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https://www.readbyqxmd.com/read/27926950/c6-and-c7-substituted-3-4-dihydro-2-1h-quinolinones-as-inhibitors-of-monoamine-oxidase
#1
L Meiring, J Petzer, A Petzer
Purpose Monoamine oxidase (MAO) inhibitors are considered to be useful therapeutic agents and isoform specific inhibitors are employed for the treatment of depression and Parkinson's disease. MAO inhibitors are also under investigation for the treatment of disorders ranging from Alzheimer's disease, prostate cancer and certain cardiomyopathies. While a number of irreversible MAO inhibitors are available in the clinic, reversible inhibitors, particularly of the MAO-B isoform are still being developed. Based on our interest in discovering reversible inhibitors with specificity for MAO-B, we have recently reported that, among a series of 10 3,4-dihydro-2(1H)-quinolinone derivatives, are high potency MAO-B inhibitors, with a number of homologues displaying good selectivities for MAO-B over the MAO-A isoform...
December 7, 2016: Drug Research
https://www.readbyqxmd.com/read/27926600/supporting-rural-women-during-pregnancy-baby-beep-nurses
#2
Emily C Evans, Linda F C Bullock
PURPOSE: The aim of this study was to characterize nursing care provided by the research nurses from the Baby Behavioral Educational Enhancement of Pregnancy (Baby BEEP) study as they delivered a telephone social support intervention to low-income, pregnant women in the Midwestern United States. STUDY DESIGN AND METHODS: This was a descriptive qualitative study that used Peplau's Theory of Interpersonal Relations to frame and interpret the analysis. RESULTS: Research nurses from the Baby BEEP study found a novel way to reach a vulnerable population through weekly telephone interactions...
January 2017: MCN. the American Journal of Maternal Child Nursing
https://www.readbyqxmd.com/read/27926532/novel-parp1-2-inhibitor-mefuparib-hydrochloride-elicits-potent-in-vitro-and-in-vivo-anticancer-activity-characteristic-of-high-tissue-distribution
#3
Jin-Xue He, Meng Wang, Xia-Juan Huan, Chuan-Huizi Chen, Shan-Shan Song, Ying-Qing Wang, Xue-Mei Liao, Cun Tan, Qian He, Lin-Jiang Tong, Yu-Ting Wang, Xiao-Hua Li, Yi Su, Yan-Yan Shen, Yi-Ming Sun, Xin-Ying Yang, Yi Chen, Zhi-Wei Gao, Xiao-Yan Chen, Bing Xiong, Xiu-Lian Lu, Jian Ding, Chun-Hao Yang, Ze-Hong Miao
The approval of poly(ADP-ribose) polymerase (PARP) inhibitor AZD2281 in 2014 marked the successful establishment of the therapeutic strategy targeting homologous recombination repair defects of cancers in the clinic. However, AZD2281 has poor water solubility, low tissue distribution and relatively weak in vivo anticancer activity, which appears to become limiting factors for its clinical use. In this study, we found that mefuparib hydrochloride (MPH) was a potent PARP inhibitor, possessing prominent in vitro and in vivo anticancer activity...
December 1, 2016: Oncotarget
https://www.readbyqxmd.com/read/27926382/prediction-of-anti-cancer-drug-response-by-kernelized-multi-task-learning
#4
Mehmet Tan
MOTIVATION: Chemotherapy or targeted therapy are two of the main treatment options for many types of cancer. Due to the heterogeneous nature of cancer, the success of the therapeutic agents differs among patients. In this sense, determination of chemotherapeutic response of the malign cells is essential for establishing a personalized treatment protocol and designing new drugs. With the recent technological advances in producing large amounts of pharmacogenomic data, in silico methods have become important tools to achieve this aim...
October 2016: Artificial Intelligence in Medicine
https://www.readbyqxmd.com/read/27925188/a-human-3d-in-vitro-model-to-assess-the-relationship-between-osteoporosis-and-dissemination-to-bone-of-breast-cancer-tumour-cells
#5
F Salamanna, V Borsari, S Brogini, P Torricelli, S Cepollaro, M Cadossi, M Fini
Despite consistent improvements in diagnostic and therapeutic strategies for breast cancer, up to 40% of patients will develop bone metastases. To reduce the morbidity and complications related with bone metastases, it is imperative to reduce their etiological factors. Osteoporosis, being characterized by a sudden estrogen deficiency, may provide a favorable condition for bone metastasis. This work, using a humanized 3D in vitro model, aims at evaluating the relationship between osteoporosis and breast cancer-derived bone metastases...
December 7, 2016: Journal of Cellular Physiology
https://www.readbyqxmd.com/read/27924643/risk-of-infections-using-anti-tnf-agents-in-rheumatoid-arthritis-psoriatic-arthritis-and-ankylosing-spondylitis-a-systematic-review-and-meta-analysis
#6
Silvia Minozzi, Stefanos Bonovas, Theodore Lytras, Valentina Pecoraro, Marien González-Lorenzo, Anan Judina Bastiampillai, Eugenia Maria Gabrielli, Andrea Carlo Lonati, Lorenzo Moja, Michela Cinquini, Valentina Marino, Andrea Matucci, Giuseppe Maria Milano, Giuliano Tocci, Raffaele Scarpa, Delia Goletti, Fabrizio Cantini
Five anti-tumor necrosis factor (anti-TNF) agents have received regulatory approval for use in rheumatology: adalimumab, golimumab, infliximab, certolizumab, and etanercept. Apart from their well-documented therapeutic value, it is still uncertain to what extent they are associated with an increased risk of infectious adverse events. Areas covered: We conducted a systematic review and meta-analysis of published randomized studies to determine the effect of anti-TNF drugs on the occurrence of infectious adverse events (serious infections; tuberculosis; opportunistic infections; any infection)...
December 2016: Expert Opinion on Drug Safety
https://www.readbyqxmd.com/read/27924341/structure-activity-relationship-of-novel-macrocyclic-biased-apelin-receptor-agonists
#7
Alexandre Murza, Xavier Sainsily, Jérôme Côté, Laurent Bruneau-Cossette, Élie Besserer-Offroy, Jean-Michel Longpré, Richard Leduc, Robert Dumaine, Olivier Lesur, Mannix Auger-Messier, Philippe Sarret, Éric Marsault
Apelin is the endogenous ligand for the G protein-coupled receptor APJ and exerts a key role in regulating cardiovascular functions. We report herein a novel series of macrocyclic analogues of apelin-13 in which the N- and C-terminal residues as well as the macrocycle composition were chemically modified to modulate structure-activity relationships on the APJ receptor. To this end, the binding affinity and the ability to engage G protein-dependent and G protein-independent signalling pathways of the resulting analogues were assessed...
December 7, 2016: Organic & Biomolecular Chemistry
https://www.readbyqxmd.com/read/27924018/disgenet-a-comprehensive-platform-integrating-information-on-human-disease-associated-genes-and-variants
#8
Janet Piñero, Àlex Bravo, Núria Queralt-Rosinach, Alba Gutiérrez-Sacristán, Jordi Deu-Pons, Emilio Centeno, Javier García-García, Ferran Sanz, Laura I Furlong
The information about the genetic basis of human diseases lies at the heart of precision medicine and drug discovery. However, to realize its full potential to support these goals, several problems, such as fragmentation, heterogeneity, availability and different conceptualization of the data must be overcome. To provide the community with a resource free of these hurdles, we have developed DisGeNET (http://www.disgenet.org), one of the largest available collections of genes and variants involved in human diseases...
October 19, 2016: Nucleic Acids Research
https://www.readbyqxmd.com/read/27923701/prognostic-significance-of-repeat-biopsy-in-lupus-nephritis-histopathologic-worsening-and-a-short-time-between-biopsies-is-associated-with-significantly-increased-risk-for-end-stage-renal-disease-and-death
#9
Cristina Arriens, Sixia Chen, David R Karp, Ramesh Saxena, Kamalanathan Sambandam, Eliza Chakravarty, Judith A James, Joan T Merrill
BACKGROUND/PURPOSE: Approximately half of patients with systemic lupus erythematosus (SLE) develop lupus nephritis (LN), a major cause of morbidity and early mortality in that disease. Prolonged renal inflammation is associated with irreversible kidney damage which confers a 30% risk of end stage renal disease (ESRD), making early, aggressive treatment mandatory. Failure to achieve therapeutic response or recurrence of renal flare often prompts repeat biopsy. However, the role of repeat biopsy in determining long-term renal prognosis remains controversial...
December 3, 2016: Clinical Immunology: the Official Journal of the Clinical Immunology Society
https://www.readbyqxmd.com/read/27923046/mitochondria-and-caspases-tune-nmnat-mediated-stabilization-to-promote-axon-regeneration
#10
Li Chen, Derek M Nye, Michelle C Stone, Alexis T Weiner, Kyle W Gheres, Xin Xiong, Catherine A Collins, Melissa M Rolls
Axon injury can lead to several cell survival responses including increased stability and axon regeneration. Using an accessible Drosophila model system, we investigated the regulation of injury responses and their relationship. Axon injury stabilizes the rest of the cell, including the entire dendrite arbor. After axon injury we found mitochondrial fission in dendrites was upregulated, and that reducing fission increased stabilization or neuroprotection (NP). Thus axon injury seems to both turn on NP, but also dampen it by activating mitochondrial fission...
December 6, 2016: PLoS Genetics
https://www.readbyqxmd.com/read/27922982/mir-21-is-overexpressed-in-hydatidiform-mole-tissues-and-promotes-proliferation-migration-and-invasion-in-choriocarcinoma-cells
#11
Ya-Xin Wang, Jiu-Ru Zhao, Yue-Ying Xu, Wei-Bin Wu, Hui-Juan Zhang
OBJECTIVE: The aims of this study were to make clear whether miR-21 was dysregulated in hydatidiform mole (HM) tissues and choriocarcinoma (CCA) cells, to elucidate whether aberrant miR-21 expression would affect the function of CCA cells, and to find out whether there was a relationship between miR-21 and AKT, PDCD4, and PTEN in CCA cells. METHODS: Fresh and formalin-fixed, paraffin-embedded trophoblastic tissues (normal first trimester placentas and HMs) were retrieved from the biobank in the International Peace Maternity and Child Health Hospital, Shanghai Jiao Tong University...
December 3, 2016: International Journal of Gynecological Cancer
https://www.readbyqxmd.com/read/27922681/cxcr4-promotes-cisplatin-resistance-of-non-small-cell-lung-cancer-in-a-cyp1b1-dependent-manner
#12
Songping Xie, Zhenbo Tu, Jie Xiong, Ganjun Kang, Lina Zhao, Weidong Hu, Haiyan Tan, Kingsley Miyanda Tembo, Qianshan Ding, Xinzhou Deng, Jie Huang, Qiuping Zhang
Chemoresistance is the main cause of treatment failure and high mortality in advanced lung cancer. Cisplatin, an important chemotherapeutic agent for lung cancer, has been observed to show enormously reduced chemotherapeutic efficacy owing to the development of chemoresistance. CXCR4, a stromal-derived-factor-1 specific chemokine receptor, is highly expressed in non-small cell lung cancer (NSCLC) tissues and participates in cancer progression by regulating cell growth, apoptosis or invasion. In this study, we therefore investigated whether CXCR4 plays a role in the cisplatin associated resistance in NSCLC...
December 2, 2016: Oncology Reports
https://www.readbyqxmd.com/read/27922498/inclusion-body-myositis
#13
Steven A Greenberg
PURPOSE OF REVIEW: Inclusion body myositis (IBM) is an enigmatic progressive disease of skeletal muscle. This review provides a summary of the clinical and pathophysiologic aspects of IBM. RECENT FINDINGS: The development of diagnostic blood testing for IBM followed from the discovery of a B-cell pathway in IBM muscle and circulating autoantibodies against NT5C1A, further establishing IBM's status as an autoimmune disease. The key role of cytotoxic T cells in IBM is further supported by the identification of a link between IBM and T-cell large granular lymphocytic leukemia...
December 2016: Continuum: Lifelong Learning in Neurology
https://www.readbyqxmd.com/read/27919211/development-of-mlr-and-svm-aided-qsar-models-to-identify-common-sar-of-gaba-uptake-herbal-inhibitors-used-in-the-treatment-of-schizophrenia
#14
Sahila Mohammed Marunnan, Babitha Pallikkara Pulikka, V K Gopalakrishnan, Srinivas Bandaru, Mukesh Yadav, Anuraj Nayarisseri, Victor Arokia Doss
Deficits in GABAnergic system is implicated in the pathophysiology of schizophrenia. Available antipsychotics that target GABA receptor form a desirable therapeutic strategy in the treatment regimen of schizophrenia but, unfortunately, suffers serious setback due to their prolonged side effects. The present investigation focuses on developing QSAR models from the biological activity of herbal compounds and their derivatives that promise to be alternative candidates to GABA uptake inhibitors. Three sets of compounds were undertaken in the study to develop the QSAR models...
December 5, 2016: Current Neuropharmacology
https://www.readbyqxmd.com/read/27919206/differences-and-similarities-in-therapeutic-mode-use-between-occupational-therapists-and-occupational-therapy-students-in-norway
#15
Tove Carstensen, Tore Bonsaksen
BACKGROUND: The Intentional Relationship Model (IRM) is a new model of the therapeutic relationship in occupational therapy practice. Two previous studies have focused on therapist communication style, or 'mode' use, but to date no group comparisons have been reported. AIM: To explore differences between occupational therapists and occupational therapy students with regard to their therapeutic mode use. METHODS: The study had a cross-sectional design, and convenience samples consisting of occupational therapists (n = 109) and of second-year occupational therapy students (n = 96) were recruited...
December 5, 2016: Scandinavian Journal of Occupational Therapy
https://www.readbyqxmd.com/read/27918638/small-molecule-microarray-based-discovery-of-parp14-inhibitors
#16
Bo Peng, Ann-Gerd Thorsell, Tobias Karlberg, Herwig Schüler, Shao Q Yao
Poly(ADP-ribose) polymerases (PARPs) are key enzymes in a variety of cellular processes. Most small-molecule PARP inhibitors developed to date have been against PARP1, and suffer from poor selectivity. PARP14 has recently emerged as a potential therapeutic target, but its inhibitor development has trailed behind. Herein, we describe a small molecule microarray-based strategy for high-throughput synthesis, screening of >1000 potential bidentate inhibitors of PARPs, and the successful discovery of a potent PARP14 inhibitor H10 with >20-fold selectivity over PARP1...
December 5, 2016: Angewandte Chemie
https://www.readbyqxmd.com/read/27918470/vitamin-d-status-and-efficacy-of-vitamin-d-supplementation-in-atopic-dermatitis-a-systematic-review-and-meta-analysis
#17
Min Jung Kim, Soo-Nyung Kim, Yang Won Lee, Yong Beom Choe, Kyu Joong Ahn
Recent literature has highlighted the possible role of vitamin D in atopic dermatitis (AD), and that vitamin D supplementation might help to treat AD. This study determined the relationship between vitamin D level and AD, and assessed the efficacy of vitamin D supplementation. We searched the MEDLINE, EMBASE, and Cochrane databases up to May 2015. Observational studies and randomized controlled trials were included based on the available data on the serum 25-hydroxyvitamin D (25(OH)D) level and quantified data available for severity assessed using the Scoring Atopic Dermatitis (SCORAD) index or Eczema Area and Severity Index (EASI) score...
December 3, 2016: Nutrients
https://www.readbyqxmd.com/read/27917872/advances-in-the-study-of-berberine-and-its-derivatives-a-focus-on-anti-inflammatory-and-anti-tumor-effects-in-the-digestive-system
#18
REVIEW
Kun Zou, Zhao Li, Yong Zhang, Hao-Yue Zhang, Bo Li, Wei-Liang Zhu, Ji-Ye Shi, Qi Jia, Yi-Ming Li
It has been widely recognized that inflammation, particularly chronic inflammation, can increase the risk of cancer and that the simultaneous treatment of inflammation and cancer may produce excellent therapeutic effects. Berberine, an alkaloid isolated from Rhizoma coptidis, has broad applications, particularly as an antibacterial agent in the clinic with a long history. Over the past decade, many reports have demonstrated that this natural product and its derivatives have high activity against both cancer and inflammation...
December 5, 2016: Acta Pharmacologica Sinica
https://www.readbyqxmd.com/read/27916565/the-association-of-exosomes-with-lymph-nodes
#19
REVIEW
Joshua L Hood
Cells produce extracellular nanovesicles known as exosomes that transport information between tissue microenvironments. Exosomes can engage and regulate the function of various immune cell types facilitating both normal and pathological processes. It follows that exosomes should also associate with lymph nodes containing immune cells. Herein, data derived from investigations that incorporate experiments pertaining to the trafficking of exosomes to lymph nodes is reviewed. Within lymph nodes, direct evidence demonstrates that exosomes associate with dendritic cells, subcapsular sinus macrophages, B lymphocytes and stromal cells...
December 1, 2016: Seminars in Cell & Developmental Biology
https://www.readbyqxmd.com/read/27916418/knockdown-of-tktl1-additively-complements-cisplatin-induced-cytotoxicity-in-nasopharyngeal-carcinoma-cells-by-regulating-the-levels-of-nadph-and-ribose-5-phosphate
#20
Yuke Dong, Ming Wang
BACKGROUND: Transketolase-like 1 (TKTL1) plays an important role in pentose phosphate pathway (PPP) branch, the main pathway generating nicotinamide adenine dinucleotide phosphate (NADPH) and nucleotides for DNA synthesis. TKTL1 is closely related to DNA damage and has a close relationship with incidence and progression of cancers. Cisplatin is the main chemotherapeutic drug by inducing DNA damage. Whether TKTL1 knockdown additively complements cisplatin-induced cytotoxicity in nasopharyngeal carcinoma cells, however, remains largely undefined...
December 1, 2016: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
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