32 results about "Adenylyl Cyclases" patented technology

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.

This invention relates to the application of exosomes in reversing tumor resistance to immune checkpoint (PD-1) inhibitors. A novel application of exosomes in the preparation of pharmaceutical compositions reversing tumor resistance to immune checkpoint inhibitors is disclosed. Exosomes generated from tumor cells recombinantly expressing adenylate cyclase 7 (ADCY7) can significantly reverse tumor resistance to PD-1 inhibitors, and the exosomes exhibit a synergistic effect with the PD-1 inhibitors.

This invention discloses a maize adenylate cyclase ZmSnRK1.2, its encoding gene, expression vector, and applications, aiming to address the current technical problem of scarce maize heat-resistant gene resources and germplasm resources. This application verifies that maize kinase ZmSnRK1.2, as a novel adenylate cyclase, has high catalytic activity and can rapidly produce cAMP in the presence of ATP. This application also verifies... ZmSnRK1.2 The positive regulatory role of genes in the heat tolerance of maize. This application provides new ideas and technical approaches for solving the damage caused by heat stress in maize and for breeding heat-tolerant varieties.

A method of reducing fear memory in a mammal comprising the step of inhibiting or reducing cAMP signaling in the mammal. The cAMP signaling can be reduced using an adenylyl cyclase 1 (AC1) inhibitor or using a phosphodiesterase, such as a cAMP-specific phosphodiesterase, such as PDE4.

The present invention relates to a recombinant protein comprising one or more fragments of the surface protein A (PspA) of the pneumococcal, and an adenylate cyclase (CyaA) from the genus Bordetella, in particular Bordetella pertussis, in which the fragments of the PspA are selected from the group consisting of clades 1 to 4, or a combination of two or more thereof. Furthermore, the present invention relates to an expression cassette comprising a DNA sequence encoding said recombinant protein, in particular a DNA sequence selected from the nucleotide sequences represented by SEQ ID NO: 12 to 18 and a degenerate sequence thereof, which respectively encode the recombinant protein represented by SEQ ID NO: 5 to 11. In addition, immunogenic compositions comprising the recombinant protein or the expression cassette and further pharmaceutically acceptable carriers and / or adjuvants are disclosed. Finally, the present invention relates to the use of said recombinant protein, said expression cassette or said immunogenic composition for the preparation of a vaccine for the prevention of infection by Streptococcus pneumoniae wherein said vaccine provides broad spectrum protection against different pneumococcal isolates regardless of serotypes.

A fusion protein is provided that blocks both a calcitonin gene related peptide (CGRP) pathway and a pituitary adenylate cyclase activated peptide (PACAP) pathway, where the fusion protein comprises at least one single domain antibody, at least one Fc fragment, and at least one extracellular domain fragment of pituitary adenylate cyclase 1 (PAC1 ECD). The fusion protein can block CGRP and PACAP pathways at the same time, and the response rate of drugs for treating migraine is improved.

The purpose of the present invention is to provide a novel method whereby a methyl compound can be produced by efficiently regenerating S-adenosylmethionine (SAM) and promoting a methylation reaction, through the use of general organic raw materials such as glycine, serine, formic acid, methanol, or glucose.　The present invention provides a method for producing a methyl compound using cells that have been modified so as to enhance the activity or expression of SAM-dependent methyltransferase, S-adenosylhomocysteine hydrolase (SahH), and adenosine kinase (ADO1) and reduce the activity or expression of adenylate cyclase (CyaA) and / or S-adenosylmethionine decarboxylase (SpeD).

The invention relates to the technical field of immune preparations, in particular to application of Forskolin or pharmaceutically acceptable salt thereof in preparation of a vaccine immunopotentiator. Aiming at the defects of vaccine immunomodulators in the prior art, the invention provides a novel method for enhancing the immune effect of a vaccine by using a natural plant extract Forskolin (as an adenylate cyclase activator), the Forskolin can promote high expression of CXCR4 by plasma cells to obviously enhance the homing ability, the residence ability and the service life of the plasma cells, so that the immune effect of the vaccine is enhanced. Therefore, the long-term immune response of the antibody is improved. The Forskolin directly targets the effector cytoplasm cells immunized by the vaccine, so that the potential safety hazard of the traditional technology is avoided, and meanwhile, more lasting and stable immune protection is provided.

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 refers to a new use of a composition comprising a calcimimetic for enhancing engraftment and lineage reconstitution of hematopoietic stem and progenitor cells (HSPCs) in hematopoietic cell transplantation (HCT) recipients, wherein before transplantation, said HSPCs are pre-treated in vitro ("primed") with a prostacyclin analogue and an adenylate cyclase sensitizer, and the composition is administered shortly before, or at the time of transplantation of said HSPCs, and after transplantation of said HSPCs. The invention further refers to a therapeutic combination comprising HSPCs and a calcimimetic and a method for enhancing engraftment capabilities of HSPCs.

Methods of reducing serum low density lipoprotein (LDL) levels in a subject are disclosed. The methods comprise inhibiting the expression or function of adenylate cyclase in the subject, where the inhibiting comprises administering to the subject an inhibitory nucleic acid molecule, such as siRNA.

The present invention relates to a method of treatment for chronic pain, opioid dependence, alcohol use disorder or autism using a class of pyrimidinone compounds, an adenylyl cyclase 1 (AC1) inhibitor. The invention described herein also pertains to pharmaceutical compositions and methods for treating diseases in mammals using those compounds disclosed herein.

The invention provides a kit for detecting pyruvate kinase and application, and belongs to the technical field of pyruvate kinase detection. The kit comprises a cell ATP removal reagent and a pyruvate kinase detection reagent, the cell ATP removal reagent comprises adenylate cyclase; the pyruvate kinase detection reagent comprises a bioluminescent enzyme, a bioluminescent enzyme substrate, phosphoenolpyruvic acid, adenosine diphosphate and a non-PK kinase inhibitor; the non-PK kinase inhibitor is a myokinase inhibitor and / or a nucleoside diphosphate kinase inhibitor. The kit for detecting the pyruvate kinase can be used for qualitatively or quantitatively detecting the PK activity in a sample. When the kit is used for detecting the light-emitting signal generated by the ATP of the PK reaction product, the kit is suitable for long-time detection, and the enzyme activity is in positive correlation with the amount of the ATP. The kit provided by the invention can be used for detecting the enzyme activity of PK in different samples, and has the advantages of high sensitivity, high specificity, good linear relationship and stable fluorescence signal.

A protein according to one embodiment of the present invention has a photoactivated adenylyl cyclase activity, and consists of the amino acid sequence of SEQ ID No. 1 with 1-18 amino acid residues deleted from the C-terminus, or an amino acid sequence having 90% or more sequence identity therewith. According to the present invention, a novel photoactivated adenylyl cyclase having a higher photoactivation efficiency compared to a wild-type OaPAC protein can be provided.

The present application discloses novel compounds, and compositions comprising said compounds, that are effective small-molecule agonists that stimulate overproduction of cytosolic cyclic AMP (cAMP) in Mycobacterium tuberculosis (Mtb) which inhibits cholesterol metabolism. These small-molecule agonists demonstrate potentiation of current tuberculosis (TB) therapeutics, exhibiting potential as a promising new class of agents for the treatment of TB. The application further discloses methods of treatment of TB using compositions comprising the disclosed novel compounds in combination therapy with current TB therapeutics.

A pituitary adenylate cyclase activating peptide (PACAP) is a neuropeptide associated with a broad range of functions such as nociceptive feelings and primary headache. PACAP is a member of the trypsin / vasoactive intestinal peptide (VIP) / growth hormone releasing hormone (GHRH) family. The present disclosure relates generally to anti-PACAP antibodies, pharmaceutical compositions comprising such antibodies, and methods of producing and using such antibodies.

Disclosed are methods of decreasing serum low density lipoprotein (LDL) level in a subject. The methods include inhibiting expression or function of an adenylate cyclase in the subject, wherein the inhibiting includes administration of an inhibitory nucleic acid molecule, such as an siRNA, to the subject.

The invention discloses an AC (at) Mg / Ce-UiO nano particle, a preparation method thereof and application of the nano particle in medicines for treating inflammatory dermatosis, and belongs to the technical field of biological medicines. Adenylate cyclase (AC) is encapsulated in situ in an Mg / Ce-UiO metal organic framework designed by defect engineering, and a unique structure brings dual treatment strategies: the encapsulated AC catalyzes pro-inflammatory ATP to be converted into anti-inflammatory cAMP to restore balance; defective Mg / Ce-UiO simulates SOD (superoxide dismutase) and CAT (catalase) to remove excessive ROS. The nanoparticles can down-regulate the expression of various inflammatory factors and pruritus mediators, inhibit the excessive proliferation of keratinocytes and reduce the infiltration of immune memory T cells. Therefore, the effects of treating inflammatory skin disease skin lesion, remarkably relieving itching and preventing relapse are achieved. The preparation method is simple and easy for large-scale production. The invention introduces a reform mode to the treatment of inflammatory dermatosis, provides a curative strategy, establishes a multifunctional treatment framework, and is expected to be suitable for more extensive inflammation and autoimmune diseases.

Pituitary adenylate cyclase-activating peptide (PACAP) is a neuropeptide involved in a wide range of functions, including nociception and primary headaches. PACAP is a member of the secretin / vasoactive intestinal peptide (VIP) / growth hormone-releasing hormone (GHRH) family. The present disclosure generally relates to anti-PACAP antibodies, pharmaceutical compositions comprising such antibodies, and methods for producing and using such antibodies. For example, the present invention provides an anti-pituitary adenylate cyclase-activating polypeptide (PACAP) antibody, comprising the full-length heavy chain amino acid sequence set forth in SEQ ID NO:1 and the full-length light chain amino acid sequence set forth in SEQ ID NO:2.

The invention discloses a composition for constructing a complex PNET organ-like model, a model construction method and application. The composition comprises a penicillin-streptomycin double antibody solution, GlutaMax, a serum-free supplement, a Wnt signal channel activator, a human recombinant Noggin protein, a human recombinant FGF10 protein, HEPES, N-acetyl-L-cysteine, gastrin, nicotinamide, an adenylate cyclase activator, an ALK inhibitor, a ROCK inhibitor and a p38MAPK inhibitor. The composition provided by the invention comprises a plurality of growth factors required for vascularization growth of PNET organs, and can meet the requirements of PNET organ cells on nutrient substances and regulation and control substances in a complex structure growth process; in the culture process, a complex PNET organ-like biological model which is closer to the real tumor microenvironment of a human body and is more simulated and more comprehensive is developed, and the PNET organ-like biological model has wider and more important application value in the aspects of clinical diagnosis of PNET diseases, drug research, development and screening, precision medical treatment and the like.

The invention relates to a bile duct cancer organoid culture medium and application thereof, and belongs to the technical field of biomedicine. The bile duct cancer organ culture medium provided by the invention is prepared from the following components: a TGF (Transforming Growth Factor)-beta signal channel inhibitor A83-01, an epidermal growth factor (EGF), a fibroblast growth factor FGF10, a hepatocyte growth factor HGF, an adenylate cyclase activator Forskolin, a gastrin analogue Gastrin I, nicotinamide Nicotinamide, a ROCK kinase inhibitor Y-27632, glucocorticoid dexamethasone, a compound antibiotic, a cell factor oncostatin M and FGF-23. The culture medium disclosed by the invention is reasonable in formula design, all the components have a synergistic effect, long-term stable amplification of bile duct cancer organs can be effectively maintained, and a good cryopreservation resuscitation characteristic is maintained. A liver cancer organ model established on the basis of the culture medium provides a reliable experimental platform for exploring pathogenesis of bile duct cancer and developing related drug research and development.

The present invention discloses a 7-fluoro-5-substituted tryptamine compound, a preparation method and a use thereof. The compound is characterized in that the compound has a 7-fluoro-5-substituted tryptamine of the structural formula shown in formula I or a pharmaceutically acceptable salt, ester or solvate thereof. The preparation method comprises the steps of 1) reacting the compound shown in formula II with iron and ammonium chloride to obtain a compound shown in formula III; 2) reacting the compound shown in formula III with sodium nitrite to obtain a compound shown in formula IV; 3) reacting the compound shown in formula IV with stannous chloride to obtain a compound shown in formula V; 4) reacting the compound shown in formula V with a compound shown in formula VI to obtain a compound shown in formula VII; and 5) reacting the compound shown in formula VII with a compound shown in formula VIII to obtain a compound shown in formula I. The compound has the advantage that the compound can effectively bind to 5-HT by coupling with G protein. 1B It binds to the receptor and inhibits the activity of adenylate cyclase.

The disclosure is directed to methods of generating induced pluripotent Procavia capensis stem cells that combine transfection and chemical reprogramming. Specifically, the disclosure provides methods of generating induced pluripotent P. capensis stem cells that include generating primed P. capensis cells by chemically reprogramming primary P. capensis cells transfected with OCTA. 80X2. KI.F4. CMYC. and GLIS1 by culturing the cells, generating pre-induced P. capensis cells from the primed P. capensis cells by transfecting the primed P. capensis cells with OCT4. 80X2. KLF4, CMYC, and NANOG and culturing these cells, and generating the induced pluripotent P. capensis stem cells from the pre-induced P. capensis cells by transfecting the pre-induced P. capensis cells with OCT4, SOX2, KLF4. CMYC, NANOG, IJN28A. and SV40 and culturing the transfected cells. In other embodiments, the primary P. capensis cells are cultured to generate pre-induced P. capensis cells, which are then transfected with at least OCT4ISOX2IKLF4ICMYC. and SV40 T-antigen or an shRNA targeting TP53 and cultured again. The culturing uses a culture medium supplemented with an HD AC inhibitor, a GSK-3 inhibitor, a monoamine oxidase inhibitor, an activator of eukaryotic adenylyl cyclase, a retinoid, a DOT1L inhibitor, and a TGF-β inhibitor. The disclosure is also directed to cell culture media useful in such methods and induced pluripotent P. capensis stem cells expressing at least OCT4, 80X2, KLF4, CMYC, NANOG, LIN28A, and SV40.

The invention relates to the field of genetic engineering and biological catalysis, in particular to an adenylate cyclase mutant and application thereof in catalytic synthesis of cyclic adenosine monophosphate. The amino acid sequence of the mutant is obtained by mutating one or more of asparagine at the 76th site, methionine at the 119th site and valine at the 247th site in the sequence shown as SEQ ID NO.1. The invention further discloses a preparation method of the mutant. The enzyme activity of the mutant M119C at the optimum temperature of 40 DEG C is improved by 21.34% compared with that of wild type ArAC (the optimum temperature of 35 DEG C). And in the aspect of thermal stability, the half-life periods of the three mutants under different temperature conditions are obviously longer than those of a wild type, and the thermal stability of the enzyme is effectively improved. Meanwhile, the substrate affinity of the mutant M119C is enhanced compared with that of the wild type ArAC, and the catalytic efficiency of the mutant M119C is 2.43 times that of the wild type ArAC. In the application of catalytic synthesis of cyclic adenosine monophosphate by using the mutant M119C, the total yield of cyclic adenosine monophosphate is obviously increased by 22.94% compared with that of a wild type. The adenylate cyclase mutant disclosed by the invention provides a new scheme for industrial production of cyclic adenosine monophosphate.

The present invention relates to use of an adenylyl cyclase inhibitor represented by formula (1) or a pharmaceutically acceptable salt thereof in the preparation of a drug for treating perioperative pain. The perioperative period comprises a preoperative period, an intraoperative period, and a postoperative period. The drug comprises an active ingredient for gastrointestinal or non-gastrointestinal administration, and a suitable pharmaceutical organic or inorganic inert carrier material. In the drug for treating perioperative pain, the adenylyl cyclase inhibitor represented by formula (1) or the pharmaceutically acceptable salt thereof is the only active ingredient. The drug of the present invention can relieve the stresses of undergoing surgery, has a therapeutic effect on pain in the entire perioperative period, and does not have side effects such as addiction.

The peptide of the present invention has ability to bind to pituitary adenylate cyclase 1 receptor PAC1R, promotes activation of a PAC1R signaling pathway, and induces nerve cell differentiation, and thus has tear secretion promoting activity. In addition, the peptide of the present invention promotes the expression and secretion of mucoprotein of a tear component in conjunctival goblet cells, and has an activity of inhibiting inflammatory responses and cellular damage in human corneal epithelial cells. The peptide of the present invention can be used as an active substance for treating, preventing and ameliorating xerophthalmia.

The present disclosure provides methods of treating an individual for a muco-obstructive, the methods including: administering to the individual a b-adrenergic agonist or an adenylate cyclase activator, in combination with a cholinergic agonist to treat the individual for the muco-obstructive disorder.

Described herein are compositions and methods useful for reducing the risk of a major adverse cardiovascular event, treating a cardiovascular condition, as well as decreasing glucose levels, reducing a risk of developing hyperglycemia, and treating hyperglycemia in a subject by decreasing the presence of an adenylate cyclase type 9 (AC9) and / or glucose-6-phosphatase catalytic subunit (G6PC) using inhibitory nucleic acid molecules.