin has served as a potential and novel therapeutic drug in SCI. Our study was intended to investigate the precise effect of MP and curcumin in SCI. We examined the function of MP and curcumin in a SCI model rat, both in vivo and in vitro, and found that there was a momentous improvement in Basso-Beattie-Bresnahan (BBB) scores in the MP-treated group when compared to Cur-treated group within 14 days...
November 18, 2017: Anatomical Record: Advances in Integrative Anatomy and Evolutionary Biology
https://www.readbyqxmd.com/read/29150946/lncrna-tcons_00034812-in-cell-proliferation-and-apoptosis-of-pulmonary-artery-smooth-muscle-cells-and-its-mechanism
#2
Yun Liu, Zengxian Sun, Jinquan Zhu, Bingxin Xiao, Jie Dong, Xiaomin Li
Long noncoding RNAs (lncRNAs) have been discovered to be playing important role in various biological processes. However, the contribution of lncRNAs to pulmonary artery hypertension (PAH) remains largely unknown. Pulmonary vascular remodeling is an important pathological feature of PAH, leading to increased vascular resistance and reduced compliance. Here, we investigated the biological role of lncRNAs in PAH. Differences in the lncRNAs and mRNAs between hypoxia PAH rats and normoxia rats were screened using microarray analysis...
November 18, 2017: Journal of Cellular Physiology
https://www.readbyqxmd.com/read/29150865/enhanced-mu-opioid-receptor-dependent-opioidergic-modulation-of-striatal-cholinergic-transmission-in-dyt1-dystonia
#3
Giulia Ponterio, Annalisa Tassone, Giuseppe Sciamanna, Valentina Vanni, Maria Meringolo, Massimo Santoro, Nicola Biagio Mercuri, Paola Bonsi, Antonio Pisani
BACKGROUND: Mu opioid receptor activation modulates acetylcholine release in the dorsal striatum, an area deeply involved in motor function, habit formation, and reinforcement learning as well as in the pathophysiology of different movement disorders, such as dystonia. Although the role of opioids in drug reward and addiction is well established, their involvement in motor dysfunction remains largely unexplored. METHODS: We used a multidisciplinary approach to investigate the responses to mu activation in 2 mouse models of DYT1 dystonia (Tor1a(+/Δgag) mice, Tor1a(+/-) torsinA null mice, and their respective wild-types)...
November 18, 2017: Movement Disorders: Official Journal of the Movement Disorder Society
https://www.readbyqxmd.com/read/29150765/finite-element-design-optimization-of-a-hyaluronic-acid-based-hydrogel-drug-delivery-device-for-improved-retention
#4
Jourdan Colter, Barbara Wirostko, Brittany Coats
Drug-loaded hydrogel devices are emerging as an effective means of localized and sustained drug delivery for the treatment of corneal conditions and injuries. One such device uses a novel, thiolated crosslinked carboxymethylated, hyaluronic acid-based hydrogel (CMHA-S) film to deliver drug to the ocular surface upon placement into the inferior fornix of the eye. While proven to be very safe and effective, the CMHA-S film tends to dislodge in the highly-lubricated ocular environment, thereby reducing drug delivery efficiency and drug efficacy...
November 17, 2017: Annals of Biomedical Engineering
https://www.readbyqxmd.com/read/29150609/atomic-resolution-snapshot-of-leishmania-ribosome-inhibition-by-the-aminoglycoside-paromomycin
#5
Moran Shalev-Benami, Yan Zhang, Haim Rozenberg, Yuko Nobe, Masato Taoka, Donna Matzov, Ella Zimmerman, Anat Bashan, Toshiaki Isobe, Charles L Jaffe, Ada Yonath, Georgios Skiniotis
Leishmania is a single-celled eukaryotic parasite afflicting millions of humans worldwide, with current therapies limited to a poor selection of drugs that mostly target elements in the parasite's cell envelope. Here we determined the atomic resolution electron cryo-microscopy (cryo-EM) structure of the Leishmania ribosome in complex with paromomycin (PAR), a highly potent compound recently approved for treatment of the fatal visceral leishmaniasis (VL). The structure reveals the mechanism by which the drug induces its deleterious effects on the parasite...
November 17, 2017: Nature Communications
https://www.readbyqxmd.com/read/29150506/the-swinholide-biosynthetic-gene-cluster-from-a-terrestrial-cyanobacterium-nostoc-sp-uhcc-0450
#6
Anu Humisto, Jouni Jokela, Liwei Liu, Matti Wahlsten, Hao Wang, Perttu Permi, João Paulo Machado, Agostinho Antunes, David P Fewer, Kaarina Sivonen
Swinholides are 42-carbon ring polyketides with a twofold axis of symmetry. They are potent cytotoxins that disrupt the actin cytoskeleton. Swinholides were discovered from the marine sponge Theonella sp. and were long-suspected to be produced by symbiotic bacteria. Misakinolide, a structural variant of swinholide, was recently demonstrated to be the product of the symbiotic heterotrophic proteobacterium. Here we report the production of swinholide A by an axenic strain of the terrestrial cyanobacterium Nostoc sp...
November 17, 2017: Applied and Environmental Microbiology
https://www.readbyqxmd.com/read/29150490/gut-roundtable-meeting-paper-selected-recent-advances-in-hepatocellular-carcinoma
#7
REVIEW
Alexander Gerbes, Fabien Zoulim, Herbert Tilg, Jean-François Dufour, Jordi Bruix, Valérie Paradis, Riad Salem, Markus Peck-Radosavljevic, Peter R Galle, Tim F Greten, Jean-Charles Nault, Matias A Avila
Hepatocellular carcinoma (HCC) ranks number three among the most frequent causes of death from solid tumors worldwide. With obesity and fatty liver diseases as risk factors on the rise, HCC represents an ever increasing challenge. While there is still no curative treatment for most patients numerous novel drugs have been proposed, but most ultimately failed in phase III trials. This manuscript targets therapeutic advances and most burning issues. Expert key point summaries and urgent research agenda are provided regarding risk factors, including microbiota, need for prognostic and predictive biomarkers and the equivocal role of liver biopsy...
November 17, 2017: Gut
https://www.readbyqxmd.com/read/29150397/fragment-based-design-synthesis-biological-evaluation-and-sar-of-1h-benzo-d-imidazol-2-yl-1h-indazol-derivatives-as-potent-pdk1-inhibitors
#8
Ting Chen, Venkataswamy Sorna, Susie Choi, Lee Call, Jared Bearss, Kent Carpenter, Steven L Warner, Sunil Sharma, David J Bearss, Hariprasad Vankayalapati
In this work, we describe the use of the rule of 3 fragment-based strategies from biochemical screening data of 1100 in-house, small, low molecular weight fragments. The sequential combination of in silico fragment hopping and fragment linking based on S160/Y161/A162 hinge residues hydrogen bonding interactions leads to the identification of novel 1H-benzo[d]imidazol-2-yl)-1H-indazol class of Phosphoinositide-Dependent Kinase-1 (PDK1) inhibitors. Consequent SAR and follow-up screening data led to the discovery of two potent PDK1 inhibitors: compound 32 and 35, with an IC50 of 80 nM and 94 nM, respectively...
October 28, 2017: Bioorganic & Medicinal Chemistry Letters
https://www.readbyqxmd.com/read/29150282/artesunate-quercetin-luteolin-dual-drug-nanofacilitated-synergistic-treatment-for-malaria-a-plausible-approach-to-overcome-artemisinin-combination-therapy-resistance
#9
Nethravathi Puttappa, Raman Suresh Kumar, Karthik Yamjala
Malaria is one of the major global health challenge with 300 million new cases annually. The best regimen for treating Plasmodium falciparum induced malaria is based on artemisinin and its derivatives which were prescribed as artemisinin combination therapy (ACT). These are highly effective drugs resulting in rapid clearance of parasites even in severe P. falciparum induced malaria patients. However, from the past few years parasites resistant to ACT's have begun to emerge in various parts of the world such as Cambodia and Greater Mekong Subregion...
November 2017: Medical Hypotheses
https://www.readbyqxmd.com/read/29150266/interleukin-35-and-hepatocyte-growth-factor-as-a-novel-combined-immune-gene-therapy-for-multiple-sclerosis-disease
#10
Samira Moghadam, Maryam Erfanmanesh, Abdolreza Esmaeilzadeh
An autoimmune demyelination disease of the Central Nervous System, Multiple Sclerosis, is a chronic inflammation which mostly involves young adults. Suffering people face functional loss with a severe pain. Most current MS treatments are focused on the immune response suppression. Approved drugs suppress the inflammatory process, but factually, there is no definite cure for Multiple Sclerosis. Recently developed knowledge has demonstrated that gene and cell therapy as a hopeful approach in tissue regeneration...
November 2017: Medical Hypotheses
https://www.readbyqxmd.com/read/29149958/efficacy-of-prolonged-and-immediate-release-tacrolimus-in-kidney-transplantation-a-pooled-analysis-of-two-large-randomized-controlled-trials
#11
B K Krämer, L Albano, B Banas, B Charpentier, L Bäckman, H Tedesco-Silva, F Lehner, G A Mondragón-Ramírez, M Glyda, E Cassuto-Viguier, O Viklický, G Mourad, P Rigotti, S Schleibner, N Kamar
BACKGROUND: Two large, prospective studies (12-03; OSAKA) compared the efficacy and tolerability of prolonged-release versus immediate-release tacrolimus in kidney transplant patients also receiving mycophenolate mofetil and low-dose corticosteroids (without induction therapy). METHODS: Data were combined into one database to compare results over 24 weeks using 3 alternative endpoints: biopsy-confirmed acute rejection (BCAR); the Food and Drug Administration composite endpoint (graft loss, BCAR, and loss to follow-up), and the European Medicines Agency composite endpoint (graft loss, BCAR, and graft dysfunction)...
November 2017: Transplantation Proceedings
https://www.readbyqxmd.com/read/29149911/the-analysis-of-novel-microrna-mimic-sequences-in-cancer-cells-reveals-lack-of-specificity-in-stem-loop-rt-qpcr-based-microrna-detection
#12
Patrick Winata, Marissa Williams, Eileen McGowan, Najah Nassif, Nico van Zandwijk, Glen Reid
OBJECTIVE: MicroRNAs are frequently downregulated in cancer, and restoring expression has tumour suppressive activity in tumour cells. Our recent phase I clinical trial investigated microRNA-based therapy in patients with malignant pleural mesothelioma. Treatment with TargomiRs, microRNA mimics with novel sequence packaged in EGFR antibody-targeted bacterial minicells, revealed clear signs of clinical activity. In order to detect delivery of microRNA mimics to tumour cells in future clinical trials, we tested hydrolysis probe-based assays specific for the sequence of the novel mimics in transfected mesothelioma cell lines using RT-qPCR...
November 17, 2017: BMC Research Notes
https://www.readbyqxmd.com/read/29149826/novel-functions-of-microrna-17-92-cluster-in-the-endocrine-system
#13
Shan Wan, Xiang Chen, Yuedong He, Xijie Yu
BACKGROUND: MiR-17-92 cluster is coded by MIR17HG in chromosome 13, which is highly conserved in vertebrates. Published literatures have proved that miR-17-92 cluster critically regulates tumorigenesis and metastasis. Recent researches showed that the miR-17-92 cluster also plays novel functions in the endocrine system. OBJECTIVE: To summarize recent findings on the physiological and pathological roles of miR-17-92 cluster in bone, lipid and glucose metabolisms...
November 17, 2017: Current Drug Targets
https://www.readbyqxmd.com/read/29149784/anti-inflammatory-property-of-%C3%AE-d-mannuronic-acid-m2000-on-expression-and-activity-of-matrix-metalloproteinase-2-and-9-through-cd147-molecule-in-phorbol-myristate-acetate-differentiated-thp-1-cells
#14
Mohadese M Farahani, Elahe Motevaseli, Faezeh Maghsood, Maryam Heidari-Kharaji, Abbas Mirshafiey
The aim of this study was to evaluate the effects of M2000, a novel non-steroidal anti-inflammatory drug (NSAID) with immunosuppressive property and without gastro-nephrotoxicitic effects on matrix metalloproteinases (MMP)-2 and (MMP)-9 in phorbol myristate acetate (PMA)-differentiated THP-1 cells. Gene expression and activity of MMP-2 and MMP-9 are inhibited respectively by the tissue inhibitor of matrix metalloproteinase (TIMP)-2 and (TIMP)-1 and are induced by extracellular matrix metalloproteinase inducer (CD147/EMMPRIN)...
October 2017: Iranian Journal of Allergy, Asthma, and Immunology
https://www.readbyqxmd.com/read/29149783/hematological-improvement-of-patients-with-active-rheumatoid-arthritis-by-%C3%AE-d-mannuronic-acid-m2000-as-a-novel-nsaid-with-immunosuppressive-property
#15
Hossein Ahmadi, Ahmad Reza Jamshidi, Mahdi Mahmoudi, Farhad Gharibdoost, Mahdi Vojdanian, Mohammad Javad Fattahi, Noushin Rastkari, Zahra Aghazadeh, Abbas Mirshafiey
The aim of this study was to investigate the effect of β-D-mannuronic acid (M2000) on hematological parameters in patients with active rheumatoid arthritis. This study was conducted on 25 patients with active rheumatoid arthritis (RA) (identifier: IRCT2014011213739N2). M2000 was administered orally for anemic and non-anemic RA patients at a dose of 500 mg twice daily for 12 weeks. The patients were permitted to continue the conventional treatments excluding NSAIDs. Blood samples were collected at baseline, 4 and 12 weeks after drug administration and were tested for hematological parameters...
October 2017: Iranian Journal of Allergy, Asthma, and Immunology
https://www.readbyqxmd.com/read/29149502/annual-banned-substance-review-analytical-approaches-in-human-sports-drug-testing
#16
Mario Thevis, Tiia Kuuranne, Hans Geyer
A number of high profile revelations concerning anti-doping rule violations over the past 12 months has outlined the importance of tackling prevailing challenges and reducing the limitations of the current anti-doping system. At this time, the necessity to enhance, expand and improve analytical test methods in response to the substances outlined in the World Anti-Doping Agency's (WADA) Prohibited List represents an increasingly crucial task for modern sports drug testing programs. The ability to improve analytical testing methods often relies on the expedient application of novel information regarding superior target analytes for sports drug testing assays, drug elimination profiles, alternative test matrices, together with recent advances in instrumental developments...
November 17, 2017: Drug Testing and Analysis
https://www.readbyqxmd.com/read/29149148/current-impact-and-application-of-abuse-deterrent-opioid-formulations-in-clinical-practice
#17
Ya-Han Lee, Daniel L Brown, Hsiang-Yin Chen
BACKGROUND: Abuse-deterrent formulations (ADFs) represent one novel strategy for curbing the potential of opioid abuse. OBJECTIVE: We aim to compare and contrast the characteristics and applications of current abuse-deterrent opioid products in clinical practice. METHODS: Literature searches were conducted in databases (Pubmed Medline, International Pharmaceutical Abstracts, Google Scholar) and official reports. Relevant data were screened and organized into: 1) epidemiology of opioid abuse, 2) mitigation strategies for reducing opioid abuse, 3) development of ADFs, and 4) clinical experience with these formulations...
November 2017: Pain Physician
https://www.readbyqxmd.com/read/29148866/drugs-of-abuse-and-novel-psychoactive-substances-at-outdoor-music-festivals-in-colorado
#18
Jacob Fox, Alexis Smith, Alexander Yale, Christopher Chow, Elsa Alaswad, Tracy Cushing, Andrew A Monte
BACKGROUND: Drugs of abuse (DOA) are widely used in the United States and are ubiquitous at outdoor music festivals. Attendees at music festivals are at high-risk for novel psychoactive substance (NPS) use, which is becoming more prevalent worldwide. No U.S. studies have employed an qualitative approach to investigate the etiologies of both traditional DOA and NPS use amongst music festival attendees. OBJECTIVES: The objective of this study was to improve understanding of the knowledge, attitudes, beliefs, and practices of festival attendees using NPS and DOA...
November 17, 2017: Substance Use & Misuse
https://www.readbyqxmd.com/read/29148850/atad2-in-cancer-a-pharmacologically-challenging-but-tractable-target
#19
Muzammal Hussain, Yang Zhou, Yu Song, H M Adnan Hameed, Hao Jiang, Yaoquan Tu, Jiancun Zhang
ATAD2 protein is an emerging oncogene that has strongly been linked to the etiology of multiple advanced human cancers. Therapeutically, despite the fact that genetic suppression/knockdown studies have validated it as a compelling drug target for future therapeutic development, recent druggability assessment data suggest that direct targeting of ATAD2's bromodomain (BRD) may be a very challenging task. ATAD2's BRD has been predicted as a "difficult to drug" or "least druggable" target due to the concern that its binding pocket, and the areas around it, seem to be unfeasible for ligand binding...
November 17, 2017: Expert Opinion on Therapeutic Targets
https://www.readbyqxmd.com/read/29148755/novel-anti-tubercular-6-dialkylaminopyrimidine-carboxamides-from-phenotypic-whole-cell-high-throughput-screening-of-a-softfocus-library-structure-activity-relationship-and-target-identification-studies
#20
Colin R Wilson, Richard K Gessner, Atica Moosa, Ronnett Seldon, Digby F Warner, Valerie Mizrahi, Candice Soares de Melo, Sandile B Simelane, Aloysius T Nchinda, Efrem Abay, Dale Taylor, Mathew Njoroge, Christel Brunschwig, Nina Lawrence, Helena I M Boshoff, Clifton E Barry, Frederick A Sirgel, Paul van Helden, C John Harris, Richard Gordon, Sonja Ghidelli-Disse, Hannah Pflaumer, Markus Boesche, Gerard Drewes, Olalla Sanz, Gracia Santos, Maria José Rebollo-Lopez, Beatriz Urones, Carolyn Selenski, Maria Jose Lafuente-Monasterio, Matthew Axtman, Joël Lelièvre, Lluis Ballell, Rudolf Mueller, Leslie J Street, Sandeep R Ghorpade, Kelly Chibale
A BioFocus DPI SoftFocus library of ~35,000 compounds was screened against Mycobacterium tuberculosis (Mtb) in order to identify novel hits with anti-tubercular activity. The hits were evaluated in biology triage assays to exclude compounds suggested to function via frequently encountered promiscuous mechanisms of action including inhibition of the QcrB subunit of the cytochrome bc1 complex, disruption of cell-wall homeostasis, and DNA damage. Among the hits which passed this screening cascade, a 6-dialkylaminopyrimidine carboxamide series was prioritized for hit to lead optimization...
November 17, 2017: Journal of Medicinal Chemistry
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