36results about How to "Increase drug sensitivity" patented technology

Described herein is a network biology approach useful for the identification of multiple therapeutic targets, which can be targeted simultaneously using an agent (or a plurality of agents) to modulate cellular phenotypes, or in combination with pharmaceutical compounds to improve drug sensitivity and / or reduce drug doses to maintain efficacy while minimizing side effects. The preferred approach disclosed herein relies on first identifying the mediators of a condition of interest, and second, selecting gene combinations that are in competing / parallel pathways as targets for combination therapy.

The invention belongs to the technical field of genetic engineering, and discloses long noncoding RNA SNHG15 and application thereof in preparation of cancer diagnosis and treatment drugs. Cancers include colorectal cancer, breast cancer, kidney cancer and the like. Expression of the long noncoding RNA SNHG15 in tumor tissues of patients suffering from the colorectal cancer, the breast cancer andthe kidney cancer is up-regulated. The patients with highly-expressed long noncoding RNA SNHG15 have poor prognosis. Through expression knock-down of the long noncoding RNA SNHG15 in colorectal cancercell lines, invasion, migration and multiplication capabilities of cells can be inhibited, and drug susceptibility of colorectal cancer cell lines to antitumor drugs including gemcitabine and cis-platinum can be improved.

The invention relates to Nanodrug nanoparticles for realizing pH (Potential of Hydrogen) imaging of a tumor microenvironment, drug controlled release and cooperated chemotherapy effect on tumors. The Nanodrug nanoparticles are prepared through commonly coordinating a clinical commonly used chemotherapy drug Doxorubicin and a biological reduction drug (Banoxantrone) with bivalent copper ions through a self-assembling synthesis method. The Nanodrug nanoparticles provided by the invention can be used for intelligently adjusting a nano-scale according to different pH gradients of the tumor microenvironment and can effectively permeate tumor epithelial cells and express drug controlled release and cooperated anti-tumor activity under an aerobic / anoxic condition; the tumor anoxic tolerance of the drugs is solved and the potential toxic and side effects caused by the anthracycine chemotherapy drugs on patients is reduced.

The present invention relates to a peptide having eight amino acid sequences derived from CAGE and retaining anticancer activity and activity to promote anticancer drug sensitivity of anticancer drug resistant cancer cells and, specifically, to a peptide, which has an amino acid sequence of SEQ ID NO: 1 (AQTGTGKT) and thus binds to the CAGE protein, thereby inhibiting an inter-linkage between CAGE and GSK3β, thus exhibiting anticancer activity and activity to promote anticancer drug sensitivity of anticancer drug resistant cancer cells, and to a pharmaceutical composition, containing the peptide, for anticancer use or anticancer drug aiding.

Described herein are methods for diagnosing ovarian cancer. In particular, certain microRNAs are useful to the response to chemotherapy of ovarian cancer patients.

The present invention relates to a peptide having eight amino acid sequences derived from CAGE and retaining anticancer activity and activity to promote anticancer drug sensitivity of anticancer drug resistant cancer cells and, specifically, to a peptide, which has an amino acid sequence of SEQ ID NO: 1 (AQTGTGKT) and thus binds to the CAGE protein, thereby inhibiting an inter-linkage between CAGE and GSK3β, thus exhibiting anticancer activity and activity to promote anticancer drug sensitivity of anticancer drug resistant cancer cells, and to a pharmaceutical composition, containing the peptide, for anticancer use or anticancer drug aiding.

The invention provides an adhesive protein sourced from Bifidobacterium longum. An amino acid sequence of the protein is determined, on the basis, an expression strain of the protein is obtained with a genetic engineering technology, innovative design is performed in the aspects of induction expression, purification by chromatography, ultrafiltration concentration and the like aiming at characteristics of the strain and the adhesive protein, and an efficient preparation method of the adhesive protein is obtained. Furthermore, experiments find that the adhesive protein not only can adhere to an enterocyte, but also has a function of improving antibiotics sensibility of microorganisms, on the basis of the beneficial discovery, an application of the protein as an anti-bacterial synergist for antibiotics is determined, an application range of the protein is extended, and a new path for improving the drug sensitivity of the microorganisms is provided. Prominent technological effects are obtained on the basis of strict experimental measures, and broad application prospect is provided.

It is intended to provide a set of yeast gene knockout strains whose drug sensitivity has been significantly improved. A set of yeast cells of the invention is a set of yeast cells comprising two or more species of yeast cells, wherein at least one mutually different gene has been deleted or mutated in each of the two or more species of yeast cells, and all the two or more species of yeast cells are drug hypersensitive yeast cells in which the expression of at least one drug sensitivity-related gene has been regulated.

The invention belongs to the field of biotechnologies, and relates to a gene vaccine capable of inhibiting cancer cell growth. The gene vaccine can express a cell membrane surface protein metadherin (MTDH) and thus being named as a MTDH gene vaccine. The MTDH gene vaccine is utilized for immunization in an oral way. The MTDH gene vaccine can activate an immune response of CD8+ cytotoxic T cells on breast cancer cells 4T1 expressing MTDH antigens. The MTDH gene vaccine can inhibit breast cancer cell growth and pulmonary metastasis. Through being combined with adriamycin, the MTDH gene vaccine can improve adriamycin effects of inhibiting breast cancer cell growth and pulmonary metastasis, and prolong a life of a mouse loaded with cancer. More significantly, the MTDH gene vaccine does not produce obvious damages on main organs of a human body. Therefore, the MTDH gene vaccine provides a novel approach for improvement of the existing breast cancer treatment method.

The invention belongs to the technical field of biomedicine, and particularly relates to a glioma malignant progress and survival prognosis detection molecular marker, a temozolomide drug resistance detection target and application. An m6A methylation reader HNRNPC which is highly expressed in glioma tissue and closely related to the tumor occurrence and development process is screened out by a bioinformatics method, further analysis finds that the expression level of the m6A methylation reader HNRNPC is closely related to the survival rate and prognosis of patients, and through clinical masstumor tissue sample verification, the m6A methylation reader HNRNPC can be used as a molecular marker and an independent survival prognosis factor for glioma malignant progress. Meanwhile, it is foundthat knockout of the HNRNPC can increase medicine sensitivity of glioma cells to temozolomide. A new diagnosis, treatment and prognosis predicting target is provided for glioma treatment, and a new molecular target can be provided for improving temozolomide drug resistance.

The invention provides an adhesive protein sourced from Bifidobacterium longum. An amino acid sequence of the protein is determined, on the basis, experiments find that the adhesive protein not only can adhere to an enterocyte, but also has a function of improving antibiotics sensibility of microorganisms, and the antibiotics synergy on Salmonella typhimurium is particularly prominent. On the basis of the beneficial discovery, an application of the protein as an anti-bacterial synergist for Salmonella typhimurium is determined, an application range of the protein is extended, and a new path for improving the drug sensitivity of the microorganisms is provided. Prominent technological effects are obtained on the basis of strict experimental measures, and broad application prospect is provided.

The invention belongs to the technical field of biology, and especially relates to a Chinese herbal medicine micro-ecological preparation for subsidiarily preventing and treating pulmonary tuberculosis. The employed technical scheme is shown as follows: firstly preparing a kombucha mother solution and secondly preparing a Chinese herbal medicine extraction solution; inoculating a filtered Chinese herbal medicine extraction solution to the kombucha mother solution for fermentation, so as to use the fermentation solution to subsidiarily prevent and treat pulmonary tuberculosis; and additionally, performing low-temperature freeze drying on the completely-fermented Chinese herbal medicine micro-ecological preparation to form a bacterial powder of the Chinese herbal medicine micro-ecological preparation, and performing vacuum packaging for long-term storage. The product is capable of inhibiting growth and breeding of mycobacterium trberculosis through multiple action mechanisms. When for treatment, the product can be used in an oral administration way or in a spraying way. The product is non-toxic, can be used for subsidiary prevention, also can be used for subsidiary treatment, and can be used to treat pulmonary tuberculosis through both alimentary canal and respiratory tract. Therefore, the preparation has good comprehensive subsidiary prevention and treatment effects on pulmonary tuberculosis.

The invention relates to an application of solasodine to preparation of an antitumor drug sensitizer. According to the embodiment of the invention, the solamargine is used as a sensitizer of the antitumor drug for the first time, so that the drug sensitivity of tumor cells to the antitumor drug can be effectively improved, and the dosage of the antitumor drug can be reduced when the antitumor curative effect of the antitumor drug is remarkably improved. Reducing toxic and side effects of the antitumor drug on normal cells of a human body is facilitated. Therefore, according to the embodiment of the invention, the solasodine is used as the sensitizer of the antitumor drug, and has the advantages of high efficiency and low toxicity.

The invention relates to a composition and pharmaceutical preparation and application thereof. The composition and pharmaceutical preparation comprises docetaxel and YK-4-279, the molar concentration ratio of which is 1:1000, the compounding is reasonable, the combination of the two not only can improve the pharmaceutical sensitivity of docetaxel, but also realizes the effects of the YK-4-279 in aspects of anti-prostate cancer as an ETV1 small-molecular inhibitor, and the treatment effect of docetaxel can be synergistically enhanced. Experiments proved that the combination of docetaxel and YK-4-279 has obviously enhanced inhibition activity to human prostate cancer cells compared with single medication, furthermore, the administration dose in cancer treatment can be decreased, the toxic and side effects of the medicines can be reduced, the harm to a human body can be decreased, and the composition and pharmaceutical preparation hopefully becomes a high-efficiency and low-toxicity anti-prostate cancer drug.

The invention discloses siRNA for targeted inhibition of SOS1 gene expression and application of the siRNA. The sequence of the siRNA is as follows: a sense strand is 5'-GCAGAATCTTCACCATCTA-3', and anantisense strand is 5'-TAGATGGTGAAGATTCTGC-3'. According to the SiRNA, by detecting the change of expression quantity of the mRNA level and protein level of SOS1, the effective siRNA sequence of SOS1, namely the SOS1-siRNA # 3 is screened out, the multiplication capacity and clonality of CML cells can be effectively inhibited, the growth of transplanted tumors can be effectively inhibited in animal bodies, and meanwhile, the drug sensitivity of the CML cells to imatinib is improved. Therefore, the SOS1 is a potential new target for treating chronic granulocytic leukemia, and the SOS1 siRNA has a potential value of overcoming the drug resistance of the imatinib.

The invention provides an extracellular regulatory protein kinase probe as shown in a formula I. A ring A on the structure can be covalently bound with 178 cysteine of an inactive site on the outer side of an ERK1 / 2 kinase structure in a specific targeting manner, and can effectively target ERK1 / 2; and the extracellular regulatory protein kinase probe does not inhibit the binding capacity of ERK1 / 2 and ATP and the kinase activity, but has targeting property on ERK1 / 2, so a small-molecule guiding group is provided for protein modification and marking research of targeted ERK kinase, the drug sensitivity of an inhibitor on extracellular regulatory protein kinase is improved, the probe is provided for an extracellular regulatory protein kinase inhibitor, and the extracellular regulatory protein kinase inhibitor is guided to act on the extracellular regulatory protein kinase site in a targeted manner so as to enable the inhibitor to play a role and to improve effect.

The invention provides an attachment protein derived from bifidobacterium longum, and discloses the amino acid sequence thereof; on the basis, experiments discover that the attachment protein not only can attach to enterocyte, but also has the function of improving microorganism antibiotic sensitivity, and especially for escherichia coli O157:H7, the antibiotic synergy is particularly prominent. Based on the beneficial discovery, the application of the protein as an anti-bacteria synergist, escherichia coli O157:H7, is determined, so that the application range of the protein is expanded, and at the same time, a new approach is provided for improving microorganism drug sensitivity. The prominent technological effect is achieved on the basis of strict experimental measures, and a broad application prospect is obtained.

The invention relates to a construction method for an acute hyperuricemia tree shrew model. The method comprises the following steps: (1) selecting adult healthy tree shrew with body weight of 110 to 150 g and an age of 1 to 3 years; (2) respectively measuring fasting serum uric acid values of males and females of tree shrew selected in the step (1); (3) carrying out conventional breeding on the tree shrew selected in the step (1) and pretreating the tree shrew by grasping and releasing the tree shrew with hand; and (4) injecting the tree shrew treated in the step (3) with an oteracil potassium suspension so as to obtain the acute hyperuricemia tree shrew model, wherein the amount of the used oteracil potassium suspension is 40 mg / kg to 100 mg / kg on the basis of the body weight of the tree shrew. The model has typical disease symptoms, a quantity index has statistical significance, and serum urea nitrogen and serum creatinine values and histopathological results prove that such a model making dosage range is safe and does not result in influence on the liver and the kidney.

The invention relates to a pharmaceutical composition for preventing and treating avian salmonellosis and a preparation method of the pharmaceutical composition. The pharmaceutical composition comprises the following components: artemisinic acid, ampicillin sodium, ciprofloxacin and polysaccharide and probiotic microcapsules. According to the pharmaceutical composition disclosed by the invention, monomer traditional Chinese medicine effective components are selected to be combined with the antibiotics, so that the use amount of traditional Chinese medicines and antibiotics can be reduced on the premise of improving the antibacterial inhibition and killing effects, and the bioavailability and efficacy of medicines are improved. Meanwhile, immune enhancement regulation is taken as an auxiliary treatment means, polysaccharide and probiotics are selected to regulate intestinal flora of the diseased chickens and reconstruct a good microbial system, so that the immune function of the chickens is enhanced, and the production performance is improved. The pharmaceutical composition disclosed by the invention can be administrated through mixed feeding, is suitable for clinical application, has an exact curative effect and is suitable for being applied to intensive large-scale farms.

The invention belongs to the technical field of bioengineering, and discloses a method for improving the anti-tumor effect of rituximab and application. The method comprises the following steps that sgRNA and cas9mRNA of specific PIG-A are packaged through lipid nanoparticles; a CD20 antibody is coupled by utilizing a lipid nanoparticle transmission system, and B-NHL lymphoma cells and lymphoma cells PIG-A are accurately targeted; and by editing PIG-A of the B-NHL cells, synthesis of GPI in the cells is impaired, and proteins including extracellular ankyrin CD59 are lost. According to the method, through gene editing of PIG-A, synthesis of GPI and expression and distribution of ankyrin such as CD59 and CD55 are reduced, and drug sensitivity and tumor killing effect of rituximab can be greatly improved; and a lipid nanoparticle transmission system is used for coupling a CD20 antibody, so that rituximab drug-resistant B-NHL cells can kill 99% of lymphoma cells in initial treatment.

The present application provides an extracellular regulatory protein kinase probe as shown in formula I, the A loop on the structure can specifically target the cysteine ​​at position 178 of the inactive site on the outside of the ERK1 / 2 kinase structure Amino acid covalently combined, can effectively target ERK1 / 2; and the extracellular regulatory protein kinase probe will not inhibit the ability of ERK1 / 2 to bind to ATP and the kinase activity, but through its targeting of ERK1 / 2, Provide small molecule guiding groups for protein modification and labeling research targeting ERK kinases, improve the drug sensitivity of inhibitors to extracellular regulated protein kinases, provide probes for extracellular regulated protein kinase inhibitors, and guide extracellular regulated protein kinases The inhibitor can target the extracellular regulatory protein kinase site, so that the inhibitor can work and improve the effect.

The invention relates to a PI3K and MTH1 targeting drug composition and applications thereof. The small-molecule targeting drug composition and a drug preparation provided by the invention comprise afirst preparation formed by a PI3K inhibitor or a pharmaceutically-acceptable carrier thereof, and a second preparation formed by a MTH1 inhibitor or a pharmaceutically-acceptable carrier thereof. Thecompatibility is reasonable. The combination of the two preparations can improve the drug sensitivity of the PI3K inhibitor, play the role of the MTH1 small-molecule inhibitor in the anti-tumor aspect and increase the treatment effect of the PI3K inhibitor. Experiments prove that: the combined administration of the PI3K inhibitor and the MTH1 inhibitor obviously enhances the tumor cell activity inhibition compared with the single administration, reduces the single administration dosage, can reduce the drug toxicity, is expected to become a new tumor treatment scheme aiming at the non-ideal treatment effect of the PI3K inhibitor, and has wide application prospect.

The invention provides an application of mycobacterium tuberculosis protein Rv1508c to preparation of an antituberculotic drug sensitizer, and belongs to the technical field of biology. It is determined for the first time that the mycobacterium tuberculosis functional protein Rv1508c can improve sensitivity of mycobacterium tuberculosis to streptomycin, that is, the protein can promote a streptomycin drug to kill mycobacterium, and the protein can serve as a drug resistance reversal agent and a streptomycin sensitizer of an antituberculotic drug. New path and means can be provided for tuberculosis treatment by the mycobacterium tuberculosis functional protein Rv1508c as a new auxiliary component of the antituberculotic drug.

The present invention provides a tumor-targeting polypeptide, including: (a) a novel tumor-targeting therapeutic polypeptide; (b) a fusion protein formed by the polypeptide (a) and a penetrating peptide element; (c) a fusion protein formed by the polypeptide (a) or ( b) A derivative polypeptide derived by adding, deleting, or changing one or more amino acids and having effects on RAD51 ubiquitination modification, foci formation in the nucleus, and reduced DNA repair function; (d) the amino acid sequence corresponds to C of the RAD51 protein end (331-339aa), or a fusion protein formed by the C-terminus and the penetrating peptide element, and the polypeptide or fusion protein (d) can affect the ubiquitination modification of RAD51, the formation of foci in the nucleus, and reduce the DNA repair function. By administering the polypeptide of the present invention, only the ubiquitination modification of RAD51 is affected, thereby affecting the formation of foci in the nucleus, and the side effects are small; the concentration of chemotherapy drugs can be effectively reduced, and the drug sensitivity of tumor cells can be improved.

The invention relates to an EGFR and CDK4 / 6 small-molecule targeted drug composition and application thereof. The EGFR and CDK4 / 6 small-molecule targeted drug composition is composed of two targeted drugs of an EGFR small-molecule inhibitor and a CDK4 / 6 small-molecule inhibitor, wherein the EGFR small-molecule inhibitor is Erlotinib, and the CDK4 / 6 small molecule inhibitor is Palbociclib. According to the EGFR and CDK4 / 6 small molecule targeted drug composition and the application thereof, the compatibility is reasonable, the medicine sensitivity of the EGFR small molecule inhibitor can be improved and the effect of the CDK4 / 6 small molecule inhibitor in the aspect of colorectal tumor resistance can be further exerted by the combination of the EGFR small molecule inhibitor and the CDK4 / 6 small molecule inhibitor, so that the treatment effect of the EGFR small molecule inhibitor is improved, experiments prove that the combined medication of the EGFR small-molecule inhibitor and the CDK4 / 6 small-molecule inhibitor significantly enhances the inhibition of the activity of colorectal tumor cells compared with the single medication, reduces the single medication dosage, can reduce the drug toxicity, is expected to become a new treatment solution for colorectal cancer with unsatisfactory treatment effect on the EGFR inhibitor, and broad application prospects are achieved.

The invention relates to a pharmaceutical composition for preventing and treating poultry salmonellosis and a preparation method thereof. The pharmaceutical composition comprises the following components: artemisinic acid, ampicillin sodium, ciprofloxacin, polysaccharide + probiotic microcapsules. The pharmaceutical composition of the present invention selects active components of monomeric traditional Chinese medicines and uses them in combination with antibiotics, which can reduce the amount of conventional traditional Chinese medicines and antibiotics and improve the bioavailability and efficacy of the medicines on the premise of improving the antibacterial and killing effects. At the same time, using immune enhancement and regulation as an auxiliary treatment method, polysaccharides and probiotics are selected to regulate the intestinal flora of sick chicks and rebuild a good microbial flora, so as to strengthen the immune function of chicks and improve production performance. The pharmaceutical composition of the invention can be administered through mixed feeding, is suitable for clinical application and has definite curative effect, and is suitable for application in intensive scale farms.

The invention provides attachment protein derived from bifidobacterium longum. The amino acid sequence of the protein is defined. On the basis, it is found through experiments that the attachment protein can be attached to enterocytes and has the effect of improving the sensitivity of microorganisms to the antibiotics, and the synergistic effect on the antibiotics is particularly outstanding especially for mononuclear Lister monocytogenes. Based on the beneficial discovery, application of the protein as an antibacterial synergist for the mononuclear Lister monocytogenes is confirmed, the application range of the protein is expanded accordingly, and meanwhile a new way for improving the drug sensitivity of the microorganisms is provided. An outstanding technical effect is achieved based on a strict experiment measure, and wide application prospects are achieved.

The invention provides a tumor targeted polypeptide, which comprises: (a) a novel tumor targeted therapy polypeptide; (b) a fusion protein formed by the polypeptide (a) and a cell-penetrating peptideelement; (c) a derived polypeptide which is derived from the polypeptide (a) or (b) by adding, deleting or changing one or more amino acids and has the functions of influencing RAD51 ubiquitination modification and intracellular foci formation and reducing DNA repair; and (d) a polypeptide of which the amino acid sequence corresponds to the C terminal (331-339aa) of the RAD51 protein, or a fusionprotein formed by the C terminal and a cell-penetrating peptide element, wherein the polypeptide or the fusion protein (d) has the functions of influencing RAD51 ubiquitination modification and intracellular foci formation and reducing DNA repair. By giving the polypeptide, only the ubiquitination modification of RAD51 is influenced, and the formation of intracellular foci is influenced, so that the side effect is small; and the use concentration of chemotherapeutic drugs can be effectively reduced, and the drug sensitivity of tumor cells is improved.

The invention relates to a PI3K and MTH1 targeting drug composition and applications thereof. The small-molecule targeting drug composition and a drug preparation provided by the invention comprise afirst preparation formed by a PI3K inhibitor or a pharmaceutically-acceptable carrier thereof, and a second preparation formed by a MTH1 inhibitor or a pharmaceutically-acceptable carrier thereof. Thecompatibility is reasonable. The combination of the two preparations can improve the drug sensitivity of the PI3K inhibitor, play the role of the MTH1 small-molecule inhibitor in the anti-tumor aspect and increase the treatment effect of the PI3K inhibitor. Experiments prove that: the combined administration of the PI3K inhibitor and the MTH1 inhibitor obviously enhances the tumor cell activity inhibition compared with the single administration, reduces the single administration dosage, can reduce the drug toxicity, is expected to become a new tumor treatment scheme aiming at the non-ideal treatment effect of the PI3K inhibitor, and has wide application prospect.