53 results about "Noggin" patented technology

The invention discloses a culture medium and a method for performing in-vitro 3D cell model construction on skin tissues. The invention provides a culture medium for constructing a skin tissue in-vitro 3D (three-dimensional) cell model. The culture medium is prepared from an antibacterial and antifungal agent tri-antibody, HEPES, GlutaMax, MEM non-essential amino acid, human recombinant protein EGF, bFGF, HGF, FGF-10, Wnt-3a, Noggin, R-spondin 1, IL-2, IL-15, IGF-I, CHIR99021, SB202190, A83-01, Primocin, N-acetyl-L-cysteine, nicotine, an N2 additive, B27, ITS-X, Y-27632, dexamethasone, calomel and a basal culture medium. The skin tissue in-vitro 3D cell model constructed by the invention has a wide application prospect in the fields of basic scientific research and clinical diagnosis and treatment of skin diseases.

The invention discloses a culture medium of a lacrimal gland organ and a culture method of the lacrimal gland organ, and the culture medium of the lacrimal gland organ is composed of a basic culture medium, R-spodin3, Noggin, B27, N-acetyl-L-cysteine, trehalose, vitamin C, glutathione, an adenylate cyclase activator, A8301, PGE2 and FGF10. The culture medium for lacrimal gland organ culture, provided by the invention, is prepared from various cell factor components according to an optimized proportion, and is simple and reasonable in components and rich in nutrition; when the culture medium is used for culturing the lacrimal gland organoid, the formation and growth of the organoid can be promoted, an in-vivo complex microenvironment is further simulated, the organoid is closer to an in-vivo physiological state, an organoid model is better constructed so as to evaluate the influence of drugs on lacrimal gland functions, and a new platform is provided for drug screening; and a new way is opened up for follow-up treatment of diseases such as xerophthalmia in the future.

The present invention relates to a linker compound having a fused nitrogen-containing heteroaromatic ring and a vinyl substituent for conjugating to a protein or peptide. The present invention further relates to a conjugate comprising the linker and an active agent and to a conjugate comprising the linker, a protein or peptide, and an active agent, such as a drug or labelling moiety. More specifically, the conjugate may be an antibody conjugate, such as an antibody drug conjugate (ADC).

The invention relates to the technical field of biological medicine, and particularly discloses a culture medium formula for constructing ovarian cancer organoid and a culture method. The culture medium comprises the following components: L-glutamine 100x (L-Glutamine), L-glutamine 100x (L-Glutamine), L-glutamine 100x (L-Glutamine 4-hydroxyethylpiperazine ethanesulfonic acid (1M (hepes)); b-27 is free of a serum additive (B27); the preparation method comprises the following steps of: extracting the raw materials, namely nicotinamide; the preparation method comprises the following steps: adding N, N-acetylcysteine amide (N-Acetylcysteine); a forskolin element (Forskolin); and estradiol (beta-Estradiol), which is used for preparing the pharmaceutical composition. A TGF-[beta] inhibitor (A83-01); a p38 MAPK inhibitor (SB202190), and a p38 MAPK inhibitor, a p160ROCK small molecule inhibitor (Y27632); hepatocyte growth factor (HGF); the invention relates to a recombinant human Hergulin beta-1 protein product (Hergulin beta-1) and a preparation method of the recombinant human Hergulin beta-1 protein product. An epidermal growth factor (EGF); a fibroblast growth factor (FGF10); the invention relates to a method for preparing hydrocortisone. The method comprises the following steps: preparing hydrocortisone; and a primary cell antibiotic (Primocin). The culture solution and the culture method have the advantages that ovarian high-grade serous cancer cells can be effectively cultured and induced to develop into organoid. Noggin is not needed in the scheme, and the method is different from a traditional organoid culture method and is low in cost and simple in manufacturing process. Meanwhile, preparation of a conditioned culture medium is not needed, time can be remarkably saved, the situation that the conditioned culture medium is unstable due to too long time is avoided, and the success rate is high and is about 50%.

The invention provides an organoid culture medium, an organoid culture method and application of the organoid culture medium, the organoid culture medium comprises a first-stage culture medium, the first-stage culture medium comprises a first-stage basic culture medium and first-stage addition factors, and the first-stage addition factors comprise N-acetylcysteine, nicotinamide, a ROCK inhibitor, Noggin, R-spondin, EGF, HGF, Gastrin, FGF10, Blebbistatin, Forskolin, A83-01, LDN193189, DAPT, TGF-alpha and UDAC. By using the organoid culture medium, the liver organoid and the fatty liver organoid can be effectively obtained, and the obtained fatty liver organoid has obvious fat deposition, is sensitive to fatty liver treatment drugs, highly restores the physiological status when human body fatty liver diseases occur, and has high application value.

The invention relates to a serum-free culture medium with limited chemical components for mesenchymal stem cells as well as a preparation method and application of the serum-free culture medium. The culture medium comprises a basic culture medium, growth factors and a carrier protein stabilizer, the growth factors comprise a proliferation promoting factor, an activating agent, a signal factor and nutrients; the activating agent comprises Wnt7a protein and LIF protein. According to the invention, Wnt7a, LIF, Noggin, Activin A and TGF-beta3 are combined together according to a specific concentration and proportion (especially Wnt7a and LIF) for the first time, and cooperate with other factors (FGF-2 and IGF-1) to construct a brand new signal network capable of simulating an in-vivo dry microenvironment.

A culture medium and a culture method for constructing prostate cancer organoids are provided. The culture medium includes a basic culture medium, and the following components with final concentrations: R-spondin1 15-200 ng / mL, Noggin 20-150 ng / mL, FGF2 5-15 ng / mL, FGF10 1-10 ng / mL, CHIR99021 0.5-1 μM, ALK inhibitor 0.25-1 μM, ROCK inhibitor 5-30 μM, nicotinamide 5-10 mM and sodium pyruvate 0.5-3 mM. The present culture medium and culture method can effectively improve the survival rate and formation efficiency of organoids through the compounding of each component.

The invention discloses an application of a protease cleavage site mutant of a natural immune signal linker protein MAVS in resisting African swine fever viruses, aiming at three sites of African swine fever protease pS273R cleavage MAVS, the research finds that the site mutant can efficiently inhibit the replication of the African swine fever viruses; and breeding the variety pigs capable of resisting African swine fever by utilizing a gene editing technology.

This invention discloses a crayfish head protein peptide with uric acid-lowering effect and its application, belonging to the field of biotechnology. The amino acid sequence of the crayfish head protein peptide is shown in any one of SEQ ID NO. 1-4. This invention uses ultrasonic and microwave technology to assist protein hydrolysis, prepares xanthine oxidase inhibitory peptides from crayfish heads, explores the material basis of its activity, and studies its mechanism of action, laying a theoretical foundation for the high-value utilization of crayfish processing by-products and the development of food-derived xanthine oxidase inhibitors.

The present invention relates to the use of a composition comprising the following compounds: activin A, BMP4, CHIR99, EGF, FGF 8, FGF 10, IGF1, LY3, Noggin, retinoic acid and Y27 for carrying out a process of inducing the differentiation of pluripotent stem cells or iPSc into functional thymic epithelial progenitor cells or TEP, preferably in vitro or ex vivo.

The invention provides a preparation method of a long-term stable passage mouse nasopharyngeal epithelial cell line, which comprises the following steps: firstly, acquiring a mouse nasopharyngeal tissue, and extracting and separating primary mouse nasopharyngeal epithelial cells; purifying the nasopharyngeal epithelial cell line through time digestion; an NEC culture medium added with growth factors such as Wnt3a, R-spondin, Noggin and the like is used for culturing primary mouse nasopharyngeal epithelial cells for a long time. According to the method provided by the invention, the nasopharyngeal epithelial cells of the mouse can be stably proliferated for a long time, high proliferative activity is kept, and EMT transformation tendency is avoided. The invention provides a valuable cell tool for researching nasopharyngeal epithelium related diseases and formulating treatment strategies.

The invention provides a human normal thyroid organoid culture medium and application thereof, and belongs to the technical field of organoid culture, the culture medium takes a DMEM-F12 culture medium as a basic culture medium, and the culture medium comprises the following components with final concentration: A83-01495-505nM, A83-01495-505nM, A83-01495-505nM, A83-01495- 0.4%-0.6% (v / v) of B27; the concentration of Noggin is 20 to 30 ng / mL; the concentration of R-spondin is 1250 to 500 ng / mL; the weight of the Wnt signal protein is 100 to 300 ng / mL; an epidermal growth factor (EGF) is 15 to 25 ng / mL; the concentration of FGF-2 is 15 to 25 ng / mL; the concentration of Glutamax is 1.5 to 2.5 mM. The diameter of the thyroid organ cultured by the culture medium is 50-200 microns, free tetraiodothyronine (FT4) and free triiodothyronine (FT3) are secreted, the stability is good, and degradation is avoided in the passage process.

This invention discloses a degradation-targeting chimera, nanomedicine, and composition of an anti-PRRSV biotype protein, and their applications, belonging to the field of bioengineering technology. Specifically, this invention discloses a degradation-targeting chimera of an anti-PRRSV biotype protein, wherein the degradation-targeting chimera is obtained by linking a PRRSV N protein-specific nanobody to the BTB domain of the E3 ubiquitin ligase adaptor protein SPOP via Nnb-SPOP. This lays a research foundation for the efficient in vivo delivery of novel biological drugs and their clinical application against PRRSV, and provides a new strategy for the comprehensive prevention and eradication of PRRSV in my country.

The invention relates to the technical field of organoid construction and culture, and discloses a yolk sac tumor organoid culture medium and application thereof. The culture medium comprises a basic culture medium and specific addition factors, and the specific addition factors comprise L-glutamine, a TGF-BI type receptor inhibitor A83-01, nicotinamide, an N2 supplement, a vitamin A-removed B27 supplement, N-acetylcysteine, beta-estradiol, a P38MAPK inhibitor SB202190, a bone morphogenetic protein antagonist Noggin, a Wnt pathway related protein R-Spondin-1, an epidermal growth factor, an insulin-like growth factor 1, an insulin-like growth factor 2, an insulin-like growth factor 3, an insulin-like growth factor 4, an insulin-like growth factor 5 and an insulin-like growth factor 6. The medicine composition is prepared from a liver cell growth factor, a neuroregulatory protein-1, a ROCK inhibitor Y27632, activin A and interleukin-6. By adopting the culture medium disclosed by the invention, the successful construction of the egg cystic tumor organoid can be realized, and the stable passage of the egg and the stable and rapid growth after passage can be realized.

The application discloses a culture medium for constructing a gastric cancer ovary metastasis microtumor model and application. The application relates to the technical field of biotechnology, and provides a culture medium for constructing a gastric cancer ovary metastasis microtumor model, which is composed of three antibacterial and antifungal agents, HEPES, GlutaMax, human recombinant protein EGF, bFGF, HGF, FGF-10, Wnt-3a, Noggin, R-spondin 1, Follistatin, CHIR99021, SB202190, A83-01, Primocin, N-acetyl-L-cysteine, nicotinamide, N2 additives, cholera toxin, B27, ITS-X, Y-27632, gastrin, prostaglandin E2, beta-estradiol, progesterone, Galunisertib and a basic culture medium. The culture success rate of the gastric cancer ovary metastasis microtumor model is effectively improved.

The invention discloses a prostate cancer organoid culture medium and a culture method thereof, and particularly relates to the technical field of prostate cancer organoid culture, and the prostate cancer organoid culture medium comprises a basic culture medium and the following components: 20-100ng / ml of epidermal growth factors, 20-100ng / ml of prostate cancer organoid and 20-100ng / ml of The concentration of Noggin is 50 to 500 ng / ml; the concentration of R-spondin is 50 to 500 ng / ml; the weight of Wnt3a is 50 to 500 ng / ml; the concentration of FGF is 101 to 50ng / ml; 1 to 50 ng / ml of FGF (fibroblast growth factor); stem cell factors are 1 to 50 ng / mL; the concentration of antibiotics is 50-500 ng / ml; dHT is 1 to 50 ng / ml; the method comprises the following steps: 1, obtaining a prostate cancer tissue sample, placing the prostate cancer tissue in a sampling bottle containing a tissue preservation solution at 2-8 DEG C, and rapidly transferring the prostate cancer tissue to a clean laboratory for subsequent treatment; 2, preparing a plurality of culture dishes, adding a 4 DEG C precooled prostate cancer organoid culture buffer solution for later use, disinfecting a sampling bottle, putting the tissue into the culture dishes, and cleaning the tissue for three times by using the prostate cancer organoid culture buffer solution; the culture medium and the culture method provided by the invention can promote the growth of organs with prostatic cancer, so that the culture medium has a better actual use effect and is convenient to popularize and use.

The invention relates to a liver cancer organoid culture medium and application thereof, and belongs to the technical field of medicines. The liver cancer organ-like culture medium disclosed by the invention is prepared from the following components: AdvDMEM F12, HEPES, GlutaMAX, B27, EGF (Epidermal Growth Factor), N-acetyl-L-cysteine, gastrin, HGF (Hepatocyte Growth Factor), FGF-10 (Fibroblast Growth Factor), A83-01, nicotinamide, N2, an adenylate cyclase activator, a three-antibody antibiotic, R-spondin1, Wnt-3a, Y-2763, Noggin, oncostatin M and FGF-23. The culture medium is rich in nutrition and reasonable in component; the liver cancer organoid cell spheres cultured by using the culture medium can stably grow for a long time, continuously amplify and repeatedly cryopreserve. When the culture medium is used for preparing the liver cancer organ model, a foundation is laid for knowing the pathogenesis of liver cancer and screening drugs.

The present invention discloses a culture medium and a method for constructing an in vitro 3D micro-tumor model of head and neck tumors. The present invention provides a culture medium for constructing an in vitro 3D micro-tumor model of head and neck tumors, which is composed of three antibacterial and antifungal agents, HEPES, GlutaMax, MEM non-essential amino acids, human recombinant proteins EGF, bFGF, HGF, MSP, Wnt-3a, Noggin, R-spondin 1, IL-2, IL-15, forskolin, CHIR99021, SB202190, A83-01, Primocin, N-acetyl-L-cysteine, nicotinamide, N2 additives, B27, ITS-X, Y-27632 and basal culture medium. The in vitro 3D micro-tumor model of head and neck tumors constructed by the present invention can accurately reflect the characteristics of the original lesions of patients, and is a good scientific research experimental model and preclinical experimental model in the field of precise diagnosis and treatment of tumors.

The invention relates to the technical field of organoid culture, and discloses an induction culture medium for culturing a pig lung organoid. Advanced DMEM / F12 is used as a basic culture solution of the culture medium; the invention relates to a basic fibroblast growth factor composition, which is prepared from the following added components with the final concentration: 1500ng / mL of R-Spondinin, 25ng / mL of basic fibroblast growth factor 7 (FGF7), 10100ng / mL of basic fibroblast growth factor, 100ng / mL of Noggin protein, 50ng / mL of epidermal growth factor, 50ng / mL of Wnt3a protein, 500nM of TGF-beta pathway inhibitor, 5mM of ROCK inhibitor, 500nM of p38MAPK inhibitor, 1X of B27 supplement, 1.25 mM of N-acetyl-L-cysteine, 10mM of nicotinamide, 1X of glutamine supplement GlutaMAX1X, 1X of HEPES buffer solution and 1X of broad-spectrum antibiotic (Primocin). According to the method disclosed by the invention, the lung organ with the complex multi-cell lineage is efficiently and stably constructed from the pig lung adult tissue by a one-step method. The obtained organoid is high in biomimetic property and good in stability, provides a tool platform for pig lung development research, disease model construction, drug toxicology testing and regenerative medicine research, and has great scientific research value and wide application prospects.

The invention provides a culture medium for maintaining expression of key receptors of breast cancer organs and a preparation method of the culture medium. The culture medium comprises the following components: a basic culture medium, 1.25 to 2 mM of N-acetyl-L-cysteine, 1 * of N2, 1 * of B27, 1 * of Glutamax, 10 mM of HEPES, 1 [mu] M of SB202190, 5 to 10 mM of nicotinamide, 0.5 to 1 [mu] M of A83-01, 5 [mu] M of Y27632, 0.1 to 1 [mu] M of Verteporfin, 10 [mu] M of Sovesudil, 50 to 100 ng / mL of R-Spondin, 250 ng / mL of Noggin, 5 ng / mL of EGF, 5 ng / mL of Neuregulin 1, 200 ng / mL of The culture medium for maintaining the expression of the key receptor in the breast cancer organoid realizes stable maintenance of the expression of the key receptor in the breast cancer organoid, and provides a more accurate and reliable organoid model for research and treatment of breast cancer.

A system is disclosed for de novo protein generation. The system receives a set of design condition(s) that specify target characteristics of a synthetic protein. The system defines a modular energy function as a composition of a diffusion energy component and one or more conditioner energy components. The system applies a diffusion model to determine a denoised protein backbone. In applying the diffusion model, in each sampling step: the system transforms one prior sampled state of the synthetic protein from unconstrained space into constrained space based on the one or more design conditions, denoises the prior sampled state in the constrained space, and samples a subsequent sampled stated by applying a gradient of the modular energy function to the denoised prior sampled state in the constrained space. The final sampled state is a denoised protein backbone for the synthetic protein that satisfies the set of design condition(s).

The invention discloses a culture medium and a method for constructing a head and neck tumor in-vitro 3D micro-tumor model. The invention provides a culture medium for constructing an in-vitro 3D (three-dimensional) micro-tumor model of head and neck tumors. The culture medium is prepared from antibacterial and antifungal agents, namely three antibodies, HEPES, GlutaMax, MEM non-essential amino acid, human recombinant protein EGF, bFGF, HGF, MSP, Wnt-3a, Noggin, R-spondin 1, IL-2, IL-15, calomel, CHIR99021, SB202190, A83-01, Primocin, N-acetyl-L-cysteine, nicotine, an N2 additive, B27, ITS-X, Y-27632 and a basal culture medium. The head and neck tumor in-vitro 3D micro-tumor model constructed by the invention can accurately reflect the original focus characteristics of a patient, and is a good scientific research experiment model and a preclinical experiment model in the field of precise tumor diagnosis and treatment.

The invention discloses a culture system and a culture method for intestinal organs of euryhaline fish, and belongs to the technical field of bioengineering. The culture system is composed of a basic culture medium and a complete culture medium, wherein the basic culture medium is Advanced DMEM / F12, and is supplemented with a GlutaMax, Hepes and mycillin double-antibody solution; and on the basis of the complete culture medium, N-2, B-27, N-acetylcysteine, EGF (Epidermal Growth Factor), Noggin, R-Spondin 1 and other key cell factor combinations are further added. By optimizing the tissue pretreatment and digestion process, the efficient fish intestinal tract organoid culture and passage method is established, the organoid model with the crypt-villus-like structure, the cell heterogeneity and the intestinal tract barrier function is successfully constructed, and the model provides a highly bionic in-vitro research tool for fish physiology and toxicology research.

Disclosed are vaccine compositions, in particular, polyvalent icosahedral compositions for presentation of an HA1 influenza antigen. The disclosed compositions may contain an S particle comprising a norovirus (NoV) S domain and an HA1 influenza antigen, which may be linked via a linker protein domain operatively connected to the norovirus S domain and an influenza antigen. Fusion proteins for producing the vaccine compositions, and methods of using the disclosed vaccine composition are also provided.

This invention belongs to the field of regenerative medicine, specifically relating to a lacrimal gland organoid culture medium and a method for in vitro culture of lacrimal gland organoids. In one aspect, a lacrimal gland stem cell proliferation culture medium is provided, comprising: lacrimal gland stem cell basal culture medium, EGF, Wnt3a, FGF7, FGF10, RSP1, and Noggin; the lacrimal gland stem cell basal culture medium comprises: DMEM medium, F12 medium, L-glutamine, fetal bovine serum, hydrocortisone, cholera toxin, B27, penicillin, streptomycin, amphotericin B, and fasudil. In another aspect, a lacrimal gland stem cell differentiation culture medium is provided, comprising: lacrimal gland stem cell basal culture medium, EGF, Wnt3a, FGF7, FGF10, RSP1, Noggin, and BMP7. The lacrimal gland organoids constructed by this invention are larger in volume than those of existing technologies, possessing numerous branched ducts and vesicular acinar structures, extending radially and multidirectionally in a three-dimensional manner, forming a complex and regular three-dimensional tubular acinar network, and possessing secretory function.

The invention belongs to the field of cell culture, and relates to a mesothelioma organoid culture composition, the mesothelioma organoid culture composition comprises Rspondin-1, Noggin, Y27632, a growth factor and glutamic acid or a derivative thereof, the mesothelioma organoid culture composition is simple in component and reasonable in collocation, the mesothelioma organoid culture composition is combined with a specific culture method, mesothelioma cells from thoracic / peritoneum can be rapidly cultured, and the mesothelioma organoid culture composition is suitable for large-scale production. And mesothelioma organs with physiological characteristics are generated.

The present invention provides activatable preprotein homodimers comprising two separate but identical polypeptide chains, each chain comprising a fragment antigen binding (Fab) region that specifically binds to human PD-1 or human PD-L1 or human B7H3, a hinge / Fc domain, a linker, an IL-15 protein, a protease cleavable linker, and an IL-15R [alpha] protein. Related pharmaceutical compositions and methods of use thereof are also provided.

The invention discloses an ameloblastoma organoid improved culture medium and application thereof, and belongs to the field of organoid culture. According to the improved culture medium for the ameloblastoma organoid, the L-cysteine is added on the basis of an organoid culture medium, and formation and stable growth of the ameloblastoma organoid can be promoted by adding the L-cysteine. The improved culture medium for the ameloblastoma organs, disclosed by the invention, can be specifically prepared from a basic culture medium, L-cysteine, a B27 supplement, N-acetyl-l-cysteine, nicotinamide, a human epidermal growth factor, A83-01, human FGF10 (Fibroblast Growth Factor), human FGF2 (Fibroblast Growth Factor 2), prostaglandin E2, Laduvillib, Y-27632, Forskolin, R-spondin-1 and Noggin. The ameloblastoma organ is successfully obtained by culturing the ameloblastoma by adopting the ameloblastoma organ improved culture medium disclosed by the invention, and the ameloblastoma organ improved culture medium has important significance in researching a heterogeneity mechanism of the ameloblastoma and developing a new treatment method.

A system is disclosed for de novo protein generation. The system receives a set of design condition(s) that specify target characteristics of a synthetic protein. The system defines a modular energy function as a composition of a diffusion energy component and one or more conditioner energy components. The system applies a diffusion model to determine a denoised protein backbone. In applying the diffusion model, in each sampling step: the system transforms one prior sampled state of the synthetic protein from unconstrained space into constrained space based on the one or more design conditions, denoises the prior sampled state in the constrained space, and samples a subsequent sampled stated by applying a gradient of the modular energy function to the denoised prior sampled state in the constrained space. The final sampled state is a denoised protein backbone for the synthetic protein that satisfies the set of design condition(s).

The invention discloses a degradation targeting chimera of anti-PRRSV (porcine reproductive and respiratory syndrome virus) biological protein, a nano-drug, a composition and application of the degradation targeting chimera, the nano-drug and the composition, and belongs to the technical field of bioengineering. The invention discloses a degradation targeting chimera of anti-PRRSV (Porcine Reproductive and Respiratory Syndrome Virus) biological type protein. The degradation targeting chimera is prepared by mixing Nnb-SPOP (N-methylpyrrolidone) with SPOP; the Nnb-SPOP is obtained by connecting a PRRSV (Porcine Reproductive and Respiratory Syndrome Virus) N protein specific nano antibody with a BTB structural domain in an E3 ubiquitin ligase linker protein SPOP. A research foundation is laid for the aspects of in-vivo efficient delivery of novel biological drugs, anti-PRRSV clinical application and the like, and a new strategy is provided for comprehensive prevention, control and purification of PRRSV in China.