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https://www.readbyqxmd.com/read/28202430/vespro-an-individual-patient-data-prospective-meta-analysis-of-selective-internal-radiation-therapy-versus-sorafenib-for-advanced-locally-advanced-or-recurrent-hepatocellular-carcinoma-of-the-sarah-and-sirvenib-trials
#1
Val Gebski, Emma Gibbs, Mihir Gandhi, Gilles Chatellier, Aurelia Dinut, Helena Pereira, Pierce Kh Chow, Valérie Vilgrain
BACKGROUND: Untreated advanced hepatocellular carcinoma (HCC) has an overall poor prognosis. Currently there are 2 ongoing prospective randomized controlled trials that are evaluating the efficacy and safety of sorafenib and selective internal radiation therapy (SIRT) with yttrium-90 resin microspheres in patients with advanced HCC. The SorAfenib versus Radioembolisation in Advanced Hepatocellular carcinoma (SARAH; 459 patients) trial is being performed in Europe and the SIRt VErsus SorafeNIB (SIRveNIB; 360 patients) trial in the Asia Pacific region...
February 15, 2017: JMIR Research Protocols
https://www.readbyqxmd.com/read/28197553/the-role-of-sirt1-in-epileptogenesis
#2
Alicia M Hall, Gary P Brennan, Tiffany M Nguyen, Akanksha Singh-Taylor, Hyun-Seung Mun, Mary J Sargious, Tallie Z Baram
The mechanisms by which brain insults lead to subsequent epilepsy remain unclear. Insults, including trauma, stroke, tumors, infections, and long seizures [status epilepticus (SE)], create a neuronal state of increased metabolic demand or decreased energy supply. Neurons express molecules that monitor their metabolic state, including sirtuins (Sirts). Sirtuins deacetylate cytoplasmic proteins and nuclear histones, and their epigenetic modulation of the chromatin governs the expression of many genes, influencing neuronal properties...
January 2017: ENeuro
https://www.readbyqxmd.com/read/28197299/sirtuins-expression-and-their-role-in-retinal-diseases
#3
REVIEW
Sankarathi Balaiya, Khaled K Abu-Amero, Altaf A Kondkar, Kakarla V Chalam
Sirtuins have received considerable attention since the discovery that silent information regulator 2 (Sir2) extends the lifespan of yeast. Sir2, a nicotinamide adenine dinucleotide- (NAD-) dependent histone deacetylase, serves as both a transcriptional effector and energy sensor. Oxidative stress and apoptosis are implicated in the pathogenesis of neurodegenerative eye diseases. Sirtuins confer protection against oxidative stress and retinal degeneration. In mammals, the sirtuin (SIRT) family consists of seven proteins (SIRT1-SIRT7)...
2017: Oxidative Medicine and Cellular Longevity
https://www.readbyqxmd.com/read/28177190/improving-patient-selection-for-selective-internal-radiation-therapy-of-intra-hepatic-cholangiocarcinoma-a-meta-regression-study
#4
Alessandro Cucchetti, Alberta Cappelli, Cristina Mosconi, Jian-Hong Zhong, Matteo Cescon, Antonio Daniele Pinna, Rita Golfieri
BACKGROUND & AIMS: Selective Internal Radiation Therapy (SIRT) is emerging as a potential therapy for unresectable intra-hepatic cholangiocarcinoma (iCCA), able to prolong life-expectancy. Aim of the study was to collect available literature, meta-analyze data and results and investigate sources of heterogeneity through a meta-regression approach, before suggesting SIRT as a valuable option. METHODS: A systematic review of studies published until 1 September 2016 in PubMed and Scopus databases was performed...
February 8, 2017: Liver International: Official Journal of the International Association for the Study of the Liver
https://www.readbyqxmd.com/read/28168178/aging-related-correlation-between-serum-sirtuin-1-activities-and-basal-metabolic-rate-in-women-but-not-in-men
#5
Hee Jae Lee, Soo Jin Yang
Sirtuin (SIRT) is a main regulator of metabolism and lifespan, and its importance has been implicated in the prevention against aging-related diseases. The purpose of this study was to identify the pattern of serum SIRT1 activity according to age and sex, and to investigate how serum SIRT1 activity is correlated with other metabolic parameters in Korean adults. The Biobank of Jeju National University Hospital, a member of the Korea Biobank Network, provided serum samples from 250 healthy adults. Aging- and metabolism-related factors were analyzed in serum, and the data were compared by the stratification of age and sex...
January 2017: Clinical Nutrition Research
https://www.readbyqxmd.com/read/28164517/prognostic-and-predictive-role-of-sirtuin1-expression-in-lung-adenocarcinoma
#6
Jun Wang, Changli Wang
BACKGROUND: SIRT1 is the homologue of sir2 in mammals, which is a nicotinamide adenine dinucleotide (NAD+) dependent histone deacetylase. Several studies have reported that the overexpression of Sirtuin1 (SIRT1) was associated with poor prognosis in various human cancers. However, little is known regarding the prognostic value of SIRT1 in lung adenocarcinoma. METHODS: SIRT 1 expression in tissues of 60 lung adenocarcinoma (LAC) patients was evaluated using immunohistochemistry...
October 1, 2016: Clinical Laboratory
https://www.readbyqxmd.com/read/28153032/analyses-of-caspase-1-regulated-transcriptomes-in-various-tissues-lead-to-identification-of-novel-il-1%C3%AE-il-18-and-sirtuin-1-independent-pathways
#7
Ya-Feng Li, Gayani Nanayakkara, Yu Sun, Xinyuan Li, Luqiao Wang, Ramon Cueto, Ying Shao, Hangfei Fu, Candice Johnson, Jiali Cheng, Xiongwen Chen, Wenhui Hu, Jun Yu, Eric T Choi, Hong Wang, Xiao-Feng Yang
BACKGROUND: It is well established that caspase-1 exerts its biological activities through its downstream targets such as IL-1β, IL-18, and Sirt-1. The microarray datasets derived from various caspase-1 knockout tissues indicated that caspase-1 can significantly impact the transcriptome. However, it is not known whether all the effects exerted by caspase-1 on transcriptome are mediated only by its well-known substrates. Therefore, we hypothesized that the effects of caspase-1 on transcriptome may be partially independent from IL-1β, IL-18, and Sirt-1...
February 2, 2017: Journal of Hematology & Oncology
https://www.readbyqxmd.com/read/28135086/thienopyrimidinone-based-sirtuin-2-sirt2-selective-inhibitors-bind-in-the-ligand-induced-selectivity-pocket
#8
Sandeep Sundriyal, Sébastien Moniot, Zimam Mahmud, Shang Yao, Paolo Di Fruscia, Christopher R Reynolds, David T Dexter, Michael J E Sternberg, Eric W-F Lam, Clemens Steegborn, Matthew J Fuchter
Sirtuins (SIRTs) are NAD-dependent deacylases, known to be involved in a variety of pathophysiological processes and thus remain promising therapeutic targets for further validation. Previously, we reported a novel thienopyrimidinone SIRT2 inhibitor with good potency and excellent selectivity for SIRT2. Herein, we report an extensive SAR study of this chemical series and identify the key pharmacophoric elements and physiochemical properties that underpin the excellent activity observed. New analogues have been identified with submicromolar SIRT2 inhibtory activity and good to excellent SIRT2 subtype-selectivity...
February 15, 2017: Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/28130175/up-regulation-of-sirt6-in-the-hippocampus-induced-rats-with-depression-like-behavior-via-the-block-akt-gsk3%C3%AE-signaling-pathway
#9
Qiang Mao, Xue Gong, Chanjuan Zhou, Zhe Tu, Libo Zhao, Ling Wang, Xinfa Wang, Lu Sun, Jinjun Xia, Bin Lian, Jianjun Chen, Jun Mu, Deyu Yang, Peng Xie
Major depression is the leading cause of disability worldwide, which is associated with diverse alterations in brain such as neuro-inflammation, synaptic dysfunction, and cognitive deficit. Accumulating evidences suggest sirtuins (SIRTs) are involved in brain developmental disorders, metabolic diseases and play a key role in cognition and synaptic plasticity, yet the role in mood regulation remains controversial. Hence, Western blotting and RT-qPCR were used to investigate whether SIRTs (SIRT1-7) expression levels were altered in the hippocampus of rats, which followed 5 weeks of chronic unpredictable mild stress (CUMS) treatment, the results showed depressive-like behaviors: like body weight, forced swim test and sucrose preference test and SIRT6 was a significant increase in the hippocampal of CUMS rats...
January 24, 2017: Behavioural Brain Research
https://www.readbyqxmd.com/read/28128062/a-review-on-sirtuins-in-diabetes
#10
R Aditya, A Ravi Kiran, D Sai Varma, Ravichandra Vemuri, Rohit Gundamaraju
BACKGROUND: Type-2 Diabetes is a long lasting disease characterized by high glucose concentration in the blood due to insulin resistance. One of the recent treatment strategies is using activators against SIRT-1, which has been in clinical trials. Hence, it is necessary to know the effects of the SIRT-1 modulators against various metabolic pathways. METHODS: Many cellular processes, including insulin secretion, cell cycle, and apoptosis are imperatively regulated by a family of mediators called SIRTuins...
January 25, 2017: Current Pharmaceutical Design
https://www.readbyqxmd.com/read/28127745/5-fluorouracil-causes-endothelial-cell-senescence-potential-protective-role-of-glucagon-like-peptide-1
#11
Paola Altieri, Roberto Murialdo, Chiara Barisione, Edoardo Lazzarini, Silvano Garibaldi, Patrizia Fabbi, Clarissa Ruggeri, Silvia Borile, Federico Carbone, Andrea Armirotti, Marco Canepa, Alberto Ballestrero, Claudio Brunelli, Fabrizio Montecucco, Pietro Ameri, Paolo Spallarossa
BACKGROUND AND PURPOSE: 5-fluorouracil (5FU) and its prodrug, capecitabine, can damage endothelial cells, whilst endothelial integrity is preserved by glucagon-like peptide 1 (GLP-1). Here, we studied the effect of 5FU on endothelial senescence and whether GLP-1 antagonizes it. EXPERIMENTAL APPROACH: EA.hy926 cells were exposed to 5FU or sera from patients taking capecitabine, with or without pre-incubation with GLP-1. Senescence was identified by expression of senescence-associated β-galactosidase and p16(INK4a) and reduced cell proliferation...
January 27, 2017: British Journal of Pharmacology
https://www.readbyqxmd.com/read/28113081/effect-of-6-gingerol-on-ampk-nf-%C3%AE%C2%BAb-axis-in-high-fat-diet-fed-rats
#12
Reem M Hashem, Laila A Rashed, Kamel M A Hassanin, Mona H Hetta, Asmaa O Ahmed
OBJECTIVES: Adenosine monophosphate (AMP)-activated protein kinase (AMPK) plays a central role in metabolic homeostasis and regulation of inflammatory responses through attenuation of nuclear factor kappa-B (NF-κB), Thus AMPK may be a promising pharmacologic target for the treatment of various chronic inflammatory diseases. We examined the effect of 6-gingerol, an active ingredient of ginger on AMPK-NF-κB pathway in high fat diet (HFD) rats in comparison to fish oil. METHODS: Protein levels of AMPK-α1 and phosphorylated AMPK-α1 were measured by western blot while Sirtuin 6 (Sirt-6), resistin and P65 were estimated by RT-PCR, TNF-α was determined by ELISA, FFAs were estimated chemically as well as the enzymatic determination of the metabolic parameters...
January 20, 2017: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/28106504/insulin-like-growth-factor-1-mediated-dna-repair-in-irradiated-salivary-glands-is-sirtuin-1-dependent
#13
S Meyer, A M Chibly, R Burd, K H Limesand
Ionizing radiation is one of the most common cancer treatments; however, the treatment leads to a wide range of debilitating side effects. In patients with head and neck cancer (HNC), the surrounding normal salivary gland is extremely sensitive to therapeutic radiation, and damage to this tissue results in various oral complications and decreased quality of life (QOL). In the current study, mice treated with targeted head and neck radiation showed a significant increase in double-stranded breaks (DSB) in the DNA of parotid salivary gland cells immediately after treatment, and this remained elevated 3 h posttreatment...
February 2017: Journal of Dental Research
https://www.readbyqxmd.com/read/28104916/trpv1-activation-counters-diet-induced-obesity-through-sirtuin-1-activation-and-prdm-16-deacetylation-in-brown-adipose-tissue
#14
P Baskaran, V Krishnan, K Fettel, P Gao, Z Zhu, J Ren, B Thyagarajan
BACKGROUND/OBJECTIVE: An imbalance between energy intake and expenditure leads to obesity. Increasing metabolism and thermogenesis in brown adipose tissue (BAT) can help in overcoming obesity. Here, we investigated the effect of activation of transient receptor potential vanilloid subfamily 1 (TRPV1) in the upregulation of thermogenic proteins in BAT to counter diet-induced obesity. SUBJECTS/METHODS: We investigated the effect of dietary supplementation of capsaicin (CAP) (TRPV1 agonist) on the expression of metabolically important thermogenic proteins in BAT of wild-type and TRPV1(-/-) mice that received either a normal chow or high-fat (±CAP; TRPV1 activator) diet by immunoblotting...
February 14, 2017: International Journal of Obesity: Journal of the International Association for the Study of Obesity
https://www.readbyqxmd.com/read/28093238/a-model-of-the-mitochondrial-basis-of-bipolar-disorder
#15
REVIEW
Gerwyn Morris, Ken Walder, Sean L McGee, Olivia M Dean, Susannah J Tye, Michael Maes, Michael Berk
BACKGROUND: Bipolar disorder phenomenologically is a biphasic disorder of energy availability; increased in mania and decreased in depression. In consort, there is accumulating evidence indicating increased mitochondrial respiration and ATP production in bipolar mania which contrasts with decreased mitochondrial function in patients in the euthymic or depressive phase of the illness. Consequently, the central thesis of this paper is that bipolar disorder is due to a phasic dysregulation of mitochondrial biogenergetics...
January 14, 2017: Neuroscience and Biobehavioral Reviews
https://www.readbyqxmd.com/read/28090296/endotoxin-and-mechanical-stress-induced-epigenetic-changes-in-the-regulation-of-the-nicotinamide-phosphoribosyltransferase-promoter
#16
Venkateswaran Ramamoorthi Elangovan, Sara M Camp, Gabriel T Kelly, Ankit A Desai, Djanybek Adyshev, Xiaoguang Sun, Stephen M Black, Ting Wang, Joe G N Garcia
Mechanical ventilation, a lifesaving intervention for patients with acute respiratory distress syndrome (ARDS), also unfortunately contributes to excessive mechanical stress and impaired lung physiological and structural integrity. We have elsewhere established the pivotal role of increased nicotinamide phosphoribosyltransferase (NAMPT) transcription and secretion as well as its direct binding to the toll-like receptor 4 (TLR4) in the progression of this devastating syndrome; however, regulation of this critical gene in ventilator-induced lung injury (VILI) is not well characterized...
December 2016: Pulmonary Circulation
https://www.readbyqxmd.com/read/28078116/pretreatment-tumor-volume-as-a-prognostic-factor-in-metastatic-colorectal-cancer-treated-with-selective-internal-radiation-to-the-liver-using-yttrium-90-resin-microspheres
#17
Neha Bhooshan, Navesh K Sharma, Shahed Badiyan, Adeel Kaiser, Fred M Moeslein, Young Kwok, Pradip P Amin, Svetlana Kudryasheva, Michael D Chuong
BACKGROUND: Yttrium-90 ((90)Y)-resin microspheres can prolong intrahepatic disease control and improve overall survival (OS) in patients with metastatic colorectal cancer (CRC). Prognostic factors for improved outcomes in patients undergoing selective internal radiation therapy (SIRT) have been studied, but the relationship between pre-SIRT liver tumor volume and outcomes has not well described. METHODS: We retrospectively reviewed the records of patients with metastatic CRC who were treated at our institution with (90)Y-resin microspheres...
December 2016: Journal of Gastrointestinal Oncology
https://www.readbyqxmd.com/read/28074772/-nuclear-medicine-techniques-for-selective-internal-radiotherapy-of-liver-cancer
#18
Peter Frøhlich Staanum, Anne Kirstine Arveschoug, Stine Maria Jentoft Kramer, Jens Erik Nielsen, Dennis Tønner Nielsen, Peter Ott, Henning Grønbæk, Gerda Elisabeth Villadsen
Selective internal radiation therapy (SIRT) of hepatocellular carcinoma has been introduced at Aarhus University Hospital. 90Y-microspheres are implanted in the tumour by catheterization of the tumour feeding liver artery. Pretreatment angiography and test treatment using 99mTc-labelled particles followed by scintigraphy ensure a feasible and effective treatment. Post-treatment imaging of radiation from 90Y visualize the localization of microspheres. Currently, SIRT is also applied for liver metastases of neuroendocrine tumours...
January 2, 2017: Ugeskrift for Laeger
https://www.readbyqxmd.com/read/28071652/the-local-nature-of-incompressibility-of-quantum-hall-effect
#19
E M Kendirlik, S Sirt, S B Kalkan, N Ofek, V Umansky, A Siddiki
Since the experimental realization of the integer quantum Hall effect in a two-dimensional electron system, the interrelation between the conductance quantization and the topological properties of the system has been investigated. Assuming that the two-dimensional electron system is described by a Bloch Hamiltonian, system is insulating in the bulk of sample throughout the quantum Hall plateau due to a magnetic field induced energy gap. Meanwhile, the system is conducting at the edges resembling a 2+1 dimensional topological insulator without time-reversal symmetry...
January 10, 2017: Nature Communications
https://www.readbyqxmd.com/read/28065600/lysyl-oxidase-3-is-a-dual-specificity-enzyme-involved-in-stat3-deacetylation-and-deacetylimination-modulation
#20
Li Ma, Chao Huang, Xiong-Jun Wang, Dazhuan Eric Xin, Li-Shun Wang, Quanli C Zou, Ya-Nan S Zhang, Min-Dian Tan, Yu-Mei Wang, Ting C Zhao, Devasis Chatterjee, Rachel A Altura, Chuangui Wang, Yan S Xu, Jing-Hua Yang, Yong-Sheng Fan, Bao-Hui Han, Jianmin Si, Xiaoren Zhang, Jinke Cheng, Zhijie Chang, Y Eugene Chin
In mammalian cells, histone deacetylase (HDAC) and Sirtuin (SIRT) are two families responsible for removing acetyl groups from acetylated proteins. Here, we describe protein deacetylation coupled with deacetylimination as a function of lysyl oxidase (LOX) family members. LOX-like 3 (Loxl3) associates with Stat3 in the nucleus to deacetylate and deacetyliminate Stat3 on multiple acetyl-lysine sites. Surprisingly, Loxl3 N-terminal scavenger receptor cysteine-rich (SRCR) repeats, rather than the C-terminal oxidase catalytic domain, represent the major deacetylase/deacetyliminase activity...
January 19, 2017: Molecular Cell
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