194 results about "Hsp70" patented technology

The present invention relates to compounds, and methods utilizing compounds, which exhibit one or more of the following properties: i) disrupts organization of an actin cytoskeleton of a cell; ii) disrupts organization of a microtubule network of a cell; iii) induces accumulation of tubulin at centrosomes but does not induce accumulation of tubulin in a nucleus of a cell; iv) induces accumulation of tubulin at centrosomes at a concentration of 500 nM or less within four hours; v) induces accumulation of Hsp70 and has weak-to-moderate proteasome inhibitory activity; and vi) does not have proteasome inhibitory activity when assayed on purified proteasomes.

The present invention relates to a pharmaceutical composition for treating heart diseases, neurodegenerative diseases, and diseases and conditions caused by apoptosis, which contains a conjugate of a heat shock protein (Hsp) and a protein transduction domain (PTD). According to the present invention, PTD-Hsp70 effectively suppresses apoptosis under low-oxygen conditions.

The present invention relates to methods and compositions for eliciting an immune response and the prevention and treatment of primary and metastatic neoplastic diseases and infectious diseases. The methods of the invention comprise administering a composition comprising an effective amount of a complex, in which the complex consists essentially of a heat shock protein (hsp) noncovalently bound to an antigenic molecule. Optionally, the methods further comprise administering antigen presenting cells sensitized with complexes of hsps noncovalently bound to an antigenic molecule. "Antigenic molecule" as used herein refers to the peptides with which the hsps are endogenously associated in vivo as well as exogenous antigens / immunogens (i.e., with which the hsps are not complexed in vivo) or antigenic / immunogenic fragments and derivatives thereof. In a preferred embodiment, the complex is autologous to the individual. In a specific embodiment, the effective amounts of the complex are in the range of 0.1 to 9.0 micrograms for complexes comprising hsp70, 5 to 49 micrograms for hsp90, and 0.1 to 9.0 micrograms for gp96.

The present invention relates to pharmaceutical compositions and methods for the prevention and treatment of autoimmune diseases, infectious diseases, neurodegenerative diseases, and primary and metastatic neoplastic diseases. In the practice of the invention, the compositions are employed comprising: (a) a heat shock protein (hsp) or an alpha(2)macroglobulin (alpha2M); (b) a saponin; and, optionally, (c) an antigenic molecule. The antigenic molecule displays the antigenicity of an antigen of: (a) a cell that elicits an autoimmune response; (b) an agent of an infectious disease; (c) a cancerous cell; or (d) a cell or structure associated with a neurodegenerative or amyloid disease. The hsps that can be used in the practice of the invention include but are not limited to hsp70, hsp90, gp96, calreticulin, hsp 110, grp 170, and PDI, alone or in combination with each other. The antigenic molecule can be covalently or noncovalently bound to the hsp or alpha2M, free in solution, and / or covalently bound to the saponin. The compositions of the invention can be administered alone or in combination with the administration of antigen presenting cells sensitized with an hsp- or alpha2M-antigenic molecule complex.

The present invention relates to receptors for heat shock proteins (HSPs), such as gp96, Hsp70 and Hsp90. The heat shock receptor is associated with the cell membranes of a subset of antigen presenting cells, such as macrophages and dendritic cells. The present invention relates to the use of the heat shock protein receptor positive cells, heat shock protein receptor protein, and heat shock protein receptor genes in methods for screening a molecule for the ability to modulate heat shock protein levels or activities.

Disclosed are compounds and methods of using compounds of the invention for treating a subject with a proliferative disorder, such as cancer, and methods for treating disorders responsive to Hsp70 induction and / or natural killer induction. Also, disclosed are pharmaceutical compositions comprising compounds of the invention and a pharmaceutically acceptable carrier.

The present invention relates to the technical field of biology, particularly to development and applications of a heat shock induced Cas9 enzyme transgene danio rerio. The present invention firstly provides a Cas9 enzyme expression vector, which utilizes a heat shock induced promoter HSP70 to drive the expression of a downstream Cas9 gene. According to the present invention, the Cas9 enzyme expression vector and Tol2 mRNA are co-injected into wild type danio rerio single cell fertilized egg, and selection is performed to obtain the heat shock induced Cas9 enzyme transgene danio rerio, such that the gene editing research of the CRISPR-Cas9 system in the danio rerio is successfully achieved, and the know-out of the MC4R gene in the transgene danio rerio is firstly achieved; and the Cas9 enzyme expression vector is further suitable for heat shock induced gene knockout, gene knock-in, gene expression modification and other applications of other fishes.

The present invention concerns a method for modulating the enzymatic activity of an enzyme, wherein said enzyme interacts with BMP, said method comprising the step of administering or inducing Hsp70, or a functional fragment or variant thereof, in a form suitable for allowing interaction between BMP and Hsp70, or said functional fragment or variant thereof, and thereby modulating the enzymatic activity of an enzyme interacting with BMP.

The present invention relates to methods of improving a treatment outcome comprising administering a heat shock protein (HSP) preparation or an α-2-macroglobulin (α2M) preparation with a non-vaccine treatment modality. In particular, an HSP preparation or an α2M preparation is administered in conjunction with a non-vaccine treatment modality for the treatment of cancer or infectious diseases. In the practice of the invention, a preparation comprising HSPs such as but not limited to, hsp70, hsp90 and gp96 alone or in combination with each other, noncovalently or covalently bound to antigenic molecules or α2M, noncovalently or covalently bound to antigenic molecules is administered in conjunction with a non-vaccine treatment modality.

The present invention relates to methods of improving a treatment outcome comprising administering a heat shock protein (HSP) preparation or an alpha-2-macroglobulin (alpha2M) preparation with a non-vaccine treatment modality. In particular, an HSP preparation or an alpha2M preparation is administered in conjunction with a non-vaccine treatment modality for the treatment of cancer or infectious diseases. In the practice of the invention, a preparation comprising HSPs such as but not limited to, hsp70, hsp90 and gp96 alone or in combination with each other, noncovalently or covalently bound to antigenic molecules or alpha2M, noncovalently or covalently bound to antigenic molecules is administered in conjunction with a non-vaccine treatment modality.

The present invention relates to methods and compositions for eliciting an immune response and the prevention and treatment of primary and metastatic neoplastic diseases and infectious diseases. The methods of the invention comprise administering a composition comprising an effective amount of a complex, in which the complex consists essentially of a heat shock protein (hsp) noncovalently bound to an antigenic molecule. "Antigenic molecule" as used herein refers to the peptides with which the hsps are endogenously associated in vivo as well as exogenous antigens / immunogens (i.e., with which the hsps are not complexed in vivo) or antigenic / immunogenic fragments and derivatives thereof. In a preferred embodiment, the complex is autologous to the individual. The effective amounts of the complex are in the range of 10-600 micrograms for complexes comprising hsp70, 50-1000 micrograms for hsp90, and 10-600 micrograms for gp96. The invention also provides a method for measuring tumor rejection in vivo in an individual, preferably a human, comprising measuring the generation by the individual of MHC Class I-restricted CD8+ cytotoxic T lymphocytes specific to the tumor. Methods of purifying hsp70-peptide complexes are also provided.

A non-natural HSP70 activating region that activates dendritic cells. Polypeptides that bind to the HSP70 activating region can be used to treat autoimmune diseases, such as vitiligo, by binding to HSP70 and preventing HSP70 form activating dendritic cells. The HSP70 binders can be constructed in the form of fusions proteins with a trimerizing structural element that may associate to form a trimeric complex. Pharmaceutical compositions and methods for treating vitiligo using the HSP70 binding proteins, fusion proteins and complexes.

The invention relates to a method for culturing gamma-delta-T cells, and in particular relates to a method for in-vitro amplification of gamma-delta-T cells, wherein the method comprises the following operating steps of: pre-coating a T75 culture bottle by a TCR-gamma-delta resisting antibody and CD28McAb for later use use; isolating the peripheral blood mononuclear cell (PBMC) of a patient; regulating the PBMC concentration to 1*10<6> 6 / ml by a serum-free culture medium which contains 5% of autologous plasma, and transferring PBMC cell suspension into the T75 culture bottle; adding an initial culture medium which contains proper concentrations of Zoledronat, HSP70, 1L-2, 1L-7 and 1L-15; culturing in a saturated humid environment containing 5% of CO2 at 37 DEG C; depending on growth situation of the cell, changing the culture medium every 2-3days, to control the cell concentration at about 2.5*10<6> / ml; meanwhile, compensating full doses of Zoledronat, HSP70, 1L-2, 1L-7 and 1L-15; and continuously culturing for 12-16days, to obtain a great amount of gamma-delta-T cells which are comparatively high in purity.

The present disclosure provides methods for increasing drought resistance and heat resistance of a plant. The methods encompass expression of at least one heat shock protein (HSP) from the group consisting of HSP40, HSP60 or HSP70 together with a phosphoenolpyruvate carboxylase (PEPC) comprising an aspartic acid (D) at a position that corresponds to the position 509 of SEQ ID NO: 4, in the plant. In comparison to a plant not manipulated in this manner, the disclosed, genetically-modified, plants display improved drought resistance and heat resistance. Also provided are plants that can be obtained by the method according to the invention, and nucleic acid vectors to be used in the described methods.

The invention discloses a test kit of HSP70 double antibody sandwich method used in the sample drawn from human, big mice and small mice, and comprises a kit body, an enzyme-labeled plate of solidified HSP70 monoclonal antibody provided in the kit body and substances provided in the kit body; the substances provided in the kit body comprises a HIS-HSP70 protein standard reagent, a HSP70 polyclonal antibody labeled by biotin, a sample dilution solution, a cleaning buffer solution, an antibody solution, a horseradish enzyme-labeled avidin, a horseradish enzyme-labeled avidin dilution solution, a substrate visualization solution A solution, a substrate visualization solution B solution and a stop solution. The invention has the advantages of high detection sensitivity, big accuracy and low cost; the invention can detect the HSP70 protein in a cell lysis solution, a tissue extracting solution, plasma and serum drawn from human, big mice and small mice at the same time.

This document provides methods and materials related to treating cancer. For example, methods and materials that include using CD40L polypeptide, an hsp70 polypeptide, and a cytotoxic polypeptide to trigger an immune response directed against cancer cells are provided.

Disclosed are compounds of Formula (I) and methods of using compounds of the invention for treating a subject with a proliferative disorder, such as cancer, and methods for treating disorders responsive to Hsp70 induction and / or natural killer induction. Also, disclosed are pharmaceutical compositions comprising compounds of the invention and a pharmaceutically acceptable carrier.

The invention relates to the field of medical diagnostics. More specifically, the invention relates to methods to diagnose or screen for inflammatory conditions or disease, including auto-inflammatory disease and affective disorder, in a subject, preferably a human subject, by assaying for a marker for an inflammatory disease. Provided is a method to diagnose, screen for or predict the development of an affective disorder (AD), preferably bipolar disorder (BP), in a subject, the method comprising determining the level of at least one, preferably at least two, more preferably at least three, most preferred at least four, AD-specific gene product(s) in a biological sample isolated from the subject, preferably peripheral blood monocytes, wherein the gene is selected from the group comprising ATF3, phosphodiesterase 4 B, CXCL2, BCL2-related protein A2, Dual specificity phosphatase 2, TNFα-induced protein 3 / A20, BTEB1 CXCL3, Chemokine CCL-3 like, CCL-4, CCL20, CX2CR1, Amphiregulin, Thrombomodulin, Heparin-binding EGF-like growth factor, DNA-damaged inducible transcript, V28 chemokine-like receptor, TRAIL. MAPK6, B4BP4, PBEF1, Thrombospondin 1, MAFF, HSP70, CCL2, MCP-3, CCR2, CX3CR1, DOK1, HBB, G-gamma globin, THBD, PHLDA1, DTR and GNLY.

The invention discloses a tetrahymena transgenic carrier containing HSP70 promoter and GFP and preparation method and use thereof. Plasmid T-GFP is constructed by using plasmid rDNA-GFP in the methods such as enzyme cutting and PCR enzyme cutting site mutation; thermophile tetrahymena genome DNA is used for constructing plasmid T-HSP702 in the methods such as PCR augmentation and clone; Plasmids T-GFP, T-HSP702 and pD5H8 are used for construction and finally obtaining plasmid HSP702-GFP-pD5H8 by enzyme cutting and connection. The carrier contains HSP702 promoter, thereby being capable of realizing high-efficient expression of exogenous gene; the carrier contains replaceable exogenous gene gfp so that an exogenous gene expression system is realized for tetrahymena by replacing different exogenous genes; with the sieving effect of paromomycin medicine, the carrier replaces most rDNAs originally in the tetrahymena so that the exogenous genes are largely increased in the tetrahymena so as to realize genetic transformation of target genes. The method in the invention is easy and has convenient operation, and the carrier can be used for detection of environmental tributyl tin in transfection in tetrahymena.

The present disclosure is directed to new compounds useful as modulators of Heat Shock Proteins (HSP). In particular, the present disclosure provides new small molecule peptide-derived compounds having HSP modulation activity, especially Hsp70 modulation activity, and methods of preventing or ameliorating beta-amyloid or polyglutamine aggregation, decreasing cell proliferation, or increasing chaperon activity of the HSPs.

The invention belongs to the field of application of feed additive, and relates to a porcine heat stress resistance selenium-rich composite bacteria feed additive and application thereof. Saccharomyces cerevisiae, lactobacillus acidophilus and streptococcus thermophilus are selected as strains, inoculated in a proper fermentation broth containing sodium selenite, transformation of selenium and probiotics growth accelerating agent in a volume ratio of 1:2:2, and fermented for 30 to 40 hours at a temperature of between 20 and 40 DEG C, throughput of 0.05m<3> / h, revolution of 70r / min and tank pressure of 0.04Mpa; and the selenium enriched composite bacteria preparation can be prepared through proper subsequent treatment. The daily gain and feed-weight ratio of a pig can be remarkably improved in a high-temperature environment by feeding the preparation, the oxidation resistance and immunity functions can be enhanced, the mRNA (messenger ribonucleic acid) level of heat shock proteins Hsp70 and Hsp27 can be reduced, and the effect of porcine heat stress resistance can be effectively played.

The present invention relates to the use of fragments of heat shock proteins for the treatment and / or prevention of autoimmune diseases such as arthritis or inflammatory diseases such as Inflammatory Bowel Diseases. Preferably bacterial and / or mammalian heat shock proteins belonging to the HSP70 families are used.

Compositions and methods for modulating HSP70 function, particularly for the targeted killing of cancer cells, are disclosed.

Methods and compositions for the detection, prevention and treatment of infectious diseases, primary and metastatic neoplastic diseases, including, but not limited to human sarcomas and carcinomas are described. In particular, specific antibodies are provided, which are capable of binding an epitope of Hsp70 that is extracellularly localized on diseased tissue and cells, in particular on tumor cells and infected cells.

The invention relates to a method for culturing gamma-delta-T cells, and more specifically relates to a method for in-vitro amplification of gamma-delta-T cells. The method comprises the following operating steps: pre-coating a T75 culture bottle with a TCR-gamma-delta resisting antibody and CD28McAb for later use; isolating peripheral blood mononuclear cells (PBMC) of patients; regulating PBMC concentration to 1*10<6> / ml with a serum-free culture medium which contains 5% of autologous plasma, and transferring the PBMC cell suspension into the T75 culture bottle; adding an initial culture medium which contains proper concentrations of Zoledronat, HSP70, Toll-like Receptors7 (TLR7) ligand, Levamisole (LMS), IL-2, IL-7 and IL-15; culturing in a saturated humid environment containing 5% of CO2 at 37 DEG C; according to growth situation of the cell, changing the culture medium every 2 to 3 days so as to control the cell concentration at about 2.5*10<6> / ml; meanwhile, compensating full doses of Zoledronat, HSP70, Toll-like Receptors7 (TLR7) ligand, Levamisole (LMS), IL-2, IL-7 and IL-15;; and continuously culturing for 12to 16 days so as to obtain a great amount of gamma-delta-T cells which are comparatively high in purity.

The present invention provides a host cell suitable for enhanced production of a protein product of choice characterised in that the host cell is genetically modified to cause over-expression of two or more helper proteins selected from a DnaJ-like protein (such as JEM1), an Hsp70 family protein (such as LHS1) and SIL1 wherein at least one of the over-expressed two or more helper proteins is selected from JEM1, LHS1 and SIL1, and wherein the DnaJ-like protein is not SCJ1.

The invention discloses an efficient and simple biological sensitive detecting method for heavy metal cadmium in seawater. Particularly, the method includes respectively placing Chinese Venuses in seawater containing heavy metal cadmium (two-valence Cd) and no cadmium (two-valence Cd), dissecting for 96 hours to obtain liver tissue of the Chinese Venuses, extracting total RNA (ribonucleic acid) and transcribing into cDNA (deoxyribonucleic acid), and measuring difference of expression quantity of HSP70 (hot shock protein 70) genes of the Chinese Venuses in an experiment group and that of the Chinese Venuses in a control group by a fluorescence quantitative PCR (polymerase chain reaction) method. The larger the content of the heavy metal cadmium (two-valence Cd) in water, the larger the relative expression quantity of HSP genes, and low-concentration cadmium (two-valence Cd) in water, which is hard to detect by analytic instruments, can be observed. The method can be used as a normal biological technique for detecting pollution level of the heavy metal cadmium in seawater and difference among different water areas, has the advantages of high analytic sensitivity, high comparison and the like and can be used to judge harmful risks of the heavy metal cadmium (two-valence Cd) to water areas and biological bodies, and irreparable loss caused by severe situation is avoided.

Compositions and methods for modulating HSP70 function, particularly for the targeted killing of cancer cells, are disclosed.