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https://www.readbyqxmd.com/read/29454280/8-chrysoeriol-as-a-potential-bcl-2-inhibitor-triggers-apoptosis-of-sw1990-pancreatic-cancer-cells
#1
Yiwen Zhang, Zhimei Li, Qiuxia Min, Abulizi Palida, Yiyuan Zhang, Ruotian Tang, Lixia Chen, Hua Li
8-Chrysoeriol, a bioactive flavanoid, was firstly identified to bind directly to BCL-2 as BH3 mimetics by structure-based virtual ligand screening. And 3D docking model revealed the molecular basis of 8-Chrysoeriol targeting to BCL-2. The interaction between 8-Chrysoeriol and BCL-2 was further confirmed using Microscale Thermophoresis (MST) technique. Meanwhile, high expression level of antiapoptotic protein BCL-2 was detected in SW1990 pancreatic cancer cells and 8-Chrysoeriol showed obvious proapoptosis effect against SW1990 in vitro...
February 2, 2018: Bioorganic Chemistry
https://www.readbyqxmd.com/read/29454192/phytophthora-sojae-effectors-orchestrate-warfare-with-host-immunity
#2
REVIEW
Yan Wang, Yuanchao Wang
Phytophthora sojae is one of the most damaging plant pathogens of soybean. To aid establishment of a compatible interaction with its host, P. sojae deploys many secreted effectors. These effectors act either in the apoplastic space to cope with hostile conditions or inside of host cells to reprogram host physiology favoring pathogen growth. Effectors have been used as molecular probes, which revealed in Phytophthora that effectors execute their virulence function via manipulating host targets. In addition, recent studies have discovered 'pseudo-effectors' in Phytophthora that act as decoys to shield virulence effectors from host defense, a new paradigm in plant-pathogen interactions...
February 14, 2018: Current Opinion in Microbiology
https://www.readbyqxmd.com/read/29454191/show-me-the-way-rust-effector-targets-in-heterologous-plant-systems
#3
REVIEW
Cécile Lorrain, Benjamin Petre, Sébastien Duplessis
For years, the study of rust fungal effectors has been impeded by the lack of molecular genetic tools in rust pathosystems. The recent use of heterologous plants to perform effector screens (effectoromics)-including effector localisation (cellular targets) and protein interactors (molecular targets) in plant cells-has changed the game. These screens revealed that many candidate effectors from various rust fungi target specific plant cell compartments, including chloroplasts, and associate with specific plant protein complexes...
February 14, 2018: Current Opinion in Microbiology
https://www.readbyqxmd.com/read/29454076/the-biological-basis-of-treating-jaw-discrepancies-an-interplay-of-mechanical-forces-and-skeletal-configuration
#4
REVIEW
Konstantinos Karamesinis, Efthimia K Basdra
Jaw discrepancies and malrelations affect a large proportion of the general population and their treatment is of utmost significance for individuals' health and quality of life. The aim of their therapy is the modification of aberrant jaw development mainly by targeting the growth potential of the mandibular condyle through its cartilage, and the architectural shape of alveolar bone through a suture type of structure, the periodontal ligament. This targeted treatment is achieved via external mechanical force application by using a wide variety of intraoral and extraoral appliances...
February 14, 2018: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/29453988/silencing-calreticulin-gene-might-protect-cardiomyocytes-from-angiotensin-ii-induced-apoptosis
#5
Wen Zhang, Zhiyue Liu, Yanmei Zhang, Qinxue Bao, Wenchao Wu, He Huang, Xiaojing Liu
AIMS: Calreticulin (CRT), as a chaperone, contributes to protein folding and quality control cycle. CRT is an important factor regulating Ca 2+ that participates in cell apoptosis. However, the function of CRT in the heart is still controversial. Therefore, we aimed to investigate the potential role of CRT in angiotensin II-induced cardiomyocytes apoptosis. MAIN METHODS: Primary cultured neonatal cardiomyocytes were stimulated with angiotensin II to induce the apoptosis...
February 14, 2018: Life Sciences
https://www.readbyqxmd.com/read/29453901/shedding-light-on-aberrant-interactions-a-review-of-modern-tools-for-studying-protein-aggregates
#6
REVIEW
Franziska Kundel, Laura Tosatto, Daniel R Whiten, David C Wirthensohn, Mathew H Horrocks, David Klenerman
The link between protein aggregation and neurodegenerative disease is well established. However, given the heterogeneity of species formed during the aggregation process, it is difficult to delineate details of the molecular events involved in generating pathological aggregates from those producing soluble monomers. As aberrant aggregates are possible pharmacological targets for the treatment of neurodegenerative diseases, the need to observe and characterise soluble oligomers has pushed traditional biophysical techniques to their limits, leading to the development of a plethora of new tools capable of detecting soluble oligomers with high precision and specificity...
February 17, 2018: FEBS Journal
https://www.readbyqxmd.com/read/29453889/mitochondrial-dysfunction-and-axon-degeneration-in-progressive-multiple-sclerosis
#7
REVIEW
Graham Campbell, Don Mahad
The neuron is the target of inflammatory demyelinating processes in multiple sclerosis (MS). In progressive MS, however, there is a gathering body of evidence indicating that molecular changes converge on mitochondria within neuronal cell bodies. The most reproducible change relates to mitochondrial respiratory chain complex deficiency, which compromises the capacity of neurons to generate ATP. The resulting energy failure state is coupled with an increase in demand for energy by the demyelinated axon, being particularly relevant to the long tracts such as corticospinal tracts with long projection axons...
February 17, 2018: FEBS Letters
https://www.readbyqxmd.com/read/29453833/ketamine-induces-apoptosis-in-lung-adenocarcinoma-cells-by-regulating-the-expression-of-cd69
#8
Xuhui Zhou, Peihong Zhang, Wei Luo, Lei Zhang, Rong Hu, Yu Sun, Hong Jiang
Ketamine, an anesthetic, analgesic, or sedative, is widely used for the treatment of cancer pain. Recently, ketamine has been also reported to be tumor repressor for inhibiting proliferation, invasion, and migration, and inducing apoptosis in many cancers. However, whether ketamine can induce the apoptosis of lung adenocarcinoma (LUAD) and which downstream molecular mediates its function remain largely unknown. A LUAD cell line A549 was incubated with ketamine at 0, 1, 10, and 100 μmol/L for 24 h. Trypan blue staining was used to detect the cell viability...
February 17, 2018: Cancer Medicine
https://www.readbyqxmd.com/read/29453696/interrelationship-between-diabetes-mellitus-and-heart-failure-the-role-of-peroxisome-proliferator-activated-receptors-in-left-ventricle-performance
#9
REVIEW
Evangelos Oikonomou, Konstantinos Mourouzis, Petros Fountoulakis, Georgios Angelos Papamikroulis, Gerasimos Siasos, Alexis Antonopoulos, Georgia Vogiatzi, Sotiris Tsalamadris, Manolis Vavuranakis, Dimitris Tousoulis
Heart failure (HF) is a common cardiac syndrome, whose pathophysiology involves complex mechanisms, some of which remain unknown. Diabetes mellitus (DM) constitutes not only a glucose metabolic disorder accompanied by insulin resistance but also a risk factor for cardiovascular disease and HF. During the last years though emerging data set up, a bidirectional interrelationship between these two entities. In the case of DM impaired calcium homeostasis, free fatty acid metabolism, redox state, and advance glycation end products may accelerate cardiac dysfunction...
February 17, 2018: Heart Failure Reviews
https://www.readbyqxmd.com/read/29453691/effect-of-phosphorylation-and-single-nucleotide-polymorphisms-on-caspase-substrates-processing
#10
Sonu Kumar, Piotr Cieplak
Posttranslational modifications that involve either reversible covalent modification of proteins or irreversible proteolysis are central to the regulation of key cellular mechanisms, including apoptosis, cell-cycle regulation and signal transduction. There is mounting evidence suggesting cross-talk between proteases and kinases. For instance: caspases, a class of proteases involved in programmed cell death-apoptosis, cleave a large set of various types of proteins. Simultaneously, kinases restrict caspase activity by phosphorylating their protein substrates in the vicinity of cleavage site...
February 16, 2018: Apoptosis: An International Journal on Programmed Cell Death
https://www.readbyqxmd.com/read/29453566/profiling-signaling-proteins-in-sertoli-cells-by-co-immunoprecipitation
#11
Maria João Freitas, Margarida Fardilha
Sertoli cells are crucial for germ cell support, create a suitable environment for spermatogenesis, and integrate information from the nervous system and germ cell line. To fully understand the role of Sertoli cells, it is necessary to characterize the protein-protein interactions. Identifying the interactome of a given protein may provide leads about the role and molecular mechanism of such protein in Sertoli cells. One of the techniques to characterize protein interactomes consists of co-immunoprecipitation followed by mass spectrometry or Western blot...
2018: Methods in Molecular Biology
https://www.readbyqxmd.com/read/29453499/screening-for-gene-environment-g%C3%A3-e-interaction-using-omics-data-from-exposed-individuals-an-application-to-gene-arsenic-interaction
#12
Maria Argos, Lin Tong, Shantanu Roy, Mekala Sabarinathan, Alauddin Ahmed, Md Tariqul Islam, Tariqul Islam, Muhammad Rakibuz-Zaman, Golam Sarwar, Hasan Shahriar, Mahfuzar Rahman, Md Yunus, Joseph H Graziano, Farzana Jasmine, Muhammad G Kibriya, Xiang Zhou, Habibul Ahsan, Brandon L Pierce
Identifying gene-environment interactions is a central challenge in the quest to understand susceptibility to complex, multi-factorial diseases. Developing an understanding of how inter-individual variability in inherited genetic variation alters the effects of environmental exposures will enhance our knowledge of disease mechanisms and improve our ability to predict disease and target interventions to high-risk sub-populations. Limited progress has been made identifying gene-environment interactions in the epidemiological setting using existing statistical approaches for genome-wide searches for interaction...
February 16, 2018: Mammalian Genome: Official Journal of the International Mammalian Genome Society
https://www.readbyqxmd.com/read/29453446/environmental-genetic-and-epigenetic-contributions-to-cocaine-addiction
#13
REVIEW
R Christopher Pierce, Bruno Fant, Sarah E Swinford-Jackson, Elizabeth A Heller, Wade H Berrettini, Mathieu E Wimmer
Decades of research on cocaine has produced volumes of data that have answered many important questions about the nature of this highly addictive drug. Sadly, none of this information has translated into the development of effective therapies for the treatment of cocaine addiction. This review endeavors to assess the current state of cocaine research in an attempt to identify novel pathways for therapeutic development. For example, risk of cocaine addiction is highly heritable but genome-wide analyses comparing cocaine-dependent individuals to controls have not resulted in promising targets for drug development...
February 5, 2018: Neuropsychopharmacology: Official Publication of the American College of Neuropsychopharmacology
https://www.readbyqxmd.com/read/29453377/optimized-peptide-based-inhibitors-targeting-the-dihydrofolate-reductase-pathway-in-cancer
#14
Amrinder Singh, Neha Deshpande, Nilkamal Pramanik, Siddharth Jhunjhunwala, Annapoorni Rangarajan, Hanudatta S Atreya
We report the first peptide based hDHFR inhibitors designed on the basis of structural analysis of dihydrofolate reductase (DHFR). A set of peptides were rationally designed and synthesized using solid phase peptide synthesis and characterized using nuclear magnetic resonance and enzyme immunoassays. The best candidate among them, a tetrapeptide, was chosen based on molecular mechanics calculations and evaluated in human lung adenocarcinoma cell line A549. It showed a significant reduction of cell proliferation and an IC 50 of 82 µM was obtained...
February 16, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29453314/ar-expression-in-breast-cancer-ctcs-associates-with-bone-metastases
#15
Nicola Aceto, Aditya Bardia, Ben S Wittner, Maria C Donaldson, Ryan O'Keefe, Amanda Engstrom, Francesca Bersani, Yu Zheng, Valentine Comaills, Kira Niederhoffer, Huili Zhu, Olivia MacKenzie, Toshi Shioda, Dennis Sgroi, Ravi Kapur, David T Ting, Beverly Moy, Sridhar Ramaswamy, Mehmet Toner, Daniel A Haber, Shyamala Maheswaran
Molecular drivers underlying bone metastases in human cancer are not well understood, in part due to constraints in bone tissue sampling. Here, RNA sequencing (RNA-seq) was performed of circulating tumor cells (CTCs) isolated from blood samples of women with metastatic estrogen receptor (ER)+ breast cancer, comparing cases with progression in bone versus visceral organs. Among the activated cellular pathways in CTCs from bone-predominant breast cancer is androgen receptor (AR) signaling. AR gene expression is evident, as is its constitutively active splice variant AR-v7...
February 16, 2018: Molecular Cancer Research: MCR
https://www.readbyqxmd.com/read/29453313/multigene-profiling-of-ctcs-in-mcrpc-identifies-a-clinically-relevant-prognostic-signature
#16
Udit Singhal, Yugang Wang, James Henderson, Yashar S Niknafs, Yuanyuan Qiao, Amy Gursky, Alexander Zaslavsky, Jae-Seung Chung, David C Smith, R Jeffrey Karnes, S Laura Chang, Felix Y Feng, Ganesh S Palapattu, Russell S Taichman, Arul M Chinnaiyan, Scott A Tomlins, Todd M Morgan
The trend towards precision-based therapeutic approaches dictated by molecular alterations offers substantial promise for men with metastatic castration resistant prostate cancer (mCRPC). However, current approaches for molecular characterization are primarily tissue based, necessitating serial biopsies to understand changes over time and are limited by the challenges inherent to extracting genomic material from predominantly bone metastases. Therefore, a circulating tumor cell (CTC)-based assay was developed to determine gene expression across a panel of clinically relevant and potentially actionable prostate cancer related genes...
February 16, 2018: Molecular Cancer Research: MCR
https://www.readbyqxmd.com/read/29453308/sex-specific-mechanisms-of-resistance-vessel-endothelial-dysfunction-induced-by-cardiometabolic-risk-factors
#17
Ana P Davel, Qing Lu, M Elizabeth Moss, Sitara Rao, Imran J Anwar, Jennifer J DuPont, Iris Z Jaffe
BACKGROUND: The incidence of obesity is rising, particularly among women. Microvascular dysfunction is more common with female sex, obesity, and hyperlipidemia and predicts adverse cardiovascular outcomes, but the molecular mechanisms are unclear. Because obesity is associated with mineralocorticoid receptor (MR) activation, we tested the hypothesis that MR in endothelial cells contribute to sex differences in resistance vessel dysfunction in response to cardiometabolic risk factors. METHODS AND RESULTS: Male and female endothelial cell-specific MR knockout mice and MR-intact littermates were randomized to high-fat-diet-induced obesity or obesity with hyperlipidemia induced by adeno-associated virus-based vector targeting transfer of the mutant stable form (DY mutation) of the human PCSK9 (proprotein convertase subtilisin/kexin type 9) gene and compared with control diet...
February 16, 2018: Journal of the American Heart Association
https://www.readbyqxmd.com/read/29453280/elevated-expression-of-il-33-and-tslp-in-the-airways-of-human-asthmatics-in-vivo-a-potential-biomarker-of-severe-refractory-disease
#18
Yan Li, Wei Wang, Zhe Lv, Yun Li, Yan Chen, Kewu Huang, Chris J Corrigan, Sun Ying
The epithelial cytokines IL-33, thymic stromal lymphopoietin (TSLP), and IL-25 have been implicated in asthma pathogenesis because they promote Th2-type cytokine synthesis, but their expression is relatively poorly documented in "real-life" human asthma. Using bronchoalveolar lavage fluid (BALF), we measured airway concentrations of these mediators and compared them with those of Th1- and Th2-type cytokines, airway infiltration of neutrophils and eosinophils, and lung function in a large group of asthmatic patients with a range of disease severity ( n = 70) and control subjects ( n = 30)...
February 16, 2018: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/29453276/entropy-drives-selective-fluorine-recognition-in-the-fluoroacetyl-coa-thioesterase-from-streptomyces-cattleya
#19
Amy M Weeks, Ningkun Wang, Jeffrey G Pelton, Michelle C Y Chang
Fluorinated small molecules play an important role in the design of bioactive compounds for a broad range of applications. As such, there is strong interest in developing a deeper understanding of how fluorine affects the interaction of these ligands with their targets. Given the small number of fluorinated metabolites identified to date, insights into fluorine recognition have been provided almost entirely by synthetic systems. The fluoroacetyl-CoA thioesterase (FlK) from Streptomyces cattleya thus provides a unique opportunity to study an enzyme-ligand pair that has been evolutionarily optimized for a surprisingly high 10 6 selectivity for a single fluorine substituent...
February 16, 2018: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/29453204/circulating-mirna-profiles-associated-with-hyperglycemia-in-patients-with-type-1-diabetes-mellitus
#20
Eiichiro Satake, Marcus G Pezzolesi, Zaipul I Md Dom, Adam M Smiles, Monika A Niewczas, Andrzej S Krolewski
We investigated plasma microRNA (miRNA) profiles associated with variation of hyperglycemia, measured as hemoglobin A 1c (HbA 1c ), in two panels of patients with type 1 diabetes (T1D). Using the HTG Molecular Diagnostics EdgeSeq platform, 2,083 miRNAs were measured in plasma from 71 patients included in a screening panel. Quantitative real-time polymerase chain reaction was used to measure the candidate miRNAs in plasma from 95 patients included in an independent replication panel. We found 10 miRNAs replicated in both panels and four with high statistical significance...
February 16, 2018: Diabetes
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