96 results about "Telomerase" patented technology

The invention relates to the technical field of cell engineering, and particularly discloses a construction method and application of a sika deer immortalized renal epithelial cell line, and the construction method comprises the following steps: taking renal epithelial primary cells from healthy sika deer renal cortex tissues to obtain primary renal epithelial cells; treating the primary renal epithelial cells with trypsin to obtain a cell suspension; inoculating the cell suspension into a complete culture medium, and transfecting with lentivirus loaded with SV40 large T antigen genes to obtain transfected cells; 3 [mu] g / mL puromycin is applied to the transfected cells for selective culture, so that non-transfected cells are eliminated, and drug-resistant cells are obtained; carrying out continuous passage on the drug-resistant cells for at least 30 generations to obtain the immortalized renal epithelial cell line of the sika deer; according to the invention, through a specific action mechanism (inhibiting a p53 / pRb pathway and blocking cell cycle exit) of the SV40 large T antigen, a proliferation limit caused by inhibition of telomerase activity of primary cells of the cervidae animals is overcome, and a cell resource library capable of realizing continuous passage is established.

The invention provides a composition for delaying senescence by activating telomerase activity. The composition is prepared from the following raw materials in parts by weight: 12.5 parts of wheat germ concentrated powder, 0.25 to 5 parts of ergothioneine, 0.25 to 5 parts of pyrroloquinoline quinone disodium salt and 0.25 to 5 parts of alpha-ketoglutaric acid. The invention further provides a preparation method and application of the composition for delaying senescence by activating telomerase activity. Through the synergistic effect of the ergothioneine and the pyrroloquinoline quinone disodium salt, the telomerase activity can be activated, the telomerase expression can be improved, the telomere length can be maintained, and the effect of delaying senescence can be achieved, so that the functional metabolism of a human body can be promoted, and the health state of the body can be improved; through the synergistic effect of the wheat germ concentrated powder and alpha-ketoglutaric acid, cell aging can be delayed; through the multi-target synergistic effect of'telomerase activation + mitochondrial repair + autophagy enhancement ', the anti-aging effect is delayed, the metabolic capability is high, the anti-aging effect is good, and safety and high efficiency are achieved; belongs to the technical field of food and health care product processing.

The invention provides a DNA library screening method and application of an intracellular mRNA sensor switch. The DNA library screening method comprises the following steps: designing a DNA library containing a switch sequence of a degenerate basic group; preparing a circular expression vector library; preparing a minimum linear expression vector library; performing seamless cloning; carrying out RCA rolling circle amplification; carrying out telomerase digestion; carrying out cell transfection; extracting RNA (Ribonucleic Acid) and carrying out reverse transcription; carrying out library building of next-generation sequencing by taking the cDNA as a template; carrying out next-generation sequencing; analyzing data and comparing to obtain the DNA library of the mRNA sensor switch. According to the DNA library screening method provided by the invention, more sensor switch sequences can be provided for a single site on mRNA in cells, and more selection possibilities are further provided for subsequent targeted therapy.

The present disclosure relates to methods of treating myelodysplastic syndrome. The present disclosure provides methods of treating myelodysplastic syndrome (MDS) in a subject not treated with an agent selected from a hypomethylating agent (HMA) and lenalidomide, or both. The methods comprise administering to the subject an effective amount of a telomerase inhibitor, such as, for example, imestat or imestat sodium. In some cases, a subject being treated is classified as a low or moderate-1IPSS risk MDS subject and / or has an erythropoiesis stimulating agent (ESA) recurrent / refractory MDS.

The invention provides a recombinant herpes simplex virus and a herpes simplex virus modification method. The herpes simplex virus modification method comprises the step of replacing an ICP4 protein coding gene in a herpes simplex virus genome containing an infected cell protein 4 (ICP4) gene with an hTERTp-fluorescent protein expression cassette. The expression cassette comprises an hTERTp promoter and a fluorescent protein coding sequence controlled by the hTERTp promoter, and the transcription direction is opposite to that of an ICP4 promoter in a genome. The hTERTp-fluorescent protein expression cassette in the recombinant virus obtained by the method disclosed by the invention can be normally expressed in response to telomerase activity. Therefore, the recombinant virus is capable of expressing a fluorescent protein, such as mBaoJin, in a cell having human telomerase activity. Cells infected by the virus can be identified through fluorescence signals, and the higher the telomerase activity is, the stronger the fluorescence intensity is. The virus has wide application value in research of tumor action mechanisms and stem cell action mechanisms, health assessment, screening of tumor drugs, research and development of diagnostic reagents and establishment of animal models.

The invention provides a method and a kit for detecting full-length mRNA of a human cell telomerase subunit TERT transcript, and belongs to the technical field of biology. The invention provides a method for detecting human cell telomerase subunit TERT transcript full-length mRNA, a specific reverse transcription primer TERT rt1 is adopted for reverse transcription to obtain cDNA, and if a sixth exon and a seventh exon of the telomerase subunit TERT can be detected in the cDNA, it is judged that a sample to be detected contains the human cell telomerase subunit TERT transcript full-length mRNA. The method disclosed by the invention can be used for distinguishing the full-length mRNA of TERT mRNA and other shear isomer mRNA, and a new technical means is provided for more conveniently, accurately and indirectly evaluating the activity of telomerase in cells.

The present disclosure provides transgenic mice for use as mouse models, and methods related thereto. The transgenic mice described herein comprise a humanized mouse telomerase (hmTert) gene included in a background mouse germline that provides shortened telomeres capable of reproducing humans and various human disease states.

The application discloses application of falcarinol-7-methyl ether and derivatives thereof in preparation of medicines and functional foods for delaying aging or immune regulation. In the application, the falcarinol-7-methyl ether and derivatives thereof are derived from falcarinol-7-methyl ether, and can effectively delay replicative senescence of mesenchymal stem cells, inhibit expression of aging-related markers of mouse liver and lung induced by adriamycin, improve grip strength of the mouse, enhance muscle function, and promote proliferation of T cells separated from human peripheral blood mononuclear cells, and have an immune regulation effect. Therefore, the falcarinol-7-methyl ether and derivatives thereof have good effects of improving telomerase activity, anti-aging and immune regulation, and can be developed into anti-aging or immune regulation products.

The invention belongs to the field of food science and engineering, and discloses a preparation method of an active medicinal and edible composite nutrient AMCN with an anti-aging effect, and the preparation method comprises the following steps: putting a ganoderma lucidum monoclonal strain into a liquid culture medium for controllable culture to obtain supernate with beta-glucosidase activity of over 100mU / mL; and adding rhizoma polygonati powder, lucid ganoderma powder and mulberry leaf powder, carrying out enzymatic biotransformation, carrying out lactobacillus plantarum fermentation, adding a freeze-drying protective additive, carrying out freeze-drying, grinding to obtain the active medicinal and edible composite nutrient AMCN, and storing the finished product in a dry and dark place. The active medicinal and edible composite nutrient can be used for preparing anti-aging functional foods or nutritional health-care products. A D-galactose induced zebrafish aging model verifies that the active medicinal and edible composite nutrient prepared by the application plays an anti-aging role by relieving oxidative stress, inhibiting cell aging and maintaining telomere stability, can reduce beta-galactosidase activity and intracellular ROS (reactive oxygen species) level, improves telomerase protein concentration, and has a good anti-aging effect. And the telomere length can be effectively recovered by medium and high concentrations.

This disclosure provides methods of treating a myelodysplastic syndrome (MDS) in a subject that is naive to treatment with an agent selected from a hypomethylating agent (HMA) and lenalidomide, or both. The method includes administering to the subject an effective amount of a telomerase inhibitor, such as e.g. imetelstat or imetelstat sodium. In some cases, the subject treated is classified as low or intermediate-1 IPSS risk MDS and / or have MDS relapsed / refractory to Erythropoiesis-Stimulating Agent (ESA).

The application provides a DNA library screening method of intracellular mRNA sensor switch and application. The DNA library screening method comprises the following steps: designing a DNA library containing a switch sequence with a complementary base; preparing a circular expression vector library; preparing a minimized linear expression vector library; seamless cloning; RCA rolling circle amplification; telomerase enzyme cutting; cell transfection; RNA extraction and reverse transcription; library construction by performing second-generation sequencing with the cDNA as a template; second-generation sequencing; data analysis and comparison, and obtaining the DNA library of the mRNA sensor switch. The DNA library screening method provided by the application can provide more sensor switch sequences for a single site on intracellular mRNA, and further provides more selection possibilities for subsequent targeted treatment.

Disclosed are use of a circRNA molecule as a diagnostic marker in a cell senescence diagnosis kit, and use thereof as a treatment target for cell senescence. The present invention finds that circHERC1 is lowly expressed in both cell models of natural senescence and induced senescence. Overexpression of circHERC1 in endothelial cells can improve the proliferation capacity of the endothelial cells, effectively extend the telomere length of the cells, activate telomerase, reduce the β-galactosidase positive rate of the cells, and reduce the expression of all senescence-associated proteins. Introduction of exogenous circHERC1 into mice can effectively delay the senescence of various organs and the shortening of telomeres in aged mice and reduce the β-galactosidase positive rates of various organs of aged mice.

Disclosed herein are dietary supplements, and nutraceutical compositions thereof, comprising a polypeptide having at least 80%, 85%, 90%, 95%, 98% or 99% sequence identity to the amino acid sequence set forth in SEQ ID NO 1 and 2; and methods of increasing telomerase activity and extending the length of telomeres using a composition comprising a polypeptide having at least 80%, 85%, 90%, 95%, 98% or 99% sequence identity to the amino acid sequence set forth in SEQ ID NO 1 or 2. Also disclosed is an isolated polypeptide according to SEQ ID NO 2.

The present invention relates to a drug delivery composition comprising a telomerase activator and nanoparticles, and a composition for preventing, improving, or treating hair loss comprising the same. More specifically, the present invention relates to a nanoliposome, nanosilica particle, or nanobubble composition encapsulating drugs such as the plant extract component TA-65 and its derivatives that increase telomerase activity, the telomerase activating compound GPC and its derivatives, and having the efficacy of promoting the regeneration and growth of hair follicles.

This disclosure provides methods of treating a myelodysplastic syndrome (MDS) or acute myeloid leukemia (AML) in a subject in need thereof, wherein the subject treated is classified as having an intermediate-2 or high IPSS risk MDS or AML; or has MDS or AML relapsed, refractory, or intolerant to HMA, venetoclax, or a combination thereof. The method includes administering to the subject an effective amount of a telomerase inhibitor or a pharmaceutically acceptable salt thereof, such as e.g. imetelstat or imetelstat sodium.

The present invention is directed to methods and uses of a series of compounds and compositions comprising the same for treating diseases, disorders and / or conditions related to fertility and preserving same and conditions related to same. In some aspects, the compounds and or compositions as herein described promote, improve, recover or restore fertility in a subject in need thereof, including in male and / or female subjects. Such methods / uses include promoting, enhancing or improving fertility-associated cell or tissue yield as part of an in vitro fertilization protocol.

Provided herein are compounds and isolated enantiomers useful for inhibiting telomerase, pharmaceutically acceptable salts thereof, and pharmaceutical compositions comprising at least one such compound, isolated enantiomer, or pharmaceutically acceptable salt thereof. Also described is the use of such compounds, isolated enantiomers, or pharmaceutically acceptable salts thereof, and the use of pharmaceutical compositions comprising at least one such compound, isolated enantiomer, or pharmaceutically acceptable salt thereof, in methods of treating disorders or conditions such as cancer, where the cancer may be a hematological malignancy or a solid tumor.

This invention discloses a protein-degrading DNA material, its preparation method, and its applications. The protein-degrading DNA material includes a degradation initiation module, a protein targeting module, and a response module. The degradation initiation module is an E3 ubiquitin ligase targeting module, and the response module is a telomerase response module. The preparation method includes the following steps: dissolving the ssDNA strand used in the degradation initiation module in a solvent and annealing it to obtain the degradation initiation module; dissolving the ssDNA strand used in the protein targeting module in a solvent and annealing it to obtain the protein targeting module; dissolving the ssDNA strand used in the response module in a solvent and annealing it to obtain the response module; and mixing the degradation initiation module, the protein targeting module, and the response module to obtain the protein-degrading DNA material. The protein-degrading DNA material of this invention possesses tumor microenvironment triggering characteristics, can precisely target tumor cells, and has a high efficiency in degrading pathogenic proteins.

The invention provides a recombinant herpes simplex virus and a preparation method thereof. The preparation method comprises the step of replacing an original ICP4 coding sequence in a herpes simplex virus genome containing an infected cell protein 4 (ICP4) gene with an hTERTp-ICP4-fluorescent protein expression cassette. The expression cassette comprises an ICP4 coding sequence and a fluorescent protein coding sequence under the control of an hTERTp promoter, and the transcription direction of the expression cassette is opposite to that of an original ICP4 promoter. The recombinant viruses are capable of selectively replicating and indicating telomerase activity in cells having human telomerase activity. Cells infected by the virus can be identified through fluorescence signals, and the higher the telomerase activity is, the stronger the fluorescence intensity is. The virus has wide application value in research of tumor action mechanisms and stem cell action mechanisms, health diagnosis, immune assessment, screening of tumor drugs, research and development of diagnostic reagents and establishment of animal models.

The present disclosure provides a method of inhibiting telomerase activity to reduce human herpesvirus (e.g., HMCV, EBV, HSV-1, and / or HHV-6 / 7 / 8) replication. The method comprises treating cells with a telomerase inhibitor prior to and after HCMV infection. The telomerase inhibitor may be a pharmaceutical inhibitor such as BIBR1532 or MST312, or an siRNA construct targeting the hTERT catalytic subunit of telomerase. Treatment with the telomerase inhibitor results in reduced viral titer, decreased viral gene expression, and diminished viral protein levels across different temporal phases of herpesvirus infection. The method provides a novel approach for inhibiting herpesvirus replication through targeting of host cell telomerase activity.

According to the TelN prokaryotic telomerase variant and the preparation method thereof, compared with wild type TelN prokaryotic telomerase, the TelN prokaryotic telomerase variant has the advantages that the activity is obviously improved, and the TelN prokaryotic telomerase variant has a good industrial application prospect.

The present invention provides methods and kits for determining telomerase processivity. These methods and kits may be used to screen for drugs that inhibit or enhance telomerase repeat addition activity, and are readily adapted to an ultra-high-throughput format.

The invention discloses an anti-aging two-factor composition based on epigenetic reprogramming and application thereof, and belongs to the technical field of biological medicine. The composition comprises a Wnt pathway small molecule activator Laduvilliub and an ERK pathway activator bFGF, and through synergistic activation of Wnt and ERK signal pathways, epigenetic reprogramming of senescent cells is induced, and senescence-related chromatin open change, histone modification imbalance and DNA methylation clock drift are significantly reversed. At the cellular level, the composition can reverse various senescence phenotypes, namely restoring multiplication capacity, down-regulating expression of senescence-related secretory phenotype factors, relieving DNA damage, improving telomerase activity and telomere length and increasing nucleofibrin. At an individual level (an old mouse model), the composition is injected in the intraperitoneal cavity, so that the cognitive ability and the exercise ability are remarkably improved, the aging pathological characteristics of multiple organs are reduced, and the aging-related gene expression profiles of the organs such as the liver and muscles are reversed. The double-factor composition can be applied to anti-aging drugs, health care products or cosmetics.

Disclosed herein are dietary supplements, and nutraceutical compositions thereof, comprising a polypeptide having at least 80%, 85%, 90%, 95%, 98% or 99% sequence identity to the amino acid sequence set forth in SEQ ID NO 1 and 2; and methods of increasing telomerase activity and extending the length of telomeres using a composition comprising a polypeptide having at least 80%, 85%, 90%, 95%, 98% or 99% sequence identity to the amino acid sequence set forth in SEQ ID NO 1 or 2. Also disclosed is an isolated polypeptide according to SEQ ID NO 2.

The invention provides a nucleoside analogue as shown in a formula (I), a preparation method and a pharmaceutical composition thereof. The invention also discloses application of the compound or the pharmaceutical composition thereof in preparation of anti-cancer drugs.

The invention discloses a primer combination for quantitatively detecting cell telomerase activity, a kit and application, and relates to the technical field of telomerase activity detection. According to the primer combination for detecting telomerase activity and the detection method provided by the invention, the primer TS and the primer ACX-UP1 with specific sequences are selected, and the primer ACX-UP1 is provided with a stem-loop structure containing a fluorophore and a quenching group, so that not only can the functions of the primer be realized, but also the functions of a probe can be realized; therefore, the problems that a probe cannot be designed on a telomere repetitive sequence and the specificity of a dye method is poor are solved. The primer combination and the detection method provided by the invention have the characteristics of reliability, stability, convenience, rapidness and accuracy, so that the manpower, material resources and time cost required by telomerase activity detection are greatly reduced, and the accuracy is greatly improved.

This invention relates to the NBLS (Niobium Bovine Kidney Cell Line), with accession number CCTCC NO: C2022197. This invention also provides its application in culturing BVDV virus. This invention successfully introduced the SV40-LT gene into primary Niobium Bovine Kidney Cells, activating their telomerase activity and extending the cell lifespan in vitro. Experiments showed that the NBLS Niobium Bovine Kidney Cell Line of this invention can be passaged for more than 50 generations without changing its growth and proliferation characteristics, thus obtaining an immortalized cell line. This F50 generation Niobium Bovine Kidney Cell Line NBLS is highly sensitive to BVDV virus and can efficiently proliferate the virus. The virus titer proliferated using this cell line shows increased sensitivity compared to primary Niobium Bovine Kidney Cells, reducing production costs. Therefore, this invention provides a new technical means for the large-scale production of BVDV vaccines.

The invention discloses an R-configuration telomerase inhibitor and application thereof, and belongs to the technical field of medicinal chemistry. The prepared R-configuration telomerase inhibitor has telomerase inhibition activity obviously superior to that of a racemate of the R-configuration telomerase inhibitor, and the anti-tumor activity of the R-configuration telomerase inhibitor in various tumor cell lines is obviously higher than that of the racemate of the R-configuration telomerase inhibitor. Meanwhile, the R-configuration telomerase inhibitor has a definite effect of remodeling an anti-tumor immune microenvironment in vivo, can effectively inhibit tumor progression and induce tumor tissue regression when being combined with a PD-L1 inhibitor, is high in safety, and provides a theoretical basis for combined immunotherapy.

An anti-aging traditional Chinese medicine composition and its preparation method belong to the field of traditional Chinese medicine technology. The composition consists of the following components by weight: 3-60 parts of Polygonatum sibiricum, 1-70 parts of Astragalus membranaceus, 2-40 parts of Lycium barbarum, and 1-40 parts of Ganoderma lucidum spore powder. The method is as follows: soak the raw materials except for Ganoderma lucidum spore powder; decoct the raw materials 1-3 times; combine the decoctions obtained after several decoctions and concentrate them to obtain concentrated decoction; prepare the concentrated decoction into freeze-dried powder; add Ganoderma lucidum spore powder to the freeze-dried powder and stir evenly. The pharmacodynamic research results of the anti-aging of the present invention are as follows: (1) The test drug can significantly prolong the average lifespan of naturally aging nematodes by 30%, which is better than Erjingwan and the Western medicine NMN; (2) improve exercise, feeding ability and nervous system function; (3) improve antioxidant capacity: reduce the fluorescence intensity of ROS and lipofuscin, and improve the survival rate of nematodes after H2O2 stress stimulation; (4) improve telomerase activity; (5) improve cognitive dysfunction and learning and memory ability.

The invention belongs to the technical field of medicines, and particularly relates to preparation of CD146 + MSC cells and application of the CD146 + MSC cells in treatment of type 2 diabetes mellitus. Researches find that the CD146 + MSC has better pluripotency in the aspect of being differentiated into fat cells, bone cells and cartilage cells; the proliferation speed is low; the in-vivo and in-vitro immunosuppressive activity is enhanced. Meanwhile, the CD146 + MSC has higher differentiation capacity and immunosuppressive activity, the CD146 + MSC has higher dryness, lower telomerase activity and higher migration and homing capacities, shows higher biological characteristics of immunosuppression and cytokine secretion, and is remarkable in proliferation and angiogenesis activity, so that the CD146 + MSC has better immunosuppressive activity and immunosuppressive activity. A cell type with higher stemness and more original characteristics is represented. In addition, the CD146 + MSC cells can treat type 2 diabetes mellitus by reconstructing beta cells, enhancing and regulating blood glucose homeostasis, relieving insulin resistance, and reducing or regulating systemic inflammation.