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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/28088717/removal-of-antibiotic-resistance-genes-from-wastewater-treatment-plant-effluent-by-coagulation
#2
Na Li, Guo-Ping Sheng, Yong-Ze Lu, Raymond J Zeng, Han-Qing Yu
Antibiotic resistance genes (ARGs), as emerging environmental contaminants, have become a threat to human health. Recent studies have demonstrated that the effluent from wastewater treatment plants is a significant point source of ARGs released into the environment. In this study, we investigated the effectiveness of coagulation technology in the removal of ARGs from treated wastewater. Specifically, we measured the removal of five ARGs (two sulfonamide resistance genes, sulI and sulII, and three tetracycline resistance genes, tetO, tetW and tetQ) and the class 1 integron intI1 gene via the application of two coagulants: FeCl3 and polyferric chloride (PFC)...
January 4, 2017: Water Research
https://www.readbyqxmd.com/read/28088621/4-hydroxynonenal-causes-impairment-of-human-subcutaneous-adipogenesis-and-induction-of-adipocyte-insulin-resistance
#3
Mohamed Elrayess, Shamma Al-Muraikhy, Wael Kafienah, Afnan Al-Menhali, Fatima Al-Khalaifi, Moataz Bashah, Kamelija Zarkovic, Neven Zarkovic, Georg Waeg, Mohammed Alsayrafi, Morana Jaganjac
OBJECTIVE: Increased adipose production of 4-hydroxynonenal (4-HNE), a bioreactive aldehyde, directly correlates with obesity and insulin resistance. The aim of this study was to elucidate the impact of 4-HNE in mediating adipocyte differentiation and function in two metabolically distinct obese groups; the insulin sensitive (IS) and the insulin resistant (IR). METHODS: Subcutaneous (SC) adipose tissues were obtained from eighteen clinically well characterized obese premenopausal women undergoing weight reduction surgery...
January 11, 2017: Free Radical Biology & Medicine
https://www.readbyqxmd.com/read/28088542/interaction-of-earthworms-microbe-facilitating-biofilm-dewaterability-performance-during-wasted-activated-sludge-reduction-and-stabilization
#4
Yadan Zheng, Meiyan Xing, Luziyu Cai, Tao Xiao, Yufan Lu, Jinzhou Jiang
Sludge dewaterability was chemically and morphologically explored during sewage sludge treatment by vermifiltration. The results, with a conventional biofilter (BF, no earthworms) as a control, demonstrated that the capillary suction time(CST) and specific resistance of filtration(SRF) of vermifilter (VF, with earthworms) treated sludge were 64.9±1.7s and (23.1±1.3)×10(12)m/kg,16.8% and 36.0% lower than that of the BF, respectively. Additionally, the VF could efficiently decompose loosely bound extracellular polymeric substances (LB-EPS), releasing more water trapped inside biofilm...
January 11, 2017: Science of the Total Environment
https://www.readbyqxmd.com/read/28088530/distribution-of-antibiotic-resistance-in-the-effluents-of-ten-municipal-wastewater-treatment-plants-in-china-and-the-effect-of-treatment-processes
#5
Weiwei Ben, Jian Wang, Rukun Cao, Min Yang, Yu Zhang, Zhimin Qiang
Municipal wastewater treatment plant (WWTP) effluents represent an important contamination source of antibiotic resistance, threatening the ecological safety of receiving environments. In this study, the release of antibiotic resistance to sulfonamides and tetracyclines in the effluents of ten WWTPs in China was investigated. Results indicate that the concentrations of antibiotic-resistant bacteria (ARB) and antibiotic resistance genes (ARGs) ranged from 1.1 × 10(1) to 8.9 × 10(3) CFU mL(-1) and 3.6 × 10(1) (tetW) to 5...
January 6, 2017: Chemosphere
https://www.readbyqxmd.com/read/28088511/brief-report-egfr-l858m-l861q-cis-mutations-confer-selective-sensitivity-to-afatinib
#6
Jamie A Saxon, Lynette M Sholl, Pasi A Jänne
INTRODUCTION: Tyrosine kinase inhibitors (TKIs) have been developed to treat patients with epidermal growth factor receptor (EGFR)-mutant lung cancers. However, the therapeutic efficacy of TKIs in patients with uncommon EGFR mutations remains unclear. METHODS: Next-generation sequencing was performed on a patient's lung adenocarcinoma tumor sample, revealing rare combined in cis (on the same allele) EGFR mutations. Stable Ba/F3 and NIH-3T3 cell lines harboring the mutations were established to investigate the effect of first, second, and third generation EGFR TKIs on cell proliferation by MTS assay and EGFR phosphorylation by Western blotting...
January 11, 2017: Journal of Thoracic Oncology
https://www.readbyqxmd.com/read/28088467/stat3-signaling-mediates-tumour-resistance-to-egfr-targeted-therapeutics
#7
Ahmad A Zulkifli, Fiona H Tan, Tracy L Putoczki, Stanley S Stylli, Rodney B Luwor
Several EGFR inhibitors are currently undergoing clinical assessment or are approved for the clinical management of patients with varying tumour types. However, treatment often results in a lack of response in many patients. The majority of patients that initially respond eventually present with tumours that display acquired resistance to the original therapy. A large number of receptor tyrosine and intracellular kinases have been implicated in driving signaling that mediates this tumour resistance to anti-EGFR targeted therapy, and in a few cases these discoveries have led to overall changes in prospective tumour screening and clinical practice (K-RAS in mCRC and EGFR T790M in NSCLC)...
January 11, 2017: Molecular and Cellular Endocrinology
https://www.readbyqxmd.com/read/28088439/antimicrobial-activity-of-photodynamic-therapy-in-combination-with-colistin-against-a-pan-drug-resistant-acinetobacter-baumannii-isolated-from-burn-patient
#8
Ebrahim Boluki, Hossein Kazemian, Hadi Peeridogaheh, Mohammad Yousef Alikhani, Sima Shahabi, Leili Beytollahi, Roghayeh Ghorbanzadeh
Nosocomially-acquired multi-, extensively-, and pandrug resistant (MDR, XDR, and PDR) strains of microorganisms such as Acinetobacter baumannii remain a serious cause of infection and septic mortality in burn patients. Treatment of patients with nosocomial burn wound infections is often complicated by drug-resistant strains of A. baumannii. Today, many researchers are focusing on the investigation of novel non-antibiotic strategies such as photodynamic therapy (PDT). We report a new PDT strategy that suppresses colistin resistance in PDR A...
January 11, 2017: Photodiagnosis and Photodynamic Therapy
https://www.readbyqxmd.com/read/28088384/the-signalling-mechanisms-of-a-novel-mitochondrial-complex-i-inhibitor-prevent-lipid-accumulation-and-attenuate-tnf-%C3%AE-induced-insulin-resistance-in-vitro
#9
Siobhán Leonard, Laura M Tobin, John B C Findlay
RTC-1 has recently been identified as a member of a new class of anti-diabetic compounds acting through the inhibition of complex I of the mitochondrial respiratory chain (NADH:ubiquinone oxidoreductase) to improve glucose handling and inhibit weight gain in mice fed a high-fat diet (HFD). The exact mechanism by which the reduced activity of NADH:ubiquinone oxidoreductase, in response to RTC-1, promotes these improved metabolic parameters remains to be established. Through extensive in vitro analysis, new molecular insights into these downstream signalling pathways have been obtained...
January 11, 2017: European Journal of Pharmacology
https://www.readbyqxmd.com/read/28088378/antimicrobial-coated-implants-in-trauma-and-orthopaedics-a-clinical-review-and-risk-benefit-analysis
#10
REVIEW
Volker Alt
Implant-associated infections remain a major issue in orthopaedics and antimicrobial functionalization of the implant surface by antibiotics or other anti-infective agents have gained interest. The goal of this article is to identify antimicrobial coatings, for which clinical data are available and to review their clinical need, safety profile, and their efficacy to reduce infection rates. PubMed database of the National Library of Medicine was searched for clinical studies on antimicrobial coated implants for internal fracture fixation devices and endoprostheses for bone surgery, for which study design, level of evidence, biocompatibility, development of resistance, and effectiveness to reduce infection rates were analyzed...
December 21, 2016: Injury
https://www.readbyqxmd.com/read/28088308/effect-of-various-polishing-systems-on-the-surface-roughness-and-phase-transformation-of-zirconia-and-the-durability-of-the-polishing-systems
#11
Chan Park, Mong-Sook Vang, Sang-Won Park, Hyun-Pil Lim
STATEMENT OF PROBLEM: Although many systems are used to polish zirconia, a comparison of the performance of zirconia and feldspathic porcelain polishing systems is lacking. PURPOSE: The purpose of this in vitro study was to compare the effects of 3 polishing systems on surface roughness, zirconia phase transformation, and durability of the polishing systems when applied to zirconia and feldspathic porcelain. MATERIAL AND METHODS: Three polishing systems were evaluated: Z1, a zirconia polishing system; Z2, a zirconia polishing system, and F1, a feldspathic porcelain polishing system...
January 11, 2017: Journal of Prosthetic Dentistry
https://www.readbyqxmd.com/read/28088237/association-between-diabetes-mellitus-and-multi-drug-resistant-tuberculosis-a-protocol-for-a-systematic-review-and-meta-analysis
#12
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/28088113/modulatory-effect-of-vanillic-acid-on-antioxidant-status-in-high-fat-diet-induced-changes-in-diabetic-hypertensive-rats
#13
Kolanji Vinothiya, Natarajan Ashokkumar
The worldwide incidence of diabetes has increased dramatically along with widespread lifestyle and dietary changes. Diets high in fat are strongly associated with the development of obesity and can induce insulin resistance in humans and animals. It is clear that obesity constitutes a risk factor for contributing to the development of type 2 diabetes. In the present study, we investigated the therapeutic potential action of vanillic acid on diabetes associated complications using a rat model. Rats were made diabetic hypertensive by high fat diet (HFD) for 20 weeks and were treated with vanillic acid (50mg/kg bw) for last 8 weeks...
January 11, 2017: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/28088075/development-of-a-hypoxia-triggered-and-hypoxic-radiosensitized-liposome-as-a-doxorubicin-carrier-to-promote-synergetic-chemo-radio-therapy-for-glioma
#14
Hongmei Liu, Yandong Xie, Yafei Zhang, Yifan Cai, Baiyang Li, Honglin Mao, Yingguo Liu, Jun Lu, Longzhen Zhang, Rutong Yu
The treatment of malignant primary brain tumors is challenging. Concomitant radiochemotherapy has become the standard clinical treatment for malignant glioma, but there are two critical challenges to overcome in order to increase efficacy. First, glioma is known to have increased resistant to radiation due to its intra-tumoral hypoxia. In addition, the blood-brain barrier (BBB) restricts the distribution of the chemotherapeutic agent to the brain. Therefore, we developed a hypoxic radiosensitizer-prodrug liposome (MLP), in order to deliver DOX to the tumor and to overcome the above challenges, achieving a synergistic chemo-/radiotherapy treatment of malignant glioma...
January 3, 2017: Biomaterials
https://www.readbyqxmd.com/read/28087985/prophylactic-tributyrin-treatment-mitigates-chronic-binge-alcohol-induced-intestinal-barrier-and-liver-injury
#15
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/28087935/diagnosis-treatment-and-prevention-of-urinary-tract-infection
#16
Paula Pietrucha-Dilanchian, Thomas M Hooton
UTI may involve the lower or upper urinary tract and may be uncomplicated or complicated. The emphasis of this chapter is uncomplicated UTI. The diagnosis of uncomplicated cystitis (bladder infection) and pyelonephritis (kidney infection) is usually easily made based on the clinical presentation, whereas the diagnosis in patients with complicated UTI is often more complex. Thus uncomplicated cystitis is usually manifested by dysuria, frequency and/or urgency without fever, and pyelonephritis is usually manifested by fever and back pain/costovertebral angle tenderness...
December 2016: Microbiology Spectrum
https://www.readbyqxmd.com/read/28087926/urinary-tract-infections-in-infants-and-children
#17
Theresa A Schlager
Urinary tract infections (UTI) are one of the most common infections in children and symptoms may be nonspecific. The risk of renal scarring is highest in children under 1 year of age with febrile UTI and high-grade vesicoureteral reflux (VUR). Although treatment of UTI is usually straightforward, given increased rates of antimicrobial resistance worldwide, the choice of treatment for pediatric UTI should be guided by community resistance patterns whenever feasible. The benefit of antimicrobial prophylaxis after first UTI and/or in the presence of VUR remains controversial, but a recent meta-analysis supports continuous antimicrobial prophylaxis in children with VUR, indicating a need for more research in this area...
October 2016: Microbiology Spectrum
https://www.readbyqxmd.com/read/28087741/14-3-3sigma-contributes-to-radioresistance-by-regulating-dna-repair-and-cell-cycle-via-parp1-and-chk2
#18
Yifan Chen, Zhaomin Li, Zizheng Dong, Jenny Beebe, Ke Yang, Liwu Fu, Jian-Ting Zhang
: 14-3-3sigma has been implicated in the development of chemo and radiation resistance and in poor prognosis of multiple human cancers. While it has been postulated that 14-3-3sigma contributes to these resistances via inhibiting apoptosis and arresting cells in G2/M phase of the cell cycle, the molecular basis of this regulation is currently unknown. In this study, we tested the hypothesis that 14-3-3sigma causes resistance to DNA-damaging treatments by enhancing DNA repair in cells arrested in G2/M phase following DNA-damaging treatments...
January 13, 2017: Molecular Cancer Research: MCR
https://www.readbyqxmd.com/read/28087739/tnf-signaling-through-rip1-kinase-enhances-sn38-induced-death-in-colon-adenocarcinoma
#19
Lucia Cabal-Hierro, Peter J O'Dwyer
: Elucidation of tumor necrosis factor (TNF)-directed mechanisms for cell death induction and maintenance of tumor growth has revealed a role for receptor-interacting protein kinases 1 and 3 (RIPK1/RIP1 and RIPK3/RIP3), components of the necrosome complex, as determinants of cell fate. Here the participation of TNF signaling was analyzed with regard to the cytotoxic action of different DNA damaging agents in a panel of colon cancer cells. While most of these cell lines were insensitive to TNF, combination with these drugs increased sensitivity by inducing cell death and DNA damage, especially in the case of the topoisomerase inhibitor SN38...
January 13, 2017: Molecular Cancer Research: MCR
https://www.readbyqxmd.com/read/28087660/the-morphophysiological-dormancy-in-amborella-trichopoda-seeds-is-a-pleisiomorphic-trait-in-angiosperms
#20
Bruno Fogliani, Gildas Gâteblé, Matthieu Villegente, Isabelle Fabre, Nicolas Klein, Nicolas Anger, Carol C Baskin, Charlie P Scutt
BACKGROUND AND AIMS: Recent parsimony-based reconstructions suggest that seeds of early angiosperms had either morphophysiological or physiological dormancy, with the former considered as more probable. The aim of this study was to determine the class of seed dormancy present in Amborella trichopoda, the sole living representative of the most basal angiosperm lineage Amborellales, with a view to resolving fully the class of dormancy present at the base of the angiosperm clade. METHODS: Drupes of A...
January 13, 2017: Annals of Botany
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