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https://www.readbyqxmd.com/read/28441070/the-thr300ala-variant-of-atg16l1-is-associated-with-decreased-risk-of-brain-metastasis-in-patients-with-non-small-cell-lung-cancer
#1
Qian-Xia Li, Xiao Zhou, Ting-Ting Huang, Yang Tang, Bo Liu, Ping Peng, Li Sun, Yi-Hua Wang, Xiang-Lin Yuan
Non-small cell lung cancer (NSCLC) often metastasizes to the brain, but identifying which patients will develop brain metastases (BM) is difficult. Macroautophagy/autophagy is critical for cancer initiation and progression. We hypothesized that genetic variants of autophagy-related genes may affect brain metastases (BM) in NSCLC patients. We genotyped 16 single nucleotide polymorphisms (SNPs) in 7 autophagy-related (ATG) genes (ATG3, ATG5, ATG7, ATG10, ATG12, ATG16L1, and MAP1LC3/LC3) by using DNA from blood samples of 323 NSCLC patients...
April 25, 2017: Autophagy
https://www.readbyqxmd.com/read/28439929/the-roles-of-autophagy-and-hypoxia-in-human-inflammatory-periapical-lesions
#2
H Y Huang, W C Wang, P Y Lin, C P Huang, C Y Chen, Y K Chen
AIM: To determine the expressions of hypoxia-related [hypoxia-inducible transcription factors (HIF)-1α, BCL2/adenovirus E1B 19 kDa protein-interacting protein 3 (BNIP3), and phospho-adenosine monophosphate activated protein kinase (pAMPK)] and autophagy-related [microtubule-associated protein 1 light chain 3 (LC3), beclin-1 (BECN-1), autophagy-related gene (Atg)5-12, and p62] proteins in human inflammatory periapical lesions. METHODOLOGY: Fifteen samples of radicular cysts (RCs) and 21 periapical granulomas (PGs), combined with 17 healthy dental pulp tissues were examined...
April 25, 2017: International Endodontic Journal
https://www.readbyqxmd.com/read/28428343/mechanisms-of-autophagy-induction-by-sex-steroids-in-bovine-mammary-epithelial-cells
#3
Katarzyna Zielniok, Agnieszka Sobolewska, Malgorzata Gajewska
In dairy cattle mammary gland involution serves to remodel the secretory tissue, and occurs in a period of overlap between mammogenic stimulation caused by next developing pregnancy and tissue regression induced by milk stasis. At this time high concentrations of 17β-estradiol (E2) and progesterone (P4) support regeneration of the mammary tissue, as well as enhance autophagy, a cellular process induced in response to stressful conditions for energy generation and homeostasis maintenance. This study aimed to elucidate the mechanisms of autophagy induction by E2 and P4 using an in vitro model of involution based on 20-fold reduction of FBS content (from 10% to 0...
April 20, 2017: Journal of Molecular Endocrinology
https://www.readbyqxmd.com/read/28423666/negative-lc3b-immunoreactivity-in-cancer-cells-is-an-independent-prognostic-predictor-of-prostate-cancer-specific-death
#4
Ashkan Mortezavi, Souzan Salemi, Niels J Rupp, Jan Hendrik Rüschoff, Thomas Hermanns, Cedric Poyet, Marco Randazzo, Hans-Uwe Simon, Holger Moch, Tullio Sulser, Peter Wild, Daniel Eberli
BACKGROUND: Autophagy is a catabolic cellular process used for degradation of cytoplasmic organelles and preservation of cell viability. In this study we aimed to analyse the level of autophagy markers in benign and malignant prostate tissue and to evaluate the prognostic properties for patients with prostate cancer (PCa). RESULTS: LC3b expression was significantly upregulated in PCa, especially in metastatic and castration-resistant PCa samples compared to benign prostate tissue (p<0...
March 7, 2017: Oncotarget
https://www.readbyqxmd.com/read/28420437/bidirectional-nucleolar-dysfunction-in-c9orf72-frontotemporal-lobar-degeneration
#5
Sarah Mizielinska, Charlotte E Ridler, Rubika Balendra, Annora Thoeng, Nathan S Woodling, Friedrich A Grässer, Vincent Plagnol, Tammaryn Lashley, Linda Partridge, Adrian M Isaacs
An intronic GGGGCC expansion in C9orf72 is the most common known cause of both frontotemporal lobar degeneration (FTLD) and amyotrophic lateral sclerosis (ALS). The repeat expansion leads to the generation of sense and antisense repeat RNA aggregates and dipeptide repeat (DPR) proteins, generated by repeat-associated non-ATG translation. The arginine-rich DPR proteins poly(glycine-arginine or GR) and poly(proline-arginine or PR) are potently neurotoxic and can localise to the nucleolus when expressed in cells, resulting in enlarged nucleoli with disrupted functionality...
April 18, 2017: Acta Neuropathologica Communications
https://www.readbyqxmd.com/read/28419317/high-dose-and-high-frequency-lanreotide-autogel-in-acromegaly-a-randomized-multicenter-study
#6
Andrea Giustina, Gherardo Mazziotti, Salvatore Cannavò, Roberto Castello, Giorgio Arnaldi, Giovanna Bugari, Renato Cozzi, Diego Ferone, Anna Maria Formenti, Enza Gatti, Silvia Grottoli, Pietro Maffei, Filippo Maffezzoni, Marcella Montini, Massimo Terzolo, Ezio Ghigo
Context: The increase in drug frequency or dose is recommended for acromegaly patients with partial response to long-acting somatostatin receptor ligands (SRLs). However, the efficacy and safety data with lanreotide autogel (LAN-ATG) at high-dose (HD) or high-frequency (HF) are still scanty and anecdotal. Objective: To evaluate the biochemical efficacy and safety of HF- and HD LAN-ATG in patients with active acromegaly. Design: 24-week prospective, multicentre, randomized, open-label trial...
April 17, 2017: Journal of Clinical Endocrinology and Metabolism
https://www.readbyqxmd.com/read/28415024/glucocorticoids-differentially-regulate-the-innate-immune-responses-of-tlr4-and-the-cytosolic-dna-sensing-pathway
#7
Jinli Wang, Ruining Wang, Jiahui Yang, Xiaofan Yang, Shengfeng Hu, Hui Wang, Chaoying Zhou, Wenjing Xiong, Qian Wen, Li Ma
Glucocorticoids (GCs) are widely used to treat the chronic inflammatory disorders because of their powerful anti-inflammatory properties; however, their effects on macrophage-mediated immune responses are not completely understood. In the present study, we found that GCs decreased LPS-mediated TBK1 activation and the expression of IFN-β, RANTES and CXCL-10; however, poly(dA:dT)-induced TBK1 activity and cytokine expression were not affected by GCs treatment. Furthermore, GCs decreased the expression of key autophagy-related genes (ATGs), including ATG5, ATG7 and ATG12, and inhibited autophagy in macrophages after LPS stimulation...
April 14, 2017: International Immunopharmacology
https://www.readbyqxmd.com/read/28413119/the-two-dictyostelium-discoideum-autophagy-8-proteins-have-distinct-autophagic-functions
#8
Susanne Meßling, Jan Matthias, Qiuhong Xiong, Sarah Fischer, Ludwig Eichinger
Autophagy is a highly conserved cellular degradation pathway which is crucial for various cellular processes. The autophagic process is subdivided in the initiation, autophagosome maturation and lysosomal degradation phases and involves more than forty core and accessory autophagy-related (ATG) proteins. Autophagy 8 (ATG8, in mammals LC3) is a well-established marker of autophagy and is linked to the autophagic membrane from initiation until fusion with the lysosome. We generated single and double knock-out mutants of the two Dictyostelium paralogues, ATG8a and ATG8b, as well as strains that expressed RFP-ATG8a and/or GFP-ATG8b, RFP-ATG8b, RFP-GFP-ATG8a or RFP-GFP-ATG8b in different knock-out mutants...
April 4, 2017: European Journal of Cell Biology
https://www.readbyqxmd.com/read/28411887/from-christian-de-duve-to-yoshinori-ohsumi-more%C3%A2-to-autophagy-than-just-dining-at-home
#9
REVIEW
Margaret M Harnett, Miguel A Pineda, Perle Latré de Laté, Russell J Eason, Sébastien Besteiro, William Harnett, Gordon Langsley
Christian de Duve first coined the expression "autophagy" during his seminal work on the discovery of lysosomes, which led to him being awarded the Nobel Prize in Physiology or Medicine in 1974. The term was adopted to distinguish degradation of intracellular components from the uptake and degradation of extracellular substances that he called "heterophagy". Studies until the 1990s were largely observational/morphological-based until in 1993 Yoshinori Oshumi described a genetic screen in yeast undergoing nitrogen deprivation that led to the isolation of autophagy-defective mutants now better known as ATG (AuTophaGy-related) genes...
February 2017: Biomedical Journal
https://www.readbyqxmd.com/read/28411883/horning-cell-self-digestion-autophagy-wins-the%C3%A2-2016-nobel-prize-in-physiology-or-medicine
#10
EDITORIAL
Po-Yuan Ke
Autophagy is an evolutionarily conserved process by which eukaryotic cells eliminate intracellular components via the lysosomal degradation process. This cell self-digestion process was first discovered and morphologically characterized in the late 1950s and early 1960s. The genetic screen studies in baker's yeast in the 1990s further identified the essential genes functioning in the autophagic process. In the past two decades, the detailed molecular process involved in the completion of autophagy was delineated...
February 2017: Biomedical Journal
https://www.readbyqxmd.com/read/28410195/antagonistic-effects-of-selenium-on-lead-induced-autophagy-by-influencing-mitochondrial-dynamics-in-the-spleen-of-chickens
#11
Yujing Han, Chunqiu Li, Mingjun Su, Zhihui Wang, Ning Jiang, Dongbo Sun
Lead (Pb) may damage the immune function in human and animal. Selenium (Se) has antagonistic effects on Pb. In our study, brown layer chickens were randomly allocated to control group, Se group (1 mg/kg Se), Se+Pb group (1 mg/kg Se and 350 mg/kg Pb), and Pb group (350 mg/kg Pb). The chickens were sacrificed on the 90th day; spleen tissues were subjected to observation of ultrastructure and detection of spleen-related indexes. The results revealed that in the Pb group, expression levels of the cytokines IL-1 and TNF-α significantly increased, and expression levels of IL-2 and INF-γ significantly decreased; activities of antioxidant enzyme GPX, SOD and CAT significantly decreased, and expression level of malondialdehyde (MDA) significantly increased; expression levels of mitochondrial fission-related genes (Mff and Drp1) significantly increased, and expression levels of mitochondrial fusion-related genes (Opa1, Mfn1 and Mfn2) significantly decreased; expression of autophagy-related genes (Beclin 1, Dynein, Atg 5, LC3-I and LC-II) was upregulated, while expression of mammalian target of rapamycin (mTOR) was downregulated...
March 31, 2017: Oncotarget
https://www.readbyqxmd.com/read/28409999/histone-hist1h1c-h1-2-regulates-autophagy-in-the-development-of-diabetic-retinopathy
#12
Wenjun Wang, Qing Wang, Danyang Wan, Yue Sun, Lin Wang, Hong Chen, Chengyu Liu, Robert B Petersen, Jianshuang Li, Weili Xue, Ling Zheng, Kun Huang
Autophagy plays critical and complex roles in many human diseases, including diabetes and its complications. However, the role of autophagy in the development of diabetic retinopathy remains uncertain. Core histone modifications have been reported involved in the development of diabetic retinopathy, but little is known about the histone variants. Here, we observed increased autophagy and histone HIST1H1C/H1.2, an important variant of the linker histone H1, in the retinas of type 1 diabetic rodents. Overexpression of histone HIST1H1C upregulates SIRT1 and HDAC1 to maintain the deacetylation status of H4K16, leads to upregulation of ATG proteins, then promotes autophagy in cultured retinal cell line...
March 2, 2017: Autophagy
https://www.readbyqxmd.com/read/28408137/4-acetylantroquinonol-b-suppresses-autophagic-flux-and-improves-cisplatin-sensitivity-in-highly-aggressive-epithelial-cancer-through-the-pi3k-akt-mtor-p70s6k-signaling-pathway
#13
Mingche Liu, Oluwaseun Adebayo Bamodu, Wen-Chien Huang, Muhammad Ary Zucha, Yen-Kuang Lin, Alexander T H Wu, Chun-Chih Huang, Wei-Hwa Lee, Chiou-Chung Yuan, M Hsiao, Li Deng, Yew-Min Tzeng, Chi-Tai Yeh
Targeting residual self-renewing, chemoresistant cancerous cells may represent the key to overcoming therapy resistance. The entry of these quiescent cells into an activated state is associated with high metabolic demand and autophagic flux. Therefore, modulating the autophagy pathway in aggressive carcinomas may be beneficial as a therapeutic modality. In this study, we evaluated the anti-tumor activities of 4-acetylantroquinonol B (4-AAQB) in chemoresistant ovarian cancer cells, particularly its ability to modulate autophagy through autophagy-related genes (Atg)...
April 10, 2017: Toxicology and Applied Pharmacology
https://www.readbyqxmd.com/read/28399862/chitosan-nanoparticle-mediated-co-delivery-of-shatg-5-and-gefitinib-synergistically-promoted-the-efficacy-of-chemotherapeutics-through-the-modulation-of-autophagy
#14
Yan Zheng, Chang Su, Liang Zhao, Yijie Shi
BACKGROUND: Autophagy reportedly plays vital and complex roles in many diseases. During times of starvation or energy deficiency, autophagy will occur at higher levels to provide cells with the nutrients or energy necessary to survive in stressful conditions. Some anti-cancer drugs induce protective autophagy and reduce cell apoptosis. Autophagy can adversely affect apoptosis, and blocking autophagy will increase the sensitivity of cells to apoptosis signals. METHODS: We designed chitosan nanoparticles (NPs) to promote the co-delivery of gefitinib (an anti-cancer drug) and shRNA-expressing plasmid DNA that targets the Atg-5 gene (shAtg-5) as an autophagy inhibitor to improve anti-cancer effects and autophagy mediation...
April 11, 2017: Journal of Nanobiotechnology
https://www.readbyqxmd.com/read/28396953/autologous-hematopoietic-stem-cell-transplantation-in-relapsing-remitting-multiple-sclerosis-comparison-with-secondary-progressive-multiple-sclerosis
#15
Bonaventura Casanova, Isidro Jarque, Francisco Gascón, Juan Carlos Hernández-Boluda, Francisco Pérez-Miralles, Javier de la Rubia, Carmen Alcalá, Jaime Sanz, Javier Mallada, Angeles Cervelló, Arantxa Navarré, María Carcelén-Gadea, Isabel Boscá, Sara Gil-Perotin, Carlos Solano, Miguel Angel Sanz, Francisco Coret
The main objective of our work is to describe the long-term results of myeloablative autologous hematopoietic stem cell transplant (AHSCT) in multiple sclerosis patients. Patients that failed to conventional therapies for multiple sclerosis (MS) underwent an approved protocol for AHSCT, which consisted of peripheral blood stem cell mobilization with cyclophosphamide and granulocyte colony-stimulating factor (G-CSF), followed by a conditioning regimen of BCNU, Etoposide, Ara-C, Melphalan IV, plus Rabbit Thymoglobulin...
April 10, 2017: Neurological Sciences
https://www.readbyqxmd.com/read/28395546/post-transplant-cyclophosphamide-a-promising-anti-graft-versus-host-disease-prophylaxis-where-do-we-stand
#16
Alberto Mussetti, Raffaella Greco, Jacopo Peccatori, Paolo Corradini
Post transplant cyclophosphamide (PT/Cy) in association to other immunosuppressive agents or alone has emerged as a promising pharmacological strategy in the setting of allogeneic hematopoietic cell transplant (allo-HCT). Its safety profile and effectiveness in reducing GvHD (acute GvHD incidence comprised between 15 and 30%, chronic GvHD 20-30% in the haploidentical setting) contributed to the spreading of this technique all over the world. Areas covered: This review summarizes the use of PT/Cy in the setting of allo-HCT, both for oncological and non-malignant hematological diseases...
April 11, 2017: Expert Review of Hematology
https://www.readbyqxmd.com/read/28390983/allogeneic-stem-cell-transplantation-for-relapsed-refractory-b-cell-lymphomas-results-of-a-multicenter-phase-ii-prospective-trial-including-rituximab-in-the-reduced-intensity-conditioning-regimen
#17
Anna Dodero, Francesca Patriarca, Giuseppe Milone, Barbara Sarina, Rosalba Miceli, Anna Iori, Francesco Barretta, Elisabetta Terruzzi, Alberto Mussetti, Massimo Pini, Alberto Bosi, Alida Dominietto, Nicola Cascavilla, Francesco Onida, Franco Narni, Lucia Farina, Alessandro Rambaldi, Paolo Corradini
The treatment of patients with refractory/relapsed B-Cell non-Hodgkin lymphoma (NHL) is evolving due to the availability of novel drugs. Allogeneic stem cell transplantation (alloSCT) can be curative, but its morbidity and mortality remain a matter of concern. We conducted a multicentre prospective phase II trial to evaluate the benefit of including only one dose of Rituximab (R) in the conditioning regimen before alloSCT. The primary end-point was progression-free survival. The study enrolled 121 patients with relapsed/refractory B-cell lymphomas...
April 5, 2017: Biology of Blood and Marrow Transplantation
https://www.readbyqxmd.com/read/28389319/in-vitro-immunoregulatory-effects-of-thymoglobulin-on-human-immune-cell-subpopulations
#18
Maja Buszko, Bojana Jakic, Christian Ploner, Paul Hoertnagl, Christina Mayerl, Georg Wick, Giuseppe Cappellano
Thymoglobulin (ATG) is a polyclonal rabbit antibody against human thymocytes used as a T cell-depleting agent in organ transplantation. Its polyclonal character suggests that its effect may go far beyond just T cell depletion. The aim of this study was to further elucidate possible mechanisms underlying the suppressive activity of ATG. For in vitro studies, human peripheral blood mononuclear cells (PBMC) were incubated with ATG or control Ig for various time points. Foxp3(+) regulatory cells (Tregs) and monocytes were phenotypically analyzed by flow cytometry and functionally tested by in vitro suppression assays...
April 4, 2017: Immunology Letters
https://www.readbyqxmd.com/read/28388905/biodistribution-of-arctigenin-loaded-nanoparticles-designed-for-multimodal-imaging
#19
Qingxin Cui, Yuanyuan Hou, Yanan Wang, Xu Li, Yang Liu, Xiaoyao Ma, Zengyong Wang, Weiya Wang, Jin Tao, Qian Wang, Min Jiang, Dongyan Chen, Xizeng Feng, Gang Bai
BACKGROUND: Tracking targets of natural products is one of the most challenging issues in fields ranging from pharmacognosy to biomedicine. It is widely recognized that the biocompatible nanoparticle (NP) could function as a "key" that opens the target "lock". RESULTS: We report a functionalized poly-lysine NP technique that can monitor the target protein of arctigenin (ATG) in vivo non-invasively. The NPs were synthesized, and their morphologies and surface chemical properties were characterized by transmission electron microscopy (TEM), laser particle size analysis and atomic force microscopy (AFM)...
April 7, 2017: Journal of Nanobiotechnology
https://www.readbyqxmd.com/read/28384479/mutant-huntingtin-disrupts-the-nuclear-pore-complex
#20
Jonathan C Grima, J Gavin Daigle, Nicolas Arbez, Kathleen C Cunningham, Ke Zhang, Joseph Ochaba, Charlene Geater, Eva Morozko, Jennifer Stocksdale, Jenna C Glatzer, Jacqueline T Pham, Ishrat Ahmed, Qi Peng, Harsh Wadhwa, Olga Pletnikova, Juan C Troncoso, Wenzhen Duan, Solomon H Snyder, Laura P W Ranum, Leslie M Thompson, Thomas E Lloyd, Christopher A Ross, Jeffrey D Rothstein
Huntington's disease (HD) is caused by an expanded CAG repeat in the Huntingtin (HTT) gene. The mechanism(s) by which mutant HTT (mHTT) causes disease is unclear. Nucleocytoplasmic transport, the trafficking of macromolecules between the nucleus and cytoplasm, is tightly regulated by nuclear pore complexes (NPCs) made up of nucleoporins (NUPs). Previous studies offered clues that mHTT may disrupt nucleocytoplasmic transport and a mutation of an NUP can cause HD-like pathology. Therefore, we evaluated the NPC and nucleocytoplasmic transport in multiple models of HD, including mouse and fly models, neurons transfected with mHTT, HD iPSC-derived neurons, and human HD brain regions...
April 5, 2017: Neuron
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