63 results about "Hsp70" patented technology

The invention discloses application of spermidine in preparation of a medicine for relieving copper exposure injury, and relates to the field of biological medicine. The invention provides an application of spermidine in preparation of a medicine for relieving copper exposure injury, and the injury is liver injury and / or intestinal injury caused by copper exposure. Spermidine can reduce the copper content in serum and liver, promote the expression of liver copper transporters ATP7B and CTR1, copper death proteins FDX1, LIAS and Lip-DLAT, and reduce the oligomerization of HSP70 and DLAT proteins; meanwhile, transaminase activity in serum and liver and intestinal tissue damage are reduced. The medicine provided by the invention can improve intestinal health, improve liver copper metabolism capability and relieve body injury caused by copper exposure, effectively solves the problem that no reliable medicine exists for related injury caused by copper exposure, and is expected to be developed into a medicine or health food for preventing and treating copper exposure injury.

The invention discloses dsRNA of a targeted potato beetle heat shock protein HSP70-KDa3 gene as well as a preparation method and application of the dsRNA of the targeted potato beetle heat shock protein HSP70-KDa3 gene. In order to solve the problems that an existing RNAi target gene is prone to off-target, poor in field stability and the like, the potato beetle heat shock protein gene LdHSP70-KDa3 serves as an RNA interference target for the first time, and a double-stranded RNA molecule shown as SEQ ID NO: 1 and a preparation method for preparing the double-stranded RNA are provided. Feeding experiments prove that the double-stranded RNA can efficiently silence target genes, the survival rate of potato beetle larvae is remarkably reduced, and feeding and growth development of the potato beetle larvae are inhibited. In addition, the invention further provides a biological preparation containing the double-stranded RNA and application of the biological preparation in prevention and treatment of potato beetles. The dsRNA targeting the HSP70-KDa3 gene provided by the invention has the characteristics of high efficiency, specificity, environmental friendliness and the like, and a new technical scheme is provided for green prevention and control of potato beetles.

The invention discloses a chimera for targeted degradation of GPX4 based on HSP70 protein as well as a preparation method and application of the chimera, and belongs to the technical field of biological medicines. According to the invention, 12 chimeras for targeted degradation of GPX4 are prepared by using the technology. The HSP70 molecular chaperone complex mediated protein targeted degradation chimera provided by the invention can rapidly and durably induce the degradation of GPX4. Meanwhile, the chimeras have obvious anti-proliferative activity on GPX4 high-expression cell strains and high-selectivity induction of ferroptosis of cells, and have important significance on tumor targeted therapy and drug resistance overcoming.

The invention belongs to the field of molecular marker screening of aquatic animals, and provides a KASP molecular marker for identifying high temperature resistance of procambarus clarkii and application of the KASP molecular marker. According to the procambarus clarkia high-temperature-resistant gene Hsp70-1 and the procambarus clarkia high-temperature-resistant gene Hsp70-2 disclosed by the invention, two SNP (Single Nucleotide Polymorphism) sites of the procambarus clarkia high-temperature-resistant gene Hsp70-1 and the procambarus clarkia high-temperature-resistant gene Hsp70-2 are remarkably related to high-temperature resistance, Hsp70-1-Hap1 haplotypes and Hsp70-2-Hap1 haplotypes are high-temperature-resistant dominant haplotypes, and the application potential of high-temperature-resistant application through combination of the double genes of KSAP markers developed aiming at the loci are good in typing effect, high in specificity, good in stability, convenient to detect, economical and efficient, and can be widely applied to breeding of high-temperature-resistant varieties of the procambarus clarkii. The KASP marker disclosed by the invention can screen out the procambarus clarkii with the SNP haplotype combination with the high-temperature-resistant advantage, and meets the technical requirements of high-temperature-resistant molecule-assisted breeding of the procambarus clarkii.

Disclosed is a novel class of fusion proteins to recruit the cell's innate chaperone machinery, specifically the Hsp70-mediated system, to specifically reduce TDP-43-mediated protein aggregation and associated protein conformational diseases.

The invention relates to the technical field of biological medicine, and provides application of a PDLIM4 inhibitor in preparation of a medicine for regulating and controlling sensitivity of gastric cancer to cis-platinum. According to the present invention, the PDLIM4 inhibitor is applied to the preparation of the drug for regulating the sensitivity of the gastric cancer cells to the cis-platinum, and the expression of the PDLIM4 in the gastric cancer cells is inhibited so as to reduce the expression of the HSP70 and promote the DNA damage signal channel, such that the sensitivity of the gastric cancer cells to the cis-platinum is enhanced;

The invention provides application of combination of an HSP70 inhibitor and sorafenib in treatment of mTOR activated liver cancer, and belongs to the technical field of drug combination. According to the invention, the HSP70 inhibitor is used as a sorafenib sensitizer, so that the drug resistance of hepatoma carcinoma cells to sorafenib caused by activation of mTOR is overcome, the sensitivity of the mTOR activated hepatoma carcinoma cells to sorafenib is improved, and the occurrence of ferroptosis is promoted, thereby enhancing the anti-tumor effect of sorafenib.

The invention discloses an HSP70-targeting chimeric antigen receptor-macrophage and application thereof in treatment of noise-induced hearing loss, an extracellular domain of the HSP70-targeting chimeric antigen receptor comprises an HSP70 specific binding fragment, an intracellular domain comprises an IL-4 signal channel functional element, a signal switch type CAR structure of the HSP70 is formed, and the macrophage can be used for treating noise-induced hearing loss, so that the HSP70-targeting chimeric antigen receptor-macrophage can be used for treating noise-induced hearing loss. The HSP70-targeted chimeric antigen receptor-macrophage can be used for preparing the HSP70-targeted chimeric antigen receptor-macrophage, is used for mediating polarization of the macrophage to an M2 type and exerting an anti-inflammatory function, is proved to be capable of specifically responding to an inner ear inflammation microenvironment, switching an anti-inflammatory phenotype and protecting hair cells and auditory nerves, can be used for treating noise-induced hearing loss, and can be used for preparing the HSP70-targeted chimeric antigen receptor-macrophage. The limitation that traditional hearing-aid equipment supports treatment on symptoms is broken through, and the hearing-aid device has a remarkable application prospect.

This invention relates to a detection kit and preparation method for enhancing the detection efficacy of autoimmune encephalitis (CBA) antibodies. The kit comprises genetically engineered 293T cells stably integrating and co-expressing the eIF2α S52A mutant and HSP70, and transiently transfected with CBA-associated antigens. The preparation method includes constructing a co-expression vector, establishing a stable transfection cell line, stress preconditioning treatment, antigen transfection, and kit assembly. A method for assessing antibody affinity maturation using this kit is also provided. By synergistically modifying detection cells at three levels—translational regulation, protein folding, and anti-apoptosis—the invention significantly increases antigen expression, reduces apoptosis, and improves detection sensitivity and specificity. Furthermore, it integrates antibody affinity assessment into CBA detection for the first time, providing auxiliary information for clinical staging.

A recombinant heat shock protein (hsp70) or domains thereof is derived from filarial worm Setaria digitata or Homo sapiens so as to provide therapeutic and prophylactic anti-viral agents against respiratory viral infections. In that respect, a method of preparation of the recombinant heat shock protein (hsp70) is used. And the recombinant heat shock protein (hsp70) or domains thereof may be used for treatment and / or prophylaxis of one or more symptoms of respiratory viral infections in a subject.

The application discloses a plant coding gene and protein with improved cadmium resistance and promoted biomass and a transgenic strain. The application carries out RNA-seq sequencing on switchgrass under cadmium stress treatment, screens a differential expression gene with the highest up-regulation fold, and genome annotation shows that the gene codes a member of a heat shock protein 70 family (Hsp70), a chaperone BiP (Binding Protein) protein, and the gene is named as PvBiP2. An overexpression vector of the gene is constructed and is transferred into a cadmium-sensitive yeast mutant strain (ycf1), and the growth condition of the transgenic yeast on a cadmium-containing culture medium is obviously better than that of a control group. Overexpression of the PvBiP2 gene in switchgrass is found to significantly improve the cadmium resistance of the transgenic switchgrass and promote the biomass of the switchgrass.

The invention relates to the technical field of cell culture. The invention provides a liver cancer tumor antigen-loaded DC-CIK cell as well as a preparation method and application thereof. The preparation method comprises the following steps: (1) incubating a liver cancer cell under an acidic condition, and centrifuging to obtain supernate; (2) centrifuging the supernate at a high speed, collecting precipitate, and drying to obtain the liver cancer tumor antigen peptide; (3) mixing the liver cancer tumor antigen peptide with Hsp70 protein, and reacting to obtain compound protein; (4) mixing the compound protein and the DC cells, and co-culturing to obtain modified DC cells; and (5) mixing the modified DC cell and the CIK cell, and co-culturing to obtain the DC-CIK cell loaded with the liver cancer tumor antigen. The Hsp70 protein is combined with the liver cancer tumor antigen peptide, so that the presentation efficiency of the DC cells is improved. By dynamically regulating and controlling parameters such as proportion, time and cell factors, the specific killing ability of the CIK cells is improved.

The invention discloses an application of a corn Zm00001eb409950 gene and an encoding protein thereof in improving or regulating corn kernel traits, a breeding method and a product, and relates to an application of the Zm00001eb409950 gene related to the corn kernel traits in the aspect of high-yield corn breeding, and a breeding method for improving the corn kernel traits. In the gene breeding research process, it is found that the corn gene Zm00001eb409950 for coding the heat shock protein HSP70-22 is related to the characters of corn kernels, and the hundred-grain weight and the vitamin E content of the corn kernels can be increased by overexpressing the gene in corn. When the gene is used for high-yield corn breeding, the breeding period is short, the efficiency is high, and the nutrition of corn kernels can be improved while the corn yield can be accurately improved.

The invention provides a method for cultivating high-temperature-resistant barley pests, which comprises the following steps: putting barley pest larvae under a high-temperature condition for intermittent high-temperature domestication treatment: culturing for 24 hours under a proper-temperature condition after 24 hours of high-temperature treatment each time, and the high temperature is 35 DEG C. Experimental results show that after intermittent high-temperature domestication treatment, CTmax and LTmax of the barley pests are remarkably improved, and the relative content of HSP70 generated under the same high-temperature stress is lower than that of undomesticated barley pests. In addition, the heat tolerance generated by temperature domestication has a certain genetic effect. The invention provides a method for effectively improving the heat resistance of the barley pests, and a high-temperature-resistant barley pest variety is cultivated through the method and has important practical application value.

The invention discloses a blood metabolism marker for screening heat-stress-resistant dairy cows and application of the blood metabolism marker. The method comprises the following steps: firstly, under typical heat stress environmental conditions, collecting indexes such as rectum temperature, respiratory rate, milk yield change and HSP70, Cortisol, potassium ions and the like in serum of the cows in the lactation period, and comprehensively scoring the heat stress response capability of individual cows based on an entropy weight TOPSIS model to construct a heat stress resistant group and heat sensitive group reference group; on the basis, blood samples of two groups of dairy cows are collected, non-targeted metabolome detection is carried out by adopting a liquid chromatography-mass spectrometry technology, differential metabolites remarkably related to the heat tolerance of the dairy cows are screened out through multivariate statistical analysis, and 6-ketoprostaglandin F1 alpha is further identified as a candidate metabolic marker. And a heat stress tolerance identification model is constructed. The method can be used for molecular level evaluation of heat resistance of dairy cattle individuals and heat-resistant cattle screening, has the advantages of high stability, strong specificity, good generalizability and the like, and is suitable for dairy cattle seed selection, breeding and feeding management in a high-temperature environment.

The invention discloses an EML4-ALK targeted degradation agent based on molecular chaperone HSP70 mediation as well as a preparation method and application thereof, and belongs to the technical field of medicines, the degradation agent does not depend on von Hippel-Lindeau E3 ligase and Cerebron E3 ligase ligands, and depends on a specific HSP70 molecular chaperone degradation pathway in cancers. Compared with the existing EML4-ALK degradation agent, the HSP70 molecular chaperone EML4-ALK degradation agent disclosed by the invention has the advantages that the anti-tumor activity is obviously improved, and the target spot selectivity is improved by more than 7 times. The degradation agent is simple in synthetic route and mild in reaction condition, can be used for being developed into a new generation of EML4-ALK targeted drugs, and has great clinical application value and considerable market potential.

Provided in the present invention are a heterobifunctional compound for targeted degradation of BRD4 based on HSP70, preparation, and use, belonging to the technical fields of pharmaceutical synthesis and chemical engineering. In the present application, an HSP70 inhibitor is selected as a ligand moiety A that binds to HSP70, a BRD4 inhibitor is selected as a ligand moiety B that binds to BRD4, and the ligand A of HSP70 and the ligand B of BRD4 are linked by means of a linking chain, Linker, to obtain a series of bifunctional degradation agents that can degrade BRD4 to different degrees. The obtained degradation agents have the characteristics of high selectivity and strong activity, and can overcome the disadvantages of BRD4 inhibitors, such as poor selectivity for tumor tissues and strong toxic and side effects.

The invention discloses an application of mexatinib as a copper death inhibitor in preparation of a medicine for preventing and treating copper death related diseases, and relates to the technical field of medicines. Cell and mouse experiments prove that the Merestinib remarkably recovers the levels of Fe-S cluster protein (LIAS / DLAT) and esterification protein (FDX1) related to copper death and reduces the level of heat shock protein HSP70, so that the sensitivity of various cells to copper death is reduced, and the recovery effect on acute liver injury is enhanced. Meanwhile, the Merestinib can also obviously reduce the levels of glutamic oxalacetic transaminase and glutamic-pyruvic transaminase in serum and the levels of inflammatory factors IL-1beta, IL-6 and TNF-alpha, effectively promotes the repair of liver tissues and plays an anti-inflammatory role. The invention provides theoretical support for treating copper death related diseases.

The present invention provides a peptide containing 8 or more consecutive amino acid residues in an amino acid sequence of any of SEQ ID NOS: 1 to 15 and consisting of 11 or less amino acid residues.

Provided herein is an agent that targets HSP70, such as antibody and chimeric antigen receptor.Provided is a method for treating cancer, comprising administering an effective amount of an agent that targets HSP70 to a patient in need thereof.HSP70-specific antibody can enhance the uptake of HSP70 by antigen-presenting cells. TIFF2023523890000061.tif79128

The application discloses a chimeric antigen receptor-macrophage targeting HSP70 and application thereof in the treatment of noise-induced hearing loss, wherein the extracellular domain of the chimeric antigen receptor targeting HSP70 comprises an HSP70 specific binding fragment, and the intracellular domain comprises an IL-4 signal pathway functional element, forming a'signal switch type' CAR structure targeting HSP70, which can be used for preparing the chimeric antigen receptor-macrophage targeting HSP70 and mediating the polarization of the macrophage to M2 type and exerting the anti-inflammatory function. It has been verified that the chimeric antigen receptor-macrophage targeting HSP70 can specifically respond to the inner ear inflammatory microenvironment, switch the anti-inflammatory phenotype and protect the hair cells and auditory nerves, and can be used for treating the noise-induced hearing loss, breaking through the limitation of the symptomatic support treatment of the traditional hearing aid device and having a significant application prospect.

The present disclosure provides compositions and methods of treating or preventing neurodegenerative diseases, including tau-related diseases or tauopathies. A variant or mutant of a heat shock protein, such as an Hsp70 family member protein, may be used in the present method. Alternatively, a modulator of a heat shock protein may be used.

The invention belongs to the technical field of biological medicines, and provides a heat stress protein HSP70 inhibitor and application thereof in preparation of antitumor drugs. Experiments prove that the heat stress protein HSP70 inhibitor can enhance the replication capacity of oncolytic viruses in tumor cells and enhance the anti-tumor immune activation capacity at the same time; the invention further proves that the oncoVV-shHSP70 can effectively inhibit the expression of the HSP70 protein, so that the survival rate of various cancer cells can be obviously reduced, the effect is obviously superior to that of a control virus oncoVV only lacking the TK gene, and meanwhile, the oncoVV-shHSP70 can promote the infiltration of CD8 < + >-T cells in tumor tissues. The HSP70 inhibitor can be used for preparing an anti-tumor virus drug, particularly, the HSP70 inhibitor and the vaccinia virus are recombined into a recombinant vector, the advantages of the HSP70 inhibitor and the vaccinia virus can be combined, a new target spot is provided for virus treatment of tumors, and the HSP70 inhibitor has a wide clinical application prospect.

The invention provides a chimeric polypeptide for enhancing immunogenicity of a tumor vaccine as well as a preparation method and application of the chimeric polypeptide. The chimeric polypeptide comprises at least two connected immunological enhancement molecular fragments, and the immunological enhancement molecular fragments comprise CD40L or a functional fragment thereof, and one or more selected from a group consisting of GM-CSF or a functional fragment thereof, HMGB1 or a functional fragment thereof, HSP70 or a functional fragment thereof, FLT3L or a functional fragment thereof, and OX40L or a functional fragment thereof. According to the chimeric polypeptide provided by the invention, the mRNA has a good immunological enhancement effect in cells, antigen-specific cellular immune response can be remarkably induced, and the chimeric polypeptide serving as an immunologic adjuvant can be used for constructing an anti-tumor drug (such as an mRNA vaccine) with a better tumor treatment effect.

The disclosure provides in one aspect compounds, and compositions comprising such compounds, that can be used to treat, ameliorate, and / or prevent cancer, especially colorectal cancer (CRC). In certain embodiments, the compounds of the disclosure inhibit HSP70. In other embodiments, the compounds of the disclosure promote or increase immune cell recruitment to a cancer. In yet other embodiments, the compounds of the disclosure promote and / or increase immune cell infiltration in a cancer.

The invention provides an anti-eperythrozoon ovine HSP70 protein polyclonal antibody as well as a preparation method and application thereof, and belongs to the technical field of bioengineering. The polyclonal antibody disclosed by the invention is prepared by immunizing an animal with an immunogen containing 109th-266th amino acids of the eperythrozoon ovine HSP70 protein, and has the characteristics of high titer and strong specificity. The preparation method of the polyclonal antibody comprises the steps of gene synthesis, protein expression and purification, animal immunization, antibody purification and the like. The invention also provides an application of the polyclonal antibody in immunological detection such as Western Blot, ELISA (Enzyme-Linked Immunosorbent Assay) and the like, and a detection kit containing the polyclonal antibody. The polyclonal antibody provides a core reagent for serological diagnosis of sheep eperythrozoonosis, and has important application value.

Provided herein is a gene therapy for BAG3 (B-cell Lymphoma 2-Associated Anthanogene 3), e.g., using an adeno-associated virus (AAV) vector. The promoter of the vector may be a MHCK7 promoter, a cardiac troponin T (hTNNT2) promoter, a heat shock protein 70 (HSP70) promoter, or a ubiquitin C (UBC) promoter. The capsid may be an AAVrh.74 or AAV9 capsid or a functional variant thereof. In certain embodiments, the capsid is an AAVrh.74 capsid or functional variant thereof. Other promoters or capsids may be used. Further provided are methods of treatment, such as by intravenous, intracoronary, intracarotid or intracardiac administration of the AAV vector, and other compositions and methods.

The invention belongs to the technical field of gene editing and molecular diagnosis, and particularly relates to a CRISPR-Cas system for improving trans-cleavage activity by using a molecular chaperone and application of the CRISPR-Cas system, and the CRISPR-Cas system comprises 1pM-1mM Cas enzyme, 1pM-1mM CrRNA, a 1 * reaction buffer solution, 0.1 pM-1mM target substrate, 1nM-1mM ssDNA reporter gene and 1pM-1mM molecular chaperone. According to the design, molecular chaperones ClpB, HSP70, Spy or HSP20 are added into a CRISPR-Cas system, so that the Cas enzyme trans-cleavage activity can be improved to different degrees, and the detection sensitivity is enhanced.

The present invention relates to the technical field of Microsporidia cryopreservation. Provided is a cryoprotectant for Enterocytozoon hepatopenaei. The cryoprotectant is mainly prepared from glycerol, dimethyl sulfoxide, and propylene glycol, with PBS buffer as a base solution. A volume percentage ratio of the raw materials dimethyl sulfoxide, glycerol, propylene glycol and PBS buffer is 10%:10%:10%:70%. The raw materials of the cryoprotectant are preferred, such that the obtained cryoprotectant achieves the optimal effect in indicators such as the mortality rate of Enterocytozoon hepatopenaei, the infection load in healthy shrimps, and the influence on polar tube protein 2 (EHP-ptp2) and heat shock protein 70 (hsp70). The present invention lays the foundation for achieving indoor preservation of Enterocytozoon hepatopenaei. The present invention solves the technical problem in the prior art that no cryoprotectant or preservation technique suitable for Enterocytozoon hepatopenaei is currently available.