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https://www.readbyqxmd.com/read/28088333/mitochondrial-uncoupling-in-cancer-cells-liabilities-and-opportunities
#1
REVIEW
Gyorgy Baffy
Acquisition of the endosymbiotic ancestor of mitochondria was a critical event in eukaryote evolution. Mitochondria offered an unparalleled source of metabolic energy through oxidative phosphorylation and allowed the development of multicellular life. However, as molecular oxygen had become the terminal electron acceptor in most eukaryotic cells, the electron transport chain proved to be the largest intracellular source of superoxide, contributing to macromolecular injury, aging, and cancer. Hence, the 'contract of endosymbiosis' represents a compromise between the possibilities and perils of multicellular life...
January 11, 2017: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/28087735/relationships-linking-emotional-motor-cognitive-and-gabaergic-dysfunctions-in-dystrophin-deficient-mdx-mice
#2
Cyrille Vaillend, Rémi Chaussenot
Alterations in the Duchenne muscular dystrophy (DMD) gene have been associated with enhanced stress reactivity in vertebrate species, suggesting a role for brain dystrophin in fear-related behavioral and cognitive processes. Because the loss of dystrophin (Dp427) reduces clustering of central GABAA receptors, it is suspected that local inhibitory tuning and modulation of neuronal excitability are perturbed in a distributed brain circuit that normally controls such critical behavioral functions. In this study we undertook a large-scale behavioral study to evaluate fear-related behavioral disturbances in dystrophin-deficient mdx mice...
January 13, 2017: Human Molecular Genetics
https://www.readbyqxmd.com/read/28087168/synthesis-structure-activity-relationships-studies-of-benzoxazinone-derivatives-as-%C3%AE-chymotrypsin-inhibitors
#3
Bishnu P Marasini, Fazal Rahim, Shahnaz Perveen, Aneela Karim, Khalid Mohammed Khan, Atta-Ur-Rahman, M Iqbal Choudhary
A series of benzoxazinones 1-28 were synthesized via reaction of anthranilic acid with various substituted benzoyl chlorides in the presence of triethylamine in chloroform. Compounds 1-18 showed a good inhibition of α-chymotrypsin with IC50±SEM values between 6.5 and 341.1μM. Preliminary structure-activity relationships studies indicated that the presence of substituents on benzene ring reduces the inhibitory potential of benzoxazinone. Also the increased inhibitory potential due to fluoro group at phenyl substituent was observed followed by chloro and bromo substituents...
January 4, 2017: Bioorganic Chemistry
https://www.readbyqxmd.com/read/28087066/use-of-water-soluble-contrast-medium-gastrografin-does-not-decrease-the-need-for-operative-intervention-nor-the-duration-of-hospital-stay-in-uncomplicated-acute-adhesive-small-bowel-obstruction-a-multicenter-randomized-clinical-trial-adhesive-small-bowel-obstruction
#4
Michel Scotté, Francois Mauvais, Michael Bubenheim, Cyril Cossé, Leslie Suaud, Celine Savoye-Collet, Isabelle Plenier, Aurelien Péquignot, Thierry Yzet, Jean Marc Regimbeau
BACKGROUND: This study evaluated the association between oral gastrografin administration and the need for operative intervention in patients with presumed adhesive small bowel obstruction. METHODS: Between October 2006 and August 2009, 242 patients with uncomplicated acute adhesive small bowel obstruction were included in a randomized, controlled trial (the Adhesive Small Bowel Obstruction Study, NCT00389116) and allocated to a gastrografin arm or a saline solution arm...
January 10, 2017: Surgery
https://www.readbyqxmd.com/read/28086960/the-relationship-between-synovitis-quantified-by-an-ultrasound-7-joint-inflammation-score-and-physical-disability-in-rheumatoid-arthritis-a-cohort-study
#5
Jakub Závada, Petra Hánová, Jana Hurňáková, Lenka Szczuková, Michal Uher, Šárka Forejtová, Martin Klein, Herman Mann, Marta Olejárová, Olga Růžičková, Olga Šléglová, Karel Hejduk, Karel Pavelka
BACKGROUND: Restoring normal physical functioning is a major therapeutic aim in the management of rheumatoid arthritis (RA). It is unknown, whether the extent of synovial inflammation quantified by musculoskeletal ultrasound (US) can predict current or future capacity for physical functioning. To answer this question we investigated the longitudinal relationship between physical function assessed by the health assessment questionnaire (HAQ) and the German 7-joint ultrasound score (US7S) in a prospective cohort of patients with RA...
January 13, 2017: Arthritis Research & Therapy
https://www.readbyqxmd.com/read/28086775/rapid-decline-in-the-susceptibility-of-plasmodium-falciparum-to-dihydroartemisinin-piperaquine-in-the-south-of-vietnam
#6
Ngo Viet Thanh, Nguyen Thuy-Nhien, Nguyen Thi Kim Tuyen, Nguyen Thanh Tong, Nguyen Thuy Nha-Ca, Le Thanh Dong, Huynh Hong Quang, Jeremy Farrar, Guy Thwaites, Nicholas J White, Marcel Wolbers, Tran Tinh Hien
BACKGROUND: Artemisinin resistant Plasmodium falciparum has emerged in the countries of the Greater Mekong sub-region posing a serious threat to global malaria elimination efforts. The relationship of artemisinin resistance to treatment failure has been unclear. METHODS: In annual studies conducted in three malaria endemic provinces in the south of Vietnam (Binh Phuoc, Ninh Thuan and Gia Lai) between 2011 and 2015, 489 patients with uncomplicated P. falciparum malaria were enrolled in detailed clinical, parasitological and molecular therapeutic response assessments with 42 days follow up...
January 13, 2017: Malaria Journal
https://www.readbyqxmd.com/read/28081468/role-of-mir-15a-in-intervertebral-disc-degeneration-through-targeting-map3k9
#7
Ping Cai, Ting Yang, Xingjie Jiang, Minghui Zheng, Gang Xu, Jianlong Xia
BACKGROUND: Accumulating evidence indicates that microRNAs are involved in various cellular processes, including cell proliferation, differentiation, apoptosis and metastasis. miR-15a is an important regulator of immune responses and angiogenesis, endogenous controls as well as potential targets and hallmarks of cancer. However, the role of miR-15a in intervertebral disc degeneration (IDD) has not been elucidated. METHODS: Total RNA was extracted from degenerative nucleus pulposus (NP) tissues of 20 patients with IDD and NP cells, respectively...
January 9, 2017: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/28079874/cerebral-modulation-of-the-autonomic-nervous-system-in-term-infants
#8
N Schneebaum Sender, R B Govindan, M T Whitehead, A N Massaro, M Metzler, J Wang, Y I Cheng, A J du Plessis
OBJECTIVE: Central topography of autonomic nervous system (ANS) function has yet to be fully deciphered. In adults it has been shown to lateralize sympathetic and parasympathetic influence predominantly to the right and left cerebral hemispheres, respectively. We examined functional topography of central ANS in newborn subjects utilizing spectral analysis of heart rate variability (HRV), an established measure of ANS function. STUDY DESIGN: We studied newborns with hypoxic-ischemic encephalopathy participating in a prospective study undergoing a therapeutic hypothermia protocol...
January 12, 2017: Journal of Perinatology: Official Journal of the California Perinatal Association
https://www.readbyqxmd.com/read/28079601/infliximab-optimization-based-on-therapeutic-drug-monitoring-in-pediatric-ibd
#9
Tatyana Hofmekler, Madeline Bertha, Courtney McCracken, Benadette Martineau, Elizabeth McKinnon, Bess T Schoen, Barbara O McElhanon, Gayathri Tenjarla, Subra Kugathasan, Cary Sauer
BACKGROUND: Infliximab (IFX) is an effective treatment for the management of moderate to severe inflammatory bowel disease (IBD). Low serum IFX levels are associated with the development of antibodies to IFX (ATI) which subsequently associated with clinical relapse and increased morbidity. The purpose of this study is to examine the relationship between dose and interval to IFX level. Secondary goal is to evaluate the relationship between IFX level and ATI in a pediatric IBD population...
June 21, 2016: Journal of Pediatric Gastroenterology and Nutrition
https://www.readbyqxmd.com/read/28079261/effect-of-parthanatos-on-ropivacaine-induced-damage-in-sh-sy5y-cells
#10
Ting Zheng, Chun-Ying Zheng, Xiao-Chun Zheng, Ruo-Guang Zhao, Yan-Qing Chen
Ropivacaine is one of the most common but toxic local anesthetics, and the mechanisms underlying its neurotoxicity are still largely unknown. This study was conducted to prepare a ropivacaine-induced neuronal injury model and research the effects of ropivacaine on PARP-1 activation and NAD(+) depletion. The cell death and apoptosis of ropivacaine-induced SH-SY5Y cells were detected with flow cytometry. The lactate dehydrogenase cycling reaction measured the NAD(+) level, and Western blots were used to analyze the expression levels of PARP-1 and AIF after ropivacaine treatments with different concentrations and durations...
January 12, 2017: Clinical and Experimental Pharmacology & Physiology
https://www.readbyqxmd.com/read/28078827/fam83-family-oncogenes-are-broadly-involved-in-human-cancers-an-integrative-multi-omics-approach
#11
Antoine M Snijders, Sun-Young Lee, Bo Hang, Wenshan Hao, Mina J Bissell, Jian-Hua Mao
The development of novel targeted therapies for cancer treatment requires identification of reliable targets. FAM83 ('family with sequence similarity 83') family members A, B, and D were shown recently to have oncogenic potential. However, the overall oncogenic abilities of FAM83 family genes remain largely unknown. Here, we used a systematic and integrative genomics approach to investigate oncogenic properties of the entire FAM83 family members. We assessed transcriptional expression patterns of eight FAM83 family genes (FAM83A-H) across tumor types, the relationship between their expression and changes in DNA copy number, and the association with patient survival...
October 26, 2016: Molecular Oncology
https://www.readbyqxmd.com/read/28078479/follow-up-cancer-care-perspectives-of-aboriginal-and-torres-strait-islander-cancer-survivors
#12
J A Meiklejohn, G Garvey, R Bailie, E Walpole, J Adams, D Williamson, J Martin, C M Bernardes, B Arley, B Marcusson, P C Valery
PURPOSE: The purpose of this study was to explore Indigenous Australian cancer survivors' perspectives of follow-up cancer care and management.. METHODS: This is a qualitative study employing individual interviews with 21 Indigenous cancer survivors (13 females, 8 males) recruited from a rural primary health service and large tertiary hospital in Brisbane, Queensland. Yarning methods were used to conduct semi-structured interviews. Yarning is a culturally appropriate, informal conversational process emphasising the importance of storytelling...
January 12, 2017: Supportive Care in Cancer: Official Journal of the Multinational Association of Supportive Care in Cancer
https://www.readbyqxmd.com/read/28077793/integrated-proteomic-and-n-glycoproteomic-analyses-of-doxorubicin-sensitive-and-resistant-ovarian-cancer-cells-reveal-glycoprotein-alteration-in-protein-abundance-and-glycosylation
#13
Yanlong Ji, Shasha Wei, Junjie Hou, Chengqian Zhang, Peng Xue, Jifeng Wang, Xiulan Chen, Xiaojing Guo, Fuquan Yang
Ovarian cancer is one of the most common cancer among women in the world, and chemotherapy remains the principal treatment for patients. However, drug resistance is a major obstacle to the effective treatment of ovarian cancers and the underlying mechanism is not clear. An increased understanding of the mechanisms that underline the pathogenesis of drug resistance is therefore needed to develop novel therapeutics and diagnostic. Herein, we report the comparative analysis of the doxorubicin sensitive OVCAR8 cells and its doxorubicin-resistant variant NCI/ADR-RES cells using integrated global proteomics and N-glycoproteomics...
January 6, 2017: Oncotarget
https://www.readbyqxmd.com/read/28077724/trem2-promotes-microglial-survival-by-activating-wnt-%C3%AE-catenin-pathway
#14
Honghua Zheng, Lin Jia, Chia-Chen Liu, Zhouyi Rong Li Zhong, Longyu Yang, Xiao-Fen Chen, John D Fryer, Xin Wang, Yun-Wu Zhang, Huaxi Xu, Guojun Bu
: Triggering Receptor Expressed on Myeloid cells 2 (TREM2), expressed on myeloid cells including microglia in the central nervous system (CNS), has recently been identified as a risk factor for Alzheimer's disease (AD). TREM2 transmits intracellular signals through its trans-membrane binding partner DNAX-activating protein 12 (DAP12). Homozygous mutations inactivating TREM2 or DAP12 lead to Nasu-Hakola disease (NHD); however, how AD risk-conferring variants increase AD risk is not clear...
January 11, 2017: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
https://www.readbyqxmd.com/read/28077345/tips-and-traps-lessons-from-codesigning-a-clinician-e-monitoring-tool-for-computerized-cognitive-behavioral-therapy
#15
Frederick Sundram, Susan J Hawken, Karolina Stasiak, Mathijs Fg Lucassen, Theresa Fleming, Matthew Shepherd, Andrea Greenwood, Raechel Osborne, Sally N Merry
BACKGROUND: Computerized cognitive behavioral therapy (cCBT) is an acceptable and promising treatment modality for adolescents with mild-to-moderate depression. Many cCBT programs are standalone packages with no way for clinicians to monitor progress or outcomes. We sought to develop an electronic monitoring (e-monitoring) tool in consultation with clinicians and adolescents to allow clinicians to monitor mood, risk, and treatment adherence of adolescents completing a cCBT program called SPARX (Smart, Positive, Active, Realistic, X-factor thoughts)...
January 11, 2017: JMIR Mental Health
https://www.readbyqxmd.com/read/28077324/grk2-as-negative-modulator-of-no-bioavailability-implications-for-cardiovascular-disease
#16
REVIEW
Alessandro Cannavo, Walter J Koch
Nitric oxide (NO), initially identified as endothelium-derived relaxing factor (EDRF), is a gaso-transmitter with important regulatory roles in the cardiovascular, nervous and immune systems. In the former, this diatomic molecule and free radical gas controls vascular tone and cardiac mechanics, among others. In the cardiovascular system, it is now understood that β-adrenergic receptor (βAR) activation is a key modulator of NO generation. Therefore, it is not surprising that the up-regulation of G protein-coupled receptor kinases (GRKs), in particular GRK2, that restrains βAR activity contributes to impaired cardiovascular functions via alteration of NO bioavailability...
January 7, 2017: Cellular Signalling
https://www.readbyqxmd.com/read/28076825/polar-aromatic-periphery-increases-agonist-potency-of-spirocyclic-free-fatty-acid-receptor-gpr40-agonists-inspired-by-ly2881835
#17
Mikhail Krasavin, Alexey Lukin, Daria Bagnyukova, Nikolay Zhurilo, Aleksei Golovanov, Sergey Zozulya, Ihor Zahanich, Daniel Moore, Irina G Tikhonova
A series of spirocyclic compounds inspired by Eli Lilly's phase 1 antidiabetic FFA1 receptor agonist LY2881835 was designed to include polar aromatic periphery groups and explore a possibility of building additional contacts with the target near the agonist binding site. The frontrunner compound in the series (9i) was shown to be a potent (EC50 = 260 nM) FFA1 agonist with excellent aqueous (PBS) solubility and good Caco-2 permeability. The observed structure-activity relationships were rationalized by a docking study...
January 4, 2017: European Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/28074664/recent-advances-in-molecular-biomarkers-for-diabetes-mellitus-a-systematic-review
#18
Ty Lees, Najah Nassif, Ann Simpson, Fatima Shad-Kaneez, Rose Martiniello-Wilks, Yiguang Lin, Allan Jones, Xianqin Qu, Sara Lal
CONTEXT: Diabetes is a growing global metabolic epidemic. Current research is focusing on exploring how the biological processes and clinical outcomes of diabetes are related and developing novel biomarkers to measure these relationships, as this can subsequently improve diagnostic, therapeutic and management capacity. OBJECTIVE: To identify the most recent advances in molecular biomarkers of diabetes and directions that warrant further research. METHODS: Using a systematic search strategy, the MEDLINE, CINAHL and OVID MEDLINE databases were canvassed for articles that investigated molecular biomarkers for diabetes...
January 11, 2017: Biomarkers: Biochemical Indicators of Exposure, Response, and Susceptibility to Chemicals
https://www.readbyqxmd.com/read/28074433/partial-contribution-of-rho-kinase-inhibition-to-the-bioactivity-of-ganoderma-lingzhi-and-its-isolated-compounds-insights-on-discovery-of-natural-rho-kinase-inhibitors
#19
Yhiya Amen, Qinchang Zhu, Hai-Bang Tran, Mohamed S Afifi, Ahmed F Halim, Ahmed Ashour, Kuniyoshi Shimizu
Recent studies identified Rho-kinase enzymes (ROCK-I and ROCK-II) as important targets that are involved in a variety of diseases. Synthetic Rho-kinase inhibitors have emerged as potential therapeutic agents to treat disorders such as hypertension, stroke, cancer, diabetes, glaucoma, etc. Our study is the first to screen the total ethanol extract of the medicinal mushroom Ganoderma lingzhi with thirty-five compounds for Rho-kinase inhibitory activity. Moreover, a molecular binding experiment was designed to investigate the binding affinity of the compounds at the active sites of Rho-kinase enzymes...
January 10, 2017: Journal of Natural Medicines
https://www.readbyqxmd.com/read/28074265/pharmacokinetic-and-exposure-response-analyses-of-pertuzumab-in-combination-with-trastuzumab-and-docetaxel-during-neoadjuvant-treatment-of-her2-%C3%A2-early-breast-cancer
#20
Angelica L Quartino, Hanbin Li, Jin Y Jin, D Russell Wada, Mark C Benyunes, Virginia McNally, Lucia Viganò, Ihsan Nijem, Bert L Lum, Amit Garg
PURPOSE: The NeoSphere trial evaluated pertuzumab in the neoadjuvant setting [early breast cancer (EBC)] with pathological complete response (pCR) as the primary efficacy end point. This analysis of pertuzumab aimed to (1) compare its pharmacokinetics (PK) in patients with EBC versus advanced cancers, (2) to further evaluate PK drug-drug interactions (DDIs) when given in combination with trastuzumab, and (3) to assess the relationship between exposure and efficacy to assess the clinical dosing regimen in the EBC patients...
January 10, 2017: Cancer Chemotherapy and Pharmacology
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