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miRNA-218 Targets Lipin-1 and Glucose Transporter Type 4 Genes in 3T3-L1 Cells Treated With Lopinavir/Ritonavir
Conclusion: 3T3-L1 cells, treated with LPV/RTV, show altered lipid content due to increased miRNA-218 levels, which affects lipin-1 mRNA. Moreover, increased miRNA-218 levels were inversely correlated with changes in GLUT-4 expression, which suggests a role for miRNA-218 in mediating the insulin resistance consequent to cART. Introduction Metabolic syndrome is a serious consequence of combined Antiretroviral Therapy (cART). HIV-associated metabolic syndrome is often accompanied by lipodystrophy (LS), the redistribution of body fat with loss of subcutaneous adipose tissue in face, limbs and buttocks, concomitant wit...
Source: Frontiers in Pharmacology - April 29, 2019 Category: Drugs & Pharmacology Source Type: research

Tangshen Formula Alleviates Hepatic Steatosis by Inducing Autophagy Through the AMPK/SIRT1 Pathway
Conclusion In conclusion, the present study demonstrated that autophagy was involved in relieving the effects of TSF against NAFLD, which were mediated by the AMPK/SIRT1 pathway (Figure 7D). These findings may improve our current understanding of the role of TSF in treating hepatic steatosis and provide an experimental basis for the clinical application of TSF in NAFLD and its related metabolic syndrome. Ethics Statement This study was carried out in accordance with the recommendations in the Guide for the Care and Use of Laboratory Animals of the National Institutes of Health. The protocol was approved by the Ethics Co...
Source: Frontiers in Physiology - April 25, 2019 Category: Physiology Source Type: research

Sanguinarine Induces Apoptosis Pathway in Multiple Myeloma Cell Lines via Inhibition of the JaK2/STAT3 Signaling
In this study, we aimed to investigate the potential anti-proliferative and pro-apoptotic activities of SNG in a panel of MM cell lines (U266, IM9, MM1S, and RPMI-8226). SNG treatment of MM cells resulted in a dose-dependent decrease in cell viability through mitochondrial membrane potential loss and activation of caspase 3, 9, and cleavage of PARP. Pre-treatment of MM cells with a universal caspase inhibitor, Z-VAD-FMK, prevented SNG mediated loss of cell viability, apoptosis, and caspase activation, confirming that SNG-mediated apoptosis is caspase-dependent. The SNG-mediated apoptosis appears to be resulted from suppres...
Source: Frontiers in Oncology - April 16, 2019 Category: Cancer & Oncology Source Type: research

Genetic Regulation of Liver Metabolites and Transcripts Linking to Biochemical-Clinical Parameters
Conclusion In summary, this study is the first to combine metabolomics, transcriptomics, and genome-wide association studies in a porcine model. Our results improve understanding of the genetic regulation of metabolites which link to transcripts and finally biochemical-clinical parameters. Further, high-performance profiling of metabolites as intermediate phenotypes is a potentially powerful approach to uncover how genetic variation affects metabolic and health status. Our results advance knowledge in areas of biomedical and agricultural interest and identify potential correlates of biomarkers, SNPs-metabolites, SNPs-tran...
Source: Frontiers in Genetics - April 16, 2019 Category: Genetics & Stem Cells Source Type: research

lncRNA ZEB1-AS1 Mediates Oxidative Low-Density Lipoprotein-Mediated Endothelial Cells Injury by Post-transcriptional Stabilization of NOD2
Conclusion We report the discovery that ZEB1-AS1 functionally participates in ox-LDL-induced ECs injury via LRPPRC-mediated stabilization of NOD2. Uncovering the precise role of ZEB1-AS1/LRPPRC/NOD2 pathway in the progression of ox-LDL-induced ECs death and AS will not only increase our knowledge of ox-LDL-induced AS, but also enable the development of novel therapeutic strategies to overcome oxidation product-induced diseases. Author Contributions XX and CL designed and mainly did the study. CM, ZD, and YD helped and did the study. Conflict of Interest Statement The authors declare that the research was conducted in ...
Source: Frontiers in Pharmacology - April 15, 2019 Category: Drugs & Pharmacology Source Type: research

Complement C5b-9 and Cancer: Mechanisms of Cell Damage, Cancer Counteractions, and Approaches for Intervention
In conclusion, osmotic burst of inflated complement-damaged cells may occur, but these bursts are most likely a consequence of metabolic collapse of the cell rather than the cause of cell death. The Complement Cell Death Mediator: A Concerted Action of Toxic Moieties Membrane pores caused by complement were first visualized by electron microscopy on red blood cell membranes as large ring structures (22). Similar lesions were viewed on E. coli cell walls (23). Over the years, ample information on the fine ultrastructure of the MAC that can activate cell death has been gathered (24) and has been recently further examined (...
Source: Frontiers in Immunology - April 9, 2019 Category: Allergy & Immunology Source Type: research

Lactate-mediated mitoribosomal defects impair mitochondrial oxidative phosphorylation and promote hepatoma cell invasiveness Gene Regulation
Impaired mitochondrial oxidative phosphorylation (OXPHOS) capacity, accompanied by enhanced glycolysis, is a key metabolic feature of cancer cells, but its underlying mechanism remains unclear. Previously, we reported that human hepatoma cells that harbor OXPHOS defects exhibit high tumor cell invasiveness via elevated claudin-1 (CLN1). In the present study, we show that OXPHOS-defective hepatoma cells (SNU354 and SNU423 cell lines) exhibit reduced expression of mitochondrial ribosomal protein L13 (MRPL13), a mitochondrial ribosome (mitoribosome) subunit, suggesting a ribosomal defect. Specific inhibition of mitoribosomal ...
Source: Journal of Biological Chemistry - December 8, 2017 Category: Chemistry Authors: Young-Kyoung Lee, Jin J. Lim, Un-woo Jeoun, Seongki Min, Eun-beom Lee, So Mee Kwon, Changhan Lee, Gyesoon Yoon Tags: Molecular Bases of Disease Source Type: research

The 2-oxoglutarate carrier promotes liver cancer by sustaining mitochondrial GSH despite cholesterol loading
Publication date: April 2018 Source:Redox Biology, Volume 14 Author(s): Anna Baulies, Joan Montero, Nuria Matías, Naroa Insausti, Oihana Terrones, Gorka Basañez, Carmen Vallejo, Laura Conde de La Rosa, Laura Martinez, David Robles, Albert Morales, Joaquin Abian, Montserrat Carrascal, Keigo Machida, Dinesh B.U. Kumar, Hidekazu Tsukamoto, Neil Kaplowitz, Carmen Garcia-Ruiz, José C. Fernández-Checa Cancer cells exhibit mitochondrial cholesterol (mt-cholesterol) accumulation, which contributes to cell death resistance by antagonizing mitochondrial outer membrane (MOM) permeabilization. Hepatocellular mt-cholesterol loadin...
Source: Redox Biology - September 28, 2017 Category: Biology Source Type: research

miR-107-mediated decrease of HMGCS2 indicates poor outcomes and promotes cell migration in hepatocellular carcinoma.
Abstract Mitochondrial 3-hydroxy-3-methylglutaryl-CoA synthase (HMGCS2) has been implicated in human cancers, but its role and clinical significance in hepatocellular carcinoma (HCC) remain unknown. Here, we show that HMGCS2 is downregulated and exhibits antimetastatic potential in HCC. Low expression of HMGCS2 was associated with poor tumor differentiation, vascular invasion and worse overall and disease-free survivals in two independent cohorts consisting of 743 cases. In vitro data demonstrated HMGCS2 overexpression suppressed, whereas HMGCS2 silence promoted HCC cell migration via Epithelial-Mesenchymal Transi...
Source: The International Journal of Biochemistry and Cell Biology - August 31, 2017 Category: Biochemistry Authors: Su SG, Yang M, Zhang MF, Peng QZ, Li MY, Liu LP, Bao SY Tags: Int J Biochem Cell Biol Source Type: research

Mitochondrially Mediated HSF1 Activation Induces Cln-1 Molecular Bases of Disease
In this study, we demonstrated that mitochondrial respiratory defects induced Cln-1 transcription via reactive oxygen species (ROS)-mediated heat shock factor 1 (HSF1) activation, which contributed to hepatoma invasiveness. We first confirmed the inverse relationship between mitochondrial defects and Cln-1 induction in SNU hepatoma cells and hepatocellular carcinoma tissues. We then examined five different respiratory complex inhibitors, and complex I inhibition by rotenone most effectively induced Cln-1 at the transcriptional level. Rotenone increased both mitochondrial and cytosolic ROS. In addition, rotenone-induced Cln...
Source: Journal of Biological Chemistry - August 28, 2015 Category: Chemistry Authors: Lee, J.-H., Lee, Y.-K., Lim, J. J., Byun, H.-O., Park, I., Kim, G.-H., Xu, W. G., Wang, H.-J., Yoon, G. Tags: Signal Transduction Source Type: research

Metabolic profiling reveals that PNPLA3 induces widespread effects on metabolism beyond triacylglycerol remodeling in Huh-7 hepatoma cells
PNPLA3 was recently associated with the susceptibility to nonalcoholic fatty liver disease, a common cause of chronic liver disease characterized by abnormal triglyceride accumulation. Although it is established that PNPLA3 has both triacylglycerol lipase and acylglycerol O-acyltransferase activities, is still unknown whether the gene has any additional role in the modulation of the human liver metabolome. To uncover the functional role of PNPLA3 on liver metabolism, we performed high-throughput metabolic profiling of PNPLA3 siRNA-silencing and overexpression of wild-type and mutant Ile148Met variants (isoleucine/methionin...
Source: AJP: Gastrointestinal and Liver Physiology - July 1, 2014 Category: Gastroenterology Authors: Min, H.-K., Sookoian, S., Pirola, C. J., Cheng, J., Mirshahi, F., Sanyal, A. J. Tags: LIVER AND BILIARY TRACT Source Type: research

Metabolic profiling reveals that pnpla3 induces widespread effects on metabolism beyond triacylglycerol remodeling in huh-7 hepatoma cells.
METABOLIC PROFILING REVEALS THAT PNPLA3 INDUCES WIDESPREAD EFFECTS ON METABOLISM BEYOND TRIACYLGLYCEROL REMODELING IN HUH-7 HEPATOMA CELLS. Am J Physiol Gastrointest Liver Physiol. 2014 Apr 24; Authors: Min HK, Sookoian SC, Pirola CJ, Cheng J, Mirshahi F, Sanyal AJ Abstract PNPLA3 was recently associated with the susceptibility to nonalcoholic fatty liver disease, a common cause of chronic liver disease characterized by abnormal triglyceride accumulation. While it is established that PNPLA3 has both triacylglycerol lipase and acylglycerol O-acyltransferase activities, is still unknown whether the gene...
Source: American Journal of Physiology. Gastrointestinal and Liver Physiology - April 24, 2014 Category: Physiology Authors: Min HK, Sookoian SC, Pirola CJ, Cheng J, Mirshahi F, Sanyal AJ Tags: Am J Physiol Gastrointest Liver Physiol Source Type: research