50 results about "M2 Macrophage" patented technology

The invention discloses an M2M-SeMSN-coated C176 nano-particle, a preparation method and application thereof, the nano-particle comprises an STING inhibitor C176 and a carrier, and the carrier is based on an M2 macrophage membrane and a selenium-bridged mesoporous silica nano-particle. Specifically, the M2M-SeMSN-coated C176 nano-particles are obtained by loading an STING inhibitor C176 by using a selenium-bridged mesoporous silica nano-particle SeMSN and M2 macrophage cell membrane. The invention further discloses a preparation method of the M2M-SeMSN-coated C176 nano-particles. The M2M-SeMSN-coated C176 nanoparticles can be used for preparing a medicine for treating acute kidney injury.

The invention discloses a high-activity injectable self-healing temperature-sensitive hydrogel dressing and a preparation method and application thereof, the high-activity injectable self-healing temperature-sensitive hydrogel dressing is obtained by forming a temperature-sensitive hydrogel through a two-dimensional nano material MXene aqueous solution and F127 under the hydrogen-bond interaction, combining an M2 macrophage source exosome on MXene under the electrostatic adsorption action, and wrapping the MXene through a network structure of the hydrogel. The preparation method is simple, an obtained sample is free of organic solution residues, reaction conditions are mild, operation is convenient, the raw material cost is low, the hydrogel dressing has temperature-sensitive, injectable and self-healing performance, the hydrogel dressing has temperature-sensitive and injectable performance, is sol at normal temperature, forms gel after making contact with skin and is convenient to smear and use on wounds, and experimental results prove that the hydrogel dressing has good application prospects. The hydrogel has good biocompatibility and relatively strong antibacterial performance, and can effectively play anti-inflammatory and vascular regeneration promoting roles in diabetic wounds and promote rapid repair of the diabetic wounds.

The invention discloses an immunomodulatory composition based on a cordycepin-selenium nano chelate and a preparation method thereof, and belongs to the technical field of biological medicines.The immunomodulatory composition is characterized in that 15-25 nm zero-valent selenium nano particles are chelated through hydroxyl of cordycepin and N7 site bidentate coordination, and a stable five-membered ring structure with the molar ratio is formed; the preparation method comprises the following steps: reducing sodium selenite in an inert atmosphere to generate selenium colloid, chelating the selenium colloid with a cordycepin ethanol solution, and carrying out ultrafiltration and freeze-drying to obtain the product. The invention aims to solve the problems of fuzzy structure, inconsistent batch, uncontrollable immunomodulatory function and the like caused by non-specific mixing in the prior art, and the composition can bidirectionally regulate and control IRF3 pathways, promote polarization of M2 type macrophages and proliferation of Treg cells, and has a clear immunomodulatory mechanism and excellent stability.

The present application relates to a kind of water gel support prepared by self-assembled polypeptide and the use of support obtained therefrom, the preparation method includes: 1) self-assembled peptide sequence is linked nerve growth factor analog peptide by covalent bond to obtain bonded functional polypeptide;2) macrophage is separated and cultured, and is induced to be " alternative activation " anti-inflammatory M2 macrophage, obtain culture supernatant and carry out filtration, obtain filtered cell culture supernatant;3) filtered cell culture supernatant is mixed with bonded functional polypeptide, obtain mixed solution and adjust the concentration of the mixed solution, the bonded functional polypeptide self-assembles and forms water gel support.The present application uses M2 macrophage condition culture supernatant to construct regenerative microenvironment, combines polypeptide functional water gel support, realizes better overall interaction, and prepares the water gel support that can supplement and regulate nerve regeneration, the support can promote nerve cell regeneration behavior, provides new selection for tissue engineering biomaterials.

The invention discloses a rheumatoid arthritis targeted therapeutic drug and a preparation method thereof, and relates to the field of medicines. The invention relates to an acid response nano-particle CEC NPs, which is specifically composed of the following components: a carrier, which is an M2 type macrophage derived exosome; and loading the medicine. According to the acid response nano-particles based on the CXB and the CC-90011 loaded on the exosome derived from the M2 type macrophage, the M2Exo can specifically target an inflammatory environment, and the specific anti-inflammatory biological function of the M2Exo can be exerted; under the acidic condition, CEC NPs responds to release CE NPs and CC-90011, the CE NPs can repolarize M1 type macrophages and inhibit FLS activation to effectively relieve arthritis inflammatory response and synovial hyperplasia, and the CC-90011 can inhibit LSD1 to interfere the energy metabolism pathway of osteoclasts and inhibit osteoclast formation, so that the pathological bone resorption process is blocked, and bone erosion is relieved.

This invention discloses a biomimetic nanocomposite, its preparation method, and its application in the preparation of products for treating atherosclerosis, belonging to the field of pharmaceutical preparation technology. The biomimetic nanocomposite is an Ir-TiO2 metal nanozyme encapsulated in an M2 macrophage membrane. This invention prepares a structurally biomimetic nanocomposite by coating Ir-TiO2 nanoparticles with an M2 macrophage membrane. After intravenous injection, the formed biomimetic nanocomposite actively targets endothelial cells in atherosclerotic lesions, releasing Ir-TiO2 antagonistically into the cytoplasm of plaque-containing endothelial cells and inflammatory macrophages. Once Ir-TiO2 reaches the lesion site, it exerts an enzymatic effect to achieve anti-inflammatory activity and promotes cholesterol excretion from inflammatory cells such as macrophages and smooth muscle cells at the lesion site, reducing intracellular lipid deposition, reducing foam cell formation, and promoting plaque growth. This nanotherapy can effectively prevent the progression of inflammation in atherosclerotic lesions and alleviate atherosclerosis.

A treatment composition for inhibiting systemic sclerosis Vimentin mutant protein activity by using an STAT6 inhibitor, which inhibits the expression of an M2 macrophage and a profibrotic T cell which are immunocytes related to systemic sclerosis, and increases the expression of a Treg, and inhibits the expression of TGF-β, Col1a1, and α-SMA which are fibrosis factors related to systemic sclerosis. The presence of a pSTAT6 expression CD8 T cell in a fibrosis tissue has been identified, and that the expression of a pSTAT6 expression CD8 T positive cell is controlled via injection of the STAT6 inhibitor. In an animal model with increased Vimentin-specific disease symptom activity, the STAT6 inhibitor inhibits antigen-specific tissue fibrosis of systemic sclerosis with activated disease symptoms, and that the STAT6 inhibitor inhibits the expression of IL-17 cytokine expression CD8 positive TRM capable of inducing fibrosis and cell inflammation which are systemic sclerosis diseases.

The application provides a macrophage-targeted FGF19 sustained-release delivery system, a preparation method and an application. The system comprises FGF19-loaded macrophage membrane-derived nanoparticles and a temperature-sensitive hydrogel embedding the nanoparticles. The temperature-sensitive hydrogel is made of chitosan, poloxamer and beta-glycerophosphate sodium. The size of the macrophage membrane-derived nanoparticles is 300-800 nm. The system is an injectable liquid at 0-10 DEG C and forms a gel at 20-37 DEG C, achieving sustained release of FGF19 and drug-loaded vesicles. The system can promote re-epithelialization, collagen deposition, angiogenesis and M2 macrophage infiltration of a wound surface and is used for preparing a medicine or a dressing for promoting skin wound repair.

A nanoparticle for treating hepatocellular carcinoma (HCC) in which the nanoparticle includes a lipid phase and a core that contains one or more nucleic acids encoding a chimeric antigen receptor (CAR), a T-cell engager (TCE), and / or a therapeutic gene. The CAR and the TCE each binding specifically to an HCC tumor-associated antigen and the nanoparticle selectively delivers the one or more nucleic acids to M2 macrophages in vitro and in vivo. Also provided is a therapeutic composition that contains a plurality of the nanoparticle described above and a pharmaceutically acceptable excipient. Further provided are methods for converting HCC tumor-resident M2 macrophages into M1 macrophages, and for treating HCC.

The invention discloses a bionic nano drug delivery system for treating pterygium as well as a preparation method and application of the bionic nano drug delivery system. The bionic nano drug delivery system comprises an inner core and a bionic membrane shell, the inner core is composed of polylactic acid-glycolic acid copolymer nano-particles, and curcumin is encapsulated in the inner core to serve as a therapeutic drug; the biomimetic membrane shell is composed of an M2 type macrophage membrane and wraps the surfaces of the polylactic acid-glycolic acid copolymer nanoparticles. The drug-loading system can be administered in the form of eye drops, is used for treating pterygium, particularly shows a good treatment effect in a mouse corneal alkali burn model, and can promote polarization of macrophages to M2 type and regulate the ocular surface inflammation microenvironment. According to the invention, the biodegradability and slow release characteristics of PLGA, the anti-inflammatory activity of curcumin and the targeting and immunoregulation functions of M2 type macrophage membrane are combined, the stability and bioavailability of the medicine are remarkably improved, and an efficient and safe new strategy is provided for treatment of pterygium.

This application discloses the application of PLAC8 as a target in the preparation of tumor therapeutic drugs, involving the field of biomedical technology. This application clarifies that the "sympathetic nervous system-β2-AR-PLAC8-cholesterol metabolism-M2 polarization" pathway is the core driving pathway for stress-related tumor progression and chemotherapy resistance. It reveals the molecular mechanism by which PLAC8 inhibits cholesterol synthesis through phosphorylation at the S67 site, binding to the N-terminal domain of SREBP2, recruiting OGT to mediate SREBP2O-GlcNAc glycosylation. Through strategies such as gene silencing, β2-AR antagonist intervention, and targeted delivery of siPLAC8 via mannose-modified lipid nanoparticles (LNPs), the application achieved the effects of inhibiting M2 macrophage accumulation, inhibiting tumor growth, and reversing chemotherapy resistance in various tumor models, including gallbladder cancer, intrahepatic cholangiocarcinoma, and prostate cancer. Furthermore, the LNPs delivery system showed no significant toxicity. This research provides a novel therapeutic target centered on PLAC8 and a safe and effective targeted intervention strategy for stress-related tumors, highlighting its clinical translational value.

The invention provides a responsive hydrogel of chidamide extracellular vesicles and a preparation method thereof, engineered EVs loaded chidamide, and a TSPBA / TVA hydrogel with a pH responsive characteristic is prepared, the preparation can realize sustained and controlled release of EVs under an acidic condition, effectively overcome the defect of direct injection, establish a linkage regulation mechanism of a microenvironment pH value and disease progression, and improve the treatment effect of the chidamide extracellular vesicles. According to the mechanism, the administration dosage is reduced, the action time is prolonged, tumor microenvironment targeted drug delivery is realized, a new thought is provided for tumor treatment, and the mechanism has important clinical transformation value.

This invention provides a method and system for processing hepatocellular carcinoma data. The method utilizes the CIBERSORT tool combined with weighted gene co-expression network analysis to screen a gene set positively correlated with M2 macrophage infiltration. Through differential expression analysis and prognostic correlation analysis, target genes with prognostic value are identified from the gene set. A dataset containing the target genes is acquired, and a comprehensive machine learning algorithm is used to generate several corresponding prognostic prediction models for each dataset. The C-index of the dataset in the corresponding prognostic prediction model is calculated, and target prognostic prediction models are selected based on the C-index and the complexity of the prognostic prediction model. Compared to the traditional method of selecting an algorithm for modeling at the beginning of the study, the final selected target prognostic prediction model reflects more objective and realistic prediction results. Furthermore, the prediction accuracy of this target prognostic prediction model is improved.

The present application relates to the technical field of biological medicine, in particular to a new application of a BTK PROTAC compound NX-5948, especially to a new application of a Bruton's tyrosine kinase protein degradation targeting chimera BTK PROTAC compound NX-5948 in a drug for treating secondary hemophagocytic syndrome (HLH). In the present application, the BTK PROTAC compound NX-5948 inhibits the activation of the macrophage BTK / NF-κB axis signaling pathway through targeting, on the one hand, reduces the number of activated macrophages by inhibiting the proliferation and survival of macrophages, on the other hand, induces the polarization of macrophages from pro-inflammatory M1 macrophages to anti-inflammatory M2 macrophages through the immunoregulatory effect on macrophages, and then inhibits the release of cytokines and the occurrence and development of HLH, so that the effect of the new application of the present application is that it can inhibit the abnormal activation of macrophages and improve the clinical symptoms or laboratory indexes existing in patients with secondary hemophagocytic syndrome.

This invention belongs to the field of biomedical technology and provides the application of exosome-derived TRIM59 inhibitors in regulating macrophage M2 polarization and combating oral squamous cell carcinoma. The TRIM59 inhibitor uses exosomes derived from oral squamous cell carcinoma tissue as carriers, with the surface modified with the M2 macrophage-targeting molecule M2pep, internally loaded with TRIM59 inhibitors and KRT6B inhibitors, and loaded with STING pathway agonists. This invention relies on the microenvironment targeting and membrane surface targeting modification of tumor-derived exosomes to precisely deliver TRIM59 inhibitors and KRT6B inhibitors to M2 macrophages and tumor cells. By silencing TRIM59, the resistance of M2 macrophages to the STING pathway is relieved, forming a temporal synergistic effect of first unlocking and then activating with the STING agonist, driving macrophages to M1 polarization.

This invention provides a resveratrol-sulfated Hericium erinaceus β-glucan-chitosan nanocomposite, its preparation method, and its applications, belonging to the field of nanomaterials technology. This invention uses sulfated Hericium erinaceus β-glucan and chitosan as nanocarriers, and prepares the resveratrol-sulfated Hericium erinaceus β-glucan-chitosan nanocomposite through electrostatic interaction self-assembly. This significantly improves the solubility, chemical stability, and bioavailability of resveratrol, thereby enhancing its anti-inflammatory effect, and exhibits an in vitro sustained-release effect compared to free resveratrol. The results of the examples show that the resveratrol-sulfated Hericium erinaceus β-glucan-chitosan nanocomposite of this invention can enter M1 macrophages through endocytosis, effectively inhibiting the pro-inflammatory capacity of M1 macrophages, realizing the polarization of pro-inflammatory M1 macrophages into anti-inflammatory M2 macrophages, and exerting an anti-inflammatory effect.

The present invention discloses a chimeric switch receptor for macrophages and its application, which belongs to the field of biomedicine technology. The chimeric switch receptor for macrophages provided by the present invention includes: an extracellular region, the extracellular region includes the extracellular domain of IL-2α, IL-2β or IL-2γ receptor; a transmembrane region, the transmembrane region includes the transmembrane domain of CD8 or CD28 molecule; an intracellular region, the intracellular region includes the intracellular domain of CD3ζ, TLR4, CD40 or Dectin1 molecule. The chimeric switch receptor of the present invention is expressed on the surface of tumor-associated macrophages, which can induce M2 macrophages to transform towards M1 phenotype after binding of exogenous IL-2 to the chimeric switch receptor on the cell surface, thereby fully exerting the phagocytic and killing effect on tumor cells.

The invention provides an M2 macrophage exosome loaded canagliflozin nano-drug and application thereof, an M2 macrophage exosome is used as a carrier, and canagliflozin is loaded on the M2 macrophage exosome. The Exo-CANA delivery system is constructed for the first time, the exosomes are small in size, the phagocytosis of mononuclear macrophages can be effectively avoided, the exosomes can freely penetrate through vascular walls and extracellular matrixes, Th2 type airway inflammation, goblet cell metaplasia and pulmonary interstitial collagen deposition can be remarkably improved, and the treatment effect is remarkably superior to that of a CANA single-drug treatment group and an M2-Exos single-drug treatment group.

The invention belongs to the technical field of biological medicine, and particularly relates to an M2 macrophage membrane wrapped ROS response type bionic nano delivery system as well as a preparation method and application thereof. The ROS response type bionic nano delivery system wrapped by the M2 macrophage membrane is composed of ROS response nano particles carrying therapeutic drugs and the M2 macrophage membrane wrapping the ROS response nano particles. The ROS response type bionic nano delivery system wrapped by the M2 macrophage membrane provided by the invention is excellent in biocompatibility, has the functions of immune escape, precise targeting, removal of ROS in cells, inhibition of inflammatory injury and cell apoptosis and the like, and provides a bionic nano delivery system with targeting delivery, intelligent drug release and multi-dimensional regulation and control for atherosclerosis.

The present invention relates to a metal-organic framework for inhibiting the activity of M2 macrophages, and a pharmaceutical composition comprising same, wherein the metal-organic framework of the present invention is non-toxic to cells and can exhibit an effect of inhibiting the activity of M2 macrophages. More specifically, the metal-organic framework of the present invention can be provided as an anticancer composition for tumor-related macrophage-mediated diseases, particularly solid cancer, through the inhibition of M2 macrophages capable of increasing the expression of genes associated with parasite invasion, tissue remodeling, and tumor proliferation (immunomodulatory function), and can also be provided as a pharmaceutical composition for treating chronic infectious diseases, liver cirrhosis, obesity-related metabolic diseases, scar formation and idiopathic lung diseases.

The invention discloses co-delivery lipid nanoparticles targeting M2 type macrophages as well as a preparation method and application of the co-delivery lipid nanoparticles. The lipid nanoparticle is prepared from an ionizable cationic lipid, a neutral auxiliary lipid, cholesterol, a PEGylated lipid containing disulfide bonds, a PEGylated lipid of which the tail end is connected with mannose, and an encapsulated nucleic acid drug containing miR-99b and SIRP alpha siRNA, and glutathione responsive PEG exfoliation in a tumor microenvironment is realized by introducing DSPE-S-S-PEG3000; and DSPE-PEG2000-mannose is utilized to realize active targeting based on CD206 recognition, so that the therapeutic nucleic acid is co-delivered to the M2 type tumor-associated macrophages efficiently and specifically. The nanoparticles can synergistically reverse M2 macrophages into M1 anti-tumor phenotypes and block CD47-SIRP alpha'eating my 'signals, effectively remodel an immunosuppression microenvironment, and show excellent tumor targeting ability, tumor growth and metastasis inhibition and anti-tumor immune response promotion effects in hepatocellular carcinoma treatment.

The invention discloses a lysosome-oriented luteolin carbon dot as well as a preparation method and application thereof in the technical field of carbon dot application, luteolin and 2, 5-dihydroxyterephthalic acid are used as carbon source precursors, the luteolin carbon dot is prepared by a hydrothermal method, the particle size of the prepared luteolin carbon dot is 0.5-4 nm, and the particle size of the prepared luteolin carbon dot is 0.5-2 nm. The fluorescence excitation wavelength is 360 to 440 nm, the maximum emission wavelength is 540 nm, and the Zeta potential is-19 mv; researches find that luteolin carbon dots can guide macrophages and fat cell lysosomes, promote polarization of M2 type macrophages, and up-regulate heat production of beige fat cells and expression of a brown marker gene Ucp1; furthermore, the M2 type macrophage loaded with the luteolin carbon dots can promote expression of beige fat cells Ucp1 through carbon dot release and paracrine effects, so that heat production and energy consumption are increased, and a foundation is laid for development of intervention treatment schemes for obesity and related metabolic diseases based on the carbon dots in the future.

Method of treating secondary cancer in a lung of a subject in need thereof, comprising administering a pharmaceutical composition comprising an effective amount of an inhibitor of transcriptional enhanced associate domain (TEAD) to the subject. In addition, methods of inhibiting growth of a secondary tumor in a lung of a subject in need thereof, of increasing number of T-cells at a secondary tumor in a lung of a subject in need thereof, of increasing number of alveolar macrophages in a lung of a subject in need thereof, of decreasing number of infiltrating monocytes / macrophages in a lung of a subject in need thereof, methods of reducing lung metastases in a subject in need thereof, method of inducing polarization of one or more M2 macrophages to M1 macrophages in the lung of a subject with lung cancer, and methods of activating IL12 signaling in lung of a subject with lung cancer.

The present invention provides a tissue repair biomaterial, preparation method, and application, as well as a rotator cuff injury repair product, relating to the field of biotechnology. The tissue repair biomaterial comprises a ROS-responsive hydrogel with immunomodulatory effects and a nanofiber membrane that promotes bone and cartilage repair. The ROS-responsive hydrogel comprises a hydrogel and M2 macrophage exosomes dispersed within the hydrogel. The fibers comprising the nanofiber membrane have a core-shell structure, with the nuclear layer containing exosomes from bone marrow mesenchymal stem cells. The ROS-responsive hydrogel coats the surface of the nanofiber membrane. This tissue repair biomaterial has the advantages of low immunogenicity and good targeting, enabling the spatiotemporal therapeutic purpose of first modulating the immune-inflammatory microenvironment and then continuously promoting bone and cartilage regeneration.

The application belongs to the technical field of biological medicine, and particularly discloses a Bradyrhizobium sp. (Lupuli) exosome and application thereof in preparation of a product for treating dry eye syndrome, and provides application of the Bradyrhizobium sp. (Lupuli) exosome in preparation of a product for preventing and / or treating dry eye syndrome. The Bradyrhizobium sp. (Lupuli) exosome provided by the application can inhibit growth of Staphylococcus epidermidis, promote transformation of anti-inflammatory phenotype M2 macrophages, reduce content of M1 macrophage pro-inflammatory factors, and increase content of M2 macrophage anti-inflammatory factors. The Bradyrhizobium sp. (Lupuli) OMV is configured into eye drops and added to an ocular surface in the form of eye drops. It is observed that the Bradyrhizobium sp. (Lupuli) OMV has an improvement effect on dry eye disease phenotype of a dry eye mouse model. Pathological sections and inflammatory factor detection also find that the Bradyrhizobium sp. (Lupuli) OMV reduces inflammatory damage of an eye tissue of a dry eye model mouse. The Bradyrhizobium sp. (Lupuli) OMV provided by the application can significantly improve symptoms and signs of dry eye syndrome.

A nanoparticle for selective transfection of M2 macrophages, the nanoparticle including a lipid phase and a core that contains one or more nucleic acids. The nanoparticle selectively delivers the one or more nucleic acids to M2 macrophages in vitro and in vivo. Also provided is a therapeutic composition that contains a plurality of the nanoparticle described above and a pharmaceutically acceptable excipient. Further provided are methods for selective transfection of M2 macrophages, for converting M2 macrophages into M1 macrophages, and for treating a cancerous tumor. The methods are carried out by contacting M2 macrophages with a composition that includes a plurality of the nanoparticle mentioned above.

The invention relates to the field of biological medicines, discloses an application of icariside II in preparation of a medicine for treating pulmonary fibrosis, and further discloses a composition and a medicine for treating pulmonary fibrosis. It is verified for the first time that ISE II inhibits BLM-induced pulmonary fibrosis by regulating M2 macrophage exosome protein Hsp90aa1, the disease treatment field of ISE II is expanded, and the fundamental research depth of ISE II is increased; according to the application of the exosome derived from the M2 macrophages, the activation and migration of the fibroblasts are induced by the exosome derived from the M2 macrophages through an Hsp90aa1 / beta-catenin axis, related contents of interaction of the M2 macrophages and the fibroblasts in pulmonary fibrosis are supplemented, and a new research direction is developed for clinic; the specific component of the exosome cargo comprises Hsp90aa1 or other molecules, and can be used as a potential disease treatment target for subsequent research.

The invention discloses a triptolide-loaded engineered M2 macrophage exosome drug delivery system as well as a preparation method and application thereof, and belongs to the technical field of biological medicines. A carrier of the delivery system is an M2 type macrophage source exosome combined and modified by phospholipid polyethylene glycol glucose; a loaded drug is triptolide, the triptolide is subjected to nano-micelle phospholipid polyethylene glycol glucose surface modification to form hypoxia response nanoparticles, M2Exo can target an inflammatory environment induced by macrophages, the specific anti-inflammatory biological function of M2Exo can be played, and the hypoxia response nanoparticles can be used for preparing the anti-inflammatory drug. Under the hypoxia condition, the compound is specifically taken by M1 macrophages, the polarization level and inflammatory response of the compound are inhibited, and the drug delivery efficiency is remarkably improved. Animal experiment model verification shows that the system can regulate and control rheumatoid arthritis synovial inflammation by regulating the polarization level of macrophages and improve the condition of arthropathy. According to the scheme, a new technical scheme is provided for precise treatment of inflammatory lesions such as rheumatoid arthritis caused by macrophages.

A method of treating cancer in a subject is provided, the method including administering to the subject a therapeutic amount of a composition including phosphatidylglycerol nanovesicles (NVs). A method of inhibiting M2 macrophage polarization in a tumor microenvironment by administering phosphatidylglycerol NVs is also provided, together with pharmaceutical compositions including phosphatidylglycerol NVs.

This invention provides siRNA that specifically binds to CD206 on M2 macrophages. The siRNA is at least one of siRNA-1, siRNA-2, and siRNA-3, or at least one of siRNA-4, siRNA-5, and siRNA-6. The siRNA provided by this invention specifically binds to CD206 on M2 macrophages, thereby reducing CD206 expression and promoting M2 macrophage proliferation, which in turn inhibits tumor cell proliferation and migration.