22 results about "Pulmonary myofibroblast" patented technology

The invention relates to the technical field of organoid culture, in particular to a pulmonary fibrosis organoid model and a construction method and application thereof. The pulmonary fibrosis organ-like model is obtained by co-culturing lentivirus stably transfected alveolar epithelial cells, human embryonic lung fibroblasts MRC-5 and macrophages. According to the invention, macrophages are innovatively introduced, a ternary co-culture system of lentivirus stably transfected alveolar epithelial cells, human embryonic lung fibroblasts MRC-5 and macrophages is constructed, and a key'epithelial injury-immune infiltration-fibroblast activation 'pathological triangle in a pulmonary fibrosis pathogenesis process can be more comprehensively simulated; the finally obtained pulmonary fibrosis organ-like model provides an efficient tool for pulmonary fibrosis mechanism research and research, development and screening of anti-pulmonary fibrosis drugs.

The application relates to application of a sesquiterpenoid compound in preparation of a medicine for preventing and / or treating pulmonary fibrosis. The sesquiterpenoid compound has obvious inhibiting collagen deposition effect on TGF-beta 1 induced human embryo lung fibroblasts, does not show cytotoxicity, has good anti-pulmonary fibrosis activity, and can be used for preparing the medicine for preventing and / or treating pulmonary fibrosis.

The application belongs to the technical field of biological medicine, and particularly relates to application of calcium chelator BAPTA and a pharmaceutical composition. The calcium chelator BAPTA delays aging of lung fibroblasts and lung tissues by eliminating calcium accumulation in lung fibroblasts, reducing accumulation of reactive oxygen species ROS (ROS) in lung fibroblasts, DNA damage, and release of inflammatory factors. The calcium chelator BAPTA ultimately realizes the function of treating pulmonary fibrosis by inhibiting weight loss, lung tissue inflammatory cell infiltration, lung collagen deposition, and expression of fibrosis markers. The application provides a new drug source for delaying aging of lung fibroblasts and lung tissues and studying occurrence and development of pulmonary fibrosis. The drug is safe and reliable, has strong pharmacological action, small side effects, and definite curative effect.

The invention relates to a construction method of a perfusion vascularized cervical cancer organoid chip, and relates to the technical field of biology. Comprising the following steps: S1, constructing a cervical cancer organ; s2, mixing the cervical cancer organ small cell cluster, the human umbilical vein endothelial cells and the human embryonic lung fibroblasts in proportion, and centrifugally gathering the mixed cells in a low-adsorption U-shaped plate to form a pre-vascularized cervical cancer organ; s3, re-suspending the pre-vascularized cervical cancer organoid and the human umbilical vein endothelial cells in the fibrous protein hydrogel, transferring the pre-vascularized cervical cancer organoid and the human umbilical vein endothelial cells into the organoid chip, and adding a vascularized cervical cancer organoid culture medium for culture, so that the endothelial cells form perfused blood vessels, and finally obtaining the perfused vascularized cervical cancer organoid chip. The prepared perfusion vascularized cervical cancer organoid can well solve the in-vitro vascularization problem of the organoid, simulates the in-vivo tumor angiogenesis process, is close to the in-vivo real tumor microenvironment, and provides technical support for exploration of cervical cancer disease mechanisms and related treatment.

The application relates to an aromatic amide compound, a preparation method thereof and application of the aromatic amide compound in preparation of a medicine for treating and / or preventing pulmonary fibrosis. The aromatic amide compound has a structure as shown in the formula (I). In the formula (I), Ar is R is The aromatic amide compound can significantly inhibit TGF-beta 1 induced collagen deposition of human embryo lung fibroblasts, has good anti-pulmonary fibrosis activity, and can be used for preparing a medicine for preventing and / or treating pulmonary fibrosis.

The invention represents new hybrid compounds of two natural products sclareol and doxorubicin in the form of their conjugates. These compounds are in the form of conjugates, where doxorubicin and sclareol are covalently linked by a linker in a 1:1 molar ratio. The hybrids have shown to possess anticancer properties and are effective in treating resistant cancer cells that have P-glycoprotein membrane transporter, responsible for resistance to doxorubicin. The hybrids have been tested on different types of cell lines, including human glioblastoma, non-small cell lung carcinoma, and colorectal carcinoma. Also, a method for their preparation and their use in medical products or pharmaceutical preparations has been determined. The results of the study include the cytotoxic activity of single, combined, and conjugated compounds in pairs of sensitive and resistant cancer cells, with and without P-glycoprotein expression. The selectivity towards cancer cells was determined by comparing with commercially available normal human lung fibroblast cells. The study also investigated the nanoparticle nature of hybrid compounds, their intracellular localization and toxicity in vivo.

The invention discloses a new application of benzbromarone or pharmaceutically acceptable salt thereof in preparation of a medicine for treating pulmonary fibrosis. The invention belongs to the technical field of medicine. Experimental results show that the benzbromarone can significantly reduce collagen deposition and inflammatory infiltration in lung tissues, reduce fibrosis area, improve lung functions of patients with pulmonary fibrosis, inhibit lung fibroblast activation and inhibit fibrosis progress. The action mechanism of the gene is related to inhibition of expression of BAG2, FN1, Collagen I and protein. The invention provides a brand new medicine choice for treating pulmonary fibrosis, has the unique advantage of new use of old medicine, and has the potential of short research and development period, known safety and definite curative effect. Meanwhile, the invention further expands the application of benzbromarone in preparation of the protein inhibitor and the in-vitro reagent.

The invention discloses a biomarker for diagnosing pulmonary fibrosis and application thereof, and belongs to the technical field of clinical medicine. The pulmonary fibrosis biomarker lncRNA DLEU2 provided by the invention can effectively assist in diagnosing patients with pulmonary fibrosis, and activation of human lung fibroblasts can be effectively inhibited in the human lung fibroblasts through a knock-down agent sh-DLEU2.

The invention discloses a biomarker for diagnosing pulmonary fibrosis and application of the biomarker, and belongs to the technical field of biomarkers in clinical medicine. The biological marker for preparing and diagnosing pulmonary fibrosis is a nerve growth factor NGF, the nerve growth factor NGF can remarkably promote differentiation of lung fibroblast MRC5 cells, and along with expression increase of a receptor TrkA of the lung fibroblast MRC5 cells, the migration capacity and the multiplication capacity of the lung fibroblast MRC5 cells are remarkably enhanced. Meanwhile, the NGF also aggravates the formation of the BLM-induced pulmonary fibrosis of the mouse. Therefore, the nerve growth factor NGF as the biomarker has accurate and specific detection and auxiliary diagnosis on pulmonary fibrosis, especially idiopathic pulmonary fibrosis (IPF).

Disclosed are a biomimic system simulating lung tissue, a method for manufacturing same, and a microfluidic control method using same, wherein the biomimic system comprises lung epithelial cells and lung fibroblasts, which are isolated from human lungs, and commercially available vascular endothelial cells, and wherein a microfluid flows through the biomimic system. Each chamber inside the corresponding system can allow a fluid, which contains gas and a medium, to flow therethrough and simulate respiration-like movement, wherein all of the three types of cells can survive inside the system even when one week or more have elapsed after through-flow of the fluid. In addition, the pH and pO2 in the chamber can be monitored by using a pH sensor and a gas partial pressure sensor inside the system, and thus the three types of cells inside the system can be exposed to external environments, drugs, and the like under the same conditions as in the lungs in vivo. Therefore, a wide range of studies including modeling of lung diseases by harmful substances and testing of therapeutic drug efficacy can be conducted, and further, the utilization to in vitro disease modeling, customized medicine prescriptions, and the like can also be made.

The present disclosure provides a newly-identified transitional cell state in alveolar regeneration, models to ablate lung alveolar type-1 cells that leads to lung fibrosis and emphysema, a scalable, an ex vivo lung fibrosis model that uses co-cultured lung fibroblasts and pre-alveolar type-1 transitional cell state (PATS) for the use of disease modeling and drug screening, and methods of using same.

The invention relates to extracellular vesicles derived from human mesenchymal stem cells and application of the extracellular vesicles. The mesenchymal stem cell-derived extracellular vesicles according to the present invention inhibit the expression of fibrosis-related proteins, wound closure, and cell infiltration, which are increased due to TGF-beta1 treatment in pulmonary epithelial cells. In addition, a large amount of microRNAs contained in the extracellular vesicles inhibit gene expression of fibrosis-related proteins in pulmonary epithelial cells and pulmonary fibroblasts. In pulmonary fibrosis model mice, the extracellular vesicles significantly reduce the expression of fibrosis-related proteins, collagen production and fibrosis regions. Therefore, the extracellular vesicles according to the present invention can be used for preventing and treating pulmonary fibrosis.

The invention belongs to the technical field of biological medicine, discloses application of PARVA as a target spot in treatment of pulmonary fibrosis, and particularly relates to application of a PARVA down-regulating agent in preparation of medicine for treating pulmonary fibrosis. Aiming at the problem that the existing pulmonary fibrosis treatment medicine is difficult to target the pain point of a core pathological link, the medicine disclosed by the invention takes a PARVA gene in lung fibroblasts or an encoding protein thereof as a target spot, and comprises a knockdown medicine (such as shRNA, siRNA and miRNA), a knockout medicine (such as a Cre / LoxP system) or a targeted blocking medicine (such as a small molecule compound and polypeptide), preferably an injection, an atomizing agent and other dosage forms. The down-regulating agent realizes inhibition of activation and proliferation of lung fibroblasts and extracellular matrix deposition by down-regulating PARVA expression or inhibiting PARVA activity, so as to block pulmonary fibrosis progress. The invention has the advantages of strong target specificity, clear action mechanism, various drug types, obvious treatment effect and the like, and provides a new effective strategy for pulmonary fibrosis treatment.

The invention discloses a lung protection function exosome based on resveratrol-astragalus membranaceus-ginseng induction, an inhalation preparation and application, and belongs to the technical field of biology. The exosome is obtained by inducing lung fibroblasts by active ingredients containing resveratrol, an astragalus extract and a ginseng extract and then secreting the lung fibroblasts; wherein the content of astragaloside in the astragalus extract is not less than 2.0%, and the total content of ginsenoside Rg1 and Rb1 in the ginseng extract is not less than 5.0%. The invention also provides a dry powder inhalant or an aerosol inhalation solution containing the exosome. The exosome and the preparation thereof play a lung protection role through multiple mechanisms such as inflammation regulation and control, oxidative stress resistance and repair promotion, can be used for preventing and / or treating various lung injury diseases such as acute lung injury and pneumonia, and have the advantages of good biocompatibility and strong targeting property.

The invention relates to an application of circular RNA (Ribonucleic Acid) in preparation of a reagent for screening chronic obstructive pulmonary disease. The circular RNA is miR-377-3p. The invention finds that miR-377-3p is up-regulated in chronic obstructive pulmonary disease patients, most of miR-377-3p is located in lung fibroblasts, and the chronic obstructive pulmonary disease can be improved by inhibiting miR-377-3p. The invention also finds that ZFP36L1 is a direct target of the miR-377-3p, and the ZFP36L1 mediates the senescence promoting activity of the miR-377-3p in the lung fibroblasts. The miR-377-3p is crucial to the attack of the chronic obstructive pulmonary disease and is expected to become a new target spot for treating the chronic obstructive pulmonary disease.

Provided is a fluidic chip, comprising: a bottom region, the bottom region comprising a central channel and at least one side channel adjacent thereto, the central channel having therein a plurality of cells disposed in a matrix; and a middle region, the middle region having a chamber defined therein, the chamber optionally being an open-top chamber, the chamber being in register with at least one of the central channel and the at least one side channel of the bottom region. Also provided is a method, comprising co-culturing airway epithelial cells, pulmonary microvascular endothelial cells, and lung fibroblasts using a fluidic chip; the airway epithelial cells comprising airway cells or alveolar cells. Also disclosed is causing contact between (1) at least one of an agent and a stimulus, and (2) epithelial cells disposed within the chamber of a fluidic chip, and monitoring at least one marker indicative of exposure of the epithelial cells to the sample.

Disclosed herein are methods for treating an individual having, or at risk of having, pulmonary fibrosis, wherein volasertib, a salt thereof, or hydrate thereof, is administered to the individual in need thereof. In one aspect, the pulmonary fibrosis may be idiopathic pulmonary fibrosis. The volasertib may be administered in an amount and for a duration of time effective to achieve one or more outcomes selected from decreased invasiveness of pulmonary fibroblasts, increased clearance of myofibroblasts, decreased migration of pulmonary fibroblasts, decreased pulmonary fibroblast proliferation, decreased cell adhesion of pulmonary fibroblasts, decreased myofibroblast activation, decreased extracellular matrix (ECM) accumulation or production, and improved lung function.

The application provides application of chamaecyparis funebris polysaccharide in preparation of a medicine for preventing and / or treating pulmonary fibrosis, and belongs to the technical field of medicines.The application finds that chamaecyparis funebris polysaccharide can effectively prevent and / or treat pulmonary fibrosis, and can effectively reduce lung injury and inhibit lung inflammation; chamaecyparis funebris polysaccharide inhibits fibrosis and migration of human embryo lung fibroblasts induced by recombinant human transforming growth factor, improves lung function injury and pulmonary fibrosis of a bleomycin-induced pulmonary fibrosis mouse, inhibits inflammatory cell infiltration of bronchial alveoli and expression of NOD-like receptor family pyridine domain-containing protein 3 (NLRP3) in lung tissue of the pulmonary fibrosis mouse, and further inhibits lung inflammation; chamaecyparis funebris polysaccharide can also inhibit the Hedgehog signal pathway in vitro and in vivo, and the improvement of lung function of the bleomycin-induced pulmonary fibrosis mouse and the treatment of pulmonary fibrosis by chamaecyparis funebris polysaccharide are further enhanced when assisted by a Hedgehog pathway inhibitor.

The invention discloses an application of carnosine in preparation of a medicine for improving pulmonary fibrosis, and belongs to the technical field of medicines. According to the present invention, the puberine VOM can induce disulfiram death by improving the protein expression level of the SLC7A11 of lung fibroblasts so as to alleviate the pulmonary fibrosis symptom, the treatment strategy of the pulmonary fibrosis disease can be further expanded, and the treatment of the pulmonary fibrosis by using the VOM has good application prospects.

The invention discloses application of k-252a in preparation of a medicine for inhibiting pulmonary fibrosis, and belongs to the technical field of clinical medicine. The k-252a is an inhibitor of the nerve growth factor NGF, the nerve growth factor NGF can significantly enhance the differentiation of lung fibroblast MRC5 cells, and induced differentiation is increased along with the expression of a receptor TrkA of the nerve growth factor NGF, so that the migration ability and the activation ability of the lung fibroblast are significantly enhanced. The k-252a provided by the invention achieves the purpose of inhibiting pulmonary fibrosis, especially idiopathic pulmonary fibrosis, by inhibiting protein expression of TGF-beta1 and immune response factors IL-2RA and IFN-gamma caused by a nerve growth factor NGF.

The application discloses application of an RRBPl protein inhibitor in preparation of a product with a protective effect on lung fibrosis, and belongs to the technical field of biological medicines. The product with the protective effect on lung fibrosis refers to a medicine or a recombinant carrier for inhibiting expression of RRBPl protein, and the recombinant carrier contains or carries a polynucleotide for coding RRBPl shRNA. The application further discloses an adeno-associated virus carrier with the protective effect on lung fibrosis and carrying RRBPl shRNA, which is beneficial to protecting lung fibrosis induced by bleomycin, reducing infiltration of myofibroblasts and deposition of extracellular matrix. In-vivo cell experiments find that RRBPl knockdown can inhibit transdifferentiation of human primary lung fibroblasts into myofibroblasts and deposition of extracellular matrix. These results show that RRBPl can be targeted to treat or prevent fibroproliferative diseases. The application provides a new method for treating fibroproliferative diseases.