314 results about "Cellular death" patented technology

The invention belongs to the field of tumor drug research, and particularly relates to a cell vesicle co-delivery system, an anti-tumor drug and application. The cell vesicle-like co-delivery system is constructed according to the following steps: co-transfecting a recombinant expression vector of tumor targeting protein or targeting peptide and a recombinant plasmid of circRNA of effector molecules related to pyroptosis to a tool cell, and collecting to obtain the cell vesicle-like co-delivery system, a recombinant expression vector of the tumor targeting protein or the targeting peptide contains a DNA sequence for coding MCP protein, and a recombinant plasmid of circRNA of an effector molecule related to pyroptosis contains a DNA sequence for coding MS2 protein. According to the cell vesicle co-delivery system provided by the invention, tumor cell death is directly induced by delivering the cell death related effector molecule RNA through the cell vesicles, the killing efficiency is high, the side effect is relatively small, and the problems of mass production and drug loading can be solved.

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 invention discloses a polyethylene glycol modified gold and manganese dioxide nano particle and a preparation method and application thereof, and belongs to the technical field of biological medicine, the polyethylene glycol modified gold and manganese dioxide nano particle (GMCN and PEG) has good biocompatibility under neutral physiological conditions, can relieve tumor hypoxia and increase generation of active oxygen in acidic TME, and has a good anti-tumor effect. The radiotherapy sensitivity is improved; and immune cell death is induced. Meanwhile, a cGAS-STING signal channel can be activated, dendritic cell maturation, macrophage M1 polarization and T cell infiltration are promoted, and the immunosuppression state in TME is counteracted. In addition, the GMCN-coated PEG also has an MR-CT bimodal imaging enhancement function, and integration of diagnosis and treatment is realized. The nano sensitizer disclosed by the invention has huge potential in the aspects of improving the radiotherapy curative effect, remodeling the tumor microenvironment, promoting the anti-tumor immunity, enhancing the biomedical imaging and the like.

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 present invention relates to the use of TDP1 and eltrombopag in the treatment of myotonic dystrophy type 2. The present invention uses a fruit fly model to identify that TDP1 knockdown can effectively rescue neurodegeneration in the CCTG repeat fruit fly model, reduce pigment production block, cell death and ommatidium fusion, and improve motor defects. At the same time, in vitro screening using small molecules found that eltrombopag can be used as a TDP1 inhibitor and can significantly reduce disease cytotoxicity. The present invention provides a new target and pharmacological substance for CCTG repeat expansion diseases in myotonic dystrophy type 2, and expands the medical use of eltrombopag. The present invention provides a new drug with clinical application prospects for the treatment of CCTG repeat expansion diseases in myotonic dystrophy type 2.

The present invention relates to a nucleic acid molecule capable of controlling innate immunity by RNA and, more specifically, to a short duplex hairpin RNA (sdhRNA) that binds to protein kinase R (PKR), which is activated upon recognition of RNA, thereby inhibiting the activity of PKR and suppressing PKR-mediated innate immunity and which, when introduced into the 3'-UTR of mRNA, can increase the expression level of an antigen. The sdhRNA motif according to the present invention inhibits the activity of protein kinase R (PKR) by binding to PKR activated by recognizing RNA. Therefore, when administered into cells in combination with exogenous RNA or as an insert into the 3'-UTR of mRNA, the sdhRNA motif exhibits the effect of reducing RNA-indued PKR activation, mitigating RNA-induced cell death, and downregulating the expression of interferon-stimulated gene (ISG) as well as improving the expression efficiency of a protein encoded by the mRNA. With the effects, the motif is applied to various RNA-based uses, for example, vaccines, in vivo / ex vivo gene therapeutic agents, 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.

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 invention generally relates to fluidic droplets and systems and methods for determining immune or other cells. Some aspects of the invention are generally directed to assays that combine sensitive detection of secreted products with detection of target cell death in droplets containing an effector cell, systems and methods to isolate droplets in which one or more cell interactions have occurred, or systems and methods to generate nucleic acid information from cell interactions. In addition, some embodiments of the invention are generally directed to containing two (or more) cells in droplets, e.g., an effector cell and one or more target cells, and determining various interactions between the cells within the droplets, such as whether the effector cell kills the target cell, whether the effector cell releases antibodies, cytokines or other substances that are able to interact with the target cell or are released in the presence of the target cell, or the like.

The present invention provides molecules that bind to cellular components or parts thereof (e.g., filaments or histones forming the cytoskeleton or nucleoskeleton) that are exposed to the extracellular environment upon cell death, which are specifically observed in diseased tissues, and simultaneously bind to target molecules on or in cells that act specifically in tissues where cell death is observed, such as diseased tissues, abnormal tissues, etc. The molecules of the present invention are useful as drugs that provide significant therapeutic or preventive effects while reducing side effects.

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 pertains to use of a composition comprising propionic acid and / or salt thereof and at least one fatty acid having 6 to 12 carbon atoms for reducing dormant spore viability, for inactivating dormant conidia, for eliminating or reducing germination of conidia, for increasing cell damage and / or cell death of hyphae, and / or for reducing or eliminating germ tube formation.

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 invention belongs to the technical field of biomedicine, and particularly relates to a nucleic acid combination product for detecting SIAH2, a diagnostic kit for osteoarthritis and application of the diagnostic kit. According to the application, the models are established by using machine learning to analyze various cell death modes, and the application finds that in the models of the four cell death modes, the ferroptosis model has the highest diagnosis efficiency on the OA and identifies the corresponding biomarkers. It is found that SIAH2 is used as a biomarker to regulate occurrence and development of OA through cartilage cells, and a new diagnosis and treatment strategy is provided for OA.

The invention provides a THP-1 mononuclear cell culture medium and a culture method thereof. The THP-1 mononuclear cell culture medium comprises the following components: a complete culture medium, 8v / v%-12v / v% of fetal calf serum, 20mM-30mM of HEPES, 0.8 mM-1.2 mM of sodium pyruvate and 0.8 v / v%-1.2 v / v% of antibiotics. Wherein the HEPES is 2-4M HEPES mother liquor prepared by using a complete culture medium, the sodium pyruvate is 2-4M sodium pyruvate mother liquor prepared by using a complete culture medium, the complete culture medium is an RPMI 1640 culture medium, and the antibiotic is mycillin. The invention provides a series of optimized processes of a THP-1 cell culture method, passage, culture medium and the like, so that the THP-1 cell culture method is improved, the resuscitation state of the cryopreserved THP-1 cells is improved, and the phenomena of cell death and the like are reduced; besides, the THP-1 cell culture medium provided by the invention is optimized in formula and scientific in proportioning, the sensitivity degree of THP-1 cells to serum quality is reduced, and the good growth state of the THP-1 cells is further improved.

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.