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Ramiya Kumar, Linda C Mota, Elizabeth J Litoff, John P Rooney, W Tyler Boswell, Elliott Courter, Charles M Henderson, Juan P Hernandez, J Christopher Corton, David D Moore, William S Baldwin
Targeted mutant models are common in mechanistic toxicology experiments investigating the absorption, metabolism, distribution, or elimination (ADME) of chemicals from individuals. Key models include those for xenosensing transcription factors and cytochrome P450s (CYP). Here we investigated changes in transcript levels, protein expression, and steroid hydroxylation of several xenobiotic detoxifying CYPs in constitutive androstane receptor (CAR)-null and two CYP-null mouse models that have subfamily members regulated by CAR; the Cyp3a-null and a newly described Cyp2b9/10/13-null mouse model...
2017: PloS One
Kuan Ning, Teng Wang, Xu Sun, Pengfei Zhang, Yun Chen, Jian Jin, Dong Hua
BACKGROUND: Chemotherapy resistance has become a serious challenge in the treatment of breast cancer. Previous studies showed cells can transfer proteins, including those responsible for drug resistance to adjacent cells via exosomes. METHODS: The switches of drug resistance via exosomes transfer were assessed by CellTiter-Blue Viability assay, flow cytometry, and immunostaining analysis. Relative protein levels of Ubiquitin carboxyl terminal hydrolase-L1 (UCH-L1), P-glycoprotein (P-gp), extracellular-signal regulated protein kinase1/2 (ERK1/2), and phospho-extracellular-signal regulated protein kinase1/2 (p-ERK1/2) were measured by Western blot...
March 23, 2017: Journal of Surgical Oncology
Claire Ara-Somohano, Agnès Bonadona, Francoise Carpentier, Patricia Pavese, Aurélien Vesin, Rebecca Hamidfar-Roy, Clémence Minet, Gerald Vanzetto, Carole Schwebel, Jean F Timsit
BACKGROUND: Being able to better predict risk and optimal care for patients presenting with acute dyspnea is critical. Prognostic biomarkers are well known: amino-terminal pro-Btype Natriuretic Peptide, troponin, C-reactive protein, procalcitonin. Some were more recently developed: mid-regional pro-A-type natriuretic peptide (Mid Pro-ANP), mid-regional-proadrenomedullin (MR-proADM), pro-endothelin, copeptin. The aim of the paper was to evaluate prognostic value of clinical findings and 8 biomarkers in patients with severe acute dyspnea...
March 8, 2017: Minerva Anestesiologica
A S Ertugrul, A Bozoglan, M Taspınar
BACKGROUND AND AIMS: The aim of this study is to compare patients with atherosclerosis and chronic periodontitis and patients who are systemically healthy and chronic periodontitis using alteration of adrenomedullin (ADM), chemokine (C-C motif) ligand 28 (CCL-28), white blood cell levels, platelet levels, high-density lipoprotein, low-density lipoprotein, high-sensitivity C-reactive protein, creatinine, and fibrinogen. MATERIALS AND METHODS: Totally, 40 patients were involved in study; a test group of 20 patients with atherosclerosis-chronic periodontitis and a control group of 20 patients who were nonatherosclerosis-chronic periodontitis...
March 2017: Nigerian Journal of Clinical Practice
Xin Zeng, Yi Yuan, Ting Wang, Han Wang, Xianyun Hu, Ziyi Fu, Gen Zhang, Bin Liu, Guangming Lu
BACKGROUND: Currently, graphene oxide has attracted growing attention as a drug delivery system due to its unique characteristics. Furthermore, utilization of microRNAs as biomarkers and therapeutic strategies would be particularly attractive because of their biological mechanisms and relatively low toxicity. Therefore, we have developed functionalized nanocompounds consisted of graphene oxide, quantum dots and microRNA, which induced cancer cells apoptosis along with targeted imaging...
January 23, 2017: Journal of Nanobiotechnology
Heli Tolppanen, Mercedes Rivas-Lasarte, Johan Lassus, Jordi Sans-Roselló, Oliver Hartmann, Matias Lindholm, Mattia Arrigo, Tuukka Tarvasmäki, Lars Köber, Holger Thiele, Kari Pulkki, Jindrich Spinar, John Parissis, Marek Banaszewski, Jose Silva-Cardoso, Valentina Carubelli, Alessandro Sionis, Veli-Pekka Harjola, Alexandre Mebazaa
BACKGROUND: The clinical CardShock risk score, including baseline lactate levels, was recently shown to facilitate risk stratification in patients with cardiogenic shock (CS). As based on baseline parameters, however, it may not reflect the change in mortality risk in response to initial therapies. Adrenomedullin is a prognostic biomarker in several cardiovascular diseases and was recently shown to associate with hemodynamic instability in patients with septic shock. The aim of our study was to evaluate the prognostic value and association with hemodynamic parameters of bioactive adrenomedullin (bio-ADM) in patients with CS...
December 2017: Annals of Intensive Care
Qing Li, Hao Wang, George Zogopoulos, Qin Shao, Kun Dong, Fudong Lv, Karam Nwilati, Xian-Yong Gui, Adeline Cuggia, Jun-Li Liu, Zu-Hua Gao
Pancreatic ductal adenocarcinoma (PDAC) is a highly aggressive malignant tumor. Acinar-to-ductal metaplasia (ADM) and pancreatic intraepithelial neoplasia (PanIN) are both precursor lesions that lead to the development of PDAC. Reg family proteins (Reg1A, 1B, 3A/G, 4) are a group of calcium-dependent lectins that promote islet growth in response to inflammation and/or injuries. The aim of this study was to establish a role for Reg proteins in the development of PDAC and their clinical value as biomarkers. We found that Reg1A and Reg3A/G were highly expressed in the ADM tissues by immunohistochemistry...
November 22, 2016: Oncotarget
Francisco Valenzuela-Sánchez, Blanca Valenzuela-Méndez, Juan Francisco Rodríguez-Gutiérrez, Ángel Estella-García, María Ángela González-García
Mid-regional pro-adrenomedullin (MR-proADM) has a good biomarker profile: its half-life is several hours, and its plasma concentrations can be determined in clinical practice, it is essentially irrelevant, but proportionally represents the levels and activity of adrenomedullin (ADM). ADM synthesis is widely distributed in tissues, including bone, adrenal cortex, kidney, lung, blood vessels and heart. Its fundamental biological effects include vasodilator, positive inotropic, diuretic, natriuretic and bronchodilator...
September 2016: Annals of Translational Medicine
Giuseppe Agapito, Cirino Botta, Pietro Hiram Guzzi, Mariamena Arbitrio, Maria Teresa Di Martino, Pierfrancesco Tassone, Pierosandro Tagliaferri, Mario Cannataro
BACKGROUND: The identification of biomarkers for the estimation of cancer patients' survival is a crucial problem in modern oncology. Recently, the Affymetrix DMET (Drug Metabolizing Enzymes and Transporters) microarray platform has offered the possibility to determine the ADME (absorption, distribution, metabolism, and excretion) gene variants of a patient and to correlate them with drug-dependent adverse events. Therefore, the analysis of survival distribution of patients starting from their profile obtained using DMET data may reveal important information to clinicians about possible correlations among drug response, survival rate, and gene variants...
September 23, 2016: Microarrays
Christopher L Cioffi, Shuang Liu, Mark A Wolf, Peter R Guzzo, Kashinath Sadalapure, Visweswaran Parthasarathy, David T J Loong, Jun-Ho Maeng, Edmund Carulli, Xiao Fang, Kalesh Karunakaran, Lakshman Matta, Sok Hui Choo, Shailijia Panduga, Ronald N Buckle, Randall N Davis, Samuel A Sakwa, Priya Gupta, Bruce J Sargent, Nicholas A Moore, Michele M Luche, Grant J Carr, Yuri L Khmelnitsky, Jiffry Ismail, Mark Chung, Mei Bai, Wei Yee Leong, Nidhi Sachdev, Srividya Swaminathan, Andrew J Mhyre
We previously disclosed the discovery of rationally designed N-((1-(4-(propylsulfonyl)piperazin-1-yl)cycloalkyl)methyl)benzamide inhibitors of glycine transporter-1 (GlyT-1), represented by analogues 10 and 11. We describe herein further structure-activity relationship exploration of this series via an optimization strategy that primarily focused on the sulfonamide and benzamide appendages of the scaffold. These efforts led to the identification of advanced leads possessing a desirable balance of excellent in vitro GlyT-1 potency and selectivity, favorable ADME and in vitro pharmacological profiles, and suitable pharmacokinetic and safety characteristics...
September 22, 2016: Journal of Medicinal Chemistry
Petra Schneiderova, Tomas Pika, Petr Gajdos, Regina Fillerova, Pavel Kromer, Milos Kudelka, Jiri Minarik, Tomas Papajik, Vlastimil Scudla, Eva Kriegova
Serum protein fingerprints associated with MGUS and MM and their changes in MM after autologous stem cell transplantation (MM-ASCT, day 100) remain unexplored. Using highly-sensitive Proximity Extension ImmunoAssay on 92 cancer biomarkers (Proseek Multiplex, Olink), enhanced serum levels of Adrenomedullin (ADM, Pcorr= .0004), Growth differentiation factor 15 (GDF15, Pcorr= .003), and soluble Major histocompatibility complex class I-related chain A (sMICA, Pcorr= .023), all prosurvival and chemoprotective factors for myeloma cells, were detected in MM comparing to MGUS...
August 12, 2016: Oncotarget
Javier I Ottaviani, Gina Borges, Tony Y Momma, Jeremy P E Spencer, Carl L Keen, Alan Crozier, Hagen Schroeter
Diet is a major life style factor affecting human health, thus emphasizing the need for evidence-based dietary guidelines for primary disease prevention. While current recommendations promote intake of fruit and vegetables, we have limited understanding of plant-derived bioactive food constituents other than those representing the small number of essential nutrients and minerals. This limited understanding can be attributed to some extent to a lack of fundamental data describing the absorption, distribution, metabolism and excretion (ADME) of bioactive compounds...
July 1, 2016: Scientific Reports
Domenico Galati, Serena Zanotta
A higher incidence of cancer has been observed in Human Immunodeficiency Virus (HIV) infected individuals as compared with healthy people of the same age. A complex relationship between HIV-induced immune suppression, chronic antigenic stimulation, and oncogenic virus co-infections may promote carcinogenesis and increase the risk of developing tumors in these patients. Cancers in HIV subjects include the AIDS-defining malignancies (ADMs) and other non-AIDS-defining malignancies (NADMs). Antiretroviral therapy has reduced the incidence of ADMs whereas a concurrent increase of NADMs was observed in the last years...
2016: Current Medicinal Chemistry
Stuart M Grieve, Mayuresh S Korgaonkar, Evian Gordon, Leanne M Williams, A John Rush
OBJECTIVE: Over 50% of outpatients with nonpsychotic major depressive disorder (MDD) do not achieve remission with any single antidepressant medication (ADM). There are currently no clinically useful pretreatment measures that inform the decision to prescribe or select ADMs. This report examines whether a biomarker based on diffusion tensor imaging (DTI) measures of brain connectivity can identify a subset of nonremitting patients with a sufficiently high degree of specificity that use of a medication that is likely to fail could be avoided...
April 2016: Journal of Clinical Psychiatry
Teresa Mary MacDonald, Tu'uhevaha Joy Kaitu'u-Lino, Susan Philippa Walker, Kirsten Margaret Dane, Elizabeth Beatrice Lockie, Stephen Tong, Clare Louise Whitehead, Lisa Hui
BACKGROUND: It is not known whether fasting affects levels of circulating placenta-specific transcripts. OBJECTIVE: To assess whether a glucose load affects circulating placenta-specific transcripts. METHOD: RNA was extracted from paired blood samples (fasting and 1-h post 75 g oral glucose) from 22 women. Placenta-specific genes were measured by RT-qPCR. RESULTS: There was no change in ADM, CSH1, PAPPA2, PSG1 or TAC3 expression between fasting and post-glucose states...
March 2017: Journal of Maternal-fetal & Neonatal Medicine
Hai Yang Wang, Zi Li Lin, Xian Feng Yu, Yuan Bao, Xiang-Shun Cui, Nam-Hyung Kim
As the most common neurodegenerative diseases, Alzheimer's disease (AD) and Parkinson's disease (PD) are two of the main health concerns for the elderly population. Recently, microRNAs (miRNAs) have been used as biomarkers of infectious, genetic, and metabolic diseases in humans but they have not been well studied in domestic animals. Here we describe a computational biology study in which human AD- and PD-associated miRNAs (ADM and PDM) were utilized to predict orthologous miRNAs in the following domestic animal species: dog, cow, pig, horse, and chicken...
June 2016: Asian-Australasian Journal of Animal Sciences
M Ingelman-Sundberg, I Cascorbi
Interindividual differences in expression of ADME genes are controlled by both genetic and epigenetic factors. Much emphasis has been made to describe the genetic influence, whereas the epigenetic part is not fully understood. Currently, we utilize mainly genetic biomarkers for optimization of drug therapy, although many rare genetic variants are not taken into consideration. Now, also epigenomic biomarkers are at hand and together genetic and epigenetic biomarkers can indeed improve the predictability of drug treatment...
May 2016: Clinical Pharmacology and Therapeutics
Mingqun Li, L I Hong, Meimei Liao, Guanglin Guo
The aim of the present study was to investigate the expression of focal adhesion kinase (FAK) and adrenomedullin (ADM) and determine their clinical significance and cooperative role in human epithelial ovarian cancer. The expression of FAK and ADM was investigated in epithelial ovarian cancer, benign ovarian tumors and normal control tissues by immunohistochemical staining and optical microscopy. The FAK and ADM expression and correlation with clinicopathological parameters was analyzed using SPSS 13.0 software...
August 2015: Oncology Letters
Wesley H Self, Alan B Storrow, Oliver Hartmann, Tyler W Barrett, Gregory J Fermann, Alan S Maisel, Joachim Struck, Andreas Bergmann, Sean P Collins
OBJECTIVE: The objective was to evaluate the prognostic performance of a new biomarker, plasma bioactive adrenomedullin (bio-ADM), for short-term clinical outcomes in acute heart failure. METHODS: A multicenter prospective cohort study of adult emergency department (ED) patients suspected of having acute heart failure was conducted to evaluate the association between plasma bio-ADM concentration and clinical outcomes. The primary outcome was a composite of the following within 30 days: death, cardiac arrest with resuscitation, respiratory failure, emergency dialysis, acute coronary syndrome, hospitalization >5 days, and repeat ED visit or hospitalization...
February 2016: American Journal of Emergency Medicine
Kee F Chi, Mayuresh Korgaonkar, Stuart M Grieve
BACKGROUND: We review what is currently known about neuroimaging predictors of remission in major depressive disorder (MDD) after antidepressant medication (ADM) treatment. METHODS: A systematic literature search found a total of twenty-seven studies comparing baseline neuroimaging findings in depressed patients who achieved remission with non-remitters following treatment with ADMs. RESULTS: Eighteen of these studies utilised structural magnetic resonance imaging (MRI)...
November 1, 2015: Journal of Affective Disorders
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