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https://www.readbyqxmd.com/read/29778537/a-new-indanedione-derivative-alleviates-symptoms-of-diabetes-by-modulating-rage-nf-kappab-pathway-in-db-db-mice
#1
Gulnaz Khan, Meha Fatima Aftab, Bilquees Bano, Khalid Mohammed Khan, Munazza Murtaza, Sonia Siddiqui, M Hafizur Rehman, Rizwana Sanaullah Waraich
Accumulating evidence indicates that a number of tissues are damaged due to build-up of abnormal amount of Advanced Glycation End products (AGEs) in several diseases including diabetes. Currently AGE inhibitors are scarce in clinical use indicating a need for development of new anti-AGE agents. The aim of the current study is to identify the new AGE inhibitors and to decipher their mechanism of action for alleviating symptoms of diabetes in mice. Among several derivatives, one of the derivatives of indanedione, IDD-24 demonstrated highest inhibition of AGE formation and AGE mediated reactive oxygen species production in HepG-2 and mature 3T3-L1 adipocytes...
May 17, 2018: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/29778137/deciphering-natural-control-of-hiv-1-a-valuable-strategy-to-achieve-antiretroviral-therapy-termination
#2
REVIEW
Hamza Loucif, Steven Gouard, Xavier Dagenais-Lussier, Armstrong Murira, Simona Stäger, Cécile Tremblay, Julien Van Grevenynghe
Antiretroviral therapy (ART) has dramatically reduced HIV-1-associated morbidity and mortality, and has transformed HIV-1 infection into a manageable chronic condition by suppressing viral replication. However, despite recent patient care improvements, ART still fails to cure HIV-1 infection due to the inability to counteract immune defects and metabolic disturbances that are associated with residual inflammation alongside viral persistence. Life-long drug administration also results in multiple side-effects in patients including lipodystrophy and insulin resistance...
April 2018: Cytokine & Growth Factor Reviews
https://www.readbyqxmd.com/read/29777999/targeted-delivery-of-cd44s-sirna-by-scfv-overcomes-de-novo-resistance-to-cetuximab-in-triple-negative-breast-cancer
#3
Wenyan Fu, Hefen Sun, Yang Zhao, Mengting Chen, Lipeng Yang, Xueli Yang, Wei Jin
The overexpression of EGFR often occurs in TNBC, and the anti-EGFR receptor antibody cetuximab is used widely to treat metastatic cancer in the clinic. However, EGFR-targeted therapies have been developed for TNBC without clinical success. In this study, we show that impaired EGFR degradation is crucial for resistance to cetuximab, which depends on the cell surface molecule CD44. To further investigate the role of CD44 in EGFR signaling and its treatment potential, we developed a targeting fusion protein composed of an anti-EGFR scFv generated from cetuximab and truncated protamine, called Ce-tP...
May 16, 2018: Molecular Immunology
https://www.readbyqxmd.com/read/29777865/a-prospective-non-interventional-registry-study-of-patients-initiating-a-course-of-drug-therapy-for-overactive-bladder-perspective-rationale-design-and-methodology
#4
Eric S Rovner, Kevin V Carlson, Anna S Deal, Kavita V Nair, Eva E Oakkar, Julie Park, Eric Gemmen, Rita M Kristy, Katherine L Gooch, Carol R Schermer
INTRODUCTION: Pharmacotherapy of overactive bladder (OAB) typically involves treatment with an antimuscarinic or mirabegron, a β3-adrenoceptor agonist, but real-world evidence on their use, including treatment access, persistence, and switching, is limited. Here, we describe the design of a prospective, multicenter, non-interventional registry of patients beginning a new course of OAB pharmacological therapy in routine clinical practice. METHODS: Adults with an OAB diagnosis for at least 3 months who either initiated a new course of mirabegron or antimuscarinic, or who switched therapy were enrolled into PERSPECTIVE (A Prospective, Non-intErventional Registry Study of Patients Initiating a Course of Drug Therapy for OveractIVE Bladder)...
May 16, 2018: Contemporary Clinical Trials
https://www.readbyqxmd.com/read/29777694/gapdh-targeted-therapy-a-new-approach-for-secondary-damage-after-traumatic-brain-injury-on-rats
#5
Vladimir F Lazarev, Elizaveta A Dutysheva, Elena Y Komarova, Elena R Mikhaylova, Irina V Guzhova, Boris A Margulis
Massive neuronal death caused by a neurodegenerative pathology or damage due to ischaemia or traumatic brain injury leads to the appearance of cytosolic proteins in the extracellular space. We found that one of the most abundant cellular polypeptides, glyceraldehyde-3-phosphate dehydrogenase (GAPDH), appearing in the medium of dying cells or body fluids is able to form aggregates that are cytotoxic to adjacent cells. Since we previously showed that the hydrocortisone derivative RX624 can inhibit the ability of GAPDH to transport the enzyme complex with polyglutamine and reduce the cytotoxicity of the complex, we explored the effects of GAPDH on SH-SY5Y neuroblastoma cells...
May 16, 2018: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/29777521/an-early-view-of-real-world-patient-response-to-sacubitril-valsartan-a-retrospective-study-of-patients-with-heart-failure-with-reduced-ejection-fraction
#6
Dana Drzayich Antol, Adrianne Waldman Casebeer, Richard W DeClue, Stephen Stemkowski, Patricia A Russo
INTRODUCTION: Sacubitril/valsartan has been established as an effective treatment for heart failure (HF) with reduced ejection fraction based on clinical trial data; however, little is known about its use or impact in real-world practice. METHODS: This study included data from medical and pharmacy claims and medical records review for patients (n = 200) who initiated sacubitril/valsartan between August 2015 and March 2016 preceding issuance of American College of Cardiology (ACC)/American Heart Association (AHA)/Heart Failure Society of America (HFSA) focused update on new pharmacological therapy for HF (May 2016), which included recommendations for sacubitril/valsartan...
May 17, 2018: Advances in Therapy
https://www.readbyqxmd.com/read/29777201/novel-smoothened-inhibitors-for-therapeutic-targeting-of-na%C3%A3-ve-and-drug-resistant-hedgehog-pathway-driven-cancers
#7
Qing-Rou Li, Hui Zhao, Xue-Sai Zhang, Henk Lang, Ker Yu
The G protein-coupled receptor (GPCR) smoothened (SMO) is a key signaling component of the sonic hedgehog (Hh) pathway and a clinically validated target for cancer treatment. The FDA-approved SMO inhibitors GDC-0449/Vismodegib and LDE225/Sonidegib demonstrated clinical antitumor efficacy. Nevertheless, relatively high percentage of treated patients would eventually develop acquired cross resistance to both drugs. Here, based on published structure and activity of GDC-0449 inhibitor class, we replaced its amide core with benzimidazole which retained bulk of the SMO-targeting activity as measured in our Hh/SMO/Gli1-reporter system...
May 18, 2018: Acta Pharmacologica Sinica
https://www.readbyqxmd.com/read/29777154/calcimimetic-acts-on-enteric-neuronal-casr-to-reverse-cholera-toxin-induced-intestinal-electrolyte-secretion
#8
Lieqi Tang, Lingli Jiang, Megan E McIntyre, Ekaterina Petrova, Sam X Cheng
Treatment of acute secretory diarrheal illnesses remains a global challenge. Enterotoxins produce secretion through direct epithelial action and indirectly by activating enteric nervous system (ENS). Using a microperfused colonic crypt technique, we have previously shown that R568, a calcimimetic that activates the calcium-sensing receptor (CaSR), can act on intestinal epithelium and reverse cholera toxin-induced fluid secretion. In the present study, using the Ussing chamber technique in conjunction with a tissue-specific knockout approach, we show that the effects of cholera toxin and CaSR agonists on electrolyte secretion by the intestine can also be attributed to opposing actions of the toxin and CaSR on the activity of the ENS...
May 18, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29777004/development-of-a-novel-spect-tracer-to-image-c-met-expression-in-non-small-cell-lung-cancer-in-a-human-tumor-xenograft
#9
Zhaoguo Han, Yadi Xiao, Kai Wang, Ji Yan, Zunyu Xiao, Fang Fang, Zhongnan Jin, Yang Liu, Xilin Sun, Baozhong Shen
Rationale: Elevated expression of the c-Met receptor plays a crucial role in cancers. In non-small cell lung cancer (NSCLC), aberrant activation of c-Met signaling pathway contributes to tumorigenesis and cancer progression, and may mediate acquired resistance to epidermal growth factor receptor-targeted therapy. c-Met is therefore emerging as a promising therapeutic target for treating NSCLC, and the methods for noninvasive in vivo assessment of c-Met expression will improve NSCLC treatment and diagnosis. Methods: A new peptide-based (cMBP) radiotracer targeting c-Met, 99m Tc-hydrazine nicotinamide (HYNIC)-cMBP, was developed for single photon emission computed tomography (SPECT) imaging...
May 18, 2018: Journal of Nuclear Medicine: Official Publication, Society of Nuclear Medicine
https://www.readbyqxmd.com/read/29776349/randomised-controlled-trial-rct-of-cannabinoid-replacement-therapy-nabiximols-for-the-management-of-treatment-resistant-cannabis-dependent-patients-a-study-protocol
#10
Anjali K Bhardwaj, David J Allsop, Jan Copeland, Iain S McGregor, Adrian Dunlop, Marian Shanahan, Raimondo Bruno, Nghi Phung, Mark Montebello, Craig Sadler, Jessica Gugusheff, Melissa Jackson, Jennifer Luksza, Nicholas Lintzeris
BACKGROUND: The cannabis extract nabiximols (Sativex®) effectively supresses withdrawal symptoms and cravings in treatment resistant cannabis dependent individuals, who have high relapse rates following conventional withdrawal treatments. This study examines the efficacy, safety and cost-effectiveness of longer-term nabiximols treatment for outpatient cannabis dependent patients who have not responded to previous conventional treatment approaches. METHODS/DESIGN: A phase III multi-site outpatient, randomised, double-blinded, placebo controlled parallel design, comparing a 12-week course of nabiximols to placebo, with follow up at 24 weeks after enrolment...
May 18, 2018: BMC Psychiatry
https://www.readbyqxmd.com/read/29775954/a-new-methodology-based-on-functional-principal-component-analysis-to-study-postural-stability-post-stroke
#11
M Luz Sánchez-Sánchez, Juan-Manuel Belda-Lois, Silvia Mena-Del Horno, Enrique Viosca-Herrero, Celedonia Igual-Camacho, Beatriz Gisbert-Morant
BACKGROUND: A major goal in stroke rehabilitation is the establishment of more effective physical therapy techniques to recover postural stability. Functional Principal Component Analysis provides greater insight into recovery trends. However, when missing values exist, obtaining functional data presents some difficulties. The purpose of this study was to reveal an alternative technique for obtaining the Functional Principal Components without requiring the conversion to functional data beforehand and to investigate this methodology to determine the effect of specific physical therapy techniques in balance recovery trends in elderly subjects with hemiplegia post-stroke...
May 5, 2018: Clinical Biomechanics
https://www.readbyqxmd.com/read/29775812/virus-entry-and-its-inhibition-to-prevent-and-treat-hepatitis-b-and-hepatitis-d-virus-infections
#12
REVIEW
Thomas Tu, Stephan Urban
While chronic infection with the human hepatitis B virus (HBV) and hepatitis delta virus (HDV) inflict major health burdens worldwide, current therapies cannot cure patients. One possible novel approach is blocking virus entry to prevent the establishment of infection in naïve hepatocytes. As HBV and HDV use identical viral envelope proteins and the same entry mechanisms, such a strategy would target both viruses. Entry inhibitors (e.g. neutralizing antibodies) have been relegated to the limited role of prophylaxis...
May 15, 2018: Current Opinion in Virology
https://www.readbyqxmd.com/read/29775273/the-role-of-clpp-protease-in-bacterial-pathogenesis-and-human-diseases
#13
Vaibhav Bhandari, Keith S Wong, Jin Lin Zhou, Mark F Mabanglo, Robert A Batey, Walid A Houry
In prokaryotic cells and eukaryotic organelles, the ClpP protease plays an important role in proteostasis. The disruption of ClpP function has been shown to influence the infectivity and virulence of a number of bacterial pathogens. More recently, ClpP has been found to be involved in various forms of carcinomas and in Perrault syndrome, which is an inherited condition characterized by hearing loss in males and females and by ovarian abnormalities in females. Hence, targeting ClpP is a potentially viable, attractive option for the treatment of different ailments...
May 18, 2018: ACS Chemical Biology
https://www.readbyqxmd.com/read/29774607/impact-of-current-and-scaled-up-levels-of-hepatitis-c-prevention-and-treatment-interventions-for-people-who-inject-drugs-in-three-uk-settings-what-is-required-to-achieve-the-who-s-hcv-elimination-targets
#14
Zoe Ward, Lucy Platt, Sedona Sweeney, Vivian D Hope, Lisa Maher, Sharon Hutchinson, Norah Palmateer, Josie Smith, Noel Craine, Avril Taylor, Natasha Martin, Rachel Ayres, John Dillon, Matthew Hickman, Peter Vickerman
AIMS: To estimate the impact of existing high-coverage needle and syringe provision (HCNSP, defined as obtaining more than one sterile needle and syringe per injection reported) and opioid substitution therapy (OST) on hepatitis C virus (HCV) transmission among people who inject drugs (PWID) in three UK settings and to determine required scale-up of interventions, including HCV treatment, needed to reach the World Health Organization (WHO) target of reducing HCV incidence by 90% by 2030...
May 17, 2018: Addiction
https://www.readbyqxmd.com/read/29774214/the-expression-of-aqp1-is-modified-in-lung-of-patients-with-idiopathic-pulmonary-fibrosis-addressing-a-possible-new-target
#15
Ana Galán-Cobo, Elena Arellano-Orden, Rocío Sánchez Silva, José Luis López-Campos, César Gutiérrez Rivera, Lourdes Gómez Izquierdo, Nela Suárez-Luna, María Molina-Molina, José A Rodríguez Portal, Miriam Echevarría
Activation of the epithelial-mesenchymal transition process (EMT) by which alveolar cells in human lung tissue undergo differentiation giving rise to a mesenchymal phenotype (fibroblast/miofibroblasts) has been well recognized as a key element in the origin of idiopathic pulmonary fibrosis (IPF). Here we analyzed expression of AQP1 in lung biopsies of patients diagnosed with IPF, and compared it to biopsies derived from patients with diverse lung pneumonies, such as hypersensitivity pneumonitis, sarcoidosis or normal lungs...
2018: Frontiers in Molecular Biosciences
https://www.readbyqxmd.com/read/29774079/long-non-coding-rnas-ac026904-1-and-uca1-a-one-two-punch-for-tgf-%C3%AE-induced-snai2-activation-and-epithelial-mesenchymal-transition-in-breast-cancer
#16
Guo-Yin Li, Wei Wang, Jian-Yong Sun, Bo Xin, Xiang Zhang, Ting Wang, Qian-Feng Zhang, Li-Bo Yao, Hua Han, Dai-Ming Fan, An-Gang Yang, Lin-Tao Jia, Lei Wang
Transforming growth factor-β (TGF-β) has received much attention as a major inducer of epithelial-mesenchymal transition (EMT) during cancer progression, mainly by activating a set of pleiotropic transcription factors including SNAI2/Slug. However, the involvement of long non-coding RNAs (lncRNAs) in TGF-β-induced Slug activation and EMT remains largely unknown. Methods: In this study, we used microarray analysis to compare lncRNA expression profiles between TGF-β treated and untreated breast cancer cells...
2018: Theranostics
https://www.readbyqxmd.com/read/29774025/co-stimulation-impaired-bone-marrow-derived-dendritic-cells-prevent-dextran-sodium-sulfate-induced-colitis-in-mice
#17
Carl Engman, Yesica Garciafigueroa, Brett Eugene Phillips, Massimo Trucco, Nick Giannoukakis
Dendritic cells (DC) are important in the onset and severity of inflammatory bowel disease (IBD). Tolerogenic DC induce T-cells to become therapeutic Foxp3+ regulatory T-cells (Tregs). We therefore asked if experimental IBD could be prevented by administration of bone marrow-derived DC generated under conventional GM-CSF/IL-4 conditions but in the presence of a mixture of antisense DNA oligonucleotides targeting the primary transcripts of CD40, CD80, and CD86. These cell products (which we call AS-ODN BM-DC) have demonstrated tolerogenic activity in preventing type 1 diabetes and preserving beta cell mass in new-onset type 1 diabetes in the NOD mouse strain, in earlier studies...
2018: Frontiers in Immunology
https://www.readbyqxmd.com/read/29773993/diabetic-cardiomyopathy-impact-of-biological-sex-on-disease-development-and-molecular-signatures
#18
REVIEW
Ryan Toedebusch, Anthony Belenchia, Lakshmi Pulakat
Diabetic cardiomyopathy refers to a unique set of heart-specific pathological variables induced by hyperglycemia and insulin resistance. Given that cardiovascular disease (CVD) is the leading cause of death in the world, and type 2 diabetes incidence continues to rise, understanding the complex interplay between these two morbidities and developing novel therapeutic strategies is vital. Two hallmark characteristics specific to diabetic cardiomyopathy are diastolic dysfunction and cardiac structural mal-adaptations, arising from cardiac cellular responses to the complex toxicity induced by hyperglycemia with or without hyperinsulinemia...
2018: Frontiers in Physiology
https://www.readbyqxmd.com/read/29773595/therapeutic-effects-of-the-novel-subtype-selective-histone-deacetylase-hdac-inhibitor-chidamide-on-myeloma-associated-bone-disease
#19
Jingsong He, Qingxiao Chen, Huiyao Gu, Jing Chen, Enfan Zhang, Xing Guo, Xi Huang, Haimeng Yan, DongHua He, Yang Yang, Yi Zhao, Gang Wang, Huang He, Qing Yi, Zhen Cai
Histone deacetylases are promising therapeutic targets in hematological malignancies. In the present work, we investigated the effect of chidamide, a new subtype-selective histone deacetylase inhibitor that was independently produced in China, on multiple myeloma and its associated bone diseases using different models. The cytotoxicity of chidamide toward myeloma is due to its induction of cell apoptosis and cell cycle arrest by increasing the levels of caspase family proteins, including p21 and p27, among others...
May 17, 2018: Haematologica
https://www.readbyqxmd.com/read/29772526/marine-derived-bioactive-compounds-for-treatment-of-alzheimer-s-disease
#20
Sreeja Lakshmi, Parvathi Prakash, Musthafa M Essa, Walid M Qoronfleh, Mohammed Akbar, Byoung-Joon Song, Suresh Kumar, Preetham Elumalai
Alzheimer's disease (AD ) is mounting as social and economic encumbrance which are accompanied by deficits in cognition and memory. Over the past decades, Alzheimer's disease (AD) holds the frontline as one of the biggest healthcare issues in the world. AD is an age related neurodegenerative disorder marked by a decline in memory and an impairment of cognition. Inspite of tedious scientific effort, AD is still devoid of pharmacotherapeutic strategies for treatment as well as prevention. Current treatment strategies using drugs are symbolic in nature as they treat disease manifestation though are found effective in treating cognition...
June 1, 2018: Frontiers in Bioscience (Elite Edition)
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