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https://www.readbyqxmd.com/read/28819100/blockage-of-the-lysosome-dependent-autophagic-pathway-contributes-to-complement-membrane-attack-complex-induced-podocyte-injury-in-idiopathic-membranous-nephropathy
#1
Wei Jing Liu, Zhi-Hang Li, Xiao-Cui Chen, Xiao-Lu Zhao, Zhen Zhong, Chen Yang, Hong-Luan Wu, Ning An, Wei-Yan Li, Hua-Feng Liu
Dysregulation of autophagy-mediated podocyte homeostasis is proposed to play a role in idiopathic membranous nephropathy (IMN). In the present study, autophagic activity and lysosomal alterations were investigated in podocytes of IMN patients and in cultured podocytes exposed to sublytic terminal complement complex, C5b-9. C5b-9 upregulated the number of LC3 positive puncta and the expression of p62 in patient podocytes and in C5b-9 injuried podocyte model. The lysosomal turnover of LC3-II was not influenced, although the BECN1 expression level was upregulated after exposure of podocytes to C5b-9...
August 17, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28817115/administration-of-follicle-stimulating-hormone-induces-autophagy-via-upregulation-of-hif-1%C3%AE-in-mouse-granulosa-cells
#2
Jilong Zhou, Wang Yao, Chengyu Li, Wangjun Wu, Qifa Li, Honglin Liu
Recent studies reported the important role of autophagy in follicular development. However, the underlying molecular mechanisms remain elusive. In this study, we investigated the effect of follicle-stimulating hormone (FSH) on mouse granulosa cells (MGCs). Results indicated that autophagy was induced by FSH, which is known to be the dominant hormone regulating follicular development and granulosa cell (GC) proliferation. The activation of mammalian target of rapamycin (mTOR), a master regulator of autophagy, was inhibited during the process of MGC autophagy...
August 17, 2017: Cell Death & Disease
https://www.readbyqxmd.com/read/28815720/pharmacological-evidence-of-involvement-of-nitric-oxide-pathway-in-anti-pruritic-effects-of-sumatriptan-in-chloroquine-induced-scratching-in-mice
#3
Nazgol-Sadat Haddadi, Sattar Ostadhadi, Saeed Shakiba, Khashayar Afshari, Nastaran Rahimi, Arash Foroutan, Ahmad-Reza Dehpour
Chloroquine (CQ) induces histamine-independent itch in human and mice. We recently reported the role of intradermal nitric oxide (NO)/ cyclic guanosine monophosphate (cGMP) pathway in CQ-evoked scratching in mice. Chloroquine stimulates neuronal nitric oxide synthase (nNOS) activity to over-producing NO in the skin. Sumatriptan, a 5-hydroxytryptamine 1b/1d receptors (5-HTR1b/1d) agonist, is involved in pain and used to treat migraine and cluster headaches. According to previous studies, sumatriptan inhibits NOS activity...
August 16, 2017: Fundamental & Clinical Pharmacology
https://www.readbyqxmd.com/read/28813452/plasma-metabolomics-reveals-membrane-lipids-aspartate-asparagine-and-nucleotide-metabolism-pathway-differences-associated-with-chloroquine-resistance-in-plasmodium-vivax-malaria
#4
Karan Uppal, Jorge L Salinas, Wuelton M Monteiro, Fernando Val, Regina J Cordy, Ken Liu, Gisely C Melo, Andre M Siqueira, Belisa Magalhaes, Mary R Galinski, Marcus V G Lacerda, Dean P Jones
BACKGROUND: Chloroquine (CQ) is the main anti-schizontocidal drug used in the treatment of uncomplicated malaria caused by Plasmodium vivax. Chloroquine resistant P. vivax (PvCR) malaria in the Western Pacific region, Asia and in the Americas indicates a need for biomarkers of resistance to improve therapy and enhance understanding of the mechanisms associated with PvCR. In this study, we compared plasma metabolic profiles of P. vivax malaria patients with PvCR and chloroquine sensitive parasites before treatment to identify potential molecular markers of chloroquine resistance...
2017: PloS One
https://www.readbyqxmd.com/read/28812437/autophagy-induced-kdr-vegfr-2-activation-promotes-the-formation-of-vasculogenic-mimicry-by-glioma-stem-cells
#5
Hai-Bo Wu, Shuai Yang, Hai-Yan Weng, Qian Chen, Xi-Long Zhao, Wen-Juan Fu, Qin Niu, Yi-Fang Ping, Ji Ming Wang, Xia Zhang, Xiao-Hong Yao, Xiu-Wu Bian
Antiangiogenesis with bevacizumab, an antibody against vascular endothelial growth factor (VEGF), has been used for devascularization to limit the growth of malignant glioma. However, the benefits are transient due to elusive mechanisms underlying resistance to the antiangiogenic therapy. Glioma stem cells (GSCs) are capable of forming vasculogenic mimicry (VM), an alternative microvascular circulation independent of VEGF-driven angiogenesis. Herein, we report that the formation of VM was promoted by bevacizumab-induced macroautophagy/autophagy in GSCs, which was associated with tumor resistance to antiangiogenic therapy...
August 16, 2017: Autophagy
https://www.readbyqxmd.com/read/28811357/autophagy-attenuates-endothelial-to-mesenchymal-transition-by-promoting-snail-degradation-in-human-cardiac-microvascular-endothelial-cells
#6
Jin Zou, Yanhua Liu, Bingong Li, Zeqi Zheng, Xuan Ke, Yanqin Hao, Xuelian Li, Xingxing Li, Fuyou Liu, Zhiyong Zhang
Endothelial-to-mesenchymal transition (EndMT) mainly exists in cardiovascular development and disease progression, and is well known to contribute to cardiac fibrosis. Recent studies indicated that autophagy also participates in the regulation of cardiac fibrosis. However, the precise role of autophagy in cardiac fibrosis and the underlying molecular mechanism remain unclear. This study aimed to explore the role of autophagy in EndMT, reveal the underlying molecular mechanism and seek new therapy for cardiac fibrosis...
August 15, 2017: Bioscience Reports
https://www.readbyqxmd.com/read/28810849/in-vitro-antiplasmodial-activity-and-prophylactic-potentials-of-extract-and-fractions-of-trema-orientalis-linn-stem-bark
#7
John Oludele Olanlokun, Oluwole Moses David, Anthony Jide Afolayan
BACKGROUND: Trema orientalis (T. orientalis Linn) has been used in the management of malaria in the western part of Nigeria and despite its application in ethnomedicine, there is dearth of scientific evidence to justify the acclaimed prophylactic antimalarial usage of the plant. The aim of this study is to assess the in vitro antiplasmodial cell-free assay and chemopreventive efficacy of the methanol extract of the stem bark of T. orientalis and its fractions as a prophylactic regimen for malaria prevention...
August 15, 2017: BMC Complementary and Alternative Medicine
https://www.readbyqxmd.com/read/28808396/catechin-isolated-from-garcinia-celebica-leaves-inhibit-plasmodium-falciparum-growth-through-the-induction-of-oxidative-stress
#8
Rizky Abdulah, Eka W Suradji, Anas Subarnas, Unang Supratman, Milyadi Sugijanto, Ajeng Diantini, Keri Lestari, Melisa I Barliana, Shinichiro Kawazu, Hiroshi Koyama
BACKGROUND: Resistance of antimalarial drugs to Plasmodium falciparum has become a major concern in malaria eradication. Although it is also affected by several socioeconomic factors, a new antiplasmodial agent is needed for a global malaria control program. OBJECTIVE: In this study, we attempted to uncover the antiplasmodial properties of Garcinia celebica, an Indonesian medicinal plant, along with the responsible compound and its possible mechanism. MATERIALS AND METHODS: The G...
July 2017: Pharmacognosy Magazine
https://www.readbyqxmd.com/read/28807879/apigenin-induced-abcc1-mediated-efflux-of-glutathione-from-mature-erythrocytes-inhibits-the-proliferation-of-plasmodium-falciparum
#9
Ohud Fallatah, Elias Georges
Plasmodium falciparum infection of mature normal erythrocytes leads to heightened oxidative stress that is tolerated in normal but not in erythrocytes from sickle-cell, β-thalassemia, and glucose-6-phosphate dehydrogenase (G6PD) deficiency hosts. In this report, it was of interest to perturb the redox homeostasis of normal erythrocytes through drug-induced active efflux of glutathione via erythrocyte ABCC1 (member of the C- subfamily of the human ATP-binding cassette (ABC) transporters). To achieve this objective, we made use of apigenin, shown previously to activate ABCC1 glutathione efflux in mature erythrocytes...
August 11, 2017: International Journal of Antimicrobial Agents
https://www.readbyqxmd.com/read/28806961/molecular-analysis-demonstrates-high-prevalence-of-chloroquine-resistance-but-no-evidence-of-artemisinin-resistance-in-plasmodium-falciparum-in-the-chittagong-hill-tracts-of-bangladesh
#10
Mohammad Shafiul Alam, Benedikt Ley, Maisha Khair Nima, Fatema Tuj Johora, Mohammad Enayet Hossain, Kamala Thriemer, Sarah Auburn, Jutta Marfurt, Ric N Price, Wasif A Khan
BACKGROUND: Artemisinin resistance is present in the Greater Mekong region and poses a significant threat for current anti-malarial treatment guidelines in Bangladesh. The aim of this molecular study was to assess the current status of drug resistance in the Chittagong Hill Tracts of Bangladesh near the Myanmar border. METHODS: Samples were obtained from patients enrolled into a Clinical Trial (NCT02389374) conducted in Alikadam, Bandarban between August 2014 and January 2015...
August 15, 2017: Malaria Journal
https://www.readbyqxmd.com/read/28804611/antimalarial-evaluation-of-selected-medicinal-plant-extracts-used-in-iranian-traditional-medicine
#11
Mohammad Hossein Feiz Haddad, Hamidreza Mahbodfar, Zahra Zamani, Ali Ramazani
OBJECTIVES: In an attempt to discover new natural active extracts against malaria parasites, the present study evaluated the antiplasmodial properties of selected plants based on Iranian traditional medicine. MATERIALS AND METHODS: Ten plant species found in Iran were selected and collected based on the available literature about the Iranian traditional medicine. The methanolic extracts of these plants were investigated for in vitro antimalarial properties against chloroquine-sensitive (3D7) and multi-drug resistant (K1) strains of Plasmodium falciparum...
April 2017: Iranian Journal of Basic Medical Sciences
https://www.readbyqxmd.com/read/28804003/effect-and-proposed-mechanism-of-vitamin-c-modulating-amino-acid-regulation-of-autophagic-proteolysis
#12
Md Razaul Karim, Motoni Kadowaki
Autophagy is an intracellular bulk degradation process, induced under nutrient starvation. Failure of autophagy has been recognized as a contributor to aging and multiple age related neurodegenerative diseases. Improving autophagy is a beneficial anti-aging strategy, however very few physiological regulators have been identified. Here, we demonstrate that vitamin C is a nutritional stimulator of autophagy. Supplementation of fresh hepatocytes with vitamin C increased autophagic proteolysis significantly in the presence of amino acids in a dose- and time-dependent manner, although no effect was observed in the absence of amino acids...
August 10, 2017: Biochimie
https://www.readbyqxmd.com/read/28799637/facilitating-the-analysis-of-the-multifocal-electroretinogram-using-the-free-software-environment-r
#13
Richard Bergholz, Mirjam Rossel, Ralf M Dutescu, Klaas P Vöge, Daniel J Salchow
PURPOSE: The large amount of data rendered by the multifocal electroretinogram (mfERG) can be analyzed and visualized in various ways. The evaluation and comparison of more than one examination is time-consuming and prone to create errors. Using the free software environment R we developed a solution to average the data of multiple examinations and to allow a comparison of different patient groups. METHODS: Data of single mfERG recordings as exported in .csv format from a RETIport 21 system (version 7/03, Roland Consult) or manually compiled ...
August 7, 2017: European Journal of Ophthalmology
https://www.readbyqxmd.com/read/28797031/regulation-of-hypoxia-induced-autophagy-in-glioblastoma-involves-atg9a
#14
Siti Aminah Abdul Rahim, Anne Dirkse, Anais Oudin, Anne Schuster, Jill Bohler, Vanessa Barthelemy, Arnaud Muller, Laurent Vallar, Bassam Janji, Anna Golebiewska, Simone P Niclou
BACKGROUND: Hypoxia is negatively associated with glioblastoma (GBM) patient survival and contributes to tumour resistance. Anti-angiogenic therapy in GBM further increases hypoxia and activates survival pathways. The aim of this study was to determine the role of hypoxia-induced autophagy in GBM. METHODS: Pharmacological inhibition of autophagy was applied in combination with bevacizumab in GBM patient-derived xenografts (PDXs). Sensitivity towards inhibitors was further tested in vitro under normoxia and hypoxia, followed by transcriptomic analysis...
August 10, 2017: British Journal of Cancer
https://www.readbyqxmd.com/read/28783177/autophagy-dependent-generation-of-axin2-cancer-stem-like-cells-promotes-hepatocarcinogenesis-in-liver-cirrhosis
#15
J Li, S B Hu, L Y Wang, X Zhang, X Zhou, B Yang, J H Li, J Xiong, N Liu, Y Li, Y Z Wu, Q C Zheng
Autophagy is a pathophysiological phenomenon in liver cirrhosis that can further progress into hepatocarcinoma. Liver cancer stem cells (CSCs) are believed to initiate hepatocarcinogenesis. To investigate the precise mechanism related to the origin of CSCs in liver cirrhosis and hepatocarcinogenesis, we labeled Axin2+ hepatic cells with EGFP in Axin2Cre;Rosa26EGFP transgenic rats, and then stratified clinical and rat liver cirrhosis samples by autophagy flux. Clinical follow-up and lineage tracing in transgenic rat liver cirrhosis revealed that while Axin2/EGFP+ hepatic cells were present in normal livers and cirrhotic livers without aberrant autophagy, hepatic Axin2/EGFP+CD90+ cells were generated exclusively in cirrhotic livers with aberrant autophagy and promoted hepatocarcinogenesis...
August 7, 2017: Oncogene
https://www.readbyqxmd.com/read/28776937/synthesis-and-evaluation-of-chloroquine-containing-dmaema-copolymers-as-efficient-anti-mirna-delivery-vectors-with-improved-endosomal-escape-and-antimigratory-activity-in-cancer-cells
#16
Ying Xie, Fei Yu, Weimin Tang, Bolutito Oluwole Alade, Zheng-Hong Peng, Yazhe Wang, Jing Li, David Oupický
Chloroquine-containing 2-(dimethylamino)ethyl methacrylate copolymers (PDCs) are synthesized by reversible addition-fragmentation chain-transfer polymerization. Systematic evaluation is performed to test the hypothesis that presence of chloroquine (CQ) in the PDC structure will improve miRNA delivery due to enhanced endosomal escape while simultaneously contribute to anticancer activity of PDC/miRNA polyplexes through inhibition of cancer cell migration. The results show that miRNA delivery efficiency is dependent both on the molecular weight and CQ...
August 4, 2017: Macromolecular Bioscience
https://www.readbyqxmd.com/read/28774427/synthesis-of-antimalarial-amide-analogues-based-on-the-plant-serrulatane-diterpenoid-3-7-8-trihydroxyserrulat-14-en-19-oic-acid
#17
Rohitesh Kumar, Sandra Duffy, Vicky M Avery, Rohan A Davis
A plant-derived natural product scaffold, 3,7,8-trihydroxyserrulat-14-en-19-oic acid (1) was isolated in high yield from the aerial parts of the endemic Australian desert plant Eremophila microtheca. This scaffold (1) was subsequently used in the generation of a series of new amide analogues via a one-pot mixed anhydride amidation using pivaloyl chloride. The structures of all analogues were characterized using MS, NMR, and UV data. The major serrulatane natural products (1-3), isolated from the plant extract, and all amide analogues (6-15) together with several pivaloylated derivatives of 3,7,8-trihydroxyserrulat-14-en-19-oic acid (16-18) were evaluated for their antimalarial activity against 3D7 (chloroquine sensitive) and Dd2 (chloroquine resistant) Plasmodium falciparum strains, and preliminary cytotoxicity data were also acquired using the human embryonic kidney cell line HEK293...
July 15, 2017: Bioorganic & Medicinal Chemistry Letters
https://www.readbyqxmd.com/read/28772270/induction-of-the-vitamin-d-receptor-attenuates-autophagy-dysfunction-mediated-cell-death-following-traumatic-brain-injury
#18
Changmeng Cui, Jianzhong Cui, Feng Jin, Ying Cui, Ran Li, Xiaohua Jiang, Yanxia Tian, Kaijie Wang, Pei Jiang, Junling Gao
BACKGROUND/AIMS: Traumatic brain injury (TBI) is a major public health problem in the world and causes high rates of mortality and disability. Recent evidence suggests that vitamin D (VD) has neuroprotective actions and can promote function recovery after TBI. In vitro and in vivo studies have demonstrated that autophagy could be enhanced following supplementation with an active metabolite of VD (calcitriol). However, it is unclear whether autophagy participates in the protective effects of calcitriol after TBI...
August 3, 2017: Cellular Physiology and Biochemistry
https://www.readbyqxmd.com/read/28772211/autophagy-as-a-potential-therapeutic-target-during-epithelial-to-mesenchymal-transition-in-renal-cell-carcinoma-an-in-vitro-study
#19
Mamta Singla, Shalmoli Bhattacharyya
Cancer progression toward invasive and metastatic disease is aided by reactivation of epithelial-mesenchymal transition (EMT), involving transdifferentiation of epithelial cells into mesenchymal phenotype. This leads to increased migratory and stem cell-like features in the cells. These EMT cells are more resistant to chemotherapy and it is hypothesized that the phenomenon of autophagy induces resistance, providing a survival strategy for cells. In the present study, we induced EMT-like phenotype in renal carcinoma cells and identified corresponding higher autophagy flux in these cells...
July 31, 2017: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/28768767/iron-is-a-substrate-of-the-plasmodium-falciparum-chloroquine-resistance-transporter-pfcrt-in-xenopus-oocytes
#20
Naziha Bakouh, Sebastiano Bellanca, Britta Nyboer, Sonia Moliner Cubel, Zoubida Karim, Cecilia P Sanchez, Wilfred D Stein, Gabrielle Planelles, Michael Lanzer
The chloroquine resistance transporter of the human malaria parasite Plasmodium falciparum, PfCRT, is an important determinant of resistance to several quinoline and quinoline-like antimalarial drugs. PfCRT also plays an essential role in the physiology of the parasite during development inside erythrocytes. However, the function of this transporter besides its role in drug resistance is still unclear. Using electrophysiological and flux experiments conducted on PfCRTexpressing Xenopus laevis oocytes, we show here that both wild type PfCRT and a PfCRT variant associated with chloroquine resistance transport both ferrous and ferric iron, albeit with different kinetics...
August 2, 2017: Journal of Biological Chemistry
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