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drug target disease

Yu-Ting Cheng, Jer-An Lin, Jhih-Jia Jhang, Gow-Chin Yen
Oxidative stress contributes to the progression of non-steroidal anti-inflammatory drug (NSAID)-induced gastrointestinal (GI) cell apoptosis. In our previous study, we reported that nuclear factor erythroid 2-related factor 2 (Nrf2) plays a protective role against ketoprofen-induced GI mucosal oxidative injury. Recent reports suggest that Nrf2 could exhibit antioxidative and antiapoptosis responses through up-regulation of DJ-1 (PARK7). In the current study, we proposed that induction of DJ-1 expression by protocatechuic acid (PCA) might provide a potential therapeutic approach for treating oxidative stress-associated GI ulcer diseases...
October 13, 2018: Free Radical Biology & Medicine
Yunes Panahi, Reza Yekta, Gholamreza Dehghan, Samaneh Rashtbari, Nematollah Jonaidi Jafari, Ali A Moosavi-Movahedi
Aspirin (ASP) and pioglitazone (PGL) are the most common drugs that are widely used by diabetic patients to control the blood sugar and hinder cardiovascular diseases. The interaction between PGL and ASP is one of the important medical issues to clarify the safety of co-administration of these drugs. In the present study, the effect of co-administered ASP with PGL was investigated on the structure and catalytic function of catalase as a potential target in the liver. Based on our data, co-administration of ASP-PGL significantly enhanced the catalase activity in comparison with PGL alone...
October 13, 2018: Biochimie
John P Bourke, Teofila Bueser, Rosaline Quinlivan
BACKGROUND: The dystrophinopathies include Duchenne muscular dystrophy (DMD), Becker muscular dystrophy (BMD), and X-linked dilated cardiomyopathy (XLDCM). In recent years, co-ordinated multidisciplinary management for these diseases has improved the quality of care, with early corticosteroid use prolonging independent ambulation, and the routine use of non-invasive ventilation signficantly increasing survival. The next target to improve outcomes is optimising treatments to delay the onset or slow the progression of cardiac involvement and so prolong survival further...
October 16, 2018: Cochrane Database of Systematic Reviews
Aliye Uc, Dana K Andersen, Drucy Borowitz, Marshall J Glesby, Julia Mayerle, Robert Sutton, Stephen J Pandol
A workshop was sponsored by the Division of Digestive Diseases and Nutrition, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, on July 25, 2018, in Pittsburgh, Penn. The workshop was designed to bring together a multidisciplinary group of experts to accelerate the development of therapeutics for clinical application in inflammatory diseases of the exocrine pancreas. Three separate working groups (acute pancreatitis, recurrent acute pancreatitis, and chronic pancreatitis) were formed to address the needs, gaps, and opportunities...
November 2018: Pancreas
Nur Adibah Mohidem, Zailina Hashim, Malina Osman, Rafiza Shaharudin, Farrah Melissa Muharam, Punitha Makeswaran
Background Tuberculosis (TB) is making a comeback and has remained one of the main causes of mortality among the list of infectious diseases in Malaysia. Objective To evaluate the burden and demographic, socio-economic and behavior as risk factors of TB among communities in Malaysia. Method A comprehensive search of Scopus, Sciencedirect, PubMed, DOAJ, CINAHL Plus, MyJournal, BIREME, BMC Public Health, Medline, CAB, EMBASE (Excerpta Medica dataBASE), and Web of Science (WoS) was undertaken from the articles published from 1st January 2008 to 31st December 2017 using medical subject heading (MeSH) key terms...
October 16, 2018: Reviews on Environmental Health
Xing Chen, Na-Na Guan, Ya-Zhou Sun, Jian-Qiang Li, Jia Qu
Small molecule is a kind of low molecular weight organic compound with variety of biological functions. Studies have indicated that small molecules can inhibit a specific function of a multifunctional protein or disrupt protein-protein interactions and may have beneficial or detrimental effect against diseases. MicroRNAs (miRNAs) play crucial roles in cellular biology, which makes it possible to develop miRNA as diagnostics and therapeutic targets. Several drug-like compound libraries were screened successfully against different miRNAs in cellular assays further demonstrating the possibility of targeting miRNAs with small molecules...
October 16, 2018: Briefings in Bioinformatics
Hong-Kai Wang, Wen-Hao Xu, Chun-Guang Ma, Liang-Ping Zhou, Guo-Hai Shi, Hai-Liang Zhang, Ding-Wei Ye
OBJECTIVES: To investigate the role of tumor growth velocity in defining tumor progression in metastatic renal cell carcinoma patients treated with the vascular endothelial growth factor tyrosine kinase inhibitor, sorafenib. METHODS: A modified calculation for tumor growth velocity was introduced to evaluate the tumor growth velocity, before and after sorafenib withdrawal. Known prognostic factors together with tumor growth velocity before drug withdrawal and tumor growth velocity after drug withdrawal were compared using a χ2 -test from a contingency table, and partial likelihood test from a Cox regression model for overall survival...
October 16, 2018: International Journal of Urology: Official Journal of the Japanese Urological Association
Bismark Sarfo, Zelalem Haile, Selase Deletsu, Eric Akpanja Mensah
Background Tumor necrosis factor and its receptors (sTNFR1 and sTNFR2) have been implicated in many infectious diseases. Identification of the key receptor (sTNFR1 or sTNFR2) which drives the immunopathogenesis of HIV infection is crucial in developing adjunctive therapy for HIV. Objective This study determined the expression levels of sTNFR1 and sTNFR2 in antiretroviral therapy (ART) - experienced and naïve HIV patients. Method: A total of 40 HIV patients comprising 30 with ART and 10 without ART were enrolled from the Pantang Hospital located in the Greater Accra Region of Ghana for data and blood collection...
October 16, 2018: Infectious Disorders Drug Targets
Rakesh Kumar, Ritika Sharma, Inder Kumar, Pooja Upadhyay, Ankit Kumar Dhiman, Rohit Kumar, Rakesh Kumar, Rituraj Purohit, Dinkar Sahal, Upendra Sharma
BACKGROUND: Malaria remains a common life-threatening infectious disease across the globe due to the development of resistance by Plasmodium parasite against most antimalarial drugs. The situation demands new and effective drug candidates against Plasmodium. OBJECTIVES: The objective of this study is to design, synthesize and test novel quinoline based molecules against the malaria parasite. METHOD: C-2 and C-8 modified quinoline analogs obtained via C-H bond functionalization approach were synthesized and evaluated for inhibition of growth of P...
October 15, 2018: Medicinal Chemistry
Kelly Lynn Summers
Malaria is a potentially life-threatening disease, affecting approx. 214 million people world-wide. Malaria is caused by protozoan, Plasmodium falciparum, which is transmitted through the Anopheles mosquito. Malaria treatment is becoming more challenging due to rising resistance against the antimalarial drug, chloroquine. Novel compounds that target aspects of parasite development are being explored in attempts to overcome this wide-spread problem. Anti-malarial drugs target specific aspects of parasite growth and development within the human host...
October 15, 2018: Mini Reviews in Medicinal Chemistry
Xin Li, Daniel Staub, Vasileios Rafailidis, Mohammed Al-Natour, Sanjeeva Kalva, Sasan Partovi
Ultrasound has been established as an important diagnostic tool in assessing vascular abnormalities. Standard B-mode and Doppler techniques have inherent limitations with regards to detection of slow flow and small vasculature. Contrast-enhanced ultrasound (CEUS) is a complementary tool and is useful in assessing both the macro- and microvascular anatomy of the aorta. CEUS can also provide valuable physiological information in real-time scanning sessions due to the physical and safety profiles of the administered microbubbles...
October 16, 2018: VASA. Zeitschrift Für Gefässkrankheiten
Eran Zimran, Alla Keyzner, Camelia Iancu-Rubin, Ronald Hoffman, Marina Kremyanskaya
Despite the dramatic progress made in the treatment of patients with myelofibrosis since the introduction of the JAK1/2 inhibitor ruxolitinib, a therapeutic option that can modify the natural history of the disease and prevent evolution to blast-phase is still lacking. Recent investigational treatments including immunomodulatory drugs and histone deacetylase inhibitors benefit some patients but these effects have proven modest at best. Several novel agents do show promising activity in preclinical studies and early-phase clinical trials...
October 16, 2018: Expert Review of Hematology
Punnaka Pongpanich, Pasvich Pitakpaiboonkul, Kullaya Takkavatakarn, Kearkiat Praditpornsilpa, Somchai Eiam-Ong, Paweena Susantitaphong
BACKGROUND: The prevalence of hypertension and its associated complications are markedly growing. Most patients need more than one drug to achieve blood pressure (BP) target. However, most guidelines only focus on the first-line treatment. We conducted a meta-analysis to explore the benefits of angiotensin-converting enzyme inhibitors (ACEIs)/angiotensin II receptor blockers (ARBs) combined with calcium channel blockers (CCBs) on metabolic, renal, and cardiovascular outcomes in hypertensive patients...
October 15, 2018: International Urology and Nephrology
Charles Chesnelong, Ian Restall, Samuel Weiss
Cancer stem cells (CSCs) have been identified in glioblastoma (GBM) and are proposed to be the main actors of post-treatment recurrence contributing to the very dismal prognosis of this devastating disease. Consequently, this important population of cells needs to be further studied to uncover potential vulnerabilities, identify novel therapeutic targets, and develop drugs that can be translated to the clinic. One obstacle preventing progress in understanding the biology of GBM and the development of novel therapies has arguably been the absence of biologically relevant in vitro models representative of the CSC population in GBM...
2019: Methods in Molecular Biology
Alexey Stupnikov, Paul G O'Reilly, Caitriona E McInerney, Aideen C Roddy, Philip D Dunne, Alan Gilmore, Hayley P Ellis, Tom Flannery, Estelle Healy, Stuart A McIntosh, Kienan Savage, Kathreena M Kurian, Frank Emmert-Streib, Kevin M Prise, Manuel Salto-Tellez, Darragh G McArt
Purpose: Gene expression profiling can uncover biologic mechanisms underlying disease and is important in drug development. RNA sequencing (RNA-seq) is routinely used to assess gene expression, but costs remain high. Sample multiplexing reduces RNAseq costs; however, multiplexed samples have lower cDNA sequencing depth, which can hinder accurate differential gene expression detection. The impact of sequencing depth alteration on RNA-seq-based downstream analyses such as gene expression connectivity mapping is not known, where this method is used to identify potential therapeutic compounds for repurposing...
September 13, 2018: JCO Precision Oncology
Tatsuya Osaki, Sebastien G M Uzel, Roger D Kamm
Amyotrophic lateral sclerosis (ALS), a progressive neurodegenerative disease involving loss of motor neurons (MNs) and muscle atrophy, still has no effective treatment, despite much research effort. To provide a platform for testing drug candidates and investigating the pathogenesis of ALS, we developed an ALS-on-a-chip technology (i.e., an ALS motor unit) using three-dimensional skeletal muscle bundles along with induced pluripotent stem cell (iPSC)-derived and light-sensitive channelrhodopsin-2-induced MN spheroids from a patient with sporadic ALS...
October 2018: Science Advances
Mohamad Elbaz, Dinesh Ahirwar, Zhang Xiaoli, Xinyu Zhou, Maryam Lustberg, Mohd W Nasser, Konstantin Shilo, Ramesh K Ganju
Transient receptor potential vanilloid type-2 (TRPV2) is an ion channel that is triggered by agonists like cannabidiol (CBD). Triple negative breast cancer (TNBC) is an aggressive disease with limited therapeutic options. Chemotherapy is still the first line for the treatment of TNBC patients; however, TNBC usually gains rapid resistance and unresponsiveness to chemotherapeutic drugs. In this study, we found that TRPV2 protein is highly up-regulated in TNBC tissues compared to normal breast tissues. We also observed that TNBC and estrogen receptor alpha negative (ERβ-) patients with higher TRPV2 expression have significantly higher recurrence free survival compared to patients with lower TRPV2 expression especially those who were treated with chemotherapy...
September 11, 2018: Oncotarget
Huensuk Kim, Christoph Schaniel
The advent of induced pluripotent stem cells (iPSCs) together with recent advances in genome editing, microphysiological systems, tissue engineering and xenograft models present new opportunities for the investigation of hematological diseases and cancer in a patient-specific context. Here we review the progress in the field and discuss the advantages, limitations, and challenges of iPSC-based malignancy modeling. We will also discuss the use of iPSCs and its derivatives as cellular sources for drug target identification, drug development and evaluation of pharmacological responses...
2018: Frontiers in Immunology
Laura Thei, Jennifer Imm, Eleni Kaisis, Mark L Dallas, Talitha L Kerrigan
Alzheimer's disease is the most common form of dementia, it is estimated to affect over 40 million people worldwide. Classically, the disease has been characterized by the neuropathological hallmarks of aggregated extracellular amyloid-β and intracellular paired helical filaments of hyperphosphorylated tau. A wealth of evidence indicates a pivotal role for the innate immune system, such as microglia, and inflammation in the pathology of Alzheimer's disease. The over production and aggregation of Alzheimer's associated proteins results in chronic inflammation and disrupts microglial clearance of these depositions...
2018: Frontiers in Neuroscience
Yong Wu, En Lin Goh, Dong Wang, Shaocheng Ma
Osteoarthritis is the most prevalent chronic joint condition worldwide. The principles of osteoarthritis treatment are to alleviate pain and stiffness as well as maintain function, with current consensus guidelines recommending the use of a combination of conservative measures including physical therapy, analgesia, and surgical interventions such as arthroplasty. In recent years, several pharmacological therapies have emerged as potential alternatives. Although a disease-modifying osteoarthritis drug has yet to be identified, promising results have been reported in recent trials especially with serotonin-norepinephrine reuptake inhibitors, IL-1 antagonists, and antibodies to nerve growth factor...
2018: Open Access Rheumatology: Research and Reviews
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