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https://www.readbyqxmd.com/read/28427237/oxidative-dna-double-strand-breaks-and-autophagy-in-the-antitumor-effect-of-sterically-hindered-platinum-ii-complexes-in-nsclcs
#1
Feihong Chen, Xinyi Wang, Xiufeng Jin, Jian Zhao, Shaohua Gou
A series of novel platinum(II) complexes with (1R,2R)-N1,N2-diisobutyl-1,2-diaminocyclohexane as a carrier ligand, while N1,N2-diisobutyl moiety serving as steric hindrance were designed, synthesized and characterized. The in vitro biological assays demonstrated that complex 3 had increased cytotoxicity against lung cancer cells, especially non-small-cell lung cancer (NSCLC) compared to its mono-substituted complex 3a, indicating that the sterically hindered alkyl moieties have significant influences on its antitumor property...
March 6, 2017: Oncotarget
https://www.readbyqxmd.com/read/28427229/nadph-accumulation-is-responsible-for-apoptosis-in-breast-cancer-cells-induced-by-fatty-acid-synthase-inhibition
#2
Yanfen Cui, Pan Xing, Yuanyuan Wang, Miao Liu, Li Qiu, Guoguang Ying, Binghui Li
Fatty acid synthase (FAS), as a key enzyme involved in de novo lipogenesis, is highly expressed in many cancers. FAS inhibition induces cell death in vivo and in vitro, rendering FAS as an attractive target for cancer therapy, but the defined mechanism is still not well understood. Herein, we confirmed that FAS was highly expressed in breast cancers and FAS inhibition by its inhibitors or knockdown induced apoptosis in breast cancer cells. Our results showed that a significantly high level of reactive oxygen species was induced but not responsible for apoptosis in breast cancer cells by FAS inhibition...
March 6, 2017: Oncotarget
https://www.readbyqxmd.com/read/28427200/idh1-r132h-mutation-regulates-glioma-chemosensitivity-through-nrf2-pathway
#3
Kaishu Li, Leping Ouyang, Mingliang He, Ming Luo, Wangqing Cai, Yalin Tu, Rongbiao Pi, Anmin Liu
PURPOSE: Numerous studies have reported that glioma patients with isocitrate dehydrogenase 1(IDH1) R132H mutation are sensitive to temozolomide treatment. However, the mechanism of IDH1 mutations on the chemosensitivity of glioma remains unclear. In this study, we investigated the role and the potential mechanism of Nrf2 in IDH1 R132H-mediated drug resistance. METHODS: Wild type IDH1 (R132H-WT) and mutant IDH1 (R132H) plasmids were constructed. Stable U87 cells and U251 cells overexpressing IDH1 were generated...
March 3, 2017: Oncotarget
https://www.readbyqxmd.com/read/28427159/genome-wide-analysis-of-long-noncoding-rna-and-mrna-co-expression-profile-in-intrahepatic-cholangiocarcinoma-tissue-by-rna-sequencing
#4
Wenhui Yang, Yuan Li, Xia Song, Jun Xu, Jun Xie
Long noncoding RNAs (lncRNAs), which are pervasively transcribed in the genome, are emerging in molecular biology as crucial regulators of cancer. RNA-seq data were downloaded from GEO of NCBI and further analyzed to identify novel targets in intrahepatic cholangiocarcinoma (iCCA).We investigated differences in lncRNA and mRNA profiles between 7 pairs of iCCA and adjacent normal tissues. 230 lncRNAs were differentially expressed more than four-fold change in iCCA tissues. Among these, 97 were upregulated and 133 downregulated relatively to normal tissues...
February 24, 2017: Oncotarget
https://www.readbyqxmd.com/read/28427089/editor-s-highlight-exposure-to-crvi-during-early-pregnancy-increases-oxidative-stress-and-disrupts-the-expression-of-antioxidant-proteins-in-placental-compartments
#5
Sakhila K Banu, Jone A Stanley, Kirthiram K Sivakumar, Robert J Taylor, Joe A Arosh, Robert C Burghardt
Epidemiologic studies document relationships between chromium VI (CrVI) exposure and increased risk of spontaneous abortion, stillbirth, preterm birth, and neonatal death in pregnant women. Environmental contamination with CrVI is a growing problem both in the United States and developing countries. CrVI is widely used in numerous industries. This study was designed to understand the mechanism of CrVI toxicity on placental oxidative stress and antioxidant (AOX) machinery. Pregnant mother rats were treated with or without CrVI (50 ppm K2Cr2O7) through drinking water from gestational day (GD) 9...
February 1, 2017: Toxicological Sciences: An Official Journal of the Society of Toxicology
https://www.readbyqxmd.com/read/28427061/emerging-insights-into-pathogenesis
#6
Edoardo Midena, Elisabetta Pilotto
Diabetic retinopathy (DR) is a frequent complication of diabetes mellitus (DM). Persistent hyperglycemia leads to the activation of multiple cellular pathways involved in the pathogenesis of DR, resulting in increased inflammation, oxidative stress, and vascular dysfunction. DR has been considered a "chronic, low-grade inflammatory disease of the retina". However, an increasing body of evidence suggests that inflammation and neurodegeneration both occur in human diabetes even before the development of clinical signs of DR...
2017: Developments in Ophthalmology
https://www.readbyqxmd.com/read/28427016/synthesis-and-in%C3%A2-vitro-antitumour-activity-of-crassalactone-d-its-stereoisomers-and-novel-cinnamic-ester-derivatives
#7
Ivana Kovačević, Mirjana Popsavin, Goran Benedeković, Jelena Kesić, Vesna Kojić, Dimitar Jakimov, Tatjana Srdić-Rajić, Gordana Bogdanović, Vladimir Divjaković, Velimir Popsavin
Naturally occurring styryl lactone, crassalactone D (1), unnatural 4-epi-crassalactone D (2), and the corresponding 7-epimers (3 and 4) have been synthesized starting from d-glucose. The key step of the synthesis is a new one-pot sequence that commenced with a Z-selective Wittig olefination of suitably functionalized sugar lactols with a stabilized ylide, (methoxycarbonylmethylene)-triphenylphosphorane, in dry methanol, to afford 1 or 3, in the mixtures with the corresponding 4-epimers (2 or 4, respectively)...
April 13, 2017: European Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/28426964/ipsc-derived-human-microglia-like-cells-to-study-neurological-diseases
#8
Edsel M Abud, Ricardo N Ramirez, Eric S Martinez, Luke M Healy, Cecilia H H Nguyen, Sean A Newman, Andriy V Yeromin, Vanessa M Scarfone, Samuel E Marsh, Cristhian Fimbres, Chad A Caraway, Gianna M Fote, Abdullah M Madany, Anshu Agrawal, Rakez Kayed, Karen H Gylys, Michael D Cahalan, Brian J Cummings, Jack P Antel, Ali Mortazavi, Monica J Carson, Wayne W Poon, Mathew Blurton-Jones
Microglia play critical roles in brain development, homeostasis, and neurological disorders. Here, we report that human microglial-like cells (iMGLs) can be differentiated from iPSCs to study their function in neurological diseases, like Alzheimer's disease (AD). We find that iMGLs develop in vitro similarly to microglia in vivo, and whole-transcriptome analysis demonstrates that they are highly similar to cultured adult and fetal human microglia. Functional assessment of iMGLs reveals that they secrete cytokines in response to inflammatory stimuli, migrate and undergo calcium transients, and robustly phagocytose CNS substrates...
April 19, 2017: Neuron
https://www.readbyqxmd.com/read/28426958/elucidating-the-role-of-trem2-in-alzheimer-s-disease
#9
REVIEW
Jason D Ulrich, Tyler K Ulland, Marco Colonna, David M Holtzman
Alzheimer's disease (AD) is the sixth leading cause of death in the United States and the most common cause of dementia in the elderly. Genetic factors, such as rare variants in the microglial-expressed gene TREM2, strongly impact the lifetime risk of developing AD. Several recent studies have described dramatic TREM2-dependent phenotypes in mouse models of amyloidosis that point to an important role for TREM2 in regulating the response of the innate immune system to Aβ pathology. Furthermore, elevations in the CSF levels of soluble TREM2 fragments implicate changes in inflammatory pathways as occurring coincident with markers of neuronal damage and the onset of clinical dementia in AD...
April 19, 2017: Neuron
https://www.readbyqxmd.com/read/28426892/-i-am-still-passionate-despite-the-challenges-nurses-navigating-the-care-for-refugees
#10
Olayide Ogunsiji, Harrison Ng Chok, Gladys Mashingaidze, Lesley Wilkes
AIMS AND OBJECTIVES: The aim of this study is to report the challenges faced by the nursing workforce in refugee health. BACKGROUND: Nurses are in the forefront of care provision for refugees who are recognised as one of the most vulnerable population groups in the world. The number of refugees in Australia is increasing and more nurses are needed as care providers. Research on the challenges faced by refugee health nurses is sparse. DESIGN: Qualitative research methodology was used to study the experience of refugee health nurses...
April 20, 2017: Journal of Clinical Nursing
https://www.readbyqxmd.com/read/28426816/ex-vivo-cultures-combined-with-vivo-morpholino-induced-gene-knockdown-provide-a-system-to-assess-the-role-of-wt1-and-gata4-during-gonad-differentiation
#11
Lucas J Rudigier, Christof Dame, Holger Scholz, Karin M Kirschner
Gonad morphogenesis relies on the correct spatiotemporal expression of a number of genes that together fulfill the differentiation of the bipotential gonad into testes or ovaries. As such, the transcription factors WT1 and GATA4 are pivotal for proper gonadal development. Here we address the contributions of GATA4 and WT1 to the sex differentiation phase in testes and ovaries. We applied an ex vivo technique for cultivating gonads in hanging droplets of media that were supplemented with vivo-morpholinos to knockdown WT1 and GATA4 either alone or in combination at the same developmental stage...
2017: PloS One
https://www.readbyqxmd.com/read/28426798/glucotoxicity-induces-abnormal-glucagon-secretion-through-impaired-insulin-signaling-in-inr1g-cells
#12
Takashi Katsura, Dan Kawamori, Eri Aida, Taka-Aki Matsuoka, Iichiro Shimomura
The significance of glucagon in the pathophysiology of diabetes mellitus is widely recognized, but the mechanisms underlying dysregulated glucagon secretion are still unclear. Here, we explored the molecular mechanisms of glucagon dysregulation, using an in vitro model. Hamster-derived glucagon-secreting InR1G cells were exposed to high glucose (25 mM) levels for 12 h before analyzing glucagon secretion and the activity of components involved in insulin signaling. High-glucose treatment induced increased glucagon secretion in InR1G cells, which represents a hallmark of diabetes mellitus...
2017: PloS One
https://www.readbyqxmd.com/read/28426789/gre-factors-mediated-control-of-hild-transcription-is-essential-for-the-invasion-of-epithelial-cells-by-salmonella-enterica-serovar-typhimurium
#13
Tania Gaviria-Cantin, Youssef El Mouali, Soazig Le Guyon, Ute Römling, Carlos Balsalobre
The invasion of epithelial cells by Salmonella enterica serovar Typhimurium is a very tightly regulated process. Signaling cascades triggered by different environmental and physiological signals converge to control HilD, an AraC regulator that coordinates the expression of several virulence factors. The expression of hilD is modulated at several steps of the expression process. Here, we report that the invasion of epithelial cells by S. Typhimurium strains lacking the Gre factors, GreA and GreB, is impaired...
April 2017: PLoS Pathogens
https://www.readbyqxmd.com/read/28426764/structural-characterization-of-core-bradavidin-in-complex-with-biotin
#14
Nitin Agrawal, Juha A E Määttä, Markku S Kulomaa, Vesa P Hytönen, Mark S Johnson, Tomi T Airenne
Bradavidin is a tetrameric biotin-binding protein similar to chicken avidin and bacterial streptavidin, and was originally cloned from the nitrogen-fixing bacteria Bradyrhizobium diazoefficiens. We have previously reported the crystal structure of the full-length, wild-type (wt) bradavidin with 138 amino acids, where the C-terminal residues Gly129-Lys138 ("Brad-tag") act as an intrinsic ligand (i.e. Gly129-Lys138 bind into the biotin-binding site of an adjacent subunit within the same tetramer) and has potential as an affinity tag for biotechnological purposes...
2017: PloS One
https://www.readbyqxmd.com/read/28426747/metabolic-analysis-of-radioresistant-medulloblastoma-stem-like-clones-and-potential-therapeutic-targets
#15
Lue Sun, Takashi Moritake, Kazuya Ito, Yoshitaka Matsumoto, Hironobu Yasui, Hidehiko Nakagawa, Aki Hirayama, Osamu Inanami, Koji Tsuboi
Medulloblastoma is a fatal brain tumor in children, primarily due to the presence of treatment-resistant medulloblastoma stem cells. The energy metabolic pathway is a potential target of cancer therapy because it is often different between cancer cells and normal cells. However, the metabolic properties of medulloblastoma stem cells, and whether specific metabolic pathways are essential for sustaining their stem cell-like phenotype and radioresistance, remain unclear. We have established radioresistant medulloblastoma stem-like clones (rMSLCs) by irradiation of the human medulloblastoma cell line ONS-76...
2017: PloS One
https://www.readbyqxmd.com/read/28426740/uncovering-the-molecular-and-physiological-processes-of-anticancer-leads-binding-human-serum-albumin-a-physical-insight-into-drug-efficacy
#16
Chuanbo Liu, Zuojia Liu, Jin Wang
Human serum albumin (HSA) has its ability to bind drug molecules and influence their efficacies. Although anticancer leads NSC48693 and NSC290956 functioned at the same mechanism, the drug efficacies were obviously distinct. To gain insight into the distinct drug efficacy, the molecular and physiological processes of anticancer leads binding HSA have been investigated via a combined experimental and theoretical approach. The binding site, as characterized by fluorescence quenching and molecular modeling, is found to be located at site II in subdomain III A for NSC48693 with tight binding and at site FA1 in subdomain I B for NSC290956 with negatively cooperative binding, respectively...
2017: PloS One
https://www.readbyqxmd.com/read/28426719/transcriptome-of-interstitial-cells-of-cajal-reveals-unique-and-selective-gene-signatures
#17
Moon Young Lee, Se Eun Ha, Chanjae Park, Paul J Park, Robert Fuchs, Lai Wei, Brian G Jorgensen, Doug Redelman, Sean M Ward, Kenton M Sanders, Seungil Ro
Transcriptome-scale data can reveal essential clues into understanding the underlying molecular mechanisms behind specific cellular functions and biological processes. Transcriptomics is a continually growing field of research utilized in biomarker discovery. The transcriptomic profile of interstitial cells of Cajal (ICC), which serve as slow-wave electrical pacemakers for gastrointestinal (GI) smooth muscle, has yet to be uncovered. Using copGFP-labeled ICC mice and flow cytometry, we isolated ICC populations from the murine small intestine and colon and obtained their transcriptomes...
2017: PloS One
https://www.readbyqxmd.com/read/28426652/cheminformatics-aided-discovery-of-small-molecule-protein-protein-interaction-ppi-dual-inhibitors-of-tumor-necrosis-factor-tnf-and-receptor-activator-of-nf-%C3%AE%C2%BAb-ligand-rankl
#18
Georgia Melagraki, Evangelos Ntougkos, Vagelis Rinotas, Christos Papaneophytou, Georgios Leonis, Thomas Mavromoustakos, George Kontopidis, Eleni Douni, Antreas Afantitis, George Kollias
We present an in silico drug discovery pipeline developed and applied for the identification and virtual screening of small-molecule Protein-Protein Interaction (PPI) compounds that act as dual inhibitors of TNF and RANKL through the trimerization interface. The cheminformatics part of the pipeline was developed by combining structure-based with ligand-based modeling using the largest available set of known TNF inhibitors in the literature (2481 small molecules). To facilitate virtual screening, the consensus predictive model was made freely available at: http://enalos...
April 2017: PLoS Computational Biology
https://www.readbyqxmd.com/read/28426518/pathophysiologic-insight-into-mesoamerican-nephropathy
#19
Magdalena Madero, Fernando E García-Arroyo, Laura-Gabriela Sánchez-Lozada
PURPOSE OF REVIEW: Mesoamerican nephropathy (MeN) is an emerging pathophysiological entity of Chronic kidney desease (CKD) not related to traditional risk factors (diabetes and hypertension) that have caused thousands of deaths in Central America, mainly in sugarcane workers. The focus of this review is to discuss the risk factors and probable mechanisms involved in the initiation and progression of this devastating disease. RECENT FINDINGS: Frequent episodes of subclinical Acute kidney injury caused by repetitive heat stress, dehydration, and strenuous work have been regarded as the main risk factors for MeN...
April 19, 2017: Current Opinion in Nephrology and Hypertension
https://www.readbyqxmd.com/read/28426396/current-status-of-and-recommendations-for-nutrition-education-in-gastroenterology-fellowship-training-in-canada
#20
Jing Hu, Maitreyi Raman, Leah Gramlich
PURPOSE: Knowledge and skill in the area of nutrition are a key competency for the gastroenterologist. However, standards for nutrition education for gastroenterology fellows in Canada do not exist, and gastroenterologists in training and in practice do not feel confident in their knowledge or skill as it relates to nutrition. This study was undertaken to identify the current status of nutrition education in gastroenterology (GI) fellowship training programs in Canada and to provide insight into the development of nutrition educational goals, processes, and evaluation...
April 1, 2017: Nutrition in Clinical Practice
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