30 results about "MTOR signaling pathway" patented technology

The invention discloses application of neoplasm vine and cis-platinum in preparation of a medicine for preventing and treating lung cancer. Belongs to the technical field of biological medicine. The invention finds that the synergy of the neoplasm vine ethyl acetate part extract and cis-platinum can effectively treat the non-small cell lung cancer, the mechanism has the characteristics of multiple components, multiple targets and multiple pathways, and the PI3K / AKT / mTOR signal pathway may be one of the therapeutic action pathways of the PI3K / AKT / mTOR signal pathway.

This application relates to the technical field of biological products, and provides an application, extraction method and composition of TGL-ELNs in the treatment of glioma. The TGL-ELNs are applied in any one or more of the following aspects: a) Preparation of products for promoting apoptosis of glioma cells; b) Preparation of products for inhibiting proliferation of glioma cells; c) Preparation of products for inhibiting autophagy of glioma cells; d) Preparation of products for treating glioma. Verified through cell and animal experiments, the TGL-ELNs in this application can effectively induce apoptosis of glioma cells and inhibit autophagy of glioma cells to induce glioma cell death, and act on glioma cells through the AKT / mTOR signaling pathway and by inhibiting the production of autophagosomes in glioma cells.

This application relates to the field of biotechnology, and more particularly to the application of a U2AF homologous motif kinase 1 in gastric cancer cells. The application includes using UHMK1 as a regulator to modulate the proliferation of gastric cancer cells by regulating the zDHHC17-mediated palmitoylation-modified AKT / mTOR signaling pathway. This application is based on previous research finding that UHMK1 is highly expressed during the proliferation of gastric cancer cells. Knocking down or interfering with UHMK1 expression can clearly observe apoptosis in gastric cancer cells. Subsequent analysis of the expression levels of genes related to the UHMK1 signaling pathway, as well as changes in zDHHC17 expression levels, suggests that UHMK1 drives gastric cancer cell proliferation by regulating the zDHHC17-mediated palmitoylation-modified AKT / mTOR signaling pathway, thus filling a gap in the correlation between UHMK1 and gastric cancer.

This invention belongs to the field of biomedical technology and provides the application of 16'-DEC in the preparation of anti-hepatocellular carcinoma drugs. This bisindole alkaloid compound can inhibit the proliferation and migration of hepatocellular carcinoma cells and can produce a synergistic anti-tumor effect with lenvatinib, solving the problems of limited efficacy and insufficient patient survival benefit of existing targeted drugs in hepatocellular carcinoma treatment. Experiments have confirmed that 16'-DEC exerts its anti-tumor effect by directly inhibiting mTOR kinase activity. This compound can specifically bind to mTOR protein, significantly upregulate the expression of autophagy-related genes by blocking the mTOR signaling pathway, and induce autophagic cell death in tumor cells. In vitro and in vivo experiments have demonstrated that inhibiting autophagy can reverse the anti-cancer effect of 16'-DEC, indicating that its pharmacodynamic mechanism mainly depends on the activation of the autophagy pathway. This invention is applicable to the development of novel targeted therapies for hepatocellular carcinoma, especially specific inhibitors of the mTOR signaling pathway.

The invention discloses application of an AMSCs-derived exosome in preparation of a medicine for treating diabetic vasculopathy, and relates to the technical field of medicines. The exosome is separated and extracted from the AMSCs, the HUVECs under the high glucose condition are intervened, it is proved for the first time that the exosome derived from the AMSCs can improve the HUVECs autophagy obstacle induced by the high glucose, it is also proved that the exosome derived from the AMSCs can weaken the activation effect of the high glucose on AKT / mTOR, meanwhile, an AKT / mTOR signaling pathway activator MHY1485 can block the activation of the exosome on the HUVECs autophagy, and therefore the HUVECs autophagy obstacle induced by the high glucose is inhibited. It is prompted that the exosome derived from the AMSCs and the AKT / mTOR signal channel inhibitor have a certain curative effect on the vascular endothelial cell autophagy disorder related diseases.

This invention belongs to the field of antitumor drugs, disclosing a sulfated Polygonatum sibiricum polysaccharide, its preparation method, and its application in the preparation of drugs for treating liver cancer. The invention uses dried Polygonatum sibiricum rhizome as raw material, purifies it to obtain Polygonatum sibiricum polysaccharide, and then uses a sulfur trioxide-pyridine complex as a sulfation reagent to perform sulfation modification, thus preparing sulfated Polygonatum sibiricum polysaccharide. Sulfated Polygonatum sibiricum polysaccharide significantly improves water solubility, optimizes molecular spatial conformation and charge distribution, and induces cancer cell apoptosis by damaging mitochondrial membrane potential, increasing intracellular ROS levels, and downregulating the expression of key phosphorylated proteins in the PI3K / Akt / mTOR signaling pathway. In animal experiments, it effectively inhibited tumor growth without causing significant systemic toxicity in mice, demonstrating good in vivo biocompatibility. Therefore, it has important application value.

The invention relates to the technical field of biomedicine, in particular to application of RAB26 as a prognosis evaluation marker and a treatment target of osteosarcoma. System research finds that RAB26 has significant differential expression between osteosarcoma primary lesion and metastasis lesion, high expression of RAB26 is closely related to poor overall lifetime and event-free lifetime of patients, and RAB26 can be used as an effective biomarker for evaluating osteosarcoma development risk and prognosis state. The RAB26 quantitative detection scheme established by the invention can accurately reflect the real change of RAB26 in tumor tissues or related samples, and provides a reliable basis for risk stratification, disease monitoring and prognosis judgment of clinical patients. On the other hand, the invention clarifies that RAB26 activates autophagy by up-regulating PDCD6IP and inhibiting an mTOR signal channel for the first time, so that the invasion and migration capabilities of osteosarcoma cells are enhanced, and malignant phenotypes of the cells can be remarkably weakened by inhibiting and intervening RAB26.

The invention belongs to the technical field of biological medicines, discloses a ganoderma lucidum oligopeptide for inhibiting tumor cell growth and a preparation method and application thereof, and aims to overcome the technical defects of unknown active ingredients, low yield, poor purity and high toxicity of the existing ganoderma lucidum oligopeptide. The sequence of the ganoderma lucidum oligopeptide is Trp-Gly-Ala-Pro-Arg, the molecular weight is 623.7 Da, the isoelectric point is 8.92, and the ganoderma lucidum oligopeptide plays a tumor inhibition role by reducing a PI3K / Akt / mTOR signal channel in a targeted manner. The preparation method comprises the following steps: carrying out superfine grinding on a lucid ganoderma raw material, carrying out composite enzymatic hydrolysis by using papain, alkaline protease and flavourzyme (5: 3: 2), and carrying out ultrafiltration, gel chromatography and RP-HPLC (Reverse Phase-High Performance Liquid Chromatography) purification, so that the yield is 1.16-1.20%, and the purity is greater than or equal to 98%. The ICs of the peptide to six tumor cells such as lung cancer A549 are 0.8-1.4 [mu] mol / L, and the ICs of the peptide to normal cells are ICgt; the therapeutic index is greater than or equal to 15.4; the cells PPappgt of Caco-2 are subjected to cell culture; 1 * 10 cm / s, the plasma protein binding rate is 65%-68%, LDgt; the density is 500 mg / kg. The compound can be prepared into dosage forms such as injections and the like, and the tumor inhibition rate reaches 85% when the compound is combined with cis-platinum, and CI is equal to 0.65. The process is stable, and the product is high in activity, safe, suitable for tumor treatment and adjuvant therapy and good in industrialization prospect.

The invention discloses a cytochalasin compound with an anti-tumor effect as well as a preparation method and application of the cytochalasin compound. The compound disclosed by the invention is derived from a fermentation product of a cynanchum chinense endophytic fungus Aspergilusizukae RD-16. The compound disclosed by the invention has the advantages that the compound can be used for preparing the cynanchum chinense endophytic fungus; the compound has remarkable cytotoxic activity to various tumor cells and almost has no toxicity to normal colonic epithelial cells. Meanwhile, the compound also has an effect of inhibiting angiogenesis. A Western Blot experiment result proves that the compound activates the expression of tumor cell autophagy related protein by inhibiting a PI3K-AKT-mTOR signal channel and induces tumor cells to generate autophagy; on the other hand, by inhibiting expression of angiogenesis related protein p-VEGFR2, tumor angiogenesis is blocked, and the anti-tumor effect is synergistically enhanced through multiple paths. The compound has potential application in preparation of novel anti-tumor drugs, and provides scientific basis for research and development of novel anti-tumor drugs.

This invention discloses the use of LAPTM5 in the preparation of drugs regulating renal tubular epithelial-mesenchymal transition (EMT). Through bioinformatics analysis and multi-level experimental verification, this invention found that LAPTM5 is significantly upregulated in an aging kidney model and is positively correlated with renal aging and the severity of fibrosis. Mechanistic studies show that LAPTM5 interacts with the deubiquitinating enzyme USP10 and promotes its lysosomal degradation, weakening the deubiquitination effect of USP10 on PTEN. This leads to proteasomal degradation of PTEN via the K48-linked polyubiquitination pathway, thereby relieving PTEN's inhibition of the PI3K / AKT / mTOR signaling pathway, inhibiting autophagy activity, promoting renal tubular epithelial-mesenchymal transition, and accelerating the process of renal fibrosis. At the cellular level, PTEN overexpression can rescue LAPTM5-induced EMT; in animal models, the PTEN agonist matrine significantly improves D-galactose-induced renal fibrosis in aging mice and protects renal function by restoring autophagy.

The invention discloses a traditional Chinese medicine composition for treating post-stroke sarcopenia as well as a preparation method and application of the traditional Chinese medicine composition. The traditional Chinese medicine composition is prepared from radix rehmanniae preparata, fructus corni, radix morindae officinalis, herba cistanche, herba dendrobii, radix ophiopogonis, fructus schizandrae, poria cocos, radix aconiti lateralis preparata, cortex cinnamomi, radix astragali seu hedysari, radix codonopsis, fructus jujubae and caulis spatholobi. The 14 medicinal materials are prepared according to a specific weight ratio. Based on a traditional Chinese medicine treatment method of tonifying liver and kidney, strengthening spleen and stomach and dredging meridians and collaterals, the composition is precise and appropriate, and the pertinence is strong. Clinical research proves that the composition can remarkably improve the muscle strength, muscle quality and movement function of a patient suffering from post-stroke sarcopenia, and the curative effect is remarkably superior to that of conventional rehabilitation treatment. The research on the mechanism of action shows that muscle synthesis can be promoted by up-regulating an IGF-1 / Akt / mTOR (Insulin-like Growth Factor 1 / Akt / mTOR) signal channel, and muscle decomposition can be inhibited by down-regulating the expression of MuRF-1 / Atrogin-1 at the same time. A detailed dose ratio optimization research proves that a specific ratio (an optimal embodiment) has a synergistic effect. The invention provides an innovative traditional Chinese medicine treatment scheme with definite curative effect and high safety for the post-stroke sarcopenia, and has important clinical value and development prospect.

The application discloses a gene for treating AKT / mTOR signal path related diseases. The application proves through experiments that FAM64A promotes proliferation, invasion, lipid droplet formation and chemotherapy resistance of colorectal cancer through the Akt / mTOR signal path. Up-regulation of FAM64A expression is closely related to occurrence and subsequent development of the colorectal cancer. Abnormal expression of FAM64A can be used as an index of invasive behavior and poor prognosis of the colorectal cancer. The finding provides a new direction for treatment and drug resistance of the Akt / mTOR signal path related diseases, especially treatment and drug resistance of the colorectal cancer.

The application relates to the technical field of pharmaceutical preparations, in particular to application of Thalia dealbata in inhibiting a PI3K / Akt / mTOR signal path to slow down animal cell aging, which finds that Thalia dealbata can delay body aging after being applied to an aging model, and can slow down the animal cell aging process by inhibiting the activity of the PI3K / Akt / mTOR signal path, and effectively improves the efficiency of Thalia dealbata in slowing down aging.

The application provides a kind of licorice chalcone A and the application of the composition of light glycyrrhizin and licorice chalcone A in preparing the drug for treating colorectal cancer.Belongs to the technical field of antitumor biological medicine.The inhibitory activity of LCA and CMC on human colon cancer cells is verified by CCK-8 method, and the survival rate is significantly reduced.The influence of high-dose and medium-dose LCA and CMC on the apoptosis of human colon cancer cells is detected by flow cytometry technology, and the apoptosis rate is increased.The influence of LCA and CMC on the migration of human colon cancer cells is studied by cell scratch test, and the migration ability of cells can be significantly inhibited.The influence of LCA and CMC on the invasion ability of human colon cancer cells is studied by Transwell experiment, and the number of invasive cells is significantly reduced.LCA and CMC can inhibit the proliferation of human colon cancer cells in vitro, and induce tumor cell apoptosis, and the mechanism may be related to the inhibition of PI3K / AKT / mTOR signal pathway.

The application discloses a kind of film type L-arginine-alpha-ketoglutarate salt sustained-release particles and its preparation method and application.The sustained-release particles include internal core material and external wall material, internal core material is L-arginine-alpha-ketoglutarate salt, external wall material is homogeneous complex matrix of stearic acid and sodium alginate, and the mass ratio of core material and wall material is 7:3 to 8:2.The sustained-release particles are obtained by stearic acid-sodium alginate complex wall material cold spray coating L-arginine-alpha-ketoglutarate salt, realize the synergistic effect of gastric acid tolerance and intestinal target release.Under 0.75%-1.00% additive dose, the sustained-release particles can significantly repair fish intestinal physical barrier, up-regulate tight junction protein and oligopeptide transporter expression, reduce serum intestinal permeability markers, and simultaneously activate muscle mTOR signaling pathway, promote collagen deposition, reduce drip loss rate, and comprehensively improve fish intestinal health and muscle quality.

The application provides a peptide lipid nanoparticle, a preparation method, an application and a cancer combined treatment drug combination, and belongs to the technical field of biological medicines.The application proposes a novel synergistic anti-tumor strategy based on the combination of a peptide lipid nanoparticle and a low-dose mTOR inhibitor, synergistically inhibits a PI3K / AKT / mTOR signal pathway, co-applies the peptide lipid nanoparticle loaded with p53 circular RNA and the mTOR inhibitor to cancer cells, restores p53 function, reactivates PTEN, blocks the feedback activation of PI3K / AKT, and directly inhibits mTOR by the mTOR inhibitor, thereby producing a persistent cascade double blocking. Moreover, p53 inhibits the evirolimus-induced pro-survival autophagy, converts it into a stress-induced process, and realizes the double inhibition and persistent blocking of the PI3K / AKT / mTOR pathway.

The invention discloses application of an AMSCs-derived exosome in preparation of a medicine for treating diabetic vasculopathy, and relates to the technical field of medicines. The exosome is separated and extracted from the AMSCs, the HUVECs under the high glucose condition are intervened, it is proved for the first time that the exosome derived from the AMSCs can improve the HUVECs autophagy obstacle induced by the high glucose, it is also proved that the exosome derived from the AMSCs can weaken the inhibition effect of the high glucose on AKT / mTOR, meanwhile, an AKT / mTOR signaling pathway inhibitor AZD8055 can block activation of the exosome on HUVECs autophagy, and therefore the HUVECs can be used for treating the HUVECs autophagy obstacle induced by the high glucose. It is prompted that the exosome derived from AMSCs may have a certain curative effect on vascular endothelial cell autophagy disorder related diseases.

The invention belongs to the technical field of biology, and discloses an application of Compound C in inhibition of uterine contraction of sheep, the Compound C significantly reduces expression of autophagy related genes LC3, BECN1, ATG5 and ATG7 by regulating an AMPK / mTOR signal channel, further inhibits autophagy of sheep uterine smooth muscle cells, and realizes targeted inhibition of uterine contraction. The optimal concentration of the Compound C in the preparation is 10 <-6 > mol / L, the administration dosage is 0.01 mg / kg of sheep body weight, the administration mode is intramuscular injection, and the Compound C can be combined with oxytocin to reverse the uterine contraction promoting effect of oxytocin. Cell experiments and animal experiments prove that the Compound C can improve uterine smooth muscle cell ultramicrostructure disorder, reduce autophagosome formation, delay the recovery speed of uterine horn of postpartum sheep, effectively inhibit abnormal uterine contraction and provide a new strategy for pregnancy maintenance and abortion reduction, and the action is milder.

The application provides application of LBP in preparation of drugs for preventing or treating kidney injury. Research results show that LBP intervention can significantly improve cisplatin-induced kidney injury and presents a certain dose dependence; specifically, the serum Cre and BUN levels are significantly reduced, thereby improving kidney function, and the pathological structure damage of kidney tissue is obviously reduced. Further research shows that LBP can enhance the antioxidant capacity of the body and inhibit the inflammatory response by regulating the Nrf2 / NF-kappa B signal pathway, and promote kidney cell survival and regulate metabolism by regulating the PI3K / Akt / mTOR signal pathway, thereby playing a kidney protection role. The application provides a theoretical basis for application of natural active polysaccharides in prevention and treatment of kidney injury.

This invention discloses a siRNA or shRNA construct for inhibiting RSRC1 expression and its application, relating to the field of biomedical technology. It includes a specific nucleotide sequence targeting human RSRC1 gene mRNA; this specific nucleotide sequence can specifically bind to the coding region (CDS) or 3' untranslated region (3'UTR) of the RSRC1 gene, mediating the degradation or translational repression of RSRC1 mRNA, thereby reducing the intracellular expression level of RSRC1 protein; the construct is configured to block the direct interaction between RSRC1 protein and DVL2 protein, thereby inhibiting the activation of downstream Wnt / β-catenin signaling pathways and AKT / mTOR signaling pathways. This invention, while inducing tumor cell apoptosis, inhibiting colony formation, and reducing metastatic nodules in vivo, avoids the limitations of single-target silencing in completely blocking multi-pathway cross-talk, ultimately achieving a synergistic therapeutic effect of significantly reducing chemotherapy resistance, inhibiting metastasis of advanced ovarian cancer, and prolonging patient survival.

The invention discloses application of an mTOR signal channel inhibitor in preparation of a medicine for treating myocarditis, belongs to the technical field of biological medicine, and relates to application of mTOR signal abnormal activation in myocarditis treatment. Researches find that mTOR signal pathways in heart tissues and immune cells are remarkably activated in explosive myocarditis and experimental autoimmune myocarditis and are related to inflammatory response enhancement, cardiac function impairment and poor prognosis. By inhibiting abnormal activation of mTOR signals, the inflammation level can be effectively reduced, the cardiac function can be improved, and the survival rate can be increased. The result shows that the abnormal activation of the mTOR signal can be used as an effective intervention target spot for treating myocarditis, and has a good application prospect.

The application belongs to the field of medicine and relates to a preparation method and application of arabinogalactan in larch; wherein the arabinogalactan derivative in larch is sulfated arabinogalactan, and the sulfated arabinogalactan can be applied in the preparation of a medicine for treating inflammatory bowel disease or colon cancer; the sulfated arabinogalactan mainly regulates NCOA4-mediated ferritin autophagy by activating the AMPK-mTOR signal pathway and increases the relative abundance of Limosilactobacillus reuteri strain HDB1243 and Lactobacillus johnsonii strain 1696 to antagonize colon cancer, thereby providing a new means for the treatment of colon cancer.

The application discloses application of 1-aminocyclopropane carboxylic acid in preparation of a glioma treatment drug. The 1-aminocyclopropane carboxylic acid of the application not only significantly inhibits the expression level of glial fibrillary acidic protein of glioma cells, but also effectively inhibits the expression and phosphorylation modification of extracellular signal-regulated kinase 1 / 2 and protein kinase B, blocks the cell proliferation signal mediated by the MAPK / ERK and PI3K / Akt / mTOR signal pathways, and activates the cell apoptosis signal mediated by caspase 3, so that the proliferation of glioma cells is inhibited, the growth speed of a xenograft of a nude mouse is effectively slowed down, the volume and mass of tumor tissues are significantly reduced, and a significant therapeutic effect is achieved.

The present invention relates to a novel compound that inhibits the mTOR signaling pathway, a method for preparing same, and a pharmaceutical composition comprising same as an active ingredient. The compound of the present invention was found to inhibit mTORC1 and mTORC2 activities, activate autophagy, and alleviate a series of disease symptoms associated with Alzheimer's-type dementia in dementia model animals, and thus can be effectively used as a pharmaceutical composition capable of preventing or treating nervous system diseases comprising neurodegenerative diseases and mTORopathy.

The application discloses application of IMMU-132 and IACS010759 in preparation of an anti-esophageal squamous carcinoma drug and related drugs, relates to the technical field of biological medicine, and the combined drug comprises IMMU-132 and IACS010759. The IMMU-132 and IACS010759 are synergistically combined, PI3K-AKT-mTOR signal pathways are inhibited, and thus, ESCC cell proliferation is inhibited; the combined drug increases the intracellular ROS level and destroys the mitochondrial membrane potential, and thus, the apoptosis of cells in the mitochondrial pathway is synergistically induced. The IMMU-132 and IACS010759 provided by the application exhibit a significant synergistic anti-tumor effect, the PI3K-AKT-mTOR survival signal pathway is inhibited, and thus, the apoptosis of cancer cells is triggered, and the problems of limited curative effect and easy drug resistance of an existing ESCC treatment scheme are reduced, so that a new strategy is provided for clinic.

The invention discloses an asymmetric hydrogel dressing with double properties and a preparation method and application thereof, and belongs to the field of biomedical materials, the asymmetric hydrogel dressing has a double-layer asymmetric structure comprising a spear layer and a shield layer; wherein the spear layer is a low-crosslinking-density layer and encapsulates liposome of targeted macrophages, the liposome contains a dimer artesunate conjugate and phosphatidylserine, and the spear layer has tissue adhesion; the shield layer is a high-crosslinking-density layer and is used for providing mechanical support and foreign matter adhesion resistance; the hydrogel dressing can synergistically release artesunate and copper ions, and strongly activates autophagy of macrophages by synergistically acting on PI3K / AKT / mTOR and AMPK / mTOR signal pathways, so that chronic inflammation is relieved, collagen deposition is promoted, and wound healing is accelerated. The invention provides an innovative intelligent dressing for treating complicated chronic wounds such as diabetic foot ulcer.

The invention discloses application of combination of IMMU-132 and IACS010759 in preparation of a medicine for resisting esophageal squamous cell carcinoma and related medicines, and relates to the technical field of biological medicines, and the combination medicine comprises IMMU-132 and IACS010759. The IMMU-132 and the IACS010759 are synergistically combined, and the proliferation of the ESCC cells is inhibited by inhibiting a PI3K-AKT-mTOR signal channel; according to the combined medicine, the ROS level in cells is increased and the mitochondrial membrane potential is destroyed, so that the apoptosis of the mitochondrial pathway is synergistically induced. The IMMU-132 and IACS010759 provided by the invention show a remarkable synergistic anti-tumor effect and inhibit a PI3K-AKT-mTOR survival signal channel, so that cancer cell apoptosis is triggered, the problems that an existing ESCC treatment scheme is limited in curative effect and prone to drug resistance are solved, and a new strategy is provided for clinic.

The present application is suitable for the field of biological medicine technology, and provides application of a YAP agonist in preparation of a drug for treating intestinal lymphatic vessel dysfunction. The present application analyzes a molecular mechanism of the YAP agonist in improving high-fat diet induced lymphatic vessel dysfunction through targeted regulation of a VEGFR3 / YAP / mTOR signal pathway and a therapeutic application thereof, the YAP agonist antagonizes excessive phosphorylation of YAP, restores the nuclear translocation ability of YAP, activates the mTOR signal pathway, significantly improves the proliferation, migration and tube formation functions of LECs, and up-regulates VE-cadherin expression to repair endothelial barrier integrity; the YAP agonist can effectively relieve intestinal lymphatic vessel dysfunction and structural abnormalities induced by HFD.

The present application relates to the use of chicory ethyl acetate extract. In vitro experiments, using CellTiter-Glo luminescence method to evaluate the effect of chicory ethyl acetate extract on triple negative breast cancer cells, the results show that the extract significantly inhibits tumor cell proliferation. In vivo experiments: the anti-tumor effect of chicory ethyl acetate extract is verified by triple negative breast cancer animal model, the results show that: chicory ethyl acetate extract can effectively inhibit tumor growth. Further experiments show that the anti-tumor effect of chicory ethyl acetate extract is related to its regulation on PI3K / Akt / mTOR signaling pathway. The chicory ethyl acetate extract provided by the present application can be used for preparing drugs or pharmaceutical compositions for preventing and treating triple negative breast cancer.