32 results about "Matrix metalloproteases" patented technology

This invention discloses a multi-enzyme preparation for industrial cell dissociation, its usage method, and applications, belonging to the field of seed cell extraction technology for industrial meat culture. The invention employs a multi-enzyme preparation composed of component 1 and component 2; component 1 includes neutral protease, hyaluronidase, and elastase; component 2 includes matrix metalloproteinase, papain, and plasmin. The invention also discloses the preparation method and applications of the multi-enzyme preparation. The rational enzyme ratio and optimized treatment conditions of this invention help protect cell membrane integrity, maintain high cell activity, and significantly improve dissociation efficiency and cell recovery. The compound enzyme preparation is highly adaptable, applicable to various tissue types and dissociation requirements, and facilitates standardized and large-scale production. Combined with automated dissociation equipment, the compound enzyme preparation enables efficient and stable industrial operation, providing important technical support and broad application prospects for the cultured meat industry, tissue engineering, and cell therapy.

The invention discloses a method for generating collagen peptide based on combined action of MMP3 and MMP16 and application of the collagen peptide. The method comprises the following steps: firstly, extracting type I collagen from pleopod muscles of haliotis discus hannai; the method comprises the following steps: designing specific primers, and respectively amplifying target gene segments of catalytic structural domains of matrix metalloproteinase MMP3 and MMP16; respectively cloning the gene segments into a prokaryotic expression vector pET-22b to construct a recombinant expression vector, and expressing the two recombinant proteins in escherichia coli; and under the combined action of the recombinant protein of MMP3 and MMP16 and the extracted type I collagen, the collagen peptide is generated through catalytic degradation. The collagen peptide prepared by the invention can be widely applied to the fields of biological medicines, cosmetics, health food and the like.

The invention provides inter alia a method for enzymatic digestion of an extracellular matrix protein in a tissue sample, comprising the steps of:—providing an aqueous medium that comprises (i) a matrix metalloproteinase and (ii) a cation that is Ca2+ at a concentration of at least 2 mmol / L;—contacting said aqueous medium with a tissue sample that comprises an extracellular matrix protein under conditions that allow for enzymatic digestion of said extracellular matrix protein; wherein said tissue sample is a cartilage tissue sample.

The invention discloses a serum protein marker combination for detecting cerebral microhemorrhage, and belongs to the field of biological medicine detection.The serum protein marker combination comprises four serum proteins including matrix metalloproteinase 3, fibronectin-like extracellular matrix protein 1 containing epidermal growth factors, a metalloproteinase inhibiting factor 1 and uromodulin; through efficient and accurate serum protein marker combination, the defects that brain function magnetic resonance SWI examination is high in cost and long in time consumption, operation depends on high-level imaging physicians and the like are overcome, an innovative tool is provided for rapid, accurate and non-invasive screening and auxiliary diagnosis of cerebral microhemorrhage, and wide clinical application prospects are achieved.

The invention relates generally to polypeptides that include at least a first cleavable moiety (CM1) that is a substrate for at least one matrix metalloprotease (MMP) and at least a second cleavable moiety (CM2) that is a substrate for at least one serine protease (SP), to activatable antibodies and other larger molecules that include these polypeptides that include at least a CM1 that is a substrate for at least one MMP protease and at least a CM2 that is a substrate for at least one SP protease, and to methods of making and using these polypeptides that include at least a CM1 that is a substrate for at least one MMP protease and at least a CM2 that is a substrate for at least one SP protease in a variety of therapeutic, diagnostic and prophylactic indications.

Methods of decreasing shedding of CD28, decreasing soluble CD28 levels, treating cancer and improving immunotherapies comprising inhibiting matrix metalloproteases are provided. Methods of producing agents for performance of the methods of the invention are also provided.

The invention provides a temperature-sensitive hydrogel for resisting bacteria and promoting repair and a preparation method thereof, the temperature-sensitive hydrogel comprises PEG-NB, a matrix metalloproteinase degradable peptide cross-linking agent, gelatin, indocyanine green and levofloxacin, and the temperature-sensitive hydrogel is prepared by photo-crosslinking. According to the temperature-sensitive hydrogel provided by the invention, the structure and the performance of the hydrogel are optimized through the synergistic effect of the gelatin and the PEG-NB, and the mechanical strength, the biocompatibility, the degradability and the like of the hydrogel are remarkably improved; meanwhile, the photo-thermal antibacterial function of the photo-thermal agent indocyanine green and the chemical antibacterial function of levofloxacin are integrated, and near-infrared light irradiation is combined, so that the antibacterial and skin repair promoting effects of the hydrogel are synergistically improved.

This invention discloses a Bifidobacterium that promotes collagen production and its applications, belonging to the field of microbial technology. The Bifidobacterium animalis BBS 01 provided by this invention can promote the expression levels of collagen synthesis-related genes and matrix metalloproteinase inhibitor genes, and reduce the expression levels of matrix metalloproteinase-related genes, thereby promoting collagen production. The Bifidobacterium animalis BBS 01 can be used to prepare edible nutrients or skin nutrients.

The invention relates to a method for the diagnosis, prognosis, risk assessment, risk stratification, monitoring, therapy guidance and / or therapy control of an infectious disease in a subject, wherein said method comprises providing a sample of said subject; determining a level of matrix metalloprotease-8 (MMP-8) or fragment(s) thereof in a sample of said subject, wherein said level of MMP-8 or fragment(s) thereof distinguishes between the presence and absence of an infectious disease in a patient with symptoms of a systemic inflammatory condition. In a preferred embodiment the invention relates to the determination of procalcitonin (PCT) and MMP-8 and their combined use to distinguish between the presence and absence of infectious disease in patients with symptoms of systemic inflammatory condition. The invention also relates to a computer-implemented method and a kit for conducting the method of the invention.

An in vitro method for assessing or predicting the response of human patients to treatment of periodontal disease is disclosed. This method is based on insights into identifying biomarker proteins. Therefore, the concentration of a specific combination of proteins is measured in a saliva sample from the patient. One such combination is at least one of interleukin-1-β (IL-1β) and matrix metalloproteinase-8 (MMP-8), and α-1-acid glycoprotein (A1AGP). Based on the measured concentrations, at least one value reflecting the combined concentration of these proteins is determined. This at least one value can indicate the likelihood that the human patient has been or will be successfully treated for periodontitis. This at least one value can be compared to at least one threshold, which in the same manner reflects the combined concentration associated with successful treatment of periodontitis. This comparison allows assessment of whether the test value is an indicator of the patient's periodontal treatment status.

The present application relates to the field of biological medicine, and more particularly to a nano-composite system for treating vitiligo, an intelligent controlled-release microneedle patch and a preparation method thereof, wherein the nano-composite system contains enzyme-responsive micelles and polyethylene glycol modified polydopamine nanoparticles; the enzyme-responsive micelles are formed by glyceryl monostearate encapsulating ginseng root-derived exosomes; and the polyethylene glycol modified polydopamine nanoparticles are formed by covalent connection of a polydopamine core and methoxy-polyethylene glycol-amine. Compared with the prior art, the nano-composite system of the present application can realize the spatiotemporal programmed release of drugs in response to the pathological microenvironment, wherein the polydopamine nanoparticles provide instant antioxidant effect, and the exosome micelles trigger release under the condition of overexpression of matrix metalloproteinase-9, thereby synergistically exerting anti-inflammatory and promoting pigment regeneration effects; animal experiments have proved that the patch can effectively reverse the white spots and realize the recoloring of hair and skin. The microneedle patch thus prepared can realize transdermal self-administration, is convenient and painless.

The application discloses a preparation method and application of a dual-immune checkpoint inhibitor modified glycosyl nanoparticle, relates to the technical field of biological medicine, and comprises (a) a core-shell structure nano carrier formed by self-assembly of amphiphilic quaternary ammonium chitosan oligosaccharide, wherein the nano carrier is loaded with a dabrafenib; (b) a PD-1 / PD-L1 pathway blocking polypeptide AUNP-12, which is coupled to the surface of the nano carrier through a covalent bond; and (c) a CTLA-4 pathway blocking antibody alpha-CTLA-4, which is coupled to the surface of the nano carrier through a Schiff base reaction; wherein the amphiphilic quaternary ammonium chitosan oligosaccharide is composed of a hydrophilic quaternary ammonium chitosan oligosaccharide segment, a hydrophobic vitamin E succinate segment and an enzyme-sensitive polypeptide GPLGVRGDG connecting the two segments and capable of being specifically cut by matrix metalloproteinase 2; the dual-immune checkpoint inhibitor modified glycosyl nanoparticle provided by the application has good biological tissue compatibility, and the dual-immune checkpoint inhibitor modified glycosyl nanoparticle (LTHAC) has strong killing effect and targeting capacity on B16F10 melanoma cells with high expression of PD-L1 and abnormal activation of a MAPK pathway.

Disclosed is an in vitro method for assessing whether a human patient suffering from periodontitis has mild periodontitis or advanced periodontitis. The method is based on the insight to determine a selection of two biomarker proteins. Accordingly, in a sample of saliva a patient suffering from periodontitis, the concentrations are measured of the proteins Pyruvate Kinase (PK) and at least one of Matrix metalloproteinase-9 (MMP9), S100 calcium-binding protein A8 (S100A8), and Hemoglobin subunit beta (Hb-beta); or of the proteins Matrix metalloproteinase-9 (MMP9) and at least one of S 100 calcium-binding protein A8 (S100A8) and S100 calcium-binding protein A9 (S100A9). Based on the concentrations as measured, a value is determined reflecting the joint concentrations for said proteins. This value is compared with a threshold value reflecting in the same manner the joint concentrations associated with advanced periodontitis. The comparison allows assessing whether the testing value is indicative of the presence of advanced periodontitis or of mild periodontitis in said patient. Thereby, typically, a testing value reflecting a joint concentration below the joint concentration reflected by the threshold value is indicative for mild periodontitis in said patient, and a testing value reflecting a joint concentration at or above the joint concentration reflected by the threshold value, is indicative for advanced periodontitis in said patient.

Peptides of D-amino acids and their use in therapy, for example treating or preventing brain cancer, as well as pharmaceutical compositions comprising the peptides, the peptides being effective modulators of matrix metalloproteinases (MMPs).

The invention relates to the field of biological medicine, in particular to a nano-composite system and an intelligent controlled-release microneedle patch for treating leucoderma and a preparation method of the nano-composite system and the intelligent controlled-release microneedle patch. The enzyme responsive micelle is formed by encapsulating a ginseng root exosome with glyceryl monostearate; the polyethylene glycol modified polydopamine nano particles are formed by covalent linkage of a polydopamine core and methoxyl-polyethylene glycol-amine. Compared with the prior art, the nano-composite system disclosed by the invention can respond to a lesion microenvironment to realize space-time programmed controlled release of a drug, the polydopamine nano-particles provide an instant anti-oxidation effect, and exosome micelles are triggered to release under an overexpression condition of matrix metalloproteinase-9 so as to synergistically exert anti-inflammatory and pigment regeneration promoting effects; animal experiments prove that the patch can effectively reverse white spots and realize color recovery of hair and skin. The prepared microneedle patch can realize transdermal self-administration, and is convenient and painless.

The application discloses a hyaluronic acid modified co-loaded all-trans retinoic acid and arginine liposome and a preparation method and application thereof, and belongs to the field of pharmaceutical preparations.The liposome components comprise phospholipid, cholesterol, hyaluronic acid, all-trans retinoic acid and arginine.The prepared liposome can generate nitric oxide in response to a large amount of active oxygen existing in a liver fibrosis microenvironment, the generated nitric oxide is further oxidized into peroxynitrite by ROS, matrix metalloproteinase is activated, an extracellular matrix barrier is reduced, and nanoparticles are promoted to penetrate into a perisinusoidal space of the liver.The liver stellate cells are targeted through receptor-ligand specific combination, and the uptake efficiency of the liver stellate cells is improved.The released all-trans retinoic acid in cells is converted into a resting state by inducing activated liver stellate cells, and the regression of liver fibrosis diseases is promoted.The liposome penetrates through an extracellular matrix to promote nanoparticle penetration, enhances drug delivery, and provides a new way and strategy for efficient delivery of therapeutic drugs.

The invention relates to the field of cosmetic preparations, and discloses a ganoderma lucidum mycelium freeze-dried powder liposome face cream and a formula process, and the ganoderma lucidum mycelium freeze-dried powder liposome face cream is prepared by the following steps: firstly, selectively separating a first active matter rich in polysaccharide-polypeptide and a second active matter rich in triterpene-sterol from ganoderma lucidum mycelium by adopting a subcritical water gradient extraction technology; then constructing a dual-liposome delivery system: wrapping a first active matter in a first liposome with a relatively large particle size to act on a skin surface layer; a second active matter and a copolymer capable of being specifically split by matrix metalloproteinase (MMPs) are jointly wrapped in a second liposome with a small particle size, so that penetration and responsive release towards the deep layer of the skin are realized. And finally, compounding the two liposomes into a cream matrix with a lamellar liquid crystal structure. Accurate active matter separation, layered targeted delivery and intelligent response release technologies are integrated, the technical problems that the active matter utilization rate is low and the efficacy is not fully played are solved, and the stability and the synergistic repair effect of the product are remarkably improved.

The invention discloses camel placenta polypeptide with matrix metalloproteinase I inhibitory activity and application of the camel placenta polypeptide, and belongs to the field of application of enzymolysis processing products. Fresh camel placenta is used as a raw material, enzymatic hydrolysate is obtained after flavourzyme enzymolysis and passes through an ultrafiltration membrane (the molecular weight cut-off is 10 kDa), a filtered solution is obtained and freeze-dried, and the camel placenta polypeptide is prepared and has matrix metalloproteinase I inhibitory activity. The invention also discloses a small molecule polypeptide with matrix metalloproteinase I inhibitory activity. After a polypeptide sequence of the filtrate is identified by adopting a polypeptide mass spectrum, screening is performed through molecular docking with matrix metalloproteinase I protein, polypeptide activity is verified through a matrix metalloproteinase I in-vitro enzyme inhibition experiment, seven micromolecule polypeptides with matrix metalloproteinase I inhibitory activity are obtained, the sequence of the micromolecule polypeptides is shown as any one of SEQ ID NO.1-7, and the micromolecule polypeptides with matrix metalloproteinase I inhibitory activity can be obtained. The traditional Chinese medicine composition can be used for preparing medicines for inhibiting skin aging.

Methods for treating joint diseases, disorders, and conditions, such as osteoarthritis, with a composition containing a therapeutically effective amount of tissue inhibitors of matrix metalloproteinases (TIMPs) are provided. The composition can contain TIMPs as part of amniotic fluid, or the TIMPs can be isolated from another source or recombinantly produced. The methods are particularly useful for treating osteoarthritis associated with degradation of articular cartilage by proteases. Also provided are methods of lubricating a joint, such as an osteoarthritic joint.

Disclosed herein are means, methods, and compositions of matter useful for stimulation of elastin / collagen production and suppression of matrix metalloprotease activity. The disclosure further provides compositionally useful preparations derived from regenerative cells that have been manipulated for optimum growth factor and anti-aging properties. In one embodiment cellular mixtures derived from regenerative cells contacted with activating signals. Said activating signals include stimulation of toll like receptors and other "danger" sensing molecules. In one embodiment regenerative factors are harvested from stem cells and compounded into composition preparations.

The invention relates to the technical field of biological medicine, and discloses a cell-penetrating CPP-SOD1 compound and application thereof in relieving cisplatin-induced renal toxicity, the cell-penetrating CPP-SOD1 compound comprises the following components: a cell-penetrating peptide, the amino acid sequence of the CPP is selected from at least one of TAT, Penetratin or polyarginine, and the amino acid sequence of the SOD1 is selected from at least one of TAT, Penetratin or polyarginine; the amino acid sequence of the superoxide dismutase 1 is as shown in SEQ ID NO: 1; the ROS sensitive connecting peptide is used for connecting the CPP and the SOD1, and the sequence of the connecting peptide comprises a thioketal bond or a matrix metalloproteinase cleavage site; wherein the transmembrane efficiency of the compound is greater than or equal to 70%, the SOD1 activity retention rate is greater than or equal to 85%, and the compound is used for preventing or relieving renal tubular epithelial cell oxidative damage caused by cisplatin chemotherapy. According to the invention, pathological response release is realized by dynamically screening the kidney-targeted cell-penetrating peptide and combining with the ROS sensitive connecting peptide, cell penetrating and enzyme activity are optimized by using two parameters, and delivery-release is tracked based on FRET, so that the problems of poor cell penetrating property and insufficient activity retention are solved, and the renal toxicity protection curative effect of cis-platinum is improved.

The invention discloses an application of D-mannose in preparation of a medicine for treating plantar fasciitis and related pains, the active ingredient in the medicine is D-mannose, and the D-mannose inhibits the expression of matrix metalloproteinase-3 (MMP3) caused by inflammation stimulation in plantar fasciitis tissues through a metabolite mannose-6-phosphoric acid (M6P). The invention discloses and verifies that the natural product D-mannose realizes an inhibition effect on a key pathogenic factor MMP3 of plantar fasciitis through a specific metabolic pathway of 'Man-M6P' for the first time, and not only is the drug effect obvious, but also the safety is far better than that of the existing common drugs. Besides, the traditional Chinese medicine composition not simply relieves pain and resists inflammation, but targets an upstream key link MMP3 causing degeneration of fascia tissues, and by inhibiting the MMP3, damage to fascia collagen structures is reduced fundamentally, and conditions are created for self-repairing and regeneration of tissues, so that radical treatment and recurrence prevention are expected to be realized.

This invention belongs to the field of electrochemical analysis technology and relates to an electrochemiluminescence peptide sensing method for detecting matrix metalloproteinases, comprising: 1) mixing a peptide chain solution, an iridium metal complex solution, and a magnetic microparticle MB@SA suspension, adding a protease standard solution, and incubating in one pot; 2) magnetically enriching the magnetic bead complex on the electrode surface and measuring the electrochemiluminescence intensity; 3) changing the volume of the protease standard solution to obtain magnetic bead complexes after reacting with different concentrations of protease and measuring the electrochemiluminescence intensity; obtaining a standard regression equation with protease concentration as the abscissa and the change in electrochemiluminescence intensity as the ordinate; 4) taking the test solution to obtain the corresponding electrochemiluminescence intensity, substituting it into the standard regression equation to obtain the protease concentration. This invention has the advantages of mild probe synthesis conditions, rapid labeling, high sensitivity of the detection method, and ease of operation, realizing rapid, sensitive, and highly selective determination of matrix metalloproteinases.

A lipid nano drug delivery system targeting a brain lesion and a preparation method and application thereof. The drug delivery system comprises a lipid, a delivery drug, and a functional penetrating peptide, and the functional penetrating peptide is formed by covalently connecting a peptide chain linking a nanocarrier end, an arginine-rich penetrating peptide, a matrix metalloproteinase-9 sensitive peptide, and a polyanion inhibitory peptide. The lipid nano drug delivery system can be used for targeting the brain lesion and realizing mitochondrial enrichment by means of modification of the functional penetrating peptide. The repair of mitochondria is realized by encapsulating peptide drug cyclosporin A by means of a lipid nanoparticle core by utilizing a dilution-induced precipitation technique, thereby solving the problems that current cyclosporin A is difficult to effectively reach a brain lesion and the therapeutic window is small, and improving the ability to repair cells around the brain lesion with a small administration dose.

To provide an isolated polypeptide comprising a tandem substrate, an activatable antibody that specifically binds to a target and a production method therefor, and methods for using these in a variety of therapeutic, diagnostic and prophylactic indications.SOLUTION: The invention provides polypeptides that include at least a first cleavable moiety (CM1) that is a substrate for at least one matrix metalloprotease (MMP) and at least a second cleavable moiety (CM2) that is a substrate for at least one serine protease (SP) or at least one cysteine protease (CP).SELECTED DRAWING: Figure 1

The present disclosure relates to nucleic acid-peptide-nucleic acid conjugate molecules and to methods for synthesizing nucleic acid-peptide-nucleic acid conjugate molecules. In some embodiments, a method for synthesizing a nucleic acid-peptide-nucleic acid conjugate molecule using proximity-enhanced synthesis includes covalently linking a peptide with a first nucleic acid strand via a first reaction, hybridizing the first nucleic acid strand with a second nucleic acid strand to bring the second nucleic acid strand in proximity to the peptide, and covalently linking the peptide with the second nucleic acid strand via a second reaction to provide the nucleic acid-peptide-nucleic acid conjugate molecule. In some embodiments, the peptide of the nucleic acid-peptide-nucleic acid conjugate molecule is a substrate for cleavage by an enzyme, such as matrix metalloproteinase-8 (MMP-8). Exemplary applications of the nucleic acid-peptide-nucleic acid conjugate molecule for drug delivery, molecular assembly of hybrid structures, and constraining the peptide to a biologically active conformation are also disclosed.

To discover a substance having estrogen receptor β mRNA expression-promoting activity, type III collagen mRNA expression-promoting activity, elastin mRNA expression-promoting activity, matrix metalloproteinase-1 mRNA expression-inhibiting activity, or matrix metalloproteinase-3 mRNA expression-inhibiting activity, and to provide an estrogen receptor β mRNA expression promoter, a type III collagen mRNA expression promoter, an elastin mRNA expression promoter, a matrix metalloproteinase-1 mRNA expression inhibitor, and a matrix metalloproteinase-3 mRNA expression inhibitor, comprising such a substance as an active ingredient.SOLUTION: An estrogen receptor β mRNA expression promoter, a type III collagen mRNA expression promoter, an elastin mRNA expression promoter, a matrix metalloproteinase-1 mRNA expression inhibitor, and a matrix metalloproteinase-3 mRNA expression inhibitor, comprise a Citrus junos extract as an active ingredient.SELECTED DRAWING: None

This invention discloses a novel application of walnut bark extract. The invention employs a complex enzymatic hydrolysis combined with gradient solvent extraction, supplemented by macroporous resin purification technology, to obtain a walnut bark extract enriched with polyphenolic compounds. It has been demonstrated that this extract can increase the elastin content in human dermal fibroblasts, inhibit the expression of various types of matrix metalloproteinases, and has the effects of improving skin firmness and anti-photoaging. Therefore, it can be applied in the preparation of cosmetics with firming and anti-photoaging functions.

The invention provides an intelligent drug delivery system for treating osteoarthritis as well as a preparation method and application thereof, the intelligent drug delivery system is a drug-loaded micelle of which the surface is covalently coupled with a virus glycoprotein mimic peptide, and the hydrodynamic diameter is 16 + / -5 nm; the sequence of the mimic peptide comprises a type II collagen adhesion domain and a matrix metalloproteinase 13 specific lysis domain, and the mimic peptide can simulate a dual action mechanism of a virus: firstly, the mimic peptide is non-specifically adhered to a cartilage matrix to realize long-acting retention, and then the mimic peptide is specifically activated in a microenvironment in which pathological cells overexpress MMP13, a cell penetrating peptide is exposed, and efficient intracellular delivery of a drug is driven. The technical bottlenecks of short drug residence time, poor cartilage penetrability and lack of lesion cell targeting in the traditional treatment method are solved, the breakthrough from cartilage targeting to precise lesion cartilage cell targeting is realized, cartilage degeneration can be obviously delayed, symptoms can be improved, and excellent curative effects and clinical transformation prospects are shown.