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https://www.readbyqxmd.com/read/28530221/micu1-drives-glycolysis-and-chemoresistance-in-ovarian-cancer
#1
Prabir K Chakraborty, Soumyajit Banerjee Mustafi, Xunhao Xiong, Shailendra Kumar Dhar Dwivedi, Vasyl Nesin, Sounik Saha, Min Zhang, Danny Dhanasekaran, Muralidharan Jayaraman, Robert Mannel, Kathleen Moore, Scott McMeekin, Da Yang, Rosemary Zuna, Kai Ding, Leonidas Tsiokas, Resham Bhattacharya, Priyabrata Mukherjee
Cancer cells actively promote aerobic glycolysis to sustain their metabolic requirements through mechanisms not always clear. Here, we demonstrate that the gatekeeper of mitochondrial Ca(2+) uptake, Mitochondrial Calcium Uptake 1 (MICU1/CBARA1) drives aerobic glycolysis in ovarian cancer. We show that MICU1 is overexpressed in a panel of ovarian cancer cell lines and that MICU1 overexpression correlates with poor overall survival (OS). Silencing MICU1 in vitro increases oxygen consumption, decreases lactate production, inhibits clonal growth, migration and invasion of ovarian cancer cells, whereas silencing in vivo inhibits tumour growth, increases cisplatin efficacy and OS...
May 22, 2017: Nature Communications
https://www.readbyqxmd.com/read/28530168/microbe-profile-akkermansia-muciniphila-a-conserved-intestinal-symbiont-that-acts-as-the-gatekeeper-of-our-mucosa
#2
Willem M de Vos
Akkermansia muciniphila is an abundant inhabitant of the intestinal tract of humans and many other animals. It is the sole intestinal representative of the verrucomicrobia in human stools and depleted in adults suffering from obesity, diabetes and several other diseases. A. muciniphila degrades intestinal mucin into mainly propionic and acetic acid, and lives in symbiosis with its host, marked by signalling to immune and metabolic pathways, priming trophic chains and likely providing competitive exclusion at the host-microbe interface...
May 22, 2017: Microbiology
https://www.readbyqxmd.com/read/28526938/reducing-liver-cancer-risk-in-african-born-immigrants-through-culturally-targeted-hepatitis-b-group-education-programs
#3
Kemi Bolutayo, Alexandre Ly van Manh, Noah Cohen, Daouda Ndiaye, Lina Jandorf, Ponni V Perumalswami
Of 900 West African-born immigrants living in New York City who were tested for hepatitis B virus (HBV), over 9% were found to have the infection (Shankar H et al. Clin Infectious Dis 62(S4):S289-s297, 2016). Community targeted group education programs (EP) have been shown to improve immigrant population's health (Bailey E et al. J Natl Med Assoc 92(3):136-42, 2000). Our aim is to enhance HBV screening in at-risk West African immigrants through the development of a group EP as a first critical step to reducing liver cancer risk...
May 19, 2017: Journal of Cancer Education: the Official Journal of the American Association for Cancer Education
https://www.readbyqxmd.com/read/28526268/structural-and-functional-aspects-of-the-nonribosomal-peptide-synthetase-condensation-domain-superfamily-discovery-dissection-and-diversity
#4
REVIEW
Kristjan Bloudoff, T Martin Schmeing
Nonribosomal peptide synthetases (NRPSs) are incredible macromolecular machines that produce a wide range of biologically- and therapeutically-relevant molecules. During synthesis, peptide elongation is performed by the condensation (C) domain, as it catalyzes amide bond formation between the nascent peptide and the amino acid it adds to the chain. Since their discovery more than two decades ago, C domains have been subject to extensive biochemical, bioinformatic, mutagenic, and structural analyses. They are composed of two lobes each with homology to chloramphenicol acetyltransferase, have two binding sites for their two peptidyl carrier protein-bound ligands, and have an active site with conserved motif HHxxxDG located between the two lobes...
May 16, 2017: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/28520529/synthesis-of-theranostic-epithelial-cell-adhesion-molecule-targeted-mesoporous-silica-nanoparticle-with-gold-gatekeeper-for-hepatocellular-carcinoma
#5
Maryam Babaei, Khalil Abnous, Seyed Mohammad Taghdisi, Sara Amel Farzad, Mohammad Taghi Peivandi, Mohammad Ramezani, Mona Alibolandi
AIM: In this study, we report the fabrication of epithelial cell adhesion molecule targeted 5-fluorouracil (5-FU) encapsulated PEGylated mesoporous silica nanoparticles (NPs) hybridized with gold NPs (PEG-Au@Si-5-FU) as gatekeeper for theranostic applications. MATERIALS & METHODS: The prepared targeted and nontargeted formulations were evaluated in vitro in terms of their cellular internalization and toxicity. The prepared theranostic hybrid system was also implemented for computed tomography of HepG2 tumor-bearing nude mice in vivo...
May 18, 2017: Nanomedicine
https://www.readbyqxmd.com/read/28516954/histone-deacetylase-10-structure-and-molecular-function-as-a-polyamine-deacetylase
#6
Yang Hai, Stephen A Shinsky, Nicholas J Porter, David W Christianson
Cationic polyamines such as spermidine and spermine are critical in all forms of life, as they regulate the function of biological macromolecules. Intracellular polyamine metabolism is regulated by reversible acetylation and dysregulated polyamine metabolism is associated with neoplastic diseases such as colon cancer, prostate cancer and neuroblastoma. Here we report that histone deacetylase 10 (HDAC10) is a robust polyamine deacetylase, using recombinant enzymes from Homo sapiens (human) and Danio rerio (zebrafish)...
May 18, 2017: Nature Communications
https://www.readbyqxmd.com/read/28512262/alternative-promotion-and-suppression-of-metastasis-by-jnk2-governed-by-its-phosphorylation
#7
Sike Hu, Xiaoli Dong, Wenjuan Gao, Dwayne Stupack, Yanhua Liu, Rong Xiang, Na Li
Fos-related antigen 1 (Fra1) has been proposed as a gatekeeper of the mesenchymal-epithelial transition to epithelial-mesenchymal transition. Here, we showed that de-phosphorylated JNK2 increased the expression of Fra1 by promoting the expression of c-Jun and Jun-B. Conversely, phosphorylated JNK2 suppressed its expression via enhancing the ubiquitination of c-Jun and Jun-B. These data provided insights into the regulatory mechanism of JNK2 on the expression of Fra1. Our study thus demonstrated that the conversion of JNK2 from its phosphorylation to de-phosphorylation status promoted the switch of breast cancer cells from mesenchymal-epithelial transition to epithelial-mesenchymal transition...
April 28, 2017: Oncotarget
https://www.readbyqxmd.com/read/28507889/does-parental-support-influence-children-s-active-school-travel
#8
S K Mah, L Nettlefold, H M Macdonald, M Winters, D Race, C Voss, H A McKay
Today's 'backseat generation' of children is more often driven to school. Active school travel (AST) can contribute up to 30% of recommended daily physical activity. Although governed by a complex set of factors, parents are considered 'gatekeepers' of children's travel mode decisions. Therefore, we investigate the relationship between parental support and children's AST. Data were from Active Streets, Active People-Junior (British Columbia, Canada). Children self-reported travel mode to/from school for 1 week (10 trips)...
June 2017: Preventive Medicine Reports
https://www.readbyqxmd.com/read/28504359/changing-the-paradigm-for-diagnostic-mri-in-pediatrics-don-t-hold-your-breath
#9
Melissa M Masaracchia, Michael J Tsapakos, Nancy J McNulty, Michael L Beach
Increasingly complex pediatric patients and improvements in technology warrant reevaluation of the risk associated with anesthesia for diagnostic imaging. Although magnetic resonance imaging is the imaging modality of choice for children given the potentially harmful effects of computerized tomography-associated ionizing radiation, we dare to suggest that certain patients would benefit from the liberalization of our current standard. Incorporating the use of newer computerized tomography technology may improve safety for those that are already at higher risk for adverse events...
May 15, 2017: Paediatric Anaesthesia
https://www.readbyqxmd.com/read/28503686/mesoporous-nanocarriers-with-a-stimulus-responsive-cyclodextrin-gatekeeper-for-targeting-tumor-hypoxia
#10
Jeonghun Lee, Eun-Taex Oh, Haerry Yoon, Chan Woo Kim, Yeji Han, Jaehun Song, Hyunil Jang, Heon Joo Park, Chulhee Kim
Tissue hypoxia developed in most malignant tumors makes a significant difference to normal tissues in the reduction potential and the activity of various bioreductive enzymes. Given the superior enzymatic activity of NAD(P)H:quinone oxidoreductase 1 (NQO1, a cytosolic reductase up-regulated in many human cancers) in hypoxia relative to that in normoxia, NQO1 has great potential for targeting hypoxic tumor cells. In the present report, the core concept of hypoxic NQO1-responsive mesoporous silica nanoparticles (MSNs) is based on the reasoning that the superior enzymatic activity of NQO1 within hypoxic cancer cells can be utilized as a key stimulus for the selective cleavage of an azobenzene stalk triggering the on-off gatekeeping for controlled release of guest drugs...
May 25, 2017: Nanoscale
https://www.readbyqxmd.com/read/28497681/ph-sensitive-delivery-vehicle-based-on-folic-acid-conjugated-polydopamine-modified-mesoporous-silica-nanoparticles-for-targeted-cancer-therapy
#11
Wei Cheng, Junpeng Nie, Lv Xu, Chaoyu Liang, Yunmei Peng, Gan Liu, Teng Wang, Lin Mei, Laiqiang Huang, Xiaowei Zeng
In this study, we introduced a targeting polymer poly(ethylene glycol)-folic acid (PEG-FA) on the surface of polydopamine (PDA)-modified mesoporous silica nanoparticles (MSNs) to develop the novel nanoparticles (NPs) MSNs@PDA-PEG-FA, which were employed as a drug delivery system loaded with doxorubicin (DOX) as a model drug for cervical cancer therapy. The chemical structure and properties of these NPs were characterized by transmission electron microscopy, X-ray photoelectron spectroscopy, N2 adsorption/desorption, dynamic light scattering-autosizer, thermogravimetric analysis, and Fourier transform infrared spectroscopy...
May 22, 2017: ACS Applied Materials & Interfaces
https://www.readbyqxmd.com/read/28495205/gatekeeping-and-the-utilization-of-physician-services-in-france-evidence-on-the-m%C3%A3-decin-traitant-reform
#12
Magali Dumontet, Thomas Buchmueller, Paul Dourgnon, Florence Jusot, Jérôme Wittwer
In 2005, France implemented a gatekeeping reform designed to improve care coordination and to reduce utilization of specialists' services. Under this policy, patients designate a médecin traitant, typically a general practitioner, who will be their first point of contact during an episode of care and who will provide referrals to specialists. A key element of the policy is that patients who self-refer to a specialist face higher cost sharing than if they received a referral from their médecin traitant. We consider the effect of this policy on the utilization of physician services...
April 28, 2017: Health Policy
https://www.readbyqxmd.com/read/28489299/gp-patient-communication-about-possible-cancer-in-primary-care-re-evaluating-gp-as-gatekeeper
#13
L A Brindle
As possibilities for the early detection of indolent cancers, and precursors to cancer, multiply, GPs will increasingly be involved in discussions with patients about risks and benefits of early diagnosis and treatment. Over time, improvements in evidence may decrease uncertainty about outcomes for patients and clinicians. However, where survival benefits are small, or uncertain, or risks are unacceptable to patients, grounds for preference-sensitive decision-making will remain. How risks and benefits of early detection, and the significance of indolent or low risk cancers, are communicated, will be key, if overtreatment and overdiagnosis are to be avoided...
May 2017: European Journal of Cancer Care
https://www.readbyqxmd.com/read/28482881/free-and-universal-but-unequal-utilization-of-primary-health-care-in-the-rural-and-urban-areas-of-mongolia
#14
Javkhlanbayar Dorjdagva, Enkhjargal Batbaatar, Mikael Svensson, Bayarsaikhan Dorjsuren, Burenjargal Batmunkh, Jussi Kauhanen
BACKGROUND: The entire population of Mongolia has free access to primary health care, which is fully funded by the government. It is provided by family health centers in urban settings. In rural areas, it is included in outpatient and inpatient services offered by rural soum (district) health centers. However, primary health care utilization differs across population groups. The aim of this study was to evaluate income-related inequality in primary health care utilization in the urban and rural areas of Mongolia...
May 8, 2017: International Journal for Equity in Health
https://www.readbyqxmd.com/read/28475283/cd69-from-activation-marker-to-metabolic-gatekeeper
#15
REVIEW
Danay Cibrián, Francisco Sánchez-Madrid
CD69 is a membrane-bound, type II C-lectin receptor. It is a classical early marker of lymphocyte activation due to its rapid appearance on the surface of the plasma membrane after stimulation. CD69 is expressed by several subsets of tissue resident immune cells, including resident memory T (TRM) cells and gamma delta (γδ) T cells, and is therefore considered a marker of tissue retention. Recent evidence has revealed that CD69 regulates some specific functions of selected T-cell subsets, determining the migration-retention ratio as well as the acquisition of effector or regulatory phenotypes...
May 5, 2017: European Journal of Immunology
https://www.readbyqxmd.com/read/28473450/zika-virus-induces-massive-cytoplasmic-vacuolization-and-paraptosis-like-death-in-infected-cells
#16
Blandine Monel, Alex A Compton, Timothée Bruel, Sonia Amraoui, Julien Burlaud-Gaillard, Nicolas Roy, Florence Guivel-Benhassine, Françoise Porrot, Pierre Génin, Laurent Meertens, Laura Sinigaglia, Nolwenn Jouvenet, Robert Weil, Nicoletta Casartelli, Caroline Demangel, Etienne Simon-Lorière, Arnaud Moris, Philippe Roingeard, Ali Amara, Olivier Schwartz
The cytopathic effects of Zika virus (ZIKV) are poorly characterized. Innate immunity controls ZIKV infection and disease in most infected patients through mechanisms that remain to be understood. Here, we studied the morphological cellular changes induced by ZIKV and addressed the role of interferon-induced transmembrane proteins (IFITM), a family of broad-spectrum antiviral factors, during viral replication. We report that ZIKV induces massive vacuolization followed by "implosive" cell death in human epithelial cells, primary skin fibroblasts and astrocytes, a phenomenon which is exacerbated when IFITM3 levels are low...
May 4, 2017: EMBO Journal
https://www.readbyqxmd.com/read/28467194/-on-the-doctor-s-orders-a-pilot-study-of-the-effects-of-website-marketing-for-medical-specialist-providers-under-gatekeeping-arrangements
#17
Sandra Zwier
Websites from medical specialist providers are becoming increasingly marketing oriented, but there exists a paucity of empirical research on the effects. This experimental study explored effects of exposure to real websites from medical specialist providers among Dutch adults under physician gatekeeper arrangements. Exposure led to a stronger intention to seek treatment from the specialist provider and motivation to rely on the providers' claims. Weaker to absent effects were found for intention to question the physician gatekeeper's referral and this was chiefly motivated by the belief that "the doctor knows best...
May 3, 2017: Health Marketing Quarterly
https://www.readbyqxmd.com/read/28458279/regulatory-mechanism-of-mast-cell-activation-by-zinc-signaling
#18
Keigo Nishida, Ryota Uchida
 Mast cells are hematopoietic-lineage cells that participate in immunoglobulin E (IgE)-associated immune responses, including allergic reactions and parasite resistance. Recent studies have shown that zinc (Zn) ion can behave as an intracellular signaling molecule and that Zn is involved in mast cell activation. We demonstrated that mast cells stimulated through the high-affinity IgE receptor (FcεRI) rapidly release intracellular Zn from the endoplasmic reticulum (ER), and we named this phenomenon the "Zn wave"...
2017: Yakugaku Zasshi: Journal of the Pharmaceutical Society of Japan
https://www.readbyqxmd.com/read/28458002/in-silico-drug-repurposing-of-fda-approved-drugs-to-predict-new-inhibitors-for-drug-resistant-t315i-mutant-and-wild-type-bcr-abl1-a-virtual-screening-and-molecular-dynamics-study
#19
Farzin Sohraby, Milad Bagheri, Masoud Aliyar, Hassan Aryapour
The BCR-ABL fusion gene is one of the major causes of 95% of Chronic Myeloid Leukemia (CML). While, BCR-ABL protein is currently being used as a major target to treat CML. Although, current FDA-approved drugs such as; Imatinib and Nilotinib have stupendously improved the patients 5-year's survival rates, the drug resistance has dramatically reduced their effects. So, more accurate and effective alternative treatments are crucially needed. To address this issue, we screened the FDA-approved drugs by virtual screening and binding free energy calculations to identify new inhibitors for the wild-type and T315I gatekeeper mutant ABL1...
April 13, 2017: Journal of Molecular Graphics & Modelling
https://www.readbyqxmd.com/read/28457260/your-brother-s-gatekeeper
#20
EDITORIAL
Peter M Greco
No abstract text is available yet for this article.
May 2017: American Journal of Orthodontics and Dentofacial Orthopedics
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