30 results about "Mitochondrial biogenesis" patented technology

Disclosed herein is a genetically engineered mesenchymal stem cells (MSC) comprising genetic alterations that increase gene expressions for adipogenic differentiation, mitochondrial biogenesis and a brown adipocyte marker. Also disclosed herein is a pharmaceutical composition and use of the pharmaceutical composition for preventing, ameliorating and / or treating a metabolic disorder.

The invention belongs to the technical field of terahertz wave irradiation, and particularly relates to a method for regulating mitochondrial biosynthesis through high-frequency terahertz waves and a system and application thereof. It has been found that the flow of calcium ions can be promoted by irradiating cells with a specific high-frequency terahertz wave (such as 34.5 THz), thereby activating a mitochondrial biosynthetic pathway and regulating mitochondrial functions, thereby improving symptoms and life quality of patients with diseases (such as cancers, neurodegenerative diseases and the like) associated with mitochondrial damage.

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 invention provides a potential therapeutic target for cardiac hypertrophy and heart failure, finds that the cardiac hypertrophy caused by pressure load can be obviously relieved by using adeno-associated virus (AVV9) as a carrier myocardial cell specific overexpression Ces1d gene, and finds that the Ces1d relieves the cardiac hypertrophy by promoting fatty acid oxidation; and a potential target and a new strategy are provided for heart failure treatment. According to the invention, Ces1d is taken as a regulation target, and the expression level of Ces1d is regulated, so that the fatty acid oxidation of myocardial cells can be obviously promoted, and the expression of fatty acid oxidation related genes such as Cpt1a, Cpt1b, Cpt2, Acadm, Acadvl and Acox1 can be up-regulated, thereby optimizing the utilization mode of a myocardial energy metabolism substrate; meanwhile, mitochondrial dysfunction and mitochondrial generation damage induced by pressure load can be improved. Therefore, the regulation strategy taking the Ces1d as the action target and the AVV9 as the carrier provides a new gene therapy technical approach for prevention and treatment of cardiac hypertrophy and related cardiovascular diseases, and has a good application prospect and a remarkable clinical potential value.

The present invention belongs to the field of biotechnology and specifically relates to a Trichosanthes kirilowii polypeptide having the efficacy of tonifying the kidney and strengthening yang, as well as its preparation method and application. The present invention prepares the Trichosanthes kirilowii polypeptide having the efficacy of tonifying the kidney and strengthening yang through processes such as pretreatment of Trichosanthes kirilowii raw materials, preparation of Trichosanthes kirilowii seed liquid, preparation of crude Trichosanthes kirilowii peptides, ion exchange resin chromatography, and high-performance liquid chromatography purification. The Trichosanthes kirilowii polypeptide provided by the present invention can regulate the expression of testosterone secretion-related genes and proteins in TM3 cells, enhance mitochondrial function, and promote the expression of mitochondrial biogenesis-related genes and proteins. It can significantly promote testosterone secretion in TM3 cells, has the efficacy of tonifying the kidney and strengthening yang, and expands the application range of Trichosanthes kirilowii.

The invention belongs to the technical field of pharmacy, and particularly relates to application of spermidine in sepsis treatment. Experiments prove that spermidine can regulate mitochondrial biogenesis and inhibit mitochondrial excessive autophagy to remarkably improve mitochondrial quality, maintain mitochondrial homeostasis and relieve myocardial dysfunction and heart structure damage. In addition, spermidine can inhibit oxidative stress caused by excessive inflammatory response so as to recover normal functions of mitochondria. The spermidine has a potential treatment effect on sepsis and has a good clinical application prospect in treating sepsis and related diseases caused by excessive autophagy.

The invention discloses a pGC-1alpha activator composition and application thereof, and belongs to the technical field of biological medicine and anti-aging, the pGC-1alpha activator composition comprises an active component, a delivery system and a synergistic component, and can also comprise pharmaceutically or food acceptable carriers or auxiliary materials. The active component directly activates a PGC-1alpha signal channel and promotes mitochondrial biosynthesis; the delivery system realizes targeted delivery; the synergistic components form a multi-way synergistic anti-aging effect. The composition can be applied to the field of cosmetics to improve the activity of skin cells and reduce senescence phenotypes; the compound is applied to the field of medicines for treating mitochondrial dysfunction related diseases such as Alzheimer's disease and sarcopenia; the method is applied to the field of regenerative medicine to enhance survival and function maintenance after stem cell transplantation. The mitochondrial function is recovered by directly regulating and controlling the PGC-1alpha, cell aging is delayed from the source, compared with a traditional antioxidant, the antioxidant has more advantages, systematic toxicity is reduced through dosage regulation and targeted delivery, and the antioxidant is suitable for long-term use, wide in application and wide in commercial potential.

The present disclosure relates to highly purified (R)-3'-hydroxybutyl (R)-3'-hydroxybutyrate and biomedical uses thereof. In particular highly purified (R)-3'-hydroxybutyl (R)-3'-hydroxybutyrate, is provided for enhancing bodily function and treating various disease states. The methods described herein provide for production of a highly purified (R)-3'-hydroxybutyl (R)-3'-hydroxybutyrate via processes external to the human body and administering effective amounts of highly purified (R)-3'-hydroxybutyl (R)-3'-hydroxybutyrate to human subjects to achieve a range of therapeutic benefits, including but not limited to, one or more of: inhibiting inflammasome activation, reducing pro-inflammatory cytokines, improving insulin sensitivity, enhancing mitochondrial biogenesis, and promoting muscle protein synthesis. Additionally, highly purified (R)-3'-hydroxybutyl (R)-3'-hydroxybutyrate is administered in an amount and frequency conducive to one or more of: improving cognitive function, reducing oxidative stress, enhancing cardiovascular health, and supporting neuroprotection. Methods for manufacturing and purifying (R)-3'-hydroxybutyl (R)-3'-hydroxybutyrate compositions to ensure high specificity and efficacy in therapeutic applications are also provided.

This disclosure describes the characteristics of the “energetic” cancer stem cell (e-CSC) phenotype. This distinct sub-population of cancer stem cells (CSCs) has a unique energetic profile compared to bulk CSCs, being more glycolitic, having higher mitochondrial mass and elevated oxidative metabolism. e-CSCs also show an increased capacity to undergo cell cycle progression, enhanced anchorage-independent growth, and ALDH-positivity. The e-CSC phenotype presents new targets for cancer therapeutics, and in particular the anti-oxidant response, mitochondrial energy production, and mitochondrial biogenesis of e-CSCs makes them highly susceptible to mitochondrial inhibitors that target e-CSC anti-oxidant response, mitochondrial energy production, and mitochondrial biogenesis. Gene products for e-CSCs are disclosed, as well as classes of mitochondrial inhibiting therapeutic agents. Also disclosed are methods for identifying and separating e-CSCs front bulk cell populations.

A method for treating low-level blast traumatic brain injury includes administering a phosphodiesterase-5 (PDE5) inhibitor, such as sildenafil, to a subject following exposure of the subject to one or more low-level blasts. Administration of the PDE5 inhibitor may prove useful with respect to improving the vascular integrity of a subject by increasing brain capillary respiration, mitochondrial respiration, mitochondrial density, mitochondrial biogenesis, astrocyte level or homeostasis, and / or tight junction protein expression in the brain of the subject and / or inducing positive metabolic change in the subject by increasing NAD+ / NADH metabolism. Methods for mitigating the effects of blast injury on the vascular integrity of a subject and inducing metabolic change are also provided.

The invention discloses a chemical small molecule compound and method for promoting mesenchymal stem cell mitochondria to be delivered to muscle cells. The chemical small molecule compound is composed of metformin, beta-nicotinamide mononucleotide, nicotinamide, ergothioneine and pyrroloquinoline quinone. The concentration range of each component is respectively as follows: 1 to 5mM of metformin, 0.1 to 1mM of beta-nicotinamide mononucleotide, 0.1 to 1mM of nicotinamide, 0.1 to 1mM of ergothioneine and 0.01 to 0.1 mu M of pyrroloquinoline quinone. The compound regulates and controls the mitochondrial function of mesenchymal stem cells through a staged treatment strategy: in the first stage (0-24 h), an AMPK signal channel is activated through metformin, the NAD + level is increased in combination with beta-nicotinamide mononucleotide and nicotinamide, and mitochondrial biogenesis is started; the pyrroloquinoline quinone is combined to promote DNA replication and protein synthesis of mitochondria, further increase the number of mitochondria and optimize functions.

In one aspect, the disclosure relates to pyridinylpiperazine-based compound MARY1 and derivatives thereof, methods of making the same, pharmaceutical compositions comprising the same, and methods of treating acute kidney injury and reducing senescent changes in the kidney using the same. In one aspect, the disclosed compounds are selective 5-HT2B agonists. In another aspect, the disclosed compounds are useful for stimulating mitochondrial biogenesis.

The present invention discloses an anti-aging composition synergistically enhancing mitochondrial function with AKG and PQQ, belonging to the technical field of anti-aging. The composition comprises AKG, PQQ disodium salt, Agaricus bisporus extract, and a single excipient. AKG, in anhydrous crystal form as 2-oxoglutaric acid, directly participates in mitochondrial energy metabolism and provides core substrate support. PQQ disodium salt promotes mitochondrial biogenesis, ensuring structural renewal and maintaining mitochondrial activity. The β-glucan and ergothioneine naturally contained in the Agaricus bisporus extract further support the normal physiological state of mitochondria through synergistic effects. The single excipient is only physically mixed with the active ingredients, reducing interference caused by excipient interactions and ensuring that the efficacy of each active component is fully exerted.

The invention belongs to the technical field of veterinary drug preparation, and particularly relates to a terpinen-4-ol compound preparation for preventing and treating broiler ascites syndrome as well as a preparation method and application of the terpinen-4-ol compound preparation. The compound preparation for preventing and treating the ascites syndrome of the broilers is provided by taking T4O as a main active ingredient and silicon dioxide as a carrier, and the preparation can efficiently resist oxidation, reduce abnormal expression of oxidative stress and mitochondrial biogenesis related genes, improve liver functions, reduce ascites formation and remarkably reduce the morbidity of the ascites syndrome of the broilers, so that the compound preparation for preventing and treating the ascites syndrome of the broilers can be used for preventing and treating the ascites syndrome of the broilers. The control effect is obvious, and the pesticide cost is reduced.

To provide a Trichosanthes kirilowii polypeptide having a nephrotonic effect, a preparation method and use thereof.SOLUTION: In the present invention, the Trichosanthes kirilowii polypeptide with nephrotonic effect is obtained by pre-treatment of Trichosanthes kirilowii raw materials, preparation of Trichosanthes kirilowii seed liquid, preparation of crude Trichosanthes kirilowii peptide, ion-exchange chromatography, HPLC purification and other processes. The Trichosanthes kirilowii polypeptide provided in the present invention can regulate the expression of testosterone secretion-related genes and proteins in TM3 cells, improve the mitochondrial function, promote the expression of mitochondrial biosynthesis-related genes and proteins, and significantly promote the testosterone secretion of TM3 cells, and has the effect of promoting kidney tone, thereby expanding the use range of Trichosanthes kirilowii.SELECTED DRAWING: Figure 7

The invention provides an application of a targeted succinyl-coenzyme A synthetase (SUCLG1) in treatment of mitochondrial generation dependent tumors. Specifically, the invention provides an application of an inhibitor targeting SUCLG1, and the inhibitor is used for preparing drugs for promoting succinylation modification of mitochondrial RNA polymerase (POLRMT) and inhibiting the activity of POLRMT so as to reduce mitochondrial biogenesis. And / or a composition or formulation for treating or preventing a mitochondrial biogenesis dependent tumor or cancer. The invention discloses an internal mechanism of the SUCLG1 for regulating mitochondrial biogenesis for the first time, and in-vivo and in-vitro experiments prove that the target inhibition of the SUCLG1 has a remarkable inhibition effect on the progress of mitochondrial generation dependent tumors, and a new target is provided for tumor treatment.

Disclosed herein is a genetically engineered mesenchymal stem cells (MSC) comprising genetic alterations that increase gene expressions for adipogenic differentiation, mitochondrial biogenesis and a brown adipocyte marker. Also disclosed herein is a pharmaceutical composition and use of the pharmaceutical composition for preventing, ameliorating and / or treating a metabolic disorder.

The present invention belongs to the field of biotechnology, and specifically relates to a Fructus Trichosanthis polypeptide having the efficacy of tonifying kidney yang, a preparation method and use thereof. The present invention prepares the Fructus Trichosanthis polypeptide having the efficacy of tonifying kidney and invigorating yang by processes such as pretreatment of a Fructus Trichosanthis raw material, preparation of a Fructus Trichosanthis seed solution, preparation of a crude Fructus Trichosanthis peptide, ion-exchange resin chromatography, and purification via high performance liquid chromatography. The Fructus Trichosanthis polypeptide provided by the present invention can modulate the expression of genes and proteins associated with secretion of testosterone in TM3 cells, enhance the function of mitochondria, accelerate the expression of genes and proteins associated with mitochondrial biogenesis, significantly promote the secretion of testosterone in TM3 cells, and has the efficacy of tonifying kidney and invigorating yang, thereby expanding the application range of Fructus Trichosanthis.

The invention is applicable to the technical field of biological medicines, and provides application of lisinopril in preparation of a medicine for treating amyotrophic lateral sclerosis. The invention has important value for promoting research and development of amyotrophic lateral sclerosis (ALS) treatment medicines and improving prognosis of patients. In-vitro experiments show that lisinopril can prevent mitochondria damage of NSC34 cells induced by SOD1G93A, expression of Beclin 1, LC3 and p62 is regulated by inhibiting a TGF [beta] 1 / PI3K / AKT / mTOR signal channel, cell autophagy is activated, and neuronal apoptosis is inhibited. In-vivo experiments show that lisinopril can activate in-vivo BI1 expression, regulate ALS model mouse lipid content and intervene in a glycerophospholipid metabolic process, and also can inhibit motor neuron death, myelin sheath shedding and neuromuscular junction degeneration and promote mitochondrial biogenesis by influencing autophagy regulated by a TGF [beta] 1 / PI3K / AKT / mTOR pathway.

The present disclosure relates to highly purified (R)-3′-hydroxybutyl (R)-3′-hydroxybutyrate and biomedical uses thereof. In particular highly purified (R)-3′-hydroxybutyl (R)-3′-hydroxybutyrate, is provided for enhancing bodily function and treating various disease states. The methods described herein provide for production of a highly purified (R)-3′-hydroxybutyl (R)-3′-hydroxybutyrate via processes external to the human body and administering effective amounts of highly purified (R)-3′-hydroxybutyl (R)-3′-hydroxybutyrate to human subjects to achieve a range of therapeutic benefits, including but not limited to, one or more of: inhibiting inflammasome activation, reducing pro-inflammatory cytokines, improving insulin sensitivity, enhancing mitochondrial biogenesis, and promoting muscle protein synthesis. Additionally, highly purified (R)-3′-hydroxybutyl (R)-3′-hydroxybutyrate is administered in an amount and frequency conducive to one or more of: improving cognitive function, reducing oxidative stress, enhancing cardiovascular health, and supporting neuroprotection. Methods for manufacturing and purifying (R)-3′-hydroxybutyl (R)-3′-hydroxybutyrate compositions to ensure high specificity and efficacy in therapeutic applications are also provided.

The invention relates to the technical field of medicine, in particular to application of agrimonin in hepatic lung syndrome pulmonary pathological angiogenesis, in the invention, agrimonin promotes mitochondrial biogenesis by repairing mtDNA damage, increasing mtDNA and regulating mitochondrial homeostasis so as to further improve the OXPHOS function of mitochondria, so that the agrimonin can be used for treating hepatic lung syndrome pulmonary pathological angiogenesis. The HPS liver is reduced, and the glycolysis flux of tissues is used for reducing pathological angiogenesis; according to the application of the PGC1-alpha as the target spot of the hairyvein agrimony for treating the liver cirrhosis, the hairyvein agrimony promotes expression of the PGC-1 alpha, promotes the mitochondrial biogenesis function, increases the OXPHOS capacity of PMVECs mitochondria, increases the OXPHOS / glycolysis ratio of tissues and reduces HPS angiogenesis. According to the invention, the active monomers of the traditional Chinese medicines are used for preparing the medicine for treating the pulmonary pathological angiogenesis of the liver-lung syndrome, so that the toxic and side effects of the kidney can be better avoided, the exact action target of the medicine can be analyzed, the living quality and the compliance of a patient are improved, and a new thought is provided for the prevention and treatment of the HPS by utilizing the'simultaneous treatment of the liver and the lung 'of the holism concept.

Reduced muscle contractility and mitochondrial bioenergetics are the hallmarks of systolic heart failure. There is currently no therapy targeting both. The present invention shows that gene delivery of Perml via adeno-associated virus (AAV) simultaneously enhances cardiac contractility and mitochondrial biogenesis. Moreover, PERM1 interacts with Troponin C (TnC), a key contractile protein in striated muscle, and that AAV -Perml led to upregulation of TnC. Thus, gene delivery of Perml can be a novel therapeutic approach to treat or prevent systolic heart failure by simultaneously restoring cardiac contractility and mitochondrial bioenergetics.

The application discloses application of L- kynurenine in preparation of a medicine for preventing and / or treating ultraviolet light induced skin photo-damage. The application proves that L- kynurenine has a significant anti-photo-damage effect by a UVA irradiation HaCaT cell model, can enhance mitochondrial function and promote mitochondrial biogenesis, thereby improving the antioxidant capacity of cells and reducing inflammatory reactions. The application also verifies that a hydrogel containing L- kynurenine can effectively repair mouse back skin damage caused by ultraviolet light through a UVA combined with UVB irradiation back depilation mouse model, improve the water content and antioxidant capacity of the skin, and reduce inflammatory reactions, edema, roughness, erythema or eschar and other phenomena. Therefore, the application provides a reference direction for development, utilization and popularization of L- kynurenine for preparing a medicine or a medical cosmetic product for repairing skin photo-damage.

The invention provides an improvement effect of metformin on post-traumatic stress disorder, and belongs to the technical field of biological medicine. Metformin is used for relieving unbalance of mitochondrial homeostasis in amygdala nucleus on the outer side of a post-traumatic stress disorder model rat by promoting mitochondrial biosynthesis, so that synaptic and dendritic spine abnormity is improved, finally fear memory regression of the post-traumatic stress disorder model rat is promoted, and the post-traumatic stress disorder is improved.

The invention provides an application of inhibiting THAP3 and SMYD3 in synergistic treatment of tumors. In particular, the present invention provides a THAP3 inhibitor, and uses of an active ingredient combination comprising a THAP3 inhibitor and an SMYD3 inhibitor. According to the invention, it is found for the first time that a transcription factor THAP3 is highly related to mitochondrial electron transport chain gene expression, and THAP3 collects SMYD3 to an electron transport chain gene and up-regulates H3K4me3 in a region near a gene promoter so as to realize epigenetic regulation of target gene expression; by inhibiting THAP3 and / or SMYD3, mitochondrial biogenesis of tumor cells can be remarkably inhibited. Therefore, a new target is provided for treating and / or preventing tumors or cancers.

The invention relates to a method for increasing the number of mitochondria of mesenchymal stem cells. The method comprises the following steps: culturing the mesenchymal stem cells; preparing a composite culture medium; treating the mesenchymal stem cells; and carrying out related detection on mitochondria of the mesenchymal stem cells. The method provided by the invention can significantly increase the number of mitochondria, and can effectively promote biosynthesis of mitochondria in mesenchymal stem cells and significantly increase the number of mitochondria through combined use of multiple compounds and multi-target synergistic interaction, thereby improving the energy metabolism ability of cells.

Reduced muscle contractility and mitochondrial bioenergetics are the hallmarks of systolic heart failure. There is currently no therapy targeting both. The present invention shows that gene delivery of Perml via adeno-associated virus (AAV) simultaneously enhances cardiac contractility and mitochondrial biogenesis. Moreover, PERM1 interacts with Troponin C (TnC), a key contractile protein in striated muscle, and that AAV -Perml led to upregulation of TnC. Thus, gene delivery of Perml can be a novel therapeutic approach to treat or prevent systolic heart failure by simultaneously restoring cardiac contractility and mitochondrial bioenergetics.

The invention provides application of Qixuekang in preparation of a medicine for treating renal fibrosis. Experimental research proves that the Qixuekang administration can remarkably recover the renal function of a mouse with renal fibrosis in senescence-accompanied chronic kidney diseases, reduce the mouse kidney mesenchymal fibrosis level and the levels of fibrosis markers alpha-SMA and Col1, recover the content of reductive glutathione in the mouse, improve the activity of superoxide dismutase and improve the curative effect of the kidney fibrosis in the senescence-accompanied chronic kidney diseases. Therefore, kidney fibrosis phenotypes and fibrosis-related biochemical indexes of mice are improved. Qi-blood Kang can remarkably restore kidney mesenchymal transformation related gene and protein expression, and kidney fibrosis phenotypes in chronic kidney diseases are improved by reducing related inflammatory media; qiwankang can significantly improve mitochondrial membrane potential, increase mitochondrial neogenesis related gene expression and reduce generation of active oxygen.

Orally administered low-dose formulations for medium chain di-carboxylic acids have unexpectedly a numerous of beneficial cytoprotective effects in a variety of cells. In particular, contemplated formulations compositions and methods reduce, reverse, and / or prevent liver inflammation, hepatic steatosis, and / or liver fibrosis in NASH, improve blood glucose control, and provide additional cytoprotective benefits such as stimulation of mitochondrial biogenesis, increased SIRT and NAMPT levels, increased NAD+, antioxidant capacity, and / or reduction of DNA damage.

The present disclosure provides compositions and methods for increasing mitochondrial function. The present disclosure further provides nanomaterial structures comprising high atomic vacancy concentrations which are used to stimulate mitochondrial production. The resulting mitochondria may be used for mitochondrial transplantation to treat diseases or disorders associated with decreased mitochondrial function.