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Sirt 1

María Paula Ceballos, Giulia Decándido, Ariel Darío Quiroga, Carla Gabriela Comanzo, Verónica Inés Livore, Florencia Lorenzetti, Flavia Lambertucci, Lorena Chazarreta-Cifre, Claudia Banchio, María de Luján Alvarez, Aldo Domingo Mottino, María Cristina Carrillo
Sirtuins (SIRTs) 1 and 2 deacetylases are overexpressed in hepatocellular carcinoma (HCC) and are associated with tumoral progression and multidrug resistance (MDR). In this study we analyzed whether SIRTs 1 and 2 activities blockage was able to affect cellular survival and migration and to modulate p53 and FoxO1 acetylation in HepG2 and Huh7 cells. Moreover, we analyzed ABC transporters P-glycoprotein (P-gp) and multidrug resistance-associated protein 3 (MRP3) expression. We used cambinol and EX-527 as SIRTs inhibitors...
March 12, 2018: Toxicology Letters
Shuyi Wang, Cong Wang, Subat Turdi, Kacy L Richmond, Yingmei Zhang, Jun Ren
BACKGROUND AND AIMS: Uncorrected obesity contributes to cardiac remodeling and contractile dysfunction although the underlying mechanism remains poorly understood. Mitochondrial aldehyde dehydrogenase (ALDH2) is a mitochondrial enzyme with some promises in a number of cardiovascular diseases. This study was designed to evaluate the impact of ALDH2 on cardiac remodeling and contractile property in high fat diet-induced obesity. METHODS: Wild-type (WT) and ALDH2 transgenic mice were fed low (10% calorie from fat) or high (45% calorie from fat) fat diet for 5 months prior to the assessment of cardiac geometry and function using echocardiography, IonOptix system, Lectin, and Masson Trichrome staining...
March 13, 2018: International Journal of Obesity: Journal of the International Association for the Study of Obesity
Han Jiang, Shijie Xin, Yumeng Yan, Yu Lun, Xiao Yang, Jian Zhang
BACKGROUND AND AIMS: Acetylation levels of FOXP3 could influence its expression level and SIRT1 is a deacetylase, which could regulate the acetylation level of FOXP3. We aimed to investigate the mechanism of Treg dysfunction, which might be caused by abnormal acetylation of FOXP3 regulated by SIRT1 in abdominal aortic aneurysm (AAA) patients. METHODS: Peripheral CD4+ T cells from AAA patients, abdominal aortic atherosclerotic occlusive disease (AOD) patients, and healthy donors (HC) were analyzed by flow cytometry to determine the percentage of CD4+ CD25+ Tregs and CD4+ CD25+ FOXP3+ T cells in CD4+ T cells...
February 14, 2018: Atherosclerosis
Bong-Geum Jang, Boyoung Choi, Suyeon Kim, Jae-Yong Lee, Min-Ju Kim
Neuroblastoma cell differentiation is a valuable model for studying therapeutic methods in neuroblastoma and the mechanisms of neuronal differentiation. Here, we used trichostatin A (TSA) and sirtinol, which are inhibitors of cHDACs and sirtuins, respectively, to show that classical histone deacetylases (cHDACs) and sirtuins (silent mating type information regulation 2 homolog; SIRTs) affect all-trans retinoic acid (ATRA)-induced differentiation of neuroblastoma cells. After first determining neurite elongation and expression levels of tyrosine hydroxylase and high size neurofilament as useful differentiation markers, we observed that TSA increased neuroblastoma cell differentiation, while sirtinol had the antagonistic effect of decreasing it...
March 7, 2018: Journal of Molecular Neuroscience: MN
Hanlin Yao, Zhen Yao, Shaocheng Zhang, Wenjun Zhang, Wen Zhou
Osteoporosis is a disease that significantly influences life expectancy and quality in humans. Oxidative stress may stimulate bone marrow osteoclast differentiation and inhibit osteoblast (OB) differentiation. OB proliferation and differentiation are affected by the forkhead box O (FoxO)1/β‑catenin signaling pathway. The osteogenic differentiation of mesenchymal stem cells (MSCs) may be promoted by silent information regulator type‑1 [sirtuin (SIRT)1]. However, the molecular mechanism of SIRT1 regulation of osteogenic differentiation of MSCs remains unclear, and further elucidation is needed...
March 1, 2018: Molecular Medicine Reports
Xiaojuan Wang, Jun Li, Wei Tang, Yiqiao Zhao, Xing Li
Background The development of an effective treatment for type 2 diabetes mellitus is urgently needed. This study aimed to investigate the role of micro RNA (miR)-323-3p in regulating the expression of adiponectin receptor 1 (AdipoR1), as well as the insulin secretion and cell function of pancreatic MIN6 β-cells. Methods MIN6 cells were treated with miR-323-3p mimics or inhibitors, and the effects on cell growth, proliferation, mitosis, and insulin secretion were studied. The expression levels of sirtuin-1 (SIRT-1) and AMP-activated protein kinase (AMPK) genes were also assessed...
January 1, 2018: Journal of International Medical Research
Cathal O'Leary, Megan Greally, John McCaffrey, Peter Hughes, Leo L P Lawler, Martin O'Connell, Tony Geoghegan, Cormac Farrelly
BACKGROUND: Liver metastases are the commonest cause of death for patients with colorectal cancer. Growing evidence supports the use of selective internal radiation therapy (SIRT) in combination with conventional chemotherapy regimens for liver-only or liver-dominant unresectable metastatic colorectal cancer. AIMS: To measure and evaluate outcomes of the first 20 consecutive patients with unresectable colorectal liver metastasis selected for SIRT in addition to their chemotherapy at a single Irish institution...
March 6, 2018: Irish Journal of Medical Science
Yung-Tsung Chen, Yu-Chun Lin, Jin-Seng Lin, Ning-Sun Yang, Ming-Ju Chen
SCOPE: Non-alcoholic fatty liver disease (NAFLD) is a common disease that is concomitant with obesity, resulting in increased mortality. To date, the efficiency of NAFLD treatment still needs to be improved. Therefore, we aimed to evaluate the effect of Lactobacillus mali APS1, which was isolated from sugary kefir, on hepatic steatosis in rats fed a high-fat diet (HFD). METHODS AND RESULTS: Sprague Dawley rats were fed a control diet, a high-fat diet with saline and a high-fat diet with APS1 intervention by gavage daily for 12 weeks...
March 5, 2018: Molecular Nutrition & Food Research
Aglaia Domouchtsidou, Vahé Barsegian, Stefan P Mueller, Jan Best, Judith Ertle, Sotiria Bedreli, Peter A Horn, Andreas Bockisch, Monika Lindemann
The purpose of our study was to assess the immune function of patients with inoperable hepatic malignancies after treatment with selective internal radiotherapy (SIRT) and to identify possible correlations with clinical parameters. In 25 patients receiving SIRT lymphocyte proliferation and the production of pro- and anti-inflammatory cytokines (interferon-γ and interleukin-10) after stimulation with mitogens and microbial antigens were tested prior to therapy, directly after therapy (day 1) and at day 2, 7 and 28 post therapy using the lymphocyte transformation test and enzyme-linked immunospot assays...
March 2, 2018: Cancer Immunology, Immunotherapy: CII
Weifeng Wan, Yan Ding, Zongyi Xie, Qian Li, Feng Yan, Enkhjargal Budbazar, William J Pearce, Richard Hartman, Andre Obenaus, John H Zhang, Yong Jiang, Jiping Tang
Platelet-derived growth factor receptor-β (PDGFR-β) has been reported to promote phenotypic transformation of vascular smooth muscle cells (VSMCs). The purpose of this study was to investigate the role of the PDGFR-β/IRF9/SIRT-1/NF-κB pathway in VSMC phenotypic transformation after subarachnoid hemorrhage (SAH). SAH was induced using the endovascular perforation model in Sprague-Dawley rats. PDGFR-β small interfering RNA (siRNA) and IRF9 siRNA were injected intracerebroventricularly 48 h before SAH. SIRT1 activator (resveratrol) and inhibitor (EX527) were administered intraperitoneally 1 h after SAH induction...
January 1, 2018: Journal of Cerebral Blood Flow and Metabolism
Hui-Rong Jing, Fu-Wen Luo, Xing-Ming Liu, Xiao-Feng Tian, Yun Zhou
AIM: To evaluate whether fish oil (FO) can protect liver injury induced by intestinal ischemia/reperfusion (I/R) via the AMPK/SIRT-1/autophagy pathway. METHODS: Ischemia in Wistar rats was induced by superior mesenteric artery occlusion for 60 min and reperfusion for 240 min. One milliliter per day of FO emulsion or normal saline was administered by intraperitoneal injection for 5 consecutive days to each animal. Animals were sacrificed at the end of reperfusion...
February 21, 2018: World Journal of Gastroenterology: WJG
Hyun S Kim, Walid L Shaib, Chao Zhang, Ganji Purnachandra Nagaraju, Christina Wu, Olatunji B Alese, Zhengjia Chen, Edith Brutcher, Meredith Renfroe, Bassel F El-Rayes
BACKGROUND: Neuroendocrine tumors (NETs) metastasize to the liver. Everolimus and selective internal radioembolization (SIRT) are approved treatments. Pasireotide is a somatostatin analogue with an affinity for somatostatin receptors 1, 2, 3, and 5. Everolimus and pasireotide may potentiate SIRT radiosensitization and inhibit rebound angiogenesis. This study evaluated the safety of pasireotide, everolimus, and SIRT. METHODS: This 3 + 3 phase 1 trial evaluated 3 dose levels of everolimus (2...
February 16, 2018: Cancer
Roberta Nicoleta Bogoi, Alicia de Pablo, Eulalia Valencia, Luz Martín-Carbonero, Victoria Moreno, Helem Haydee Vilchez-Rueda, Victor Asensi, Rosa Rodriguez, Victor Toledano, Berta Rodés
Background: Integration of human immunodeficiency virus type 1 (HIV-1) into the host genome causes global disruption of the chromatin environment. The abundance level of various chromatin-modifying enzymes produces these alterations and affects both the provirus and cellular gene expression. Here, we investigated potential changes in enzyme expression and global DNA methylation in chronically infected individuals with HIV-1 and compared these changes with non-HIV infected individuals...
2018: Clinical Epigenetics
Yongnan Li, Shuodong Wu
This study aims to explore the effect of epigallocatechin gallate (EGCG) on blood lipids, liver lipids, and cholesterol synthesis in hyperlipidemic rats. SREBP-2 transgenic rats were used to investigate the transcriptional level of SREBP-2 regulated by SIRT-1/FOXO1 and the molecular mechanism of rate-limiting enzyme HMGCR that affects cholesterol synthesis. Rat models of hyperlipidemia were established and administered EGCG. Cholesterol synthesis was observed. Enzyme linked immunosorbent assay was used to determine serum triglyceride (TG), total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), free fatty acid (FFA), superoxide dismutase (SOD), malondialdehyde (MDA), and T-AOC contents...
February 14, 2018: Molecular and Cellular Biochemistry
Dolores Olivares, Javier Perez-Hernandez, Maria J Forner, Cristina Pérez-Soriano, Maria C Tormos, Guillermo T Sáez, Felipe J Chaves, Josep Redón, Raquel Cortés
Identifying new markers of disease flares in lupus nephritis (LN) that facilitate patient stratification and prognosis is important. Therefore, the aim of this study was to analyze whether urinary SIRT1 expression was altered in LN and whether SIRT1 values in urine could be valuable biomarker of disease activity. In a cohort study, urinary pellets from 40 patients diagnosed with systemic lupus erythematosus (SLE) were analyzed. Clinical measures of lupus activity were assessed. The expression of SIRT1 was quantified by quantitative PCR (qRT-PCR) and immunoblot, then compared between patients with active lupus nephritis, in remission and healthy controls...
February 12, 2018: Clinical Science (1979-)
Shireen A Hedya, Marwa M Safar, Ashraf K Bahgat
Nuclear receptor related 1 (Nurr1) orphan receptor has emerged as a promising contender in ameliorating Parkinson's disease; thus, finding a suitable activator of Nurr1 receptor is an attracting target for treating PD. Cilostazol, a phosphodiesterase-3 inhibitor, recently showed a favorable neuroprotective activity in multiple devastating central disorders, yet the possible antiparkinsonian activity of the drug has not been fully elucidated. Thus, the aim of this study is to explore the neuroprotective effect of cilostazol in rotenone-induced PD model in rats...
February 10, 2018: Molecular Neurobiology
Dina Sabry, Shereen Rashad Kaddafy, Ahmed Ali Abdelaziz, Abdelfattah Kasem Nassar, Mohamed Moneer Rayan, Sadek Mostafa Sadek, Amany A Abou-Elalla
Background: We investigated SIRT-1 genetic variant and its association with vitamin D level in Egyptian patients with rheumatoid arthritis (RA). Methods: Seventy Egyptian subjects were enrolled in our study and divided into two groups: RA group (n = 50 patients) and healthy control group (n = 20 subjects). Five milliliter blood sample was withdrawn from each subject followed by laboratory investigation and DNA extraction for SIRT-1 gene polymorphism assessment (rs7895833 A>G, rs7069102 C>G and rs2273773 C>T) and vitamin D level expression...
March 2018: Journal of Clinical Medicine Research
Philipp Matthies, Milad Mesri, Francisco Alves Pinto, Jan Wuestemann, Oliver Grosser
INTRODUCTION: Clinical Bremsstrahlung imaging with gamma cameras or SPECT scanners, for example used in selective internal radiation therapy (SIRT) [1], suffers from low contrast due to a continuous spectrum and a high amount of scatter. Information about the scattering of the radionuclide within the patient's body can be obtained from Monte-Carlo simulations and subsequently being used to improve image quality. METHODS: An MAA-acquisition (CT+SPECT) of a HCC patient with a unifocal uptake in the right liver lobe is segmented (lesion) and loaded into the MC simulation framework GATE [2]...
January 2018: Physica Medica: PM
Helmut J M H Dittmann, Daniel Kopp, Juergen Kupferschlaeger, Diana Feil, Gerd Groezinger, Roland Syha, Matthias Weissinger, Christian La Fougère
Hepatopulmonary shunt fraction (LSF)-estimation using Tc-99m-Macroalbumine (MAA) imaging is performed prior to selective internal radiotherapy (SIRT) of the liver in order to reduce risk of pulmonary irradiation burden. Generally, planar scans are acquired after injection of MAA into the hepatic artery. However, validity of this approach is limited by different attenuation of liver and lung tissue as well as inaccurate segmentation of the organs. Aim of this study was to evaluate quantitative SPECT/CT for LSF-assessment in a prospective clinical cohort...
January 25, 2018: Journal of Nuclear Medicine: Official Publication, Society of Nuclear Medicine
Charlotte A Porter, Kevin M Bradley, Eero T Hippeläinen, Matthew D Walker, Daniel R McGowan
BACKGROUND: Post-therapy SPECT/CT imaging of 90Y microspheres delivered to hepatic malignancies is difficult, owing to the continuous, high-energy Bremsstrahlung spectrum emitted by 90Y. This study aimed to evaluate the utility of a commercially available software package (HybridRecon, Hermes Medical Solutions AB) which incorporates full Monte Carlo collimator modelling. Analysis of image quality was performed on both phantom and clinical images in order to ultimately provide a recommendation of an optimum reconstruction for post-therapy 90Y microsphere SPECT/CT imaging...
January 22, 2018: EJNMMI Research
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