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https://www.readbyqxmd.com/read/28534819/ginsenoside-rb2-alleviates-hepatic-lipid-accumulation-by-restoring-autophagy-via-induction-of-sirt1-and-activation-of-ampk
#1
Qi Huang, Ting Wang, Liu Yang, He-Yao Wang
Although Panax ginseng is a famous traditional Chinese medicine and has been widely used to treat a variety of metabolic diseases including hyperglycemia, hyperlipidemia, and hepatosteatosis, the effective mediators and molecular mechanisms remain largely unknown. In this study we found that ginsenoside Rb2, one of the major ginsenosides in Panax ginseng, was able to prevent hepatic lipid accumulation through autophagy induction both in vivo and in vitro. Treatment of male db/db mice with Rb2 significantly improved glucose tolerance, decreased hepatic lipid accumulation, and restored hepatic autophagy...
May 19, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28533928/leucine-nicotinic-acid-synergy-stimulates-ampk-sirt1-signaling-and-regulates-lipid-metabolism-and-lifespan-in-caenorhabditis-elegans-and-hyperlipidemia-and-atherosclerosis-in-mice
#2
Antje Bruckbauer, Jheelam Banerjee, Quiang Cao, Xin Cui, Jia Jing, Lin Zha, Fenfen Li, Bingzhong Xue, Hang Shi, Michael B Zemel
BACKGROUND/AIMS: Nicotinic acid (NA), a lipid-lowering drug, serves as a source of NAD(+), the cofactor for Sirt1. Leucine (Leu) stimulates the AMPK/Sirt1 axis and amplifies the effects of other AMPK/Sirt1 activating compounds. Therefore, we tested the interactive effects of leucine and low dose NA on AMPK/Sirt1 signaling and downstream effects of lipid metabolism in cell culture, C. elegans and mice. METHODS: LDL-receptor knockout mice were fed an atherogenic Western diet supplemented with leucine (24 g/kg diet) and sub-therapeutic NA combinations (50 mg/kg diet and 250 mg/kg diet) or low therapeutic NA (1000 mg/kg diet) for 8 weeks to evaluate markers of hyperlipidemia and atherosclerosis...
2017: American Journal of Cardiovascular Disease
https://www.readbyqxmd.com/read/28533769/celecoxib-enhances-the-efficacy-of-low-dose-antibiotic-treatment-against-polymicrobial-sepsis-in-mice-and-clinical-isolates-of-eskape-pathogens
#3
Madhavi Annamanedi, Gajapati Y N Varma, K Anuradha, Arunasree M Kalle
Treatment of multidrug resistant bacterial infections has been a great challenge globally. Previous studies including our study have highlighted the use of celecoxib, a non-steroidal anti-inflammatory drug in combination with antibiotic has decreased the minimal inhibitory concentration to limit Staphylococcus aureus infection. However, the efficacy of this combinatorial treatment against various pathogenic bacteria is not determined. Therefore, we have evaluated the potential use of celecoxib in combination with low doses of antibiotic in limiting Gram-positive and Gram-negative bacteria in vivo in murine polymicrobial sepsis developed by cecum ligation and puncture (CLP) method and against clinically isolated human ESKAPE pathogens (Enterococcus faecium, Staphylococcus aureus, Klebsiella pneumoniae, Acinetobacter baumannii, Pseudomonas aeruginosa, and Enterobacter species)...
2017: Frontiers in Microbiology
https://www.readbyqxmd.com/read/28533555/scopolin-ameliorates-high-fat-diet-induced-hepatic-steatosis-in-mice-potential-involvement-of-sirt1-mediated-signaling-cascades-in-the-liver
#4
Ahyoung Yoo, Vikram P Narayan, Eun Young Hong, Wan Kyunn Whang, Taesun Park
The present study aimed to investigate whether scopolin exhibits beneficial effects on high-fat diet (HFD)-induced hepatic steatosis in mice. The involvement of sirtuin 1 (SIRT1) as a molecular target for scopolin was also explored. Scopolin decreased the Km of SIRT1 for p53 and nicotinamide adenine dinucleotide without altering Vmax in a cell-free system. Scopolin alleviated oleic acid-induced lipid accumulation and downregulation of SIRT1 activity in HepG2 cells, and these beneficial effects of scopolin were abolished in the presence of SIRT1 inhibitor...
May 22, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28533219/obesity-linked-phosphorylation-of-sirt1-by-ck2-inhibits-its-nuclear-localization-and-promotes-fatty-liver
#5
Sung E Choi, Sanghoon Kwon, Sunmi Seok, Zhen Xiao, Kwan-Woo Lee, Yup Kang, Xiaoling Li, Kosaku Shinoda, Shingo Kajimura, Byron Kemper, Jongsook Kim Kemper
Sirtuin1 (SIRT1) deacetylase delays and improves many obesity-related diseases, including non-alcoholic fatty liver disease (NAFLD) and diabetes, and has received great attention as a drug target. SIRT1 function is aberrantly low in obesity, so understanding the underlying mechanisms is important for drug development. Here, we show that obesity-linked phosphorylation of SIRT1 inhibits its function and promotes pathological symptoms of NAFLD. In proteomic analysis, Ser-164 was identified as a major serine phosphorylation site in SIRT1 in obese, but not lean, mice, and this phosphorylation was catalyzed by casein kinase-2 (CK2), the levels of which were dramatically elevated in obesity...
May 22, 2017: Molecular and Cellular Biology
https://www.readbyqxmd.com/read/28532580/sirt1-ameliorates-systemic-sclerosis-by-targeting-the-mtor-pathway
#6
Xiaoxia Zhu, Haiyan Chu, Shuai Jiang, Qingmei Liu, Lei Liu, Yu Xue, Shucong Zheng, Weiguo Wan, Jianhua Qiu, Jiucun Wang, Hejian Zou
BACKGROUND: Systemic sclerosis (SSc) is a chronic autoimmune disease characterized by inflammation and fibrosis. Our previous research has indicated that Sirtuin1 (Sirt1) plays a role in the regulation of TNF-α-induced inflammation; however, whether Sirt1 may inhibit the progress of SSc by blocking inflammation remains unknown. OBJECTIVE: We aimed to investigate the function of Sirt1 in SSc. METHODS: The function and its mechanism of Sirt1 were evaluated in fibroblasts or scleroderma mice...
May 3, 2017: Journal of Dermatological Science
https://www.readbyqxmd.com/read/28528294/isoliquiritigenin-reduces-oxidative-damage-and-alleviates-mitochondrial-impairment-by-sirt1-activation-in-experimental-diabetic-neuropathy
#7
Veera Ganesh Yerra, Anil Kumar Kalvala, Ashutosh Kumar
Sirtuin (SIRT1) inactivation underlies the pathogenesis of insulin resistance and hyperglycaemia-associated vascular complications, but its role in diabetic neuropathy (DN) has not been yet explored. We have evaluated hyperglycaemia-induced alteration of SIRT1 signalling and the effect of isoliquiritigenin (ILQ) on SIRT1-directed AMP kinase (AMPK) and peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PGC-1α) signalling in peripheral nerves of streptozotocin (STZ) (55 mg/kg, ip)-induced diabetic rats and in high glucose (30 mM)-exposed neuro2a (N2A) cells...
May 11, 2017: Journal of Nutritional Biochemistry
https://www.readbyqxmd.com/read/28527875/magnolol-attenuates-the-inflammation-and-apoptosis-through-the-activation-of-sirt1-in-experimental-stroke-rats
#8
Dong-Quan Kou, Yan-Ling Jiang, Jia-Hua Qin, Yin-Hui Huang
BACKGROUND: Silent information regulator 1 (SIRT1), a histone deacetylase, plays a protective role in ischemic brain injury. Previous studies have shown that magnolol has a beneficial effect on ischemic stroke; however, the role of SIRT1 in the protective effect of magnolol against cerebral ischemia has not been investigated. METHODS: We used a middle cerebral artery occlusion model of stroke in rats. Before stroke induction, the rats received intraperitoneal injections of magnolol with or without the SIRT1 inhibitor, EX527...
January 10, 2017: Pharmacological Reports: PR
https://www.readbyqxmd.com/read/28526414/a-novel-sirt1-inhibitor-4bb-induces-apoptosis-in-hct116-human-colon-carcinoma-cells-partially-by-activating-p53
#9
Ananga Ghosh, Amrita Sengupta, Guru Pavan Kumar Seerapu, Ali Nakhi, E V Venkat Shivaji Ramarao, Navneet Bung, Gopalakrishnan Bulusu, Manojit Pal, Devyani Haldar
The NAD+-dependent protein deacetylase SIRT1 has emerged as an important target for epigenetic therapeutics of colon cancer as its increased expression is associated with cancer progression. Additionally, SIRT1 represses p53 function via deacetylation, promoting tumor growth. Therefore, inhibition of SIRT1 is of great therapeutic interest for the treatment of colon cancer. Here, we report discovery of a novel quinoxaline based small molecule inhibitor of human SIRT1, 4bb, investigated its effect on viability of colon cancer cells and molecular mechanism of action...
May 16, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/28526407/sirtuin-inhibition-leads-to-autophagy-and-apoptosis-in-porcine-preimplantation-blastocysts
#10
Min Gyeong Kim, Duk Hyoun Kim, Hye Ran Lee, Jun Sung Lee, Su Jin Jin, Hoon Taek Lee
Sirtuins are nicotinamide adenine dinucleotide dependent class III histone deacetylase proteins that play a crucial role in several cellular processes, including DNA repair, apoptosis, and lifespan. Previous studies have shown that sirtuin inhibition leads to embryonic developmental arrest and oxidative stress in porcine and murine. However, sirtuin-mediated mechanisms have not been examined in porcine preimplantation blastocysts. We therefore investigated the relationship between sirtuins and autophagy. Embryos were cultured with 100 μM sirtinol (SIRT1/2 inhibitor) in NCSU-23 media after in vitro fertilization...
May 16, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/28525743/bromodomain-protein-brd4-is-a-transcriptional-repressor-of-autophagy-and-lysosomal-function
#11
Jun-Ichi Sakamaki, Simon Wilkinson, Marcel Hahn, Nilgun Tasdemir, Jim O'Prey, William Clark, Ann Hedley, Colin Nixon, Jaclyn S Long, Maria New, Tim Van Acker, Sharon A Tooze, Scott W Lowe, Ivan Dikic, Kevin M Ryan
Autophagy is a membrane-trafficking process that directs degradation of cytoplasmic material in lysosomes. The process promotes cellular fidelity, and while the core machinery of autophagy is known, the mechanisms that promote and sustain autophagy are less well defined. Here we report that the epigenetic reader BRD4 and the methyltransferase G9a repress a TFEB/TFE3/MITF-independent transcriptional program that promotes autophagy and lysosome biogenesis. We show that BRD4 knockdown induces autophagy in vitro and in vivo in response to some, but not all, situations...
May 18, 2017: Molecular Cell
https://www.readbyqxmd.com/read/28524020/altered-gene-expression-of-epigenetic-modifying-enzymes-in-response-to-dietary-supplementation-with-linseed-oil
#12
Ran Li, Eveline M Ibeagha-Awemu
Recently we showed that 5% linseed oil (LSO) and 5% safflower oil (SFO) supplementation of cow's diets reduced milk fat yield by 30·38 and 32·42% respectively, accompanied by differential expression of genes and regulation by microRNAs (miRNA). This research communication addresses the hypothesis that epigenetic regulation could be involved in the observed milk fat reduction. Thus, this study investigated the gene expression pattern of major epigenetic modifying enzymes in response to dietary supplementation with LSO or SFO...
May 2017: Journal of Dairy Research
https://www.readbyqxmd.com/read/28521414/association-of-fgfr2-rs2981582-sirt1-rs12778366-stat3-rs744166-gene-polymorphisms-with-pituitary-adenoma
#13
Brigita Glebauskiene, Alvita Vilkeviciute, Rasa Liutkeviciene, Silvija Jakstiene, Loresa Kriauciuniene, Reda Zemaitiene, Dalia Zaliuniene
The aim of the present study was to determine the association between sirtuin 1 (SIRT1), fibroblast growth factor receptor 2 (FGFR2) and signal transducer and activator of transcription 3 (STAT3) polymorphisms, and pituitary adenoma (PA) development, invasiveness, hormonal activity and recurrence. The present study included 143 patients with a diagnosis of PA. The reference group involved 808 healthy subjects. The genotyping of SIRT1 rs12778366, FGFR2 rs2981582 and STAT3 rs744166 was performed using the quantitative polymerase chain reaction method...
May 2017: Oncology Letters
https://www.readbyqxmd.com/read/28521305/bushen-yizhi-formula-ameliorates-cognitive-dysfunction-through-sirt1-er-stress-pathway-in-samp8-mice
#14
Shi-Jie Zhang, Ting-Ting Xu, Lin Li, Yu-Min Xu, Zi-Ling Qu, Xin-Chen Wang, Shui-Qing Huang, Yi Luo, Na-Chuan Luo, Ping Lu, Ya-Fei Shi, Xin Yang, Qi Wang
The Chinese formula Bushen-Yizhi (BSYZ) has been reported to ameliorate cognitive dysfunction. However the mechanism is still unclear. In this study, we employ an aging model, SAMP8 mice, to explore whether BSYZ could protect dementia through SIRT1/endoplasmic reticulum (ER) stress pathway. Morris water maze and the fearing condition test results show that oral administration of BSYZ (1.46 g/kg/d, 2.92 g/kg/d and 5.84 g/kg/d) and donepezil (3 mg/kg/d) shorten the escape latency, increase the crossing times of the original position of the platform and the time spent in the target quadrant, and increase the freezing time...
May 4, 2017: Oncotarget
https://www.readbyqxmd.com/read/28514495/protective-effects-of-dioscin-against-cisplatin-induced-nephrotoxicity-via-regulating-mir-34a-sirt1-signal-pathway
#15
Yimeng Zhang, Xufeng Tao, Lianhong Yin, Lina Xu, Youwei Xu, Yan Qi, Xu Han, Shasha Song, Yanyan Zhao, Yuan Lin, Kexin Liu, Jinyong Peng
BACKGROUND AND PURPOSE: Dioscin has various pharmacological actions in our previous works, however, little is known concerning the role of it on cisplatin (CDDP)-induced nephrotoxicity. The aim of the present study was to investigate the effects and possible mechanisms of dioscin against CDDP-induced nephrotoxicity. EXPERIMENTAL APPROACH: In the present study, the in vivo models of CDDP-induced nephrotoxicity in rats and mice were used, and the in vitro models on NRK-52E and HK-2 cells were developed...
May 17, 2017: British Journal of Pharmacology
https://www.readbyqxmd.com/read/28514055/caveolin-1-deficiency-induces-premature-senescence-with-mitochondrial-dysfunction
#16
Dong-Min Yu, Seung Hee Jung, Hyoung-Tae An, Sungsoo Lee, Jin Hong, Jun Sub Park, Hyun Lee, Hwayeon Lee, Myeong-Suk Bahn, Hyung Chul Lee, Na-Kyung Han, Jesang Ko, Jae-Seon Lee, Young-Gyu Ko
Paradoxical observations have been made regarding the role of caveolin-1 (Cav-1) during cellular senescence. For example, caveolin-1 deficiency prevents reactive oxygen species-induced cellular senescence despite mitochondrial dysfunction, which leads to senescence. To resolve this paradox, we re-addressed the role of caveolin-1 in cellular senescence in human diploid fibroblasts, A549, HCT116, and Cav-1(-/-) mouse embryonic fibroblasts. Cav-1 deficiency (knockout or knockdown) induced cellular senescence via a p53-p21-dependent pathway, downregulating the expression level of the cardiolipin biosynthesis enzymes and then reducing the content of cardiolipin, a critical lipid for mitochondrial respiration...
May 17, 2017: Aging Cell
https://www.readbyqxmd.com/read/28507478/melatonin-regulates-the-aging-mouse-hippocampal-homeostasis-via-the-sirtuin1-foxo1-pathway
#17
Anorut Jenwitheesuk, Parichart Boontem, Prapimpun Wongchitrat, Jiraporn Tocharus, Sujira Mukda, Piyarat Govitrapong
Sirtuin1 (SIRT1) and forkhead box transcription factor O subfamily 1 (FOXO1) play vital roles in the maintenance of hippocampal neuronal homeostasis during aging. Our previous study showed that melatonin, a hormone mainly secreted by the pineal gland, restored the impaired memory of aged mice. Age-related neuronal energy deficits contribute to the pathogenesis of several neurodegenerative disorders. An attempt has been made to determine whether the effect of melatonin is mediated through the SIRT1-FOXO1 pathways...
2017: EXCLI journal
https://www.readbyqxmd.com/read/28506746/the-nad-dependent-deacetylase-bifidobacterium-longum-sir2-in-response-to-oxidative-stress-by-deacetylating-foxo3a-and-sigh-%C3%AF-h-in-bifidobacterium-longum-and-hek293t-cells-respectively
#18
Qing Guo, Shiyu Li, Yajie Xie, Qian Zhang, Mengge Liu, Zhenrui Xu, Hanxiao Sun, Yan Yang
Silent information regulator 2 (Sir2) enzymes which catalyze NAD+-dependent protein/histone deacetylation. The mammalian sirtuin family SIRT1, SIRT2, SIRT3 and SIRT6 can regulate oxidative stress. The probiotics (Bifidobacterium longum(B.longum) and Lactobacillus acidophilus(L. acidophilus)) have Sir2 gene family and have antioxidant activity in human body. it remains unknown whether probiotics Sir2 has a direct role in regulating oxidative stress. To this end, we knockout BL-sir2(sir2 B. longum) and LA-sir2(sir2 L...
May 12, 2017: Free Radical Biology & Medicine
https://www.readbyqxmd.com/read/28506610/decreased-serum-sirtuin-1-in-chronic-obstructive-pulmonary-disease
#19
Satoru Yanagisawa, Andriana I Papaioannou, Anastasia Papaporfyriou, Jonathan Baker, Chaitanya Vuppusetty, Stelios Loukides, Peter J Barnes, Kazuhiro Ito
BACKGROUND: The protein deacetylase sirtuin-1 (SIRT1) is an anti-aging molecule that is decreased in the lung from patients with chronic obstructive pulmonary disease (COPD). Recently, SIRT1 was reported to be detectable in serum, but serum SIRT1 levels have not yet been reported in patients with COPD. METHODS: Serum SIRT1 was measured by Western blotting, and relative ratio of band density in samples against that of a positive control were calculated. RESULTS: Several molecular sizes of SIRT1, including 120kDa (actual size) and fragments (102, 75kDa) were quantified by Western blotting...
May 12, 2017: Chest
https://www.readbyqxmd.com/read/28505155/oxidative-stress-and-expression-of-insulin-signaling-proteins-in-the-brain-of-diabetic-rats-role-of-nigella-sativa-oil-and-antidiabetic-drugs
#20
Mahmoud Balbaa, Shaymaa A Abdulmalek, Sofia Khalil
BACKGROUND AND OBJECTIVES: Insulin resistance of the brain is a specific form of type2-diabetes mellitus (T2DM) and the active insulin-signaling pathway plays a neuroprotective role against damaging conditions and Alzheimer's progression. The present study identifies the mediated emerging effects of the Nigella sativa oil (NSO) on the memory enhancing process, its anti-oxidative, acetylcholinestrase (AChE) inhibition, anti-brain insulin resistance and anti-amyloidogenic activities. In addition, the possible role of some anti-diabetic drugs in the neuro-protection processes and their effect in combination with NSO and/or the insulin receptor inhibitor IOMe-AG538 were investigated...
2017: PloS One
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