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https://www.readbyqxmd.com/read/29793165/inhibition-of-acetaminophen-induced-hepatotoxicity-in-mice-by-exogenous-thymosin%C3%AE-4-treatment
#1
Lei Wang, Xiankui Li, Cai Chen
OBJECTIVE: To study the effects of exogenous thymosinβ4 (Tβ4) treatment in acetaminophen (APAP)-induced hepatotoxicity. METHODS: Liver injury was induced in mice by a single intraperitoneal injection of APAP (500 mg/kg). Exogenous Tβ4 was intraperitoneally administrated at 0 h, 2 h and 4 h after APAP injection. Chloroquine (CQ) (60 mg/kg) was intraperitoneally injected 2 h before APAP administration to inhibit autophagy. Six hours after APAP injection liver injury was evaluated by histological examinations, biochemical measurements and enzyme linked immunosorbent assay (ELISAs)...
May 21, 2018: International Immunopharmacology
https://www.readbyqxmd.com/read/29792860/diphenyleneiodonium-enhances-oxidative-stress-and-inhibits-japanese-encephalitis-virus-induced-autophagy-and-er-stress-pathways
#2
Manish Sharma, Kiran Bala Sharma, Shailendra Chauhan, Sankar Bhattacharyya, Sudhanshu Vrati, Manjula Kalia
Diphenyleneiodonium (DPI) and N-acetyl-L-cysteine (NAC), two widely used anti-oxidants, were employed to evaluate the role of oxidative stress in Japanese encephalitis virus (JEV) induced autophagy, stress responses and replication. DPI and NAC exerted opposite effects on ROS levels in JEV infected mouse neuronal cells (Neuro2a), mouse embryonic fibroblasts (MEFs) and human epithelial cells (HeLa). While NAC effectively quenched ROS, DPI enhanced ROS levels, suggesting that DPI induces oxidative stress in JEV infected cells...
May 21, 2018: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/29792848/subthalamic-nucleus-deep-brain-stimulation-protects-neurons-by-activating-autophagy-via-pp2a-inactivation-in-a-rat-model-of-parkinson-s-disease
#3
Ting-Ting Du, Ying-Chuan Chen, Yong-Quan Lu, Fan-Gang Meng, Hui Yang, Jian-Guo Zhang
Deep brain stimulation (DBS) of the subthalamic nucleus (STN) is an effective therapeutic strategy for alleviating disability in patients with moderate to severe Parkinson's disease (PD). Preclinical studies have shown that stimulation of the rat STN can protect against nigral dopaminergic neuron loss. However, the underlying mechanism is unclear. To investigate the molecular basis of the neuroprotective effects of STN stimulation, a rat model of PD was established by unilaterally injecting 6-hydroxydopamine (6-OHDA) into the striatum...
May 21, 2018: Experimental Neurology
https://www.readbyqxmd.com/read/29792687/co-mobility-of-gabarap-and-phosphatidylinositol-4-kinase-2a-on-cytoplasmic-vesicles
#4
Yan Chen, Hui-Qiao Sun, John P Eichorst, Joseph P Albanesi, Helen Yin, Joachim D Mueller
We previously reported that recruitment of the Type IIA phosphatidylinositol 4-kinase (PI4K2A) to autophagosomes by GABARAP, a member of the Atg8 family of autophagy-related proteins, is important for autophagosome-lysosome fusion. Because both PI4K2A and GABARAP have also been implicated in the intracellular trafficking of plasma membrane receptors in the secretory/endocytic pathway, we characterized their interaction in cells under non-autophagic conditions. Fluorescence fluctuation spectroscopy measurements revealed that GABARAP exists predominantly as a cytosolic monomer in live cells, but is recruited to small cytoplasmic vesicles upon overexpression of PI4K2A...
May 24, 2018: Biochemistry
https://www.readbyqxmd.com/read/29792388/cerebral-ischaemia-reperfusion-injury-could-be-managed-by-using-tramadol
#5
Ibrahim Akkurt, Cansel Cetin, Ahmet Melih Erdogan, Gungor Cagdas Dincel, Aslı Fahriye Ceylan, Ucler Kisa, Jonathan Oppong, Adem Akkurt, Mustafa Ogden, Bulent Bakar
OBJECTIVES: No valid treatment modality that will repair stroke damage and provide neurological recovery has yet been identified in literature. Studies demonstrated that adequate quality of life could be provided if post-stroke pain could be treated sufficiently and timely. Besides its pain relief effects, tramadol has oedema-reducing and anti-inflammatory properties. With these in mind, this study investigated the influence of tramadol in acute and/or chronic ischaemia/reperfusion (I/R) injury...
May 24, 2018: Neurological Research
https://www.readbyqxmd.com/read/29792365/protective-effects-of-piceatannol-on-methylglyoxal-induced-cytotoxicity-in-mc3t3-e1-osteoblastic-cells
#6
Kwang Sik Suh, Suk Chon, Eun Mi Choi
Methylglyoxal (MG) is a reactive α-oxoaldehyde that increases under diabetic conditions and subsequently contributes to the complications associated with this disease. Piceatannol is a naturally occurring analogue of resveratrol that possesses multiple biological functions. The present study investigated the effects of piceatannol on MG-induced cytotoxicity in MC3T3-E1 osteoblastic cells. Piceatannol significantly restored MG-induced reductions in cell viability and reduced lactate dehydrogenase release in MG-treated MC3T3-E1 osteoblastic cells, which suggests that it suppressed MG-induced cytotoxicity...
June 2018: Free Radical Research
https://www.readbyqxmd.com/read/29792337/titanium-dioxide-nanoparticles-induce-in-vitro-autophagy
#7
X Dai, R Liu, N Li, J Yi
AIM: Concerns about the possible toxicity to environment and human health of titanium dioxide nanoparticles (TiO2 NPs) are increasing. The aim of this study was to investigate the relationship between toxicology and autophage in vitro. METHODS: RAW 264.7 cells were exposed to five concentrations (50, 100, 200, 300, and 400 μg/mL) and two particle size of TiO2 NPs (30 and 100 nm) for 24 h. RESULTS: The results showed that TiO2 NPs decreased cell viability, phagocytic rate, and phagocytic index in a concentration-dependent manner, thereby inducing autophagy...
January 1, 2018: Human & Experimental Toxicology
https://www.readbyqxmd.com/read/29791862/hormone-dependent-breast-cancer-targeting-autophagy-and-pi3k-overcomes-exemestane-acquired-resistance
#8
Cristina Amaral, Tiago Vieira Augusto, Elisiário Tavares-da-Silva, Fernanda M F Roleira, Georgina Correia-da-Silva, Natércia Teixeira
The leading cause of cancer death in women around the world is breast cancer. The aromatase inhibitors (AIs) are considered a first-line treatment for estrogen receptor-positive (ER+ ) breast tumors, in postmenopausal women. Exemestane (Exe) is a powerful steroidal AI, however, despite its therapeutic success, Exe-acquired resistance may occur leading to tumor relapse. Our group previously demonstrated that autophagy acts as a pro-survival process in Exe-induced cell death of ER+ sensitive breast cancer cells...
May 20, 2018: Journal of Steroid Biochemistry and Molecular Biology
https://www.readbyqxmd.com/read/29791858/a-multi-layered-quantitative-in-vivo-expression-atlas-of-the-podocyte-unravels-kidney-disease-candidate-genes
#9
Markus M Rinschen, Markus Gödel, Florian Grahammer, Stefan Zschiedrich, Martin Helmstädter, Oliver Kretz, Mostafa Zarei, Daniela A Braun, Sebastian Dittrich, Caroline Pahmeyer, Patricia Schroder, Carolin Teetzen, HeonYung Gee, Ghaleb Daouk, Martin Pohl, Elisa Kuhn, Bernhard Schermer, Victoria Küttner, Melanie Boerries, Hauke Busch, Mario Schiffer, Carsten Bergmann, Marcus Krüger, Friedhelm Hildebrandt, Joern Dengjel, Thomas Benzing, Tobias B Huber
Damage to and loss of glomerular podocytes has been identified as the culprit lesion in progressive kidney diseases. Here, we combine mass spectrometry-based proteomics with mRNA sequencing, bioinformatics, and hypothesis-driven studies to provide a comprehensive and quantitative map of mammalian podocytes that identifies unanticipated signaling pathways. Comparison of the in vivo datasets with proteomics data from podocyte cell cultures showed a limited value of available cell culture models. Moreover, in vivo stable isotope labeling by amino acids uncovered surprisingly rapid synthesis of mitochondrial proteins under steady-state conditions that was perturbed under autophagy-deficient, disease-susceptible conditions...
May 22, 2018: Cell Reports
https://www.readbyqxmd.com/read/29791786/matrine-suppresses-kras-driven-pancreatic-cancer-growth-by-inhibiting-autophagy-mediated-energy-metabolism
#10
Young-Ra Cho, Ji Hyeon Lee, Ji Hye Kim, So-Yeon Lee, Suna Yoo, Min-Kyo Jung, Su Jung Kim, Hyun Ju Yoo, Chang-Gi Pack, Jin Kyung Rho, Jaekyoung Son
Matrine is a natural compound extracted from the herb Sophora flavescens Ait which is widely used in traditional Chinese medicine for treating various diseases. Recently, matrine was reported to have antitumor effects against a variety of cancers without any obvious side effects; however, the molecular mechanisms of its antiproliferative effects on cancer are unclear. Here, we report that matrine inhibits autophagy-mediated energy metabolism, which is necessary for pancreatic cancer growth. We found that matrine significantly reduces pancreatic cancer growth in vitro and in vivo by insufficiently maintaining mitochondrial metabolic function and energy level...
May 23, 2018: Molecular Oncology
https://www.readbyqxmd.com/read/29791506/shmt2-and-the-brcc36-brisc-deubiquitinase-regulate-hiv-1-tat-k63-ubiquitylation-and-destruction-by-autophagy
#11
Muyu Xu, James J Moresco, Max Chang, Amey Mukim, Davey Smith, Jolene K Diedrich, John R Yates, Katherine A Jones
HIV-1 Tat is a key regulator of viral transcription, however little is known about the mechanisms that control its turnover in T cells. Here we use a novel proteomics technique, called DiffPOP, to identify the molecular target of JIB-04, a small molecule compound that potently and selectively blocks HIV-1 Tat expression, transactivation, and virus replication in T cell lines. Mass-spectrometry analysis of whole-cell extracts from 2D10 Jurkat T cells revealed that JIB-04 targets Serine Hydroxymethyltransferase 2 (SHMT2), a regulator of glycine biosynthesis and an adaptor for the BRCC36 K63Ub-specific deubiquitinase in the BRISC complex...
May 23, 2018: PLoS Pathogens
https://www.readbyqxmd.com/read/29790300/aspiration-pneumonia-induces-muscle-atrophy-in-the-respiratory-skeletal-and-swallowing-systems
#12
Riyo Komatsu, Tatsuma Okazaki, Satoru Ebihara, Makoto Kobayashi, Yoko Tsukita, Mayumi Nihei, Hisatoshi Sugiura, Kaijun Niu, Takae Ebihara, Masakazu Ichinose
BACKGROUND: Repetition of the onset of aspiration pneumonia in aged patients is common and causes chronic inflammation. The inflammation induces proinflammatory cytokine production and atrophy in the muscles. The proinflammatory cytokines induce muscle proteolysis by activating calpains and caspase-3, followed by further degradation by the ubiquitin-proteasome system. Autophagy is another pathway of muscle atrophy. However, little is known about the relationship between aspiration pneumonia and muscle...
May 22, 2018: Journal of Cachexia, Sarcopenia and Muscle
https://www.readbyqxmd.com/read/29790198/the-role-of-lysosomes-and-autophagosomes-in-frontotemporal-lobar-degeneration
#13
Hamish Dc Bain, Yvonne S Davidson, Andrew C Robinson, Sarah Ryan, Sara Rollinson, Anna Richardson, Matthew Jones, Julie S Snowden, Stuart Pickering-Brown, David M A Mann
INTRODUCTION: Cell biological and genetic evidence implicates failures in degrading aggregating proteins, such as tau and TDP-43, through autophagy or lysosomal pathways in the pathogenesis of Frontotemporal Lobar degeneration (FTLD). METHODS: We investigated changes in degradative pathways in 60 patients with different pathological or genetic forms of FTLD employing immunohistochemistry for marker proteins such as Lysosomal Associated Membrane Proteins 1 (LAMP-1) and 2 (LAMP-2), Cathepsin D (CTSD) and microtubule-associated protein 1 light chain 3 alpha (LC3A)...
May 23, 2018: Neuropathology and Applied Neurobiology
https://www.readbyqxmd.com/read/29790111/potential-of-the-dual-mtor-kinase-inhibitor-azd2014-to-overcome-paclitaxel-resistance-in-anaplastic-thyroid-carcinoma
#14
Zorica Milošević, Jasna Banković, Jelena Dinić, Chrisiida Tsimplouli, Evangelia Sereti, Miodrag Dragoj, Verica Paunović, Zorka Milovanović, Marija Stepanović, Nikola Tanić, Kostantinos Dimas, Milica Pešić
PURPOSE: Anaplastic thyroid carcinoma (ATC) is an aggressive, chemo-resistant malignancy. Chemo-resistance is often associated with changes in activity of the RAS/MAPK/ERK and PI3K/AKT/mTOR pathways and/or a high expression of ATP binding cassette (ABC) transporters, such as P-glycoprotein (P-gp) and breast cancer resistance protein (BCRP). To assess the therapeutic efficacy in ATC of a combination of the dual mTOR kinase inhibitor vistusertib (AZD2014) and paclitaxel (PTX), we generated a new cell line (Rho-) via the selection of human thyroid carcinoma 8505C cells that exhibit a low accumulation of rhodamine 123, which serves as a P-gp and BCRP substrate...
May 22, 2018: Cellular Oncology (Dordrecht)
https://www.readbyqxmd.com/read/29790105/physostigmine-restores-impaired-autophagy-in-the-rat-hippocampus-after-surgery-stress-and-lps-treatment
#15
Clarissa von Haefen, Marco Sifringer, Stefanie Endesfelder, Alexander Kalb, Adrián González-López, Annalena Tegethoff, Nadine Paeschke, Claudia D Spies
Tissue damage and pathogen invasion during surgical trauma have been identified as contributing factors leading to neuroinflammation in the hippocampus, which can be protected by stimulation of the cholinergic anti-inflammatory pathway using the acetylcholinesterase inhibitor physostigmine. Macroautophagy, an intracellular degradation pathway used to recycle and eliminate damaged proteins and organelles by lysosomal digestion, seems to be important for cell survival under stress conditions. This study aimed to examine the role of autophagy in physostigmine-mediated hippocampal cell protection in a rat model of surgery stress...
May 22, 2018: Journal of Neuroimmune Pharmacology: the Official Journal of the Society on NeuroImmune Pharmacology
https://www.readbyqxmd.com/read/29789637/the-proton-pump-inhibitor-pantoprazole-disrupts-protein-degradation-systems-and-sensitizes-cancer-cells-to-death-under-various-stresses
#16
Yu Cao, Min Chen, Dehua Tang, Hongli Yan, Xiwei Ding, Fan Zhou, Mingming Zhang, Guifang Xu, Weijie Zhang, Shu Zhang, Yuzheng Zhuge, Lei Wang, Xiaoping Zou
Proton pump inhibitors (PPIs) play a role in antitumor activity, with studies showing specialized impacts of PPIs on cancer cell apoptosis, metastasis, and autophagy. In this study, we demonstrated that pantoprazole (PPI) increased autophagosomes formation and affected autophagic flux depending on the pH conditions. PPI specifically elevated SQSTM1 protein levels by increasing SQSTM1 transcription via NFE2L2 activation independent of the specific effect of PPI on autophagic flux. Via decreasing proteasome subunits expression, PPI significantly impaired the function of the proteasome, accompanied by the accumulation of undegraded poly-ubiquitinated proteins...
May 22, 2018: Cell Death & Disease
https://www.readbyqxmd.com/read/29789603/vorinostat-and-quinacrine-have-synergistic-effects-in-t-cell-acute-lymphoblastic-leukemia-through-reactive-oxygen-species-increase-and-mitophagy-inhibition
#17
Bo Jing, Jin Jin, Rufang Xiang, Meng Liu, Li Yang, Yin Tong, Xinhua Xiao, Hu Lei, Wei Liu, Hanzhang Xu, Jiong Deng, Li Zhou, Yingli Wu
Despite recent progress in the treatment, the outcome of adult acute T-cell lymphoblastic leukemia (T-ALL) is poor. Development of novel approach to combat this disease is urgently required. Vorinostat, a pan-histone deacetylase (HDAC) inhibitor, exerts promising anticancer activity in a variety of solid and hematologic malignancies. However, the efficacy of vorinostat monotherapy is unsatisfactory. Here, we show that quinacrine (QC), an anti-malaria drug with potent autophagy inhibitory activity, could synergistically enhance vorinostat-induced cell death at a non-toxic concentration...
May 22, 2018: Cell Death & Disease
https://www.readbyqxmd.com/read/29789598/autophagy-promotes-the-survival-of-dormant-breast-cancer-cells-and-metastatic-tumour-recurrence
#18
Laura Vera-Ramirez, Suman K Vodnala, Ryan Nini, Kent W Hunter, Jeffrey E Green
Cancer recurrence after initial diagnosis and treatment is a major cause of breast cancer (BC) mortality, which results from the metastatic outbreak of dormant tumour cells. Alterations in the tumour microenvironment can trigger signalling pathways in dormant cells leading to their proliferation. However, processes involved in the initial and the long-term survival of disseminated dormant BC cells remain largely unknown. Here we show that autophagy is a critical mechanism for the survival of disseminated dormant BC cells...
May 22, 2018: Nature Communications
https://www.readbyqxmd.com/read/29789559/transcriptional-and-epigenetic-modulation-of-autophagy-promotes-ebv-oncoprotein-ebna3c-induced-b-cell-survival
#19
Shaoni Bhattacharjee, Priyanka Bose, Krishna Patel, Shatadru Ghosh Roy, Chandrima Gain, Harsha Gowda, Erle S Robertson, Abhik Saha
Epstein-Barr virus (EBV) oncoprotein EBNA3C is indispensable for primary B-cell transformation and maintenance of lymphoblastoid cells outgrowth. EBNA3C usurps two putative cellular pathways-cell-cycle and apoptosis, essentially through modulating ubiquitin-mediated protein-degradation or gene transcription. In cancer cells, these two pathways are interconnected with autophagy,-a survival-promoting catabolic network in which cytoplasmic material including mis/un-folded protein aggregates and damaged organelles along with intracellular pathogens are degraded and recycled in lysosomal compartments...
May 22, 2018: Cell Death & Disease
https://www.readbyqxmd.com/read/29789435/molecular-mechanisms-preventing-senescence-in-response-to-prolonged-darkness-in-a-desiccation-tolerant-plant
#20
Meriem Durgud, Saurabh Gupta, Ivan Ivanov, Amin Omidbakhshfard, Maria Benina, Saleh Alseekh, Nikola Staykov, Mareike Hauenstein, Paul Dijkwel, Stefan Hörtensteiner, Valentina Toneva, Yariv Brotman, Alisdair R Fernie, Bernd Mueller-Roeber, Tsanko Gechev
The desiccation-tolerant plant Haberlea rhodopensis can withstand months of darkness without any visible senescence. Here, we investigated the molecular mechanisms of this adaptation to prolonged (30 days) darkness and subsequent return to light. H. rhodopensis plants remained green and viable throughout the dark treatment. Transcriptomic analysis revealed that darkness regulated several transcription factor (TF) genes. Stress- and autophagy-related TFs such as ERF8, HSFA2b, RD26, TGA1, and WRKY33 were upregulated, while chloroplast- and flowering-related TFs such as ATH1, COL2, COL4, RL1, and PTAC7 were repressed...
May 22, 2018: Plant Physiology
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