Antiarthritis Effect of Morin is Associated with Inhibition of Synovial Angiogensis
This study investigated its effect on type II collagen‐induced arthritis (CIA) in rats and explored the underlying mechanisms in view of synovial angiogenesis. Morin administered po attenuated arthritic progression as indicated by reduction of arthritis scores and paw swelling. It also markedly reduced serum levels of the proinflammatory cytokines, tumor necrosis factor alpha (TNF‐α) and interleukin‐6 (IL‐6), but increased the level of anti‐inflammatory cytokine interleukin‐10, and ameliorated histopathological changes of joints. Morin markedly inhibited expression of CD31, vascular endothelial growth factor (...
Source: Drug Development Research - September 1, 2015 Category: Drugs & Pharmacology Authors: Ni Zeng, Bei Tong, Xinyu Zhang, Yannong Dou, Xin Wu, Yufeng Xia, Yue Dai, Zhifeng Wei Tags: Research Article Source Type: research
Steroid Sulfatase Inhibitors Based on Phosphate and Thiophosphate Flavone Analogs
ABSTRACT
A series of phosphate and thiophosphate flavone derivatives were synthesized and biologically evaluated in vitro for inhibition of steroid sulfatase (STS) activity. The described synthesis includes the straightforward preparation of 7‐hydroxy‐2‐phenyl‐4H‐chromen‐4‐one 3a, 2‐(4‐fluorophenyl)‐7‐hydroxy‐4H‐chromen‐4‐one 3b, 7‐hydroxy‐2‐(4‐(trifluoromethyl)phenyl)‐4H‐chromen‐4‐one 3c, 7‐hydroxy‐2‐(p‐tolyl)‐4H‐chromen‐4‐one 3d modified with different phosphate or thiophosphate moieties. The inhibitory properties of the synthesized compounds were teste...
Source: Drug Development Research - September 1, 2015 Category: Drugs & Pharmacology Authors: Witold Kozak, Mateusz Daśko, Maciej Masłyk, Konrad Kubiński, Janusz Rachon, Sebastian Demkowicz Tags: Research Article Source Type: research
Targeting c‐Met in Cancer by MicroRNAs: Potential Therapeutic Applications in Hepatocellular Carcinoma
ABSTRACT
Cancer is one of the world's deadliest diseases, with very low survival rates and increased occurrence in the future. Successfully developed target‐based therapies have significantly changed cancer treatment. However, primary and/or acquired resistance in the tumor is a major challenge in current therapies and novel combinational therapies are required. RNA interference‐mediated gene inactivation, alone or in combination with other current therapies, provides novel promising therapeutics that can improve cure rate and overcome resistance mechanisms to conventional therapeutics. Hepatocyte Growth Factor/...
Source: Drug Development Research - September 1, 2015 Category: Drugs & Pharmacology Authors: Zeynep F. Karagonlar, Peyda Korhan, Neşe Atabey Tags: Research Overview Source Type: research
Targeting MicroRNAs in Prevention and Treatment of Neurodegenerative Disorders
ABSTRACT
microRNAs (miRNAs) are small noncoding RNAs (ncRNAs) that are key regulators of gene expression. They act on wide range of targets by binding to mRNA via imperfect complementarity at 3′ UTR. Evidence suggests that miRNAs regulate many biological processes including neuronal development, differentiation, and disease. Altered expression of several miRNAs has been reported in many neurodegenerative disorders (NDDs). Many miRNAs are altered in these diseases, but miRNA 15, miRNA 21, and miRNA 146a have been shown to play critical role in many neurodegenerative conditions. As these miRNAs regulate many genes, ...
Source: Drug Development Research - September 1, 2015 Category: Drugs & Pharmacology Authors: Smriti Gupta, Savita Verma, Shrikant Mantri, Nancy E. Berman, Rajat Sandhir Tags: Research Overview Source Type: research
Therapeutic Targeting of microRNAs in Cancer: Future Perspectives
ABSTRACT
The discovery of microRNAs (miRNAs) and their link with cancer has opened a new era in cancer therapeutics. Approximately, 18 − 24 nucleotides long, miRNAs can up‐regulate or down‐regulate gene expression in many cancer types and are respectively categorized as oncogenes (oncomirs) or tumor suppressors. Expression profiles of miRNAs with biomarker potential can be used for the classification, diagnosis, therapeutic treatment, and prognosis of different cancer types. miRNA mimics and miRNA antagonists are the two main approaches to miRNA‐based cancer therapies that respectively inhibit oncomirs o...
Source: Drug Development Research - August 26, 2015 Category: Drugs & Pharmacology Authors: Lütfi Tutar, Esen Tutar, Aykut Özgür, Yusuf Tutar Tags: Research Review Source Type: research
MicroRNA Regulation of Airway Inflammation and Airway Smooth Muscle Function: Relevance to Asthma
ABSTRACT
Genetic and environmental factors contribute to the onset and severity of asthma. Molecular pathogenesis of asthma involves changes in gene expression by a variety of inflammatory mediators acting in autocrine and paracrine fashion on effector cells of the airways. Transcriptional regulation of gene expression in resident airway cells has been studied extensively. However, protein function in a target cell can be regulated at multiple levels starting from transcription followed by post‐transcription, translation, and post‐translation steps. In this context, small noncoding RNAs known as microRNAs (miRNA...
Source: Drug Development Research - August 26, 2015 Category: Drugs & Pharmacology Authors: Deshpande DA, Dileepan M, Walseth TF, Subramanian S, Kannan MS Tags: Research Overview Source Type: research
Does miRNA‐155 Promote Cyclooxygenase‐2 Expression in Cancer?
ABSTRACT
MicroRNA (miR)‐155 and cyclooxygenase (COX)‐2 are both elevated in numerous cancers including colorectal cancer. MiR‐155 enhances COX‐2 expression and is an established regulator of epithelial‐mesenchymal transition and inflammation. Inhibition of miR‐155 or COX‐2 exhibit similar negative effects on tumorigenicity. Thus, it is hypothesized that miR‐155 may be a promising target for antagonizing COX‐2 expression in colorectal and other cancers. (Source: Drug Development Research)
Source: Drug Development Research - August 25, 2015 Category: Drugs & Pharmacology Authors: Brian S. Comer Tags: Research Commentary Source Type: research
Impact of Histone Deacetylase Inhibitors on microRNA Expression and Cancer Therapy: A Review
ABSTRACT
Chromatin‐modifying drugs, such as histone deacetylase inhibitors (HDACi), have shown potential as cancer therapeutics, either alone or in combination with other therapies. HDACi have the ability to reverse aberrant epigenetic modifications associated with cancer, namely dysregulated histone acetylation. There are currently three FDA approved HDACi; vorinostat, romidepsin, and panobinostat. Epigenetic modifications can regulate the expression of protein coding genes, and in addition can alter expression of microRNA (miRNA) genes. Many miRNAs play key roles in cell proliferation and apoptosis, and are comm...
Source: Drug Development Research - August 25, 2015 Category: Drugs & Pharmacology Authors: Saira R. Ali, Karen J. Humphreys, Ross A. McKinnon, Michael Z. Michael Tags: Review Source Type: research
Alteration of Aging‐Dependent MicroRNAs in Idiopathic Pulmonary Fibrosis
ABSTRACT
Idiopathic Pulmonary Fibrosis (IPF) is the most severe fibrotic lung disease and characterized by the accumulation of (myo)fibroblasts and collagen within the alveolar wall resulting in obliteration of the gas‐exchange surface. Although the detailed pathogenesis is not understood, recent studies have found that several microRNAs (miRNAs) are associated with the progression of lung diseases including IPF. IPF is a fibrotic disease and, most frequently found in an aged population. In this review, the functional roles of miRNAs that are deregulated in IPF progression are discussed together with how aging aff...
Source: Drug Development Research - August 25, 2015 Category: Drugs & Pharmacology Authors: Richard Seonghun Nho Tags: Review Source Type: research
Validated MicroRNA Target Databases: An Evaluation
We examined the provided citations to determine the degree to which each interaction was experimentally supported. To assess stability, we tested at the beginning and end of a five‐month period. Results varied widely by database. Two of the databases changed significantly over the course of 5 months. Most reported evidence for miRNA: target interactions were indirect or otherwise weak, and relatively few interactions were supported by more than one publication. Some returned results appear to arise from simplistic text searches that offer no insight into the relationship of the search terms, may not even include the repo...
Source: Drug Development Research - August 19, 2015 Category: Drugs & Pharmacology Authors: Yun Ji (Diana) Lee, Veronica Kim, Dillon C. Muth, Kenneth W. Witwer Tags: Research Article Source Type: research
miRNAs as Biomarkers in Chronic Myelogenous Leukemia
ABSTRACT
Chronic myelogenous leukemia (CML) is a myeloproliferative neoplasm that is frequently characterized by the constitutive expression of the oncogenic protein BCR‐ABL tyrosine kinase. Tyrosine kinase inhibitors (TKIs) targeting breakpoint cluster region‐ABL are the first‐line therapy for most CML patients and have drastically improved the prognosis of CML. However, some CML patients are unresponsive to TKI treatment, and a notable proportion of initially responsive patients develop drug resistance. Several molecular pathways have been correlated with resistance to TKI treatment, however, the exact mecha...
Source: Drug Development Research - August 18, 2015 Category: Drugs & Pharmacology Authors: Kasuen Kotagama, Yung Chang, Marco Mangone Tags: Research Overview Source Type: research
Fosinopril Prevents the Development of Tactile Allodynia in a Streptozotocin‐Induced Diabetic Rat Model
ABSTRACT
The aim of this study was to evaluate fosinopril‐induced changes in hemodynamic parameters and tactile allodynia in a rat model of diabetes. Diabetes was induced by streptozotocin (STZ; 50 mg/kg, i.p.) in male Wistar rats. STZ produced hyperglycemia, weight loss, polydipsia, polyphagia, and polyuria as well as long‐term arterial hypotension, bradycardia, and tactile allodynia at 10–12 weeks. Daily administration of the angiotensin converting enzyme inhibitor, fosinopril (25 mg/kg, p.o., for 11 weeks) partially reduced the loss of body weight, decreased hyperglycemia, and systolic blood pressure in dia...
Source: Drug Development Research - August 1, 2015 Category: Drugs & Pharmacology Authors: Claudia Ivonne Araiza‐Saldaña, Erick Fabián Pedraza‐Priego, Jorge Elías Torres‐López, Héctor Isaac Rocha‐González, Gabriela Castañeda‐Corral, Enrique Hong‐Chong, Vinicio Granados‐Soto Tags: Research Article Source Type: research
Ustekinumab: The “New Kid on the Block” in the Treatment of Psoriatic Arthritis
ABSTRACT
Psoriatic arthritis (PsA) is a chronic inflammatory seronegative spondyloarthritis associated with psoriasis. While TNF‐α inhibitors have revolutionized the treatment of rheumatic diseases, including PsA, not all patients respond to these agents while others are unsuitable or intolerant to them. Thus, there is a need for additional treatment modalities with a novel mechanism of action. In the past years, the IL‐23/Th17 axis has emerged as an important mechanism in the pathogenesis of PsA. Ustekinumab, a fully human IgG1κ monoclonal antibody that targets the common subunit p40 of IL‐12 and IL‐23, h...
Source: Drug Development Research - August 1, 2015 Category: Drugs & Pharmacology Authors: Tiago Torres, Raquel Faria Tags: Commentary Source Type: research
The Role of MicroRNAs in the Chemoresistance of Breast Cancer
ABSTRACT
Breast cancer is the most prevalent malignancy in women with more than 1.3 million new cases every year worldwide. Chemotherapy is a critical therapeutic strategy for breast cancer, while chemoresistance remains a major obstacle to treatment success. In the past two decades, significant progress has been achieved in understanding drug resistance in breast cancer, involving drug efflux, alterations in DNA repair pathways, suppression of apoptosis as well as epithelial‐mesenchymal transition, and cancer stem cells. However, more effective therapeutic targets and novel biomarkers are still urgently needed to...
Source: Drug Development Research - August 1, 2015 Category: Drugs & Pharmacology Authors: Jing Wang, Muyi Yang, Yu Li, Bo Han Tags: Review Source Type: research
Exosomal MicroRNAs in Tissue Crosstalk
(Source: Drug Development Research)
Source: Drug Development Research - August 1, 2015 Category: Drugs & Pharmacology Authors: David Gurwitz Tags: Editorial Source Type: research
