32 results about "Selectin" patented technology

The invention discloses a functional hydrogel microsphere and a preparation method and application thereof, and relates to the technical field of medicines.The preparation method comprises the steps that a hyaluronic acid methacrylic acid precursor solution and an IL-1beta shRNA adenovirus stock solution are mixed to obtain an Ad-atHAMA precursor solution; preparing the Ad (at) HAMA precursor solution through an oil-in-water micro-fluidic technology to obtain an Ad (at) HAMA microsphere; and sequentially adding the Ad (at) HAMA microspheres, 1-ethyl-3-(3-dimethylaminopropyl) carbodiimide and N-hydroxysuccinimide into a 2-morpholinoethanesulfonic acid buffer solution, carrying out activating treatment, adding E selectin, and incubating to obtain the functionalized hydrogel microspheres. The functionalized hydrogel microspheres can inhibit a related mechanism of acute spinal cord injury pathological progress and promote neural function repair by targeting adsorption of neutrophil to regulate Nets-triggered innate immune inflammation cascade.

The invention relates to a ligand targeting neutrophil and neurons as well as a preparation method and application of the ligand. The ligand for targeting the neutrophil and the neuron is prepared from the following raw materials in parts by weight: 30 to 50 parts of DSPE-PEG-Tet1, 2 to 3 parts of ketal thiol with carboxyl groups at two ends and 30 to 50 parts of a neutrophil targeting ligand, the neutrophil targeting ligand is one or more of sialic acid, an anti-CD66b antibody, an anti-CD177 antibody, an anti-CD16b antibody, N-formylmethionine peptide (fMLF) and an analogue thereof, a CXCR1 / CXCR2 binding peptide, an integrin binding peptide, a selectin ligand and lectin. According to the invention, sequential targeting of neutrophile granulocytes-neurons can be realized, target cells of ischemic lesions can be accurately protected, and the improvement effect on the cerebral infarction area of MCAO rats can be obviously enhanced.

The inventors' primary objective was to provide a technology for screening materials that can suppress inflammation, particularly in aging tissues. [Solution] The above problem can be solved by a method that includes step B: contacting vascular endothelial cells that have been passaged 15 or more times with a test substance, and step C: evaluating the expression level of at least one inflammation-related factor selected from the group consisting of IL-6, IL-8, CXCL1, PAI-1, MMP-1, ICAM-1, VCAM-1, E-selectin, and CCL2 in the vascular endothelial cells that were contacted with the test substance in step B.

The invention provides antibodies, and antigen-binding fragments thereof, that specifically bind to E-selectin. The invention includes uses, and associated methods of using the antibodies, and antigen-binding fragments thereof.

The application discloses a cerebrospinal fluid auxiliary diagnosis marker for neuropsychiatric lupus, and relates to the application of any one or more of TCN2, CST6, Trappin-2 and L-selectin as a diagnosis marker in the preparation of a cerebrospinal fluid auxiliary diagnosis reagent for neuropsychiatric lupus. The application provides four biomarkers of TCN2, etc. with high specificity and high sensitivity for diagnosing neuropsychiatric lupus, fills the blank in the field, further improves the accuracy of diagnosis, helps to realize timely early warning in clinic, and helps to establish a new clinical diagnosis standard for lupus encephalopathy.

This invention discloses a reactive oxygen species (ROS)-responsive nanocomposite for targeting and repairing damaged endothelium, its preparation, and its application, belonging to the field of nanomedicine technology. The nanocomposite comprises a physalicylate-copper nanoparticle core and a P-selectin-targeting polypeptide linked to the core surface via thiol-copper affinity. The physalicylate-copper nanoparticle core is prepared by coordination of physalicylate and copper ions to form a primary complex, followed by ascorbic acid reduction. This composite nanosystem can specifically recognize and accumulate in the blood vessels and peritubular regions of the kidney injury area, releasing Cu in response to high concentrations of ROS in an inflammatory environment. 2+ Together with HBT, it simultaneously achieves antioxidant and anti-inflammatory functions, promotes angiogenesis and repair, and inhibits the release of inflammatory factors and macrophage infiltration and activation, effectively blocking the fibrosis process. This system has a well-defined structure and strong targeting, and can effectively rebuild microvessels, reduce inflammation, and block the process of renal fibrosis, providing a highly efficient and precise new nanomedicine strategy for the anti-fibrotic treatment of kidney diseases.

The invention discloses an application of a Yinxiaonaotong soft capsule in preparation of a medicine for preventing and treating acute lung injury, and experimental research shows that the Yinxiaonaotong soft capsule can significantly improve lung histopathologic injury of an acute lung injury mouse model activated and induced by a complement bypass and relieve inflammatory cell infiltration. The mechanism of action is as follows: the Yindanaotong can effectively inhibit the expression of key inflammatory mediators (TNF-alpha, IL-6) and adhesion molecules (ICAM-1, P-selectin) in lung tissues and serum. Meanwhile, the medicine can down-regulate the mRNA transcriptional level of NF-kappa B p65, JNK, p38 MAPK and STAT3 signal channel related genes in lung tissues and inhibit phosphorylation activation of corresponding proteins. The results comprehensively show that the Yindan Xinnaotong compound intervenes in an inflammation signal channel through multiple targets, and plays roles in resisting inflammation and protecting lung tissues, so that the Yindan Xinnaotong compound can be used for preparing medicines for preventing and / or treating acute lung injury.

There is provided a compound of formula (I), and pharmaceutically acceptable salts thereof. This compound can be used as a medicament for example for the prevention or treatment of hyperinflammation, for example lung or respiratory hyperinflammation, or for the prevention or treatment of SIRS, for example SIRS caused by sepsis. (I)

The development of a new, targeted drug delivery paradigm coupled to improved PI3K inhibitors (e.g., PI3Kα inhibitors) represents a significant advance in cancer therapy. Provided herein are compounds, such as compounds of Formula (I) and (II), and pharmaceutically acceptable salts, hydrates, solvates, polymorphs, co-crystals, tautomers, stereoisomers, isotopically labeled derivatives, and prodrugs thereof. The compounds provided herein are PI3K (e.g., PI3Kα) inhibitors and are therefore useful for the treatment and / or prevention of various diseases (e.g., proliferative diseases such as cancer). Also provided herein are nanoparticles and nanogels (e.g., P-selectin targeting nanoparticles) comprising PI3K inhibitors, such a compound described herein. In certain embodiments, a nanoparticle or nanogel described herein encapsulates a compound described herein for targeting delivery to cancer cells or tumors.

Provided herein are selectin-binding peptide ligands having both D- and L-amino acids, and peptide conjugates including the provided peptide ligands. The peptide conjugates can include a biopolymer backbone, such as dermatan sulfate, and 33 or fewer peptide ligands conjugated to the biopolymer. Also provided are methods for using the provided peptide conjugates to treat patients suffering from endothelial dysfunction.

Intracerebral hemorrhage (ICH), defined as spontaneous bleeding into the brain, is the deadliest, most disabling, and least treatable form of stroke. The aim of the present invention is to generate large amount of hemostatic mEVs to be used as hemostatic patches in different preclinical models of ICH. Indeed, the exogenous mEVs pf the present invention bearing TF and PSGL-1 improve outcome after collagenase-induced ICH by acting as intravascular hemostatic patches. The present invention thus relates to monocyte extracellular vesicles (mEVs) functionalized with tissue factor (TF) and P-Selectin Glycoprotein Ligand 1 (PSGL-1).

The invention discloses a mitochondrial delivery system of macrophages in a targeted heart ischemia reperfusion injury area as well as a preparation method and application of the mitochondrial delivery system, and relates to the technical field of biomedical engineering. The mitochondrial delivery system comprises an active mitochondrial and a physiological platelet coupled to the surface of the active mitochondrial and capable of expressing a membrane protein P-selectin. The mitochondrial delivery system provided by the invention can be adhered to the surface of circulating monocytes through physiological platelet membrane protein P-selectin, recruits by virtue of inflammatory cells, and is accurately targeted to the aggregation part of monocytes and macrophages of ischemic myocardium; and then active mitochondria is transplanted to the inflammatory macrophages to achieve the effect of relieving the heart ischemia reperfusion injury, so that the defects of the existing mitochondria targeting delivery technology are partially solved, the potential influence on other healthy organs can be avoided while the myocardial ischemia reperfusion injury is relieved, the side effect is reduced, and the clinical application prospect is broad. The efficient delivery of active mitochondria is realized.

The invention discloses a drug delivery carrier as well as a preparation method and application thereof, and relates to the field of application of a protein recombinant expression technology and a pharmaceutical preparation technology. The composition comprises a recombinant protein of ferritin and targeting peptide and an anti-inflammatory drug, the targeting peptide is used for targeting P selectin; the targeting peptide is displayed on the surface of the ferritin, the anti-inflammatory drug is arranged in an inner cavity of a nanocage formed by the ferritin, the amino acid sequence of the ferritin is as shown in SEQ ID NO: 1, the amino acid sequence of the targeting peptide is as shown in SEQ ID NO: 2, and a connecting peptide is arranged between the ferritin and the targeting peptide. According to the protein nanocage obtained through recombinant expression, the medicine can be more efficiently delivered to an inflammation part, the curative effect is enhanced, meanwhile, the off-target effect is reduced, and the side effect is relieved. And an innovative and effective delivery platform is provided for various anti-inflammatory drugs.

This invention relates to a mitochondrial composite nanosystem DTPS@Mito targeting lung inflammation, comprising a mitochondrial core and a functionalized lipid material DSPE-TK-PEG2000-SA modified on its surface. DSPE acts as a hydrophobic anchor inserted into the mitochondrial outer membrane, PEG2000 provides hydrophilicity and biocompatibility, ketithiothiol bonds serve as ROS-responsive linkers, and sialic acid targets the head group to specifically bind to E-selectin, which is highly expressed at the inflammatory site. The DTPS@Mito particles have a diameter of approximately 832 nm, maintaining intact mitochondrial morphology and protein composition. In vitro experiments show that it significantly inhibits the expression of inflammatory factors, reduces ROS levels, restores ATP production, and regulates mitochondrial dynamics. In vivo experiments show that it has enhanced retention and accumulation capacity in the lungs of ARDS mice, significantly alleviating lung inflammation, tissue damage, and oxidative stress, and reducing hyaline membrane formation. This invention achieves the synergistic integration of three major functions: mitochondrial transplantation, targeted delivery, and antioxidation, and can be used to prepare drugs for the treatment of acute respiratory distress syndrome.

The invention belongs to the technical field of medicines, and particularly relates to application of a small-molecule antioxidant to alleviation of type 2 diabetes vascular injury. In order to develop an effective scheme for dealing with vascular injury of a diabetic patient, research finds that Lithospermoside can specifically inhibit XO in a cell membrane anchoring state and effectively reduce generation of ROS in thoracic aorta, so that BUN, E-selectin, MDA and UACR are remarkably reduced, meanwhile, the fluorescence intensity of nitrotyrosine staining is inhibited, and the blood vessel injury of the diabetic patient is inhibited. Therefore, vascular endothelial injury under the state of type 2 diabetes accompanied by continuous hyperglycemia is relieved, the antioxidation effect is exerted to slow down vascular injury of diabetes and protect blood vessels, and an effective material basis and a new thought are provided for prevention and treatment of vascular injury of type 2 diabetes.

The invention relates to an application of an Adtrp virus in preparation of a medicine for treating heart failure. The invention discloses a gene therapy method for treating heart failure based on a myoAAV1A-Adtrp virus vector. According to the present invention, the deficiency of the whole genome Adtrp causes the heart dysfunction and the heart failure, the deficiency of the Adtrp further aggravates the heart dysfunction and the heart failure, the results show that the deficiency of the Adtrp causes the heart failure, the myoAAV1A-Adtrp gene therapy can effectively block the heart failure development Lepr, Apob and Col7a1 of the heart failure CAD and TAC model, the expression levels of the adhesion molecules Icam-1, Vcam-1, E-selectin, P-selectin and p65 are changed, and the MyoAAV1A-Adtrp gene therapy can reverse the effect; adtrp plays an important role in the pathogenesis of heart failure, and the MyoAAV1A-Adtrp gene is used for treating the heart failure, so that the heart dysfunction and the heart failure of CAD and TAC models can be obviously relieved.

The invention discloses a joint detection marker for diagnosis and differential diagnosis of rhinomyelitis and application of the joint detection marker. The marker comprises cell factor E-selectin protein / nucleic acid in a blood sample of an infected patient and an antibody aiming at rhinomyelitis HCP1 protein. The invention creatively provides the combined marker for diagnosing the infection of the rhinotrichum-like disease, and the combined marker can be used for differential diagnosis of the current symptom and the previous infection of the rhinotrichum-like disease. The combined marker also has the potential of being used as a target spot for preventing and treating burkholderia pseudomallei infection.

Methods of using soluble tandem selectin glycoprotein ligand (TSGL) and TSGL fusion proteins, such as TSGL-Ig, for therapeutic treatment of cancers, including in combination with T cell activation therapies or an adoptive cell transfer (ACT) therapy.

The present disclosure provides a culture medium for cell culturing, the culture medium containing a combination of specific components. The present disclosure provides a culture medium which contains a combination of components selected from the group consisting of: (1) a halcinonide component; (2) an ALK4 / 7 inhibitor or a TGFβ receptor type-1 kinase inhibitor; (3) a BRD7 / 9 double degradation factor or a BRD7 / 9 binding molecule (degradation factor); (4) an LATS1 / 2 inhibitor, a PKA inhibitor, or an AKT1 inhibitor; (5) a CK1 / 2 inhibitor, an insulin receptor inhibitor, a Tyr kinase inhibitor, a PKA inhibitor or a PKC inhibitor, or an adenosine kinase inhibitor; (6) an E-selectin inhibitor, a VCAM1 inhibitor, or an ICAM1 inhibitor; and (7) an LATS1 inhibitor + an LATS2 inhibitor.

Adverse outcomes of CAR-T such as hematotoxicity with prolonged cytopenia and infectious complications represent a challenging clinical problem after CAR-T therapy; however, current predictive models rely on blood counts and general inflammatory lab markers (ferritin, CRP) only and lack mechanistic / functional insights. Prolonged cytopenias after CAR-T are associated with endothelial alteration, characterized by reduced ANG1, E-selectin and MMP-1, and increased ANG2:ANG1 ratio, VCAM-1 and Thrombomodulin early after CAR-T. It was found that Patients with high baseline sIL-2R and VCAM-1 not only show more prolonged neutropenia and a more aplastic neutrophil recovery but also experience more severe infectious complications. High baseline VCAM-1 is associated with significantly worse peak CD8 CAR-T cell expansion and separates MM patients with worse overall response (Figure 5, Figure s5) Baseline sIL-2R and VCAM-1 have high predictive value for adverse outcomes, such as prolonged neutropenia, severe infections and death, and can further improve existing models.

The invention relates to engineered lactobacillus plantarum outer vesicles targeting a cerebral infarction area and a preparation method thereof. The engineered lactobacillus plantarum outer vesicle targeting the cerebral infarction area is obtained by modifying the lactobacillus plantarum outer vesicle with E-selectin binding oligopeptide Esbp, and the engineered lactobacillus plantarum outer vesicle can well target a new target E-selectin of the cerebral infarction area, so that the outer vesicle is delivered to the cerebral infarction area to treat cerebral infarction. The engineered lactobacillus plantarum outer vesicle has the advantages of high acquisition speed, high yield, low cost and the like, and the chemical connection method is simple in synthesis step and lower in cost, so that the engineered lactobacillus plantarum outer vesicle targeting the cerebral infarction area has the characteristics of low cost and simplicity in preparation, and is suitable for industrial popularization and application.

The invention belongs to the technical field of biological medicine nanotechnology, and particularly relates to a targeted nano-enzyme based on multiple catalysis and gas therapy of a copper-amino acid complex and a preparation method and application of the targeted nano-enzyme. The nano enzyme is of a core-shell structure and comprises a core of a copper salt-amino acid ligand, a wrapping layer made of a cationic polymer material and a targeting layer made of a P-selectin targeting ligand from inside to outside. The nano-enzyme is applied to prevention and treatment of vascular diseases such as atherosclerosis, the effect is remarkable, NO, O2 and Cu < 2 + > can be continuously released at the same time, the endothelial function is synergistically improved, the hypoxia microenvironment is relieved, the catalytic anti-oxidation effect is achieved, the surface of the nano-enzyme is modified with a targeting ligand, active targeting is achieved, the treatment efficiency is improved, and the side effects of the whole body are reduced; the nano-enzyme also has multiple enzyme simulation activity, excessive active oxygen is efficiently removed through the catalytic action of Cu < 2 + >, the vicious circle of oxidative stress is broken, and the plaque microenvironment is fundamentally improved.

Adverse outcomes of CAR-T such as hematotoxicity with prolonged cytopenia and infectious complications represent a challenging clinical problem after CAR-T therapy; however, current predictive models rely on blood counts and general inflammatory lab markers (ferritin, CRP) only and lack mechanistic / functional insights. Prolonged cytopenias after CAR-T are associated with endothelial alteration, characterized by reduced ANG1, E-selectin and MMP-1, and increased ANG2:ANG1 ratio, VCAM-1 and Thrombomodulin early after CAR-T. It was found that Patients with high baseline sIL-2R and VCAM-1 not only show more prolonged neutropenia and a more aplastic neutrophil recovery but also experience more severe infectious complications. High baseline VCAM-1 is associated with significantly worse peak CD8 CAR-T cell expansion and separates MM patients with worse overall response (Figure 5, Figure s5) Baseline sIL-2R and VCAM-1 have high predictive value for adverse outcomes, such as prolonged neutropenia, severe infections and death, and can further improve existing models.

The invention discloses a recombinant protein of recombinant human Fc and P-selectin, a detection product as well as a preparation method and application of the detection product, and relates to the technical field of tumor cell capture. The recombinant protein of the recombinant human Fc and P-selectin comprises a C-type lectin, an EGF-like domain and a human Fc segment from an N terminal to a C terminal. The recombinant protein is combined with the target cells only through the interaction structural domain of the P-selectin, so that non-specific adhesion is reduced, and the purity of the target cells and the capture efficiency of the target cells are improved.

An immunosensor device is disclosed for rapid detection of circulating biomarkers associated with thrombosis, including C-reactive protein (CRP), calprotectin, soluble platelet selectin (sP-selectin), and D-dimer. The immunosensors were fabricated using fiber-laser engraving of carbon nanotubes and CO2-laser cutting of microfluidic channels and features, along with the electrochemical deposition of gold nanoparticles to conjugate with biomarker-specific aptamers and antibody. Using unsupervised clustering based on 4-biomarker concentrations, thrombotic events were predicted in 49 of 53 patients. The 4-biomarker combination yielded an area under the receiver operating characteristic curve (AUC) of 0.95, demonstrating high sensitivity and specificity for acute thrombosis prediction compared to the AUC values for individual biomarker: CRP (0.773), calprotectin (0.711), sP-selectin (0.683), and D-dimer (0.739). The immunosensor device with unsupervised clustering provides accurate and efficient methods for predicting thrombosis, guiding personalized medicine.

The application discloses polyglucuronate-selenocystamine phenylboronic pinacol ester or a salt thereof, a preparation method and application. The preparation method comprises the following steps: (1) polyglucuronate or a salt thereof is reacted with selenocystamine to synthesize polyglucuronate-selenocystamine or a salt thereof; (2) polyglucuronate-selenocystamine or the salt thereof is reacted with 4-(hydroxymethyl) phenylboronic pinacol ester through an amide reaction to synthesize polyglucuronate-selenocystamine phenylboronic pinacol ester or a salt thereof; and (3) a protein thrombolytic drug is loaded by an ultrasonic homogenization method to prepare active oxygen-responsive nanogel. The active oxygen-responsive nanogel is combined with P-selectin, so that the active oxygen-responsive nanogel has targeting property for activated platelets at a thrombus site, the purpose of targeted drug delivery and reduced side effects is achieved, the drug is effectively enriched at the thrombus site, the active oxygen microenvironment at an ischemic cerebral stroke site is adjusted, the occurrence of ischemic cerebral stroke infarction is reduced, and a new strategy is provided for clinical treatment of ischemic cerebral stroke.

The invention provides a combined detection kit for diagnosing rhinotrichum-like and application of the combined detection kit. The combined detection kit is characterized in that firstly, Hcp1 is verified as a rhinotrichum-like specific virulence factor by constructing a rhinotrichum-like Hcp1 gene knockout strain and a back-complementing strain; cell experiments prove that the E-selectin is regulated and controlled by Hcp1, and high expression of the E-selectin is related to current infection; in combination with clinical serum sample detection, it is confirmed that E-selectin can be used as a serological index of current infection. Based on the verification, the joint detection kit containing the first reagent component, the second reagent component and the universal reagent is prepared, and an ELISA method is adopted for detection. The kit can be used for accurately diagnosing rhinomycopsis-like infection and effectively identifying current and previous infections, is rapid in detection, simple and convenient to operate and high in specificity and sensitivity, is suitable for clinical detection of medical institutions at all levels, has important clinical values in early screening, accurate diagnosis, prevention and control of rhinomycopsis-like, and makes up for the defects of an existing single detection method.

Provided herein are dimeric P-selecting inhibitors ("conjugates") comprising two P- selecting binding glycopeptides conjugated via a linker. In certain embodiments, the conjugates described herein have increased affinity for P-selectin relative to existing inhibitors.