73 results about "Metabolic reprogramming" patented technology

The invention relates to an in vitro method for classifying a subject afflicted with a cancer as suffering from a cancer with (at risk of) a metabolic reprograming towards fatty acids oxidation including a step of assaying the activation of RelB in a tumor sample form said cancer. The inventor indeed identified the pivotal role of RelB in energy metabolism and more particularly mitochondrial respiration and fatty acid oxidation. Accordingly, the invention also relates to inhibitors of RelB activity or expression, as well as of lipid metabolism for use in the treatment of cancers showing an activated RelB.

The invention relates to the technical field of osteoarthritis drugs, particularly discloses an application of DDX5-K45mRNA in preparation of drugs for treating and / or relieving osteoarthritis, and provides a drug delivery system for targeting chondrocytes at the same time, research finds that when DDX5-K45mRNA is added into the chondrocytes, the drug delivery system can be used for treating and / or relieving osteoarthritis. The medicine can restore DDX5-K45 lactic acid, block NF-kappa B inflammation signals, correct metabolic reprogramming (such as inhibition of abnormal glycolysis), and up-regulate cartilage protection factors such as COL2A1 and the like. The LNP is utilized to efficiently deliver DDX5-K45mRNA to cartilage cells, endogenous lactic acid modification defects are directly supplemented, the cartilage protection function of DDX5 is reconstructed, inflammatory response is inhibited, matrix degradation is reduced, the cartilage steady state is maintained fundamentally, and long-acting and safe OA treatment is achieved.

The invention discloses application of sorafenib in maintenance treatment of acute myelogenous leukemia after transplantation, and relates to the technical field of medicines, and the key points of the technical scheme are as follows: it is found for the first time that secretion and killing functions of NK cells can be enhanced by using sorafenib for maintenance treatment after transplantation; sorafenib enhances communication between macrophages and NK cells by promoting secretion of macrophage proinflammatory factors, so that the function of NK cells is enhanced. The invention clarifies that sorafenib enhances the GVL effect of NK cells in a low tumor load environment, discusses the molecular mechanism of sorafenib for enhancing the NK cell function by promoting macrophage metabolism reprogramming, and provides a new thought for maintaining precision and optimization of treatment after transplantation.

The invention discloses an application of a DHA-RXR-PPAR signal channel in promotion of postoperative recovery of hysteromyoma after HIFU (high intensity focused ultrasound). Clinical sample metabolic spectrum analysis and in-vitro cell function experiments are combined, and research proves that the differential metabolite DHA drives macrophage metabolism reprogramming through an RXR-PPAR signal axis, so that the macrophage is promoted to be transformed into an anti-inflammatory and phagocytosis-promoting repair phenotype, the absorption and repair process of the HIFU postoperative hysteromyoma is accelerated, and the treatment effect of the HIFU postoperative hysteromyoma is improved. A new intervention target spot (RXR-PPAR gamma axis) and a new potential medicine are provided for HIFU (high intensity focused ultrasound) postoperative rehabilitation.

The invention discloses a polyphosphate-metal nano-composite as well as a preparation method and application thereof, and belongs to the technical field of biological medicines and nano-materials. The polyphosphate-metal nano-composite is formed by self-assembly of polyphosphate and metal ions under the coordination action; wherein the chain length of the polyphosphate is 20 to 75. According to the invention, divalent metal ions are introduced, so that polyphosphate and metal ions form a spherical nano-composite through coordination self-assembly, the composite can be absorbed by tumor cells and degraded under an acidic condition, released polyphosphoric acid is separated through unique Ca < 2 + > phase, Ca < 2 + > is enriched around mitochondria, and the function of tumor treatment is realized. And tumor cell metabolism reprogramming is caused to be dominated by oxidative phosphorylation, so that copper death and immunoregulation are induced, and a triple synergistic anti-tumor effect is realized.

The invention discloses application of a PAPSS2 inhibitor in preparation of a medicine for treating bladder cancer. Based on the principle that PAPSS2 inhibits p53 expression through sulfurylation modification and mediates purine metabolism reprogramming to promote bladder cancer progress, a sulfurylation rate-limiting enzyme PAPSS2 is used as a core target spot for bladder cancer treatment, the target spot is a key upstream molecule for regulating purine metabolism reprogramming, and high expression of the target spot is directly related to poor prognosis of bladder cancer; the PAPSS2 inhibitor is adopted to specifically inhibit expression or activity of PAPSS2, so that the pathway is intervened to block a metabolic reprogramming process of bladder cancer, and the core is to inhibit PAPSS2-mediated p53 sulfurylation modification and recover an inhibition function of p53 on purine metabolism. According to the invention, the feasibility and effectiveness of bladder cancer metabolism targeted therapy are obviously improved.

This invention discloses an immune cell that secretes type 2 cytokines under hypoxic conditions and its applications, belonging to the fields of genetic engineering and cell engineering. The invention first constructs a nucleotide fragment encoding hypoxia-induced type 2 cytokines, including a signal peptide gene sequence, a CAR molecule nucleotide sequence targeting CD19 and CD22, and an IL-4 or IL-10 nucleotide sequence containing multiple HRE motifs of a hypoxia-inducible promoter. This nucleotide fragment is delivered to immune cells for stable expression, yielding an immune cell that secretes type 2 cytokines under hypoxic conditions. This immune cell secretes IL-4 or IL-10 only under hypoxic conditions, thereby leveraging the metabolic reprogramming effect of IL-4 or IL-10 on immune cells to enhance their activity under hypoxic conditions, thus achieving better long-term anti-tumor effects.

The invention discloses a nucleolin aptamer modified carboxymethyl chitosan-based glycolysis regulation nano-drug delivery system as well as a preparation method and application thereof, and relates to the field of tumor treatment. The nucleolin aptamer AS1411 is coupled with glycolysis regulation nano-particles through covalent bonds, and the carboxymethyl chitosan-based glycolysis regulation nano-drug delivery system comprises a carboxymethyl chitosan-based glycolysis regulation nano-drug delivery system, a carboxymethyl chitosan-based glycolysis regulation nano-drug delivery system and a carboxymethyl chitosan-based glycolysis regulation nano-drug delivery system, the glycolysis regulation nano-particles take carboxymethyl chitosan as a carrier skeleton, the carrier skeleton is loaded with a lonidamine derivative through grafting modification, and the nano drug delivery system can synchronously entrap paclitaxel. According to the invention, a synergistic treatment system integrating active targeting, metabolic regulation and chemotherapy is constructed, and by virtue of a multi-mechanism synergistic effect, an antitumor drug for inhibiting tumor cell activity, glycolysis or tumor metabolism reprogramming is prepared; the huge potentials of overcoming the drug resistance bottleneck of traditional chemotherapy, enhancing the curative effect and reducing the toxic and side effects are shown.

The invention discloses double-response hydrogel as well as a preparation method and application thereof. The double-response hydrogel comprises a three-dimensional porous network hydrogel matrix, and tea polyphenol and nano silicon nitride which are loaded in the hydrogel matrix, the three-dimensional porous network hydrogel matrix is prepared from o-nitrobenzene grafted hyaluronic acid and carboxyl phenylboronic acid modified methyl chitosan. According to the hydrogel disclosed by the invention, in a low-pH / high-ROS microenvironment of a diabetic periodontitis focus, boric acid ester bonds are broken, tea polyphenol is released, and the tea polyphenol plays an anti-inflammatory role by efficiently removing active oxygen and inhibiting inflammatory factors; meanwhile, the Schiff base bond is dissociated to release the nano silicon nitride, and the nano silicon nitride significantly promotes angiogenesis and osteogenic differentiation and accelerates bone defect repair by activating a redox signal, inducing cell autophagy, regulating metabolic reprogramming and other pathways.

The invention relates to the technical field of biological medicine, and particularly discloses a macrophage membrane coated plateau encephaledema drug carrier and a preparation method and application thereof, and the macrophage membrane coated plateau encephaledema drug carrier is composed of a nanoparticle core and a macrophage membrane shell layer wrapping the core; the nanoparticle core comprises an ROS-responsive carrier material and carbon monoxide release molecules MnCO entrapped in the ROS-responsive carrier material; the content of phosphatidylserine in the shell layer of the macrophage membrane is not less than 5 mol% of the total phospholipid of the membrane. According to the invention, a bionic delivery system of ROS response type MnCO nanoparticles coated with a macrophage membrane is constructed, phosphatidylserine on the surface of the membrane is utilized to actively activate a microglial cell Trem2 receptor, a positive feedback cycle of targeting phagocytosis-CO release-Trem2 up-regulation is formed, and at the same time, fatty acid oxidative metabolism reprogramming is promoted by means of degraded membrane lipid, so that the biomimetic delivery system is used for preparing the ROS response type MnCO nanoparticles. And multi-mechanism synergistic efficient brain-targeted therapy is realized.

T lymphocytes play a key role in the immune response and their functions are intimately linked to metabolic programs. During immune responses, T cells undergo a metabolic reprogramming notably characterized by an increased aerobic glycolysis. Using a quantitative phosphoproteomic approach, the inventors have identified a new transcription factor called Foxk1 as being highly phosphorylated in T cells upon T Cell Receptor (TCR) engagement. The results also indicate that Foxk1 phosphorylation and nuclear translocation is dependent of the AKT-mTOR kinase activities. Using T-cell specific Foxk1 deficient mice (Foxk1- / -), we demonstrated that Foxk1 is required for full T cell activation. Foxk1-deficient T cells exhibited reduced proliferation and cytokine secretion following TCR stimulation. Furthermore, T cells from Foxk1- / - mice were less prone to acquire an effector like phenotype than wild-type cells when challenged in vivo. Conversely, Foxk1 overexpression in T cells enhanced their effector functions in a TCR-dependent manner. In CD8+ T cells, this effect also results into enhanced cancer cell killing capacity in vitro, and improved tumor rejection in vivo. Altogether, these results indicated that Foxk1 is a major regulator of T cell metabolism and thus, of T cell effector functions. Thus, the present invention relates to host immune cells engineered to overexpress a Foxk1 polypeptide and their use of the treatment of cancer.

The application discloses a kind of biological hybrid micro machine population oral delivery system of imitating Helicobacter pylori survival mechanism, belong to oral stomach medicine delivery technical field.The system is by active power module (flagellum driven chlamydomonas reinhardtii), environmental regulation module (acid urease modified on algal surface) and multifunctional load module (macrophage membrane wrapped drug-loaded nanoparticles) synergistic assembly through polydopamine (PDA) spatial conformation control layer is formed.Active power module utilizes self-movement ability to penetrate mucus barrier and extend intracavity retention time to 12 hours or more;Environmental regulation module produces local alkalization effect by catalyzing urea hydrolysis, provides chemical shield for system in extremely acid environment of pH 1.0-3.0, protects active power module from gastric acid inactivation;Multifunctional load module is accurately delivered to gastric epithelial cells by inflammation targeting effect, such as CRISPR / Cas9 biological macromolecule, and realizes up to 31.8% in-vivo gene editing efficiency.The application provides a non-invasive, modular active delivery platform for the precise treatment of gastric diseases such as gastritis through the synergistic effect of physical penetration, metabolic reprogramming and gene intervention.

The invention belongs to the technical field of microorganisms, and discloses an amorphophallus bulbifer southern blight infection influence analysis method based on metabonomics and microbiomics. Conjoint analysis shows that core florae (such as Streptomyces, Penicillium and Bauldia) are in significant positive correlation with phenylpropanoids and glutathione (succinic acid, coniferyl alcohol and glutamic acid), succinic acid is in positive correlation with Kribbella and Terrimonas, 2 ', 2' ', 2' ', 2' ', 2' ', 2' ', 2' ', 2' ', 2' ', 2' ', 2' ', 2' ', 2' ', 2' ', 2' ', 2' ', 2' ', 2' ', 2' ', 2' ', 2' ', 2' ', 2' ', the 3, 3 '-cycle CMP is negatively correlated with pathogen-related bacteria, which indicates that the metabolite regulates and controls the abundance of specific bacteria through positive / negative feedback so as to drive the microecological balance of rhizosphere, and a collaborative defense strategy that plants recruit beneficial microorganisms and inhibit pathogenic bacteria through metabolism reprogramming is disclosed.

The application discloses a kind of for sensitizing lung cancer radiotherapy biomimetic nano delivery system and preparation method and application, it belongs to the field of biological medicine, wherein, biomimetic nano delivery system is core-shell structure, including core and the shell of the core outer layer being wrapped;Wherein, core is the lipid nanoparticle of therapeutic nucleic acid being loaded;Shell is tumor cell membrane vesicle;Therapeutic nucleic acid is the short hairpin RNA expression plasmid of targeted deubiquitinating enzyme CYLD gene.The application solves lung cancer radiotherapy resistance problem from mechanism, by therapeutic nucleic acid specific knockdown deubiquitinating enzyme CYLD gene, effectively blocks CYLD / NRP1 signal shaft, to reverse the metabolic reprogramming of tumor cell, significantly enhance its radiotherapy sensitivity, realize to the low-toxicity treatment of radiation resistance lung cancer.

The invention discloses application of a substance for reducing MMACHC expression in preparation of antitumor drugs, and relates to the field of molecular biology. The application discovers that MMACHC can regulate and control a metabolism reprogramming pathway of lipid metabolism under tumor conditions for the first time, and knockout of MMACHC can effectively inhibit the lipid metabolism pathway, so that proliferation and invasion of colorectal cancer cells are inhibited, and the development process of tumors is delayed; therefore, the MMACHC is used as a target spot for anti-tumor treatment, and the substance for reducing the expression of the MMACHC is used for preparing the anti-tumor medicine, so that the MMACHC has important significance on comprehensive treatment of tumors.

The invention discloses a bionic hybrid nano regulator for enhancing cell copper death and a preparation method and application thereof, and belongs to the technical field of biomedical materials. The invention designs a bionic nano-platform which simultaneously loads a lactic acid regulator cyclostilbene Su 3118 and a copper ion carrier disulfiram DSF, and the bionic nano-platform is combined with hybrid macrophages and tumor cell membranes to construct a nano-regulator SCTDM. The nano regulator can exert multiple functions, including tumor targeting, in-situ photothermal therapy, lactic acid regulation and enhanced copper death. The nano regulator provided by the invention is simple and convenient to manufacture, is combined with in-situ photothermal therapy and lactic acid regulation and is used for enhancing cell death immunotherapy of copper death so as to eliminate primary tumors and delay relapse, and a technical support is provided for regulating immunity by enhancing copper-induced cell death through metabolic reprogramming.

The invention relates to the technical field of pharmaceutical preparations, in particular to mRNA (messenger ribonucleic acid) lipid nanoparticles and application thereof in treatment of triple-negative breast cancer. The invention constructs an mRNA lipid nanoparticle, breaks through the dilemma of single drug curative effect of a glucose transporter (GLUT) inhibitor and a glutaminase (GLS) inhibitor for triple negative breast cancer, and realizes double-track treatment of mRNA metabolism reprogramming and small molecule energy deprivation for the first time. The mRNA lipid nanoparticles enhance the sensitivity of triple negative breast cancer to small molecule energy deprivation treatment, so that the clinical transformation feasibility of BAY-876 and CB-839 is improved to a new dimension. The delivery efficiency of the mRNA lipid nanoparticles is high, the biological safety is good, meanwhile, the production process of the nanoparticles is simpler and more standard compared with plasmids and viruses, and the drug production cost is lower.

The invention relates to application of theaflavin as a UGP2 inhibitor and application of theaflavin in preparation of a medicine for preventing and / or treating hepatocellular carcinoma, and belongs to the technical field of biology. According to the invention, the monomeric compound theaflavin derived from a natural product can be used as a UGP2 direct targeting inhibitor for the first time, and is used for preparing a liver cancer treatment medicine for regulating and controlling glucose metabolism reprogramming. The theaflavin can be specifically and directly combined at a UGP2 active site in a targeting manner through high activity to inhibit the activity of the UGP2, is the first specific inhibitor which takes the UGP2 as a target spot and is reported at present, and can be used for remarkably inhibiting tumor phenotypes such as proliferation, migration and invasion of liver cancer cells by inhibiting UGP2-mediated UDPG synthesis and intracellular glycogen accumulation.

The invention discloses a multi-source vegetable outer vesicle composition as well as a preparation method and application thereof. The multi-source vegetable outer vesicle composition is prepared from outer vesicles extracted from spinach leaves, ginger tubers, broccoli buds, bitter gourd fruits and celery stems. The spinach leaves, the ginger tubers, the broccoli flower buds, the bitter gourd fruits and the celery stems are mixed according to the fresh weight ratio of (3-5): (1-2): (2-3): (1-1.5): (2-4), and low-temperature homogenization, centrifugation and ultrafiltration purification are performed to obtain the spinach-ginger-containing beverage. The particle size of the multisource vegetable outer vesicle composition is 100-200 nm, and the multisource vegetable outer vesicle composition comprises transmembrane protein TET8 and membrane anchoring protein ANNEXIN, and further comprises active ingredients of miR159a, miR166a, quercetin and kaempferol. The outer vesicle can target a PPAR gamma / FAS pathway and regulate and control lipolysis and metabolism reprogramming of fat cells; meanwhile, an Nrf2 pathway is activated, free radicals are removed, oxidative stress injury is inhibited, and metabolic diseases such as obesity, type II diabetes mellitus and non-alcoholic fatty liver disease can be effectively improved.

The invention provides application of combination of an mTOR inhibitor and an EPAS1 inhibitor in preparation of a medicine for treating myeloproliferative tumors, through combined use of the mTOR inhibitor everolimus and the EPAS1 inhibitor PT2385, JAK2V617F mutation-driven metabolic disorder is targeted, metabolic reprogramming is effectively reversed (the lactic acid level is reduced, the alpha-ketoglutaric acid level is increased, and the lactic acid / alpha-KG ratio is corrected), and the treatment effect on myeloproliferative tumors is improved. The JAK inhibitor can be used for treating MPN, synergistically relieving splenomegaly, reversing myelofibrosis and reducing mutation allele load, the curative effect is remarkably superior to that of existing JAK inhibitor single-drug treatment, and an innovative scheme with disease modification potential is provided for MPN.

The invention provides application of pentenedioic acid (GC) in enhancing the anti-tumor effect of T cells through metabolic reprogramming, and belongs to the technical field of biological medicine. It is found that in the tumor development process, GC is supplemented in an exogenous mode, tumor growth can be rapidly inhibited, and the anti-tumor effect depends on a TME regulation and control mechanism. Through GC treatment, the TME immune landscape can be significantly remodeled; gC treatment not only can enhance the effector function of the CD8 + T cells, but also can delay the depletion process of the CD8 + T cells; and the infiltration CD8 + T cells in the tumor of the GC treatment group are obviously increased. Particularly, after the CD8-resistant antibody is used for removing mouse CD8 + T cells, the anti-tumor effect of GC completely disappears, and it is confirmed that the tumor inhibition effect depends on the CD8 + T cells. Therefore, the invention proves that the lysine catabolic metabolite GC, as an immunostimulatory metabolite, can shape the immune activated TME by reactivating the functions of tumor infiltrating CD8 + T cells.

This invention discloses a metabolically enhanced anti-tumor CAR-M cell co-expressing SLC protein, comprising the nucleotide sequence encoding the HER2 antigen-binding domain scFv and the nucleotide sequence encoding the SLC protein. The invention also discloses a method for constructing the aforementioned anti-tumor CAR-M cell and its application in the preparation of anti-tumor drugs. The anti-tumor CAR-M cell of this invention specifically recognizes HER2, thereby effectively reducing off-target toxicity, improving treatment safety and tumor specificity, and exhibiting significantly enhanced glutamine uptake capacity. It possesses a good metabolic reprogramming effect at the molecular level, resulting in stronger anti-tumor activity due to enhanced metabolism.

The application belongs to the technical field of biological medicine, and particularly relates to gRNA targeting FOXO3 gene and application thereof. The application provides sgRNA combination targeting FOXO3 gene and application thereof, and the sgRNA targets Thr32, Ser253 and Ser315 sites of the FOXO3 gene respectively. The sgRNA screened by the application has high editing efficiency, and the overall editing efficiency does not decrease when multiple sites are simultaneously edited. The application realizes efficient and accurate modification of key sites of FOXO3 under the premise of not generating DNA double-strand break through a multi-target point synergistic editing strategy, avoids cell damage and genomic instability, simultaneously expands the FOXO3 regulation spectrum from single developmental regulation to systemic metabolic reprogramming, significantly enhances the metabolic regulation and immune regulation functions of the engineered cell, and has simple and efficient preparation process, and is suitable for the treatment of aging and metabolism related diseases.

The invention relates to an application of suramine in promoting tumor radiotherapy sensitization. The invention fully proves that suramin can effectively prepare tumor cells in a state highly sensitive to ferroptosis through a novel metabolic reprogramming mechanism of inhibiting IPPK, reducing IP6 and releasing Fe < 2 + > chelated with an iron pool in cells, thereby creating necessary biochemical conditions for ferroptosis; and the sensitivity of cells to ferroptosis induced stimulation is fundamentally changed. Therefore, the compound can be used as a ferroptosis inducer and a potent sensitizer for radiotherapy at the same time. The discovery not only provides a new combined strategy for overcoming tumor treatment resistance, but also perfectly explains the transformation medicine concept of new use of old medicines, and provides a new active ingredient for human tumor treatment, thereby providing a new direction for subsequent medicine research and development, clinical treatment and the like, and having extremely high social value and market application prospects.

The invention provides a liver cancer prognosis evaluation method, system and equipment, a medium and a program product, and relates to the field of intelligent medical treatment. The invention discloses heterogeneity of liver cancer cell subpopulations, in particular characteristics and molecular mechanisms of MVI-related cell subpopulations (such as Hep-C4); a specific cell subset related to poor prognosis of a liver cancer patient is identified, the effect of the specific cell subset in tumor growth and metastasis is explored, metabolic reprogramming of liver cancer cells, particularly the effect of a methionine metabolic pathway in promotion of tumor cell invasion and metastasis, is researched, and a theoretical basis is provided for metabolic intervention of liver cancer. Potential molecular markers (such as a combined marker of STMN1 and EZH2) are identified and used for prognosis evaluation and treatment response monitoring of liver cancer patients, and personalized medical treatment and precise treatment can be achieved.

The invention discloses a multi-omics malignant pleural effusion immunometabolism reprogramming spatio-temporal heterogeneity analysis device, which comprises an integration analysis module used for carrying out multi-modal integration and consensus clustering analysis on a multi-omics data set to obtain an integration analysis result, dividing the malignant pleural effusion training samples of the malignant pleural effusion patient into an immunometabolism activation type subtype, an immunometabolism transition type subtype and an immunometabolism inhibition type subtype according to the confluence analysis result; the screening construction module is used for screening immune metabolism markers from the characteristics of the immune metabolism inhibition type subtypes, forming a candidate target point set according to the immune metabolism markers, and constructing a prediction model; and the evaluation suggestion module is used for calculating treatment response scores and combining the treatment response scores with the clinical staging information to construct a column diagram, and a prognosis risk evaluation result and personalized treatment guidance suggestions are obtained, so that the accuracy of prognosis evaluation and the reliability of treatment response prediction can be improved, and accurate risk stratification and personalized treatment guidance for patients can be realized.

The invention relates to the field of traditional Chinese medicines, in particular to a traditional Chinese medicine compound preparation capable of improving the curative effect of chemotherapy combined targeted treatment of colorectal cancer, which is prepared from six traditional Chinese medicines, namely raw astragalus membranaceus, bighead atractylodes rhizome, pericarpium citri reticulatae, ginger processed pinellia, sargentgloryvine stem and Chinese actinidia root. Glutamine and metabolism can be reduced by inhibiting expression of enzymes related to glutamine metabolism, then metabolic reprogramming of tumor cells is affected, glutamine uptake and metabolism of colorectal cancer cells can be effectively inhibited, and the effect of remarkably inhibiting colorectal cancer metastasis can be achieved when the compound is combined with chemotherapy and targeted therapy for use. Or the medicine can be used as an auxiliary medicine for colorectal cancer patients, so that the clinical problem that the response of the colorectal cancer patients to the chemotherapy combined targeted therapy is limited is effectively solved, and the medicine has a wide application prospect when being combined with the chemotherapy combined targeted therapy.

The invention relates to a nano drug delivery system loaded with nitazoxanide as well as a preparation method and application of the nano drug delivery system, and belongs to the technical field of pharmaceutical preparations. The nano drug delivery system is prepared by loading nitazoxanide on a metal organic framework ZIF-90 nano material through a simple and rapid method. The nano drug delivery system constructed by the invention can effectively improve the solubility and stability of nitazoxanide, and realizes the enrichment of drugs in tumor cell mitochondria by virtue of the mitochondrial targeting characteristic of the ZIF-90 material. The system can intelligently release drugs under the acidic and high ATP conditions of a tumor microenvironment, not only utilizes the metabolic reprogramming effect induced by nitazoxanide, but also synergistically enhances the anti-tumor effect in cooperation with the Zn < 2 + >-triggered oxidative stress disorder dual mechanism, and provides a new strategy for solving the problems of low bioavailability, poor targeting property and the like in clinical application of nitazoxanide.

This invention discloses a nucleic acid fragment, nanoliposomes, and their application in the in vivo preparation of CAR-T cells, belonging to the field of immunocellular therapy technology. This invention constructs a CAR nucleic acid fragment that can be delivered in vivo via various methods to obtain in vivo activated and induced enhanced CAR-T cells that secrete IL-4 or IL-10. These CAR-T cells do not secrete IL-4 or IL-10 in a resting state, thus avoiding the inhibitory effects of IL-4 or IL-10 on their proliferative capacity and effector function. When the CAR-T cells are specifically activated by tumor cells, they can secrete IL-4 or IL-10, thereby restoring the vitality of CAR-T cells and enhancing their long-term anti-tumor activity through metabolic reprogramming of IL-4 or IL-10. This invention achieves in vivo induced CAR-T cell generation, with the advantages of simple operation and low cost.

Downregulated miR-99b-5p and upregulated mTOR cooperatively promotes the African American (AA) PCa aggressiveness and drug resistance. Nuclear mTOR, AR, and SMARCD1 are highly expressed in AA PCa (MDA PCa 2b) compared to EA PCa (LNCaP) cell line. miR-99b-5p inhibited protein levels of mTOR, AR / AR-V7 and SMARCD1 in cytoplasm and nuclei of EA and AA PCa. miR-99b-5p effectively inhibits cell proliferation / survival and induced cell apoptosis in EA and AA PCa cells. Moreover, combination of miR-99b-5p and enzalutamide (Enz) synergistically enhances the cytotoxicity against aggressive AA PCa and castration resistant prostate cancer (CRPC). miR-99b-5p or miR-99b-5p / Enz significantly reduces the recruitment of mTOR to the genes involved in the metabolic reprogramming in CRPC. miR-99b-5p can function as an epigenomic driver to modulate the mTOR / AR / SMARCD1 signaling axis in AA PCa and resistant CRPC. miR-99b-5p can be utilized as a biomarker for identifying the presence of prostate cancer.