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https://www.readbyqxmd.com/read/29145415/plant-organ-cultures-as-masked-mycotoxin-biofactories-deciphering-the-fate-of-zearalenone-in-micropropagated-durum-wheat-roots-and-leaves
#1
Laura Righetti, Enrico Rolli, Gianni Galaverna, Michele Suman, Renato Bruni, Chiara Dall'Asta
"Masked mycotoxins" senso strictu are conjugates of mycotoxins resulting from metabolic pathways activated by the interplay between pathogenic fungi and infected plants. Zearalenone, an estrogenic mycotoxin produced by Fusarium spp, was the first masked mycotoxin ever described in the literature, but its biotransformation has been studied to a lesser extent if compared to other compounds such as deoxynivalenol. We presented herein the first application of organ and tissue culture techniques to study the metabolic fate of zearalenone in durum wheat, using an untargeted HR-LCMS approach...
2017: PloS One
https://www.readbyqxmd.com/read/29141648/polymorphisms-at-microrna-binding-sites-of-ara-c-and-anthracyclines-metabolic-pathway-genes-are-associated-with-outcome-of-acute-myeloid-leukemia-patients
#2
Hai-Xia Cao, Chao-Feng Miao, Liang Yan, Ping Tang, Li-Rong Zhang, Ling Sun
BACKGROUND: Gene polymorphisms at microRNA-binding sites (poly-miRTS) may affect gene transcription and expression through miRNA regulation, which is associated with cancer susceptibility, sensitivity to chemotherapy and prognosis. This study investigated the association between poly-miRTS of Ara-C/anthracycline metabolic pathways genes and the outcome of acute myeloid leukemia (AML) in Chinese patients after Ara-C-based chemotherapy. METHODS: A total of 17 poly-miRTS were selected from the SNPinfo Web Server and genotyped in 206 Chinese Han non-FAB-M3 AML patients using the SEQUENOM Mass-ARRAY system...
November 15, 2017: Journal of Translational Medicine
https://www.readbyqxmd.com/read/29136592/human-sirtuin-3-sirt3-deacetylates-histone-h3-lysine-56-to-promote-nonhomologous-end-joining-repair
#3
Amrita Sengupta, Devyani Haldar
Human sirtuin 3 (SIRT3) is a conserved NAD(+) dependent deacetylase, which functions in important cellular processes including transcription, metabolism, oxidative stress response. It is a robust mitochondrial deacetylase; however, few studies have indicated its nuclear functions. Here we report interaction of SIRT3 with core histones and identified acetylated histone H3 lysine 56 (H3K56ac) as its novel substrate, in addition to known substrates acetylated H4K16 and H3K9. Further, we showed in response to DNA damage SIRT3 localizes to the repair foci colocalizing with γH2AX and nonhomologous end joining (NHEJ) marker p53-binding protein 1 (53BP1)...
November 8, 2017: DNA Repair
https://www.readbyqxmd.com/read/29136555/non-targeted-metabolomics-guided-sildenafil-metabolism-study-in-human-liver-microsomes
#4
Ju-Hyun Kim, Jun Hyun Jo, Kyung-Ah Seo, Hayoung Hwang, Hye Suk Lee, Sangkyu Lee
Metabolomics combined with high-resolution mass spectrometry (HR-MS) and multivariate data analysis has broad applications in the study of xenobiotic metabolism. Although information about xenobiotic metabolism is essential to understand toxic mechanisms, pharmacokinetic parameters and excretion pathways, it is limited to predict all generated metabolites in biological fluids. Here, we revisited sildenafil metabolism in human liver microsomes using a metabolomics approach to achieve a global picture of sildenafil phase 1 metabolism...
November 7, 2017: Journal of Chromatography. B, Analytical Technologies in the Biomedical and Life Sciences
https://www.readbyqxmd.com/read/29134432/phase-iii-study-of-dulanermin-recombinant-human-tumor-necrosis-factor-related-apoptosis-inducing-ligand-apo2-ligand-combined-with-vinorelbine-and-cisplatin-in-patients-with-advanced-non-small-cell-lung-cancer
#5
Xuenong Ouyang, Meiqi Shi, Fangwei Jie, Yuxian Bai, Peng Shen, Zhuang Yu, Xiuwen Wang, Cheng Huang, Min Tao, Zhehai Wang, Conghua Xie, Qi Wu, Yongqian Shu, Baohui Han, Fengchun Zhang, Yiping Zhang, Chunhong Hu, Xitao Ma, Yongjie Liang, Anlan Wang, Bing Lu, Yi Shi, Jinfei Chen, Zhixiang Zhuang, Jiejun Wang, Jianjin Huang, Changhui Wang, Chunxue Bai, Xin Zhou, Qiang Li, Feng Chen, Hao Yu, Jifeng Feng
Background Dulanermin is a recombinant soluble human Apo2 ligand/tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) that activates apoptotic pathways by binding to proapoptotic death receptor (DR) 4 and DR5. The purpose of this study was to evaluate the efficacy and safety of dulanermin combined with vinorelbine and cisplatin (NP) as the first-line treatment for patients with advanced non-small-cell lung cancer (NSCLC). Experimental design Patients were randomly assigned to receive NP chemotherapy (vinorelbine 25 mg/m(2) on days 1 and 8 and cisplatin 30 mg/m(2) on days 2 to 4) for up to six cycles plus dulanermin (75 μg/kg on days 1 to 14) or placebo every three weeks until disease progression, intolerable toxicity, or withdrawal of consent...
November 14, 2017: Investigational New Drugs
https://www.readbyqxmd.com/read/29131568/diisonitrile-natural-product-sf2768-functions-as-a-chalkophore-that-mediates-copper-acquisition-in-streptomyces-thioluteus
#6
Lijuan Wang, Mengyi Zhu, Qingbo Zhang, Xu Zhang, Panlei Yang, Zihui Liu, Yun Deng, Yiguang Zhu, Xueshi Huang, Li Han, Shengqing Li, Jing He
A non-ribosomal peptide synthetase (NRPS) gene cluster (sfa) was identified in Streptomyces thioluteus to direct the biosynthesis of the diisonitrile antibiotic SF2768. Its biosynthetic pathway was reasonably proposed based on bioinformatics analysis, metabolic profiles of mutants and the elucidation of the intermediate and shunt product structures. Bioinformatics-based alignment found a putative ATP-binding cassette (ABC) transporter related to iron import within the biosynthetic gene cluster, which implied that the product might be a siderophore...
November 13, 2017: ACS Chemical Biology
https://www.readbyqxmd.com/read/29125808/monocyte-derived-procoagulant-microvesicles-induced-by-high-glucose-can-be-attenuated-by-the-antioxidant-n-acetyl-l-cysteine-partly-through-the-p38-mapk-pathway
#7
Mingzhen Li, Xiao Zhang, Jing Yu, Xin Wu, Lirong Sun
BACKGROUND: Microvesicles (MVs) are small membrane vesicles that are derived from many different cell types by a process of exocytic budding of the plasma membrane. MVs may be associated with a higher incidence of vascular disease in diabetic patients, but the mechanism of this association is unclear. Diabetic patients also show hypercoagulability and platelet hyperaggregability. In this study, we investigated the generation and activity of high glucose (HG)-induced MVs from monocytes to elucidate the potential mechanism of such MVs in diabetes...
November 10, 2017: Metabolic Syndrome and related Disorders
https://www.readbyqxmd.com/read/29125028/molecular-basis-of-citrus-sunki-susceptibility-and-poncirus-trifoliata-resistance-upon-phytophthora-parasitica-attack
#8
Ronaldo J D Dalio, Heros José Máximo, Tiago Silva Oliveira, Thamara Azevedo, Henrique Leme Felizatti, Magnólia Araújo Campos, Marcos Antonio Antonio Machado
Coevolution has shaped the molecular basis of an extensive number of defense mechanisms in plant-pathogen interactions. Phytophthora parasitica, a hemibiothrophic oomycete pathogen and the causal agent of citrus root rot and gummosis, interacts differently with Citrus sunki and Poncirus trifoliata; two commonly favored citrus rootstocks that are recognized as susceptible and resistant, respectively, to P. parasitica. The molecular core of these interactions remains elusive. Here, we provide evidences on the defense strategies employed by both susceptible and resistant citrus rootstocks, in parallel with P...
November 10, 2017: Molecular Plant-microbe Interactions: MPMI
https://www.readbyqxmd.com/read/29124000/human-papillomavirus-associated-head-and-neck-squamous-cell-carcinoma-controversies-and-new-concepts
#9
REVIEW
Nuzhat Husain, Azfar Neyaz
High-risk human papillomavirus (HR-HPV) is a causative agent for an increasing subset of oropharyngeal squamous cell carcinoma. HPV 16 accounts for 90% of cases. The chance for malignant transformation due to infection with high-risk HPV is proportional to the expression of the viral oncogene products E6 and E7, which inactivate p53 and retinoblastoma (Rb) tumor suppressor functions. P16 is a surrogate marker of HPV associated HNSCC and 2+/3+ expression in more than 75% cells is diagnostic. Molecular demonstration of integrated virus by in situ hybridization is specific but has low sensitivity...
September 2017: Journal of Oral Biology and Craniofacial Research
https://www.readbyqxmd.com/read/29123506/challenges-and-advances-for-genetic-engineering-of-non-model-bacteria-and-uses-in-consolidated-bioprocessing
#10
REVIEW
Qiang Yan, Stephen S Fong
Metabolic diversity in microorganisms can provide the basis for creating novel biochemical products. However, most metabolic engineering projects utilize a handful of established model organisms and thus, a challenge for harnessing the potential of novel microbial functions is the ability to either heterologously express novel genes or directly utilize non-model organisms. Genetic manipulation of non-model microorganisms is still challenging due to organism-specific nuances that hinder universal molecular genetic tools and translatable knowledge of intracellular biochemical pathways and regulatory mechanisms...
2017: Frontiers in Microbiology
https://www.readbyqxmd.com/read/29121675/astaxanthin-prevents-ischemia-reperfusion-injury-of-the-steatotic-liver-in-mice
#11
Shaowei Li, Terumi Takahara, Masayuki Fujino, Yasuyuki Fukuhara, Toshiro Sugiyama, Xiao-Kang Li, Shiro Takahara
Steatosis has a low tolerance against ischemia-reperfusion injury (IRI). To prevent IRI in the steatotic liver, we attempted to elucidate the protective effect of astaxanthin (ASTX) in the steatotic liver model by giving mice a methionine and choline-deficient high fat (MCDHF) diet. Levels of lipid peroxidation and apoptosis, the expression of inflammatory cytokines and heme oxygenase (HO)-1, in the liver were assessed. Reactive oxygen species (ROS), inflammatory cytokines, apoptosis-related proteins and members of the signaling pathway were also examined in isolated Kupffer cells and/or hepatocytes from the steatotic liver...
2017: PloS One
https://www.readbyqxmd.com/read/29120785/identification-and-characterization-of-pesticide-metabolites-in-brassica-species-by-liquid-chromatography-travelling-wave-ion-mobility-quadrupole-time-of-flight-mass-spectrometry-uplc-twims-qtof-ms
#12
Anna Bauer, Jens Luetjohann, Franziska S Hanschen, Monika Schreiner, Jürgen Kuballa, Eckard Jantzen, Sascha Rohn
A new mass spectrometric method for evaluating metabolite formation of the pesticides thiacloprid, azoxystrobin, and difenoconazole was developed for the Brassica species pak choi and broccoli. Both, distribution and transformation kinetics of the active compounds and their metabolites were analyzed by UPLC-TWIMS-QTOF-MS. Additionally, HR-MS analysis and structure elucidation tools such as diagnostic ions, isotopic matches, and collision cross sections were applied for metabolites identification. Following the application of two plant protection products (containing the above-mentioned active compounds) in a greenhouse study plant material was cryo-milled and extracted with water/methanol...
April 1, 2018: Food Chemistry
https://www.readbyqxmd.com/read/29119080/metastatic-breast-cancer-endocrine-therapy-landscape-reshaped
#13
REVIEW
Mohamad Adham Salkeni, Samantha June Hall
Endocrine therapy (ET) of hormone receptor (HR)-positive and human epidermal growth factor receptor 2-(HER2)-negative metastatic breast cancer (MBC) historically focused on estrogen deprivation and antagonism. The identification of several intracellular pathways promoting resistance to antiestrogen therapy led to the introduction of novel endocrine drug combinations that reformed treatment schema and expanded therapeutic options. There is no doubt that efforts to overcome or delay resistance to ET are fruiting, particularly with the introduction of cyclin-dependent kinase 4/6 inhibitors such as palbociclib and ribociclib, and mechanistic target of rapamycin inhibitors such as everolimus...
October 2017: Avicenna Journal of Medicine
https://www.readbyqxmd.com/read/29118270/upregulation-of-pir-gene-expression-induced-by-human-papillomavirus-e6-and-e7-in-epithelial-oral-and-cervical-cells
#14
Diego Carrillo, Juan P Muñoz, Hernán Huerta, Gabriel Leal, Alejandro Corvalán, Oscar León, Gloria M Calaf, Ulises Urzúa, Enrique Boccardo, Julio C Tapia, Francisco Aguayo
The hallmark of high-risk human papillomavirus (HR-HPV)-related carcinogenesis is E6 and E7 oncogene overexpression. The aim of this work was to characterize epithelial oral and cervical cancer cells that express HR-HPV E6 and E7 oncoproteins. Transcriptomic assay using DNA microarrays revealed that PIR gene expression was detected in oral cells in an HR-HPV E6/E7-dependent manner. In addition, PIR was overexpressed in HPV-positive SiHa and Ca Ski cells, whereas it was undetectable in HPV-negative C33A cells...
November 2017: Open Biology
https://www.readbyqxmd.com/read/29117471/tumor-adjacent-tissue-co-expression-profile-analysis-reveals-pro-oncogenic-ribosomal-gene-signature-for-prognosis-of-resectable-hepatocellular-carcinoma
#15
O V Grinchuk, S P Yenamandra, R Iyer, M Singh, H K Lee, K H Lim, P K H Chow, V A Kuznetsov
Currently, molecular markers are not used whilst determining the prognosis and treatment strategy for patients with hepatocellular carcinoma (HCC). Here, we proposed that the identification of common pro-oncogenic pathways in primary tumors (PT), and adjacent non-malignant tissues (AT), that typically used to predict HCC patient risks may result in HCC biomarker discovery. We examined the genome-wide mRNA expression profiles of paired PT and AT samples from 321 HCC patients. The workflow integrated differentially expressed gene selection, gene ontology enrichment, computational classification, survival predictions, image analysis and experimental validation methods...
November 8, 2017: Molecular Oncology
https://www.readbyqxmd.com/read/29117359/co-occurring-genomic-alterations-and-association-with-progression-free-survival-in-brafv600-mutated-nonmelanoma-tumors
#16
Shiraj Sen, Funda Meric-Bernstam, David S Hong, Kenneth R Hess, Vivek Subbiah
BRAFV600 mutations occur in multiple nonmelanoma tumors, but no US Food and Drug Administration-approved BRAF-targeted therapies exist for these cancers. BRAF inhibitor vemurafenib was recently found to demonstrate activity across various BRAF-mutated nonmelanoma cancer types. However, most tumors ultimately become resistant to BRAF-targeted monotherapy. To identify whether co-occurring genomic alterations drive resistance to BRAF-targeted therapies, we analyzed next-generation sequencing data from 30 advanced BRAF-mutated nonmelanoma cancers treated with BRAF inhibitor monotherapy...
October 1, 2017: Journal of the National Cancer Institute
https://www.readbyqxmd.com/read/29117186/human-papillomavirus-type-16-e6-and-nfx1-123-mislocalize-immune-signaling-proteins-and-downregulate-immune-gene-expression-in-keratinocytes
#17
Justine Levan, Portia A Vliet-Gregg, Kristin L Robinson, Rachel A Katzenellenbogen
Human papillomavirus (HPV) is the most prevalent sexually transmitted infection, affecting an estimated 11% of the world's population. The high-risk HPV types (HR HPV) account for approximately 5% of the global burden of cancer and thus cause high morbidity and mortality. Although it is known that persistent infection with HR HPV is the greatest risk factor for developing HPV-associated cancer, and that the HPV early proteins E6 and E7 dysregulate immune detection by its host cells, the mechanisms of immune evasion by HR HPV are not well understood...
2017: PloS One
https://www.readbyqxmd.com/read/29116997/hospital-differences-drive-antibiotic-delays-for-black-patients-compared-with-white-patients-with-suspected-septic-shock
#18
Stephanie Parks Taylor, Colleen H Karvetski, Megan A Templin, Brice T Taylor
OBJECTIVE: Evaluate racial disparities in sepsis processes of care. DESIGN: Observational cohort study. SETTING: Nine hospitals in the Southeastern United States between 2014 and 2016. PATIENTS: Two thousand two hundred twenty-one white and 707 black patients treated in the emergency department through "code sepsis" pathway for suspected septic shock. MEASUREMENTS AND MAIN RESULTS: Black patients were less likely to receive timely antibiotics than were white patients using multiple definitions (1 hr from code sepsis activation [odds ratio, 0...
November 7, 2017: Critical Care Medicine
https://www.readbyqxmd.com/read/29116362/homologous-recombination-mediated-repair-of-dna-double-strand-breaks-operates-in-mammalian-mitochondria
#19
Sumedha Dahal, Shubham Dubey, Sathees C Raghavan
Mitochondrial DNA is frequently exposed to oxidative damage, as compared to nuclear DNA. Previously, we have shown that while microhomology-mediated end joining can account for DNA deletions in mitochondria, classical nonhomologous DNA end joining, the predominant double-strand break (DSB) repair pathway in nucleus, is undetectable. In the present study, we investigated the presence of homologous recombination (HR) in mitochondria to maintain its genomic integrity. Biochemical studies revealed that HR-mediated repair of DSBs is more efficient in the mitochondria of testes as compared to that of brain, kidney and spleen...
November 7, 2017: Cellular and Molecular Life Sciences: CMLS
https://www.readbyqxmd.com/read/29116111/the-expression-of-mirnas-is-associated-with-tumour-genome-instability-and-predicts-the-outcome-of-ovarian-cancer-patients-treated-with-platinum-agents
#20
Tianzhen Wang, Guangyu Wang, Xiaoxiao Zhang, Di Wu, Lei Yang, Guangyou Wang, Dapeng Hao
miRNAs, a class of short but stable noncoding RNA molecules, have been revealed to play important roles in the DNA damage response (DDR). However, their functions in cancer genome instability and the consequent clinical effect as the response to chemotherapy have not been fully elucidated. In this study, we utilized multidimensional TCGA data and the known miRNAs involved in DDR to identify a miRNA-regulatory network that responds to DNA damage. Additionally, based on the expression of ten miRNAs in this network, we developed a 10-miRNA-score that predicts defects in the homologous recombination (HR) pathway and genome instability in ovarian cancer...
November 7, 2017: Scientific Reports
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