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Lingling Tang, Qingge Chen, Ziyu Meng, Li Sun, Linyun Zhu, Jinjin Liu, Junsheng Hu, Zhenhua Ni, Xiongbiao Wang
BACKGROUND/AIMS: A growing number of studies have demonstrated that the activity and expression level of sirtuin-1 (SIRT1) are decreased in asthma patients; however, the mechanisms underlying decreased SIRT1 expression and function are still not completely understood. Interleukin (IL)-6 plays important roles in inflammation during allergic asthma. In this study, we examined whether loss of SIRT1 activity regulated the expression of IL-6 and further verified the underlying mechanisms. METHODS: The human airway epithelial cell line 16HBE was used to test the effects of the SIRT1 inhibitor (salermide) on expression of IL-6...
October 20, 2017: Cellular Physiology and Biochemistry
Jie Peng, Yinghui Wu, Zhao Deng, Yuanfei Zhou, Tongxing Song, Yang Yang, Xiaming Zhang, Tao Xu, Mao Xia, Anle Cai, Zuhong Liu, Jian Peng
Obesity is associated with a wide range of metabolic disorders including inflammation and insulin-resistance. Sirtuin-1 (SIRT1) is an important regulator of metabolic homeostasis and stress response pathways in white adipose tissue. However, involvement of microRNAs (miRNAs) in regulating SIRT1 during obesity-induced inflammation and insulin-resistance remains unclear. Here, we found that miR-377 was upregulated in adipose tissue and showed a negative correlation with SIRT1 in chronic high fat diet (HFD)-fed mice...
September 19, 2017: Oncotarget
Sandra López-Domènech, Celia Bañuls, Aranzazu M de Marañón, Zaida Abab-Jiménez, Carlos Morillas, Segundo Ángel Gómez-Abril, Susana Rovira-Llopis, Víctor Manuel Víctor, Antonio Hernández-Mijares, Milagros Rocha
BACKGROUND & AIMS: It is known that pinitol acts as a mediator of the insulin-signaling pathway, though little is known about its anti-inflammatory effect in human obesity. Therefore, this study aimed to evaluate the effect of pinitol on peripheral blood mononuclear cells (PBMCs) and visceral (VAT) and subcutaneous adipose tissues (SAT), focusing on the involvement of endoplasmic reticulum (ER) stress and sirtuin 1 (SIRT1). METHODS: In the intervention study, thirteen obese subjects consumed a pinitol-enriched beverage (PEB) for 12 weeks...
October 3, 2017: Clinical Nutrition: Official Journal of the European Society of Parenteral and Enteral Nutrition
Hyung Jin Hahn, Ki Bbeum Kim, In-Sook An, Kyu Joong Ahn, Hyun Joo Han
Hydrogen peroxide (H2O2) is a reactive oxygen species (ROS) that induces numerous cellular events, including cellular senescence and inflammatory responses. Therefore, the aim of this study was to investigate the protective effect of Rosmarinic acid (RA) in H2O2‑induced oxidative stress in normal human dermal fibroblasts (NHDFs). Cytotoxicity assays were performed using a water‑soluble tetrazolium salt, and senescence‑associated β‑galactosidase activity was determined to investigate the proportion of senescent cells...
October 17, 2017: Molecular Medicine Reports
Cong Qian, Jianxiang Jin, Jingyin Chen, Jianru Li, Xiaobo Yu, Hangbo Mo, Gao Chen
Early brain injury is considered to be a major risk that is related to the prognosis of subarachnoid hemorrhage (SAH). In SAH model rats, brain edema and apoptosis have been closely related with death rate and neurological function. Sirtuin 1 (SIRT1) was reported to be involved in apoptosis in cerebral ischemia and brain tumor formation through p53 deacetylation. The present study aimed to evaluate the role of SIRT1 in a rat endovascular perforation model of SAH. The SIRT1 activator resveratrol (RES) was administered 48 h prior to SAH induction and the SIRT1 inhibitor Sirtinol (SIR) was used to reverse the effects of RES on SIRT1 expression...
October 12, 2017: Molecular Medicine Reports
Cheng Zeng, Xiaoyan Hu, Weiyang He, Yanfeng Wang, Ling Li, Yan Xiong, Qifa Ye
Hypothermic machine perfusion (HMP) effectively reduces ischemia‑reperfusion injury (IRI) in livers donated after circulatory death (DCD) when compared with cold storage (CS). However, the underlying mechanisms remain unclear. The current study aimed to investigate the cellular mechanisms by which HMP ameliorates the inflammatory response during IRI. Adult male Sprague‑Dawley rat livers were exposed to 30 min of warm ischemia following cardiac arrest and preserved by CS or HMP for 3 h (n=3 per group)...
October 6, 2017: Molecular Medicine Reports
Begoña Euba, Nahikari López-López, Irene Rodríguez-Arce, Ariadna Fernández-Calvet, Montserrat Barberán, Nuria Caturla, Sara Martí, Roberto Díez-Martínez, Junkal Garmendia
The respiratory pathogen nontypeable Haemophilus influenzae (NTHi) is an important cause of acute exacerbation of chronic obstructive pulmonary disease (AECOPD) that requires efficient treatments. A previous screening for host genes differentially expressed upon NTHi infection identified sirtuin-1, which encodes a NAD-dependent deacetylase protective against emphysema and is activated by resveratrol. This polyphenol concomitantly reduces NTHi viability, therefore highlighting its therapeutic potential against NTHi infection at the COPD airway...
October 16, 2017: Scientific Reports
Marc E Rothenberg, Hirohisa Saito, R Stokes Peebles
This review highlights advances in mechanisms of allergic disease, particularly type 2 innate lymphoid cells; TH2 lymphocytes; eicosanoid regulation of inflammation; extracellular vesicles in allergic responses; IL-33; microbiome properties, especially as they relate to mucosal barrier function; and a series of findings concerning the allergic inflammatory cells eosinophils, basophils, and mast cells. During the last year, mechanistic advances occurred in understanding type 2 innate lymphoid cells, particularly related to their response to ozone, involvement with experimental food allergy responses, and regulation by IL-33...
October 13, 2017: Journal of Allergy and Clinical Immunology
Mun Young Chang, Jihye Rhee, Shin Hye Kim, Young Ho Kim
Objectives: Local administration of 3-nitropropionic acid (3-NP) to the inner ear induces sensorineural hearing loss. Several studies have shown the otoprotective effects of ginkgo biloba extract EGb 761. Moreover, EGb 761 has been reported to activate Sirtuin 1 (SIRT1). The present study was designed to investigate whether EGb 761 prevents 3-NPinduced sensorineural hearing loss and determine its effects on the expression of SIRT1. Methods: Sprague Dawley rats were divided into four experimental groups: control group receiving vehicle of 3-NP, EGb group receiving EGb 761, 3-NP group receiving 3-NP, and EGb+3-NP group receiving EGb 761 and 3-NP...
October 17, 2017: Clinical and Experimental Otorhinolaryngology
Corina T Madreiter-Sokolowski, Armin A Sokolowski, Wolfgang F Graier
The naturally occurring polyphenol, resveratrol (RSV), is known for a broad range of actions. These include a positive impact on lifespan and health, but also pro-apoptotic anti-cancer properties. Interestingly, cell culture experiments have revealed a strong impact of RSV on mitochondrial function. The compound was demonstrated to affect mitochondrial respiration, structure and mass of mitochondria as well as mitochondrial membrane potential and, ultimately, mitochondria-associated cell death pathways. Notably, the mitochondrial effects of RSV show a very strict and remarkable concentration dependency: At low concentrations, RSV (<50 μM) fosters cellular antioxidant defense mechanisms, activates AMP-activated protein kinase (AMPK)- and sirtuin 1 (SIRT1)-linked pathways and enhances mitochondrial network formation...
October 13, 2017: Nutrients
Catherine Yzydorczyk, Na Li, Hassib Chehade, Dolores Mosig, Mickael Bidho, Basile Keshavjee, Jean Baptiste Armengaud, Katya Nardou, Benazir Siddeek, Mohamed Benahmed, Catherine Vergely, Umberto Simeoni
Unbalanced nutrition early in life is increasingly recognized as an important factor in the development of chronic, non-communicable diseases at adulthood, including metabolic diseases. We aimed to determine whether transient postnatal overfeeding (OF) leads to liver stress-induced premature senescence (SIPS) of hepatocytes in association with liver structure and hepatic function alterations. Litters sizes of male C57BL/6 mice were adjusted to 9 pups (normal feeding, NF) or reduced to 3 pups during the lactation period to induce transient postnatal OF...
October 10, 2017: Scientific Reports
Min Wang, Yanming Chen, Zhaojun Xiong, Shujie Yu, Bin Zhou, Yesheng Ling, Zhenda Zheng, Guangyao Shi, Yongxiang Wu, Xiaoxian Qian
Free fatty acids (FFAs) increase in visceral fat and are inferred to be one of the underlying inducers of adipose tissue inflammation. In our previous study, it was demonstrated that ginsenoside Rb1 stimulates endothelial nitric oxide synthase (eNOS) and Sirtuin 1 to protect against endothelial cell senescence. In the present study, 3T3‑L1 adipocytes were exposed to 0.5 mM FFAs with or without Rb1 (10‑40 µM). Monocyte chemotactic protein‑1 (MCP‑1) and interleukin‑6 (IL‑6) secretion was measured using ELISA...
October 4, 2017: Molecular Medicine Reports
Irene Chengjie Lee, Xue Yan Ho, Simi Elizabeth George, Catherine Wenhui Goh, Jeyapriya Rajameenakshi Sundaram, Karen Ka Lam Pang, Weiwei Luo, Permeen Yusoff, Newman Siu Kwan Sze, Shirish Shenolikar
Phosphorylation of the eukaryotic translation initiation factor, eIF2α, by stress-activated protein kinases and dephosphorylation by the growth arrest and DNA damage-inducible protein (GADD34)-containing phosphatase is a central node in the integrated stress response. Mass spectrometry demonstrated GADD34 acetylation at multiple lysines. Substituting K(315) and K(322) with alanines or glutamines did not impair GADD34's ability to recruit protein phosphatase 1α (PP1α) or eIF2α, suggesting that GADD34 acetylation did not modulate eIF2α phosphatase activity...
October 6, 2017: Cell Death and Differentiation
Mei Zhang, Qun Zhang, Yali Hu, Lu Xu, Yue Jiang, Chunxue Zhang, Lijun Ding, Ruiwei Jiang, Jianxin Sun, Haixiang Sun, Guijun Yan
Oxidative stress impairs follicular development by inducing granulosa cell (GC) apoptosis, which involves enhancement of the transcriptional activity of the pro-apoptotic factor Forkhead box O1 (FoxO1). However, the mechanism by which oxidative stress promotes FoxO1 activity is still unclear. Here, we found that miR-181a was upregulated in hydrogen peroxide (H2O2)-treated GCs and a 3-nitropropionic acid (NP)-induced in vivo model of ovarian oxidative stress. miR-181a overexpression promoted GC apoptosis, whereas knockdown of endogenous miR-181a blocked H2O2-induced cell apoptosis...
October 5, 2017: Cell Death & Disease
Haymanti Bhanot, Ellen L Weisberg, Mamatha M Reddy, Atsushi Nonami, Donna Neuberg, Richard M Stone, Klaus Podar, Ravi Salgia, James D Griffin, Martin Sattler
Acute myeloid leukemia (AML) cells are highly dependent on glycolytic pathways to generate metabolic energy and support cell growth, hinting at specific, targetable vulnerabilities as potential novel targets for drug development. Elevated levels of NADPH, a central metabolic factor involved in redox reactions, are common in myeloid leukemia cells, but the significance or biochemical basis underlying this increase is unknown. Using a small molecule analog that efficiently inhibits NADPH-producing enzymes, we found that AML cells require NADPH homeostasis for cell growth...
September 15, 2017: Oncotarget
Shuangjie Wu, Jinghui Jiang, Jun Liu, Xinhai Wang, Yu Gan, Yifan Tang
Sirtuin 1 (SIRT1), a well-characterized NAD(+)-dependent histone deacetylase, is generally up-regulated in gastrointestinal cancers. However, the prognostic value of SIRT1 in gastrointestinal cancer remains inconclusive. Therefore, we report a meta-analysis of the association of SIRT1 expression with overall survival (OS) in gastrointestinal cancer. PubMed was systematically searched for studies evaluating the expression of SIRT1 and OS in patients with gastrointestinal cancer. Fifteen studies (six evaluating colorectal cancer, three evaluating hepatocellular carcinoma, three evaluating gastric cancer, and one each evaluating pancreatic cancer, esophageal squamous cell carcinoma, and gastroesophageal junction cancer) with 3,024 patients were finally included...
September 22, 2017: Oncotarget
Xinke Zhou, Jitao Chen, Liangcai Chen, Xiao Feng, Zhaoyu Liu, La Hu, Zicheng Zeng, Xiaoting Jia, Min Liang, Boyun Shi, Gao Yi, Jifang Liu
Increasing evidence suggests that therapy-induced senescence (TIS), a novel therapeutic approach in which low doses of therapeutic drugs or radiation are used to induce senescence, suppresses tumor development. Our previous in vitro studies have demonstrated that a low dose of metformin promoted hepatoma cell senescence instead of apoptosis via activation of AMP-activated protein kinase (AMPK) and inactivation of Sirtuin 1 (SIRT1) deacetylase activity. However, the intricate relationship between AMPK and SIRT1, and how they cooperate to induce senescence remains elusive...
September 28, 2017: Cancer Letters
Kok-Yong Chin, Kok-Lun Pang
Osteoarthritis is a major cause of morbidity among the elderly worldwide. It is a disease characterized by localized inflammation of the joint and destruction of cartilage, leading to loss of function. Impaired chondrocyte repair mechanisms, due to inflammation, oxidative stress and autophagy, play important roles in the pathogenesis of osteoarthritis. Olive and its derivatives, which possess anti-inflammatory, antioxidant and autophagy-enhancing activities, are suitable candidates for therapeutic interventions for osteoarthritis...
September 26, 2017: Nutrients
Jing Huang, Rui Tian, Yongqiang Yang, Rong Jiang, Jie Dai, Li Tang, Li Zhang
It is generally regarded that Sirtuin 1 (SIRT1), a longevity factor in mammals, acts as a negative regulator of inflammation. However, recent studies also found that SIRT1 might be a detrimental factor under certain inflammatory circumstance. In this study, the potential pathophysiological roles and the underlying mechanisms of SIRT1 in a mouse model with endotoxemia-associated acute lung injury were investigated. The results indicated that treatment with the selective SIRT1 inhibitor EX-527 suppressed LPS-induced elevation of TNF-α and IL-6 in plasma...
January 1, 2017: Innate Immunity
Catherine Y Cheng, Julia Böhme, Amit Singhal
A wealth of scientific and clinical evidence during the past few years has lent credence to the idea that key components of the host immune effector mechanisms can be targeted to boost current tuberculosis (TB) treatment and control patient relapse. These host-directed strategies not only accelerate the clearance of pathogens but also have the ability to limit overt inflammation and pathology, which are associated with the tissue damage. Studies have indicated that inflammatory responses are intrinsically linked to cellular metabolism and together drive the fate of many host responses, coupling host survival with the capacity to respond to infectious insult...
September 26, 2017: Journal of Leukocyte Biology
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