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https://www.readbyqxmd.com/read/28088788/dual-syk-jak-inhibition-overcomes-ibrutinib-resistance-in-chronic-lymphocytic-leukemia-cerdulatinib-but-not-ibrutinib-induces-apoptosis-of-tumor-cells-protected-by-the-microenvironment
#1
Ailin Guo, Pin Lu, Greg Coffey, Pamela Conley, Anjali Pandey, Y Lynn Wang
Ibrutinib (BTK inhibitor) has generated remarkable responses in CLL. However, the drug, to a large extent, does not cause cell death directly and does not eradicate CLL malignant clones. Inability to eradicate CLL has fostered resistance generation. Once patients become resistant, they do poorly with a median survival of 3-4 months. Novel therapeutic strategies are needed to prevent resistance, improve treatment outcome and ultimately cure the disease. Herein, we explore dual targeting of the BCR and JAK-STAT pathways with a novel single agent, cerdulatinib, which selectively inhibits both SYK (a BCR component) and JAK kinases...
January 10, 2017: Oncotarget
https://www.readbyqxmd.com/read/28088638/the-dlno-dlco-ratio-physiological-significance-and-clinical-implications
#2
J M B Hughes, A T Dinh-Xuan
DLNO/DLCO directly measures the ratio of the diffusing capacities of the lung for nitric oxide (NO) and carbon monoxide (CO). In terms of the Roughton and Forster, 1957; equation, 1/DL=1/Dm+1/θVc, where Dm is the membrane (Dm) and θVc is the red cell component of the overall diffusing conductance (DL), DLNO mostly reflects the Dm component and DLCO the θVc red cell component. The DLNO/DLCO ratio is positively related to the DmCO/Vc ratio and the CO red cell resistance (1/θCOVc) as a percentage of the total resistance (1/DLCO), independent of the absolute values of DLNO or DLCO...
January 11, 2017: Respiratory Physiology & Neurobiology
https://www.readbyqxmd.com/read/28088613/adipocyte-and-epidermal-fatty-acid-binding-protein-serum-concentrations-in-patients-with-lipodystrophy
#3
Konstanze Miehle, Thomas Ebert, Susan Kralisch, Annett Hoffmann, Jürgen Kratzsch, Haiko Schlögl, Michael Stumvoll, Mathias Fasshauer
OBJECTIVE: Lipodystrophy (LD) syndromes are associated with diabetes mellitus, hypertriglyceridemia, and coronary artery disease. One pathogenetic factor of LD is dysregulation of several adipokines. However, the insulin resistance- and dyslipidemia-promoting adipokines adipocyte (AFABP) and epidermal (EFABP) fatty acid-binding protein have not been investigated in non-HIV-associated LD so far. MATERIAL AND METHODS: We performed a cross-sectional analysis of AFABP and EFABP serum concentrations in 37 LD patients and 37 age-, gender-, and body mass index-matched healthy controls...
January 12, 2017: Cytokine
https://www.readbyqxmd.com/read/28088470/the-effects-of-dietary-kefir-and-low-molecular-weight-sodium-alginate-on-serum-immune-parameters-resistance-against-streptococcus-agalactiae-and-growth-performance-in-nile-tilapia-oreochromis-niloticus
#4
Hien Van Doan, Seyed Hossein Hoseinifar, Wanaporn Tapingkae, Pimporn Khamtavee
The present study evaluates the effects of dietary kefir and low molecular weight sodium alginate (LWMSA) (singular or combined) on non-specific immune response, disease resistance and growth performance of Nile tilapia (Oreochromis niloticus). Fish with average weight of 18.60 ± 0.04 g were supplied and randomly stocked in sixteen glass tanks (150 L) at density of 20 fish per tank. Fish were fed experimental diets as follows: 0 g kg(-1) LMWSA (Control, Diet 1), 10 g kg(-1) LMWSA (Diet 2), 40 g kg(-1) kefir (Diet 3), and 10 g kg(-1) LMWSA + 40 g kg(-1) kefir (Diet 4) for 50 days...
January 11, 2017: Fish & Shellfish Immunology
https://www.readbyqxmd.com/read/28088237/association-between-diabetes-mellitus-and-multi-drug-resistant-tuberculosis-a-protocol-for-a-systematic-review-and-meta-analysis
#5
Balewgizie Sileshi Tegegne, Tesfa Dejenie Habtewold, Melkamu Merid Mengesha, Johannes G M Burgerhof
INTRODUCTION: Multi-drug-resistant tuberculosis (MDR-TB) has emerged as a challenge to global tuberculosis (TB) control and remains a major public health concern in many countries. Diabetes mellitus (DM) is an increasingly recognized comorbidity that can both accelerate TB disease and complicate its treatment. The aim of this study is to summarize available evidence on the association of DM and MDR-TB among TB patients and to provide a pooled estimate of risks. METHODS: All studies published in English before October 2016 will be searched using comprehensive search strings through PubMed, EMBASE, Web of Science, and WHO Global Health Library databases which have reported the association of DM and MDR-TB in adults with TB (age > =15)...
January 14, 2017: Systematic Reviews
https://www.readbyqxmd.com/read/28088229/clinicopathologic-significance-of-trap1-expression-in-colorectal-cancer-a-large-scale-study-of-human-colorectal-adenocarcinoma-tissues
#6
Min Gyoung Pak, Hyong Jong Koh, Mee Sook Roh
BACKGROUND: Colorectal cancer is the major cause of cancer mortality, despite development of therapeutic strategies. The novel marker tumor necrosis factor receptor-associated protein 1 (TRAP1) is a mitochondrial heat shock protein that has been related to drug resistance and protection from apoptosis in colorectal cancer. This study aims to delineate the clinicopathologic significance of TRAP1 expression in colorectal cancer. METHODS: Seven-hundred and fourteen FFPE tissues were collected from colorectal cancer patients who underwent surgery from February 2002 to July 2011 at Dong-A University Medical Center, Busan, South Korea...
January 14, 2017: Diagnostic Pathology
https://www.readbyqxmd.com/read/28088112/a-current-perspective-on-the-oncopreventive-and-oncolytic-properties-of-selective-serotonin-reuptake-inhibitors
#7
REVIEW
Daniel P Radin, Parth Patel
Current cancer research strongly focuses on identifying novel pathways that can be selectively exploited in the clinic and identifying drugs capable of exploiting cancer vulnerabilities. Occasionally, drugs identified to exploit a cancer-specific vulnerability are on the market for clinical indications in another disease area. Rebranding them as anti-cancer drugs is a process commonly referred to as drug repurposing and is typically a faster method than bringing a novel drug to market. Selective serotonin reuptake inhibitors (SSRIs) are primarily used for treating several types of depression, but over the past two decades mounting evidence suggests that drugs in this class have oncolytic properties and reduce the risk of certain cancers...
January 11, 2017: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/28087985/prophylactic-tributyrin-treatment-mitigates-chronic-binge-alcohol-induced-intestinal-barrier-and-liver-injury
#8
Gail A Cresci, Bryan Glueck, Megan R McMullen, Wei Xin, Danielle Allende, Laura E Nagy
BACKGROUND/AIM: Impaired gut-liver axis is a potential factor contributing to alcoholic liver disease. Ethanol depletes intestinal integrity and causes gut dysbiosis. Butyrate, a fermentation byproduct of gut microbiota, is altered negatively following chronic ethanol exposure. This study aimed to determine whether prophylactic tributyrin could protect the intestinal barrier and liver in mice during combined chronic-binge ethanol exposure. METHODS: C57BL/6 J mice exposed to 5% v/v ethanol-containing diet for 10 days received a single ethanol gavage (5 g/kg) 9 hrs prior to euthanasia...
January 14, 2017: Journal of Gastroenterology and Hepatology
https://www.readbyqxmd.com/read/28087937/myeloid-cell-phenotypes-in-susceptibility-and-resistance-to-helminth-parasite-infections
#9
Rick M Maizels, James P Hewitson
Many major tropical diseases are caused by long-lived helminth parasites that are able to survive by modulation of the host immune system, including the innate compartment of myeloid cells. In particular, dendritic cells and macrophages show markedly altered phenotypes during parasite infections. In addition, many specialized subsets such as eosinophils and basophils expand dramatically in response to these pathogens. The changes in phenotype and function, and their effects on both immunity to infection and reactivity to bystander antigens such as allergens, are discussed...
December 2016: Microbiology Spectrum
https://www.readbyqxmd.com/read/28087649/identification-of-unique-essential-proteins-from-a-m-tuberculosis-f15-lam4-kzn-phage-secretome-library
#10
Thamsanqa Emmanuel Chiliza, Manormoney Pillay, Balakrishna Pillay
Mycobacterium tuberculosis (Mtb) is the causative agent of tuberculosis disease (TB), the leading cause of death from bacterial infection worldwide. Although treatable, the resurgence of multi- and extensively-drug resistance TB is a major setback for the fight against TB globally. Consequently, there is an urgent need for new Mtb derived biomarkers for use in the design of new drugs and rapid point-of-care diagnostic or prognostic tools for management of TB transmission. Therefore, the present study aimed to identify unique Mtb secreted proteins from the extensively drug resistant Mtb F15/LAM4/KZN phage secretome library...
January 12, 2017: Pathogens and Disease
https://www.readbyqxmd.com/read/28087643/tumor-brca1-reversion-mutation-arising-during-neoadjuvant-platinum-based-chemotherapy-in-triple-negative-breast-cancer-is-associated-with-therapy-resistance
#11
Anosheh Afghahi, Kirsten M Timms, Shaveta Vinayak, Kristin C Jensen, Allison W Kurian, Robert W Carlson, Pei-Jen Chang, Elizabeth A Schackmann, Anne-Renee Hartman, James M Ford, Melinda L Telli
BACKGROUND: In germline BRCA1 or BRCA2 (BRCA1/2) mutation carriers, restoration of tumor BRCA1/2 function by a secondary mutation is recognized as a mechanism of resistance to platinum and PARP inhibitors, primarily in ovarian cancer. We evaluated this mechanism of resistance in newly diagnosed BRCA1/2-mutant breast cancer patients with poor response to neoadjuvant platinum-based therapy. METHODS: PrECOG 0105 was a phase II neoadjuvant study of gemcitabine, carboplatin and iniparib in patients with stage I-IIIA triple-negative or BRCA1/2 mutation-associated breast cancer (n=80)...
January 13, 2017: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/28087617/in-vitro-activity-of-the-antiasthmatic-drug-zafirlukast-against-the-oral-pathogens-porphyromonas-gingivalis-and-streptococcus-mutans
#12
Evelien Gerits, Isolde Van der Massen, Katleen Vandamme, Kaat De Cremer, Katrijn De Brucker, Karin Thevissen, Bruno P A Cammue, Serge Beullens, Maarten Fauvart, Natalie Verstraeten, Jan Michiels
Oral infections are among the most common diseases worldwide. Many protocols for the prevention and treatment of oral infections have been described, yet no golden standard has been developed so far. The antiseptic chlorhexidine and antibiotics are often used in these treatment procedures. However, long-term use of chlorhexidine can lead to side effects and extensive use of antibiotics can promote the development of antibiotic-resistant bacteria, which in turn can compromise the effectiveness of the treatment...
January 12, 2017: FEMS Microbiology Letters
https://www.readbyqxmd.com/read/28087534/mechanisms-of-horizontal-cell-to-cell-transfer-of-wolbachia-spp-in-drosophila-melanogaster
#13
Pamela M White, Jose E Pietri, Alain Debec, Shelbi Russell, Bhavin Patel, William Sullivan
: Wolbachia is an intracellular endosymbiont present in most arthropod and filarial nematode species. Transmission between hosts is primarily vertical, taking place exclusively through the female germline, though horizontal transmission has also been documented. Several studies indicate that Wolbachia is capable of transfer between somatic and germline cells during nematode development and in adult flies. However, the mechanisms underlying horizontal cell-to-cell transfer remain largely unexplored...
January 13, 2017: Applied and Environmental Microbiology
https://www.readbyqxmd.com/read/28087531/salivary-gluten-degradation-and-oral-microbial-profiles-in-health-and-celiac-disease
#14
Na Tian, Lina Faller, Daniel A Leffler, Ciaran P Kelly, Joshua Hansen, Jos A Bosch, Guoxian Wei, Bruce J Paster, Detlef Schuppan, Eva J Helmerhorst
: Celiac disease (CD) is a chronic immune-mediated enteropathy induced by dietary gluten in genetically predisposed individuals. Saliva harbors the second highest bacterial load of the GI tract after the colon. Moreover, saliva contains gluten-degrading enzymes produced by oral bacteria that may modify gluten processing in the intestine and susceptibility to celiac disease (CD). AIM: To investigate salivary enzymatic activities and oral microbial profiles in healthy subjects vs patients with classical and refractory CD...
January 13, 2017: Applied and Environmental Microbiology
https://www.readbyqxmd.com/read/28087412/pain-prediction-by-serum-biomarkers-of-bone-turnover-in-people-with-knee-osteoarthritis-an-observational-study-of-tracp5b-and-cathepsin-k-in-oa
#15
Lilian N Nwosu, Maximilian Allen, Laura Wyatt, Janet L Huebner, Victoria Chapman, David A Walsh, Virginia B Kraus
OBJECTIVES: To investigate serum biomarkers, tartrate resistant acid phosphatase 5b (TRAcP5b) and cathepsin K, indicative of osteoclastic bone resorption, and their relationship to pain and pain change in knee osteoarthritis (OA). METHODS: Sera and clinical data were collected from 129 people (97 with 3-year follow-up) with knee OA from the Prediction of Osteoarthritis Progression (POP) cohort. Knee OA-related outcomes in POP included: WOMAC pain, NHANES I (pain, aching and stiffness), subchondral sclerosis, and radiographically determined tibiofemoral and patellofemoral OA...
January 10, 2017: Osteoarthritis and Cartilage
https://www.readbyqxmd.com/read/28087069/safety-tolerability-and-antiviral-effect-of-rg-101-in-patients-with-chronic-hepatitis-c-a-phase-1b-double-blind-randomised-controlled-trial
#16
Meike H van der Ree, J Marleen de Vree, Femke Stelma, Sophie Willemse, Marc van der Valk, Svend Rietdijk, Richard Molenkamp, Janke Schinkel, Ad C van Nuenen, Ulrich Beuers, Salah Hadi, Marten Harbers, Eva van der Veer, Kai Liu, John Grundy, Amy K Patick, Adam Pavlicek, Jacqueline Blem, Michael Huang, Paul Grint, Steven Neben, Neil W Gibson, Neeltje A Kootstra, Hendrik W Reesink
BACKGROUND: miR-122 is an important host factor for hepatitis C virus (HCV) replication. The aim of this study was to assess the safety and tolerability, pharmacokinetics, and antiviral effect of a single dose of RG-101, a hepatocyte targeted N-acetylgalactosamine conjugated oligonucleotide that antagonises miR-122, in patients with chronic HCV infection with various genotypes. METHODS: In this randomised, double-blind, placebo-controlled, multicentre, phase 1B study, patients were randomly assigned to RG-101 or placebo (7:1)...
January 10, 2017: Lancet
https://www.readbyqxmd.com/read/28086955/evaluation-of-the-xpert%C3%A2-mtb-rif-assay-and-microscopy-for-the-diagnosis-of-mycobacterium-tuberculosis-in-namibia
#17
Rooyen T Mavenyengwa, Emma Shaduka, Innocent Maposa
BACKGROUND: Tuberculosis (TB) kills approximately two million people and infects around nine million worldwide annually. Its proper management, especially in resource-limited settings, has been hindered by the lack of rapid and easy-to-use diagnostic tests. Sputum smear microscopy remains the cheapest, readily available diagnostic method but it only identifies less than half of the patients with a HIV/TB co-infection because the bacilli would have disseminated from the lungs to other areas of the body...
January 11, 2017: Infectious Diseases of Poverty
https://www.readbyqxmd.com/read/28086952/glucagon-like-peptide-1-analogues-an-efficient-therapeutic-option-for-the-severe-insulin-resistance-of-lipodystrophic-syndromes-two-case-reports
#18
Joana Oliveira, Eva Lau, Davide Carvalho, Paula Freitas
BACKGROUND: Lipodystrophic syndromes are uncommon medical conditions which are normally associated with metabolic disorders, such as diabetes mellitus, dyslipidemia, and fatty liver disease. These complications are generally difficult to treat, particularly diabetes, due to severe insulin resistance. We present two case reports of successful treatment of diabetes with glucagon-like peptide-1 analogues in patients with clinical features of lipodystrophic syndromes. CASE PRESENTATION: Two white women aged 49 and 60 years manifested marked central body fat deposition with severe lipoatrophy of their limbs and buttocks and pronounced acanthosis nigricans...
January 13, 2017: Journal of Medical Case Reports
https://www.readbyqxmd.com/read/28086874/new-developments-in-anti-malarial-target-candidate-and-product-profiles
#19
REVIEW
Jeremy N Burrows, Stephan Duparc, Winston E Gutteridge, Rob Hooft van Huijsduijnen, Wiweka Kaszubska, Fiona Macintyre, Sébastien Mazzuri, Jörg J Möhrle, Timothy N C Wells
A decade of discovery and development of new anti-malarial medicines has led to a renewed focus on malaria elimination and eradication. Changes in the way new anti-malarial drugs are discovered and developed have led to a dramatic increase in the number and diversity of new molecules presently in pre-clinical and early clinical development. The twin challenges faced can be summarized by multi-drug resistant malaria from the Greater Mekong Sub-region, and the need to provide simplified medicines. This review lists changes in anti-malarial target candidate and target product profiles over the last 4 years...
January 13, 2017: Malaria Journal
https://www.readbyqxmd.com/read/28086863/exercise-mediated-protection-of-diabetic-heart-through-modulation-of-microrna-mediated-molecular-pathways
#20
REVIEW
Jason Kar Sheng Lew, James T Pearson, Daryl O Schwenke, Rajesh Katare
Hyperglycaemia, hypertension, dyslipidemia and insulin resistance collectively impact on the myocardium of people with diabetes, triggering molecular, structural and myocardial abnormalities. These have been suggested to aggravate oxidative stress, systemic inflammation, myocardial lipotoxicity and impaired myocardial substrate utilization. As a consequence, this leads to the development of a spectrum of cardiovascular diseases, which may include but not limited to coronary endothelial dysfunction, and left ventricular remodelling and dysfunction...
January 13, 2017: Cardiovascular Diabetology
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