sirtuin activator supplement

Endocrinol. Curcumin augments the cardioprotective effect of metformin in an experimental model of type I diabetes mellitus; Impact of Nrf2/HO-1 and JAK/STAT pathways. Deregulation of their expression and/or action may lead to tissue-specific degenerative events involved in the development of several human pathologies, including cancer, neurodegeneration, and cardiovascular disease. doi:10.1007/978-0-387-46401-5_21, Hsu, C. P., Zhai, P., Yamamoto, T., Maejima, Y., Matsushima, S., Hariharan, N., et al. Mini Rev. Rev. 73, 7183. (2011). 95, 12251231. Another phase 2 clinical study (NCT03325322) intends to evaluate the effects of oral fisetin on adipose tissue-derived mesenchymal stem/stromal cell function, kidney function, inflammation, and physical function in subjects with chronic kidney diseases and diabetes. Cur may have positive effects in T2D by mediating the reduction of NF-B expression in inflammatory pathway (Zendedel et al., 2018). Increased fatty acid synthesis and hepatocyte accumulation is associated with metabolic disorder (Liou et al., 2018). 36 (12), 23582368. However, Que was also found to have potentially toxic effects including mutagenicity, pro-oxidant activity, mitochondrial toxicity, and inhibition of enzymes involved in hormonal metabolism (Li et al., 2016). (2019). 6 (1), 287296.

J. Neurochem. Under normal conditions, the cystine-rich zinc Keap1 metalloprotein binds Nrf2 inside the cytoplasm, promoting ubiquitination and consequent proteasomal degradation and preventing Nrf2 nuclear translocation (Serafini et al., 2019). Immune Disord.

61, 4855. The molecular structure of Cur consists of two aromatic rings containing phenolic O-methoxy groups linked by a carbon bond, which has a -unsaturated -diketone fraction (Priyadarsini, 2014). showed that fisetin mediated protective effects via SIRT1 activation, enhancing NF-B deacetylation and promoting inhibition of pro-inflammatory gene expression (Singh et al., 2019). Exp. Cardiovasc. Toxicol. J. Appl. 3 (4), 437441. Heart injury and mitochondrial oxidative damage are characterized by ROS overproduction and a reduction in succinate dehydrogenase or COX activity, leading to mitochondrial respiratory chain deficiency (Yang et al., 2013). Mainly in immunity and inflammation, Que acts on leukocytes and targets many intracellular signaling kinases and phosphatases as well as enzymes and membrane proteins (Li et al., 2016). Cell Longev. Crataegus orientalis Leaves and Berries: Phenolic Profiles, Antioxidant and Anti-inflammatory Activity.

Resveratrol mitigates lipopolysaccharide- and Abeta-mediated microglial inflammation by inhibiting the TLR4/NF-kappaB/STAT signaling cascade. (2014). (2018). Berberine Alleviates Oxidative Stress in Islets of Diabetic Mice by Inhibiting miR-106b Expression and Up-Regulating SIRT1. 18 (13), 11511157. Specifically, fisetin enhanced the association between SIRT1 and the PPAR promoter, leading to a block of its transcriptional activity, adipogenesis, and lipid accumulation (Kim et al., 2015). Table 6 Fisetin in clinical trials for inflammatory disorders. Resveratrol (RSV), a non-flavonoid polyphenol found in grapes and grape products such as red wine, exerts an antioxidant action with reported cancer preventive properties (Kris-Etherton et al., 2002). 15 (5), 675690. Arch. 193, 171179. Neurochem. *Correspondence: Angela Nebbioso, angela.nebbioso@unicampania.it; Lucia Altucci, lucia.altucci@unicampania.it, Natural Product Epigenetic Modulators and Inhibitors, View all 19 (12), 3903. doi:10.3390/ijms19123903, Zordoky, B. N., Robertson, I. M., Dyck, J. R. (2015). Nat. Nature 571 (7766), 489499. 13, 97107. It can also reduce cardiac dysfunction, oxidative stress, fibrosis, and apoptosis in the heart (Gupta et al., 2014; Yamagata, 2019). Durgaprasad, S., Pai, C. G., Vasanthkumar, Alvres, J. F., Namitha, S. (2005). The antioxidant and anti-inflammatory effects of BBR were also investigated in heart (Yu et al., 2016). Front. (2017). J. Chin. The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. Med.

Cell Metab. Resveratrol Reduces Oxidative Stress and Apoptosis in Podocytes via Sir2-Related Enzymes, Sirtuins1 (SIRT1)/Peroxisome Proliferator-Activated Receptor gamma Co-Activator 1alpha (PGC-1alpha) Axis. 90, 500508. Endocr. M. Lamprecht (Boca Raton, FL: CRC Press/Taylor & Francis), Kris-Etherton, P. M., Hecker, K. D., Bonanome, A., Coval, S. M., Binkoski, A. E., Hilpert, K. F., et al. Biochem. Most of these studies tested RSV-mediated effects in central nervous system disorders (Friedreich ataxia, Alzheimers disease, Parkinsons disease), metabolic disorders [T2D, insulin resistance, dyslipidemia, hypercholesterolemia, metabolic syndrome X, non-alcoholic fatty liver disease (NAFLD)]. BBR was described as a potential antitumor agent that induces cell cycle arrest in G0/G1 phase, increases Cip/p21 and Kip/p27 protein expression, decreases expression of cyclin D1, D2, and DE, and the cyclin-dependent kinases Cdk2, Cdk4, and Cdk6, promoting apoptosis in HL-60 human leukemia cells (Li et al., 2017). (2020a). J. Med. However, its effect in vivo is very likely not direct but due to its ability to modulate the cells antioxidant defense mechanisms; moderate oxidative stress can in fact increase the cells antioxidant defenses, resulting in general cytoprotection (Halliwell et al., 2005). In oral carcinoma cell lines and in SCC-4 cells, BBR inhibits expression of COX2 and AP-1 bond, decreases prostaglandin E2 (PGE2) production, and suppresses NF-B, IKK, ERK, and JNK activities. doi:10.1016/j.biopha.2018.11.064, PubMed Abstract | CrossRef Full Text | Google Scholar, Araki, T., Sasaki, Y., Milbrandt, J. Data suggested that fisetin may be a suitable therapeutic candidate for aging and neurological diseases. However, it remains unclear whether (or not) the effects of these compounds are mostly related to SIRT activation and what drug dose/concentration is required. Quercetin disrupts tyrosine-phosphorylated phosphatidylinositol 3-kinase and myeloid differentiation factor-88 association, and inhibits MAPK/AP-1 and IKK/NF-kappaB-induced inflammatory mediators production in RAW 264.7 cells. doi:10.1159/000493650, Ma, X., Sun, Z., Han, X., Li, S., Jiang, X., Chen, S., et al. 665, 7889. Fisetin was shown to have neuroprotective activity in various Huntingtons disease models through ERK activation and to inhibit melanoma growth by suppressing Akt/mTOR1 pathway (Sechi et al., 2018). Mitochondrial Dynamic Dysfunction as a Main Triggering Factor for Inflammation Associated Chronic Non-Communicable Diseases. Calorie restriction mimetics: an emerging research field. doi:10.18632/aging.103059, Huang, S. X., Qiu, G., Cheng, F. R., Pei, Z., Yang, Z., Deng, X. H., et al. Recent research showed that oxidized LDL (oxLDL) induces oxidative stress (Lara-Guzman et al., 2018). (2019). Resveratrol improves insulin sensitivity, reduces oxidative stress and activates the Akt pathway in type 2 diabetic patients. Sirtuins (SIRT) 17 are enzymes classified as class III HDACs. doi:10.3892/etm.2016.3958, Tian, X. Y., Wong, W. T., Wang, N., Lu, Y., Cheang, W. S., Liu, J., et al. 119 (12), 1029110300. Indeed, SIRT1 has been reported to play a key role in tumorigenesis, as an oncogene or tumor suppressor depending on the context specificity (Biason-Lauber et al., 2013). doi:10.1007/978-1-4419-1599-3_6, Wu, Z., Zhao, J., Xu, H., Lyv, Y., Feng, X., Fang, Y., et al. In vitro and in vivo studies as well as clinical trials in humans show that SIRT-activating compounds derived from natural sources could preserve human health and might prove beneficial for the prevention and treatment of a plethora of human diseases. A recent in vitro study showed that RSV reduces hypoxia-induced apoptosis in H9C2 cells through activation of SIRT1/miR-30d-5p/NF-B axis (Han et al., 2020). Br. Antioxid. Neurosci. The chemistry of curcumin: from extraction to therapeutic agent. (2009). So countries with the highest consumption of seaweed are Japan and South Korea; people in these countries have the highest life expectancy and they eat a lot of seaweed, so weve been screening different preparations of seaweed and fucoidan and we have identified those that are really strong inducers of sirtuin 6 activity. J. Clin. doi:10.1016/s0167-4889(02)00328-2, Oboh, G., Ademosun, A. O., Ogunsuyi, O. Antioxid. RSV was shown to be involved in the activation of macrophages, T cells, and natural killer cells, as well as in the suppression processes of CD4+ CD25+ regulatory T cells (Yang et al., 2008; Svajger and Jeras, 2012). B. doi:10.1016/j.cellsig.2013.06.007, Khan, N., Syed, D. N., Ahmad, N., Mukhtar, H. (2013). In different organisms (S. cerevisiae, C. elegans, and D. melanogaster) expressing SIRT1 (or its homologous genes), RSV treatment is able to extend life span. (2017). 43 (9), 18141825. Front. Silent information regulator 1 protects the heart from ischemia/reperfusion. Front. doi:10.1002/jcb.28255, Theodotou, M., Fokianos, K., Mouzouridou, A., Konstantinou, C., Aristotelous, A., Prodromou, D., et al. After we showed that not all harvests of this ingredient activate Sirtuin 6, we set about finding those that did. Pharmacol. Natural compounds such as metformin and resveratrol display the ability to mimic the effects of caloric restriction, acting on stress response and metabolic pathways (Ingram et al., 2006).

(2018). In addition, Que reduces T cell proliferation by blocking IL-12-induced tyrosine phosphorylation of JAK2, TYK2, STAT3, and STAT4 (Muthian and Bright, 2004; Nabavi et al., 2012). Caloric restriction and its mimetics. A., Lertpiriyapong, K., Steelman, L. S., Abrams, S. L., Yang, L. V., Murata, R. M., et al. Biol. There are already some natural compounds that have been identified, a sugar-like molecule that is purified from seaweed, and amazingly, consumption of seaweed is linked to longer lifespan in humans. Toxicol. Pharmacol. 11:1225. doi: 10.3389/fphar.2020.01225. Furthermore, some in vitro and in vivo studies show that Cur can downregulate TLR4, MyD88, and NF-B signaling at neuronal level by inducing the release of pro-inflammatory cytokines (TNF-, IL-1, IL-6), producing an anti-inflammatory effect. Modulation of Keap1/Nrf2/ARE Signaling Pathway by Curcuma- and Garlic-Derived Hybrids. This event stimulates an increase in NAD+ levels and SIRT1 activation (Zendedel et al., 2018). Specifically, BBR and RSV co-treatment was able to reduce lipid accumulation more robustly than single treatments. (2012). Quercetin and Its Role in Chronic Diseases. The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. Oxidation can lead to harmful damage to DNA, and SIRT6 recruits. doi:10.1038/nature03354, Romagnolo, D. F., Selmin, O. I. Our current knowledge of the potential pharmacological activation of the expression/activity of other SIRTs is largely incomplete. Med. Berberine attenuated the cytotoxicity induced by t-BHP via inhibiting oxidative stress and mitochondria dysfunction in PC-12 cells. A very recent report described the protective effect of BBR against doxorubicin-induced cardiovascular damage (Wu et al., 2019). Fucoidan can be extracted from various brown seaweeds; an Agriculture and Food Development Authority study into seaweed discovered that Fucus distichus, Fucus vesiculous and Cytoseira tamariscofolia all yielded significantly enhanced SIRT6 activity, and the effect was most pronounced for F. distichus [6]. Que may reduce oxLDL-induced oxidative damage by upregulating SIRT1 and AMPK (Hung et al., 2015), therefore potentially preventing oxLDL-impaired SIRT1 inhibition linked to endothelial dysfunction. doi:10.1089/ars.2012.4581, Donniacuo, M., Urbanek, K., Nebbioso, A., Sodano, L., Gallo, L., Altucci, L., et al. Vasc. 750 (1), 6082. 9:19:19. doi:10.3389/fphar.2018.00019, Svajger, U., Jeras, M. (2012). (2004). Rev. Histone acetyltransferase (HAT) and histone deacetylase (HDAC) enzymes control the levels of histone acetylation, modulating gene expression (Cavalli and Heard, 2019). Biophys. Acta 1852 (6), 11551177. Specifically, in a study to develop a therapeutic strategy for osteoarthritis, Que was shown to increase expression levels of SIRT1, PGC-1, NRF1 and NFR2, TFAM, and phospho-AMPK in osteoarthritis rats, confirming the hypothesis that Que might act via the AMPK/SIRT1 signaling pathway (Qiu et al., 2018). Berberine Protects Secondary Injury in Mice with Traumatic Brain Injury Through Anti-oxidative and Anti-inflammatory Modulation. Curcumin (Cur) or 1,7-bis(4-hydroxy-3-methoxyphenyl)-1,6-heptadiene-3,5-dione (diferuloylmethane) is a natural bioactive polyphenol compound mediating a wide spectrum of biological functions. Unfortunately, where it is grown and other conditions tend not to have an effect on the Sirtuin activating properties, so this means we just have to get multiple samples from multiple harvests all around the world. Fisetin targets YB-1/RSK axis independent of its effect on ERK signaling: insights from in vitro and in vivo melanoma models. doi:10.1142/S0192415X19500861, Zendedel, E., Butler, A. E., Atkin, S. L., Sahebkar, A. Oncogene 36 (50), 69066918. Ed. Moreover, BBR pre-treatment seemed to counteract SIRT1 downregulation (Zhu et al., 2018). 467 (4), 638644. In recent years, the scientific community has focused on the potential antiproliferative, chemopreventive and anticarcinogenic activities of Que as well as on its role as a modulator of gene expression. Exp. FIRST LONGEVITY, increasing life expectancy in mice by 30%, https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4614943/, https://www.ahajournals.org/doi/10.1161/CIRCRESAHA.120.318353, https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5389893/, https://www.cell.com/cell/fulltext/S0092-8674(19)30344-7, https://www.sciencedirect.com/science/article/pii/S2213453019300254, https://www.researchgate.net/publication/317755025_The_Identification_of_a_SIRT6_Activator_from_Brown_Algae_Fucus_distichus, The weight loss supplement that boosts the benefits of exercise, From movement to industry a longevity journey, HIV speeds up bodys aging processes, new study shows, Study disproves benefits of probiotics for vaginal health, Cinnamon a little compound which could slow diabetes, New supplement slows aging and promotes weight loss, FuturSelf a new digital approach to mental health, Research reverses aging in human skin cells by 30 years, YouthBio CEO: The time is right to develop epigenetic reprogramming therapies, Andrew Steele: Our goal must be to cure aging, Dr Frank Lipman explains how supplementing with NMN can help boost cellular energy, New research shows urolithin A improves mitochondrial health and reduces joint cartilage damage, GLYLO the weight loss supplement that boosts the benefits of exercise, Supplement trials go step-by-step for success, Winning strategy Tour de France riders supplement with urolithin A, Senostatic study shows admirable results for longevity supplement, Studies show NOVOS ingredient combo maintains DNA and targets senescence, Longevity startup Avea closes CHF 2.5 million in first financing round, Elevants longevity routine aims to improve your health and help you live better for longer, Wonderfeel launch Youngr a new supplement targeting the root causes of aging, A new longevity supplement that speaks for itsCELLF, Science breakthrough shows the way to faster muscle recovery, New immune supplement launches with NAD+ boost for optimal maintenance of aging cells, New gluten-free, soy-free spermidine supplement launches, Swiss scientists crack muscle recovery, repairing age-related fatigue. (2018). (2017). Rep. 8 (1), 15726. doi:10.1038/s41598-018-33879-w, Serafini, M. M., Catanzaro, M., Fagiani, F., Simoni, E., Caporaso, R., Dacrema, M., et al. doi:10.1016/j.jnutbio.2018.07.014, Cheang, W. S., Wong, W. T., Wang, L., Cheng, C. K., Lau, C. W., Ma, R. C. W., et al. doi:10.1007/s00204-005-0014-8, Ingram, D. K., Zhu, M., Mamczarz, J., Zou, S., Lane, M. A., Roth, G. S., et al. doi:10.1016/j.intimp.2007.12.006, Yang, Y., Duan, W., Lin, Y., Yi, W., Liang, Z., Yan, J., et al. doi:10.3390/molecules19068289, Kauppinen, A., Suuronen, T., Ojala, J., Kaarniranta, K., Salminen, A. doi:10.1039/c4fo00948g, Cicero, A. F., Baggioni, A. doi:10.1111/j.1474-9726.2006.00202.x, Iskender, H., Dokumacioglu, E., Sen, T. M., Ince, I., Kanbay, Y., Saral, S. (2017). (2018). It was found to exert protective antioxidative effects in different physiologic and pathologic conditions (Huang et al., 2018; Li et al., 2020b). Copyright 2020 Iside, Scafuro, Nebbioso and Altucci. We thank C. Fisher for linguistic editing. Biochem. In addition, Que is known to exert a modulating action on immunity (Galleggiante et al., 2019). 80 (2), 6273. Nutr. doi:10.3390/molecules191220091, Qiu, L., Luo, Y., Chen, X. Anti-inflammatory effects of resveratrol and its potential use in therapy of immune-mediated diseases. doi:10.1038/onc.2017.296, Sampaio, S. F., Branco, A. F., Wojtala, A., Vega-Naredo, I., Wieckowski, M. R., Oliveira, P. J. RSV-SIRT1 interaction modifies SIRT1 structure and promotes binding activity with its substrates including p65/RelA (Yeung et al., 2004), a component of the NF-B complex, which regulates activation of leukocytes and inflammatory cytokines. Regulation of SIRT1 by oxidative stress-responsive miRNAs and a systematic approach to identify its role in the endothelium. The imbalance between oxidants and antioxidants can result in cellular dysfunction, apoptosis, and necrosis (Liguori et al., 2018). Med. SIRT1 protects against oxidative stress via regulation of FOXO protein acetylation, which is involved in antioxidant processes, apoptosis, and cell proliferation (Wong and Woodcock, 2009). Biol. Quercetin ameliorates diabetic encephalopathy through SIRT1/ER stress pathway in db/db mice. Thousands of years ago, Indians and Chinese described the health-giving effects of this substance, derived from the turmeric plant (Gupta et al., 2014). In recent years, the scientific community has focused on the role of apoptosis in cardiovascular disease, showing that oxidative stress, myocardial ischemia, hypoxia, and ischemia/reperfusion injury may induce myocardial apoptosis (Donniacuo et al., 2019). p66Shc signaling is involved in stress responses elicited by anthracycline treatment of rat cardiomyoblasts. Food Chem. doi:10.1016/j.clnu.2019.06.026, Miceli, M., Bontempo, P., Nebbioso, A., Altucci, L. (2014). (2017). Nutrients 10 (11), 1651. doi:10.3390/nu10111651, Chassot, L. N., Scolaro, B., Roschel, G. G., Cogliati, B., Cavalcanti, M. F., Abdalla, D. S. P., et al. However, there are only six currently available clinical trials using fisetin, most of which are still recruiting (Table 6). A recent study reported that fisetin reduces myocardial tissue damage in a reperfusion ischemia model by suppressing mitochondrial oxidative stress and inhibiting glycogen synthase kinase 3 (Shanmugam et al., 2018). Front. Pharmacol.

Authors were supported by VALERE: Vanvitelli per la Ricerca Program, MIUR20152TE5PK, EPICHEMBIO CM1406, the Campania Regional Government Lotta alle Patologie Oncologiche iCURE (CUP B21c17000030007), Campania Regional Government FASE 2:IDEAL (CUP B63D18000560007), MIUR Proof of Concept (POC01_00043), Vanvitelli per la Ricerca Program AdipCare (ID 263). (2010).

T2D is a chronic illness requiring continuing care to prevent long-term and acute complications. Indian J. Med. Redox Signal 19 (2), 151162. It is not intended to be a substitute for professional medical advice, diagnosis or treatment. doi:10.1093/jn/137.10.2190, Geto, Z., Molla, M. D., Challa, F., Belay, Y., Getahun, T. (2020). Substantial amounts of the compounds and their metabolites are degraded in the colon by intestinal microbiota, giving rise to small phenolic acids and aromatic catabolises which are absorbed by the circulatory system (Del Rio et al., 2013). Figure 2 Nutraceutical action on SIRT1 expression. In mammalians, RSV administration can improve SIRT1-dependent cellular processes such as axonal protection (Araki et al., 2004), fat mobilization (Chaplin et al., 2018), and inhibition of NF-B-dependent transcription (Yeung et al., 2019); these effects are abolished in SIRT1 knockdown models. Nutr. Annu. 39 (3), 283299. Metab. In the RAW 264.7 cell line, Que was also shown to counteract LPS-induced inflammation by phosphorylation of tyrosine phosphatidylinositol-3-kinase (PI3K)-p85 and complex formation of toll-like receptor 4 (TLR4)/MyD88/PI3K (Endale et al., 2013). Am. MiR-34a/sirtuin-1/foxo3a is involved in genistein protecting against ox-LDL-induced oxidative damage in HUVECs. Fisetin treatment in NAFLD mice reduced epididymal adipose tissue, hepatocyte steatosis, and fatty acid synthesis. doi:10.1016/j.archoralbio.2013.07.005, Gupta, S. C., Patchva, S., Koh, W., Aggarwal, B. Oxidative injuries promote ROS generation in human endothelial cells and SIRT1 regulates endothelial function. Physiol. (2018). The fact that studies indicate that the majority of SIRT activators (or at least SIRT1-targeting activators) exert both direct activating effects and indirect effects via modulation of SIRT1 downstream pathways complicates the interpretation of results and, particularly, the mining of data specifically dependent on direct SIRT1 binding and activation. CI, MS, AN, and LA contributed to the redaction of the manuscript and gave final approval of the manuscript. SIRT1 activation by curcumin pretreatment attenuates mitochondrial oxidative damage induced by myocardial ischemia reperfusion injury. J. Nutr. (2004). Exp. 2016:1689602. doi:10.1155/2016/1689602, Yu, Y., Sun, J., Wang, R., Liu, J., Wang, P., Wang, C. (2019). doi:10.1016/j.mrrev.2011.11.001, Price, N. L., Gomes, A. P., Ling, A. J., Duarte, F. V., Martin-Montalvo, A., North, B. J., et al. The fact that many of these natural molecules are introduced through diet underscores the importance of dietary intervention to correct predisposition and life-style disorders. Cell Biochem. A nutraceutical combination reduces left ventricular mass in subjects with metabolic syndrome and left ventricular hypertrophy: A multicenter, randomized, double-blind, placebo-controlled trial. J. Physiol. (2016). Treatment with higher bioavailable preparations of Cur derivatives may result in increased SIRT1-activating action, further substantiating the link between SIRT1, Cur, and therapeutic effects. SIRT6 is a protein with an important job; it is vital for both normal base excision repair and double-strand break repair of DNA damage, as this damage leads to genomic instability, ultimately contributing to aging. AMP activated protein kinase (AMPK) is also a target of RSV, as it controls SIRT1 activity via regulation of cellular levels of NAD+, thus acting as an energy sensor (Price et al., 2012). A recent study investigated the neuroprotective effects of fisetin as a possible CRM against apoptosis, oxidative stress, aging, and neurodegeneration (Singh et al., 2018). 928, 2745. Oral. (2016). Numerous studies have provided evidence of the protective effects of natural polyphenolic substances such as resveratrol, quercetin, curcumin, and fisetin, and of natural non-polyphenolic substances such as berberine (McCubrey et al., 2017). Nutr. Protective effect of curcumin on TNBS-induced intestinal inflammation is mediated through the JAK/STAT pathway. 127 (7), 618627. A further question is related to the cell/context-specific expression of some SIRTs, cofactor availability, and context-specific action of some of the described modulators. doi:10.2337/db12-0117, Wafi, A. M., Hong, J., Rudebush, T. L., Yu, L., Hackfort, B., Wang, H., et al. Several molecules, including natural phytochemical compounds, can modulate SIRT1 activity (Miceli et al., 2014).

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