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https://www.readbyqxmd.com/read/29668110/phenylbutyl-isoselenocyanate-induces-reactive-oxygen-species-to-inhibit-androgen-receptor-and-to-initiate-p53-mediated-apoptosis-in-lncap-prostate-cancer-cells
#1
Wei Wu, Deepkamal Karelia, Kartick Pramanik, Shantu G Amin, Arun K Sharma, Cheng Jiang, Junxuan Lu
Previous studies have established the in vivo bioavailability and efficacious dosages of phenylbutyl isoselenocyanate (ISC-4), a selenium-substituted isothiocyanate, against mouse xenograft models of human melanoma and colorectal cancer. To explore its potential attributes against prostate cancer, we treated human LNCaP prostate cancer cells with ISC-4 and examined their apoptosis responses, and interrogated the signaling mechanisms through pharmacological and siRNA knockdown approaches. Our results show that ISC-4 was more potent at inducing apoptosis than its sulfur analog phenylbutyl isothiocyanate (PBITC) without suppressing protein kinase AKT Ser473 phosphorylation...
April 18, 2018: Molecular Carcinogenesis
https://www.readbyqxmd.com/read/29668064/assessment-of-a-panel-of-cellular-biomarkers-and-the-kinetics-of-their-induction-in-comparing-genotoxic-modes-of-action-in-hepg2-cells
#2
Benjamin Kopp, Morgane Dario, Daniel Zalko, Marc Audebert
One major challenge for in vitro genotoxicology is the determination of the genotoxic mode of action of tested compounds. The quantification of the phosphorylation of the histones H3 (pH3) and H2AX (γH2AX) allows an efficient discrimination between aneugenic and clastogenic compounds. However, these two biomarkers do not permit to deduct the specific mechanisms involved in the action of clastogenic compounds. The aim of this study was to investigate other possible cellular biomarkers allowing differentiating clastogenic properties...
April 18, 2018: Environmental and Molecular Mutagenesis
https://www.readbyqxmd.com/read/29667627/propofol-inhibits-hela-cells-by-impairing-autophagic-flux-via-amp-activated-protein-kinase-ampk-activation-and-endoplasmic-reticulum-stress-regulated-by-calcium
#3
Xi Chen, Kai Li, Guoqing Zhao
BACKGROUND Propofol has antitumor effects against various cancers. However, the mechanism of action of propofol in HeLa human cervical cancer cells has not been elucidated. MATERIAL AND METHODS We treated HeLa human cervical cancer cells with different concentrations of propofol. Cell viability was evaluated with Cell Counting Kit-8 and apoptosis was analyzed by annexin V-fluorescein isothiocyanate and propidium iodide staining and flow cytometry. Autophagosome formation was evaluated based on microtubule-associated protein light chain (LC)3 conversion and light chain 3 puncta formation...
April 18, 2018: Medical Science Monitor: International Medical Journal of Experimental and Clinical Research
https://www.readbyqxmd.com/read/29667261/apple-s-rnase-interacts-with-an-actin-binding-protein-mdmvg-to-reduce-pollen-tube-growth-by-inhibiting-its-actin-severing-activity-at-the-early-stage-of-self-pollination-induction
#4
Qing Yang, Dong Meng, Zhaoyu Gu, Wei Li, Qiuju Chen, Yang Li, Hui Yuan, Jie Yu, Chunsheng Liu, Tianzhong Li
In S-RNase-mediated self-incompatibility (SI), S-RNase secreted from the style destroys the actin cytoskeleton of the self-pollen tubes, eventually halting its growth, but the mechanism remains unclear. In vitro biochemical assays revealed that S-RNase does not bind or sever filamentous actin (F-actin). In apple (Malus×domestica), we identified an actin-binding protein containing myosin, villin and GRAM, MdMVG, that physically interacts with S-RNase and directly binds and severs F-actin. Immunofluorescence assays and total internal reflection fluorescence microscopy (TIRFM) indicated that S-RNase inhibits the F-actin-severing activity of MdMVG in vitro...
April 18, 2018: Plant Journal: for Cell and Molecular Biology
https://www.readbyqxmd.com/read/29667004/the-development-of-hiv-vaccines-targeting-gp41-membrane-proximal-external-region-mper-challenges-and-prospects
#5
REVIEW
Huan Liu, Xiaojie Su, Lulu Si, Lu Lu, Shibo Jiang
A human immunodeficiency virus type-1 (HIV-1) vaccine which is able to effectively prevent infection would be the most powerful method of extinguishing pandemic of the acquired immunodeficiency syndrome (AIDS). Yet, achieving such vaccine remains great challenges. The membrane-proximal external region (MPER) is a highly conserved region of the envelope glycoprotein (Env) gp41 subunit near the viral envelope surface, and it plays a key role in membrane fusion. It is also the target of some reported broadly neutralizing antibodies (bNAbs)...
April 17, 2018: Protein & Cell
https://www.readbyqxmd.com/read/29666611/genome-sequence-assembly-and-characterization-of-two-metschnikowia-fructicola-strains-used-as-biocontrol-agents-of-postharvest-diseases
#6
Edoardo Piombo, Noa Sela, Michael Wisniewski, Maria Hoffmann, Maria L Gullino, Marc W Allard, Elena Levin, Davide Spadaro, Samir Droby
The yeast Metschnikowia fructicola was reported as an efficient biological control agent of postharvest diseases of fruits and vegetables, and it is the bases of the commercial formulated product "Shemer." Several mechanisms of action by which M. fructicola inhibits postharvest pathogens were suggested including iron-binding compounds, induction of defense signaling genes, production of fungal cell wall degrading enzymes and relatively high amounts of superoxide anions. We assembled the whole genome sequence of two strains of M...
2018: Frontiers in Microbiology
https://www.readbyqxmd.com/read/29666508/intrinsic-mechanisms-of-neuronal-axon-regeneration
#7
REVIEW
Marcus Mahar, Valeria Cavalli
Permanent disabilities following CNS injuries result from the failure of injured axons to regenerate and rebuild functional connections with their original targets. By contrast, injury to peripheral nerves is followed by robust regeneration, which can lead to recovery of sensory and motor functions. This regenerative response requires the induction of widespread transcriptional and epigenetic changes in injured neurons. Considerable progress has been made in recent years in understanding how peripheral axon injury elicits these widespread changes through the coordinated actions of transcription factors, epigenetic modifiers and, to a lesser extent, microRNAs...
April 17, 2018: Nature Reviews. Neuroscience
https://www.readbyqxmd.com/read/29666503/regulatory-t-cell-derived-extracellular-vesicles-modify-dendritic-cell-function
#8
Sim L Tung, Dominic A Boardman, Monica Sen, Marilena Letizia, Qi Peng, Nicole Cianci, Laura Dioni, Leo M Carlin, Robert Lechler, Valentina Bollati, Giovanna Lombardi, Lesley A Smyth
Regulatory T cells (Treg) are a subpopulation of T cells that maintain tolerance to self and limit other immune responses. They achieve this through different mechanisms including the release of extracellular vesicles (EVs) such as exosomes as shown by us, and others. One of the ways that Treg derived EVs inhibit target cells such as effector T cells is via the transfer of miRNA. Another key target for the immunoregulatory function of Tregs is the dendritic cells (DCs). In this study we demonstrate directly, and for the first time, that miRNAs are transferred from Tregs to DCs via Treg derived EVs...
April 17, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29666278/deubiquitylation-and-stabilization-of-p21-by-usp11-is-critical-for-cell-cycle-progression-and-dna-damage-responses
#9
Tanggang Deng, Guobei Yan, Xin Song, Lin Xie, Yu Zhou, Jianglin Li, Xiaoxiao Hu, Zhen Li, Jun Hu, Yibin Zhang, Hui Zhang, Yang Sun, Peifu Feng, Dong Wei, Bin Hu, Jing Liu, Weihong Tan, Mao Ye
p21WAF1/CIP1 is a broad-acting cyclin-dependent kinase inhibitor. Its stability is essential for proper cell-cycle progression and cell fate decision. Ubiquitylation by the multiple E3 ubiquitin ligase complexes is the major regulatory mechanism of p21, which induces p21 degradation. However, it is unclear whether ubiquitylated p21 can be recycled. In this study, we report USP11 as a deubiquitylase of p21. In the nucleus, USP11 binds to p21, catalyzes the removal of polyubiquitin chains conjugated onto p21, and stabilizes p21 protein...
April 16, 2018: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/29666185/hepatocyte-nuclear-receptor-shp-suppresses-inflammation-and-fibrosis-in-a-mouse-model-of-nonalcoholic-steatohepatitis
#10
An Zou, Nancy Magee, Fengyan Deng, Sarah Lehn, Cuncong Zhong, Yuxia Zhang
Nonalcoholic fatty liver disease (NAFLD) is a burgeoning health problem worldwide, ranging from nonalcoholic fatty liver (NAFL, steatosis without hepatocellular injury) to the more aggressive nonalcoholic steatohepatitis (NASH, steatosis with ballooning, inflammation, or fibrosis). Although many studies have greatly contributed to the elucidation of NAFLD pathogenesis, the disease progression from NAFL to NASH still remains incompletely understood. Nuclear receptor small heterodimer partner (Nr0b2, SHP) is a transcriptional regulator critical for the regulation of bile acid, glucose, and lipid metabolism...
April 17, 2018: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/29666166/type-i-interferons-in-tuberculosis-foe-and-occasionally-friend
#11
REVIEW
Lúcia Moreira-Teixeira, Katrin Mayer-Barber, Alan Sher, Anne O'Garra
Tuberculosis remains one of the leading causes of mortality worldwide, and, despite its clinical significance, there are still significant gaps in our understanding of pathogenic and protective mechanisms triggered by Mycobacterium tuberculosis infection. Type I interferons (IFN) regulate a broad family of genes that either stimulate or inhibit immune function, having both host-protective and detrimental effects, and exhibit well-characterized antiviral activity. Transcriptional studies have uncovered a potential deleterious role for type I IFN in active tuberculosis...
April 17, 2018: Journal of Experimental Medicine
https://www.readbyqxmd.com/read/29665406/sn56-neuronal-cell-death-after-24-h-and-14-days-chlorpyrifos-exposure-through-glutamate-transmission-dysfunction-increase-of-gsk-3%C3%AE-enzyme-%C3%AE-amyloid-and-tau-protein-levels
#12
Paula Moyano, María Teresa Frejo, María José Anadon, José Manuel García, María Jesús Díaz, Margarita Lobo, Emma Sola, Jimena García, Javier Del Pino
Chlorpyrifos (CPF) is an organophosphate insecticide described to induce cognitive disorders, both after acute and repeated administration. However, the mechanisms through which it induces these effects are unknown. CPF has been reported to produce basal forebrain cholinergic neuronal cell death, involved on learning and memory regulation, which could be the cause of such cognitive disorders. Neuronal cell death was partially mediated by oxidative stress generation, P75NTR and α7 -nAChRs gene expression alteration triggered through acetylcholinesterase (AChE) variants disruption, suggesting other mechanisms are involved...
April 14, 2018: Toxicology
https://www.readbyqxmd.com/read/29665367/suppression-of-akt-mediated-hdac3-expression-and-cdk2-t39-phosphorylation-by-a-bichalcone-analog-contributes-to-s-phase-retardation-of-cancer-cells
#13
Kuang-Chen Hung, Meng-Liang Lin, Shih-Wei Hsu, Chuan-Chun Lee, Ren-Yu Huang, Tian-Shung Wu, Shih-Shun Chen
Targeting cell cycle regulators has been a suggested mechanism for therapeutic cancer strategies. We report here that the bichalcone analog TSWU-CD4 induces S phase arrest of human cancer cells by inhibiting the formation of cyclin A-phospho (p)-cyclin-dependent kinase 2 (CDK2, threonine [Thr] 39) complexes, independent of mutant p53 expression. Ectopic expression of CDK2 (T39E), which mimics phosphorylation of the Thr 39 residue of CDK2, partially rescues the cells from TSWU-CD4-induced S phase arrest, whereas phosphorylation-deficient CDK2 (T39A) expression regulates cell growth with significant S phase arrest and enhances TSWU-CD4-triggered S phase arrest...
April 14, 2018: European Journal of Pharmacology
https://www.readbyqxmd.com/read/29665121/homoharringtonine-could-induce-quick-protein-synthesis-of-psmd11-through-activating-mek1-erk1-2-signaling-pathway-in-pancreatic-cancer-cells
#14
Lele Wang, Linlin Zhao, Guo Wei, Dieter Saur, Barbara Seidler, Junyan Wang, Chuanxin Wang, Tonggang Qi
Pancreatic ductal adenocarcinoma (PDAC) remains one of the most devastating disease with the 5-year survival rate less than 6%. In this study, we investigated if inhibiting protein synthesis directly with homoharringtonine (HHT) could induce acute apoptosis in pancreatic cancer cells through quick depletion of multiple short-lived critical members of the central proteome, example, PSMD11(26S proteasome non-ATPase regulatory subunit 11). It was shown that although HHT could inhibit proliferation and growth of MiaPaCa-2 and PANC-1 cells in a time- and dose-dependent manner, only part of pancreatic cancer cells could be induced to die through acute apoptosis...
April 17, 2018: Journal of Cellular Biochemistry
https://www.readbyqxmd.com/read/29665074/parkin-deficiency-modulates-nlrp3-inflammasome-activation-by-attenuating-an-a20-dependent-negative-feedback-loop
#15
François Mouton-Liger, Thibault Rosazza, Julia Sepulveda-Diaz, Amélie Ieang, Sidi-Mohamed Hassoun, Emilie Claire, Graziella Mangone, Alexis Brice, Patrick P Michel, Jean-Christophe Corvol, Olga Corti
Neuroinflammation and mitochondrial dysfunction, key mechanisms in the pathogenesis of Parkinson's disease (PD), are usually explored independently. Loss-of-function mutations of PARK2 and PARK6, encoding the E3 ubiquitin protein ligase Parkin and the mitochondrial serine/threonine kinase PINK1, account for a large proportion of cases of autosomal recessive early-onset PD. PINK1 and Parkin regulate mitochondrial quality control and have been linked to the modulation of innate immunity pathways. We report here an exacerbation of NLRP3 inflammasome activation by specific inducers in microglia and bone marrow-derived macrophages from Park2-/- and Pink1-/- mice...
April 17, 2018: Glia
https://www.readbyqxmd.com/read/29664738/pharmacological-induction-of-hypoxia-inducible-transcription-factor-arnt-attenuates-chronic-kidney-failure
#16
Björn Tampe, Désirée Tampe, Gunsmaa Nyamsuren, Friederike Klöpper, Gregor Rapp, Anne Kauffels, Thomas Lorf, Elisabeth M Zeisberg, Gerhard A Müller, Raghu Kalluri, Samy Hakroush, Michael Zeisberg
Progression of chronic kidney disease associated with progressive fibrosis and impaired tubular epithelial regeneration is still an unmet biomedical challenge, because once chronic lesions have manifested, no effective therapies are available as of yet for clinical use. Prompted by various studies across multiple organs demonstrating that preconditioning regimens to induce endogenous regenerative mechanisms protect various organs from later incurring acute injuries, we here aimed to gain insights into the molecular mechanisms underlying successful protection and to explore whether such pathways could be utilized to inhibit progression of chronic organ injury...
April 17, 2018: Journal of Clinical Investigation
https://www.readbyqxmd.com/read/29663828/effect-of-participation-in-a-randomised-controlled-trial-of-an-integrated-palliative-care-intervention-on-hiv-associated-stigma
#17
Keira Lowther, Richard Harding, Victoria Simms, Nancy Gikaara, Aabid Ahmed, Zipporah Ali, Hellen Kariuki, Lorraine Sherr, Irene J Higginson, Lucy Selman
We conducted in Kenya a mixed-methods randomised controlled trial (RCT) of a nurse-led palliative care intervention integrated with anti-retroviral therapy (ART) provision for the management of HIV. Here we report qualitative findings showing increased resistance to HIV-associated stigma among trial participants. A mixed method design was chosen to enable identification of the active ingredients of the intervention and exploration of participants' experiences of receiving the intervention. The RCT was conducted from July 2011 to November 2012 in a community hospital in the city of Mombasa, Kenya, with a sample of 120 adults with HIV on ART...
April 17, 2018: AIDS Care
https://www.readbyqxmd.com/read/29663660/7-12-dimethylbenz-%C3%AE-anthracene-increases-cell-proliferation-and-invasion-through-induction-of-wnt-%C3%AE-catenin-signaling-and-emt-process
#18
Yeo-Jung Kwon, Dong-Jin Ye, Hyoung-Seok Baek, Young-Jin Chun
7,12-Dimethylbenz[α]anthracene (DMBA) is a hazardous component present in polluted environments. DMBA has been used as an experimental tool for in vivo tumor formation owing to its carcinogenic effects, but the detailed molecular mechanism of DMBA has not been fully established. To comprehend the carcinogenic mechanism of DMBA, we explored its effects in the breast cancer cell lines, MCF-7 and MDA-MB-231, and the cervical cancer cell line, HeLa. Cell viability assay and measurement of a proliferation marker showed that DMBA markedly increased cancer cell proliferation...
April 16, 2018: Environmental Toxicology
https://www.readbyqxmd.com/read/29663645/genetically-engineered-supercharged-polypeptide-fluids-fast-and-persistent-self-ordering-induced-by-a-touch
#19
Lei Zhang, Chao Ma, Jing Sun, Baiqi Shao, Giuseppe Portale, Dong Chen, Kai Liu, Andreas Herrmann
Mechanically induced disorder-order transitions have been studied in fluid surfactant solutions or polymer thermotropic liquid crystals. However, the isothermally induced ordered phases do not persist after cessation of shear, which limits their technological applicability to a great extent. Moreover, no such stimuli-responsive materials involving biomacromolecules have been reported although biopolymer liquids are gaining a lot of attention. Here we introduce a new type of biological fluid system in which anionic polypeptides are complexed with cationic surfactants...
April 16, 2018: Angewandte Chemie
https://www.readbyqxmd.com/read/29663416/autophagy-induction-by-trehalose-molecular-mechanisms-and-therapeutic-impacts
#20
REVIEW
Kiana Hosseinpour-Moghaddam, Michele Caraglia, Amirhossein Sahebkar
The balance between synthesis and degradation is crucial to maintain cellular homeostasis and different mechanisms are known to keep this balance. In this review, we will provide a short overview on autophagy as an intracellular homeostatic degradative machinery. We will also describe the involvement of downregulation of autophagy in numerous diseases including neurodegenerative diseases, cancer, aging, metabolic disorders, and other infectious diseases. Therefore, modulation of autophagic processes can represent a promising way of intervention in different diseases including neurodegeneration and cancer...
April 16, 2018: Journal of Cellular Physiology
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