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2.
Article in Chinese | WPRIM | ID: wpr-879024

ABSTRACT

The aim of this paper was to study the protective effect of total flavonoids from Rosa multiflora(TF-RM) on the injury of HUVEC induced by oxidized low density lipoprotein(ox-LDL). SPF male SD rats were randomly divided into blank group, simvastatin group(1.8 mg·kg~(-1)·d~(-1)) and TF-RM group(2.5 g·kg~(-1)·d~(-1)), with 10 rats in each group. They were intragastrically administered with drugs for 7 days, and then blood was collected from the abdominal aorta to prepare drug-containing serum. The HUVEC injury model was established through ox-LDL induction, and added with 15% simvastatin, 5% TF-RM, 10% TF-RM, 15% TF-RM drug-containing serum and blank serum, respectively. Reactive oxygen species(ROS) was determined by flow cytometry. Nitric oxide(NO) content was determined by nitrate reductase method. The contents of ET-1, P-selectin, E-selectin, ICAM-1, VCAM-1, IL-1β, IL-6 and TNF-α were determined by ELISA. The expression of Lox-1 protein was determined by Western blot. Compared with the blank group, ROS level in HUVEC and the contents of ET-1, P-selectin, E-selectin, ICAM-1, VCAM-1 and IL-1β in HUVEC were significantly increased(P<0.05), NO decreased significantly(P<0.01),Lox-1 protein expression increased significantly(P<0.05), and TNF-α and IL-6 showed an increasing trend. Compared with the model group, TF-RM significantly reduced ROS level in HUVEC and ET-1, P-selectin, E-selectin, ICAM-1, TNF-α, IL-1β content in supernatant(P<0.05), significantly increased NO content(P<0.01), and inhibited Lox-1 protein expression(P<0.05). VCAM-1, IL-6 contents showed a decreasing trend. Serum containing TF-RM acts on lectin-like oxidized low-density lipoprotein receptors, and exerts a protective effect on vascular endothelial cells by reducing cell oxidative damage, regulating vasoactive substances, and reducing adhesion molecules and inflammatory cascades.


Subject(s)
Animals , Cells, Cultured , Endothelial Cells , Endothelium, Vascular , Flavonoids/pharmacology , Intercellular Adhesion Molecule-1/genetics , Lipoproteins, LDL , Male , Rats , Rats, Sprague-Dawley , Rosa
3.
Acta Physiologica Sinica ; (6): 69-81, 2021.
Article in Chinese | WPRIM | ID: wpr-878237

ABSTRACT

Phospholipids are important components of biomembrane and lipoproteins. Phospholipids can be oxidized by free radicals/nonradicals and enzymes to form oxidized phospholipids (OxPLs), which can lead to further generation of oxidation products with different biological activities. Clinical evidence shows that OxPLs are constantly generated and transformed during the pathogenesis of atherosclerosis and accumulated at the lesion sites. OxPLs are highly heterogeneous mixtures that can influence the progress of atherosclerosis through a variety of related receptors or signaling pathways. This review summarizes the process of phospholipid oxidation, the related products, the interaction of OxPLs with endothelial cells, monocytes/macrophages, smooth muscle cells, platelets and lipoproteins involved in the pathological process of atherosclerosis, and the progress of the researches using OxPLs as a target to inhibit atherosclerosis in recent years.


Subject(s)
Atherosclerosis , Endothelial Cells , Humans , Myocytes, Smooth Muscle , Oxidation-Reduction , Phospholipids
4.
Braz. j. med. biol. res ; 54(10): e11028, 2021. tab, graf
Article in English | LILACS | ID: biblio-1285653

ABSTRACT

Engeletin is a natural derivative of Smilax glabra rhizomilax that exhibits anti-inflammatory activity and suppresses lipid peroxidation. In the present study, we sought to elucidate the mechanistic basis for the neuroprotective and pro-angiogenic activity of engeltin in a human umbilical vein endothelial cells (HUVECs) oxygen-glucose deprivation and reoxygenation (OGD/R) model system and a middle cerebral artery occlusion (MCAO) rat model of cerebral ischemia and reperfusion injury. These analyses revealed that engeletin (10, 20, or 40 mg/kg) was able to reduce the infarct volume, increase cerebral blood flow, improve neurological function, and bolster the expression of vascular endothelial growth factor (VEGF), vasohibin-2 (Vash-2), angiopoietin-1 (Ang-1), phosphorylated human angiopoietin receptor tyrosine kinase 2 (p-Tie2), and platelet endothelial cell adhesion molecule-1 (PECAM-1/CD31) in MCAO rats. Similarly, engeletin (100, 200, or 400 nM) markedly enhanced the migration, tube formation, and VEGF expression of HUVECs in an OGD/R model system, while the VEGF receptor (R) inhibitor axitinib reversed the observed changes in HUVEC tube formation activity and Vash-2, VEGF, and CD31 expression. These data suggested that engeletin exhibited significant neuroprotective effects against cerebral ischemia and reperfusion injury in rats, and improved cerebrovascular angiogenesis by modulating the VEGF/vasohibin and Ang-1/Tie-2 pathways.


Subject(s)
Animals , Rats , Reperfusion Injury/prevention & control , Brain Ischemia/prevention & control , Infarction, Middle Cerebral Artery , Endothelial Cells , Flavonols , Angiopoietin-1 , Vascular Endothelial Growth Factors , Vascular Endothelial Growth Factor A , Glycosides
5.
Rev. ADM ; 77(6): 306-311, nov.-dic. 2020. tab
Article in Spanish | LILACS | ID: biblio-1151096

ABSTRACT

Introducción: Se realiza una revisión bibliográfica con base en artículos científicos con la finalidad de exponer la posible relación entre periodontitis (PD) y disfunción eréctil (DE), así como las variables contundentes que se encuentran implicadas. Material y métodos: Como estrategia de búsqueda primaria se emplea una combinación de vocabulario controlado (erectile dysfunction and periodontal disease) y términos de texto libre basado en la estrategia de búsqueda en MEDLINE a través de PubMed. Como estrategia de búsqueda secundaria se revisaron las referencias bibliográficas contenidas en los artículos seleccionados. Resultados: Diez estudios de casos y controles encontraron asociaciones positivas significativas entre estas dos condiciones. Conclusión: La evidencia de la literatura indica un vínculo positivo entre la PD y la DE (AU)


Introduction: A bibliographic review was carried out in scientific articles in order to expose the possible relationship between periodontitis (PD) and erectile dysfunction (ED), as well as the overwhelming variables that are involved. Material and methods: A combination of controlled vocabulary (erectile dysfunction and periodontal disease) and free text terms based on the MEDLINE search strategy through PubMed was used as the primary search strategy. As a secondary search strategy, the bibliographic references contained in the selected articles were reviewed. Results: Ten case-control studies found significant positive associations between these two conditions. Conclusion: The evidence in the literature indicates a positive link between PD and ED (AU)


Subject(s)
Humans , Periodontitis , Erectile Dysfunction , Periodontal Diseases , Endothelial Cells/pathology
6.
Rev. bras. cir. cardiovasc ; 35(5): 675-682, Sept.-Oct. 2020. tab, graf
Article in English | LILACS, SES-SP | ID: biblio-1137356

ABSTRACT

Abstract Objective: To elucidate the effect of diabetes mellitus (DM) on the atherosclerotic process in saphenous vein grafts by determining urotensin-II (U-II) levels in harvested saphenous veins of patients who underwent coronary artery bypass grafting (CABG). Methods: Coronary artery disease (CAD) patients who underwent CABG were divided into two groups: Group I (eight non-diabetic patients; CAD group) and Group II (13 patients; DM+CAD group). All patients underwent coronary angiography prior to surgery and Gensini score was used to determine the severity of coronary atherosclerosis. Saphenous vein samples were stained with hematoxylin-eosin and U-II, then damage score, H-Score, and vein layer thicknesses were calculated and statistically evaluated. Results: In light microscopic evaluation, significant difference was observed between the groups in terms of endothelial cells damage, internal elastic lamina degradation, and tunica media vascular smooth muscle cells (VSMCs) damage (P<0.001). U-II immunoreactivity was increased in tunica adventitia in the DM+CAD group (P=0.002). The increase in foam cells was directly proportional to the thickening of the subendothelial layer, and this increased U-II immunoreactivity. Gensini score was higher in the DM+CAD group than in the CAD group (P=0.002). Conclusion: Our results show that saphenous vein grafts are already atherosclerotic before they are grafted in CAD patients. This disease is more severe in diabetic CAD patients and these changes can be detected using U-II immunoreactivity.


Subject(s)
Humans , Male , Female , Urotensins , Coronary Artery Disease/surgery , Coronary Artery Disease/diagnostic imaging , Saphenous Vein/diagnostic imaging , Coronary Artery Bypass , Endothelial Cells
7.
Rev. cuba. oftalmol ; 33(1): e831, ene.-mar. 2020. tab
Article in Spanish | LILACS, CUMED | ID: biblio-1126719

ABSTRACT

RESUMEN Objetivo: Determinar las características del endotelio corneal mediante microscopia endotelial. Métodos: Se realizó un estudio descriptivo y retrospectivo en córneas donantes del banco de ojos del Instituto Cubano de Oftalmología "Ramón Pando Ferrer" en el período de enero a junio del año 2019. La muestra estuvo conformada por 224 córneas donantes. Las variables del estudio fueron: edad, cirugías previas, gerontoxón, pterigion, defectos epiteliales, infiltrado corneal, opacidad corneal, edema, pigmentos endoteliales, guttas, desprendimiento de la Descemet, densidad celular, hexagonalidad y polimegatismo. Resultados: El gerontoxon fue el hallazgo más frecuente (56,69 por ciento); la densidad celular media fue de 2 501 cel/mm2; el coeficiente de variación medio fue 43,32 y la hexagonalidad media 50,02. La densidad celular endotelial entre 2 000 y 2 500 cel/mm2 fue más frecuente entre 60 y 79 años de edad (76,72 por ciento), mientras que entre 20 y 29 años todas las córneas donantes presentaron una densidad endotelial mayor de 2 500 cel/mm2. Conclusiones: En el examen biomicroscópico de la córnea donante fue más frecuente el gerontoxon. Por microscopia endotelial la mayoría de las córneas fueron aptas para trasplante corneal. Un endotelio corneal con densidad celular mayor de 2 500 cel/mm2 no es exclusivo de córneas con menos de 60 años de edad(AU)


ABSTRACT Objective: Determine the characteristics of the corneal endothelium by endothelial microscopy. Methods: A retrospective descriptive study was conducted of donor corneas from the eye bank of Ramón Pando Ferrer Cuban Institute of Ophthalmology from January to June 2019. The sample was 224 donor corneas. The variables analyzed were age, previous surgery, gerontoxon, pterygium, epithelial defects, corneal infiltrate, corneal opacity, edema, endothelial pigments, guttae, Descemet's membrane detachment, cell density, hexagonality and polymegethism. Results: Gerontoxon was the most common finding (56.69 percent), mean cell density was 2 501 cell/mm2, mean variation coefficient was 43.32 and mean hexagonality was 50.02. Endothelial cell density from 2 000 to 2 500 cell/mm2 was more common in the 60-79 years age group (76.72 percent), whereas in the 20-29 years age group all the donor corneas had an endothelial density above 2 500 cell/mm2. Conclusions: Gerontoxon was the most common finding in the biomicroscopic examination of the cornea. Endothelial microscopy found that most corneas were suitable for corneal transplantation. A corneal endothelium with a cell density above 2 500 cell/mm2 is not exclusive of corneas under 60 years of age(AU)


Subject(s)
Humans , Corneal Transplantation/adverse effects , Eye Banks/ethics , Microscopy/methods , Cell Count/trends , Epidemiology, Descriptive , Retrospective Studies , Endothelial Cells/pathology , Donor Selection/methods
8.
Article in Chinese | WPRIM | ID: wpr-828901

ABSTRACT

OBJECTIVE@#To explore the effect of heparanase (HPSE) on apoptosis of microvascular endothelial cells (MVECs) and trans-endothelial migration of hepatocellular carcinoma (HCC) cells.@*METHODS@#A HCC cell line with high HPSE expression was selected by real-time quantitative PCR (qRT-PCR) and Western blotting and transefected with a lentiviral vector containing an interfering RNA sequence of HPSE. Transwell migration assay was performed to detect the trans-endothelial migration (TEM) rate of the transfected HCC cells across human umbilical vein endothelial cells (HUVECs). In a Transwell indirect co-culture system, the effect of HPSE silencing in the HCC cells was determined on apoptosis of HUVECs . A nude mouse model of HCC was used to verify the effect of HPSE on apoptosis of MVECs and liver metastasis of the tumor.@*RESULTS@#HCCLM3 cell line highly expressing HPSE was selected for the experiment. Transfection of the HCC cells with the lentiviral vector for HPSE interference the HCC cells resulted in significantly lowered TEM rate as compared with the cells transfected with the control vector ( < 0.01). In the indirect co-culture system, the survival rate of HUVECs co-cultured with HCCLM3 cells with HPSE interference was significantly higher and their apoptotic index was significantly lower than those in the control group ( < 0.05). Ultrastructural observation showed no obvious apoptosis of HUVECs co-cultured with HCCLM3 cells with HPSE interference but revealed obvious apoptotic changes in the control group. In the animal experiment, the tumor formation rate in the liver was 100% (6/6) in the control group, significantly higher than that in RNAi group (33.3%, 2/6) ( < 0.05). Under optical microscope, necrosis and apoptosis of the MVECs was detected in the liver of the control mice, while the endothelial cells remained almost intact in RNAi group.@*CONCLUSIONS@#HPSE promotes the metastasis of HCC cells by inducing apoptosis of MVECs.


Subject(s)
Animals , Apoptosis , Carcinoma, Hepatocellular , Cell Line, Tumor , Cell Movement , Cell Proliferation , Endothelial Cells , Gene Expression Regulation, Neoplastic , Glucuronidase , Humans , Liver Neoplasms , Mice
9.
Protein & Cell ; (12): 707-722, 2020.
Article in English | WPRIM | ID: wpr-828750

ABSTRACT

The 2019 novel coronavirus disease (COVID-19), caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has occurred in China and around the world. SARS-CoV-2-infected patients with severe pneumonia rapidly develop acute respiratory distress syndrome (ARDS) and die of multiple organ failure. Despite advances in supportive care approaches, ARDS is still associated with high mortality and morbidity. Mesenchymal stem cell (MSC)-based therapy may be an potential alternative strategy for treating ARDS by targeting the various pathophysiological events of ARDS. By releasing a variety of paracrine factors and extracellular vesicles, MSC can exert anti-inflammatory, anti-apoptotic, anti-microbial, and pro-angiogenic effects, promote bacterial and alveolar fluid clearance, disrupt the pulmonary endothelial and epithelial cell damage, eventually avoiding the lung and distal organ injuries to rescue patients with ARDS. An increasing number of experimental animal studies and early clinical studies verify the safety and efficacy of MSC therapy in ARDS. Since low cell engraftment and survival in lung limit MSC therapeutic potentials, several strategies have been developed to enhance their engraftment in the lung and their intrinsic, therapeutic properties. Here, we provide a comprehensive review of the mechanisms and optimization of MSC therapy in ARDS and highlighted the potentials and possible barriers of MSC therapy for COVID-19 patients with ARDS.


Subject(s)
Adoptive Transfer , Alveolar Epithelial Cells , Pathology , Animals , Apoptosis , Betacoronavirus , Body Fluids , Metabolism , CD4-Positive T-Lymphocytes , Allergy and Immunology , Clinical Trials as Topic , Coinfection , Therapeutics , Coronavirus Infections , Allergy and Immunology , Disease Models, Animal , Endothelial Cells , Pathology , Extracorporeal Membrane Oxygenation , Genetic Therapy , Methods , Genetic Vectors , Therapeutic Uses , Humans , Immunity, Innate , Inflammation Mediators , Metabolism , Lung , Pathology , Mesenchymal Stem Cell Transplantation , Methods , Mesenchymal Stem Cells , Physiology , Multiple Organ Failure , Pandemics , Pneumonia, Viral , Allergy and Immunology , Respiratory Distress Syndrome , Allergy and Immunology , Pathology , Therapeutics , Translational Medical Research
10.
Article in Chinese | WPRIM | ID: wpr-828664

ABSTRACT

OBJECTIVE@#To study the biomarkers for human coronary artery endothelial cell (HCAEC) injury induced by Kawasaki disease (KD) using isobaric tags for relative and absolute quantitation (iTRAQ) proteomics.@*METHODS@#HCAECs cultured with the serum of children with KD were used as the KD group, and those cultured with the serum of healthy children was used as the healthy control group. The iTRAQ technique was used to measure the expression of proteins in two groups. The data on proteins were analyzed by bioinformatics. Western blot was used for the validation of protein markers.@*RESULTS@#A total of 518 significantly differentially expressed proteins were identified (with an absolute value of difference fold of >1.2, P<0.05). The gene ontology analysis showed that the differentially expressed proteins were significantly enriched in biological processes (including cellular processes, metabolic processes, and biological regulation), cellular components (including cell parts, cells, and organelles), and molecular functions (including binding, catalytic activity, and molecular function regulators). The KEGG analysis showed that the proteins were significantly enriched in the signaling pathways of ribosomes, PI3K-Akt signaling pathway, and transcriptional dysregulation in cancer. The PPI network showed that the top 9 protein markers in relation density were PWP2, MCM4, MCM7, MCM5, MCM3, MCM2, SLD5, HDAC2, and MCM6, which were selected as the protein markers for coronary endothelial injury in KD. Western blot showed that the KD group had significantly lower expression levels of the protein markers HDAC2, PWP2, and MCM2 than the healthy control group (P<0.05).@*CONCLUSIONS@#The serum of children with KD significantly changes the protein expression pattern of HCAECs and affects the signaling pathways associated with the cardiovascular system, which provides a new basis for the pathophysiological mechanism and therapeutic targets of KD.


Subject(s)
Child , Computational Biology , Coronary Vessels , Endothelial Cells , Humans , Mucocutaneous Lymph Node Syndrome , Phosphatidylinositol 3-Kinases , Proteomics
11.
Article in Chinese | WPRIM | ID: wpr-828625

ABSTRACT

OBJECTIVE@#To study the effect and related signaling pathways of ginsenoside Rb1 in the treatment of coronary artery lesion (CAL) in a mouse model of Kawasaki disease (KD).@*METHODS@#BALB/c mice were randomly divided into a control group, a model group, an aspirin group, a low-dose ginsenoside Rb1 group (50 mg/kg), and a high-dose ginsenoside Rb1 group (100 mg/kg), with 12 mice in each group. All mice except those in the control group were given intermittent intraperitoneal injection of 10% bovine serum albumin to establish a mouse model of KD. The mice in the aspirin group, the low-dose ginsenoside Rb1 group, and the high-dose ginsenoside Rb1 group were given the corresponding drug by gavage for 20 days after modeling. Hematoxylin and eosin staining was used to observe the pathological changes of coronary artery tissue. ELISA was used to measure the levels of the inflammatory cytokines tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), and interleukin-1β (IL-1β) in serum and coronary artery tissue. Western blot was used to measure the relative expression levels of proteins involved in the regulation of the AMPK/mTOR autophagy signaling pathway and the PI3K/Akt oxidative stress signaling pathway in coronary artery tissue.@*RESULTS@#The observation of pathological sections showed that compared with the model group, the high-dose ginsenoside Rb1 group had significant improvement in the symptoms of vascular wall thickening, intimal edema, fiber rupture, and inflammatory infiltration of endothelial cells. Compared with the control group, the model and low-dose ginsenoside Rb1 groups had significant increases in the levels of TNF-α, IL-6, and IL-1β in serum and coronary artery tissue (P0.05) and had significant increases in the expression levels of P-AKT/AKT and P-GSK-3β/GSK-3β (P<0.05), while the high-dose ginsenoside Rb1 group had significant increases in the relative protein expression levels of the above three proteins (P<0.05). Compared with the low-dose ginsenoside Rb1 group, the aspirin group and the high-dose ginsenoside Rb1 group had significant reductions in the levels of TNF-α, IL-6, and IL-1β (P<0.05); the high-dose ginsenoside Rb1 group had significant increases in the expression levels of P-PI3K/PI3K and P-AKT/AKT (P<0.05).@*CONCLUSIONS@#Ginsenoside Rb1 can effectively alleviate CAL in a mouse model of KD in a dose-dependent manner, possibly by regulating the AMPK/mTOR/P70S6 autophagy signaling pathway to inhibit CAL inflammation and regulating the PI3K/AKT/GSK-3β oxidative stress signaling pathway to exert a biological activity of protection against coronary artery endothelial cell injury.


Subject(s)
Animals , Coronary Vessels , Endothelial Cells , Ginsenosides , Glycogen Synthase Kinase 3 beta , Mice , Mice, Inbred BALB C , Mucocutaneous Lymph Node Syndrome , Phosphatidylinositol 3-Kinases , Proto-Oncogene Proteins c-akt
12.
Protein & Cell ; (12): 707-722, 2020.
Article in English | WPRIM | ID: wpr-828586

ABSTRACT

The 2019 novel coronavirus disease (COVID-19), caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has occurred in China and around the world. SARS-CoV-2-infected patients with severe pneumonia rapidly develop acute respiratory distress syndrome (ARDS) and die of multiple organ failure. Despite advances in supportive care approaches, ARDS is still associated with high mortality and morbidity. Mesenchymal stem cell (MSC)-based therapy may be an potential alternative strategy for treating ARDS by targeting the various pathophysiological events of ARDS. By releasing a variety of paracrine factors and extracellular vesicles, MSC can exert anti-inflammatory, anti-apoptotic, anti-microbial, and pro-angiogenic effects, promote bacterial and alveolar fluid clearance, disrupt the pulmonary endothelial and epithelial cell damage, eventually avoiding the lung and distal organ injuries to rescue patients with ARDS. An increasing number of experimental animal studies and early clinical studies verify the safety and efficacy of MSC therapy in ARDS. Since low cell engraftment and survival in lung limit MSC therapeutic potentials, several strategies have been developed to enhance their engraftment in the lung and their intrinsic, therapeutic properties. Here, we provide a comprehensive review of the mechanisms and optimization of MSC therapy in ARDS and highlighted the potentials and possible barriers of MSC therapy for COVID-19 patients with ARDS.


Subject(s)
Adoptive Transfer , Alveolar Epithelial Cells , Pathology , Animals , Apoptosis , Betacoronavirus , Body Fluids , Metabolism , CD4-Positive T-Lymphocytes , Allergy and Immunology , Clinical Trials as Topic , Coinfection , Therapeutics , Coronavirus Infections , Allergy and Immunology , Disease Models, Animal , Endothelial Cells , Pathology , Extracorporeal Membrane Oxygenation , Genetic Therapy , Methods , Genetic Vectors , Therapeutic Uses , Humans , Immunity, Innate , Inflammation Mediators , Metabolism , Lung , Pathology , Mesenchymal Stem Cell Transplantation , Methods , Mesenchymal Stem Cells , Physiology , Multiple Organ Failure , Pandemics , Pneumonia, Viral , Allergy and Immunology , Respiratory Distress Syndrome , Allergy and Immunology , Pathology , Therapeutics , Translational Medical Research
13.
Article in Chinese | WPRIM | ID: wpr-828066

ABSTRACT

According to traditional Chinese medicine, "spleen transport" is closely related to the metabolism of substance and energy. Studies have shown that Alzheimer's disease(AD) is a disease related to glucose and lipid metabolism and energy metabolism. The traditional Chinese medicine Jiangpi Recipe can improve the learning ability and memory of AD animal model. Sijunzi Decoction originated from Taiping Huimin Hefang Prescription is the basic prescription for strengthening and nourishing the spleen, with the effects of nourishing Qi and strengthening the spleen. In this experiment, human brain microvascular endothelial cells(HBMEC) and Sijunzi Decoction water extract(0.25, 0.5, 1 mg·L~(-1)) were pre-incubated for 2 h, and then Aβ_(25-35) oligomers(final concentration 40 μmol·L~(-1)) was added for co-culture for 22 hours. The effect of Sijunzi Decoction on the activity of Aβ_(25-35) oligomer injured cells and the expression of related proteins were investigated. Q-TOF-LC-MS was used first for principal component analysis of Sijunzi Decoction water extract. Then MTT assay was used to investigate the effect of Sijunzi Decoction water extract on the proliferation of HBMEC cells. Real-time fluorescence quantitative PCR(RT-qPCR) was employed to detect the mRNA expression of GLUT1, RAGE, and LRP1. The expression of Aβ-related proteins across blood-brain barrier(RAGE, LRP1) was detected by Western blot. The results showed that 40 μmol·L~(-1) Aβ_(25-35) oligomers could induce endothelial cell damage, reduce cell survival, increase expression of RAGE mRNA and RAGE protein, and reduce expression of GLUT1 mRNA, LRP1 mRNA, and LRP1 protein. Sijunzi Decoction water extract could reduce the Aβ_(25-35) oligomer-induced cytotoxicity of HBMEC, decrease the expression of RAGE mRNA and RAGE protein, and increase the expression of GLUT1 mRNA, LRP1 mRNA and LRP1 protein. The results indicated that Sijunzi Decoction could reduce the injury of HBMEC cells induced by Aβ_(25-35) oligomer, and regulate the transport-related proteins GLUT1, RAGE and LRP1, which might be the mechanism of regulating Aβ_(25-35) transport across the blood-brain barrier.


Subject(s)
Amyloid beta-Peptides , Animals , Blood-Brain Barrier , Drugs, Chinese Herbal , Endothelial Cells , Humans
14.
Article in Chinese | WPRIM | ID: wpr-828042

ABSTRACT

To explore whether paeonol can play an anti-atherosclerotic role by regulating the expression of aortic caveolin-1 and affecting NF-κB pathway, so as to inhibit the inflammatory response of vascular endothelium in atherosclerotic rats. The atherosclerotic model of rats was induced by high-fat diet and vitamin D_2. The primary culture of vascular endothelial cells(VECs) was carried out by tissue block pre-digestion and adherent method. The injury model of VECs was induced by lipopolysaccharide(LPS), and filipin, a small concave protein inhibitor, was added for control. HE staining was used to observe pathological changes of aorta. TNF-α, IL-6 and VCAM-1 were detected by ELISA. Western blot assay was used to detect the protein expression levels of caveolin-1 and p65 in aorta and VECs. The results showed that as compared with model group, paeonol significantly reduced aortic plaque area and lesion degree in rats, decreased the level of serum TNF-α, IL-6 and VCAM-1 in the rats and enhanced the relative expression level of caveolin-1, decreased p65 expression conversely(P<0.05 or P<0.01). In vitro, as compared to model group, paeonol obviously improved cell morphology, decreased the secretion of TNF-α, IL-6 and VCAM-1 in VECs, increased caveolin-1 expression, and decreased p65 protein expression(P<0.05 or P<0.01). Furthermore, filipin could reverse the effect of paeonol on expression of inflammatory factors and proteins(P<0.05 or P<0.01). According to the results, it was found that paeonol could play the role of anti-atherosclerosis by up-regulating the expression of caveolin-1 and inhibiting the activation of NF-κB pathway to reduce vascular inflammation in atherosclerotic rats.


Subject(s)
Acetophenones , Animals , Caveolin 1 , Endothelial Cells , Endothelium, Vascular , Inflammation , NF-kappa B , Rats , Signal Transduction , Tumor Necrosis Factor-alpha , Up-Regulation
15.
Article in Chinese | WPRIM | ID: wpr-828038

ABSTRACT

To explore the main target and signal pathway of Simiao Yongan Decoction in the treatment of psoriatic arthritis(PsA) by network pharmacology, so as to reveal the intervention mechanism of Simiao Yongan Decoction in the treatment of psoriatic arthritis. The platform of pharmacology technology of traditional Chinese medicine system(TCMSP) was used to predict and screen the active ingredients of Simiao Yongan Decoction, and GeneCards database was searched to obtain the disease target related to the psoriatic arthritis. Protein interaction network model was constructed with STRING platform; drug-component-target-disease network map was constructed with Cytoscape Software; Wayne Diagram of common target of Simiao Yongan Decoction and psoriasis arthritis was drawn with the help of ClusterProfiler R Software. At the same time, the genetic ontology(GO) enrichment analysis and the Kyoto encyclopedia of genes and genomes(KEGG) pathway analysis were conducted. Through database analysis, 1 128 targets related to 70 main active components of Simiao Yongan Decoction and psoriatic arthritis were selected. On this basis, the interaction network between Simiao Yongan Decoction and psoriatic arthritis was constructed, and 38 common targets were screened out. By GO and KEGG enrichment analysis, 135 signal pathways related to the main components of Simiao Yongan Decoction were selected. It was found that Simiao Yong-an Decoction may play a role in the treatment of psoriatic arthritis through antiviral effect, anti-inflammatory repair, protection of vascular endothelial cells, regulation of immunity and other multiple targets. The mechanism of Simiao Yongan Decoction in the treatment of psoriatic arthritis from multi-component, multi-target and multi-pathway was revealed, which provided a research direction for screening its subsequent clinical effect evaluation indexes.


Subject(s)
Arthritis, Psoriatic , Drugs, Chinese Herbal , Endothelial Cells , Humans , Medicine, Chinese Traditional , Protein Interaction Maps
16.
Acta Physiologica Sinica ; (6): 441-448, 2020.
Article in Chinese | WPRIM | ID: wpr-827043

ABSTRACT

The aim of the present study was to investigate the role of chemokine CCL2 in angiogenesis of primary adult rat cardiac microvascular endothelial cells (CMEC). The rat CMECs were isolated and identified through morphology examination and immunostaining with CD31 and factor VIII antibodies. The angiogenesis of CMEC on Matrigel was evaluated at different time points. The expression and secretion of CCL2 during the process of angiogenesis was detected by real-time RT-PCR and ELISA, respectively. The results showed that, the primary rat CMEC was isolated successfully, and the angiogenesis of CMEC was significantly induced after Matrigel treatment for 4 h. The expression of CCL2 and CCR2 were increased during angiogenesis, and the secretion of CCL2 was detected after 2 h of angiogenesis and reached the peak concentration of 1 588.1 pg/mL after 4 h. Either CCL2 blocking antibody or CCR2 antagonist significantly reduced the angiogenesis of CMEC. These results suggest that CCL2 is secreted during the process of angiogenesis of CMEC, and CCL2/CCR2 signaling pathway may play an important role in promoting angiogenesis.


Subject(s)
Animals , Chemokine CCL2 , Endothelial Cells , Endothelium, Vascular , Heart , Neovascularization, Pathologic , Rats , Signal Transduction
17.
Protein & Cell ; (12): 707-722, 2020.
Article in English | WPRIM | ID: wpr-827023

ABSTRACT

The 2019 novel coronavirus disease (COVID-19), caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has occurred in China and around the world. SARS-CoV-2-infected patients with severe pneumonia rapidly develop acute respiratory distress syndrome (ARDS) and die of multiple organ failure. Despite advances in supportive care approaches, ARDS is still associated with high mortality and morbidity. Mesenchymal stem cell (MSC)-based therapy may be an potential alternative strategy for treating ARDS by targeting the various pathophysiological events of ARDS. By releasing a variety of paracrine factors and extracellular vesicles, MSC can exert anti-inflammatory, anti-apoptotic, anti-microbial, and pro-angiogenic effects, promote bacterial and alveolar fluid clearance, disrupt the pulmonary endothelial and epithelial cell damage, eventually avoiding the lung and distal organ injuries to rescue patients with ARDS. An increasing number of experimental animal studies and early clinical studies verify the safety and efficacy of MSC therapy in ARDS. Since low cell engraftment and survival in lung limit MSC therapeutic potentials, several strategies have been developed to enhance their engraftment in the lung and their intrinsic, therapeutic properties. Here, we provide a comprehensive review of the mechanisms and optimization of MSC therapy in ARDS and highlighted the potentials and possible barriers of MSC therapy for COVID-19 patients with ARDS.


Subject(s)
Adoptive Transfer , Alveolar Epithelial Cells , Pathology , Animals , Apoptosis , Betacoronavirus , Body Fluids , Metabolism , CD4-Positive T-Lymphocytes , Allergy and Immunology , Clinical Trials as Topic , Coinfection , Therapeutics , Coronavirus Infections , Allergy and Immunology , Disease Models, Animal , Endothelial Cells , Pathology , Extracorporeal Membrane Oxygenation , Genetic Therapy , Methods , Genetic Vectors , Therapeutic Uses , Humans , Immunity, Innate , Inflammation Mediators , Metabolism , Lung , Pathology , Mesenchymal Stem Cell Transplantation , Methods , Mesenchymal Stem Cells , Physiology , Multiple Organ Failure , Pandemics , Pneumonia, Viral , Allergy and Immunology , Respiratory Distress Syndrome , Allergy and Immunology , Pathology , Therapeutics , Translational Medical Research
18.
Article in English | WPRIM | ID: wpr-786072

ABSTRACT

OBJECTIVE: Inflammation is crucial to limiting vascular disease. Previously we reported that acrolein, a known toxin in tobacco smoke, might play an important role in the progression of atherosclerosis via an inflammatory response involving cyclooxygenase-2 (COX-2) and prostaglandin production in human umbilical vein endothelial cells (HUVECs). Curcumin has been known to improve vascular function and have anti-inflammatory properties. In this study, we investigated whether curcumin prevents the induction of inflammatory response caused by acrolein.METHODS: Anti-inflammatory effects of curcumin were examined in acrolein-stimulated HUVECs. Induction of proteins, mRNA, prostaglandin and reactive oxygen species (ROS) were measured using immunoblot analysis, real-time reverse-transcription polymerase chain reaction, enzyme-linked immunosorbent assay and flow cytometry, respectively.RESULTS: Curcumin attenuates inflammatory response via inhibition of COX-2 expression and prostaglandin production in acrolein-induced human endothelial cells. This inhibition by curcumin results in the abolition of phosphorylation of protein kinase C, p38 mitogen-activated protein kinase, and cAMP response element-binding protein. Furthermore, curcumin suppresses the production of ROS and endoplasmic reticulum stress via phosphorylation of eukaryotic initiation factor-2α caused by acrolein.CONCLUSION: These results suggest that curcumin might be a useful agent against endothelial dysfunction caused by acrolein-induced inflammatory response.


Subject(s)
Acrolein , Atherosclerosis , Curcumin , Cyclic AMP Response Element-Binding Protein , Cyclooxygenase 2 , Endoplasmic Reticulum Stress , Endothelial Cells , Enzyme-Linked Immunosorbent Assay , Flow Cytometry , Human Umbilical Vein Endothelial Cells , Humans , Inflammation , Phosphorylation , Polymerase Chain Reaction , Protein Kinase C , Protein Kinases , Reactive Oxygen Species , RNA, Messenger , Smoke , Tobacco , Vascular Diseases
19.
Chinese Journal of Biotechnology ; (12): 2741-2754, 2020.
Article in Chinese | WPRIM | ID: wpr-878526

ABSTRACT

Metastasis is the leading cause of mortality for cancer patients, and lymphatic metastasis is one of the main ways of tumor metastasis. The role of CCL21 and its receptor CCR7 in lymphatic metastasis has been increasingly concerned in recent years. CCR7 is mainly expressed by both dendritic cells and T cells for immune responses. CCL21, the chemokine ligand for CCR7, secreted from lymphatic endothelial cells binds CCR7 and recruits immune cells toward lymphatic vessels and lymphatic nodes. CCR7 expressed tumor cells can also metastasize to lymphatic system by the similar way as immune cells. Targeting CCL21/CCR7 axis to inhibit lymphatic metastasis but remain potent anti-tumor immune response has increasingly become a spot light of tumor immunotherapy. In this review, we summarize the role of CCL21/CCR7 axis in lymphatic metastasis, as well as preclinical trials and clinical trials in targeting CCL21/CCR7 axis for tumor metastasis therapy, hoping to accelerate the progress on tumor metastasis therapy by targeting CCL21/CCR7 axis.


Subject(s)
Cell Line, Tumor , Chemokine CCL21 , Endothelial Cells , Humans , Lymphatic Metastasis , Neoplasms/therapy , Receptors, CCR7/genetics
20.
Acta Physiologica Sinica ; (6): 541-550, 2020.
Article in Chinese | WPRIM | ID: wpr-878199

ABSTRACT

The occurrence and development of pulmonary arterial hypertension (PAH) is closely related to the genetic mutation of bone morphogenetic protein receptor type II (BMPRII) encoding gene and the inflammatory response mediated by nuclear factor κB (NF-κB) pathway. This paper was aimed to investigate the effect of NF-κB pathway inhibitors on lipopolysaccharide (LPS)-induced pulmonary artery endothelial cell injury. Human pulmonary artery endothelial cells were treated with 1 μg/mL of LPS. The expression levels of BMPRII and interleukin-8 (IL-8) were detected by Western blot and qPCR. The rat PAH model was established by intraperitoneal (i.p.) injection of monocrotaline (MCT). The expression levels of BMPRII and IL-8 in pulmonary artery endothelial cells were detected by immunofluorescence staining. Cardiac hemodynamic changes and pulmonary vascular remodeling were detected in the MCT-PAH model rats. The results showed that LPS caused down-regulation of BMPRII expression and up-regulation of IL-8 expression in human pulmonary artery endothelial cells. NF-κB inhibitor BAY11-7082 (10 μmol/L) reversed the effect of LPS. In the pulmonary artery endothelial cells of MCT-PAH model, BMPRII expression was down-regulated, IL-8 expression was up-regulated, weight ratio of right ventricle to left ventricle plus septum [RV/(LV+S)] and right ventricular systolic pressure (RVSP) were significantly increased, cardiac output (CO) and tricuspid annular plane systolic excursion (TAPSE) were significantly reduced, and pulmonary vessel wall was significantly thickened. BAY11-7082 (5 mg/kg, i.p., 21 consecutive days) reversed the above changes in the MCT-PAH model rats. These results suggest that LPS down-regulates the expression level of BMPRII through NF-κB signaling pathway, promoting the occurrence and development of PAH. Therefore, the NF-κB pathway can be used as a potential therapeutic target for PAH.


Subject(s)
Animals , Bone Morphogenetic Protein Receptors, Type II , Down-Regulation , Endothelial Cells/metabolism , Humans , Hypertension, Pulmonary/drug therapy , Lipopolysaccharides , NF-kappa B/metabolism , Rats , Rats, Sprague-Dawley , Vascular Remodeling
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