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https://www.readbyqxmd.com/read/28937626/aspalathin-reverts-doxorubicin-induced-cardiotoxicity-through-increased-autophagy-and-decreased-expression-of-p53-mtor-p62-signaling
#1
Rabia Johnson, Samukelisiwe Shabalala, Johan Louw, Abidemi Paul Kappo, Christo John Frederick Muller
Doxorubicin (Dox) is an effective chemotherapeutic agent used in the treatment of various cancers. Its clinical use is often limited due to its potentially fatal cardiotoxic side effect. Increasing evidence indicates that tumour protein p53 (p53), adenosine monophosphate-activated protein kinase (AMPK), nucleoporin p62 (p62), and the mammalian target of rapamycin (mTOR) are critical mediators of Dox-induced apoptosis, and subsequent dysregulation of autophagy. Aspalathin, a polyphenolic dihydrochalcone C-glucoside has been shown to activate AMPK while decreasing the expression of p53...
September 22, 2017: Molecules: a Journal of Synthetic Chemistry and Natural Product Chemistry
https://www.readbyqxmd.com/read/28937612/houttuynia-cordata-facilitates-metformin-on-ameliorating-insulin-resistance-associated-with-gut-microbiota-alteration-in-oletf-rats
#2
Jing-Hua Wang, Shambhunath Bose, Soo-Kyoung Lim, AbuZar Ansari, Young-Won Chin, Han Seok Choi, Hojun Kim
Metformin and Houttuynia cordata are representative anti-diabetic therapeutics in western and oriental medicine, respectively. The current study examined the synergistic anti-diabetic effect of Houttuynia cordata extraction (HCE) and metformin combination in Otsuka Long-Evans Tokushima Fatty (OLETF) rats. Fecal microbiota were analyzed by denaturing gradient gel electrophoresis (DGGE) and real-time PCR. Combining HCE + metformin resulted in significantly ameliorated glucose tolerance (oral glucose tolerance test (OGTT))-the same as metformin alone...
September 22, 2017: Genes
https://www.readbyqxmd.com/read/28935544/metformin-improves-obesity-associated-inflammation-by-altering-macrophages-polarization
#3
Yuanyuan Jing, Fan Wu, Dai Li, Lei Yang, Qi Li, Rong Li
Obesity is reported to be a chronic low-grade inflammatory state. Adipose tissue macrophages play a key role in obesity-related inflammation. Metformin, the most widely used anti-diabetic drug, has recently been reported to have an effect on inflammation, but the mechanism is poorly understood. This study aims to investigate how metformin works on chronic low-grade inflammation in obesity and whether the mechanism underlying it is associated with macrophage polarization. Metformin was administered for 7 weeks to high fat-fed C57/6J male mice in vivo...
September 18, 2017: Molecular and Cellular Endocrinology
https://www.readbyqxmd.com/read/28934021/browning-of-abdominal-aorta-perivascular-adipose-tissue-inhibits-adipose-tissue-inflammation
#4
Run-Mei Li, Sui-Qing Chen, Ning-Xi Zeng, Shu-Hui Zheng, Li Guan, Hai-Mei Liu, Le-Quan Zhou, Jin-Wen Xu
BACKGROUND: Perivascular adipose tissue (PVAT) can regulate vascular homeostasis by secreting various adipokines. This study investigated the effects of PVAT browning on its endocrine function. METHODS: In the first section of our study, male Sprague-Dawley rats were randomly divided into cold exposure (8°C) and 24°C acclimation groups. After cold exposure for 7 days, interscapular brown adipose tissue (iBAT), subcutaneous white adipose tissue, thoracic aortic PVAT, and abdominal aortic PVAT (aPVAT) were harvested for histological and brown marker gene expression analysis...
September 21, 2017: Metabolic Syndrome and related Disorders
https://www.readbyqxmd.com/read/28933629/ezetimibe-ameliorates-steatohepatitis-via-amp-activated-protein-kinase-tfeb-mediated-activation-of-autophagy-and-nlrp3-inflammasome-inhibition
#5
Soo Hyun Kim, Gyuri Kim, Dai Hoon Han, Milim Lee, Irene Kim, Bohkyung Kim, Kook Hwan Kim, Young-Mi Song, Jeong Eun Yoo, Hye Jin Wang, Soo Han Bae, Yong-Ho Lee, Byung-Wan Lee, Eun Seok Kang, Bong-Soo Cha, Myung-Shik Lee
Impairment in macroautophagy/autophagy flux and inflammasome activation are common characteristics of nonalcoholic steatohepatitis (NASH). Considering the lack of approved agents for treating NASH, drugs that can enhance autophagy and modulate inflammasome pathways may be beneficial. Here, we investigated the novel mechanism of ezetimibe, a widely prescribed drug for hypercholesterolemia, as a therapeutic option for ameliorating NASH. Human liver samples with steatosis and NASH were analyzed. For in vitro studies of autophagy and inflammasomes, primary mouse hepatocytes, human hepatoma cells, mouse embryonic fibroblasts with Ampk or Tsc2 knockout, and human or primary mouse macrophages were treated with ezetimibe and palmitate...
September 21, 2017: Autophagy
https://www.readbyqxmd.com/read/28933601/transcriptional-regulation-of-autophagy-and-lysosomal-function-by-bromodomain-protein-brd4
#6
Jun-Ichi Sakamaki, Kevin M Ryan
Macroautophagy/autophagy is an intracellular recycling system that delivers cytoplasmic organelles and materials to lysosomes for degradation. This process is operated by autophagy-related (ATG) genes and tightly controlled by stress-responsive signaling pathways. Our recent study revealed that autophagy programs are transcriptionally suppressed by the BET family protein BRD4. This repression is alleviated during nutrient deprivation through the AMPK-SIRT1 pathway. Our findings therefore provide new insights into the regulation of autophagy...
September 21, 2017: Autophagy
https://www.readbyqxmd.com/read/28933598/autophagy-gene-atg7-regulates-ultraviolet-radiation-induced-inflammation-and-skin-tumorigenesis
#7
Lei Qiang, Ashley Sample, Christopher R Shea, Keyoumars Soltani, Kay F Macleod, Yu-Ying He
Macroautophagy (hereafter autophagy) is a cellular "self-eating" process that is implicated in many human cancers, where it can act to either promote or suppress tumorigenesis. However, the role of autophagy in regulation of inflammation during tumorigenesis remains unclear. Here we show that autophagy is induced in the epidermis by ultraviolet (UV) irradiation and autophagy gene Atg7 promoted UV-induced inflammation and skin tumorigenesis. Atg7 regulated UV-induced cytokine expression and secretion, and promoted Ptgs2/Cox-2 expression through both a CREB1/CREB-dependent cell autonomous mechanism and an IL1B/IL1β-dependent non-cell autonomous mechanism...
September 21, 2017: Autophagy
https://www.readbyqxmd.com/read/28933290/nutraceuticals-and-repurposed-drugs-of-phytochemical-origin-in-prevention-and-interception-of-chronic-degenerative-disease-and-cancer
#8
Adriana Albini, Barbara Bassani, Denisa Baci, Katiuscia Dallaglio, Matteo Gallazzi, Paola Corradino, Antonino Bruno, Douglas M Noonan
Chronic, degenerative diseases are often characterized by inflammation and aberrant angiogenesis. For many of these pathologies, including rheumatoid arthritis, cardiovascular and autoimmune diseases, cancer, diabetes, and obesity, current therapies have limited efficacy, thus the validation of novel (chemo)preventive and interceptive approaches, of new or repurposed agents, alone or in combination with registered drugs, are urgently required. Phytochemicals (triterpenoids, flavonoids, retinoids) and their derivatives, non-steroidal anti-inflammatory drugs (aspirin) as well as biguanides (metformin and phenformin) originally developed from phytochemical backbones, are multi-target agents showing anti-angiogenic and anti-anti-inflammatory proprieties...
September 20, 2017: Current Medicinal Chemistry
https://www.readbyqxmd.com/read/28931275/hempseed-peptides-exert-hypocholesterolemic-effects-with-a-statin-like-mechanism
#9
Chiara Zanoni, Gilda Aiello, Anna Arnoldi, Carmen Lammi
This study had the objective of preparing a hempseed protein hydrolysate and investigating its hypocholesterolemic properties. The hydrolysate was prepared treating a total protein extract with pepsin. Nano HPLC-ESI-MS/MS analysis permitted identifying in total 90 peptides belonging to 33 proteins. In the range 0.1-1.0 mg/mL, it inhibited the catalytic activity of 3-hydroxy-3-methylglutaryl coenzyme A reductase (HMGCoAR) in a dose-dependent manner. HepG2 cells were treated with 0.25, 0.5, and 1.0 mg/mL of the hydrolysate...
September 20, 2017: Journal of Agricultural and Food Chemistry
https://www.readbyqxmd.com/read/28930963/role-of-autophagy-and-its-molecular-mechanisms-in-mice-intestinal-tract-after-severe-burn
#10
Duan Y Zhang, Wei Qiu, PeiS Jin, Peng Wang, Yong Sun
BACKGROUND: Severe burn can lead to hypoxia/ischemia of intestinal mucosa. Autophagy is the process of intracellular degradation, which is essential for cell survival under stresses, such as hypoxia/ischemia and nutrient deprivation. The present study was designed to investigate whether there were changes in intestinal autophagy after severe burn in mice and further to explore the effect and molecular mechanisms of autophagy on intestinal injury. METHODS: This study includes three experiments...
October 2017: Journal of Trauma and Acute Care Surgery
https://www.readbyqxmd.com/read/28929674/-molecular-mechanisms-of-autophagy-in-regulating-renal-aging-and-interventional-effects-of-chinese-herbal-medicine
#11
REVIEW
Yue Tu, Wei Sun, Di-Ping Chen, Yi-Gang Wan, Wei Wu, Jian Yao
Aging is the gradual functional recession of the living tissues or organs caused by a variety of genetic and environmental factors together. Autophagy is a process of degrading cytoplasmic components mediated by lysosomes in eukaryotic cells. Kidney is a typical target organ of aging. Autophagy regulates renal aging. Decrease in autophagy can accelerate renal aging,whereas,increase in autophagy can delay renal aging. During the process of regulating renal aging,the mammalian target of rapamycin (mTOR) and its related signaling pathways including the adenosine monophosphate activated protein kinase (AMPK)/mTOR,the phosphatidylinositol 3-kinase (PI3K)/ serine-threonine kinase(Akt)/mTOR,the AMPK/silent information regulation 1 (Sirt1) and transforming growth factor β (TGF-β) play the important roles in renal aging...
November 2016: Zhongguo Zhong Yao za Zhi, Zhongguo Zhongyao Zazhi, China Journal of Chinese Materia Medica
https://www.readbyqxmd.com/read/28928671/aerobic-exercise-training-selectively-changes-oxysterol-levels-and-metabolism-reducing-cholesterol-accumulation-in-the-aorta-of-dyslipidemic-mice
#12
Guilherme Silva Ferreira, Paula R Pinto, Rodrigo T Iborra, Vanessa Del Bianco, Monique Fátima Mello Santana, Edna Regina Nakandakare, Valéria S Nunes, Carlos E Negrão, Sergio Catanozi, Marisa Passarelli
Background: Oxysterols are bioactive lipids that control cellular cholesterol synthesis, uptake, and exportation besides mediating inflammation and cytotoxicity that modulate the development of atherosclerosis. Aerobic exercise training (AET) prevents and regresses atherosclerosis by the improvement of lipid metabolism, reverse cholesterol transport (RCT) and antioxidant defenses in the arterial wall. We investigated in dyslipidemic mice the role of a 6-week AET program in the content of plasma and aortic arch cholesterol and oxysterols, the expression of genes related to cholesterol flux and the effect of the exercise-mimetic AICAR, an AMPK activator, in macrophage oxysterols concentration...
2017: Frontiers in Physiology
https://www.readbyqxmd.com/read/28927274/fluoride-induced-autophagy-via-the-regulation-of-mtor-phosphorylation-in-mice-leydig-cells
#13
Jianhai Zhang, Yuchen Zhu, Yan Shi, Yongli Han, Chen Liang, Zhiyuan Feng, Heping Zheng, Michelle Eng, Jundong Wang
Abstracts:Fluoride is known to impair testicular functions and decrease testosterone levels, yet the underlying mechanisms remain inconclusive. The objective of this study is to investigate the roles of autophagy in fluoride-induced male reproductive toxicity by both in vivo and in vitro Leydig cell models. Using Transmission Electron Microscopy (TEM) and Monodansylcadaverine (MDC) staining, we observed increasing numbers of autophagosomes in testicular tissue, especially in Leydig cells of fluoride-exposed mice...
September 20, 2017: Journal of Agricultural and Food Chemistry
https://www.readbyqxmd.com/read/28926099/anti-osteoporosis-activity-of-sanguinarine-in-preosteoblast-mc3t3-e1-cells-and-an-ovariectomized-rat-model
#14
Fuzhan Zhang, Jile Xie, Genlin Wang, Ge Zhang, Huilin Yang
Sanguinarine, a benzophenanthridine alkaloid, has been previously demonstrated to exert antimicrobial, anti-inflammatory and anti-tumor activities. A previous study has identified Sanguinarine as a potential drug candidate for osteoporosis treatment by computational bioinformatics analysis. This study further evaluated the effects of Sanguinarine on the differentiation of murine preosteoblast MC3T3-E1 cells and its anti-osteoporosis activity in an ovarietomized rat model. Sanguinarine treatment (0.25, 0.5, 1 and 2 µM) of MC3T3-E1 cells significantly increased alkaline phosphatase (ALP) activity and the phoshporalyation of AMP-activated protein kinase α subunit (AMPKα), but did not affect cell proliferation...
September 19, 2017: Journal of Cellular Physiology
https://www.readbyqxmd.com/read/28924239/the-autophagy-initiator-ulk1-sensitizes-ampk-to-allosteric-drugs
#15
Toby A Dite, Naomi X Y Ling, John W Scott, Ashfaqul Hoque, Sandra Galic, Benjamin L Parker, Kevin R W Ngoei, Christopher G Langendorf, Matthew T O'Brien, Mondira Kundu, Benoit Viollet, Gregory R Steinberg, Kei Sakamoto, Bruce E Kemp, Jonathan S Oakhill
AMP-activated protein kinase (AMPK) is a metabolic stress-sensing enzyme responsible for maintaining cellular energy homeostasis. Activation of AMPK by salicylate and the thienopyridone A-769662 is critically dependent on phosphorylation of Ser108 in the β1 regulatory subunit. Here, we show a possible role for Ser108 phosphorylation in cell cycle regulation and promotion of pro-survival pathways in response to energy stress. We identify the autophagy initiator Unc-51-like kinase 1 (ULK1) as a β1-Ser108 kinase in cells...
September 18, 2017: Nature Communications
https://www.readbyqxmd.com/read/28924233/pharmacological-inhibition-of-camkk2-with-the-selective-antagonist-sto-609-regresses-nafld
#16
Brian York, Feng Li, Fumin Lin, Kathrina L Marcelo, Jianqiang Mao, Adam Dean, Naomi Gonzales, David Gooden, Suman Maity, Cristian Coarfa, Nagireddy Putluri, Anthony R Means
Binding of calcium to its intracellular receptor calmodulin (CaM) activates a family of Ca(2+)/CaM-dependent protein kinases. CaMKK2 (Ca(2+)/CaM-dependent protein kinase kinase 2) is a central member of this kinase family as it controls the actions of a CaMK cascade involving CaMKI, CaMKIV or AMPK. CaMKK2 controls insulin signaling, metabolic homeostasis, inflammation and cancer cell growth highlighting its potential as a therapeutic target for a variety of diseases. STO-609 is a selective, small molecule inhibitor of CaMKK2...
September 18, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28924180/%C3%AE-snap-is-expressed-in-mouse-ovarian-granulosa-cells-and-plays-a-key-role-in-folliculogenesis-and-female-fertility
#17
Alexis Arcos, Matilde de Paola, Diego Gianetti, Diego Acuña, Zahady D Velásquez, María Paz Miró, Gabriela Toro, Bryan Hinrichsen, Rosa Iris Muñoz, Yimo Lin, Gonzalo A Mardones, Pamela Ehrenfeld, Francisco J Rivera, Marcela A Michaut, Luis Federico Batiz
The balance between ovarian folliculogenesis and follicular atresia is critical for female fertility and is strictly regulated by a complex network of neuroendocrine and intra-ovarian signals. Despite the numerous functions executed by granulosa cells (GCs) in ovarian physiology, the role of multifunctional proteins able to simultaneously coordinate/modulate several cellular pathways is unclear. Soluble N-ethylmaleimide-sensitive factor (NSF) attachment protein (α-SNAP) is a multifunctional protein that participates in SNARE-mediated membrane fusion events...
September 18, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28923415/diindolylmethane-and-its-halogenated-derivatives-induce-protective-autophagy-in-human-prostate-cancer-cells-via-induction-of-the-oncogenic-protein-aeg-1-and-activation-of-amp-dependent-kinase-ampk
#18
Hossam Draz, Alexander A Goldberg, Vladimir I Titorenko, Emma Guns, Stephen H Safe, J Thomas Sanderson
3,3'-Diindolylmethane (DIM) and its synthetic halogenated derivatives 4,4'-Br2- and 7,7'-Cl2DIM (ring-DIMs) have recently been shown to induce protective autophagy in human prostate cancer cells. The mechanisms by which DIM and ring-DIMs induce autophagy have not been elucidated. As DIM is a mitochondrial ATP-synthase inhibitor, we hypothesized that DIM and ring-DIMs induce autophagy via alteration of intracellular AMP/ATP ratios and activation of AMPK signaling in prostate cancer cells. We found that DIM and ring-DIMs induced autophagy was accompanied by increased autophagic vacuole formation and conversion of LC3BI to LC3BII in LNCaP and C42B human prostate cancer cells...
September 15, 2017: Cellular Signalling
https://www.readbyqxmd.com/read/28922732/physcion-8-o-%C3%AE-glucopyranosideregulates-cell-cycle-apoptosis-and-invasion-in-glioblastoma-cells-through-modulating-skp2
#19
Wen Li, Fuxia Li, Yanfang Zhu, Daqing Song
Glioblastoma multiforme (GBM) is the most common malignant glioma in the central nervous system. This study aimed to investigate the anti-tumor activity of physcion 8-O-β-glucopyranoside (PG) in GBM cells. This showed that PG could significantly block cell cycle progression, induce apoptosis, and suppress invasion in both model GBM cell lines (U87 and U251). At the molecular level, PG repressed the expression of S-phase kinase protein 2 (Skp2), which was responsible for the anti-tumor effect of PG in GBM cells...
September 14, 2017: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/28919424/adiponectin-modulates-the-function-of-endothelial-progenitor-cells-via-ampk-enos-signaling-pathway
#20
Shuhong Wang, Jie Miao, Meijie Qu, Guo-Yuan Yang, Linhui Shen
Endothelial progenitor cells have been shown to differentiate into endothelial cells and to play a pivotal role in vascular homeostasis. Adiponectin has anti-atherogenic and anti-inflammatory properties via directly acting on vascular cells. The aim of the present study is to explore the effect of adiponectin on major functions involved in survival, migration, and tube formation of endothelial progenitor cells and to explore the underlying mechanism. In this study, we transferred adiponectin gene into endothelial progenitor cells via lentiviral vectors and investigated the proliferation, migration and tube formation of these transfected cells...
September 14, 2017: Biochemical and Biophysical Research Communications
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