184 results about "Cell cycle" patented technology

The invention discloses an MSC culture medium composition and a culture method, and belongs to the field of biological medicine. Aiming at the problems of low MSC amplification efficiency and poor function maintenance in the prior art, the invention provides the MSC culture medium combination, which comprises a basic culture medium and functional factors, and the functional factors comprise an activation functional factor, an amplification functional factor and a steady-state functional factor which are sequentially added according to a preset time interval; wherein the activating functional factors comprise b-FGF, EGF and TGF-beta 1; the amplification functional factors comprise b-FGF (Fibroblast Growth Factor), PDGF-BB (Platelet Derived Growth Factor The steady-state functional factors comprise a b-FGF (Fibroblast Growth Factor) and IGF-1. The cell cycle is quickly started by activating the functional factors, differentiation is inhibited, and the functional factors are amplified to promote large-scale cell amplification; steady-state functional factor equilibrium amplification and dryness maintenance are carried out; and different functional factors are sequentially added according to a preset time interval, and the concentration of the factors is dynamically adjusted, so that differentiation tendency or aging acceleration caused by long-time high-concentration stimulation of a single factor is avoided, long-term efficient amplification of the MSC is realized, and the multifunctionality of the MSC is kept.

Metastatic uveal melanomas are highly resistant to all existing treatments. To identify actionable vulnerabilities, the inventors conducted a CRISPR-Cas9 knockout screen using a library composed of chromatin remodelers. They revealed that the histone H3 methyltransferase SETDB1 plays a critical role in metastatic uveal melanoma cell proliferation and survival. Functionally, SETDB1 knockdown triggers decreased expression of genes related to replication and cell cycle and promotes growth arrest associated with increased markers for DNA damage and senescence entry. Using pre-clinical model, they further demonstrated that anti-SETDB1 therapy tumor growth in vivo. The inventors identify SETDB1 as a new relevant therapeutic target for the treatment of metastatic uveal melanomas. The present invention relates to a method for treating uveal melanoma in a subject in need thereof comprising a step of administering said subject with a therapeutically effective amount of SETDB1 inhibitor.

The invention provides application of tea catechin in preparation of a medicine for preventing and treating bortezomib-induced peripheral neuropathy. A plurality of in-vitro model results show that tea catechin can be used as a copper death inhibitor, remarkably improves related indexes of bortezomib-induced peripheral neuropathy, improves survival rates of Schwanton cells and SH-SY5Y, improves mitochondrial functions and cell cycle abnormalities of the Schwanton cells, reduces intracellular copper ion, cuprous ion and ATP levels, and can be used for preparing the copper death inhibitor for the peripheral neuropathy of the Bortezomib-induced peripheral neuropathy of the Bortezomib-induced peripheral neuropathy. Meanwhile, the death of Schwann cells and SH-SY5Y induced by the copper death inducer is reduced. In-vivo experiments show that the tea catechin plays a role in protecting functional damage of the bortezomib, and the tea catechin remarkably improves mechanical hyperalgesia, gait abnormality and pathological changes of myelin sheath and axon of mice caused by peripheral neuropathy induced by the bortezomib. The tea catechin can be used as a medicine for peripheral neuropathy induced by bortezomib, and has high clinical application value and development prospect.

The application discloses application of a reagent for detecting LRRN3 expression level in preparation of a benign prostatic hyperplasia diagnosis product. It is proved through cell function experiments and animal experiments that overexpression of the LRRN3 gene can inhibit the proliferation of prostate cells, block the cell cycle and promote cell apoptosis, thereby effectively inhibiting the prostatic hyperplasia. The discovery provides a new target and treatment strategy for the treatment of the prostatic hyperplasia, and provides a brand-new thought and method for the treatment of the prostatic hyperplasia. Based on the research results, a gene therapy drug taking the LRRN3 gene as a target can be further developed, for example, a lentivirus vector carrying the LRRN3 gene or other gene delivery systems are constructed and used for the treatment of the prostatic hyperplasia. In addition, the LRRN3 gene can be combined with other treatment methods to improve the treatment effect.

The invention belongs to the technical field of medicines, and particularly relates to application of dioscin combined with chidamide in diffuse large B-cell lymphoma. Specifically, research finds that the dioscin can significantly inhibit DLBCL cell proliferation and induce cell cycle arrest and apoptosis by up-regulating PINK1 / Parkin mediated mitochondrial autophagy and enhancing H3K27 acetylation mediated epigenetic regulation. When the chidamide and the dioscin are combined for use, a synergistic effect can be generated, and by further increasing the H3K27ac level, the cell apoptosis induction effect is enhanced, and the in-vivo and in-vitro anti-tumor activity on DLBCL is remarkably improved. The invention provides a novel and efficient DLBCL combined treatment scheme, and provides a new pharmaceutical composition and theoretical support for clinical diagnosis and treatment of DLBCL, so that the application has good practical application value.

The invention belongs to the technical field of exosomes, and discloses an exosome preparation method and application, the exosome preparation method comprises the following steps: S1, culturing target cells in an induction medium, and collecting the cells and a culture solution; s2, separating the culture solution to obtain supernate A and cell precipitate; s3, performing chromatographic purification and concentration on the supernate A to obtain the exosome; in the step S1, colchicine is also added in the process of culturing the target cells to synchronize the cell cycle; a polycaprolactone-gelatin composite microcarrier is suspended in the induction culture medium, and nicotinamide, an epidermal growth factor (EGF) and pyruvic acid are contained in the induction culture medium; the method further comprises a step S30 before the step S3, resuspending the cell precipitate obtained in the step S2 with a vesicle protection solution containing trehalose, sucrose and EDTA to obtain a supernatant B, and then combining the supernatant A with the supernatant B. According to the preparation method provided by the invention, the total secretion amount of target cells is large, the intracellular vesicle-exosome precursor can be collected, and the obtained exosome is high in concentration and low in impurity content.

The invention belongs to the technical field of biological medicines, and particularly relates to application of dirithromycin in preparation of a product for treating LINC00516 high-expression lung adenocarcinoma. The invention discloses the effect of the long-chain non-coding RNA LINC00516 in abnormal activation of the lung adenocarcinoma cell cycle for the first time. Researches show that LINC00516 is directly combined with CDK1, the kinase activity of CDK1 is remarkably enhanced, and the inhibitory phosphorylation level of CDK1 is reduced, so that lung adenocarcinoma cells are driven to quickly enter a G2 / M phase, and tumor cell proliferation is accelerated. The invention further innovatively proposes that dirithromycin is used as an intervention means, and by blocking the combination of LINC00516 and CDK1, the activity of CDK1 is effectively reduced, and the proliferation capacity of tumor cells is inhibited. In-vivo and in-vitro experiments prove that the dirithromycin can obviously inhibit the growth of lung adenocarcinoma cells with high expression of LINC00516, so that a brand-new molecular targeting treatment strategy is provided for clinic.

The invention relates to the field of plant genetic engineering, and particularly discloses a soapberry SmCYCD3; 2 gene and application thereof. The nucleotide sequence of the gene is shown as SEQ ID NO: 1, and the sequence of the protein coded by the gene is shown as SEQ ID NO: 2. Experiments show that the gene has high specificity expression in female flowers of soapberry. By heterologous overexpression of the gene in arabidopsis thaliana, typical'female promotion and male inhibition 'phenotypes such as pistil elongation, stamen number reduction and shortening, pollen viability reduction and small fruit pods of transgenic plants can be caused. Molecular mechanism studies show that: SmCYCD3; 2, performing functions by up-regulating expression of cell cycle related genes and pistil development genes AtCRC and down-regulating expression of stamen development key genes at the same time; the invention provides a key gene resource and a theoretical basis for directionally regulating and controlling the sex ratio of plant flowers through a molecular breeding means and improving the fruit yield of woody economic tree species.

The application provides an analysis method, device and equipment based on single-cell transcriptome sequencing data, which comprises the following steps: performing quality control, downstream analysis and visual display on single-cell transcriptome sequencing expression quantitative data, performing cell filtering by using Grubbs test method to obtain effective single-cell transcriptome sequencing quantitative data, performing initialization clustering analysis on the data to obtain single-cell subgroup classification results; performing screening on the single-cell subgroup classification results to obtain target single-cell subgroups, and performing re-clustering analysis to obtain single-cell sub-subgroup classification results; performing significant difference gene screening analysis on the single-cell transcriptome sequencing quantitative data between single-cell subgroups; and performing regression analysis based on characteristic genes of cell cycles to predict cell division periods corresponding to different cell types. The application effectively solves the technical complex problems of existing single-cell transcriptome sequencing quantitative data analysis, makes data analysis more simple and reliable, and reduces the difficulty of data analysis.

The application relates to a salt type of a new cell cycle regulatory kinase inhibitor and a crystal form and a preparation method thereof, and relates to a succinate salt of a compound (6-((4-(2-(diethylamino)benzo[d]thiazol-6-yl)-5-fluoropyrimidin-2-yl)amino)pyridin-3-yl)(4-isopropylpiperazin-1-yl)methanone and a crystal form thereof, wherein two crystal forms II and III of the succinate salt are good in stability, high in solubility, and the preparation method is simple and suitable for industrial production.

The invention relates to the technical field of cosmetics, in particular to a compound active peptide with functions of resisting aging and whitening skin and application of the compound active peptide. Comprising acetyl hexapeptide-1, nonapeptide-1, acetyl tetrapeptide-11, hexapeptide-9 and palmitoyl hexapeptide-12. The compound peptide disclosed by the invention can play a synergistic anti-aging and whitening role on an epidermal layer and a corium layer, and has multiple advantages; the compound peptide acts on epidermal layer keratinocytes, dermal layer fibroblasts and B16F10 cells, and can be used for detecting the senescence of the cells by influencing the expression quantity of cell senescence marker genes, influencing the cell cycle, influencing the expression quantity of extracellular matrix related proteins, influencing melanin synthesis and influencing the secretion quantity of acetylcholine in the cells. Multiple skin anti-aging and whitening effects synergistically exerted on the epidermal layer and the corium layer are achieved.

The invention belongs to the technical field of biological medicines, and particularly relates to application of cardiac glycoside medicines or pharmaceutically acceptable salts or derivatives thereof in preparation of products for inhibition, relief, adjuvant therapy or treatment of cancers and medicines. The invention provides application of cardiac glycoside drugs or pharmaceutically acceptable salts or derivatives of the cardiac glycoside drugs in preparation of products for inhibition, alleviation, adjuvant therapy or treatment of cancers and the drugs, and the cardiac glycoside drugs comprise deacetylated chaenoside, deacetylated chaenoside, deacetylated chaenoside, deacetylated chaenoside, deacetylated chaenoside, deacetylated chaenoside, deacetylated chaenoside and deacetylated chaenoside. According to the application disclosed by the invention, the effects of inhibiting, relieving, assisting in treating or treating cancers and potential mechanisms of the Deslanoside are researched in SH-SY5Y and SK-N-SH neuroblastoma cell lines, and results show that the Deslanoside can be used for inhibiting proliferation of SH-SY5Y cells and SK-N-SH cells, promoting apoptosis and respectively inducing a cell cycle to stop at a G0 / G1 phase; and G1 / S and G2 / M periods.

The invention relates to the technical field of cosmetics, in particular to a compound active peptide with skin anti-aging, anti-inflammatory and soothing functions and application of the compound active peptide. The compound active peptide is prepared from acetyl hexapeptide-1, palmitoyl tripeptide-5, acetyl dipeptide-1 cetyl ester, copper peptide and decarboxylated carnosine hydrochloride. The compound peptide acts on dermal fibroblasts, so that expression of p16 and p21 genes is reduced, and cell cycle arrest is improved; the compound acts on epidermal keratinocytes and dermal fibroblasts and inhibits COX-2 gene expression; the compound peptide acts on epidermal keratinocytes and dermal fibroblasts, and the ROS level is reduced; the compound peptide acts on PC12 cells, inhibits secretion of acetylcholine, blocks transmission of neural signals, and plays a role in immediate wrinkle removal.

The invention provides a KIF18 inhibitor and a synthesis method thereof, and particularly provides a compound shown as a formula (I), and the compound can regulate KIF18A protein, so that the cell cycle and the cell proliferation process are influenced to treat cancers and cancer-related diseases. Also provided are pharmaceutical compositions comprising the compounds and methods for treating conditions associated with KIF18A activity.

This invention discloses the application of arginine-depleted engineered bacteria for the treatment of soft tissue sarcomas, including preliminary validation, obtaining qualified engineered bacteria SGR1, obtaining drug compositions and regimens, experimental conclusions, and clinical application promotion. During use, clinical soft tissue sarcoma samples are collected, including undifferentiated pleomorphic sarcoma, synovial sarcoma, and liposarcoma. Immunohistochemistry (IHC) is used to detect ASS1 protein expression, qPCR is used to detect ASS1 gene transcription levels, and the proportion of ASS1 deletion / low expression is statistically analyzed. Arginine auxotrophic sarcoma subpopulations are confirmed based on literature. Cells are cultured in arginine-containing or arginine-free media, and cell viability, colony formation, cell cycle, and apoptosis are detected. The sensitivity of ASS1-deficient cells to arginine deprivation is verified, and therapeutic targets are identified. The enzyme activity, substrate specificity, and immunogenicity of human ARG I / II, mycoplasma ADI, and Pseudomonas ADI are compared. High-activity, low-immunogenic enzymes or enzyme combinations (such as human ARG I + microbial ADI) are selected, and site-directed mutagenesis or codon optimization is performed on microbial ADI to increase expression levels.

The invention discloses a recombinant deubiquitination enzyme USP7 mutant, a preparation method and application of the mutant in tumor treatment, and belongs to the technical field of biomedicine.The USP7 mutant changes substrate selectivity through site-specific mutagenesis, specifically deubiquitination tumor suppression protein p53 is achieved, meanwhile, oncogenic protein MDM2 is unstable, a p53 anti-tumor pathway is activated, and the tumor suppression protein p53 is activated. The mutant induces cell cycle arrest and apoptosis in wild type p53 tumor cells, the ICvalue is 180-280nM, animal experiments show that the tumor growth inhibition rate reaches 72%, the tumor tissue enrichment is improved by 12 times by combining a folic acid targeted lipid nanoparticle delivery system, the drug resistance of an MDM2 inhibitor is overcome, the mutant has a synergistic effect with chemotherapeutic drugs, and the mutant can be used for preparing drugs for treating tumors. And a novel accurate treatment strategy is provided for wild-type p53 tumors.

This invention relates to a novel compound derived from nutmeg and an anticancer composition comprising the same. The present invention isolates several novel compounds derived from nutmeg extract and confirms that most of these novel compounds exhibit cytotoxic activity against various cancer cell lines. Five compounds (3, 4, 6, 9, and 11) were identified as having high cytotoxic activity against gastric and colorectal cancers. In particular, the compound represented by chemical formula 3 was confirmed to not only effectively induce apoptosis by regulating the cell cycle of cancer cells but also effectively inhibit tumor growth in xenograft mouse models, thus making it an effective anticancer composition.

This invention relates to the pharmaceutical field, specifically to a heteroindole derivative, its synthesis method, and its applications. The heteroindole compound derivative has the structure shown in general formula (I), wherein R1 is selected from any one of N-Boc-trans-1,4-cyclohexanediamine, N-Boc-piperazinyl, trans-1,4-cyclohexanediamine, piperazinyl, and N-methylpiperazinyl; R2 is selected from H or a halogen atom; and X, Y, and Z are all selected from CH or N. This invention demonstrates through experiments that the heteroindole derivative possesses good CDK9 inhibitory activity and selectivity, providing a theoretical basis for the treatment of diseases related to the activity or expression level of the cell cycle-dependent kinase CDK9, and exhibits good pharmaceutical potential.

This invention relates to the field of anti-aging drug technology, specifically to the application of small molecule compounds in the preparation of anti-aging drugs. These small molecule compounds competitively block the interaction between KDM6A and the vacuolar ATPase V0 domain subunit ATP6V0C by targeting a specific small molecule binding pocket of the histone demethylase KDM6A, thereby inhibiting the demethylation activity of KDM6A on lysine residue 36 of ATP6V0C. These small molecule compounds can effectively downregulate aging-related β-galactosidase activity, improve cell cycle arrest, and reverse the senescent phenotype of nerve cells induced by the environmental pollutant GenX, making them particularly suitable for combating premature aging of nerve cells induced by perfluorinated and polyfluoroalkyl compounds such as GenX. This technical solution can solve the technical problem of the lack of drugs with clearly defined components, a clear mechanism of action, stable efficacy, and the ability to specifically alleviate aging in existing technologies, and has ideal prospects for widespread application.

The invention relates to a KIF18 inhibitor with a structure as shown in a formula (I) and a synthesis method thereof, and the compound can regulate KIF18A protein so as to influence a cell cycle and a cell proliferation process to treat cancers and cancer-related diseases. And pharmaceutical compositions comprising the compounds, methods for treating conditions associated with KIF18A activity.

The application relates to the technical field of aspirin pharmaceutical chemistry, in particular to an aspirin-sulfonamide hybrid, a preparation method and application thereof. The preparation method can synthesize a plurality of novel aspirin-sulfonamide hybrids by taking piperazine as a bridge, and by a three-step continuous method of "acyl chlorination, sulfonamidation and N-acylation" according to a "molecular hybridization principle". In the process, only one separation and purification is performed, and the preparation steps are simple. The aspirin-sulfonamide hybrid prepared by the method is most effective on human non-small cell lung cancer cells A549, and the activity is more than 33 times higher than that of a parent aspirin, and is similar to the activity of an anticancer drug irinotecan. The aspirin-sulfonamide hybrid 3k prepared by the method has a certain inhibitory effect on various cancer cells. The hybrid can induce human non-small cell lung cancer A549 cell apoptosis in a concentration-dependent manner, and can induce human non-small cell lung cancer A549 cell cycle arrest in the G0 / G1 phase, and inhibit cell growth.

The invention relates to the technical field of gene engineering, in particular to an HDR enhancer for improving cell homologous recombination efficiency and application of the HDR enhancer, and the HDR enhancer for improving the cell homologous recombination efficiency comprises an inhibitor of a non-homologous end connection repair pathway and an intracellular homologous recombination accelerant; the inhibitors of the non-homologous end connection repair pathway are SCR-7 and M3814, the intracellular homologous recombination accelerators are L755507 and Romidepsin, the four agents synergistically target an NHEJ signal pathway, the cell cycle, chromatin structure opening and HDR signal pathway are regulated and controlled at the same time, and the problem that an existing reagent for improving the cell homologous recombination efficiency is insufficient in synergistic effect is solved.

The application provides an oxazinane compound, a preparation method, a pharmaceutical composition and application, and a general formula of the oxazinane compound or a pharmaceutically acceptable salt thereof is shown as formula (I). The oxazinane compound has obvious proliferation inhibition effect on cancer cells, especially human head and neck squamous cell carcinoma cell strains HSC4, HSC3, HSC2, CAL33, SCC4 and human glioma cell strain U251, can block the cell cycle, effectively inhibit the phosphorylation level of key proteins in the PI3K / AKT / mTOR pathway at the molecular level, has the potential to be prepared into a new antitumor drug, and has a good market prospect.

The invention relates to the technical field of anti-aging drugs, in particular to application of a small molecule compound in preparation of anti-aging drugs. The small molecule compound competitively blocks the interaction between the KDM6A and a vacuolar ATP enzyme V0 structural domain subunit ATP6V0C through a specific small molecule binding pocket of targeted histone demethylase KDM6A, and further inhibits the demethylation activity of the KDM6A on 36th lysine of the ATP6V0C. The small molecule compound can effectively down-regulate the activity of senescence-related beta-galactosidase, improve cell cycle arrest and reverse nerve cell senescence phenotypes induced by environmental pollutant GenX, and is especially suitable for resisting nerve cell premature senescence caused by perfluorinated and polyfluoroalkyl compounds such as GenX. According to the technical scheme, the technical problem that drugs which are definite in component, clear in action mechanism, stable in curative effect and capable of pointedly relieving senescence are lacked in the prior art can be solved, and ideal application and popularization prospects are achieved.

The utility model relates to the technical field of microalgae continuous culture, specifically discloses a continuous culture system and continuous culture method of isochrysis galbana, the culture system includes host computer and lower computer, the host computer is the remote monitoring and control platform based on mobile terminal, is connected with lower computer, is used for real -time monitoring, parameter setting and remote control, the lower computer includes pipeline type light biological reaction circulation unit, control unit, feed addition unit and liquid outlet collection unit, based on this culture system can realize the efficient, stable, low -cost continuous culture of isochrysis galbana.

The invention discloses a phototherapy nano-drug with mitochondrial / STAT3 protein double-site targeting. The phototherapy nano-drug is ATO / CR nano-particles formed by self-assembling a compound CR and atorvaquone under the action of distearoyl phosphatidyl ethanolamine-polyethylene glycol; the structure of the compound CR is shown as a formula I in the specification. The invention discloses an application of the phototherapy nano-drug with mitochondrial / STAT3 protein double-site targeting in preparation of drugs for treating tumors. The phototherapy nano-drug can target mitochondria and STAT3 protein in tumor cells through ATO, and can also passively target tumor sites through the high-permeability long-retention effect of nano-particles, so that more nano-therapeutic agents are enriched around tumors, and the curative effect is improved. The phototherapy nano-drug provided by the invention has good photothermal performance, can effectively enhance the PTT effect of gastric cancer, and exerts the tumor synergistic treatment ability by promoting cell apoptosis, inhibiting angiogenesis and hindering the cell cycle.

The present invention relates to a thiobenzimidazole derivative or a pharmaceutically acceptable salt thereof, and a composition for preventing or treating cancer, comprising the derivative as an active ingredient. The thiobenzimidazole derivative of the present invention exhibits cell toxicity by blocking the cell cycle of a cancer cell and inducing apoptosis when administered to an individual, as the derivative inhibits tubulin polymerization by being activated in the cancer cell, and, thus, the derivative can be used for prevention or treatment of cancer, desirably for prevention or treatment of triple-negative breast cancer.

Disclosed herein are topical compositions comprising Centella asiatica extract and mandelic acid, wherein the compositions have a pH of less than 5, and methods of using the compositions to decrease cellular senescence in skin and treat dermatoporosis. Topical compositions comprising Centella asiatica extract and mandelic acid are effective to reduce the number of senescent cells in mammalian dermis, reduce the senescence-associated secretory phenotype (SASP), downregulate at least one SASP-associated gene, increase the expression of at least one cell cycle-related gene in dermal fibroblasts, downregulate at least one gene associated with skin inflammation, and increase fibroblast cell turnover.

The application relates to application of a reagent for detecting expression levels of a PSIP1 gene or a coded protein LEDGF / p75 in preparation of a product for evaluating systemic lupus erythematosus disease activity, which makes up for the problems of insufficient sensitivity and specificity of existing evaluation indexes; the application also discloses a key role of the PSIP1 gene in a pathogenesis mechanism of systemic lupus erythematosus, and clearly shows the relationship between the PSIP1 gene in T cells and cell cycle arrest, cell aging and abnormal immune function, so as to provide a theoretical basis for target regulation of the PSIP1 to improve T cell function and delay or block disease progression; the application firstly proposes that the expression levels of the PSIP1 / LEDGF / p75 are detected to be used for evaluating systemic lupus erythematosus disease activity, auxiliary diagnosis, prognosis prediction and treatment effect monitoring, so as to provide a brand-new tool and direction for precise diagnosis, activity evaluation, prognosis judgment and future target treatment development of systemic lupus erythematosus.

The invention relates to the technical field of biological medicine, and particularly discloses application of nefenavir. Nefinavir is used for preparing a medicine for treating or preventing castration-resistant prostate cancer, and the medicine can specifically up-regulate expression of DHCR7, induce DNA damage of tumor cells and activate a cell cycle arrest pathway mediated by periodic protein of the cells so as to inhibit key biological processes such as proliferation of the tumor cells, cholesterol metabolism and the like; especially, formation and amplification of multinuclear giant cells in castration-resistant prostate cancer can be effectively inhibited by up-regulating expression of DHCR7, so that malignant progression of multinuclear giant cell mediated tumors and treatment of drug resistance are blocked. Finally, the castration-resistant prostate cancer is prevented and treated, and the technical bottlenecks that an existing castration-resistant prostate cancer treatment means is limited in curative effect, and the drug resistance and metastasis capability mediated by multinuclear giant cells are difficult to inhibit in a targeted manner are solved.