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Current Drug Targets

Lei Zhang, Zahid Hussain, Zhuanqin Ren
BACKGROUND: Normal pressure hydrocephalus (NPH) is a critical brain disorder in which excess cerebrospinal fluid (CSF) is accumulated in the brain's ventricles causing damage or disruption of the brain tissues. Amongst various signs and symptoms, difficulty in walking, blurred speech, impaired decision making and critical thinking, and loss of bladder and bowl control are considered the hallmark features of NPH. OBJECTIVE: The current review was aimed to present a comprehensive overview and critical appraisal of majorly employed neuroimaging techniques for rational diagnosis and effective monitoring of effectiveness of employed therapeutic intervention for NPH...
February 14, 2019: Current Drug Targets
Zahid Hussain, Lei Zhang, Zhuanqin Ren
BACKGROUND: Normal pressure hydrocephalus (NPH) is a critical brain disorder in which excess cerebrospinal fluid (CSF) is accumulated in the brain's ventricles causing damage or disruption of the brain tissues. Amongst various signs and symptoms, difficulty in walking, blurred speech, impaired decision making and critical thinking, and loss of bladder and bowl control are considered the hallmark features of NPH. OBJECTIVE: The current review was aimed to present a comprehensive overview and critical appraisal of majorly employed neuroimaging techniques for rational diagnosis and effective monitoring of effectiveness of employed therapeutic intervention for NPH...
February 14, 2019: Current Drug Targets
Natiele Carla da Silva Ferreira, Luiz Anastacio Alves, Rômulo José Soares-Bezerra
BACKGROUND: Extracellular purines and pyrimidines have important physiological functions in mammals. Purines and pyrimidines act on P1 and P2 purinergic receptors, which are widely expressed in the plasma membrane in various cell types. P2 receptors act as important therapeutic targets and are associated with several disorders, such as pain, neurodegeneration, cancer, inflammation, and thrombosis. However, the use of antagonists for P2 receptors in clinical therapy, with the exception of P2Y12, is a great challenge...
February 12, 2019: Current Drug Targets
Amna Khan, Salman Khan, Yeong Shik Kim
Pain is a complex multidimensional concept that facilitates the initiation of the signaling cascade in response to any noxious stimuli. Action potential generation in the peripheral nociceptor terminal and its transmission through various types of nociceptors corresponding to mechanical, chemical or thermal stimuli leads to the activation of receptors and further neuronal processing produces sensation of pain. Numerous types of receptors are activated in pain sensation which varies in their signaling pathway...
January 30, 2019: Current Drug Targets
Farhad Seif, Laleh Sharifi, Majid Khoshmirsafa, Yasaman Mojibi, Monireh Mohsenzadegan
Prostate cancer is a malignant cancer leading to high mortality in the male population. The existence of suppressive cells referred to as tumor-associated macrophages (TAM) is a major obstacle in prostate cancer immunotherapy. TAMs contribute to the immunosuppressive microenvironment that promote tumor growth and metastasis. In fact, they are main regulators of the complicated interactions between tumor and surrounding microenvironment. M2 macrophages, as a type of TAMs, are involved in the growth and progression of prostate cancer...
January 23, 2019: Current Drug Targets
Francesca Liva, Doretta Cuffaro, Elisa Nuti, Susanna Nencetti, Elisabetta Orlandini, Giovanni Vozzi, Armando Rossello
BACKGROUND: Advanced age-related macular degeneration (AMD) is the leading cause of blindness in the elderly with limited therapeutic options. The disease is characterized by photoreceptor loss in the macula and reduced retinal pigment epithelium (RPE) function, associated with matrix degradation, cell proliferation, neovascularization and inflammation. Matrix metalloproteinases (MMPs), a disintegrin and metalloproteinases (ADAMs) and a disintegrin and metalloproteinase with thrombospondin motifs (ADAMTSs) play a critical role in the physiology of extracellular membrane (ECM) turnover and, in turn, in ECM pathologies, such as AMD...
January 21, 2019: Current Drug Targets
Marzo J L, Jornet J M, Pierobon M
By interconnecting nanomachines and forming nanonetworks, the capacities of single nanomachines are expected to be enhanced as the ensuing information exchange will allow them to cooperate towards a common goal. Nowadays, systems normally use electromagnetic signals to encode, send and receive information, however, in a novel communication paradigm, molecular transceivers, channel models or protocols use molecules. This article presents the current developments in nanomachines along with their future architecture to better understand nanonetwork scenarios in biomedical applications...
January 15, 2019: Current Drug Targets
Antonio J Guerra, Hernan Lara-Padilla, Luiz H Catalani, Matthew L Becker, Ciro A Rodriguez, David Dean
With the advent of inexpensive and highly accurate 3D printing devices, a tremendous flurry of research activity has been unleashed into new resorbable, polymeric materials that can be printed using three approaches: hydrogels for bioprinting and bioplotting, sintered polymer powders, and solid cured (photocrosslinked) resins. Additionally, there is a race to understand the role of extracellular matrix components and cell signaling molecules and to fashion ways to incorporate these materials into resorbable implants...
January 14, 2019: Current Drug Targets
Hassan Dianat-Moghadam, Ladan Teimoori-Toolabi
Fibroblast growth factors (FGFs) are pleiotropic molecules exerting autocrine, intracrine and paracrine functions via activating four tyrosine kinase FGF receptors (FGFR), which further trigger a variety of cellular processes including angiogenesis, evasion from apaoptosis, bone formation, embryogenesis, wound repair and homeostasis. Four major mechanisms including angiogenesis, inflammation, cell proliferation, and metastasis are active in FGF/FGFR-driven tumors. Furthermore, gain-of-function or loss-of-function in FGFRs1-4 which is due to amplifications, fusions, and mutations, changes in tumor-stromal cells interactions, associates with the development and progression of cancer...
January 12, 2019: Current Drug Targets
Aditi Kaushik, Manish Kaushik, Viney Lather, J S Dua
An emerging crisis of antibiotic resistance for microbial pathogens is alarming all the nations posing a global threat to human health. The production of metallo-β-lactamase enzyme is the most powerful strategy of bacteria to produce resistance. An efficient way to combat this global health threat is the development of broad/non-specific type of metallo-β-lactamase inhibitors, which can inhibit the different isoforms of the enzyme. Till date there are no clinically active drugs against metallo-β-lactamase...
December 16, 2018: Current Drug Targets
Pedro Xavier-Elsas, Bruno Marques Vieira, Daniela Masid-de-Brito, Monica Gomes Barradas, Maria Ignez C Gaspar-Elsas
Vitamin A and its derivatives (retinoids) act as potent regulators in many aspects of mammalian reproduction, development, repair, and maintenance of differentiated tissue functioning. Unlike other vitamins, Vitamin A and retinoids, which have hormonal actions, present significant toxicity, which plays roles in clinically relevant situations, such as hypervitaminosis A and retinoic acid ("differentiation") syndrome. Although clinical presentation is conspicuous in states of insufficient or excessive Vitamin A and retinoid concentration, equally relevant effects on host resistance to specific infectious agents, and in the general maintenance of immune homeostasis, may go unnoticed, because their expression requires either pathogen exposure or the presence of inflammatory co-morbidities...
December 16, 2018: Current Drug Targets
Zhenqi Liu, Baichun Yang
Newer classes of medications have been proven useful in glycemic control in type 2 diabetes (T2D), but many do not appear capable to slow down the progressive loss of ß-cell function, or to improve population-level glycemic control. Positive energy balance, e.g. surplus energy intake over expenditure, is at the core for developing metabolic syndrome and T2D. Currently available glycemic control drugs come to the market based on their 1-2 years risk-benefit profiles, but most of them do not correct positive energy balance and lose efficacy in the long-term...
December 16, 2018: Current Drug Targets
Jieqiong You, Rong Dong, Meidan Ying, Qiaojun He, Ji Cao, Bo Yang
BACKGROUND: Cellular senescence is generally understood as permanent cell cycle arrest stemming from different causes. The mechanism of cellular senescence-induced cell cycle arrest is complex, involving interactions between telomere shortening, inflammations and cellular stresses. In recent years, a growing number of studies have revealed that cellular senescence could mediate the cancer progression of neighboring cells, but this idea is controversial and contradictory evidence argues that cellular senescence also contributes to tumor suppression...
December 16, 2018: Current Drug Targets
Manuel Yepes
The plasminogen activation (PA) system was originally thought to exclusively promote the degradation of fibrin by catalyzing the conversion of plasminogen into plasmin via two serine proteinases: tissue-type plasminogen activator (tPA) and urokinase-type plasminogen activator (uPA). However, experimental evidence accumulated over the last 30 years indicates that tPA and uPA are also found in the central nervous system (CNS), where they have a plethora of functions that not always require plasmin generation or fibrin degradation...
December 11, 2018: Current Drug Targets
Meysam Gachpazan, Hoda Kashani, Majid Khazaei, Seyed Mahdi Hassanian, Majid Rezayi, Fereshteh Asgharzadeh Yazdi, Majid Ghayour-Mobarhan, Gordon A Ferns, Amir Avan
Statins are 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitors that may play an important role in the evolution of cancers, due to their effects on cancer cell metabolism. Statins effect several potential pathways, including: cell proliferation, angiogenesis, apoptosis and metastasis. The number of trials assessing the putative clinical benefits of statins in cancer is increasing. Currently, there are several trials listed on the global trial identifier website Given the compelling evidence from these trials in a variety of clinical settings, there have been calls for a clinical trial of statins in the adjuvant gastrointestinal cancer setting...
December 11, 2018: Current Drug Targets
Xiaotong Wang, Ye Yuan, Zhenbo Han, Ying Yu, Zihang Xu, Benzhi Cai
Cardiovascular disease (CVD) is the number one killer of human beings which has long become the disease with the highest incidence and disability rate in modern society. Currently induced pluripotent stem cells (iPSCs), with the potential to form fresh myocardium and better safety than other stem cells, are widely used in the CVD therapy studies. Moreover, iPSC-derived cardiomyocytes (CMs), as a novel disease model, appear to play an important role in new drug screening, drug safety assessment, and pathological mechanisms of disease...
December 11, 2018: Current Drug Targets
Vinayak Narayanankutty, Arunaksharan Narayanankutty, Anusree Nair
BACKGROUND: Heat shock proteins (HSPs) are predominant molecular chaperone which is actively involved in the protein folding; which is essential in protecting the structure and functioning of proteins during various stress conditions. Though HSPs have important physiological roles, they have been well known for their roles in various pathogenic conditions such as carcinogenesis; however, limited literature has consolidated its potential as an anti-metastatic drug target. OBJECTIVES: The present review outlines the role of different HSPs on cancer progression and metastasis; possible role of HSP inhibitors as anti-neoplastic agents are also discussed...
December 10, 2018: Current Drug Targets
Jianting Gong, Xian Tan, Yongbing Chen, Pingping Sun, Fei He, Li Zhang, Yanwen Li, Zhiqiang Ma, Han Wang
Membrane proteins play a crucial physiological role in vivo and are the major category of drug targets for pharmaceuticals. The research on membrane protein is a significant part in drug discovery due to a membrane protein can be regarded as a vital hub while most drug effect by drug-target interaction and the biological process can be supposed as a cycled network. In this review, typical membrane protein targets are described, including GPCRs, transporters, ion channels. In addition, network servers and databases referring to the drug and target information as well as drug discovery data are concluded...
December 4, 2018: Current Drug Targets
Priscylla Andrade Volkart, Gabriela Bitencourt-Ferreira, André Arigony Souto, Walter Filgueira de Azevedo
BACKGROUND: Cyclin-dependent kinase 2 (CDK2) has been studied due to its role in the cell-cycle progression. The elucidation of the CDK2 structure paved the way to investigate the molecular basis for inhibition of this enzyme, with the coordinated efforts combining crystallography with functional studies. OBJECTIVE: Our goal here is to review recent functional and structural studies directed to understanding the role of CDK2 in cancer and senescence. METHOD: There are over four hundreds of crystallographic structures available for CDK2, many of them with binding affinity information...
December 4, 2018: Current Drug Targets
Benjamin J Buckley, Michael J Kelso, Umar Ali, Marie Ranson
Rheumatoid arthritis (RA) is a chronic and progressive inflammatory disease characterized in its early stages by synovial hyperplasia and inflammatory cell infiltration and later by irreversible joint tissue destruction. The plasminogen activation system (PAS) is associated with a wide range of physiological and pathophysiological states involving fibrinolysis, inflammation and tissue remodeling. Various components of the PAS are implicated in the pathophysiology of RA. Urokinase plasminogen activator (uPA) in particular is a pro-inflammatory mediator that appears to play an important role in the bone and cartilage destruction associated with RA...
December 4, 2018: Current Drug Targets
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