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https://www.readbyqxmd.com/read/28214365/peripheral-blood-leukocytes-show-differential-expression-of-tumour-progression-related-genes-in-colorectal-cancer-patients-who-have-a-postoperative-intra-abdominal-infection-a-prospective-matched-cohort-study
#1
S Alonso, X Mayol, L Nonell, S Salvans, M Pascual, M Pera
AIM: Anastomotic leak is associated with higher rates of recurrence after surgery for colorectal cancer. However, the mechanisms responsible are unknown. We hypothesized that the infection-induced inflammatory response may induce overexpression of tumour progression-related genes in immune cells. The aim was to investigate the effect of postoperative intra-abdominal infection on the gene expression patterns of peripheral blood leukocytes (PBL) after surgery for colorectal cancer. METHODS: Prospective matched cohort study...
February 18, 2017: Colorectal Disease: the Official Journal of the Association of Coloproctology of Great Britain and Ireland
https://www.readbyqxmd.com/read/28214350/upregulation-of-microrna-15a-contributes-to-pathogenesis-of-abdominal-aortic-aneurysm-aaa-by-modulating-the-expression-of-cyclin-dependent-kinase-inhibitor-2b-cdkn2b
#2
Peng Gao, Jiyuan Si, Bin Yang, Jixiang Yu
BACKGROUND The objective of the present study was to identify the association between miR-15a-5p and CDKN2B, and their roles in regulating the development of abdominal aortic aneurysm (AAA). MATERIAL AND METHODS We searched the miRNA database online (www.mirdb.org) and used a luciferase reporter assay system to study the regulatory relationship between miR-15a-5p and CDKN2B. We also conducted real-time PCR and Western blot analysis to study the mRNA and protein expression level of CDKN2B among different patient groups (participants with abdominal aortic aneurysm (AAA) and normal controls) or cells treated with scramble control, miR-15a-5p mimics, CDKN2B siRNA, and miR-15a-5p inhibitors...
February 18, 2017: Medical Science Monitor: International Medical Journal of Experimental and Clinical Research
https://www.readbyqxmd.com/read/28214182/opportunistic-autoimmunity-secondary-to-cancer-immunotherapy-oasi-an-emerging-challenge
#3
M Kostine, L Chiche, E Lazaro, P Halfon, C Charpin, D Arniaud, F Retornaz, P Blanco, N Jourde-Chiche, C Richez, C Stavris
With "checkpoint inhibitors" targeting PD1/PD-1-ligands or CTLA-4/CD28 pathways, immunotherapy has profoundly modified therapeutic strategies in oncology. First approved in refractory metastatic neoplasms (melanoma and lung adenocarcinoma), it is now being tested broadly in other cancers and/or as adjuvant treatment. For a significant proportion of patients, immunotherapy is responsible for "immunological" events, identified as Immune-Related Adverse Events (irAEs). Owing to the increasing number of prescriptions, identification and management of specific immunological side effects is crucial and requires close collaboration between oncologists and internists and/or other organ specialists...
February 14, 2017: La Revue de Médecine Interne
https://www.readbyqxmd.com/read/28214150/self-efficacy-for-deprescribing-a-survey-for-health-care-professionals-using-evidence-based-deprescribing-guidelines
#4
Barbara Farrell, Lisa Richardson, Lalitha Raman-Wilms, David de Launay, Mhd Wasem Alsabbagh, James Conklin
BACKGROUND: Although polypharmacy is associated with significant morbidity, deprescribing can be challenging. In particular, clinicians express difficulty with their ability to deprescribe (i.e. reduce or stop medications that are potentially inappropriate). Evidence-based deprescribing guidelines are designed to help clinicians take action on reducing or stopping medications that may be causing more harm than benefit. OBJECTIVES: Determine if implementation of evidence-based guidelines increases self-efficacy for deprescribing proton pump inhibitor (PPI), benzodiazepine receptor agonist (BZRA) and antipsychotic (AP) drug classes...
January 28, 2017: Research in Social & Administrative Pharmacy: RSAP
https://www.readbyqxmd.com/read/28214146/impact-of-anti-tnf-therapy-on-nk-cells-function-and-on-immunosurveillance-against-b-cell-lymphomas
#5
Gaetane Nocturne, Saida Boudaoud, Bineta Ly, Juliette Pascaud, Audrey Paoletti, Xavier Mariette
OBJECTIVES: Rheumatoid arthritis (RA) is associated with an increased risk of lymphoma linked to activity of the disease. Immunosuppressive drugs have been suspected to induce an additional risk. Since, NK cells have been recently shown to participate to anti-lymphoma immunosurveillance, we aimed to assess if anti-TNF might impact their anti-lymphoma activity. METHODS: NK cells have been assessed ex vivo in patients with RA treated with methotrexate (MTX) with or without anti-TNF...
February 14, 2017: Journal of Autoimmunity
https://www.readbyqxmd.com/read/28214087/targeting-the-pd-1-pd-l1-axis-in-non-small-cell-lung-cancer
#6
REVIEW
Rajiv Kumar, Dearbhaile Collins, Saoirse Dolly, Fiona McDonald, Mary E R O'Brien, Timothy A Yap
The last decade has witnessed rapid advances in the discovery and development of immune checkpoint inhibitors in cancer medicine, particularly drugs targeting programmed cell death 1 (PD-1) and programmed cell death ligand 1 (PD-L1) in non-small cell lung cancer (NSCLC). The proven antitumor efficacy coupled with low rates of drug-related toxicities observed, albeit idiosyncratic, with these novel immunotherapeutics have led to the registration of multiple PD-1 and PD-L1 inhibitors, such as nivolumab, pembrolizumab, and atezolizumab, in second-line advanced NSCLC, whereas durvalumab and avelumab are in late-phase clinical testing...
December 23, 2016: Current Problems in Cancer
https://www.readbyqxmd.com/read/28214076/erratum-to-a-triple-exon-skipping-luciferase-reporter-assay-identifies-a-new-clk-inhibitor-pharmacophore-bioorg-med-chem-lett-27-2017-406-412
#7
Yihui Shi, Jaehyeon Park, Chandraiah Lagisetti, Wei Zhou, Lidia C Sambucetti, Thomas R Webb
No abstract text is available yet for this article.
February 14, 2017: Bioorganic & Medicinal Chemistry Letters
https://www.readbyqxmd.com/read/28214069/-pharmacokinetic-drug-interaction-between-miconazole-mucoadhesive-tablet-and-tacrolimus-about-3%C3%A2-case-reports-in-transplant-patients
#8
Marion Lepelley, Sophie Logerot, Xavier Fonrose, Céline Villier
Loramyc(®) is a mucoadhesive tablet of miconazole, indicated for the treatment of oropharyngeal candidiasis in immunocompromised patients. Miconazole, as others azole antifungals, is known for its potent inhibitory properties of cytochromes P450 enzymes and P-glycoprotein (P-gp). Inhibition of cytochromes P450 enzymes and P-gp can produce pharmacokinetic drug interaction. Immunosuppressive agents, such as calcineurin inhibitors (tacrolimus, cyclosporine) are substrates of cytochromes P450 3A4 and P-gp. Nevertheless, the impact of systemic absorption of miconazole mucoadhesive tablet has not been investigated by the laboratory before regulatory approval...
January 12, 2017: Thérapie
https://www.readbyqxmd.com/read/28214027/arrested-geomorphic-trajectories-and-the-long-term-hidden-potential-for-change
#9
L Allan James
Geomorphic systems often experience morphological changes that define a trajectory over decadal time periods. These trends can be halted by natural inhibitors such as vegetation, knickpoints, bed armor, or bank cohesion, or by anthropogenic inhibitors such as revetment, levees, or dams. Details about where and how channels and floodplains are stabilized are often poorly understood, which poses a risk that modern projects could unwittingly remove critical stabilizing elements (inhibitors) and unleash an episode of rapid change...
February 14, 2017: Journal of Environmental Management
https://www.readbyqxmd.com/read/28213979/mmp-2-and-mmp-14-silencing-inhibits-vegfr2-cleavage-and-induces-the-differentiation-of-porcine-adipose-derived-mesenchymal-stem-cells-to-endothelial-cells
#10
Sami G Almalki, Yovani Llamas Valle, Devendra K Agrawal
The molecular mechanisms that control the ability of adipose-derived mesenchymal stem cells (AMSCs) to remodel three-dimensional extracellular matrix barriers during differentiation are not clearly understood. Herein, we studied the expression of matrix metalloproteinases (MMPs) during the differentiation of AMSCs to endothelial cells (ECs) in vitro. MSCs were isolated from porcine abdominal adipose tissue, and characterized by immunopositivity to CD44, CD90, CD105, and immunonegativity to CD14 and CD45. Plasticity of AMSCs was confirmed by multilineage differentiation...
February 18, 2017: Stem Cells Translational Medicine
https://www.readbyqxmd.com/read/28213978/estrogens-and-androgens-inhibit-association-of-rankl-with-the-pre-osteoblast-membrane-through-post-translational-mechanisms
#11
Anthony Martin, Jiali Yu, Jian Xiong, Aysha B Khalid, Benita Katzenellenbogen, Sung Hoon Kim, John A Katzenellenbogen, Suchinda Malaivijitnond, Yankel Gabet, Susan A Krum, Baruch Frenkel
We have recently demonstrated that RUNX2 promoted, and 17-β-Estradiol (E2) diminished, association of RANKL with the cell membrane in pre-osteoblast cultures. Here we show that, similar to E2, dihydrotestosterone (DHT) diminishes association of RANKL and transiently transfected GFP-RANKL with the pre-osteoblast membrane without decreasing total RANKL mRNA or protein levels. Diminution of membrane-associated RANKL was accompanied with marked suppression of osteoclast differentiation from co-cultured pre-osteoclasts, even though DHT increased, not decreased, RANKL concentrations in pre-osteoblast conditioned media...
February 18, 2017: Journal of Cellular Physiology
https://www.readbyqxmd.com/read/28213977/mitochondria-targeted-esculetin-inhibits-pai-1-levels-by-modulating-stat3-activation-and-mir-19b-via-sirt3-role-in-acute-coronary-artery-syndrome
#12
Sujana Katta, Santosh Karnewar, Devayani Panuganti, Mahesh Kumar Jerald, Sastry B K, Srigiridhar Kotamraju
In this study, we explored the microRNAs responsible for the regulation of PAI-1 during LPS-stimulated inflammation in human aortic endothelial cells, subsequently studied the effect of a newly synthesized mitochondria-targeted esculetin (Mito-Esc) that was shown for its anti-atherosclerotic potential in modulating PAI-1 levels and its targeted miRs during angiotensin-II-induced atherosclerosis in ApoE(-/-) mice. LPS-stimulated PAI-1 was accompanied with an upregulation of miR-19b and down-regulation of miR-30c...
February 18, 2017: Journal of Cellular Physiology
https://www.readbyqxmd.com/read/28213955/the-skin-barrier-function-gene-spink5-is-associated-with-challenge-proven-ige-mediated-food-allergy-in-infants
#13
Sarah E Ashley, Hern-Tze Tina Tan, Peter Vuillermin, Shyamali C Dharmage, Mimi L K Tang, Jennifer Koplin, Lyle C Gurrin, Adrian Lowe, Caroline Lodge, Anne-Louise Ponsonby, John Molloy, Pamela Martin, Melanie C Matheson, Richard Saffery, Katrina J Allen, Justine A Ellis, David Martino
BACKGROUND: A defective skin barrier is hypothesised to be an important route of sensitisation to dietary antigens, and may lead to food allergy in some children. Missense mutations in the Serine peptidase inhibitor kazal type 5 (SPINK5) skin barrier gene have previously been associated with allergic conditions. OBJECTIVE: To determine whether genetic variants in and around SPINK5 are associated with IgE mediated food allergy. METHOD: We genotyped 71 'tag' single nucleotide polymorphisms (tag-SNPs) within a region spanning ~263 kilobases (kb) including SPINK5 (~61kb) in n=722 (n=367 food allergic, n=199 food sensitised, tolerant and n=156 non-food allergic controls) 12-month infants (discovery sample) phenotyped for food allergy with the gold standard oral food challenge (OFC)...
February 18, 2017: Allergy
https://www.readbyqxmd.com/read/28213937/targeting-phosphodiesterase-5-as-a-therapeutic-option-against-myocardial-ischemia-reperfusion-injury-and-in-treating-heart-failure
#14
REVIEW
Sevil Korkmaz-Icöz, Tamás Radovits, Gábor Szabó
Phosphodiesterase type 5 (PDE5) selectively hydrolyses the second messenger cyclic 3´-5´guanosine monophosphate (cGMP) into 5'-GMP, thereby regulating its intracellular concentrations. Dysregulation of the cGMP-dependent pathway plays a significant role in various cardiovascular diseases. Therefore, its modulation by drugs, such as PDE5 inhibitors, may represent an effective therapeutic approach. There are currently four PDE5 inhibitors available for the treatment of erectile dysfunction: sildenafil, vardenafil, tadalafil, and avanafil...
February 18, 2017: British Journal of Pharmacology
https://www.readbyqxmd.com/read/28213892/opportunities-for-repurposing-of-poly-adp-ribose-polymerase-parp-inhibitors-for-the-therapy-of-non-oncological-diseases
#15
REVIEW
Nathan A Berger, Valerie C Besson, A Hamid Boulares, Alexander Bürkle, Alberto Chiarugi, Robert S Clark, Nicola J Curtin, Salvatore Cuzzocrea, Ted M Dawson, Valina L Dawson, György Haskó, Lucas Liaudet, Flavio Moroni, Pál Pacher, Peter Radermacher, Andrew L Salzman, Solomon H Snyder, Francisco Garcia Soriano, Robert P Strosznajder, Balázs Sümegi, Raymond A Swanson, Csaba Szabo
The recent clinical availability of the PARP inhibitor Lynparza (olaparib) opens the door for potential therapeutic repurposing for non-oncological indications. Considering (a) the preclinical efficacy data with PARP inhibitors in non-oncological diseases and (b) the risk-benefit ratio of treating patients with a compound that inhibits an enzyme that has physiological roles in the regulation of DNA repair, indications where (a) the severity of the disease is high, (b) the available therapeutic options are limited, and (c) the duration of PARP inhibitor administration could be short, provide first-line options for therapeutic repurposing...
February 18, 2017: British Journal of Pharmacology
https://www.readbyqxmd.com/read/28213877/improved-control-of-hypertension-following-laparoscopic-fundoplication-for-gastroesophageal-reflux-disease
#16
Zhiwei Hu, Meiping Chen, Jimin Wu, Qing Song, Chao Yan, Xing Du, Zhonggao Wang
This study aims to determine whether successful laparoscopic fundoplication for gastroesophageal reflux disease (GERD) can improve the control of hypertension. We conducted an observational study of GERD patients with hypertension. The esophageal and gastroesophageal symptoms of these patients were successfully treated with laparoscopic fundoplication, as measured by the reduced GERD symptoms and proton pump inhibitor consumption. A hypertension control scale was used to classify the use of antihypertensive medications and the quality of blood pressure control before and after anti-reflux surgery...
February 17, 2017: Frontiers of Medicine
https://www.readbyqxmd.com/read/28213862/apremilast-a-review-in-psoriasis-and-psoriatic-arthritis
#17
Gillian M Keating
Apremilast (Otezla(®)) is an orally administered, small molecule inhibitor of phosphodiesterase 4 (PDE4). Apremilast 30 mg twice daily reduced the severity of moderate to severe plaque psoriasis in the phase 3 ESTEEM trials, as well as improving difficult-to-treat nail, scalp and palmoplantar psoriasis. Most patient-reported outcomes, including pruritus and the total Dermatology Life Quality Index, also improved to a significantly greater extent with apremilast than with placebo, with significant improvements in pruritus and skin discomfort/pain visual analogue scale scores seen as early as week 2 with apremilast...
February 18, 2017: Drugs
https://www.readbyqxmd.com/read/28213772/the-effect-of-purinergic-signaling-via-the-p2y11-receptor-on-vascular-function-in-a-rat-model-of-acute-inflammation
#18
Maria D Dănilă, Andreea Privistirescu, Oana M Duicu, Corina D Rațiu, Denis Angoulvant, Danina M Muntean, Adrian Sturza
There is a growing body of evidence pointing to the role of purinergic signaling in the development and progression of various conditions that have inflammation as a common pathogenetic denominator. The aim of the present study was to assess the involvement of P2Y11 purinergic receptors in the regulation of vascular function in aortic segments obtained using an experimental model of acute inflammation, the lipopolysaccharide (LPS, 8 mg/kg, i.p)-treated rats. Twelve hours after LPS administration, thoracic aortas were isolated and used for studies of vascular reactivity in the organ bath and for the measurement of reactive oxygen species (ROS) generation, respectively...
February 17, 2017: Molecular and Cellular Biochemistry
https://www.readbyqxmd.com/read/28213714/-current-biomarkers-for-gastric-cancer
#19
G B Baretton, D E Aust
Gastric cancer is still a relevant malignant disease with high morbidity and mortality. Current molecular genetic data show that gastric cancer, as other solid tumors as well, is not a single entity but consists of several molecular subtypes of gastric cancer with diverse biology. The increasing understanding of molecular pathways is the basis for innovative therapies. These either directly target altered signaling pathways or genes in tumor cells or as in immune checkpoint inhibitors, indirectly target tumor cells by blocking tumor-induced immune inhibition leading to improvement in the prognosis...
February 17, 2017: Der Pathologe
https://www.readbyqxmd.com/read/28213588/a-differential-autophagy-dependent-response-to-dna-double-strand-brakes-in-bone-marrow-mesenchymal-stem-cells-from-sporadic-als-patients
#20
Shane Wald-Altman, Edward Pichinuk, Or Kakhlon, Miguel Weil
Amyotrophic Lateral Sclerosis (ALS) is an incurable motor neurodegenerative disease caused by a diversity of genetic and environmental factors leading to neuromuscular degeneration and pathophysiological implications in non-neural systems. Our previous work showed abnormal transcriptional expression levels of biomarker genes in non-neuronal cell samples from ALS patients. The same genes proved to be differentially expressed in brain, spinal cord and muscle of the SOD1(G93A) ALS mouse model. These observations support the pathophysiological relevance of the ALS biomarkers discovered in human mesenchymal stem cells (hMSC) isolated from bone marrow samples of ALS patients (ALS-hMSC)...
February 16, 2017: Disease Models & Mechanisms
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