140 results about "Cellular death" patented technology

Embodiments of the present invention include methods of targeting acidosis (low pH) within the tumor microenvironment (TME) through the use of cathodic electrochemical reactions (CER). Low pH is oncogenic by supporting immunosuppression. Electrochemical reactions create local pH effects when a current passes through an electrolytic substrate such as biological tissue. Electrolysis has been used with electroporation (destabilization of the lipid bilayer via an applied electric potential) to increase cell death areas. However, the regulated increase of pH through only the cathode electrode has been ignored as a possible method to alleviate TME acidosis, which could provide substantial immunotherapeutic benefits. Here, ex vivo modeling shows that CERs can intentionally elevate pH to an anti-tumor level and that increased alkalinity promotes activation of naïve macrophages. Embodiments of the invention include pairing CER treatment protocols with existing electric field-based cancer therapies or use as a stand-alone therapy.

A method of promoting neuroprotection in a subject from axonal degeneration, neuronal cell death, and / or glia cell damage after injury, augmenting neuronal signaling underlying learning and memory, stimulating neuronal regeneration after injury, and / or treating a disease, disorder, and / or condition of the nervous system in a subject in need thereof includes administering to the subject a therapeutically effective amount of a 15-PGDH inhibitor.

The invention discloses application of beta-nicotinamide mononucleotide in regulation and control of gene editing efficiency, belongs to the field of gene editing treatment, and finds that the beta-nicotinamide mononucleotide (NMN) can efficiently inhibit the activity of CRISPR-Cas9, CRISPR-Cas12 and CRISPR-Cas13 systems in a broad-spectrum manner for the first time. The application comprises emergency blocking of off-target effect in gene editing clinical treatment, biological safety prevention and control of a virus vector gene editing system, and CRISPR activity regulation and control of in-vitro non-diagnostic purpose. Experiments show that NMN can inhibit CRISPR-mediated gene damage and cell death in a cell model, the inhibition efficiency in an in-vitro enzyme digestion system reaches 68.7%, and cell growth or transfection efficiency is not affected. The invention provides an innovative solution for safe application of CRISPR (clustered regularly interspaced short palindromic repeats) technology, and the NMN is approved to be taken orally as a health care product, so that the NMN has extremely strong clinical application potential. Compared with the existing CRISPR (clustered regularly interspaced short palindromic repeats)-resistant protein or synthetic small-molecule inhibitor, the NMN has the advantages of endogenous property, high biocompatibility, good oral safety and the like.

The invention belongs to the technical field of biological medicines, and particularly relates to application of a marine small molecule peptide and an active variant thereof in preparation of a medicine for treating skin diseases, the marine small molecule peptide and the active variant thereof can effectively inhibit keratinocyte pan apoptosis induced by TNF-alpha and IFN-gamma, the formation of a PANoptosome complex is blocked through a multi-target synergistic effect, and the effect of treating the skin diseases is achieved. The oxidative stress is reduced, and mitochondria is stabilized, so that a skin inflammatory cell death network is inhibited from the source. The variant has the same high sequence as the peptide, retains the activity of inhibiting cell pan-apoptosis, and has enhanced stability, skin permeability, in vivo half-life or efficacy. Based on the action mechanism, the peptide and the variant thereof can be used for preparing medicines for preventing and treating intractable skin diseases such as epidermis necrolysis, psoriasis, atopic dermatitis, skin lupus erythematosus and lichen planus. The invention also provides a composition containing the peptide or the variant thereof, and dosage forms comprise an external preparation and an injection.

The present disclosure provides recombinantly manufactured fusion proteins comprising a HERV-K (HML-2) Env protein fragment or an analog thereof linked to a human Fc fragment. Embodiments include the administration of the fusion proteins to patients having a disease or a disorder with the intention of mitigating and / or reducing the duration of symptoms associated with the condition or disease (for example but not limited to muscular weakness, paralysis and respiratory failure), and / or preventing symptoms associated with the condition or disease, for example, by preventing motor neuron degeneration and cell death in ALS patients associated with the condition or disease. Accordingly, “treatment” generally means both therapeutic treatment and prophylactic or preventative measures. Improvement after treatment may be manifested as a decrease or elimination of such symptoms, e.g., by a decrease or elimination of symptoms associated with ALS, and / or by a decrease in the duration of such symptoms.

The present disclosure provides recombinantly manufactured fusion proteins comprising a HERV-K (HML-2) Env protein fragment or an analog thereof linked to a human Fc fragment. Embodiments include the administration of the fusion proteins to patients having a disease or a disorder with the intention of mitigating and / or reducing the duration of symptoms associated with the condition or disease (for example but not limited to muscular weakness, paralysis and respiratory failure), and / or preventing symptoms associated with the condition or disease, for example, by preventing motor neuron degeneration and cell death in ALS patients associated with the condition or disease. Accordingly, "treatment" generally means both therapeutic treatment and prophylactic or preventative measures. Improvement after treatment may be manifested as a decrease or elimination of such symptoms, e.g., by a decrease or elimination of symptoms associated with ALS, and / or by a decrease in the duration of such symptoms.

The present application discloses an antiviral fusion protein. Specifically, the present application provides an antiviral fusion protein, which comprises a cell death inducing domain (lethal domain), a domain inhibiting the activity of the lethal domain (inhibitory domain) and a protease recognition sequence capable of removing or destroying the function of the inhibitory domain; the fusion protein has the activity of inducing cell death after being cut by a specific viral protease, thereby killing the cells infected by the virus in a targeted manner. The present application also discloses a programmable method for inducing the death of virus-infected cells, which comprises transferring the above-mentioned fusion protein or nucleic acid into cells so that the cells die before replication and assembly after being infected by the virus, thereby achieving timely and effective elimination of the virus.

Antimicrobial eyewear features frames infused with or coated with antimicrobial additives, thereby offering continuous protection by actively destroying and inhibiting the growth of bacteria, fungi, parasites, and some viruses. The lenses may also have an antibacterial coating that destroys and inhibits bacterial growth. In some examples, the lenses are treated with a specialized strengthening liquid, wherein the liquid contains nano components that release heavy metal ions capable of invading the cell walls of bacteria, leading to bacterial elimination, destroying DNA molecules and proteases within the bacterial cells, denature viral proteins, break DNA chains, and result in cell death. Additionally, the strengthening liquid reduces dehydrogenase activity and interacts with various protein groups within the cell, thereby reducing the activity of these groups and effectively inhibiting the growth of E. coli and other bacteria on the lens surface.

[Problem]The present invention demonstrates that, when added to the culture, DHMBA inhibits the proliferation of mouse inflammatory macrophage RAW264.7 cells, promotes their cell death, and reduces their cell number. It also demonstrates that DHMBA suppresses the increased production of inflammatory cytokines in RAW264.7 cells cultured with LPS, and in particular, DHMBA treatment suppresses osteoclast formation in RAW264.7 cells stimulated with LPS. Thus, the present invention provides a useful means of treating inflammatory diseases using DHMBA.[Solution]The present invention is characterized by having an anti-inflammatory effect by including 3,5-dihydroxy-4-methoxy benzyl alcohol (DHMBA) as an active ingredient.

The invention discloses a rice disease resistance defense regulation gene SRWD2 as well as an encoding protein and application thereof. According to the invention, a rice disease spot-like mutant tb18 is taken as an experimental material, a rice disease resistance defense regulation gene SRWD2 is separated through strategies such as MutMap positioning and transgene complementation, the nucleotide sequence of the gene is shown as SEQ ID NO.1, and the sequence of a protein coded by the gene is shown as SEQ ID NO.2. The biological function of the SRWD2 gene is analyzed, a theoretical basis is provided for clarification of a molecular mechanism of programmed cell death and defense reaction of plants, the gene mutation site is introduced into the plants through gene engineering or conventional means, the disease resistance can be remarkably enhanced, and the gene has important application value in the aspect of disease-resistant variety cultivation of the plants.

The invention discloses an application of an ST6GALNAC5 gene in prevention and treatment of swine Graisseria disease (a pathogenic bacterium causing the swine Graisseria disease by a haemophilus parasuis system), and the expression of the ST6GALNAC5 gene is inhibited in a targeted manner, so that adhesion and invasion of the haemophilus parasuis to host cells can be effectively inhibited, and cytopathy is reduced. The method is helpful for resisting cell death induced by haemophilus parasuis infection, so as to prevent the occurrence of the porcine Graisseria disease. Therefore, the ST6GALNAC5 gene can be used as an important target spot for treating the swine Graisseria disease, and has important clinical application prospects and molecular disease-resistant breeding values.

Provided herein are targeting constructs for sustained transgene expression of inducible cell death systems that include degron mutants and cereblon mutants. Also provided are pharmaceutical compositions comprising the targeting constructs, and methods for use of the same. The methods of use include methods of inducing cell death in a cell, and methods of treating patients in need thereof.

The present invention relates to novel anti-PD-1 (Planned Cell Death 1) antibodies and antigen binding fragments thereof for use in therapeutic and diagnostic methods, and compositions using the same.

The present application belongs to the technical field of coordination chemistry and biomedical science, and provides a multifunctional iridium (III) complex, a preparation method and application thereof. The multifunctional iridium (III) complex (Mito-Ir) is composed of an iridium (III) complex cation and a coordination anion shown in the following formula. Mito-Ir can efficiently target mitochondria, and also has the abilities of phosphorescence imaging, type I and type II active oxygen generation, and photocatalytic oxidation of nicotinamide adenine dinucleotide. Under light irradiation, Mito-Ir triggers severe mitochondrial dysfunction through the above synergistic effect, and then specifically activates the caspase-3 / GSDME signaling pathway, and significantly induces pyroptosis; this pyroptosis-based cell death mechanism can effectively overcome the apoptosis tolerance of tumor cells, and is accompanied by the release of a large amount of inflammatory factors and damage-associated molecular patterns, stimulates immunogenic cell death, and activates the body's anti-tumor immune response.

The MYC and NMYC transcription factors (TFs) play a key role in cell proliferation and are overexpressed in most cancer cells. However, in normal cells their overexpression triggers safeguard mechanisms promoting cell death and cellular senescence, which are bypassed in cancer cells. Here, the inventors reveal that in normal cells MYC binds to the Inositol 1,4,5-Trisphosphate Receptor type 1 (ITPR1) gene and upregulates its expression, triggering an ER-mitochondria calcium (Ca2+) transfer, which is involved in MYC-induced cell death and senescence. Supporting a tumor suppressive role of MYC / ITPR1 axis, ITPR1 expression is generally decreased in cancer and reactivation of this pathway induces cancer cell death. Nevertheless, some cancer cells, generally expressing high levels of MYCN and / or MYC, also express high level of ITPR1, which correlates with high expression of BCL2, encoding an inhibitor of ITPR1. Strikingly, in high-risk MYCN-amplified neuroblastoma, ITPR1 expression is controlled by NMYC and its level correlates with worse patient survival. In these cells, blocking the interaction between BCL2 and ITPR1, via an BCL2-BH4 domain inhibitor induces mitochondrial Ca2+ accumulation and cell death, and decreases tumor size. Thus, the present invention relates to a method for treating MYChigh cancer, and in particular NMYC--amplified neuroblastoma in a subject by administering an BCL2-BH4 domain inhibitor.

The invention belongs to the technical field of recombinant adeno-associated virus production, and discloses an rAAV production method and application. The invention provides an rAAV production method. The rAAV production method comprises the following steps: adding a cell death regulation inhibitor into a cell culture solution during rAAV production; the cell death regulation and control inhibitor is a cell apoptosis (Apoptosis) inhibitor and / or a necroptosis (Necroptosis) inhibitor. The production efficiency of the rAAV and the quality and purity of the rAAV product can be remarkably improved, the purpose of improving the quality of the rAAV product is achieved, the safety and druggability of rAAV related gene therapy products are further improved, and low-cost and large-scale production of the rAAV can be effectively promoted.

The invention provides a dual-targeting nano-material photosensitizer for cervical cancer as well as a preparation method and application of the dual-targeting nano-material photosensitizer. The folic acid modified poly-beta-cyclodextrin (poly-beta-CD) is used as a nano-carrier and is used for loading a photosensitizer PAP (PAP is pyropheophorbide a covalently connected PAAKRVKLD) coupled with a nuclear localization signal (NLSs). The finally prepared FA-CD-coated PAP nano material can specifically recognize cervical cancer cells of overexpressed folate receptors (FR), so that accumulation in tumor cells is remarkably enhanced. In addition, the encapsulated PAP can achieve accurate cell nucleus localization. Under an illumination condition, reactive oxygen species (ROS) generated by PAP accumulated in nuclei can instantly oxidize and damage a DNA chain or DNA repair enzyme, so that cell death is directly induced, and the anti-tumor effect of targeted photodynamic is greatly enhanced. The novel dual-targeting nano drug-loading system prepared by the invention solves the problems of poor targeting and biological solubility and limited treatment effect of a traditional photosensitizer, and provides an innovative intelligent targeting delivery strategy for in-situ cell nucleus photodynamic therapy.

This disclosure presents compositions of anti-ceramide antibodies and their antigen-binding fragments. [Solution] This disclosure further presents a method for preventing or inhibiting cell death in a subject requiring such prevention, comprising the step of administering an anti-ceramide antibody or antigen-binding fragment to the subject. Subjects requiring such prevention may be suffering from autoimmune diseases, GI syndrome, or GvHD.

The invention belongs to the technical field of cell cryopreservation, and particularly relates to a cell cryopreservation solution, application thereof and a cell cryopreservation method. A death inhibitor and a solvent are selected for specific cells, and the cell death process related to cytolytic organelle membrane damage is intervened from the molecular level, specifically, the solvent is used for reducing ice crystal formation inside and outside the cells, the membrane protection effect is exerted to achieve the high resuscitation motility rate, a programmed death pathway is further blocked in a targeted mode through the death inhibitor, and the cell death effect is improved. The programmed death after cell resuscitation is relieved, the delayed death rate of the resuscitated cells is reduced, the long-term cell fusion degree of the resuscitated cells is improved, and the long-term survival rate of the resuscitated cells is improved.

Compounds, compositions and methods for improving the viability and / or function of cells or for the in vitro, ex vivo or in vivo protection of cells, tissue, graft or organs from various damages are described. The reagents and composition are based on activation of the heat shock response activation and / or the antioxidant response and include for example. HSP90 co-factor inhibitor such as Celastrol or Celastrol analogs used alone or in combination with an adjunct agent (e.g., a NRF-2 activator, antioxidant, etc.). Therapeutic enhancement may also include increase in paracrine effector production and signaling. Methods for improving the resistance of cells, tissue, grafts or organs to damages or stress, such as hypoxic or oxidative stress-induced cell death, and / or for improving the viability and retention of transplanted or transfused cells are also described. Therapeutic treatment or prevention of ischemic injury (e.g. myocardial infarct, ischemia / reperfusion injury) and related stressors (hypoxia, oxidative stress, inflammation, sepsis / shock, etc) are also provided.

The present invention relates to a Fab-arm (Fab-arm) exchange prevention Fc variant, the effector function of which is reduced due to elimination of binding force with Fc [gamma] Rs and C1q, and the human antibody Fc domain variant of the present invention is a novel variant different from the conventional Fab-arm exchange prevention variant, which can overcome the Fab arm exchange phenomenon, which is the disadvantage of IgG4, and which does not bind to all human Fc [gamma] Rs and C1q, and which can be used as a novel human antibody Fc domain variant having a reduced effector function due to elimination of binding force with Fc [gamma] Rs and C1q. The compound does not bind to mouse and monkey Fc [gamma] Rs, has excellent blood half-life and thermal stability, and thus can be used for preventing immune cell / normal cell death (toxicity) caused by a therapeutic antibody or an antibody Fc region of an Fc-fusion protein drug.

Described herein is a DNA nanostructure-based platform that can modulate a number of cellular functions depending on the concentration and surface decoration of the nanostructure. Utilizing different peptides for surface functionalization of DNA nanostructures, lysosomal activity was able to be modulated which in turn translated into the control of cellular functionality, ranging from changes in cell morphology to modulation of immune signaling and cell death. This demonstrates the rational design of a new generation of versatile DNA-based nanoplatforms that can be used in various biomedical applications such as the development of combinatorial anti-cancer platforms, efficient systems for endolysosomal escape, and nanoplatforms modulating lysosomal pH.

The present invention relates to a method for reducing WST-8 to formazan based on NAD(P)H for determining the susceptibility of certain bacterial isolates to infection by certain bacteriophages, thereby allowing direct observation of the results measured as cell death of the target bacteria. The reduction of tetrazolium salts to formazan by NAD(P)H is used to determine the metabolic activity of cells and as an indicator of cell viability; whereas WST-8 is used to qualitatively measure the bacteriophage killing activity of the target bacteria. The present invention thus belongs to the field of medical biology, in particular to in vitro laboratory test methods.

The present disclosure provides inhibitors of one or more subunits of polycomb repressive complex 2 (PRC2) for use in the prevention or the treatment of an eye disorder in a subject in need thereof and methods for treating an eye disorder, e.g. non-cancer disorders, in a subject using a therapeutically effective amount of one or more inhibitors of a subunit of polycomb repressive complex 2 (PRC2).In certain embodiments of the methods of the disclosure, the eye disorders are characterized by degeneration or cell death of retinal neurons.In certain embodiments of the methods of the disclosure, the subunit of PRC2 is EZH1 or EZH2, and the inhibitor is an inhibitor of H3K27 trimethylation.

The present disclosure provides recombinantly manufactured fusion proteins comprising a HERV-K (HML-2) Env protein fragment or an analog thereof linked to a human Fc fragment. Embodiments include the administration of the fusion proteins to patients having a disease or a disorder with the intention of mitigating and / or reducing the duration of symptoms associated with the condition or disease (for example but not limited to muscular weakness, paralysis and respiratory failure), and / or preventing symptoms associated with the condition or disease, for example, by preventing motor neuron degeneration and cell death in ALS patients associated with the condition or disease. Accordingly, “treatment” generally means both therapeutic treatment and prophylactic or preventative measures. Improvement after treatment may be manifested as a decrease or elimination of such symptoms, e.g., by a decrease or elimination of symptoms associated with ALS, and / or by a decrease in the duration of such symptoms.

The present invention addresses the problem of providing a cryopreservation fluid for cells and a fluid for application to mammalian cells, capable of cryopreserving such cells and effectively suppressing cell death after thawing, as well as a method for cryopreserving mammalian cells using said fluid. Cell death after thawing can be suppressed more effectively than with conventional mammalian cell cryopreservation fluids when using an isotonic solution comprising: 2.0 to 6.0% (w / v) trehalose or a derivative thereof, or a salt of trehalose or a derivative thereof; 4.0 to 7.0% (w / v) dextran or a derivative thereof, or a salt of dextran or a derivative thereof; and DMSO or glycerin as the cryopreservation fluid for mammalian cells or as the fluid for application to mammalian cells, and the mammalian cells are cryopreserved in said fluid.

The invention belongs to the field of anticancer drugs, and discloses application of a TACR3 inhibitor in preparation of drugs for treating BRCA1 defective breast cancer. In the research of the invention, it is found that TACR3 is significantly up-regulated in BRCA1-deficient tumors, deletion of TACR3 and BRCA1 causes cell death, TACR3 provides a necessary replication protection mechanism for survival of BRCA1-deficient breast cancer cells, and deletion of TACR3 can overcome drug resistance of PARP inhibitors, that is, TACR3 can be used for preventing and treating BRCA1-deficient breast cancer cells. The inhibition of TACR3 can cause the death of BRCA1 defective breast cancer cells and overcome the drug resistance of PARP inhibitors in the BRCA1 defective breast cancer cells.

To provide multispecific B7H3 target compounds and methods for using them. [Solution] A multispecific B7H3 target compound and a method of using the same are provided. The multispecific compound includes a bispecific target protein comprising a B7H3 target domain and an immune cell binding domain; and a triplicate target protein comprising a B7H3 target domain, an immune cell binding domain and an immune cell activation domain. The method of use includes a method of inducing NK-mediated cell death, a method of inducing NK expansion in vivo, and a method of treating cancer.

The present disclosure relates to compositions and methods for providing neuroprotection in a subject and for treating neurodegenerative diseases and traumatic brain or spinal cord injury. In embodiments, the present disclosure provides agents that bind to cytoplasmic heteronuclear kernel glyconucleoprotein (hnRNP) in neurons and are capable of inhibiting neuronal cell death.

The present invention provides a novel therapeutic means for cancer cells resistant to epidermal growth factor receptor (EGFR)-targeted anticancer agents. Almost no cell death was observed when cancer cells having an exon 19 deletion mutation in the EGFR gene (EGFR Del19), cancer cells having a substitution mutation in which the 790th amino acid threonine in the EGFR protein is substituted with methionine (EGFR T790M), and cancer cells having a substitution mutation in which the 858th amino acid leucine is substituted with arginine (EGFR L858R) were treated solely with aripiprazole or solely with an EGFR-targeted anticancer agent. However, cell viability decreased and cleavage of the apoptosis marker PARP was observed when the cancer cells were treated with aripiprazole in combination with an EGFR-targeted anticancer agent. Therefore, aripiprazole is provided as an enhancer of the anticancer effect of EGFR-targeted anticancer agents.