50 results about "SIRT3" patented technology

Compositions and methods useful for inducing an increase in fatty acid oxidation or mitochondrial biogenesis, reducing weight gain, inducing weight loss, or increasing Sirt1, Sirt3, or AMPK activity are provided herein. Such compositions can contain synergizing amounts of a sirtuin-pathway activators, including but not limited to resveratrol, in combination with beta-hydroxymethylbutyrate (HMB), keto isocaproic acid (KIC), leucine, or combinations of HMB, KIC and leucine.

Compositions and methods useful for inducing an increase in fatty acid oxidation or mitochondrial biogenesis, reducing weight gain, inducing weight loss, or increasing Sirt1, Sirt3, or AMPK activity are provided herein. Such compositions can contain synergizing amounts of a sirtuin-pathway activators, including but not limited to resveratrol, in combination with beta-hydroxymethylbutyrate (HMB), keto isocaproic acid (KIC), leucine, or combinations of HMB, KIC and leucine.

The invention discloses SUMOylation modification which can be carried out at the K288th site of deacetylase SIRT3 dependent on NAD in a mitochondrion as well as modulation and control of activity of SIRT3; meanwhile, SUMO specific protease 1 (SENP1) can modulate and control SUMOylation modification of the SIRT3, so that related physiological and pathological processes in which SIRT3 participatingof mitochondrion are modulated and controlled; the modulation and control effect of the SENP1 depends on phosphorylated modification of an SENP1S180 site. The invention discloses the influence of a signal modulation and control path of an SENP1-SIRT3 shaft on metabolism of the mitochondrion, the activation of macrophage and T cells, and tumor immunity and tumor growth; therefore, a significance onprevention and treatment of diseases related with mitochondria metabolism and tumor is realized.

A method of inducing NAD+ synthesis in a subject. The method comprises administering to the subject a therapeutically effective amount of resveratrol or a functionally equivalent analogue or derivative thereof. NAD+ synthesis increases the activity of Poly(ADP-ribose) polymerase (PARP) enzymes and sirtuin enzymes. The PARP enzyme is PARP-1 or PARP-2 and the sirtuin enzyme is selected from the group consisting of SIRT1, SIRT2, SIRT3, SIRT4, SIRT5, SIRT6 and SIRT7.

This invention discloses the first cellular acetylated substrate protein of SIRT3, Acetyl-CoA synthetase 2 (AceCS2), which is a mitochondrial matrix protein. AceCS2 is reversibly acetylated at lysine 642 (Lys642) in the active site of the enzyme. The mitochondrial sirtuin SIRT3 interacts with AceCS2 and deacetylates Lys642 both in vitro and in vivo. Deacetylation of AceCS2 by SIRT3 activates the acetyl-CoA synthetase activity of AceCS2. Thus, a mammalian sirtuin directly controls the activity of a metabolic enzyme via reversible lysine acetylation. Modulators of the acetylation status or the activity of AceCS2 are useful for the treatment of pathological conditions, such as type II diabetes, hypercholesterolemia, hyperlipidemia, and obesity.

Described herein are methods, systems and compositions for the diagnosis, prognosis and treatment of dementia and Alzheimer's disease. Also described are methods, systems and compositions to distinguish between Alzheimer's disease and Parkinson's disease. In various embodiments levels of PACAP and / or SIRT3 are analyzed for the diagnosis, prognosis and treatment of dementia and Alzheimer's disease.

The invention relates to a Tat-SPK2 peptide for treatment of cardiac hypertrophy or heart failure and application thereof. The amino acid sequence of the Tat-SPK2 peptide from N terminal to C terminalis YGRKRRQRRRGGSGDGLLYEVLNGLLDRPD. The Tat-SPK2 peptide can be applied to preparation of drugs treating human cardiac hypertrophy or heart failure. The Tat-SPK2 peptide can alleviate isoprenaline-induced cardiac hypertrophy in mice, has preventive and therapeutic effects on cardiac hypertrophy or heart failure, and the cardioprotective mechanism has no connection with autophagy, and is generatedby up-regulation of SIRT3 and Bcl-2 and down-regulation of BNIP3.

The invention provides a composition with the function of activating HSF-1 transcription. The composition with the function of activating HSF-1 transcription can induce the increase of in vivo HSF-1 activity, the increase of in vivo HSF-1 activity can conduct competition and synergy of a transcription enhancer NF-kappa B, so as to specifically increase the activity of adenyl cyclase, Sirt1 and Sirt3, and assist protein folding and protective properties collaboratively with HSPs, and activate anti-aging enzyme pathway. The important part of the invention is that the HSF-1 and the heat shock protein HSPs, the transcription of which is completed by HSF-1, closely involve in the expression and activity regulation of the anti-ageing enzyme. The process by activating the in vivo stress effect factor specifically activates the antioxidant and anti-apoptosis pathway, thereby achieveing the purpose of anti-aging. Therefore, the invention provides a novel target for the activation of the anti-aging enzyme pathway, and provides an effective regulator for the aging regulation and control of cells at the gene level.

The invention discloses an application of an engineered exosome rich in SIRT3 in preparation of a medicine for improving mitochondrial dysfunction. The method comprises the following steps: screening to obtain a polypeptide molecular gel G12 targeting HSP60, forming a fusion protein SIRT3-G12 from the G12 and SIRT3, constructing a recombinant plasmid for expressing the fusion protein, transfecting cells, culturing, and extracting an exosome, thereby obtaining the engineering exosome SIRT3-Exo rich in SIRT3. The SIRT3-Exo is used for treating mitochondrial dysfunction, and the research shows that the SIRT3-Exo can remarkably promote mitochondrial oxidative phosphorylation, promote expression of cell antioxidant enzymes and deacetylation of FOXO3a, enhance the antioxidant capacity of cells and remove ROS in the cells, and has the effect of promoting mitochondrial function recovery. The problem that SIRT3 cannot be used for treating mitochondrial dysfunction through exosomes is solved, and good application prospects are achieved.

The invention belongs to the technical field of medicine preparation, and particularly relates to application of DHGC in preparation of a medicine for treating acute kidney injury ferroptosis mediated by an SIRT3 / NRF2 axis. Experiments prove that DHGC can activate SIRT3 in a targeted manner, up-regulate the expression level of SIRT3, promote NRF2 deacetylation and drive NRF2 nuclear translocation, and further up-regulate the expression level of GPX4, so that the effect of resisting ferroptosis caused by acute kidney injury is achieved.

The invention relates to the field of Sirt3 gene activators, and discloses an application of atractylone in preparation of a Sirt3 gene activator. The dosage form of the Sirt3 gene activator can be a solid preparation or a liquid preparation, and the administration route can be oral administration or injection. It is found that atractylone can effectively up-regulate expression of the Sirt3 gene, can be used as an active component in a Sirt3 gene activator, and provides a new choice for treatment of SIRT3 related diseases.

The invention provides novel application of gastrodin. Application comprises application of the gastrodin in resistance to brain injury. It is found through experiments that the gastrodin can significantly enhance protection of nervous systems, and the action mechanism of the gastrodin is that the gastrodin can inhibit activated-microglial-cell-mediated activation of astrocytes, can reduce proteinexpression of inflammatory factors (TNF-alpha and iNOS), ACE, AT1 and NOX2 in the reactive astrocytes, and can promote up-regulation of SirT3, so as to achieve a neuroprotection effect; moreover, when AT1 receptor blocker-azilsartan and the gastrodin are applied in cooperation, expression of the NOX2 can be effectively reduced more, generation of the iNOS is reduced, and expression of the SirT3 is promoted at the same time to achieve a brain protection effect; meanwhile, the gastrodin promotes release of the astrocytes of a large number of neurotrophins of BDNF and IGF-1 more in the presenceof the microglial cells, so that the protection effect on the nervous systems is further enhanced; and it is proven that the gastrodin has good neuroprotection effect and brain protection effect, andhas potential clinical application prospects.

The method comprises the following steps: amplifying SIRT3 and SIRT4 genes from human, cloning the SIRT3 and SIRT4 genes to a plasmid vector to construct a pSIRT3-4 plasmid, and mediating the simultaneous expression of the two genes by using an internal ribosome entry site (IRES). According to the present invention, the insulin resistance (IR) model of the HepG2 cell is established by using the 35mM high glucose solution, and after the transfection of the pSIRT3-4 plasmid, the uptake of glucose is improved, the conduction of the insulin signal is recovered, the sensitivity of the HepG2 cell to the insulin is improved, the IR is improved, and the dysfunction of the mitochondria is recovered. The pSIRT3-4 plasmid is wrapped by insulin-coupled cationic liposome and is applied to an IR mouse model, and research proves that lipid accumulation in the IR mouse liver is obviously reduced, and the mitochondrial function of the IR mouse liver is obviously improved. The pSIRT3-4 plasmid constructed by the invention provides a new gene therapy means for the treatment of insulin resistance.

The present invention provides, inter alia, kits for selecting a chemotherapy regimen for a subject. The kits comprise one or more components for detecting the expression of at least one gene from the group of SLC12A7, GZMB, TAF6L, NFIB, METRN, ROPN1B, TTK, CCND1, PTTG1, H2AFZ, WDR45L, DEK, MCM2, USP1, CDT1, TMEM97, RER1, MCM6, LZTFL1, C11orf17, CCL5, XCL1, XCL2, MELK, CTSL2, TPX2, AURKA, CDKN2C, BRP44, PNP, SMC4, NR4A2, C3orf37, MTPAP, CDC25B, ABCF1, MTAP, SNAPC3, RANBP9, COIL, FAM86B1, ITGA6, S100P, RANBP1, PRSS16, SMARCA2, STK24, TSPYL5, SRI, LRP12, CENPF, TUBD1, KIAA1324, DBF4, CCNA2, DLGAP5, FHL1, SIRT3, GTSE1, PCNA, CCNE2, CHD3, CAP1, GPM6B, GUSBP3, GNAI3, LMO4, PSRC1, USP1, STK38, BAT2L1, PMP22, NME5, CENPA, BANK1, and derivatives thereof. Methods for selecting a chemotherapy regimen for a subject are also provided.

The invention discloses application of a human sirt3 gene or a sirt3-like gene or a product thereof in stem cell differentiation inducing, and provides a method for promoting stem cell differentiationor mitochondrial biogenesis increase. The high-expression sirt3 protein can significantly enhance aerobic metabolism of stem cells and promote conversion of stem cell metabolism from glycolysis to oxidative phosphorylation; the sirt3 improves the biogenesis of stem cell mitochondria, and is beneficial to inducing stem cell differentiation. After the stem cells are induced and differentiated by the sirt3, the stem cells can be developed into various tissues and used for artificial organ regeneration, for example, bone marrow mesenchymal stem cells are differentiated into osteoblasts used for bone tissues for 3D printing.

The invention discloses a resveratrol-loaded Prussian blue / tetrahedral framework nucleic acid nanocomposite and application thereof in preparation of a medicine for treating epilepsy. The nano-composite (R-tFNAs (at) PB) takes Prussian blue (PB) nano-enzyme as a core, and tetrahedral framework nucleic acid (tFNAs) loaded with resveratrol (Res) is anchored on the surface of the nano-composite (R-tFNAs (at) PB). The nanocomposite has excellent blood-brain barrier (BBB) penetrating ability and focus targeting ability, and can specifically gather in epilepsy hippocampus focus. In mechanism, the compound enhances the oxidation resistance of mitochondria by synergistically removing reactive oxygen species (ROS) and activating an SIRT3 / SOD2 signal channel, further inhibits activation of NLRP3 inflammasomes, and promotes polarization of microglial cells from a pro-inflammatory M1 type to an anti-inflammatory M2 type. In-vivo and in-vitro experiments show that the compound can significantly reduce neuron damage, reduce epileptic seizure frequency and severity, and significantly improve cognitive impairment caused by epilepsy, and has good biological safety.

The invention discloses a research method of 18beta-glycyrrhetinic acid on high-fat daily ration induced mitochondrial function injury mediated liver injury, which comprises the following steps: S1, test design, S2, test sample collection, S3, index determination, S4, test data statistical analysis, and S5, results, and the research method for 18beta-glycyrrhetinic acid (18beta-glyrhetinic acid, 18beta-glyrhetinic acid, 18beta-glyrhetinic acid, 18beta-glyrhetinic acid, 18beta-glyrhetinic acid, 18beta-glyrhetinic acid, 18beta-glyrhetinic acid, 18beta-glyrhetinic acid, 18beta- The liver injury of the micropterus salmoides caused by high fat ration (HF) can be improved by lowering TGF beta1-Smad2 / 3 signals to reduce aggregation of liver collagenous fibers, and the GA can activate Ampk-Pgc1alpha-Sirt3 signal pathways to reduce expression of calcium ion transporters in endoplasmic reticulum and mitochondria, relieve liver mitochondrial injury and reduce the content of ROS (reactive oxygen species), so that the liver injury of the micropterus salmoides caused by high fat ration (HF) can be relieved, and the liver injury of the micropterus salmoides caused by high fat ration (HF) can be relieved. And the HF can increase the activity of liver function related enzymes of the micropterus salmoides and increase liver lipid droplet deposition and collagen aggregation, and after the GA is added, the adverse effect caused by the HF can be obviously improved, so that the HF-induced liver injury of the micropterus salmoides can be relieved.

The invention discloses an application of an SIRT3 enriched exosome in preparation of a medicine for improving myocardial ischemia reperfusion injury. The preparation method comprises the following steps: screening to obtain polypeptide molecular gel G12 targeting HSP60, forming recombinant protein SIRT3-G12 from the G12 and SIRT3, constructing recombinant plasmids for expressing the recombinant protein, transfecting cells for co-expression, and extracting exosomes, thereby obtaining the SIRT3-enriched exosome SIRT3-Exo. In a cell experiment, the SIRT3-Exo has the effects of improving the mitochondrial metabolism function and reducing the oxidative stress and apoptosis level of the cells on hypoxia reperfusion myocardial cells. In an animal experiment, SIRT3-Exo is injected into a myocardial ischemia area of an I / R rat, so that the cardiac function is remarkably improved, the oxidative stress and inflammatory injury level is reduced, and angiogenesis is promoted. The result shows that the SIRT3-Exo has an obvious improvement effect on the myocardial ischemia reperfusion injury.

The present invention relates to targeted SIRT3 inhibitors and their use in AML treatment, belonging to the technical field of tumor therapeutic drug discovery. The present invention provides a compound having the structural formula shown in Formula I or a pharmaceutically acceptable salt thereof, wherein R1 and n are as described in the claims and the specification. The present invention also provides an intermediate for preparing a compound of Formula I or a pharmaceutically acceptable salt thereof. The compound of Formula I or a pharmaceutically acceptable salt thereof or a pharmaceutical composition thereof can be used to prepare SIRT3 inhibitors and for anti-tumor use, particularly for the treatment of leukemia.

The invention discloses an application of SIRT3 and SIRT5 double-gene co-expression in preparation of a medicine for improving Alzheimer's disease. The SIRT3 and SIRT5 double-gene co-expression plasmid is used for treating the Alzheimer's disease, and the result shows that the SIRT3 and SIRT5 double-gene co-expression plasmid can effectively improve the ATP and mtDNA content of damaged microglia and neuronal mitochondria, enhance the antioxidant enzyme activity of cells, reduce ROS, improve the mitochondrial network structure, promote metabolism reprogramming of M1 type microglia to be converted into M2 type microglia, and improve the metabolism reprogramming efficiency of the M1 type microglia. The M2 microglial cells can clear Abeta of neurons and transfer mitochondria to the neurons, so that the Alzheimer's disease is improved.

The invention belongs to novel application of hypaconitine as a Sirt3 inhibitor, and particularly discloses application of hypaconitine and a structural analogue thereof as the Sirt3 inhibitor and inducing in-vivo and in-vitro oxidative stress, influence of the hypaconitine on cell Sirt3 protein expression, application of the hypaconitine as the Sirt3 inhibitor, application of the structural analogue of the hypaconitine as the Sirt3 inhibitor. application of the hypaconitine in inhibiting Sirt3 to induce in-vivo and in-vitro oxidative stress, and application of the structural analogue of the hypaconitine in inhibiting Sirt3 to induce in-vivo and in-vitro oxidative stress. The hypaconitine has an obvious inhibition effect on the Sirt3, causes increase of the oxidative stress level, and can be used as the Sirt3 inhibitor for scientific research and drug clinic.

The invention discloses an anti-wrinkle composition containing a camellia japonica extract and capable of promoting cell energy and an application of the anti-wrinkle composition. The anti-wrinkle composition is prepared from the following components in percentage by mass: 5 to 20 percent of camellia japonica extract, 7.4 to 7.6 percent of flaxseed oil, 0.14 to 0.16 percent of sorbitan trioleate, 0.005 to 0.007 percent of celery seed extract, 0.004 to 0.006 percent of crithmum maritimum extract, 0.003 to 0.004 percent of flaxseed extract and the balance of caprylic / capric triglyceride which is supplemented to 100 percent. The invention further discloses application of the anti-wrinkle composition in promoting synthesis of NAD < + > and ATP in dermal fibroblasts and / or epidermal keratinocytes and / or SIRT3 gene expression and application of the anti-wrinkle composition in preparing cosmetics or skin care products with anti-wrinkle and tightening effects. The composition disclosed by the invention is an oil-soluble composition, is easier to absorb, and can improve the mitochondrial activity through synergistic interaction.

The invention discloses application of MV in preparation of a medicine with protection effect on neuronal injury caused by PD. The protection effect of the MV on neurotoxicity induced by Rotenone (Rot) is researched; in-vivo and in-vitro models of PD are established; then behavioristics and nerve injury, cell viability, ROS (reactive oxygen species) level, mitochondrial membrane potential (MMP), mitochondrial respiratory chain function, early apoptosis and ATP (adenosine triphosphate) level of model mice are detected; and finally, by up-regulating Sirtuin 3 (SIRT3), the action mechanism of the MV in the neuroprotection of PD is discussed.

The invention discloses application of a senescence-related differential expression gene in preparation of a cell senescence diagnostic kit, and belongs to the technical field of biomedicine. Through screening and verification, the protein expression level and m6A RNA methylation modification level of the senescence-related differential expression genes SIRT3, E2F3 and IRS2 are found for the first time, the method can be used for identifying and diagnosing the senescence state of cells, the problem that diagnostic markers in the field of cell senescence are in shortage at present is solved, and a reference basis is provided for early prevention and targeted therapy of cell premature senility and age-related diseases.

The invention provides application of miR-6858 in preventing and treating glioma through melatonin and belongs to the technical field of biomedicines. Specifically, the invention finds that melatoninhas a good antitumor function on cells U251, U87, A172 and GBM#P3. Meanwhile, through miRNA (micro ribonucleic acid) sequencing on GBM (glioblastoma multiforme) cells treated by using melatonin, target miRNA is found, growth of the GBM cells can be inhibited by increasing miR-6858 through the melatonin, and furthermore, an SIRT3 / AKT signal channel can be inhibited. The invention illuminates molecule mechanisms based on interactions melatonin and miRNA, and an effective treatment strategy is provided for treatment on GBM.

The invention discloses a 3-aryl coumarin derivative as well as a preparation method and application thereof. The preparation method comprises the following steps of: carrying out tandem condensation-lactonization reaction on substituted phenylacetic acid and substituted 2-hydroxybenzaldehyde as raw materials in the presence of triethylamine and acetic anhydride, and after the reaction is finished, respectively and independently carrying out three post-treatment methods to obtain the 3-aryl coumarin derivative. The 3-aryl coumarin derivative provided by the invention has good affinity to SIRT3 protein, can up-regulate the deacetylase activity of the SIRT3 protein and reverse ISO (isoprenaline) stimulated and induced cardiac hypertrophy, and can be used for preparing anti-cardiovascular disease or anti-diabetes drugs.