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https://www.readbyqxmd.com/read/28528519/il-6-blockade-in-the-management-of-non-infectious-uveitis
#1
Giuseppe Lopalco, Claudia Fabiani, Jurgen Sota, Orso Maria Lucherini, Gian Marco Tosi, Bruno Frediani, Florenzo Iannone, Mauro Galeazzi, Rossella Franceschini, Donato Rigante, Luca Cantarini
Several pathogenetic studies have paved the way for a newer more rational therapeutic approach to non-infectious uveitis, and treatment of different forms of immune-driven uveitis has drastically evolved in recent years after the advent of biotechnological drugs. Tumor necrosis factor-α targeted therapies, the first-line recommended biologics in uveitis, have certainly led to remarkable results in patients with non-infectious uveitis. Nevertheless, the decision-making process turns out to be extremely difficult in anti-tumor necrosis factor or multidrug-resistant cases...
May 20, 2017: Clinical Rheumatology
https://www.readbyqxmd.com/read/28528362/budesonide-fluticasone-propionate-and-azithromycin-do-not-modulate-the-membrane-vesicle-release-by-thp-1-macrophages-and-respiratory-pathogens-during-macrophage-infection
#2
Charlotte Volgers, Gert E Grauls, Pauline H M Hellebrand, Paul H M Savelkoul, Frank R M Stassen
Patients with more severe chronic obstructive pulmonary disease frequently experience exacerbations and it is estimated that up to 50% of these exacerbations are associated with bacterial infections. The mainstay treatment for these infection-related exacerbations constitutes the administration of glucocorticoids, alone or in combination with antibiotics. A recent line of evidence demonstrates that many hormones including the steroid beclomethasone can also directly affect bacterial growth, virulence, and antibiotic resistance...
May 20, 2017: Inflammopharmacology
https://www.readbyqxmd.com/read/28528338/chronic-glibenclamide-treatment-attenuates-walker-256-tumour-growth-in-prediabetic-obese-rats
#3
Claudinéia Conationi da Silva Franco, Carina Previate, Kátia Gama de Barros Machado, Silvano Piovan, Rosiane Aparecida Miranda, Kelly Valério Prates, Veridiana Mota Moreira, Júlio Cezar de Oliveira, Luiz Felipe Barella, Rodrigo Mello Gomes, Flávio Andrade Francisco, Isabela Peixoto Martins, Audrei Pavanello, Tatiane Aparecida Ribeiro, Laize Peron Tófolo, Ananda Malta, Aline Amenencia de Souza, Vander Silva Alves, Sandra da Silva Silveira, Maria Raquel Marçal Natali, Jean Carlos Fernando Besson, Hely de Morais, Helenir Medri de Souza, Juliane Rocha de Sant Anna, Marialba Avezum Alves de Castro Prado, Paulo Cezar de Freitas Mathias
BACKGROUND/AIMS: The sulphonylurea glibenclamide (Gli) is widely used in the treatment of type 2 diabetes. In addition to its antidiabetic effects, low incidences of certain types of cancer have been observed in Gli-treated diabetic patients. However, the mechanisms underlying this observation remain unclear. The aim of the present work was to evaluate whether obese adult rats that were chronically treated with an antidiabetic drug, glibenclamide, exhibit resistance to rodent breast carcinoma growth...
May 11, 2017: Cellular Physiology and Biochemistry
https://www.readbyqxmd.com/read/28528303/discovery-of-a-potent-dual-alk-and-egfr-t790m-inhibitor
#4
Jaebong Jang, Jung Beom Son, Ciric To, Magda Bahcall, So Young Kim, Seock Yong Kang, Mierzhati Mushajiang, Younho Lee, Pasi A Jänne, Hwan Geun Choi, Nathanael S Gray
The mutational activations of anaplastic lymphoma kinase (ALK) and epidermal growth factor receptor (EGFR) are validated oncogenic events and the targets of approved drugs to treat non-small cell lung cancer (NSCLC). Here we report highly potent dual small molecule inhibitors of both ALK and EGFR, particularly the T790M mutant which confers resistance to first generation EGFR inhibitors. Dual ALK/EGFR inhibitors may provide an efficient approach to prevent resistance that arises as a consequence of clinically reported reciprocal activation mechanisms...
May 3, 2017: European Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/28528299/selective-targeting-and-therapy-of-metastatic-and-multidrug-resistant-tumors-using-a-long-circulating-podophyllotoxin-nanoparticle
#5
Aniruddha Roy, Yucheng Zhao, Yang Yang, Andras Szeitz, Tara Klassen, Shyh-Dar Li
Treatment options for metastatic and multidrug resistant (MDR) tumors are limited, and most of the chemotherapeutic drugs exhibit low efficacy against MDR cancers. An anti-tubulin agent podophyllotoxin (PPT) displays high potency against MDR tumor cells. However, due to its poor solubility and non-specificity, PPT cannot be used systemically. We have developed a self-assembling nanoparticle dosage form for PPT (named Celludo) by covalently conjugating PPT and polyethylene glycol (PEG) to acetylated carboxymethyl cellulose (CMC-Ac) via ester linkages...
May 11, 2017: Biomaterials
https://www.readbyqxmd.com/read/28528294/isoliquiritigenin-reduces-oxidative-damage-and-alleviates-mitochondrial-impairment-by-sirt1-activation-in-experimental-diabetic-neuropathy
#6
Veera Ganesh Yerra, Anil Kumar Kalvala, Ashutosh Kumar
Sirtuin (SIRT1) inactivation underlies the pathogenesis of insulin resistance and hyperglycaemia-associated vascular complications, but its role in diabetic neuropathy (DN) has not been yet explored. We have evaluated hyperglycaemia-induced alteration of SIRT1 signalling and the effect of isoliquiritigenin (ILQ) on SIRT1-directed AMP kinase (AMPK) and peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PGC-1α) signalling in peripheral nerves of streptozotocin (STZ) (55 mg/kg, ip)-induced diabetic rats and in high glucose (30 mM)-exposed neuro2a (N2A) cells...
May 11, 2017: Journal of Nutritional Biochemistry
https://www.readbyqxmd.com/read/28528135/presymptomatically-applied-ampa-receptor-antagonist-prevents-calcium-increase-in-vulnerable-type-of-motor-axon-terminals-of-mice-modeling-amyotrophic-lateral-sclerosis
#7
Roland Patai, Melinda Paizs, Massimo Tortarolo, Caterina Bendotti, Izabella Obál, József I Engelhardt, László Siklós
Increased intracellular calcium (Ca), which might be the consequence of an excess influx through Ca-permeable α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptors, plays a crucial role in degeneration of motor neurons. Previously we demonstrated that the presymptomatic application of AMPA receptor antagonist, talampanel, could reduce Ca elevation in spinal motor neurons of mice carrying the G93A mutation of superoxide dismutase 1 (SOD1), modeling amyotrophic lateral sclerosis (ALS). It remained to be examined whether the remote, functionally semi-autonomous motor axon terminals could be rescued from the Ca overload, or if the terminals, where the degeneration possibly starts, already experience intractable changes at early time points...
May 17, 2017: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/28528134/enhancing-tumor-cell-response-to-multidrug-resistance-with-ph-sensitive-quercetin-and-doxorubicin-conjugated-multifunctional-nanoparticles
#8
Cenk Daglioglu
Classical chemotherapy uses chemotherapeutic agents as a mainstay of anticancer treatment. However, the development of multidrug resistance to chemotherapy limits the effectiveness of current cancer treatment. Nanosized bioconjugates combining a chemotherapeutic agent with a pharmacological approach may improve the curative effect of chemotherapeutic agents. Herein I addressed this issue by describing the synthesis, and testing of, pH-responsive Fe3O4@SiO2(FITC)-BTN/QUR/DOX multifunctional nanoparticles. The particles were designed to modulate resistance-mediating factors and to potentiate the efficacy of DOX against chemoresistance...
May 10, 2017: Colloids and Surfaces. B, Biointerfaces
https://www.readbyqxmd.com/read/28528110/effect-of-regulated-deficit-irrigation-on-quality-parameters-carotenoids-and-phenolics-of-diverse-tomato-varieties-solanum-lycopersicum-l
#9
Elena Coyago-Cruz, Mireia Corell, Carla M Stinco, Dolores Hernanz, Alfonso Moriana, Antonio J Meléndez-Martínez
This study aims to evaluate the effects of regulated deficit irrigation (RDI) and of cluster position (CI: first and second cluster; CII: third and fourth cluster; CIII: fifth and sixth cluster) on fruit quality parameters, carotenoids and phenolics in tomatoes. Three common ('Tigerella', 'Palamós' and 'Byelsa') and two cherry varieties ('Lazarino' and 'Summerbrix') were studied. The results showed that the regulated deficit irrigation with reduction of 40 and 50% in the leaf water potential in common and cherry tomatoes did not affect greatly the organoleptic quality of common tomatoes and 'Summerbrix', while cherry varieties were significantly affected with the cluster position...
June 2017: Food Research International
https://www.readbyqxmd.com/read/28528008/-role-of-therapeutic-drug-monitoring-in-pulmonary-infections
#10
REVIEW
C Padoin
Pulmonary infections are common and caused by a wide range of viruses, bacteria, parasites and fungi. They consist of lower respiratory tract infections with community and hospital acquired acute pneumonia, bronchitis, lung abscess, fungal infections and tuberculosis. The management of these infections should be based on guidelines that take into account the microorganisms most frequently involved as a basis for empirical treatment, with identification of causative microorganisms allowing targeted treatments...
May 17, 2017: Revue des Maladies Respiratoires
https://www.readbyqxmd.com/read/28527998/molecular-cloning-and-structural-modelling-of-gamma-phospholipase-a2-inhibitors-from-bothrops-atrox-and-micrurus-lemniscatus-snakes
#11
Carina G Picelli, Rafael J Borges, Carlos A H Fernandes, Fabio M Matioli, Carla F C Fernandes, Juliana C Sobrinho, Rudson J Holanda, Luiz S Ozaki, Anderson M Kayano, Leonardo A Calderon, Marcos R M Fontes, Rodrigo G Stábeli, Andreimar M Soares
Phospholipases A2 inhibitors (PLIs) produced by venomous and non-venomous snakes play essential role in this resistance. These endogenous inhibitors may be classified by their fold in PLIα, PLIβ and PLIγ. Phospholipases A2 (PLA2s) develop myonecrosis in snake envenomation, a consequence that is not efficiently neutralized by antivenom treatment. This work aimed to identify and characterize two PLIs from Amazonian snake species, Bothrops atrox and Micrurus lemniscatus. Liver tissues RNA of specimens from each species were isolated and amplified by RT-PCR using PCR primers based on known PLIγ gene sequences, followed by cloning and sequencing of amplified fragments...
May 17, 2017: International Journal of Biological Macromolecules
https://www.readbyqxmd.com/read/28527946/the-microbiome-and-hepatobiliary-pancreatic-cancers
#12
Kosuke Mima, Shigeki Nakagawa, Hiroshi Sawayama, Takatsugu Ishimoto, Katsunori Imai, Masaaki Iwatsuki, Daisuke Hashimoto, Yoshifumi Baba, Yo-Ichi Yamashita, Naoya Yoshida, Akira Chikamoto, Hideo Baba
The human intestinal microbiome encompasses at least 100 trillion microorganisms that can influence host immunity and disease conditions, including cancer. Hepatobiliary and pancreatic cancers have been associated with poor prognosis owing to their high level of tumor invasiveness, distant metastasis, and resistance to conventional treatment options, such as chemotherapy. Accumulating evidence from animal models suggests that specific microbes and microbial dysbiosis can potentiate hepatobiliary-pancreatic tumor development by damaging DNA, activating oncogenic signaling pathways, and producing tumor-promoting metabolites...
May 17, 2017: Cancer Letters
https://www.readbyqxmd.com/read/28527896/molecular-characterization-and-expression-analyses-of-the-solea-senegalensis-interferon-stimulated-gene-15-isg15-following-nnv-infections
#13
Daniel Álvarez-Torres, Ana María Podadera, M Carmen Alonso, Isabel Bandín, Julia Béjar, Esther García-Rosado
Interferons are essential in fish resistance to viral infections. They induce interferon-stimulated genes, such as isg15. In this study, the Senegalese sole isg15 gene (ssisg15) has been characterized. As other isg15, ssisg15 contains a 402-bp intron sited in the 5'-UTR, and the full length cDNA is 1492-bp, including a 480-bp ORF. The expression analyses revealed basal levels of isg15 transcripts, and a clear induction after poly I:C injection, that reached maximum values in brain, head kidney and gills. The ssisg15 induction patterns were similar in RGNNV- and SJNNV-inoculated fish, whereas the reassortant (RG/SJ) isolate, which has higher replication fitness, triggered delayed but higher transcript levels...
May 17, 2017: Fish & Shellfish Immunology
https://www.readbyqxmd.com/read/28527877/esculetin-ameliorates-hepatic-fibrosis-in-high-fat-diet-induced-non-alcoholic-fatty-liver-disease-by-regulation-of-foxo1-mediated-pathway
#14
Anuradha Pandey, Priyank Raj, Santosh Kumar Goru, Almesh Kadakol, Vajir Malek, Nisha Sharma, Anil Bhanudas Gaikwad
BACKGROUND: Non-alcoholic fatty liver disease (NAFLD), a chronic metabolic disorder is associated with oxidative stress, inflammation and fibrotic cascades. In this study, we aimed to examine the effects of Esculetin, a well-known anti-oxidant on TGF-β1 mediated liver fibrosis and FoxO1 activity. METHODS: A non-genetic murine model for NAFLD was developed by chronic high fat diet (HFD) (58% calories from fats) feeding in Wistar rats. The plasma biochemical parameters, liver function tests, oxidative stress, and histopathological alterations were assessed...
February 4, 2017: Pharmacological Reports: PR
https://www.readbyqxmd.com/read/28527808/short-communication-effect-of-whey-protein-addition-and-transglutaminase-treatment-on-the-physical-and-sensory-properties-of-reduced-fat-ice-cream
#15
Erfan Danesh, Mostafa Goudarzi, Hossein Jooyandeh
The effects of whey protein addition and transglutaminase treatment, alone and in combination, on the physical and sensory properties of reduced-fat ice cream were investigated. Adding whey protein with or without enzyme treatment decreased melting rate, overrun, and hardness of the reduced-fat ice cream; however, the enzyme-treated sample had a higher melting rate and overrun and softer texture. Whey protein-fortified samples showed higher melting resistance, but lower overrun and firmer texture compared with the enzyme-treated sample without added whey protein...
May 17, 2017: Journal of Dairy Science
https://www.readbyqxmd.com/read/28527651/clinical-efficacy-of-cycling-empirical-antibiotic-therapy-for-febrile-neutropenia-in-pediatric-cancer-patients
#16
Hideto Teranishi, Yuhki Koga, Hisanori Nishio, Wakako Kato, Hiroaki Ono, Shunsuke Kanno, Kentaro Nakashima, Hidetoshi Takada
BACKGROUND: Febrile neutropenia (FN) is the main treatment-related cause of mortality among children with cancer, as the prolonged use of broad-spectrum antibiotics can lead to antibiotic resistance in these patients. Antibiotic cycling has been reported to limit the emergence of antibiotic-resistant bacteria among adult patients. However, no studies have evaluated pediatric patients with FN. METHODS: Between September 2011 and February 2014, 126 pediatric cancer patients were admitted to our center for chemotherapy and/or hematopoietic stem cell transplantation and were included in this study...
May 17, 2017: Journal of Infection and Chemotherapy: Official Journal of the Japan Society of Chemotherapy
https://www.readbyqxmd.com/read/28527650/new-1-hydroxy-2-thiopyridine-derivatives-active-against-both-replicating-and-dormant-mycobacterium-tuberculosis
#17
Elena G Salina, Olga Ryabova, Anthony Vocat, Boris Nikonenko, Stewart T Cole, Vadim Makarov
Tuberculosis (TB) treatment is confounded by the range of metabolic states displayed by Mycobacterium tuberculosis, by the long duration required and by the increasing prevalence of drug-resistant strains. Latent TB infection is especially difficult to treat due to the phenotypic antibiotic resistance of non-replicating M. tuberculosis. Therefore, the development of new drugs effective against both active and latent TB infection is needed. New 1-hydroxy-2-thiopyridine derivatives were synthesized and found to be highly effective in vitro against both actively growing and dormant non-culturable M...
May 17, 2017: Journal of Infection and Chemotherapy: Official Journal of the Japan Society of Chemotherapy
https://www.readbyqxmd.com/read/28527577/resistance-to-thyroid-hormone-due-to-heterozygous-mutations-in-thyroid-hormone-receptor-alpha
#18
Anja L M van Gucht, Carla Moran, Marcel E Meima, W Edward Visser, Krishna Chatterjee, Theo J Visser, Robin P Peeters
BACKGROUND: Thyroid hormone (TH) acts via nuclear thyroid hormone receptors (TRs). TR isoforms (TRα1, TRα2, TRβ1, TRβ2) are encoded by distinct genes (THRA and THRB) and show differing tissue distributions. Patients with mutations in THRB, exhibiting resistance within the hypothalamic-pituitary-thyroid axis with elevated TH and nonsuppressed thyroid-stimulating hormone (TSH) levels, were first described decades ago. In 2012, the first patients with mutations in THRA were identified...
2017: Current Topics in Developmental Biology
https://www.readbyqxmd.com/read/28527522/precision-medicine-genomic-profiles-to-individualize-therapy
#19
REVIEW
Oscar E Streeter, Phillip J Beron, Prashant Natarajan Iyer
Precision medicine is the application of genotypic and Omics biomarkers to determine the most appropriate, outcome-driven therapy for individual patients. To determine the best choice of therapy, institutions use significant information technology-enabled data from imaging, electronic medical records, sensors in the clinic/hospitals, and wearable sensors to determine treatment response. With genomic profiling, targets to affect a disease course are continuing to be developed. As clonal mutational prevalence continues to be understood, information can be communicated to patients to inform them that resistance is common, requiring collection of more genetic mutations from patients with further biopsies or blood collection...
May 17, 2017: Otolaryngologic Clinics of North America
https://www.readbyqxmd.com/read/28527408/subcellular-localization-based-comparative-study-on-radioresistant-bacteria-a-novel-approach-to-mine-proteins-involve-in-radioresistance
#20
Divya Vishambra, Malay Srivastava, Kamal Dev, Varun Jaiswal
Radioresistant bacteria (RRB) are among the most radioresistant organisms and has a unique role in evolution. Along with the evolutionary role, radioresistant organisms play important role in paper industries, bioremediation, vaccine development and possibility in anti-aging and anti-cancer treatment. The study of radiation resistance in RRB was mainly focused on cytosolic mechanisms such as DNA repair mechanism, cell cleansing activity and high antioxidant activity. Although it was known that protein localized on outer areas of cell play role in resistance towards extreme condition but the mechanisms/proteins localized on the outer area of cells are not studied for radioresistance...
May 10, 2017: Computational Biology and Chemistry
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