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https://www.readbyqxmd.com/read/29160747/lipopolysaccharide-mediates-hepatic-stellate-cell-activation-by-regulating-autophagy-and-retinoic-acid-signaling
#1
Ming Chen, Jiaxing Liu, Wenqi Yang, Wenhua Ling
Bacterial translocation and lipopolysaccharide (LPS) leakage occur at a very early stage of liver fibrosis in animal models. We studied the role of LPS in hepatic stellate cell (HSC) activation and the underlying mechanisms in vitro and in vivo. Herein, we demonstrated that LPS treatment led to a dramatic increase in autophagosome formation and autophagic flux in LX-2 cells and HSCs, which was mediated through the AKT-MTOR and AMPK-ULK1 pathway. LPS significantly decreased the lipid content, including the lipid droplet (LD) number and lipid staining area in HSCs; pretreatment with macroautophagy/autophagy inhibitors or silencing ATG5 attenuated this decrease...
November 21, 2017: Autophagy
https://www.readbyqxmd.com/read/29160164/rutin-scavenges-reactive-oxygen-species-inactivates-5-adenosine-monophosphate-activated-protein-kinase-ampk-and-increases-nis-expression-in-thyroid-pccl3-cells
#2
Carlos Frederico Lima Gonçalves, Mariana Lopes de Freitas, Rodrigo Soares Fortunato, Leandro Miranda-Alves, Denise Pires de Carvalho, Andrea Claudia Freitas Ferreira
BACKGROUND: Thyroid iodide uptake, mediated by the sodium-iodide symporter (NIS), is essential for thyroid hormone synthesis and also for treatment of thyroid diseases, such as thyroid cancer, through radioiodine therapy. Therefore, compounds able to increase thyroid iodide uptake could be clinically useful, and it is of great importance to unravel the mechanisms underlying such effect. We have previously shown that the flavonoid rutin increases thyroid radioiodide uptake in vivo, in rats...
November 21, 2017: Thyroid: Official Journal of the American Thyroid Association
https://www.readbyqxmd.com/read/29159872/the-dark-side-of-glucose-transporters-in-prostate-cancer-are-they-a-new-feature-to-characterize-carcinomas
#3
REVIEW
Pedro Gonzalez-Menendez, David Hevia, Juan C Mayo, Rosa M Sainz
One of the hallmarks of cancer cells is the increased ability to acquire nutrients, particularly glucose and glutamine. Proliferating cells need precursors for cell growth and NADPH reducing equivalents for survival. The principal responsible for glucose uptake is facilitative glucose transporters (GLUTs), which usually are overexpressed in cancer cells. Besides their role in glucose uptake, GLUT transporters are able to transport other compounds such as dehydroascorbic acid or uric acid. They play a major role in tumor progression and cellular processes such as regulated cell death...
November 21, 2017: International Journal of Cancer. Journal International du Cancer
https://www.readbyqxmd.com/read/29159335/protective-effects-of-lipoic-acid-against-acrylamide-induced-neurotoxicity-involvement-of-mitochondrial-energy-metabolism-and-autophagy
#4
Ge Song, Zhigang Liu, Luanfeng Wang, Renjie Shi, Chuanqi Chu, Man Xiang, Qi Tian, Xuebo Liu
Acrylamide (ACR) is a chronic neurotoxin that is generated in high-starch foods during heat processing. Alpha-lipoic acid (LA) is an antioxidant that occurs in most plants and animals. The objective of this study was to reveal the mechanism of ACR-triggered neurotoxicity and identify the protective role of LA in SH-SY5Y cells. In this study, LA restored ACR-stimulated depletion of glutathione content and mitochondrial membrane potential, moderated the activation of inflammatory pathways, and recovered the Keap1/Nrf2 pathway...
November 21, 2017: Food & Function
https://www.readbyqxmd.com/read/29158183/serine-prevented-high-fat-diet-induced-oxidative-stress-by-activating-ampk-and-epigenetically-modulating-the-expression-of-glutathione-synthesis-related-genes
#5
Xihong Zhou, Liuqin He, Shengnan Zuo, Yumei Zhang, Dan Wan, Ciming Long, Pan Huang, Canrong Wu, Xin Wu, Gang Liu, Yulong Yin
Serine deficiency has been observed in patients with nonalcoholic fatty liver disease (NAFLD). Whether serine supplementation has any beneficial effects on the prevention of NAFLD remains unknown. The present study was conducted to investigate the effects of serine supplementation on hepatic oxidative stress and steatosis and its related mechanisms. Forty male C57BL/6J mice (9week-old) were randomly assigned into four groups (n=10) and fed: i) a low-fat diet; ii) a low-fat diet supplemented with 1% (wt:vol) serine; iii) a high-fat (HF) diet; and iv) a HF diet supplemented with 1% serine, respectively...
November 17, 2017: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/29156794/salen-mn-compounds-induces-cell-apoptosis-in-human-prostate-cancer-cells-through-promoting-ampk-activity-and-cell-autophagy
#6
Xiaoshuang Tang, Jing Jia, Feng Li, Wei Liu, Chao Yang, Bin Jin, Qi Shi, Xinyang Wang, Dalin He, Peng Guo
Currently only docetaxel has been approved to be used in the chemotherapy of prostate cancer and new drugs are urgent need. Salen-Mn is a novel type of synthetic reagent bionic and exerts remarkable anticancer activities. However, the effect of Salen-Mn on human prostate cancer has not been elucidated yet. In this study, we found that treatment of PC-3 and DU145 human prostate cancer cells with Salen-Mn inhibited cell growth in dose and time dependent manner. Moreover, Salen-Mn induced cell apoptosis, and increased the expression of apoptotic proteins, such as cleaved caspase-3, cleaved PARP, and Bax, in PC-3 and DU145 prostate cancer cells...
October 17, 2017: Oncotarget
https://www.readbyqxmd.com/read/29156790/kaempferol-induces-autophagic-cell-death-of-hepatocellular-carcinoma-cells-via-activating-ampk-signaling
#7
Bing Han, Yi-Qun Yu, Qi-Lian Yang, Chun-Ying Shen, Xiao-Juan Wang
In the present study, we demonstrate that Kaempferol inhibited survival and proliferation of established human hepatocellular carcinoma (HCC) cell lines (HepG2, Huh-7, BEL7402, and SMMC) and primary human HCC cells. Kaempferol treatment in HCC cells induced profound AMP-activated protein kinase (AMPK) activation, which led to Ulk1 phosphorylation, mTOR complex 1 inhibition and cell autophagy. Autophagy induction was reflected by Beclin-1/autophagy gene 5 upregulation and p62 degradation as well as light chain 3B (LC3B)-I to LC3B-II conversion and LC3B puncta formation...
October 17, 2017: Oncotarget
https://www.readbyqxmd.com/read/29156787/natural-compound-bavachalcone-promotes-the-differentiation-of-endothelial-progenitor-cells-and-neovascularization-through-the-ror%C3%AE-erythropoietin-ampk-axis
#8
Shuang Ling, Rong-Zhen Ni, Yunyun Yuan, Yan-Qi Dang, Qian-Mei Zhou, Shuang Liang, Fujiang Guo, Wei Feng, Yuanyuan Chen, Katsumi Ikeda, Yukio Yamori, Jin-Wen Xu
In cardiovascular diseases, endothelial function is impaired and the level of circulating endothelial progenitor cells (EPCs) is low. This study investigated whether the natural bioactive component bavachalcone (BavaC) induces the differentiation of EPCs and neovascularization in vivo; the underlying mechanisms were also examined. We observed that the treatment of rat bone marrow-derived cells with a very low dose of BavaC significantly promoted EPC differentiation. In our hindlimb ischemia models, low-dose BavaC administered orally for 14 days stimulated the recovery of ischemic hindlimb blood flow, increased circulating EPCs, and promoted capillary angiogenesis...
October 17, 2017: Oncotarget
https://www.readbyqxmd.com/read/29156779/selecting-lncrnas-in-gastric-cancer-cells-for-directed-therapy-with-bioactive-peptides-and-chemotherapy-drugs
#9
Wenyan Han, Rui Xiao, Chuanling Zhang, Qimuge Suyila, Xian Li, Xiulan Su
Selecting lncRNAs for directed therapy with bioactive peptides and chemotherapy drugs may be an effective approach to treating gastric cancer (GC). We show genome-scale identification and characterization of differentially expressed lncRNAs in GC cells treated with a novel anti-cancer bioactive peptide (ACBP) and the chemotherapy drug oxaliplatin (ASLB). A total of 17,897 lncRNAs were identified through pairwise comparison, including 2,074 novel lncRNAs. Of those, 1,386 lncRNAs were differentially expressed (over 1...
October 17, 2017: Oncotarget
https://www.readbyqxmd.com/read/29156703/preclinical-efficacy-of-the-novel-competitive-nampt-inhibitor-stf-118804-in-pancreatic-cancer
#10
Jair Machado Espindola-Netto, Claudia C S Chini, Mariana Tarragó, Enfeng Wang, Shamit Dutta, Krishnendu Pal, Debabrata Mukhopadhyay, Mauro Sola-Penna, Eduardo N Chini
NAD salvage is one of the pathways used to generate NAD in mammals. Nicotinamide phosphoribosyltransferase (NAMPT), the rate-limiting enzyme in this pathway, uses nicotinamide (NAM) to generate nicotinamide mononucleotide (NMN). NMN is one of the main precursors of NAD synthesis in cells. Our previous study showed the importance of NAMPT in maintaining NAD levels in pancreatic ductal adenocarcinoma cells (PDAC), and that the NAMPT inhibitor FK866 decreased pancreatic cancer growth. We now tested the effect of STF-118804, a new highly specific NAMPT inhibitor, in models of pancreatic ductal adenocarcinoma...
October 17, 2017: Oncotarget
https://www.readbyqxmd.com/read/29156421/impaired-mitochondrial-respiration-in-human-carotid-plaque-atherosclerosis-a-potential-role-for-pink1-in-vascular-smooth-muscle-cell-energetics
#11
Craig K Docherty, Andy Carswell, Elaine Friel, John R Mercer
BACKGROUND AND AIMS: DNA damage and mitochondrial dysfunction are thought to play an essential role in ageing and the energetic decline of vascular smooth muscle cells (VSMCs) essential for maintaining plaque integrity. We aimed to better understand VSMCs and identify potentially useful compensatory pathways that could extend their lifespan. Moreover, we wanted to assess if defects in mitochondrial respiration exist in human atherosclerotic plaques and to identify the appropriate markers that may reflect a switch in VSMC energy metabolism...
November 13, 2017: Atherosclerosis
https://www.readbyqxmd.com/read/29153408/ampk-sensing-glucose-as-well-as-cellular-energy-status
#12
REVIEW
Sheng-Cai Lin, D Grahame Hardie
Mammalian AMPK is known to be activated by falling cellular energy status, signaled by rising AMP/ATP and ADP/ATP ratios. We review recent information about how this occurs but also discuss new studies suggesting that AMPK is able to sense glucose availability independently of changes in adenine nucleotides. The glycolytic intermediate fructose-1,6-bisphosphate (FBP) is sensed by aldolase, which binds to the v-ATPase on the lysosomal surface. In the absence of FBP, interactions between aldolase and the v-ATPase are altered, allowing formation of an AXIN-based AMPK-activation complex containing the v-ATPase, Ragulator, AXIN, LKB1, and AMPK, causing increased Thr172 phosphorylation and AMPK activation...
November 15, 2017: Cell Metabolism
https://www.readbyqxmd.com/read/29152112/capsaicin-exerts-synergistic-antitumor-effect-with-sorafenib-in-hepatocellular-carcinoma-cells-through-ampk-activation
#13
Alicia Bort, Elena Spínola, Nieves Rodríguez-Henche, Inés Díaz-Laviada
In this study, we investigated the antitumoral effects of combined treatment using sorafenib and capsaicin in hepatocellular carcinoma (HCC) cells. Here we showed that the combination of the two drugs had a much stronger inhibitory effect on both HepG2 and Huh-7 human HCC cells growth than either drug alone. The isobolograms demonstrated that the combinations investigated in this study produced a synergistic interaction. In the combination treatment using capsaicin and sorafenib, increased apoptosis, followed by the activation of caspase-9 and PARP, was observed...
October 20, 2017: Oncotarget
https://www.readbyqxmd.com/read/29151980/synbiotic-effects-of-%C3%AE-glucans-from-cauliflower-mushroom-and-lactobacillus-fermentum-on-metabolic-changes-and-gut-microbiome-in-estrogen-deficient-rats
#14
Seong-Yeop Jeong, Suna Kang, Cao Shi Hua, Zhang Ting, Sunmin Park
Background: We investigated whether the long-term consumption of a symbiotic formulation with Lactobacillus fermentum (probiotic) and β-glucan from cauliflower mushroom (prebiotic) would delay the progression of post-menopausal symptoms in ovariectomized (OVX) rats and explored their mechanisms of action, including changes in gut microbiota. Methods: OVX rats were fed with high-fat diets containing 1% dextrin (control), 1% lyophilized cauliflower mushroom extract (CFM), 0...
2017: Genes & Nutrition
https://www.readbyqxmd.com/read/29151954/cpt1c-regulated-by-ampk-promotes-papillary-thyroid-carcinomas-cells-survival-under-metabolic-stress-conditions
#15
Rui Wang, Yajun Cheng, Dongwei Su, Boshen Gong, Xiaobo He, Xinyu Zhou, Zhijun Pang, Lingtao Cheng, Yuelei Chen, Zhenzhen Yao
Background: Cancer cells have to take metabolic transformation in tumor progression when facing need of increased energy and adequate vascularization. However, molecular mechanism is not fully known. In this study, we showed that expression of carnitine palmitoyltransferase 1C (Cpt1c), as a member of the gate-keeper enzymes , which transferring long-chain fatty acids into mitochondria to further oxidation, which is regulated by AMPK promotes papillary thyroid carcinomas cells survival under metabolic stress conditions...
2017: Journal of Cancer
https://www.readbyqxmd.com/read/29150352/dysregulation-of-mrna-translation-and-energy-metabolism-in-cancer
#16
REVIEW
Matthew Leibovitch, Ivan Topisirovic
Dysregulated mRNA translation and aberrant energy metabolism are frequent in cancer. Considering that mRNA translation is an energy demanding process, cancer cells must produce sufficient ATP to meet energy demand of hyperactive translational machinery. In recent years, the mammalian/mechanistic target of rapamycin (mTOR) emerged as a central regulatory node which coordinates energy consumption by the translation apparatus and ATP production in mitochondria. Aberrant mTOR signaling underpins the vast majority of cancers whereby increased mTOR activity is thought to be a major determinant of both malignant translatomes and metabolomes...
November 2, 2017: Advances in Biological Regulation
https://www.readbyqxmd.com/read/29150317/amp-activated-protein-kinase-regulation-of-the-nlrp3-inflammasome-during-aging
#17
REVIEW
Mario D Cordero, Matthew R Williams, Bernhard Ryffel
The NLRP3 inflammasome has recently emerged as an unexpected marker of stress and metabolic risk and has also been implicated in the development of major aging-related diseases such as gout, type 2 diabetes, obesity, cancer, and neurodegenerative and cardiovascular disorders. Several pathways regulating the NLRP3 inflammasome are currently being studied, but how the NLRP3 inflammasome is regulated remains unknown. AMP-activated protein kinase (AMPK), a central regulator of multiple metabolic pathways involved in the pathophysiology of aging and age-related diseases, has emerged as an important integrator of signals controlling inflammation including the inflammasome...
November 14, 2017: Trends in Endocrinology and Metabolism: TEM
https://www.readbyqxmd.com/read/29150224/reduced-gene-expression-of-sirtuins-and-active-ampk-levels-in-children-and-adolescents-with-obesity-and-insulin-resistance
#18
Zahra Arab Sadeghabadi, Mitra Nourbakhsh, Parvin Pasalar, Solaleh Emamgholipour, Abolfazl Golestani, Bagher Larijani, Maryam Razzaghy-Azar
BACKGROUND: Sirtuins, including SIRT1 and SIRT2, are longevity-associated deacetylase enzymes that modulate metabolic homeostasis in response to the cellular energy state. Adenosine monophosphate activated protein kinase (AMPK) and SIRT1 are interrelated and share several common target pathways. This study aimed to evaluate the SIRT1 and SIRT2 gene expression in peripheral blood mononuclear cells (PBMCs) as well as plasma levels of AMPK, in obese children and adolescents. MATERIALS AND METHODS: Participants included 60 children and adolescents (30 obese and 30 age- and gender-matched control subjects)...
November 14, 2017: Obesity Research & Clinical Practice
https://www.readbyqxmd.com/read/29148269/salidroside-attenuates-neuroinflammation-and-improves-functional-recovery-after-spinal-cord-injury-through-microglia-polarization-regulation
#19
Chenggui Wang, Qingqing Wang, Yiting Lou, Jianxiang Xu, Zhenhua Feng, Yu Chen, Qian Tang, Gang Zheng, Zengjie Zhang, Yaosen Wu, Naifeng Tian, Yifei Zhou, Huazi Xu, Xiaolei Zhang
Spinal cord injury (SCI) is a severe neurological disease; however, few drugs have been proved to treat SCI effectively. Neuroinflammation is the major pathogenesis of SCI secondary injury and considered to be the therapeutic target of SCI. Salidroside (Sal) has been reported to exert anti-inflammatory effects in airway, adipose and myocardial tissue; however, the role of Sal in SCI therapeutics has not been clarified. In this study, we showed that Sal could improve the functional recovery of spinal cord in rats as revealed by increased BBB locomotor rating scale, angle of incline, and decreased cavity of spinal cord injury and apoptosis of neurons in vivo...
November 17, 2017: Journal of Cellular and Molecular Medicine
https://www.readbyqxmd.com/read/29147952/gemigliptin-a-novel-dipeptidyl-peptidase-iv-inhibitor-exerts-a-synergistic-cytotoxicity-with-the-histone-deacetylase-inhibitor-pxd101-in-thyroid-carcinoma-cells
#20
S H Kim, J G Kang, C S Kim, S-H Ihm, M G Choi, H J Yoo, S J Lee
PURPOSE: The influence of the dipeptidyl peptidase-IV inhibitor gemigliptin alone or in combination with the histone deacetylase inhibitor PXD101 on survival of thyroid carcinoma cells was investigated. METHODS: SW1736, TPC-1, 8505C and BCPAP human thyroid carcinoma cells were used. To assess cell survival, cell viability, the percentage of viable cells and dead cells, cytotoxic activity, ATP levels and FACS analysis were measured. To validate the impact of gemigliptin combined with PXD101, the interactions were estimated by obtaining combination index in cells treated with two agents...
November 16, 2017: Journal of Endocrinological Investigation
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