13 results about "Pathological Angiogenesis" patented technology

The invention provides an application of Exifenone in preparation of a medicine for treating diabetic retinopathy, the Exifenone can be combined near a K412 lactic acid modification site of HDAC1, so that the lactic acid modification of the K412 site of the HDAC1 is specifically inhibited, the deacetylation activity of the HDAC1 to H3K56 is enhanced, the transcriptional activation of VEGFA (vascular endothelial growth factor A) mediated by H3K56ac and pathological angiogenesis are inhibited, and the effect of treating diabetic retinopathy is achieved. Further, vascular pathological injury caused by diabetic retinopathy is improved. The application provides a new target and a candidate drug for clinical treatment of diabetic retinopathy. The research result of the application provides experimental evidence for the epoxybenzophenone to be used for clinical specific treatment of diabetic retinopathy.

A pyrrolopyrimidine or pyrrolopyridine derivative and its medical use. Specifically, the compound has the structure shown in formula I, has good inhibitory effect on focal adhesion kinase (FAK), and can inhibit its related signal pathways, and can be prepared for treating or preventing diseases related to cancer, pulmonary arterial hypertension, pathological angiogenesis, etc., and can be particularly used for treating diseases caused by excessive or abnormal cell proliferation, such as tumors or cancers.

The invention relates to a compound shown in a formula I, a composition containing the compound and medical application of the compound. The compound provided by the invention has a relatively good treatment effect on cancers, pulmonary arterial hypertension and pathological angiogenesis.

The invention relates to the field of biological medicine and ophthalmic diseases, in particular to a target protein inhibitor for preventing and treating proliferative diabetic retinopathy and a screening method and application of the target protein inhibitor. The screening method comprises the following steps: 1) obtaining a three-dimensional crystal structure of CTSH; 2) constructing a binding pocket at an active site; 3) performing molecular docking and scoring on the small molecule library, and screening candidate compounds with binding energy lower than a preset threshold value; and 4) performing molecular dynamics simulation on the candidate compound and the CTSH compound, and selecting a compound with a stable structure and low binding free energy as an inhibitor. The inhibitor obtained by screening comprises eriodictyin, polygala tenuifolia sucrose ester B or an AP-III-a4 inhibitor. Genetic causal inference proves that CTSH has a causal driving effect on PDR, inflammation and pathological angiogenesis can be remarkably inhibited by regulating CTSH expression under a high glucose condition, and effective inhibitor components are finally screened.

The invention discloses a gene modified fibroblast as well as a preparation method and application thereof, and belongs to the technical field of biological medicines. Researches find that fibroblasts modified by the TIMP1 gene can stably secrete TIMP1 protein, the TIMP1 can promote the fibroblasts to secrete COL1A1 and Fibronectin, and the COL1A1 and the Fibronectin cooperate with each other to play a role in inhibiting growth of vascular endothelial cells, so that ingrowth of blood vessels in the intervertebral disc degeneration process is inhibited. And pathological angiogenesis in the degenerated intervertebral disc can be inhibited in a long-acting and targeted manner, so that the degeneration of the intervertebral disc is delayed.

This invention provides the application of exifone in the preparation of drugs for treating diabetic retinopathy. Exifone binds near the lactation modification site of HDAC1 K412, thereby specifically inhibiting the lactation modification of HDAC1 at the K412 site. This leads to enhanced deacetylation activity of HDAC1 on H3K56, thereby inhibiting H3K56ac-mediated VEGFA transcriptional activation and pathological angiogenesis, and thus improving the vascular pathological damage of diabetic retinopathy. This application provides a new target and candidate drug for the clinical treatment of diabetic retinopathy. The research results of this application provide experimental evidence that exifone can be used as a clinically specific treatment for diabetic retinopathy.

The present application provides a kind of composition and preparation method and application for preventing cataract, macular lesion and diabetic retinopathy, belong to biological medicine technical field.The composition of the present application includes: nano active ingredient, plant extract, glycyrrhizic acid dipotassium, nicotinamide, taurine, ikdoin, caffeine and lutein;Plant extract is composed of wild chrysanthemum flower extract and gentian extract;Nano active ingredient is composed of nano-encapsulated astaxanthin and nanometer retinol.The composition of the present application effectively inhibits key pathological links such as lens protein oxidative denaturation, retinal pigment epithelial cell function decline and pathological angiogenesis by multi-dimensional synergistic mechanism of antioxidant-anti-inflammatory-vascular protection-metabolic regulation, thereby realizing the prevention and adjuvant therapy effect on three major blinding eye diseases of cataract, age-related macular degeneration and diabetic retinopathy.

The application relates to the technical field of biological medicine, and particularly discloses a bifunctional fusion protein and application thereof in treating retinal degenerative diseases. The fusion protein is named Beva-1L, which is formed by fusing an amino acid sequence of human brain-derived neurotrophic factor (BDNF) with a light chain of an anti-vascular endothelial growth factor (VEGF) antibody, bevacizumab. The fusion protein can simultaneously inhibit VEGF-mediated pathological angiogenesis and provide neurotrophic support, and is used for treating retinal degenerative diseases such as diseases simulated by an rd10 mouse model. Experiments show that the amplitude of a retinal electrogram (ERG) of the rd10 mouse can be significantly improved by injecting the Beva-1L, and the effect is equivalent to that of a positive drug. The application also relates to a coding gene, an expression vector, a host cell, a pharmaceutical composition of the fusion protein and application thereof. The fusion protein has a bifunctional synergistic effect, and provides a new treatment strategy for retinal degenerative diseases.

This invention provides a biomarker for neovascularization, miR-1910-5p, and its application in the diagnosis and treatment of neovascularization. Detecting miR-1910-5p expression levels helps in the early prediction of neovascularization, greatly improving the timeliness of diagnosis and treatment. Detecting its expression level provides a reference for the diagnosis and prognosis of neovascularization. This invention also provides a drug for treating neovascularization, a miR-1910-5p antagonist, and its application. This miR-1910-5p antagonist reduces the silencing effect on genes related to angiogenesis inhibition by inhibiting miR-1910-5p expression, thereby slowing the occurrence and development of early angiogenesis and achieving the goal of inhibiting the development of neovascularization. Compared with other drugs, it avoids the adverse reactions of other drugs and can effectively and safely inhibit the occurrence and development of pathological angiogenesis.

The invention provides application of an NCOA3 polyQ structural domain in preparation of a medicine for relieving ocular vascular abnormal hyperplasia diseases, relates to the technical field of biomedicine, and aims to solve the problems that in the prior art, an ocular pathological angiogenesis mechanism is complex, and safe and effective targeted intervention means are lacked. The construction of a mouse corneal micropocket pathological angiogenesis model proves that Nco3polyQ structural domain deletion can significantly inhibit corneal neovascularization: compared with a WT mouse, the Nco3wt / Q mouse corneal tissue CD31 positive signal is reduced, the number of corneal neovascularization in the Nco3Q / Q mouse is minimum, and the CD31 positive area is minimum; meanwhile, qPCR (quantitative polymerase chain reaction) detection of corneal tissues shows that mRNA (messenger ribonucleic acid) expression of the vascular marker genes Pecam1 and Cdh5 is in a decreasing trend and is further decreased in an Nco3Q / Q mouse. On the basis, the intervention strategy aiming at the NCOA3 polyQ structural domain is used for preparing the medicine for relieving the abnormal hyperplasia diseases of the ocular blood vessels, and a new treatment strategy and a potential target are provided for related diseases of the ophthalmology department.

The application discloses application of SELE in treatment of wet age-related macular degeneration. The application research finds that SELE can significantly promote proliferation, migration and tube formation ability of vascular endothelial cells. SELE By inhibiting gene expression or activity, the application can significantly inhibit choroidal neovascularization in a wAMD mouse model, reduce abnormal vascular leakage, effectively reduce ocular inflammatory response, reduce inflammation-mediated vascular damage, target intervention of biological behavior of vascular endothelial cells, and block a key link of pathological angiogenesis. The application provides a novel molecular target for wAMD treatment and breaks the limitation of the existing anti-VEGF therapy.

Provided are compounds of the Formula I, and salts and solvates thereof: (I) wherein R1, R2, R3, X1, X2, X3 and Z are defined in the specification. The compounds are inhibitors of salt-inducible kinase (SIK), particular SIK2, and are useful in therapy, particularly in the treatment of a proliferative disorder, a benign neoplasm, pathological angiogenesis, an inflammatory disease or condition, a musculoskeletal disease or condition, an autoimmune disease, a haematological disease or condition, a neurological disease or condition, a psychiatric disorder, or a metabolic disorder.

The invention discloses an application of SELE in treatment of wet age-related macular degeneration. The research finds that the SELE can obviously promote the proliferation, migration and tube forming ability of vascular endothelial cells. By inhibiting SELE gene expression or activity, choroidal neovascularization in a wAMD mouse model can be significantly inhibited, and abnormal vascular leakage is reduced; meanwhile, the eye inflammatory response is effectively reduced, the inflammation-mediated vascular injury is relieved, the vascular endothelial cell biological behavior is intervened in a targeted manner, and the key link of pathological angiogenesis is blocked. The invention provides a brand new molecular target for wAMD treatment, and breaks through the limitation of the existing anti-VEGF therapy.