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https://www.readbyqxmd.com/read/29782205/nad-repletion-produces-no-therapeutic-effect-in-mice-with-respiratory-chain-complex-iii-deficiency-and-chronic-energy-deprivation
#1
Janne Purhonen, Jayasimman Rajendran, Saara Tegelberg, Olli-Pekka Smolander, Eija Pirinen, Jukka Kallijärvi, Vineta Fellman
Biosynthetic precursors of NAD+ can replenish a decreased cellular NAD+ pool and, supposedly via sirtuin (SIRT) deacetylases, improve mitochondrial function. We found decreased hepatic NAD+ concentration and downregulated biosynthesis in Bcs1lp.S78G knock-in mice with respiratory chain complex III deficiency and mitochondrial hepatopathy. Aiming at ameliorating disease progression via NAD+ repletion and improved mitochondrial function, we fed these mice nicotinamide riboside (NR), a NAD+ precursor. A targeted metabolomics verified successful administration and suggested enhanced NAD+ biosynthesis in the treated mice, although hepatic NAD+ concentration was unchanged at the end point...
May 21, 2018: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
https://www.readbyqxmd.com/read/29779969/increased-malondialdehyde-vs-reduced-sirtuin-1-in-relation-with-adiposity-atherogenicity-and-hematological-indices-in-metabolic-syndrome-patients-with-and-without-prediabetes
#2
Samar Abu Rkhaya, Nailya Bulatova, Violet Kasabri, Randa Naffa, Reema Alquoqa
BACKGROUND: Sirtuin 1 (SIRT 1) and malondialdehyde (MDA) were implicated in metabolic syndrome (MetS) and type 2 diabetes mellitus (T2DM) pathophysiology. AIMS AND METHODS: This cross-sectional study aimed to investigate both SIRT 1 and MDA in 30 lean healthy control, 31 normoglycemic MetS subjects and 30 MetS-Pre/T2DM drug naïve. C orrelation studies were established for both biomarkers with adiposity indices [conicity index (CI), waist circumference (WC), weight-to-height (WHtR) ratio, weight-to-hip (WHR) ratio, hip circumference (HC), and body adiposity index (BAI)], hematological indices [red cell distribution width (RDW), mean platelet volume (MPV), platelet-to-lymphcyte ratio (PLR), neutrophil-to-lymphocyte ratio (NLR), monocyte-to-lymphocyte ratio (MLR)] and atherogenicity indices (atherogenicity index of plasma (AIP = log10 TG/HDL-C ratio), TC/HDL-C and LDL-C/HDL-C ratios]...
May 15, 2018: Diabetes & Metabolic Syndrome
https://www.readbyqxmd.com/read/29767533/sirt1-controls-poly-i-c-dependent-mmp9-activation-in-primary-human-nasal-epithelial-cells
#3
Masanobu Suzuki, Mahnaz Ramezanpour, Clare Cooksley, Jian Li, Yuji Nakamaru, Akihiro Homma, Alkis Psaltis, Peter-John Wormald, Sarah Vreugde
BACKGROUND: Matrix metalloproteinase 9 (MMP9) is thought to be involved in the etiopathogenesis of chronic rhinosinusitis with nasal polyps (CRSwNP) and cleaves collagen IV causing hyperpermeability of the basement membrane within mucosal tissue. It is known that MMP9 expression is negatively affected by sirtuin-1 (SIRT-1) in human monocytotic cells, retinal endothelial cells and epithelial carcinoma cells. However, it is unknown which factors affect MMP9 expression and activity in human nasal epithelial cells (HNECs)...
May 16, 2018: American Journal of Respiratory Cell and Molecular Biology
https://www.readbyqxmd.com/read/29762078/resveratrol-promoted-interferon-%C3%AE-induced-growth-inhibition-and-apoptosis-of-smmc7721-cells-by-activating-the-sirt-stat1
#4
Zhanchun Yang, Qingyu Meng, Yuying Zhao, Rui Han, Shishun Huang, Meiqi Li, Xuan Wu, Wenna Cai, Haihe Wang
Interferon-α (IFN-α) resistance is a major hurdle in the treatment of hepatocellular carcinoma (HCC). Signal transducers and activators of transcription 1 (STAT1) play a key role in exerting the antiproliferative and proapoptotic effects of IFN-α on tumors. In this study, we aimed to investigate whether resveratrol can promote IFN-α-induced growth inhibition and the apoptosis on HCC cells through the SIRT/STAT1 pathway. We found that IFN-α induced growth inhibition and apoptosis of SMMC7721 cells, and the effects could be significantly enhanced and blocked by resveratrol and EX527, respectively...
May 15, 2018: Journal of Interferon & Cytokine Research
https://www.readbyqxmd.com/read/29745797/reversing-age-associated-arterial-dysfunction-insight-from-preclinical-models
#5
Venkateswara Reddy Gogulamudi, Jinjin Cai, Lisa A Lesniewski
Cardiovascular diseases (CVDs) remain the leading causes of death in the US, and advancing age is a primary risk factor. Impaired endothelium dependent dilation and increased stiffening of the arteries with aging are independent predictors of CVD. Increased tissue and systemic oxidative stress and inflammation underlie this age-associated arterial dysfunction. Calorie restriction (CR) is the most powerful intervention known to increase lifespan and improve age-related phenotypes, including arterial dysfunction...
May 10, 2018: Journal of Applied Physiology
https://www.readbyqxmd.com/read/29742611/falciform-ligament-artery-uptake-on-99mtc-maa-planning-scan-before-90y-sirt-confirmed-by-retrospective-spect-mri-fusion
#6
Nils Große Hokamp, Carsten Kobe, James K O'Donnell, Amit Gupta
Selective internal radiation therapy using Y spheres is a treatment option for patients with primary or secondary liver cancer. To avoid complications, screening using Tc macroaggregated albumin is performed to identify lung shunting and extrahepatic depositions. For the latter, deposition after the anterior abdominal wall is frequently attributed to a patent falciform artery, although the vessel itself is rarely visible on SPECT/CT scans. We demonstrate that retrospective SPECT/MRI fusion clearly attributes the nuclide accumulation to a patent falciform artery...
April 30, 2018: Clinical Nuclear Medicine
https://www.readbyqxmd.com/read/29701069/immunohistochemical-examination-of-osteopontin-and-sirtuin-1-expression-in-cattle-tuberculosis
#7
M Sevtekin, O Ozmen
We evaluated osteopontin (OPN) and sirtuin-1 (SIRT-1) expression in bovine tuberculosis lesions. The organs of cattle with tuberculosis (TB) were examined for morphology, histopathology and immunohistochemistry of OPN and SIRT-1 expression. Macroscopic lesions commonly were localized in the lungs and mediastinal lymph nodes as well as in livers and hearts. Mycobacterial agents were detected in lesions using the Ziehl-Neelsen method. No OPN or SIRT-1 expression was detected by immunohistochemistry in normal tissues, whereas a marked increase in their expressions was observed in tuberculous lesions...
April 27, 2018: Biotechnic & Histochemistry: Official Publication of the Biological Stain Commission
https://www.readbyqxmd.com/read/29696964/current-therapies-and-targets-for-type-2-diabetes-mellitus-a-review
#8
Dinesh K Chellapan, Wei Sheng Yap, Nurfatihah A Bt Ahmad Suhaimi, Gaurav Gupta, Kamal Dua
The prevalence of type 2 diabetes mellitus (T2DM) has been increasing at an alarming rate. With an increased understanding of the pathophysiology and pathogenesis of T2DM, various new therapeutic options have been developed to target different key defects in T2DM. Incremental innovations of existing therapies either through unprecedented drug combinations, modified drug molecules, or improved delivery systems are capable to nullify some of the undesirable side effects of traditional therapies as well as to enhance effectiveness...
April 24, 2018: Panminerva Medica
https://www.readbyqxmd.com/read/29696666/randomised-clinical-trial-a-leucine-metformin-sildenafil-combination-ns-0200-vs-placebo-in-patients-with-non-alcoholic-fatty-liver-disease
#9
N Chalasani, R Vuppalanchi, M Rinella, M S Middleton, M S Siddiqui, A S Barritt, O Kolterman, O Flores, C Alonso, M Iruarrizaga-Lejarreta, R Gil-Redondo, C B Sirlin, M B Zemel
BACKGROUND: Sirtuin 1 (Sirt1) is suppressed in non-alcoholic fatty liver disease (NAFLD), while its' stimulation or overexpression results in reduced disease severity in pre-clinical NAFLD models. Leucine allosterically activates Sirt1 and synergise with other Sirt/AMPK/NO pathway activators. We developed a triple combination of leucine, metformin and sildenafil (NS-0200), which was effective in a mouse model of non-alcoholic steatohepatitis (NASH). AIM: To report the results from a Phase 2, randomised clinical trial of of NS-0200 in 91 subjects with NAFLD (liver fat ≥15% by magnetic resonance imaging-proton-density fat fraction (MRI-PDFF))...
April 25, 2018: Alimentary Pharmacology & Therapeutics
https://www.readbyqxmd.com/read/29693113/role-of-sirtuin-1-in-the-pathogenesis-of-ocular-disease-review
#10
Mengwen Zhou, Jing Luo, Huiming Zhang
Sirtuin (SIRT)1, a member of the SIRT family, is a highly conserved NAD+‑dependent histone deacetylase, which has a regulatory role in numerous physiological and pathological processes by removing acetyl groups from various proteins. SIRT1 controls the activity of numerous transcription factors and cofactors, which impacts the downstream gene expression, and eventually alleviates oxidative stress and associated damage. Numerous studies have revealed that dysfunction of SIRT1 is linked with ocular diseases, including cataract, age‑associated macular degeneration, diabetic retinopathy and glaucoma, while ectopic upregulation of SIRT1 protects against various ocular diseases...
April 16, 2018: International Journal of Molecular Medicine
https://www.readbyqxmd.com/read/29686722/energy-restriction-exercise-and-atorvastatin-treatment-improve-endothelial-dysfunction-and-inhibit-mirna-155-in-the-erectile-tissue-of-the-aged-rat
#11
B Rocha, A R Rodrigues, I Tomada, M J Martins, J T Guimarães, A M Gouveia, H Almeida, D Neves
Background: Endothelial dysfunction underlies cardiovascular disease that frequently affects aged individuals. Characterized by local decrease in nitric oxide, it results from down-regulation of endothelial nitric oxide synthase (eNOS) expression/activity. Aiming to elucidate the molecular mechanisms involved in age-related endothelial dysfunction and to unveil potential therapeutic targets, we tested how diet pattern, exercise and atorvastatin modulate the expression of eNOS, inducible NOS (iNOS), endothelin-1, sirtuins (SIRT) and microRNA-155 in the erectile tissue of high-fat fed aged rats...
2018: Nutrition & Metabolism
https://www.readbyqxmd.com/read/29683787/selective-internal-radiation-therapy-sirt-as-treatment-for-hepatic-metastases-of-uveal-melanoma-a-finnish-nation-wide-retrospective-experience
#12
Sanni Tulokas, Hanna Mäenpää, Erno Peltola, Tero Kivelä, Pia Vihinen, Aku Virta, Siru Mäkelä, Raija Kallio, Micaela Hernberg
BACKGROUND: In Finland, selective internal radiation therapy (SIRT) is at present the preferred first-line loco-regional therapy for uveal melanoma patients with hepatic metastases not suitable for surgery. We retrospectively evaluate the outcome and safety of SIRT in this group of patients. MATERIAL AND METHODS: Yttrium-90 microspheres were delivered via the hepatic artery into the circulation of metastases from uveal melanoma in 18 patients with a predicted life expectancy of more than three months in three Finnish tertiary referral centers between November 2010 and December 2015...
April 23, 2018: Acta Oncologica
https://www.readbyqxmd.com/read/29680657/sirt1-s-nitrosylation-induces-acetylation-of-hmgb1-in-lps-activated-raw264-7-cells-and-endotoxemic-mice
#13
Young Min Kim, Eun Jung Park, Hye Jung Kim, Ki Churl Chang
Excessive inflammation plays a detrimental role in endotoxemia. A recent study indicated that alarmins such as high mobility group box 1 (HMGB1) have drawn attention as therapeutic targets of sepsis. Post-translational modification (i.e., acetylation of lysine residues) of HMGB1 leads to the release of HMGB1 into the cellular space, operating as a warning signal that induces inflammation. Sirtuin 1 (SIRT1) has been shown to negatively regulate HMGB1 hyperacetylation and its extracellular release in sepsis. Therefore, we hypothesized that the S-nitrosylation (SNO) of SIRT1 may disrupt the ability of SIRT1 to negatively regulate the hyperacetylation of HMGB1...
April 19, 2018: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/29678169/omega-3-polyunsaturated-fatty-acid-attenuates-the-inflammatory-response-by-modulating-microglia-polarization-through-sirt1-mediated-deacetylation-of-the-hmgb1-nf-%C3%AE%C2%BAb-pathway-following-experimental-traumatic-brain-injury
#14
Xiangrong Chen, Chunnuan Chen, Sining Fan, Shukai Wu, Fuxing Yang, Zhongning Fang, Huangde Fu, Yasong Li
BACKGROUND: Microglial polarization and the subsequent neuroinflammatory response are contributing factors for traumatic brain injury (TBI)-induced secondary injury. High mobile group box 1 (HMGB1) mediates the activation of the NF-κB pathway, and it is considered to be pivotal in the late neuroinflammatory response. Activation of the HMGB1/NF-κB pathway is closely related to HMGB1 acetylation, which is regulated by the sirtuin (SIRT) family of proteins. Omega-3 polyunsaturated fatty acids (ω-3 PUFA) are known to have antioxidative and anti-inflammatory effects...
April 20, 2018: Journal of Neuroinflammation
https://www.readbyqxmd.com/read/29672269/garlic-allium-sativum-increases-sirt1-and-sirt2-gene-expressions-in-the-kidney-and-liver-tissues-of-stz-and-stz-niacinamide-induced-diabetic-rats
#15
Zahra Arab Sadeghabadi, Nasrin Ziamajidi, Roghayeh Abbasalipourkabir, Roohollah Mohseni
BACKGROUND: Diabetic nephropathy and liver damage are important complications of diabetes mellitus (DM). Various factors, such as sirtuins (silent information regulators or SIRTs) are associated with these complications. Sirtuins are a family of NAD+-dependent proteins, and seven types of these can be found in mammalians. In this study, we evaluated the effects of aqueous garlic extract (G) on the expressions of SIRT1 and SIRT2 genes in the kidney and liver tissues of rats with types 1 and 2 diabetes...
April 19, 2018: Journal of Basic and Clinical Physiology and Pharmacology
https://www.readbyqxmd.com/read/29659739/physical-exercise-improves-aging-related-changes-in-angiotensin-igf-1-sirt-1-sirt3-and-vegf-in-the-substantia-nigra
#16
Ana Muñoz, Clynton L Corrêa, Andrea Lopez-Lopez, Maria A Costa-Besada, Carmen Diaz-Ruiz, Jose L Labandeira-Garcia
Dysregulation of tissue renin-angiotensin system (RAS) is involved in oxidative and inflammatory processes observed in major aging-related diseases, including neurodegenerative diseases such as Parkinson´s disease (PD). Physical exercise has beneficial effects against aging-related changes, dopaminergic neuron vulnerability and PD progression. The present study indicates that sedentary aged rats have an increase in activity of the nigral angiotensin (Ang) II/Ang type 1 receptor (AT1) axis (i.e. the pro-oxidative pro-inflammatory arm), and a decrease in the activity of the RAS protective arm (i...
April 12, 2018: Journals of Gerontology. Series A, Biological Sciences and Medical Sciences
https://www.readbyqxmd.com/read/29657112/high-expression-of-cpt1b-in-skeletal-muscle-in-metabolically-healthy-older-subjects
#17
C Bétry, E Meugnier, M Pflieger, G Grenet, S Hercberg, P Galan, E Kesse-Guyot, H Vidal, M Laville
AIM: Ageing is often associated with metabolic abnormalities such as insulin resistance, although some people remain metabolically healthy throughout their lives. The aim of this study was to gain more insight into metabolic health with increasing age. METHODS: Two groups of robust and of frail subjects, respectively, were identified based on a composite ageing indicator and recruited from the French SU.VI.MAX 2 cohort of older disease-free subjects. In all, 14 men and 12 women, aged 67±4 years, with similar anthropometric and metabolic characteristics at baseline (BMI: 24...
February 12, 2018: Diabetes & Metabolism
https://www.readbyqxmd.com/read/29642711/recent-advances-in-inhibitors-of-sirtuin1-2-an-update-and-perspective
#18
Ziyan Zhou, Tianfang Ma, Qihua Zhu, Yungen Xu, Xiaoming Zha
Sirtuins (SIRT) are coenzyme NAD+ -dependent histone deacetylases for the transfer of modified acetyl groups. Sirtuins are widely involved in various physiological processes and therefore associated with cardiovascular disease, diabetes, Parkinson's disease, cancer and beyond. Consequently, the development of modulators for  sirtuins has considerable clinical value. To date, a variety of SIRT1/2 inhibitors have been reported and none has been approved for the market. This review summarizes the recent progress in the discovery and development of SIRT1/2 inhibitors including their inhibitory potency, structure-activity relationship and binding mode analysis as well as discusses the perspective for the future development of SIRT1/2 inhibitors...
April 12, 2018: Future Medicinal Chemistry
https://www.readbyqxmd.com/read/29608911/renal-aquaporin-4-associated-pathology-in-tg-26-mice
#19
Joseph L Bryant, Poornachander R Guda, Sugata Ray, Girma Asemu, Avinash R Sagi, Fahad Mubariz, Muhammed I Arvas, Omar S Khalid, Vivek Shukla, Vamshi K C Nimmagadda, Tapas K Makar
Human immunodeficiency virus-associated nephropathy (HIVAN) is a leading cause of end-stage renal disease in HIV patients, which is characterized by glomerulosclerosis and renal tubular dysfunction. Aquaporin-4 (AQP-4) is a membrane bound water channel protein that plays a distinct role in water reabsorption from renal tubular fluid. It has been proven that failure of AQP-4 insertion into the renal tubular membrane leads to renal dysfunction. However, the role of AQP-4 in HIVAN is unclear. We hypothesize that impaired water reabsorption leads to renal injury in HIVAN, where AQP-4 plays a crucial role...
March 30, 2018: Experimental and Molecular Pathology
https://www.readbyqxmd.com/read/29599352/kdm4d-predicts-recurrence-in-exocrine-pancreatic-cells-of-resection-margins-from-patients-with-pancreatic-adenocarcinoma
#20
Joel Isohookana, Kirsi-Maria Haapasaari, Ylermi Soini, Peeter Karihtala
BACKGROUND/AIM: The role of histone demethylators, such as Jumonji domain 2 (JMJD2/KDM4) proteins, and histone deacetylases, such as sirtuins (SIRT) is poorly characterized in pancreatic carcinomas while they have a major role in the carcinogenesis of several other tumours. MATERIALS AND METHODS: We assessed retrospectively with immunohistochemistry the expressions of KDM4A, KDM4B and KDM4D in 81 and SIRT1-4 in 102 pancreatic adenocarcinomas. Immunostaining was evaluated separately in benign pancreatic tissues and in malignant cells...
April 2018: Anticancer Research
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