240 results about "Cellular death" patented technology

The invention relates to a wheat stem rot regulatory gene Tatrx-m, and an encoding protein, a recombinant vector and an application of the wheat stem rot regulatory gene Tatrx-m. The genomic sequence of the gene is SEQ ID NO.1, the CDS sequence of the gene is SEQ ID NO.2, and thioredoxin shown as SEQ ID NO.3 is encoded. The invention further provides a specific primer pair used for gene identification, a silent vector (Tatrx-m-VIGS) and an overexpression vector (LGY-OE3-Tatrx-m) are constructed, and the function of the primer pair is verified through a virus-induced gene silencing (VIGS) technology and agrobacterium-mediated transformation of wheat. Experiments show that silence of Tatrx-m results in significant reduction of wheat stem rot resistance, and overexpression of the gene can improve resistance. Based on hypha quantification, DAB staining, H2O2 content and cell death analysis, Tatrx-m is revealed to enhance wheat resistance by regulating active oxygen removal and cell wall strengthening pathways. The gene TaTrx-m has the positive regulation effect in wheat stem rot for the first time, can be applied to disease-resistant molecular marker development, gene editing and transgenic breeding, provides core genetic resources for disease-resistant variety breeding, and has theoretical and application values.

The present disclosure provides genetically modified iPSC-derived γδT cells and their precursors. A double genomic disruption in the suppressor of cytokine signaling 1 (SOCS1) gene and the cytokine-inducible sh2-containing protein (CISH) gene are provided, as is a triple genomic disruption in genes for SOCS1, CISH, and Bcl-2 interacting mediator of cell death (BIM), as is a quadruple genomic disruption in genes for SOCS1, CISH, BIM, and cell surface death receptor (FAS), as is a quintuple genomic disruption in genes for SOCS1, CISH, BIM, β-2-Microglobulin (B2M), and class II transactivator (CITTA), as is a sextuple genomic disruption in genes for SOCS1, CISH, BIM, B2M, CITTA, and FAS. Also provided is genetically modified iPSC-derived γδT cells and their precursors with improved proliferation and tumor killing activity. Also provided are genetically modified iPSC-derived γδT cells and their precursors further comprising CD19 CAR. The present disclosure further provides methods making and using such cells, as well as gene editing systems.

The invention discloses a device and system for conducting electric field treatment on the digestive tract, the device for conducting electric field treatment on the digestive tract comprises a slender catheter, a supporting body located at the far end of the catheter, an electrode array film and a pulse generator, the electrode array film and the pulse generator are arranged on the supporting body, and the output end of the pulse generator is coupled with an electrode pair on the electrode array film. A sequence pulse wave output by the pulse generator comprises a plurality of groups of nanosecond pulse strings, and the time interval between the adjacent nanosecond pulse strings is 1us-10000 us; the nanosecond pulse string is composed of a plurality of nanosecond pulse pairs, and the time interval between every two adjacent nanosecond pulse pairs ranges from 50 ns to 10000 ns; the nanosecond pulse pair comprises positive pulses and negative pulses which appear alternately, the pulse width of the positive pulses and the pulse width of the negative pulses are 10-1000 ns, and the time interval is 10-1000 ns. The cell membrane permeability and the cell death efficiency can be remarkably improved, and the limitation of the traditional IRE technology is broken through.

The present disclosure provides genetically modified iPSC-derived γδT cells and their precursors. A double genomic disruption in the suppressor of cytokine signaling 1 (SOCS1) gene and the cytokine-inducible sh2-containing protein (CISH) gene are provided, as is a triple genomic disruption in genes for SOCS1, CISH, and Bcl-2 interacting mediator of cell death (BIM), as is a quadruple genomic disruption in genes for SOCS1, CISH, BIM, and cell surface death receptor (FAS), as is a quintuple genomic disruption in genes for SOCS1, CISH, BIM, β-2-Microglobulin (B2M), and class II transactivator (CIITA), as is a sextuple genomic disruption in genes for SOCS1, CISH, BIM, B2M, CIITA, and FAS. Also provided is genetically modified iPSC-derived γδT cells and their precursors with improved proliferation and tumor killing activity. Also provided are genetically modified iPSC-derived γδT cells and their precursors further comprising CD19 CAR. The present disclosure further provides methods making and using such cells, as well as gene editing systems.

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 medicine, and particularly relates to application of actinomycin D in preparation of a ctDNA detection sensitizer. The invention provides a ctDNA release method based on actinomycin D as an enhancer, which can significantly improve the release level of ctDNA in early small-volume tumors and tiny residual lesions, thereby improving the sensitivity and positive detection rate of liquid biopsy in MRD detection. Under an extremely low dosage, the ActD can generally promote a plurality of human tumor cells to release ctDNA under the condition of not causing obvious cell death, and has good biological safety and adaptability. The method is especially suitable for tiny, biological inert or anatomical position hidden focuses which are difficult to identify by iconography, namely blind area patient groups in disease monitoring, and has a wide clinical application prospect.

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.

A method of reducing a latent HIV-specific memory-CD4+ T cell pool in a subject includes administering to the subject at least one HIV-1 protein and a pharmaceutically acceptable carrier, wherein the at least one HIV-1 protein is derived from an allogenic infecting HIV-1 virus, and wherein the HIV-1 protein stimulates latent HIV-specific memory CD4+ T cells to induce latent HIV-1 replication resulting in HIV-specific memory-CD4+ T cell death in the subject.

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.

This invention relates to biomimetic mineralized exosomes for programmed drug penetration in tumors that inhibit cell burial, along with their preparation method and applications. Belonging to the field of novel excipients and dosage forms for pharmaceutical formulations, this invention co-loads the small-molecule chemotherapeutic drugs 10-hydroxycamptothecin and banoanthraquinone into exosomes. Then, through a biomimetic mineralization strategy, aTIM-4 is organically combined with mineralized calcium phosphate particles to obtain biomimetic mineralized exosomes. Under the acidic response of the tumor microenvironment, the calcium phosphate shell dissolves, and the exosome nucleus enters the tumor cells, inducing cell death and generating apoptotic bodies. This programmatically delivers the drug, delivering banoanthraquinone deep into the tumor. Simultaneously, the released aTIM-4 inhibits the cell burial of tumor-associated macrophages, amplifying the programmed drug penetration based on apoptotic bodies. This invention provides a new strategy and more options for overcoming the bottleneck of nanomedicine penetration in tumors, meeting the urgent clinical need for highly effective chemotherapeutic agents.

A compound having formula (I) or (II) for use inhibiting Bax mediated cell death and / or apoptosis.

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.

The invention relates to the technical field of antibacterial liquid, and discloses a bee venom antibacterial liquid and a preparation method thereof.The preparation method includes the steps that cortex acanthopanacis and cassia twigs are smashed, then bee venom, silicon-containing chitosan, vanillyl butyl ether and deionized water are added into the smashed cortex acanthopanacis and cassia twigs, stirring is conducted, and the bee venom antibacterial liquid is obtained; the bee venom antibacterial liquid contains a large amount of sulfonic acid groups, imidazole and quaternary ammonium salt antibacterial groups, the positive charge part of quaternary ammonium salt can attract negative charges on a cell membrane to destroy the integrity of the cell membrane so as to cause cell death, and the imidazole group can inhibit synthesis of fungal cell keratin sterol, so that bacteria are killed, and the antibacterial activity of the bee venom is improved. The substitution degree of the modified antibacterial group is further increased, and the natural substance chitosan also has a better antibacterial effect, so that an antibacterial system is jointly formed, and the synergistic antibacterial effect is achieved.

The invention relates to the technical field of novel application of compounds, in particular to novel application of meclozine and analogues thereof. The invention relates to an application of at least one of meclozine and analogues thereof or pharmaceutically acceptable salts or esters thereof in preparation of drugs for preventing and / or treating pancreatitis. The meclozine and the analogue thereof can obviously improve pancreatic tissue necrosis, inflammatory response and oxidative stress of pancreatitis, inhibit alveolar cell death and improve lung injury caused by pancreatitis, so that the meclozine and the analogue thereof can be used as a medicine for treating pancreatitis.

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.

Provided are a compound capable of killing bacteria and viruses and a manufacturing method therefor. The compound comprises an effective amount of a mixture formed by an oleophylic phase ingredient and at least a food-grade nano-calcium-containing ingredient. By heating the mixture at 100 °C and then letting to stand at room temperature for cooling, the compound is obtained. When the compound is applied at pathogen-hiding sites on the skin, calcium ions in the food-grade nano-calcium-containing ingredient will trigger physiological reactions such as phagocytosis of macrophages, intercellular signal transmission, hormone secretion, and the like, to antagonize foreign pathogens; in addition, calcium ions will also be adsorbed on cell membranes of bacteria or viruses to denature cell proteins, which disables cell breath, metabolism, and proliferation and ultimately causes cell death, thus completing cell killing and achieving the effects of killing bacteria and viruses.

This application relates to the field of biomedical technology, and in particular to the application of a small molecule D6 and its derivatives in the preparation of anti-tuberculosis drugs. Through research, this application has discovered that small molecule D6 can specifically target methionine synthase in Mycobacterium tuberculosis to block the methionine synthesis pathway, thereby causing metabolic disorders and cell death in the bacteria. Furthermore, this small molecule D6 exhibits significant antibacterial activity against various Mycobacterium tuberculosis strains, including drug-resistant and dormant strains. Therefore, this small molecule D6 can be well-suited for the preparation of anti-tuberculosis drugs.

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.