15 results about "Perforin" patented technology

The invention discloses application of an ATP (adenosine triphosphate) citrate lyase (ACLY) inhibitor in preparation of a medicine for treating leucoderma, and belongs to the technical field of preparation of medicines for treating leucoderma. Through targeted inhibition of ACLY activity or specific knockout of ACLY in CD8 + T cells, abnormal activation of ACLY and secretion of killing effector molecules (Granzyme B, IFN-gamma, Perforin and the like) are inhibited, and infiltration of the CD8 + T cells to skin lesion parts is reduced, so that melanocytes are protected from immune injury, and the progress of vitiligo is blocked. The application is based on the abnormally high expression of ACLY in CD8 + T cells of vitiligo patients and the close association with disease activity, and a brand new targeted treatment thought and a medicine research and development direction are provided for vitiligo.

The application provides an immune cell culture kit, a culture method and application of gamma delta T cells, and the kit comprises a basic culture medium, a recombinant antibody, a cytokine and a cell proliferation promoting additive, the basic culture medium comprises an RPMI-1640 culture medium, and the cell proliferation promoting additive comprises 1-thioglycerol, taurine, beta-cyclodextrin, thymidine, alpha-lipoic acid, beta-mercaptoethanol and bisphosphonate. The gamma delta T cells obtained by the culture kit have high purity and activity, and have good tumor killing activity. The gamma delta T cells obtained by the method have a high positive rate of 100% of perforin expression.

The invention belongs to the technical field of pharmaceutical compositions for removing senescent cells, and discloses a pharmaceutical composition for removing senescent cells and a preparation method and application thereof, and the pharmaceutical composition for removing senescent cells contains NK cells and fisetin. According to the pharmaceutical composition for removing senescent cells, the fisetin and the NK cells are combined for use, on one hand, the fisetin can enable the NK cells to easily recognize senescent cells; on the other hand, fisetin can relieve inhibition of SASP factors on NK cell activity, enough amount of cytotoxic particles such as perforin and granzyme are synthesized and released in NK cells, the killing efficiency on senescent cells is high, fisetin can directly trigger an apoptosis pathway of the senescent cells, and the effect of killing the senescent cells is achieved. The NK cells release cytotoxic particles to further accelerate death of the senescent cells, and fisetin and the NK cells have a synergistic effect, so that the senescent cell clearing efficiency is high.

Compositions and methods are provided for isolating, manipulating and using for therapeutic and other purposes, mammalian, MHC Class I restricted, antigen-specific regulatory T cells. The regulatory T cells can be characterized as CD8+ cells that specifically suppress the responses of self-reactive and / or pathogenic CD4+ T cells by cytotoxic mechanisms including, without limitation, perforin, other components of the perforin / granzyme apoptosis pathway, etc. The regulatory T cells are antigen-specific, but are not activated by the same antigen as the self-reactive and / or pathogenic CD4+ T cells. In humans the regulatory T cells express inhibitory KIR proteins, e.g. one or more of KIR2DL2, KIR2DL3, and KIR3DL1.

The present application provides a dendrobium officinale polysaccharide extract, a preparation method and an application, the dendrobium officinale polysaccharide extract is with dendrobium officinale stem as raw material, is extracted by purified water reflux, is precipitated by ethanol, is deproteinized by Sevag, is decolorized and is deashed and is obtained by gel / film separation and purification, the mass percentage content of polysaccharide in the extract is 50-95wt%, the average molecular weight is 10-300 kDa, and the monosaccharide component includes mannose, glucose, galactose, fucose, rhamnose and arabinose.The dendrobium officinale polysaccharide extract provided by the present application has immune activation effect on natural killer cells, can promote the NK cell CD107a degranulation reaction and the expression of IFN-gamma, perforin and granzyme B in a dose-dependent manner, up-regulates the NKG2D related pathway, thereby activating the NK cell function and enhancing the killing activity of NK cells on tumor target cells such as K562.

The application relates to application of arachidonic acid inhibitors in preparation of drugs for improving tumor immune microenvironment. + The arachidonic acid inhibitors improve the ratio and expression amount of perforin and IFN-gamma secreted by T cells and improve the ratio and expression amount of IFN-gamma and IL-17A secreted by Treg cells.

The present disclosure relates generally to pharmaceutical formulations (e.g., lyophilized formulations or topical formulations) comprising a perforin inhibitor (e.g., a benzenesulfonamide). In particular embodiments, the pharmaceutical formulations of the present disclosure are useful for treating diseases or disorders associated with undesirable perforin activity.

The invention provides a dendrobium officinale polysaccharide extract as well as a preparation method and application thereof.The dendrobium officinale polysaccharide extract is prepared from dendrobium officinale stems as a raw material through purified water reflux extraction, ethanol precipitation, Sevag deproteinization, decoloration and deliming and gel / membrane separation and purification, the mass percentage content of polysaccharide in the extract is 50-95 wt%, the average molecular weight is 10-300 kDa, and the content of polysaccharide in the extract is 50-95%. The monosaccharide components comprise mannose, glucose, galactose, fucose, rhamnose and arabinose. The dendrobium officinale polysaccharide extract provided by the invention has an immune activation effect on natural killer cells, can dose-dependently promote the degranulation reaction of NK cells CD107a and the expression of IFN-gamma, perforin and granzyme B, and up-regulate NKG2D related pathways, so that the functions of the NK cells are activated, and the killing activity of the NK cells on tumor target cells such as K562 is enhanced.

The application provides an application of dodartin A1 in activating NK cells. Through in-vitro experiments, it is proved that dodartin A1 can significantly promote the synthesis and release of IFN-gamma and cytotoxic substances (such as granzyme B and perforin) of NK92 cells, and increase the expression of the surface agonistic receptors NKp46 and NKG2D of the NK92 cells; through in-vivo experiments, it is proved that dodartin A1 can promote the expression of the NK cell activation related substances CD107a and NKp46 to play an anti-hepatoma effect; in conclusion, dodartin A1 has the effect of activating NK cells.

The invention discloses application of gamma-aminobutyric acid in preparation of a synergist of an immune checkpoint inhibitor, and belongs to the technical field of tumor treatment. Compared with independent treatment, combined administration of the GABA and the immune checkpoint inhibitor can significantly inhibit tumor growth, increase the infiltration proportion of CD8 + T cells in tumor tissues, and increase the proportions of IFN-gamma +, TNF-alpha + and Perforin + CD8 + T cells, so that the cytotoxic function of the T cells is enhanced. The results show that the GABA can promote the anti-tumor immune response of an organism by adjusting immune cell composition and T cell functions in a tumor microenvironment, so that the treatment effect of the immune checkpoint inhibitor is improved, and a new theoretical basis and application prospect are provided for the GABA as an auxiliary strategy for improving the tumor immunotherapy curative effect.

The application belongs to the technical field of bacteriophages, and discloses a recombinant bacteriophage for displaying bacteriophage perforin as well as a preparation method and application of the recombinant bacteriophage. The preparation method of the recombinant bacteriophage comprises the following steps: S1, using a bacteriophage genome as a template, amplifying a bacteriophage perforin coding gene sequence by using a fusion primer to obtain the bacteriophage perforin coding gene sequence, and performing enzyme digestion and recovery on the amplification product and an expression vector; S2, connecting the bacteriophage perforin coding gene sequence with a homologous arm and the enzyme-digested expression vector skeleton, and transforming the same into Escherichia coli to obtain recombinant Escherichia coli; and S3, performing bacteriophage rescue on the recombinant Escherichia coli to obtain the recombinant bacteriophage for displaying bacteriophage perforin. The lysis spectrum of the recombinant bacteriophage prepared by the method is greatly widened, and the recombinant bacteriophage can cross-species lyse various gram-positive bacteria and mycoplasma, and the lysis efficiency is also improved, so that the recombinant bacteriophage has important significance and value in antibacterial treatment and clinical application.

The invention provides application of strepsterol in preparation of a liver cancer radiotherapy sensitizing drug, and belongs to the technical field of biological medicine. The invention discloses a technical scheme for reducing the generation of macrophage chain sterol in radiation-resistant liver cancer tissues and promoting the sensitization of liver cancer radiotherapy by using chain sterol treatment for the first time. Wherein the CD8 < + > T cells serve as anti-tumor immune core effector cells, the killing function of the CD8 < + > T cells directly affects the curative effect, and the strepsterol can promote infiltration of the cells into tumor tissues and improve secretion of killing molecules such as perforin and granzyme, so that radiation-resistant hepatoma carcinoma cells are effectively eliminated. Streptosterol treatment not only reduces radiotherapy resistance factor expression, but also amplifies the radiotherapy killing effect, finally realizes efficient radiotherapy sensitization and significantly improves the tumor recession rate, provides a brand new efficient scheme for radiation-resistant liver cancer treatment, and has great clinical and social values.

The present application relates to the technical field of NK cell culture, and discloses a method for improving the killing function of NK cells and application thereof.The method comprises the following steps: (1) adding a haem oxygenase 1 antibody to an NK cell culture medium to prepare an antibody culture medium; (2) performing sterile filtration treatment on the antibody culture medium; and (3) separating NK cells and culturing the NK cells in the antibody culture medium.The present application adds a haem oxygenase 1 antibody to treat NK cells, blocks the expression of haem oxygenase 1 in the NK cells, or inhibits the activity of an effective substance of haem oxygenase 1.After being treated with the haem oxygenase 1 antibody, the secretion of granzyme B and perforin of the NK cells can be promoted, and the killing effect of the NK cells on target cells Yac-1 and K562 can be improved, so that the anti-tumor function of the NK cells is improved.

The invention discloses a Perforin CaMACPF6 and an application of the Perforin CaMACPF6 in construction of a novel flood-resistant vegetable germplasm. According to the invention, an Agrobacterium tumefaciens-mediated inflorescence dip dyeing method is utilized to construct an arabidopsis thaliana plant of the overexpressed perforation protein CaMACPF6 gene, and the obtained transgenic plant is cultured under a hypoxia stress condition to find that compared with a wild type control, the overexpressed perforation protein CaMACPF6 gene in the plant can significantly improve the hypoxia stress resistance of the plant. On the basis, the perforation protein CaMACPF6 can be used for constructing a crop variety resistant to hypoxia stress, so that the crop variety can resist waterlogging and hypoxia stress caused by other conditions, and the adverse effect of hypoxia stress on crop growth is relieved. The method is beneficial to the construction of hypoxia stress-resistant germplasm, and further reduces the loss of crops caused by flood disasters and the like.

This invention discloses an NK cell exosome capable of targeting and killing lung cancer and its preparation method. Specifically, it is based on NK cells derived from umbilical cord blood stem cells, and involves constructing CRISPR-Cas9-PD-1 knockout recombinant plasmids to transfect cells, and rapidly inducing umbilical cord blood stem cells to transform into CD3+ cells using IL-21. ‑ CD56 + NK cell differentiation and maturation, tandem ultracentrifugation, and size exclusion chromatography were used for high-efficiency purification to obtain PD-1 knockout NK cell exosomes containing granzyme, perforin, and FasL. L NK-EXO). The PD-1 constructed in this invention L NK-EXO treatment significantly prolonged the survival of a mouse model of lung cancer and reduced tumor size, while also demonstrating clear lung cancer targeting and specific killing functions. More importantly, this invention reveals that PD-1 knockout of NK cell exosomes is crucial for tumor targeting and killing.