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https://www.readbyqxmd.com/read/28545029/tusc3-induces-autophagy-in-human-non-small-cell-lung-cancer-cells-through-wnt-%C3%AE-catenin-signaling
#1
Yun Peng, Jun Cao, Xiao-Yi Yao, Jian-Xin Wang, Mei-Zuo Zhong, Ping-Ping Gan, Jian-Huang Li
We investigated the effects of tumor suppressor candidate 3 (TUSC3) on autophagy in human non-small cell lung cancer (NSCLC) cells. A total of 118 NSCLC patients (88 males and 30 females) who underwent surgery at our institute were enrolled in the study. Immunohistochemical analysis revealed that TUSC3 protein expression was lower in NSCLC specimens than adjacent normal tissue. Correspondingly, there was greater methylation of TUSC3 in NSCLC than adjacent normal tissue. After transient transfection of A549 NSCLC cells with constructs designed to up-regulate or down-regulate TUSC3 expression, we analyzed the effects of inhibiting the Wnt pathway (XAV939) and autophagy (chloroquine, CQ) on the behavior of NSCLC cells...
May 8, 2017: Oncotarget
https://www.readbyqxmd.com/read/28545004/autophagy-as-an-emerging-arena-for-plant-pathogen-interactions
#2
REVIEW
Daniel Hofius, Liang Li, Anders Hafrén, Nuria S Coll
Autophagy is a highly conserved degradation and recycling process that controls cellular homeostasis, stress adaptation, and programmed cell death in eukaryotes. Emerging evidence indicates that autophagy is a key regulator of plant innate immunity and contributes with both pro-death and pro-survival functions to antimicrobial defences, depending on the pathogenic lifestyle. In turn, several pathogens have co-opted and evolved strategies to manipulate host autophagy pathways to the benefit of infection, while some eukaryotic microbes require their own autophagy machinery for successful pathogenesis...
May 22, 2017: Current Opinion in Plant Biology
https://www.readbyqxmd.com/read/28544853/microrna-34a-protect-myocardial-cells-against-ischemia-reperfusion-injury-through-inhibiting-autophagy-via-regulating-tnf%C3%AE-expression
#3
Haifeng Shao, Lili Yang, Li Wang, Bozan Tang, Jian Wang, Qiang Li
BACKGROUND: Ischemia/reperfusion (I/R) accompanying with the blood supply restored after myocardial infarction. Myocardial I/R injury relieves when autophagy decreased. MicroRNA-34a(miR-34a) regulate autophagy in renal I/R injury model. But whether it can affect cardiac I/R injury remains studying. This study investigated how miR-34a in protecting myocardial cells against I/R injury through inhibit autophagy via regulating tumor necrosis factor α (TNFα) . METHODS: Constructed the I/R model in vivo with Langendorff; treated Neonatal Rat cardiomyocyte to make H/R injury model in vitro with hypoxia/reoxygenation (H/R) method...
May 25, 2017: Biochemistry and Cell Biology, Biochimie et Biologie Cellulaire
https://www.readbyqxmd.com/read/28544790/roles-of-autophagy-and-endoplasmic-reticulum-stress-in-intracerebral-hemorrhage-induced-secondary-brain-injury-in%C3%A2-rats
#4
Xiao-Chun Duan, Wei Wang, Dong-Xia Feng, Jia Yin, Gang Zuo, Dong-Dong Chen, Zhou-Qing Chen, Hai-Ying Li, Zhong Wang, Gang Chen
OBJECTIVES: This study aimed to evaluate the roles of autophagy and endoplasmic reticulum (ER) stress in intracerebral hemorrhage (ICH)-induced secondary brain injury (SBI) in rats. METHODS: Autophagy inducer (rapamycin) and inhibitor (3-methyladenine), as well as ER stress activator (tunicamycin, TM) and inhibitor (tauroursodeoxycholic acid, TUDCA), were used. Bafilomycin A1, an inhibitor of autophagosome-lysosome fusion, was used to assess autophagic flux. RESULTS: Autophagy and ER stress were enhanced in the week after ICH...
May 19, 2017: CNS Neuroscience & Therapeutics
https://www.readbyqxmd.com/read/28544603/metabolic-reprogramming-of-macrophages-exposed-to-silk-poly-lactic-co-glycolic-acid-and-silica-nanoparticles
#5
Raquel Saborano, Thidarat Wongpinyochit, John D Totten, Blair F Johnston, F Philipp Seib, Iola F Duarte
Monitoring macrophage metabolism in response to nanoparticle exposure provides new insights into biological outcomes, such as inflammation or toxicity, and supports the design of tailored nanomedicines. This paper describes the metabolic signature of macrophages exposed to nanoparticles ranging in diameter from 100 to 125 nm and made from silk, poly(lactic-co-glycolic acid) or silica. Nanoparticles of this size and type are currently at various stages of preclinical and clinical development for drug delivery applications...
May 8, 2017: Advanced Healthcare Materials
https://www.readbyqxmd.com/read/28544335/p62-sequestosome-1-in-human-colorectal-carcinoma-as-a-potent-prognostic-predictor-associated-with-cell-proliferation
#6
Shun Nakayama, Hideaki Karasawa, Takashi Suzuki, Shinichi Yabuuchi, Kiyoshi Takagi, Takashi Aizawa, Yoshiaki Onodera, Yasuhiro Nakamura, Mika Watanabe, Fumiyoshi Fujishima, Hiroshi Yoshida, Takanori Morikawa, Tomohiko Sase, Takeshi Naitoh, Michiaki Unno, Hironobu Sasano
p62/sequestosome 1 (p62) is a multi-domain protein that functions as a receptor for ubiquitinated targets in the selective autophagy and serves as a scaffold in various signaling cascades. p62 have been reported to be up-regulated in several human malignancies, but the biological roles and significance of p62 are still poorly understood in colorectal carcinoma. We immunohistochemically evaluated p62 in 118 colorectal adenocarcinoma and 28 colorectal adenoma cases. We used four colon carcinoma cells (HCT8, HT29, COLO320, and SW480) in the in vitro studies...
May 23, 2017: Cancer Medicine
https://www.readbyqxmd.com/read/28544137/phenotypic-identification-of-a-novel-autophagy-inhibitor-chemotype-targeting-lipid-kinase-vps34
#7
Herbert Waldmann, Lucas Robke, Luca Laraia, Marjorie A Carnero Corrales, Georgios Konstantinidis, Makoto Muroi, André Richters, Michael Winzker, Tobias Engbring, Stefano Tomassi, Nobumoto Watanabe, Hiroyuki Osada, Daniel Rauh, Yaowen Wu, Julian Engel
Autophagy is a critical regulator of cellular homeostasis and metabolism. Interference with this process is considered a new approach for the treatment of disease, in particular cancer and neurological disorders. Therefore, novel small molecule autophagy modulators are in high demand. We describe the discovery of autophinib, a potent autophagy inhibitor with a novel chemotype. Autophinib was identified by means of a phenotypic assay monitoring formation of autophagy-induced puncta indicating accumulation of lipidated cytosolic protein LC3 on the autophagosomal membrane...
May 22, 2017: Angewandte Chemie
https://www.readbyqxmd.com/read/28543935/neurodegeneration-in-ataxia-telangiectasia-multiple-roles-of-atm-kinase-in-cellular-homeostasis
#8
REVIEW
Kay Rui Choy, Dianne J Watters
Ataxia-Telangiectasia (A-T) is characterized by neuronal degeneration, cancer, diabetes, immune deficiency and increased sensitivity to ionizing radiation. A-T is attributed to the deficiency of the protein kinase coded by the ATM (Ataxia-Telangiectasia Mutated) gene. ATM is a sensor of DNA Double Strand Breaks and signals to cell cycle checkpoints and the DNA repair machinery. ATM phosphorylates numerous substrates and activates many cell-signalling pathways. There has been considerable debate about whether a defective DNA damage response is causative of the neurological aspects of the disease...
May 22, 2017: Developmental Dynamics: An Official Publication of the American Association of Anatomists
https://www.readbyqxmd.com/read/28543180/traf6-participates-in-early-brain-injury-after-subarachnoid-hemorrhage-in-rats-through-inhibiting-autophagy-and-promoting-oxidative-stress
#9
Yang Dou, Haitao Shen, Dongxia Feng, Haiying Li, Xiaodi Tian, Jian Zhang, Zhong Wang, Gang Chen
Tumor necrosis factor receptor-associated factor 6 (TRAF6) is a member of the TRAF family and an important multifunctional intracellular adaptin of the tumor necrosis factor (TNF) superfamily and toll/IL-1 receptor (TIR) superfamily. TRAF6 has been studied in several central nervous system (CNS) diseases, including ischemic stroke, traumatic brain injury and neurodegenerative diseases, but its role in subarachnoid hemorrhage (SAH) has not been fully illustrated. This study was designed to explore changes of expression level and potential roles and mechanisms of TRAF6 in early brain injury (EBI) after SAH by using a Sprague-Dawley rat model of SAH induced in 0...
May 24, 2017: Journal of Neurochemistry
https://www.readbyqxmd.com/read/28542792/on-the-complexity-of-clinical-and-molecular-bases-of-neurodegeneration-with-brain-iron-accumulation
#10
REVIEW
Cristina Tello, Alejandra Darling, Vincenzo Lupo, Belén Pérez-Dueñas, Carmen Espinós
Neurodegeneration with brain iron accumulation (NBIA) are a group of inherited heterogeneous neurodegenerative rare disorders. These patients present with dystonia, spasticity, parkinsonism and neuropsychiatric disturbances, along with brain MRI evidence of iron accumulation. In sum, they are devastating disorders and to date, there is no specific treatment. Ten NBIA genes are accepted: PANK2, PLA2G6, C19orf12, COASY, FA2H, ATP13A2, WDR45, FTL, CP, and DCAF17, and. Nonetheless, a relevant percentage of patients remain without genetic diagnosis, suggesting that other novel NBIA genes remain to be discovered...
May 23, 2017: Clinical Genetics
https://www.readbyqxmd.com/read/28542502/in-vivo-transduction-of-neurons-with-tat-uch-l1-protects-brain-against-controlled-cortical-impact-injury
#11
Hao Liu, Marie E Rose, Xiecheng Ma, Sherman Culver, C Edward Dixon, Steven H Graham
Many mechanisms or pathways are involved in secondary post-traumatic brain injury, such as the ubiquitin-proteasome pathway (UPP), axonal degeneration and neuronal cell apoptosis. UCH-L1 is a protein that is expressed in high levels in neurons and may have important roles in the UPP, autophagy and axonal integrity. The current study aims to evaluate the role of UCH-L1 in post-traumatic brain injury (TBI) and its potential therapeutic effects. A novel protein was constructed that fused the protein transduction domain (PTD) of trans-activating transduction (TAT) protein with UCH-L1 (TAT-UCH-L1) in order to promote neuronal transduction...
2017: PloS One
https://www.readbyqxmd.com/read/28542452/the-role-of-aspartyl-aminopeptidase-ape4-in-cryptococcus-neoformans-virulence-and-authophagy
#12
Fabiano de Assis Gontijo, Amanda Teixeira de Melo, Renata C Pascon, Larissa Fernandes, Hugo Costa Paes, J Andrew Alspaugh, Marcelo A Vallim
In order to survive and cause disease, microbial pathogens must be able to proliferate at the temperature of their infected host. We identified novel microbial features associated with thermotolerance in the opportunistic fungal pathogen Cryptococcus neoformans using a random insertional mutagenesis strategy, screening for mutants with defective growth at 37°C. Among several thermosensitive mutants, we identified one bearing a disruption in a gene predicted to encode the Ape4 aspartyl aminopeptidase protein...
2017: PloS One
https://www.readbyqxmd.com/read/28542425/association-of-atg16l1-gene-haplotype-with-inflammatory-bowel-disease-in-indians
#13
Srinivasan Pugazhendhi, Kirankumar Baskaran, Srikanth Santhanam, Balakrishnan S Ramakrishna
Inflammatory bowel disease (IBD) is characterized by multigenic inheritance. Defects in autophagy related genes are considered to show genetic heterogeneity between populations. We evaluated the association of several single nucleotide polymorphisms (SNPs) in the autophagy related 16 like 1 (ATG16L1) gene with IBD in Indians. The ATG16L1 gene was genotyped for ten different SNPs using DNA extracted from peripheral blood of 234 patients with Crohn's disease (CD), 249 patients with ulcerative colitis (UC) and 393 healthy controls The SNPs rs2241880, rs4663396, rs3792106, rs10210302, rs3792109, rs2241877, rs6737398, rs11682898, rs4663402 and rs4663421 were genotyped using the Sequenom MassArray platform...
2017: PloS One
https://www.readbyqxmd.com/read/28542269/the-small-molecule-kinase-inhibitor-d11-counteracts-17-aag-mediated-up-regulation-of-hsp70-in-brain-cancer-cells
#14
Susanne Schaefer, Tina H Svenstrup, Barbara Guerra
Many types of cancer express high levels of heat shock proteins (HSPs) that are molecular chaperones regulating protein folding and stability ensuring protection of cells from potentially lethal stress. HSPs in cancer cells promote survival, growth and spreading even in situations of growth factors deprivation by associating with oncogenic proteins responsible for cell transformation. Hence, it is not surprising that the identification of potent inhibitors of HSPs, notably HSP90, has been the primary research focus, in recent years...
2017: PloS One
https://www.readbyqxmd.com/read/28542236/sphingolipids-as-a-new-factor-in-the-pathomechanism-of-preeclampsia-mass-spectrometry-analysis
#15
Karol Charkiewicz, Joanna Goscik, Agnieszka Blachnio-Zabielska, Grzegorz Raba, Agata Sakowicz, Jaroslaw Kalinka, Adrian Chabowski, Piotr Laudanski
OBJECTIVE(S) AND DESIGN: The aim of the study was to analyse a panel of 11 sphingolipids in plasma and three blood fractions (platelet-poor plasma, platelets and red blood cells) of women with mild preeclampsia. MATERIALS AND METHODS: We recruited 21 women between 25-40 weeks gestation with diagnosed mild preeclampsia to the study group and 36 healthy women with uncomplicated pregnancies, who corresponded with the study group according to gestational age, to the control group...
2017: PloS One
https://www.readbyqxmd.com/read/28542134/phosphorylated-cav1-activates-autophagy-through-an-interaction-with-becn1-under-oxidative-stress
#16
Jihoon Nah, Seung-Min Yoo, Sunmin Jung, Eun Il Jeong, Moonju Park, Bong-Kiun Kaang, Yong-Keun Jung
CAV1/Caveolin1, an integral membrane protein, is involved in caveolae function and cellular signaling pathways. Here, we report that CAV1 is a positive regulator of autophagy under oxidative stress and cerebral ischemic injury. Treatment with hydrogen peroxide enhanced autophagy flux and caused the localization of BECN1 to the mitochondria, whereas these changes were impaired in the absence of CAV1. Among many autophagy signals, only LC3 foci formation in response to hydrogen peroxide was abolished by CAV1 deficiency...
May 25, 2017: Cell Death & Disease
https://www.readbyqxmd.com/read/28540657/uch-l1-inhibition-suppresses-tau-aggresome-formation-during-proteasomal-impairment
#17
Quntao Yu, Hongmao Zhang, Yuan Li, Chao Liu, Shaohui Wang, Xiaomei Liao
In conditions of proteasomal impairment, the damaged or misfolded proteins, collectively known as aggresome, can accumulate in the perinuclear space and be subsequently eliminated by autophagy. Abnormal aggregation of microtubule-associated protein tau in the cytoplasm is a common neuropathological feature of tauopathies. The deficiency in ubiquitin carboxy-terminal hydrolase L1 (UCH-L1), a proteasomal deubiquitinating enzyme, is closely related to tau aggregation; however, the associated mechanisms remain unclear...
May 24, 2017: Molecular Neurobiology
https://www.readbyqxmd.com/read/28540646/the-molecular-mechanism-of-glucagon-like-peptide-1-therapy-in-alzheimer-s-disease-based-on-a-mechanistic-target-of-rapamycin-pathway
#18
Lin Li
The mechanistic target of rapamycin (mTOR) is an important molecule that connects aging, lifespan, energy balance, glucose and lipid metabolism, and neurodegeneration. Rapamycin exerts effects in numerous biological activities via its target protein, playing a key role in energy balance, regulation of autophagy, extension of lifespan, immunosuppression, and protection against neurodegeneration. There are many similar pathophysiological processes and molecular pathways between Alzheimer's disease (AD) and type 2 diabetes mellitus (T2DM), and pharmacologic agents used to treat T2DM, including glucagon-like peptide-1 (GLP-1) analogs, seem to be beneficial for AD...
May 24, 2017: CNS Drugs
https://www.readbyqxmd.com/read/28540642/plasma-and-white-blood-cells-show-different-mirna-expression-profiles-in-parkinson-s-disease
#19
Christine Schwienbacher, Luisa Foco, Anne Picard, Eloina Corradi, Alice Serafin, Jörg Panzer, Stefano Zanigni, Hagen Blankenburg, Maurizio F Facheris, Giulia Giannini, Marika Falla, Pietro Cortelli, Peter P Pramstaller, Andrew A Hicks
Parkinson's disease (PD) diagnosis is based on the assessment of motor symptoms, which manifest when more than 50% of dopaminergic neurons are degenerated. To date, no validated biomarkers are available for the diagnosis of PD. The aims of the present study are to evaluate whether plasma and white blood cells (WBCs) are interchangeable biomarker sources and to identify circulating plasma-based microRNA (miRNA) biomarkers for an early detection of PD. We profiled plasma miRNA levels in 99 L-dopa-treated PD patients from two independent data collections, in ten drug-naïve PD patients, and in unaffected controls matched by sex and age...
May 24, 2017: Journal of Molecular Neuroscience: MN
https://www.readbyqxmd.com/read/28540288/recent-insights-into-the-role-of-unfolded-protein-response-in-er-stress-in-health-and-disease
#20
REVIEW
Dan Lindholm, Laura Korhonen, Ove Eriksson, Sulev Kõks
Unfolded stress response (UPR) is a conserved cellular pathway involved in protein quality control to maintain homeostasis under different conditions and disease states characterized by cell stress. Although three general schemes of and genes induced by UPR are rather well-established, open questions remain including the precise role of UPR in human diseases and the interactions between different sensor systems during cell stress signaling. Particularly, the issue how the normally adaptive and pro-survival UPR pathway turns into a deleterious process causing sustained endoplasmic reticulum (ER) stress and cell death requires more studies...
2017: Frontiers in Cell and Developmental Biology
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