44 results about "Cerebral microvessel" patented technology

The invention relates to the technical field of biological tissue engineering, and discloses a nerve-blood brain barrier co-culture model, which comprises a culture chip, and nerves and blood brain barriers respectively constructed in upper culture micropores and lower culture micropores of the culture chip. Wherein a semi-permeable membrane is arranged between the lower-layer culture micropores and the upper-layer culture micropores of the culture chip; the nerves are obtained by inoculating neurons / brain organs obtained by stem cell differentiation into the upper culture micropores for co-culture, and the blood brain barrier is obtained by inoculating brain microvascular endothelial cells obtained by stem cell differentiation into one side of the semipermeable membrane in the lower culture micropores for co-culture. The co-culture model is higher in biomimetic property, and can better simulate the structure and function of the blood brain barrier, for example, the co-culture model has a barrier function closer to the physiological level, the selective permeability of a small molecule drug is matched with the in-vivo permeation condition, and the co-culture model has the function of a small molecule related transporter. The invention further discloses a construction method and application.

Provided herein are compositions including brain, brain microvascular endothelial cell-targeting peptides and / or blood-brain barrier crossing (BBB) tissue-targeting peptides linked thereto or inserted in a targeting protein of a recombinant vector having at least one exogenous peptide comprising Xn – n-mer – Xm. Compositions providing such conjugates, targeting peptides, or recombinant vectors having an engineered capsid or envelope protein are provided as are uses thereof.

The invention provides application of scEMC10 in treatment and diagnosis of cerebral vascular endothelial cell senescence, and relates to the technical field of biomedicine. The research of the inventor finds that brain microvascular endothelial cell senescence is caused by the lack of scEMC10; after the brain microvascular endothelial cells are treated by scEMC10, beta-galactosidase, SASP and classic senescence markers related to senescence can be down-regulated; after scEmc10 is supplemented to old mice and Alzheimer's disease 5XFAD model mice, the motion coordination ability and the spatial cognitive ability of the mice can be obviously improved, the relative content of a marker phosphorylated alpha-synuclein of the Parkinson's disease of the old mice can be obviously reduced, and the content of tyrosine hydroxylase phosphorylated active forms can be increased. Therefore, the scEMC10 can be used for treating brain microvascular endothelial cell senescence, improving Alzheimer's disease and Parkinson's disease and detecting brain microvascular endothelial cell senescence as a marker.

The invention belongs to the technical field of medical nano-materials, and particularly relates to a lactoferrin nano-material for sonodynamic regulation and control of blood-brain barrier permeability as well as a preparation method and application of the lactoferrin nano-material. The nanomaterial is nanoparticles LCe6 formed by self-assembly of lactoferrin and chlorin e6, can target brain microvascular endothelial cells, and can temporarily, reversibly and targeting open BBB by using the sonodynamic effect of the LCe6 in combination with transcranial ultrasonic stimulation, so that the accumulation of the nanoparticles LCe6 at a focus part is improved; in addition, the nanoparticle LCe6 also has a targeting property on brain tumor cells, the tumor cells can be accurately killed by utilizing the sonodynamic effect of the nanoparticle under secondary transcranial ultrasound, and the effect of sonodynamic treatment on brain glioma is exerted to the maximum extent; the nanoparticles LCe6 have excellent biocompatibility and low toxicity; according to the invention, the intracerebral delivery efficiency of the drug can be obviously improved, and a novel method for targeting open brain disease BBB is provided.

The invention discloses lactobacillus paracasei for improving urticaria and Alzheimer's disease and a product, and relates to the technical field of microorganisms. The lactobacillus paracasei NHNK-1701 disclosed by the invention is preserved in the China Center for Type Culture Collection on April 14, 2025, and the preservation number of the lactobacillus paracasei NHNK-1701 is CCTCC (China Center for Type Culture Collection) NO: M 2025765. The NHNK-1701 has the effects of inhibiting the growth of the klebsiella pneumoniae and / or generating alcohol, agglutinating the klebsiella pneumoniae, tolerating 10% of alcohol, reducing alcohol-induced injury of skin cutin barrier and inflammation, reducing alcohol-induced injury of brain microvascular barrier and inflammation, improving the klebsiella pneumoniae-induced injury survival rate of brain microvascular endothelial cells and improving the activity of the brain microvascular endothelial cells. Klebsiella pneumonia induced damage to brain microvascular barriers and inflammation is reduced, and Klebsiella pneumonia induced damage to intestinal barriers and inflammation is reduced.

The invention relates to the technical field of marine microorganisms, in particular to application of bifidobacterium animalis subsp. Lactis in preparation of products for improving urticaria and Alzheimer's disease, the preservation number of the bifidobacterium animalis subsp. Lactis is CCTCC NO: M 2024801, the bifidobacterium animalis subsp. Lactis is preserved in China Center for Type Culture Collection on April 25, 2024, the strain is derived from healthy baby girl feces, and the preservation number is CCTCC NO: M 2024801. After research, the inventor finds that the composition has the effects of inhibiting the growth of klebsiella pneumonia, agglutinating klebsiella pneumonia, reducing alcohol-induced injury of skin cutin barrier and inflammation, reducing alcohol-induced injury of brain microvascular barrier and inflammation, improving the klebsiella pneumonia induced injury survival rate of brain microvascular endothelial cells and improving the activity of the brain microvascular endothelial cells. Klebsiella pneumonia induced damage to brain microvascular barriers and inflammation is reduced, and Klebsiella pneumonia induced damage to intestinal barriers and inflammation is reduced. The compound can be used for preparing products for improving urticaria and Alzheimer's disease.

This invention discloses a method for constructing a three-dimensional in vitro blood-brain barrier model with barrier function and its application, belonging to the biomedical field. The method includes: preparing a light-controlled biofunctionalized hydrogel with methacrylamide gelatin as the main framework; preparing a suspension of neurovascular matrix components using astrocytes and neurons; uniformly mixing the light-controlled biofunctionalized hydrogel and the neurovascular matrix component suspension to obtain a homogeneous cell-hydrogel composite solution, and preparing it into three-dimensional hydrogel microspheres; transferring the three-dimensional hydrogel microspheres to the bottom of a Transwell culture dish insert to form a stable neurolateral matrix layer; and adding a suspension of brain microvascular endothelial cells into the lower chamber of the Transwell culture dish. This invention achieves the synergistic effect of multiple bioactive substances, overcoming the shortcomings of the single bioactive substance loading method in the prior art.

The application relates to the technical field of medicines, and particularly discloses a polypeptide and application of the polypeptide in preparation of a medicine for ischemic stroke. The amino acid sequence of the polypeptide is as shown in SEQ ID NO. 1. The polypeptide can significantly improve the nerve function defect of a mouse transient middle cerebral artery occlusion / reperfusion (tMCAO / R) model in vivo, reduce the cerebral infarction volume, and reduce the whole-body oxidative stress level. In vitro, the polypeptide has a direct protective effect on HT22 neuron cells and hCMEC / D3 brain microvascular endothelial cells injured by oxygen-glucose deprivation (OGD) induction, and can resist the injury of PC12 cells induced by corticosterone (CORT) and MPP + , and effectively inhibit the accumulation of reactive oxygen species (ROS) in cells. The results show that the polypeptide has a multi-target cell protection activity, and can play an anti-ischemic stroke role from multiple dimensions such as reduction of infarction volume, inhibition of oxidative stress level, and protection of nerve and vascular units.

The present invention provides engineered AAV vectors, and methods of using vectors, comprising capsid proteins that comprise a sequence that binds to the PL16 protein. In some embodiments, it includes a membrane protein expressed in several cell populations and tissues in the body, including brain microvascular endothelial cells in humans. By the present invention, it was discovered that engineered novel AAV vectors comprising a capsid protein having a sequence that allows the vector to bind to P116 may have an increased ability to provide a gene therapy which crosses the blood brain barrier.

The application provides an application of scEMC10 in treatment and diagnosis of brain vascular endothelial cell aging, and relates to the technical field of biomedicine. The inventor finds that scEMC10 deficiency leads to brain microvascular endothelial cell aging; brain microvascular endothelial cells treated by scEMC10 can down-regulate beta-galactosidase, SASP and classic aging markers related to aging; after old mice and 5XFAD model mice of Alzheimer's disease are supplemented with scEmc10, the movement coordination ability and spatial cognitive ability of the mice can be obviously improved, and the relative content of the Parkinson's disease marker, phosphorylated alpha-synuclein, of the old mice can be obviously reduced, and the content of the tyrosine hydroxylase phosphorylation activity form can be increased. Therefore, scEMC10 can be used for treatment of brain microvascular endothelial cell aging, improvement of Alzheimer's disease and Parkinson's disease, and detection of brain microvascular endothelial cell aging as a marker.

The invention relates to a method for establishing a blood-brain barrier organ aging model and an intervention method for the model, and the method comprises the following steps: S1, model preparation: preparing cryopreserved brain microvascular endothelial cells, resuscitating the cryopreserved brain microvascular endothelial cells, preparing a culture bottle containing a culture medium for later use, preparing a culture chip and an inducer, and treating the culture chip and the inducer for later use; s2, cell culture: taking the recovered brain microvascular endothelial cells in S1, inoculating the brain microvascular endothelial cells in a culture bottle, culturing and carrying out cell passage to obtain brain microvascular endothelial cells in a logarithmic phase; s3, constructing a blood-brain barrier, inoculating the brain microvascular endothelial cells in the logarithmic phase obtained in the S2 to a chip, and culturing to obtain a blood-brain barrier model; and S4, constructing an aging model, taking the blood-brain barrier model in S3, and performing injury treatment to obtain the blood-brain barrier organ aging model. A D-galactose drug group is used for successfully inducing the aging injury of the blood-brain barrier organ model, and a reliable in-vitro blood-brain barrier organ aging injury model is provided.

The invention relates to the technical field of ocean, in particular to an angiogenic peptide cAMP-137 derived from coral microorganisms and application of the angiogenic peptide cAMP-137. In the invention, the novel angiogenic peptide cAMP-137 is screened and identified from metagenome sequencing data of a coral reef sample of an island in Pacific Ocean for the first time. The angiogenic peptide can significantly inhibit hematoma expansion and stabilize cerebral microvessels in a 10-100 nM therapeutic window, fills the technical blank of existing polypeptide drugs, and provides a new solution for spontaneous and drug-induced cerebral hemorrhage.

The present application relates to the field of marine technology, and particularly relates to a coral microbial source pro-angiogenic peptide cAMP-137 and application thereof.In the present application, a novel pro-angiogenic peptide cAMP-137 is screened and identified for the first time from the metagenomic sequencing data of a sample of Pacific island coral reef.The pro-angiogenic peptide can significantly inhibit hematoma expansion and stabilize cerebral microvessels in a treatment window of 10-100 nM, filling the technical blank of existing polypeptide drugs and providing a new solution for spontaneous and drug-induced cerebral hemorrhage.

The invention provides bifidobacterium adolescentis for improving urticaria and Alzheimer as well as a product and application thereof. The bifidobacterium adolescentis NHNK-622 disclosed by the invention is preserved in the China Center for Type Culture Collection on December 05, 2024, and the preservation number of the bifidobacterium adolescentis NHNK-622 is CCTCC (China Center for Type Culture Collection) NO: M 20242734. The NHNK-622 has the effects of inhibiting the growth of klebsiella pneumonia and / or generating alcohol, agglutinating klebsiella pneumonia, tolerating 10% alcohol, reducing alcohol-induced damaged skin cutin barrier and inflammation, reducing alcohol-induced damaged brain microvascular barrier and inflammation, improving the klebsiella pneumonia-induced damaged survival rate of brain microvascular endothelial cells, and improving the activity of the brain microvascular endothelial cells. Klebsiella pneumonia induced damage to brain microvascular barriers and inflammation is reduced, and Klebsiella pneumonia induced damage to intestinal barriers and inflammation is reduced.

This invention discloses a method for constructing and evaluating a homeostatic neuroinflammatory microenvironment model. In this invention, brain microvascular endothelial cells and microglia are seeded into the methacrylamide gelatin layer and the paper fiber layer of a methacrylamide gelatin-paper fiber composite membrane (GCC), respectively, and co-cultured for 24–96 hours without LPS stimulation to form a homeostatic neuroinflammatory microenvironment model. The 24-hour GCC group… TNF-alpha Compared to the PET group, CX3CL1 decreased by about 60% and remained at a low level for 72 hours; CX3CL1 increased by nearly 3 times in the GCC group; based on the evaluation of 4 / 10 / 70 kDa graded probes, GCC showed better restriction on 10 kDa than PET, exhibiting molecular weight-dependent permeation characteristics opposite to PET. The homeostatic neuroinflammatory microenvironment model proposed in this application is suitable for simulating the blood-brain barrier in early pathological conditions, and can be used for anti-inflammatory drug screening and research on neurodegenerative diseases, showing good application prospects.

The present invention relates to a composition containing gintonin as an active ingredient for the prevention and treatment of ischemic cerebrovascular disorders, including cerebral infarction. The gintonin of the present invention can reduce the volume of cerebral infarction and increase survival rates after cerebral infarction, making it useful for the prevention and treatment of cerebral infarction. Furthermore, pretreatment of human brain microvascular endothelial cells (HBMECs) with gintonin has been shown to have neuroprotective and injury-preventing effects, while posttreatment with gintonin has been shown to have neuroprotective and therapeutic effects. Mechanism verification revealed that gintonin is effective in restoring reduced nitric oxide (NO) levels, which are known to be involved in the onset and pathophysiology of cerebral infarction. Therefore, the use of the present invention may improve the prevention and treatment of ischemic cerebrovascular disorders, including cerebral infarction, and reduce medical costs.

The invention relates to the technical field of cell biology, in particular to a method for extracting and purifying chicken primary brain microvascular endothelial cells. The method for extracting and purifying the chicken primary brain microvascular endothelial cells comprises the following steps: (1) acquiring and pretreating chicken embryo brain tissues; (2) primary enzyme digestion; (3) removing myelin sheath; (4) secondary enzyme digestion; (5) performing Percoll gradient centrifugal purification; and (6) performing differential adherent cell culture and screening. According to the chicken primary brain microvascular endothelial cell extraction and purification method, through collaborative optimization of double enzyme digestion, demyelination treatment and Percoll gradient centrifugation, the purity of separated cells is remarkably improved, the cell survival rate is high, the cost is low, consumed time is short, and the method is suitable for large-scale preparation.

This invention relates to the pharmaceutical field, specifically to the application of tissue inhibitor metalloproteinases-2 (TIMP2) in the preparation of drugs for the prevention or treatment of traumatic brain injury. TIMP2 protein can increase the fall latency in rotarod experiments in mice with traumatic brain injury; improve the motor balance ability of mice with traumatic brain injury on a balance beam; improve neurological function impairment in mice with traumatic brain injury; and reduce Evans blue permeability in brain tissue. In brain microvascular endothelial cells (HBMECs), TIMP2 protein can participate in maintaining the integrity of the endothelial barrier, reversing the loss of expression and altered localization of the connectome complex induced in an in vitro traumatic brain injury model, and reducing luciferase leakage. This invention also provides the application of TIMP2 protein as an Integrin α3β1 ligand in the preparation of drugs for the treatment of central nervous system diseases caused by blood-brain barrier dysfunction. TIMP2 protein exerts its function by binding to the cell membrane receptor Integrin α3β1, regulating VE-Cadherin phosphorylation. TIMP2 protein shows promising application prospects in the treatment of blood-brain barrier dysfunction caused by traumatic brain injury.

To provide a blood-brain barrier model using a human immortalized cell, and a method for producing the same.SOLUTION: A method for producing a multicellular blood-brain barrier model includes: (i) a culture step of disseminating human conditional immortalized pericytes onto a first culture medium to culture the pericytes; (ii) a pericyte differentiation step of differentiating the cultured human conditional immortalized pericyte on a second culture medium; (iii) an astrocyte culture step of disseminating human conditional immortalized astrocytes onto a third culture medium to culture the astrocytes; (iv) an astrocyte differentiation step of differentiating the cultured human conditional immortalized astrocytes on a fourth culture medium; and (v) a brain microvascular endothelial cell culture step of disseminating human conditional immortalized brain microvascular endothelial cells onto a fifth culture medium to culture the disseminated human conditional immortalized brain microvascular endothelial cells.SELECTED DRAWING: Figure 2A

The invention relates to the technical field of cell sensing, and discloses a brain microvascular endothelial cell injury assessment method, which comprises the following steps of: synchronously acquiring a metabolic vibration signal and a transcellular resistance signal of brain microvascular tissues through a sensor carrier integrating a piezoelectric sensing unit and an electrode unit, and calculating a correlation coefficient of time domain envelope of the signals; the cell damage state is judged based on continuous negative correlation, early warning of cell function instability is achieved through double-signal dynamic coupling analysis, a harmonic phase locking recognition mechanism can capture the recessive pathological state in the compensation period, and signal entropy change compensation enables the system to have the capacity of self-adaption to environment interference. And a real-time and accurate capillary function evaluation means is provided for clinic.

The invention provides a traditional Chinese medicine composition for preventing, treating and / or improving brain diseases directly related to brain microvascular endothelial cells and application of the traditional Chinese medicine composition, and belongs to the technical field of traditional Chinese medicine compositions. The traditional Chinese medicine composition is prepared from the following raw materials in parts by weight: ginseng under forest for more than 10 years, fructus lycii, fructus rosae laevigatae, rhizoma polygonati, semen cuscutae, wine-processed glossy privet fruit, radix paeoniae alba, herba epimedii, honey-fried licorice root, honey-fried astragalus membranaceus, fried malt and honey. The honey-fried licorice root is prepared from wild licorice root; the radix astragali preparata is prepared by processing high-quality organic radix astragali. According to the traditional Chinese medicine composition, the brain microvascular endothelial cell protection activity of the traditional Chinese medicine composition can be effectively improved by improving the source and grade of key medicinal materials of the traditional Chinese medicine composition; the traditional Chinese medicine composition disclosed by the invention is more outstanding in the aspects of relieving oxidative damage, improving the cell survival state and reducing oxidative stress and apoptosis.

Provided is a technology allowing for stable supply of brain microvascular endothelium-like cells. This coating agent for inducing differentiation of pluripotent stem cells into brain microvascular endothelium-like cells contains at least one component of a Laminin-221 fragment or an N-terminal Vitronectin.

The invention relates to the field of biomedicine, and discloses a capillary segment extraction method and application thereof. The method comprises a step of digesting rat brain tissues and a step of separating brain microvascular segments. The method provided by the invention is simple to operate, can be directly realized on wild animals, and does not depend on animal endogenous fluorescent labeling. According to the method, the complete vascular tissue can be obtained, meanwhile, the activity of the cells is reserved, the method is the first method capable of separating the complete vascular tree from the brain tissue and then further researching the functions of all the cells on the vascular tissue, and the method has important significance on research of the brain microvascular segment.

Brain-Assessment devices are provided. Aspects of the devices include a brain matrix chamber comprising a brain matrix composition. In embodiments, the brain matrix composition includes a three-dimensional endothelial cell vascular network (e.g., comprising brain microvascular endothelial cells) and a cellular component comprising one or more of brain parenchymal cells and peripheral immune cells. Systems comprising a device of the present disclosure and a reader (e.g., comprising an imaging system) are also provided. Methods of preparing a device of the present disclosure for use in an assay are provided. Also provided are methods of introducing a perturbation (e.g., a small molecule) to a device of the present disclosure.

The invention belongs to the field of drug delivery system construction, and particularly relates to a target-drug self-adaptive transformation cross-linking self-assembly nano platform as well as a preparation method and application of the target-drug self-adaptive transformation cross-linking self-assembly nano platform. The doxorubicin is creatively taken as a carrier and a targeting ligand for oral delivery of the doxorubicin, so that the specific targeting and treatment effects of a tumor part are realized. The doxorubicin hydrochloride is subjected to stable self-assembly by virtue of disulfide bond crosslinking through a specific crosslinking material, a hydrophilic end sugar ring of the doxorubicin hydrochloride is anchored on the surface of a nanoparticle, and an intestinal epithelial cell barrier and a blood brain barrier are crossed by recognizing SGLT1 and OCTN2 which are highly expressed on a top side membrane of an intestinal epithelial cell, GLUT2 on a substrate side and GLUT1 on the surfaces of brain microvascular endothelial cells and glioma cells. The nanoparticles not only significantly improve the oral bioavailability of adriamycin, but also have an efficient accumulation effect in the brain, further break disulfide bonds and release adriamycin in a high-GSH environment, and achieve a safe and efficient anti-tumor effect.

The application provides a use of scEMC10 in preparation of a medicine for treating sepsis, and relates to the field of biomedical technology. The inventor finds that after LPS-stimulated brain microvascular endothelial cells are treated by scEMC10, a plurality of gene mRNA transcriptions related to EndMT and classic EndMT markers (such as FN1, alpha-SMA, ZEB1, TWIST1 and Snail) induced by LPS can be down-regulated; after a LPS-induced sepsis mouse model is supplemented with scEMC10, the expression of EndMT markers of the brain, liver and kidney can be obviously improved, the bleeding of the brain, lung, liver and kidney of the mouse caused by LPS induction can be obviously inhibited, the survival rate of the mouse is improved, the movement ability of the mouse is improved, and the anxiety level of the mouse is reduced. Therefore, scEMC10 can be used for preparing a medicine for treating sepsis and inhibiting EndMT.

The invention discloses a construction method and application of a three-dimensional in-vitro blood-brain barrier model with a barrier function, and belongs to the field of biomedicines.The method comprises the steps that light-operated biological functional hydrogel is prepared with methacrylated gelatin as a main skeleton, and astrocytes and neuronal cells are used for preparing a neurovascular matrix component suspension; uniformly mixing the light-operated biological functionalized hydrogel and the neurovascular matrix component suspension to obtain a homogeneous cell-hydrogel composite liquid, and preparing the homogeneous cell-hydrogel composite liquid into three-dimensional hydrogel microspheres; the three-dimensional hydrogel microspheres are transferred to the bottom of an insert of a Transwell culture dish to form a layer of stable nerve side matrix, and brain microvascular endothelial cell suspension is added into a lower chamber of the Transwell culture dish; according to the invention, the synergistic effect of a plurality of bioactive substances is realized, and the defect of single bioactive substance loading mode in the prior art is overcome.

The invention belongs to the technical field of biological medicines, and particularly relates to treatment application of a targeted exosome in improving blood-brain barrier destruction of acute ischemic stroke, and the targeted exosome is an exosome from brain microvascular endothelial cells subjected to oxygen-glucose deprivation treatment, and is an exosome carrying CD151-siRNA (siCD151). According to the technical scheme, the screened CD151 is a key molecule for regulating and controlling the immune homeostasis of the endothelial cells. Meanwhile, the exosome from brain microvascular endothelial cells subjected to oxygen-glucose deprivation treatment is obtained to serve as a delivery carrier, and siCD151 is carried to construct an Exo-siCD151 system. The system can maintain the immune homeostasis of the endothelial cells by reducing the CD151 level of the ischemic-damaged endothelial cells in a targeted manner, so that the aims of repairing the blood-brain barrier and improving the cerebral ischemia prognosis are fulfilled.