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1.
Gene ; 766: 145128, 2021 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-32911026

RESUMO

BACKGROUND: The pathogenesis of osteonecrosis of the femoral head (ONFH) is unclear. Our previous study demonstrated that upregulated miR-335 in bone microvascular endothelial cells (BMECs) might be associated with the disease of steroid-induced ONFH. Here, we study the preventive effect of ICA on steroid-induced ONFH in rats. METHOD: 90 rats were separated into three groups: control group, methylprednisolone (MPS) group, and MPS + Icariin (ICA) group. Four weeks later, histological analyses were performed. Thrombomodulin (TM) and vascular endothelial growth factor (VEGF) were tested. MiRNA-335 expression was screened in the three groups using Agilent Gene Spring GX software. Target genes of miRNA-335 were detected by bioinformatics analysis. The functions of BMECs were analyzed by scratch, angiogenesis and cell survival rate. RESULTS: ICA can prevent the occurrence of steroid-associated ONFH in rats and reduce the amount of TM and VEGF in serum induced by glucocorticoids. ICA could regulate the overexpression of miRNA-335 induced by glucocorticoids. We predicted the Gene ontology (GO) and signaling pathways of target genes. At 24 hours, we found that ICA significantly promoted BMECs migration abilities. We also found that ICA could promote the angioplasty ability of BMECs. ICA could improve the survival rate of BMECs after steroid-induced injury. CONCLUSIONS: ICA is effective to prevent the occurrence of steroidinduced ONFH. ICA has a protective effect against steroid-induced BMECs injury. ICA regulated the imbalance of miRNA-335 expression induced by the glucocorticoid in BMECs, which provides a new viewpoint to explore the mechanism of ICA in preventing steroid-induced ONFH.


Assuntos
Células Endoteliais/efeitos dos fármacos , Necrose da Cabeça do Fêmur/tratamento farmacológico , Cabeça do Fêmur/efeitos dos fármacos , Flavonoides/farmacologia , MicroRNAs/metabolismo , Neovascularização Patológica/tratamento farmacológico , Substâncias Protetoras/farmacologia , Adipogenia/efeitos dos fármacos , Animais , Movimento Celular/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Células Endoteliais/metabolismo , Feminino , Cabeça do Fêmur/metabolismo , Necrose da Cabeça do Fêmur/induzido quimicamente , Necrose da Cabeça do Fêmur/metabolismo , Glucocorticoides/metabolismo , Metilprednisolona/farmacologia , Neovascularização Patológica/metabolismo , Osteócitos/efeitos dos fármacos , Osteogênese/efeitos dos fármacos , Ratos , Ratos Sprague-Dawley , Transdução de Sinais/efeitos dos fármacos , Esteroides/farmacologia , Fator A de Crescimento do Endotélio Vascular/metabolismo
2.
Food Chem ; 336: 127635, 2021 Jan 30.
Artigo em Inglês | MEDLINE | ID: mdl-32763734

RESUMO

A one-step, highly-efficiency, and low-cost cold atmospheric pressure plasma (CAPP)-based method for obtaining safe-to-consume beetroot juice (BRJ) with enhanced nutritional quality is presented. Three reaction-discharge systems with different CAPPs were studied to check how the composition and physicochemical properties changed during CAPP treatment of BRJ. To identify reactive species occur in gas phase of applied CAPP for BRJ treatment, optical emission spectrometry was used. Finally, the cytotoxicity of so-obtained BRJ to human epithelial colorectal adenocarcinoma (Caco-2) and human non-malignant intestine microvascular endothelial cells (HIMEC) was assessed. Based on the performed analyses it was found that controlled CAPP treatment of BRJ changes the fraction pattern of elements in addition to increase the content of phenolic compound presents in BRJ. Furthermore, the defined CAPP treatment of BRJ inhibits proliferation of Caco-2 cell lines, exhibiting non-cytotoxic effect for HIMEC non-malignant endothelial cells. As a result, safe-to-consume BRJ of improved nutritional quality was produced.


Assuntos
Beta vulgaris/química , Indústria de Processamento de Alimentos/métodos , Sucos de Frutas e Vegetais , Gases em Plasma , Antioxidantes/química , Pressão Atmosférica , Células CACO-2 , Carboidratos/análise , Células Endoteliais/efeitos dos fármacos , Sucos de Frutas e Vegetais/análise , Sucos de Frutas e Vegetais/toxicidade , Humanos , Metais/análise , Valor Nutritivo , Fenóis/análise , Testes de Toxicidade
3.
Gene ; 766: 145153, 2021 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-32950633

RESUMO

AIM: Acute lung injury (ALI) is the mild form of acute respiratory distress syndrome (ARDS) which is a common lung disease with a high incidence and mortality rate. Recent studies manifested that some circular RNAs were associated with ALI. In this study, we aimed to uncover the effect of circular RNA circ_0054633 on ALI initiation and progression and proposed a new mechanism related to ALI. METHODS: The lipopolysaccharides (LPS)-induced acute lung injury model were build both in vivo of rat and in vitro of primary murine pulmonary microvascular endothelial cells (MPVECs). Hematoxylin and eosin (H&E) was employed to observe the tissue morphology and estimate the degree of lung damage. We used real-time quantitative polymerase chain reaction (RT-qPCR) to measure the expression level of circ_0054633. The expression levels of inflammatory cytokines IL-17A and tumor necrosis factor-α (TNF-α) were detected by ELISA. The effects of circ_0054633 on MPVECs proliferation and apoptosis were detected with the help of CCK-8 and apoptosis assay, separately. The expression level of NF-κB p65 protein was measured by Western blot. RESULTS: circ_0054633, IL-17A, TNF-α and NF-κB p65 were all overexpressed in LPS-treated rat and MPVECs, and LPS enhanced the proliferation and apoptosis of MPVECs. While circ_0054633 silencing reversed the above promotion effects of LPS on IL-17A, TNF-α expression and MPVECs proliferation and apoptosis. CONCLUSIONS: Quietness of circ_0054633 alleviated LPS-induced ALI via NF-κB signaling pathway, implicating circ_0054633 may be a potential biomarker for diagnose and therapy of ALI.


Assuntos
Lesão Pulmonar Aguda/metabolismo , Proliferação de Células/fisiologia , Células Endoteliais/metabolismo , Inflamação/metabolismo , NF-kappa B/metabolismo , RNA Circular/metabolismo , Lesão Pulmonar Aguda/induzido quimicamente , Animais , Apoptose/efeitos dos fármacos , Apoptose/fisiologia , Proliferação de Células/efeitos dos fármacos , Células Cultivadas , Inflamação/induzido quimicamente , Interleucina-17/metabolismo , Lipopolissacarídeos/farmacologia , Pulmão/efeitos dos fármacos , Pulmão/metabolismo , Masculino , Camundongos , Ratos , Ratos Sprague-Dawley , Fator de Transcrição RelA/metabolismo , Fator de Necrose Tumoral alfa/metabolismo
4.
Nihon Yakurigaku Zasshi ; 155(6): 395-400, 2020.
Artigo em Japonês | MEDLINE | ID: mdl-33132257

RESUMO

In normal condition, vasculature transports only small molecules such as nutrients across vascular wall. When inflammation occurs, inflammatory stimuli increase the permeability of vessel, which induces the extravasation of molecules larger than 40 kDa including plasma proteins. These extravasated molecules cause further inflammation by promoting the infiltration of inflammatory cells and the production of inflammatory mediators. Although it is known that vascular hyper-permeability plays an important role in inflammation, the detailed mechanism of vascular permeability regulation is still unclear. It is known that vascular permeability is controlled by two types of cells: endothelial cells and vascular mural cells. Endothelial cells cover the luminal side of vascular wall in a single layer and form endothelial barrier. Vascular mural cells regulate the blood flow volume of the downstream tissue by contracting or relaxing vascular wall. Endothelial barrier enhancement and vasocontraction suppress the vascular permeability, while endothelial barrier disruption and vasorelaxation promote it. Vascular permeability is regulated by the balance between the response of endothelial cells and vascular mural cells. Prostanoids are cell membrane-derived lipid mediators which bind to each specific G protein-coupled receptor (GPCR), prostanoid receptors. Recently, several studies showed that prostanoids regulate vascular permeability by acting on endothelial cells and/or vascular mural cells. In this review, we would like to describe the role of each prostanoid in vascular permeability by focusing on the characteristics of each specific receptor.


Assuntos
Permeabilidade Capilar , Prostaglandinas , Células Endoteliais , Endotélio Vascular/metabolismo , Prostaglandinas/metabolismo , Vasodilatação
5.
J Biomed Nanotechnol ; 16(6): 810-826, 2020 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-33187578

RESUMO

Atherosclerosis (AS) is one of the leading causes of vascular disease, producing high morbidity and mortality in many countries. Autophagy plays an important role when cells are facing serious circumstances, such as oxidative stress induced by Ox-LDL (oxidized low-density lipoprotein). Recent studies have revealed that DEX (dexamethasone acetate) and RAPA (rapamycin) exhibit efficient AS therapeutic ability by protecting endothelial cells and killing foam cells, respectively. Herein, we hypothesize that combining DEX and RAPA together in a specific nanocarrier system can achieve better AS therapy while limiting harmful effects. As a proof of concept, DEX and RAPA coloaded mPEG2k-DSPE calcium phosphate (CaP) nanoparticles (DR-NPs) were prepared by using a biomineralization method. DR-NPs increased HUVEC survival and induced foam cell apoptosis in vitro, which were correlated with autophagy activity. DR-NPs efficiently aggregated at AS plaques in the carotid artery and abdominal artery in ApoE- / - mice 24 h after i.v. injection. Moreover, DR-NPs exhibited excellent plaque regression ability, with smaller necrotic cores and lipid core areas observed after in vivo treatment. Furthermore, the function of vascular endothelial cells was largely promoted, as evidenced by the dramatically decreased expression levels of adhesion factors, such as MMP-2, MMP-9 and ICAM-1. Consequently, DR-NPs can act as an effective AS therapeutic agent and broaden the AS therapeutic approach by inducing autophagy.


Assuntos
Aterosclerose , Nanopartículas , Animais , Aterosclerose/tratamento farmacológico , Autofagia , Fosfatos de Cálcio , Dexametasona/análogos & derivados , Células Endoteliais , Lipoproteínas LDL , Camundongos , Fosfatidiletanolaminas , Sirolimo
6.
J Biomed Nanotechnol ; 16(6): 985-996, 2020 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-33187593

RESUMO

Cetuximab-conjugated gold nanoparticles are known to target cancer cells, but display toxicity towards normal kidney, liver and endothelial cells in vitro. In this study, we investigated their pharmacokinetics, biodistribution and toxicity after intravenous administration in healthy mice. Our data showed that these nanoparticles were rapidly cleared from the blood and accumulated mainly in the liver and spleen with long-term retention. Acute liver injury, inflammatory activity and vascular damage were transient and negligible, as confirmed by the liver functionality tests and serum marker analysis. There was no sign of altered liver, kidney, lung and spleen morphology up to 4 weeks post-injection. After 6 months, kidney casts and splenic apoptosis appeared to be more prevalent than in the controls. Furthermore, occasional immune cell infiltration was observed in the lungs. Therefore, we recommend additional in vivo studies, in order to investigate the long-term toxicity and elimination of gold nanoparticles after multiple dosing in their preclinical validation as new targeted anti-cancer therapies.


Assuntos
Nanopartículas Metálicas , Nanopartículas , Animais , Células Endoteliais , Ouro/metabolismo , Ouro/toxicidade , Nanopartículas Metálicas/toxicidade , Camundongos , Baço/metabolismo , Distribuição Tecidual
7.
Zhongguo Zhong Yao Za Zhi ; 45(19): 4686-4691, 2020 Oct.
Artigo em Chinês | MEDLINE | ID: mdl-33164433

RESUMO

In this study, the oxygen-glucose deprivation(OGD) model in the human brain microvascular endothelial cell(HBMEC) was used to simulate the ischemic neuronal damage and observe the inflammatory response, explore the possible mechanisms for treating cerebral ischemia/reperfusion and improving memory impairment from the view point of inhibiting inflammatory response, which is of great reference significance for related Chinese medicine treatment of ischemic diseases. HBMECs were given with drugs at the same time of OGD injury, and reoxygenated for 2 h after 4 h treatment. Cell supernatant was then collected, and the inflammatory factors in cell supernatant were detected. Immunofluorescence assay was used to detect HBMECs morphology and expression of p-nuclear factor kappa-light-chain-enhancer of activated B(p-NF-κB); Western blot was used to detect expression changes of Toll like receptor 4(TLR4), myeloid differentiation primary response 88(MYD88) and p-NF-κB. The results showed that, after OGD modeling, the levels of interleukin 6(IL-6), IL-1α, IL-1ß and tumor necrosis factor-α(TNF-α) were significantly increased; baicalin protected HBMEC, inhibited intranuclear transcription of p-NF-κB, significantly decreased HBMEC release of inflammatory factors caused by OGD injury, and inhibited the expression of TLR4, MYD88, and p-NF-κB. The studies suggested that baicalin had obvious protective effect on HBMECs damaged by OGD, and could inhibit inflammatory response. Its protection mechanism may be related to inhibiting TLR4 signaling pathways.


Assuntos
NF-kappa B , Receptor 4 Toll-Like , Encéfalo/metabolismo , Células Endoteliais/metabolismo , Flavonoides , Humanos , Hipóxia , NF-kappa B/genética , NF-kappa B/metabolismo , Transdução de Sinais , Receptor 4 Toll-Like/genética , Receptor 4 Toll-Like/metabolismo
8.
Nat Commun ; 11(1): 5211, 2020 10 15.
Artigo em Inglês | MEDLINE | ID: mdl-33060583

RESUMO

Chromatin-associated RNA (caRNA) has been proposed as a type of epigenomic modifier. Here, we test whether environmental stress can induce cellular dysfunction through modulating RNA-chromatin interactions. We induce endothelial cell (EC) dysfunction with high glucose and TNFα (H + T), that mimic the common stress in diabetes mellitus. We characterize the H + T-induced changes in gene expression by single cell (sc)RNA-seq, DNA interactions by Hi-C, and RNA-chromatin interactions by iMARGI. H + T induce inter-chromosomal RNA-chromatin interactions, particularly among the super enhancers. To test the causal relationship between H + T-induced RNA-chromatin interactions and the expression of EC dysfunction-related genes, we suppress the LINC00607 RNA. This suppression attenuates the expression of SERPINE1, a critical pro-inflammatory and pro-fibrotic gene. Furthermore, the changes of the co-expression gene network between diabetic and healthy donor-derived ECs corroborate the H + T-induced RNA-chromatin interactions. Taken together, caRNA-mediated dysregulation of gene expression modulates EC dysfunction, a crucial mechanism underlying numerous diseases.


Assuntos
Cromatina/fisiologia , Células Endoteliais/metabolismo , RNA/metabolismo , Estresse Fisiológico/fisiologia , DNA/metabolismo , Diabetes Mellitus/genética , Diabetes Mellitus/metabolismo , Epigenômica , Expressão Gênica/efeitos dos fármacos , Redes Reguladoras de Genes , Glucose/metabolismo , Glucose/farmacologia , Células Endoteliais da Veia Umbilical Humana , Humanos , Inibidor 1 de Ativador de Plasminogênio/genética , Inibidor 1 de Ativador de Plasminogênio/metabolismo , Fator de Necrose Tumoral alfa/metabolismo , Fator de Necrose Tumoral alfa/farmacologia
9.
Int J Nanomedicine ; 15: 6975-6991, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33061363

RESUMO

Purpose: Small extracellular vesicles (sEV) are a heterogeneous group of vesicles that consist of proteins, lipids and miRNA molecules derived from the cell of origin. Although xenogeneic sEV have been applied for soft tissue regeneration successfully, the regeneration effect of allogeneic and xenogeneic sEV has not been compared systematically. Methods: Our previous study has shown that sEV derived from rat adipose tissue successfully induced neoadipose regeneration. In this study, sEV were isolated from rat adipose tissue (r-sEV-AT) and porcine adipose tissue (p-sEV-AT), the morphology, size distribution and marker proteins expression of r-sEV-AT and p-sEV-AT were characterized. Besides, the sEV/AT ratio was evaluated and compared between r-sEV-AT and p-sEV-AT. Rat adipose-derived stromal/stem cells (rASCs) and rat aorta endothelial cells (rECs) were adopted to test the cellular response to allogeneic and xenogeneic sEV-AT. The effects of allogeneic and xenogeneic sEV-AT on host cells migration and neoadipose formation were evaluated in a subcutaneous custom-designed model. A full-thickness skin wound healing model was used to further compare the ability of allogeneic and xenogeneic sEV-AT in inducing complex soft tissue regeneration. Results: p-sEV-AT showed similar morphology and size distribution to r-sEV-AT. Marker proteins of sEV were detected in both r-sEV-AT and p-sEV-AT. The sEV/AT ratio of porcine was slightly higher than that of rat. The effects of r-sEV-AT and p-sEV-AT on the differentiation of rASCs and rECs showed no significant difference. When allogeneic and xenogeneic sEV-AT were subcutaneously implanted into the back of SD rats, the host cells chemotactic infiltration was observed in 1 week and neoadipose tissue formation was induced in 8 weeks; no significant difference was observed between allogeneic and xenogeneic sEV-AT. For complex soft tissue regeneration, both allogeneic and xenogeneic sEV-AT significantly promoted wound re-epithelialization, granulation tissue formation and hair follicle regeneration and then accelerated skin wound healing. Conclusion: Our results demonstrated that sEV derived from the same tissues of different species might be loaded with similar therapeutic substance benefitting tissue repair and regeneration, and paved the way for future research aimed at xenogeneic sEV application.


Assuntos
Tecido Adiposo/fisiologia , Vesículas Extracelulares/transplante , Transplante Heterólogo , Transplante Homólogo , Adipócitos , Tecido Adiposo/citologia , Animais , Diferenciação Celular , Movimento Celular , Células Cultivadas , Células Endoteliais/citologia , Espaço Extracelular , MicroRNAs , Ratos Sprague-Dawley , Regeneração , Suínos , Transplante Heterólogo/métodos , Transplante Homólogo/métodos , Cicatrização
10.
Arkh Patol ; 82(5): 16-24, 2020.
Artigo em Russo | MEDLINE | ID: mdl-33054028

RESUMO

OBJECTIVE: To study ultrastructural changes in endocardial tissues and endocrine cardiomyocytes of the left atrial appendage in patients with atrial fibrillation. MATERIAL AND METHODS: Electron microscopy was used to examine the endocardium and endocrine cardiomyocytes of the left atrial appendage in 8 patients with long-standing paroxysmal and persistent atrial fibrillation and in one patient with coronary heart disease without rhythm disturbance (a control group). RESULTS: The investigation revealed that all the patients with atrial fibrillation had similar ultrastructural changes in all endocardial layers and endocrine cardiomyocytes of the left atrial appendage. The endothelium showed massive desquamation of endothelial cells. Predominantly single sharply flattened cells and small cytoplasmic fragments remained on the endocardial surface. The latter devoid of endothelial coating was represented by subendothelial loose connective tissue with noticeable signs of edema. The latter was also observed in the dense fibrous connective tissue of the endocardium. The accumulation of large amounts of edema fluid in the subendothelium led to endothelial cell flattening and desquamation. There was no leukocytic infiltration in the tissue of the endocardium or fibrin and desquamated endothelial cell accumulation on its surface. The endocrine cardiomyocytes exhibited disorders as cytoplasmic swelling, complete or partial lysis (necrosis) of individual myofibrils, and lower levels of endocrine granules and their location near or in direct contact with the sarcolemma. CONCLUSION: The study has shown that long-standing atrial fibrillation deteriorates the main factors that determine normal endothelial function: edema in subendothelial tissue disrupts its interaction with endothelial cells and leads the latter to detach from the endocardium; ultrastructural changes in the endocrine cardiomyocytes that produce hormones can impair systemic blood pressure control and intracardiac hemodynamics.


Assuntos
Apêndice Atrial , Fibrilação Atrial , Endocárdio , Células Endoteliais , Humanos , Miócitos Cardíacos
11.
Nat Commun ; 11(1): 5319, 2020 10 21.
Artigo em Inglês | MEDLINE | ID: mdl-33087700

RESUMO

Arterial networks enlarge in response to increase in tissue metabolism to facilitate flow and nutrient delivery. Typically, the transition of a growing artery with a small diameter into a large caliber artery with a sizeable diameter occurs upon the blood flow driven change in number and shape of endothelial cells lining the arterial lumen. Here, using zebrafish embryos and endothelial cell models, we describe an alternative, flow independent model, involving enlargement of arterial endothelial cells, which results in the formation of large diameter arteries. Endothelial enlargement requires the GEF1 domain of the guanine nucleotide exchange factor Trio and activation of Rho-GTPases Rac1 and RhoG in the cell periphery, inducing F-actin cytoskeleton remodeling, myosin based tension at junction regions and focal adhesions. Activation of Trio in developing arteries in vivo involves precise titration of the Vegf signaling strength in the arterial wall, which is controlled by the soluble Vegf receptor Flt1.


Assuntos
Células Endoteliais/citologia , Células Endoteliais/fisiologia , Fatores de Troca do Nucleotídeo Guanina/fisiologia , Fator A de Crescimento do Endotélio Vascular/fisiologia , Remodelação Vascular/fisiologia , Animais , Animais Geneticamente Modificados , Tamanho Celular , Células Cultivadas , Fatores de Troca do Nucleotídeo Guanina/genética , Células Endoteliais da Veia Umbilical Humana , Humanos , Modelos Cardiovasculares , Fator de Crescimento Placentário/genética , Fator de Crescimento Placentário/fisiologia , Proteínas Serina-Treonina Quinases/genética , Proteínas Serina-Treonina Quinases/fisiologia , Transdução de Sinais , Fator A de Crescimento do Endotélio Vascular/genética , Receptor 1 de Fatores de Crescimento do Endotélio Vascular/genética , Receptor 1 de Fatores de Crescimento do Endotélio Vascular/fisiologia , Remodelação Vascular/genética , Peixe-Zebra/embriologia , Peixe-Zebra/genética , Peixe-Zebra/fisiologia , Proteínas de Peixe-Zebra/genética , Proteínas de Peixe-Zebra/fisiologia , Proteínas rac1 de Ligação ao GTP/genética , Proteínas rac1 de Ligação ao GTP/fisiologia
12.
Nat Commun ; 11(1): 5292, 2020 10 21.
Artigo em Inglês | MEDLINE | ID: mdl-33087715

RESUMO

Recent advances have enabled the direct induction of human tissue-specific stem and progenitor cells from differentiated somatic cells. However, it is not known whether human hepatic progenitor cells (hHepPCs) can be generated from other cell types by direct lineage reprogramming with defined transcription factors. Here, we show that a set of three transcription factors, FOXA3, HNF1A, and HNF6, can induce human umbilical vein endothelial cells to directly acquire the properties of hHepPCs. These induced hHepPCs (hiHepPCs) propagate in long-term monolayer culture and differentiate into functional hepatocytes and cholangiocytes by forming cell aggregates and cystic epithelial spheroids, respectively, under three-dimensional culture conditions. After transplantation, hiHepPC-derived hepatocytes and cholangiocytes reconstitute damaged liver tissues and support hepatic function. The defined transcription factors also induce hiHepPCs from endothelial cells circulating in adult human peripheral blood. These expandable and bipotential hiHepPCs may be useful in the study and treatment of human liver diseases.


Assuntos
Técnicas de Reprogramação Celular/métodos , Células Endoteliais/citologia , Hepatócitos/citologia , Células-Tronco/citologia , Animais , Ductos Biliares/citologia , Ductos Biliares/fisiologia , Agregação Celular , Diferenciação Celular/genética , Diferenciação Celular/fisiologia , Células Cultivadas , Reprogramação Celular/genética , Reprogramação Celular/fisiologia , Células Endoteliais/fisiologia , Feminino , Fator 1-alfa Nuclear de Hepatócito/genética , Fator 1-alfa Nuclear de Hepatócito/fisiologia , Fator 3-gama Nuclear de Hepatócito/genética , Fator 3-gama Nuclear de Hepatócito/fisiologia , Fator 6 Nuclear de Hepatócito/genética , Fator 6 Nuclear de Hepatócito/fisiologia , Hepatócitos/fisiologia , Hepatócitos/transplante , Xenoenxertos , Células Endoteliais da Veia Umbilical Humana , Humanos , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Endogâmicos NOD , Camundongos SCID , Esferoides Celulares/citologia , Esferoides Celulares/fisiologia , Células-Tronco/fisiologia
13.
Zhongguo Shi Yan Xue Ye Xue Za Zhi ; 28(5): 1578-1584, 2020 Oct.
Artigo em Chinês | MEDLINE | ID: mdl-33067957

RESUMO

OBJECTIVE: To investigate the potential mechanisms of miR-224 affecting the proliferation and invasion of diffuse large B-cell lymphoma (DLBCL) cells. METHODS: The blood samples of 76 DLBCL patients(DLBCL group) diagnosed at the First Affiliated Hospital of Kunming Medical University from June 2011 to December 2017, and 41 healthy persons of physical examination (normal control group) as well as human lymphatic endothelial cells (HELC) and DLBCL cell lines HBL1, OCI-LY10, OCI-LY8, OCI-LY19 were collected. The expression of miR-224 and PIK3CD mRNA was measured by RT-qPCR. The proliferation of HBL1 cells was detected by CCK-8 method and colony formation test. The invasion ability of HBL1 cells was detected by Transwell test. Dual-luciferase reporter gene assay was used to verify the relationship between miR-224 and PIK3CD. The expression of PIK3CD protein was measured by Western blot. RESULTS: The expression of miR-224 in blood of DLBCL patients was very significantly lower than that in normal control group (P<0.01). The overexpression of miR-224 significantly decreased proliferation and invasion of HBL1 cells (all P<0.01). PIK3CD was a target gene of miR-224. Knockdown of PIK3CD significantly suppressed the proliferation and invasion of HBL1 cells (all P<0.01). CONCLUSION: MiR-224 plays a key role in the progression of DLBCL, and the proliferation and invasion of HBL1 cells can be suppressed by targeted inhibition of PIK3CD.


Assuntos
Linfoma Difuso de Grandes Células B , MicroRNAs , Linhagem Celular Tumoral , Proliferação de Células , Classe I de Fosfatidilinositol 3-Quinases/genética , Células Endoteliais , Humanos , Linfoma Difuso de Grandes Células B/genética , MicroRNAs/genética
14.
Wiad Lek ; 73(8): 1712-1716, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33055339

RESUMO

OBJECTIVE: The aim: Study of the patterns of structural changes in the left ventricular myocardial capillaries of rats with arterial hypertension with combined pharmacotherapy with Bisoprolol and Thiotriazolinum. PATIENTS AND METHODS: Materials and methods: Experiments were conducted on 30 line rats with congenital stress-induced arterial hypertension: 10 animals without treatment and 10 animals with treatment. Pharmacological correction of spontaneous arterial hypertension was performed with 20 mg / kg of Bisoprolol and 50 mg / kg of Thiotriazolinum per os once a day. Pharmacotherapy began at 5 months of age, that is, at a time when compensated heart failure was formed in rats with arterial hypertension. Animals were withdrawn from the experiment 100 days after the start of the correction. Control was provided by intact animals (10 rats) of the corresponding age. While extracted from the experiment rats of all experimental groups had their arterial pressure measured using a plethysmograph, electron microscopic examination of the left ventricular myocardium and morphometric study of volumetric and quantitative densities, cross-section area and form factor of micropinocytotic vesicles were conducted. RESULTS: Results: In rats with arterial hypertension after application of Bisoprolol and Thiotriazolinum, arterial pressure significantly decreases in experimental rats compared to animals without correction. The number of capillaries in the myocardium after pharmacotherapy increases up to control values, which shows their reparation. In most endothelial cells, organelles retain their integrity and presence that are characteristic of intact rats. The well-expressed processes of transcytosis are shown by the statistical similarity of the quantitative density and the size of the micropinocytotic vesicles in the endothelial cells of the myocardium capillaries of compared experimental animals. CONCLUSION: Conclusions: In rats with arterial hypertension, the combination of Bisoprolol and Thiotriazolinum prevents the decrease in the number of capillaries in the myocardium of the left ventricle, promotes the preservation of the ultrastructure of their endothelial cells and maintains the processes of transedothelial transfer of substances at the level of intact animals.


Assuntos
Células Endoteliais , Hipertensão , Animais , Bisoprolol/uso terapêutico , Coração , Hipertensão/complicações , Hipertensão/tratamento farmacológico , Miocárdio , Ratos
15.
Vestn Oftalmol ; 136(5): 87-95, 2020.
Artigo em Russo | MEDLINE | ID: mdl-33056968

RESUMO

PURPOSE: To perform a comparative analysis of clinical and functional results and efficiency of corneal astigmatism correction after femtosecond laser-assisted cataract surgery (FLACS) with implantation of toric intraocular lens (TIOL) and in combination with arcuate keratotomy (FL-AC). MATERIAL AND METHODS: The examination included 60 patients (60 eyes). The first group consisted of 30 patients (30 eyes) who underwent FLACS with implantation of TIOL (Acrysof IQ Toric, Alcon, U.S.A.); the second group consisted of 30 patients (30 eyes) who underwent FLACS in combination with FL-AC. The examination was carried out before the operation, on the 3rd day and 3 months after surgery. Corneal astigmatism correction efficiency was analyzed using the Alpins method and graphical vector analysis. RESULTS: Uncorrected visual acuity (UCVA) indices increased to 0.70±0.24 and 0.66±0.31 in the FLACS with TIOL and FLACS with FL-AC groups, respectively, without statistically significant differences between the groups (p=0.03). The value of the residual cylinder was significantly lower in the FLACS with TIOL group (-0.77±0.58 and -0.80±0.39) compared with FLACS with FL-AC (-1.08±0.81 and -1.18±0.63) both on day 3 (p=0.02), and 3 months after surgery (p=0.02). In the FLACS with TIOL group, a higher correction index (0.99±0.18) and a smaller difference vector (0.77±0.64) were achieved compared to the FLACS with FL-AC group (0.78±0.35 and 1.05±0.76, respectively). Corneal higher-order aberrations (HOA) significantly differed on the 3rd day after surgery in the 3.0 mm (p=0.04) and 5.0 mm (p=0.04) zones between the groups. Endothelial cells density was 2460.50±328.40 and 2526.125±196.74 cl/mm2 after 3 months of observation in the FLACS with TIOL and FLACS with FL-AC groups, respectively (p=0.61). CONCLUSION: Both methods had comparable visual acuity results (p=0.03). FLACS with TIOL provided more effective correction of the cylindrical component of refraction to 3.0 D.


Assuntos
Astigmatismo , Extração de Catarata , Doenças da Córnea , Lentes Intraoculares , Astigmatismo/diagnóstico , Astigmatismo/etiologia , Astigmatismo/cirurgia , Extração de Catarata/efeitos adversos , Células Endoteliais , Humanos
16.
Zhonghua Yan Ke Za Zhi ; 56(10): 754-760, 2020 Oct 11.
Artigo em Chinês | MEDLINE | ID: mdl-33059418

RESUMO

Objective: To study the diabetic keratopathy in type 2 diabetes patients with retinopathy by in vivo laser confocal microscopy. Methods: This was a case-control study. Ninety type 2 diabetes patients were involved in this study from May 2015 to December 2019 in Qingdao Eye Hospital. According to the diabetic retinopathy clinical stage, these patients were divided into the non-proliferative diabetic retinopathy (NPDR) group (30 cases), early stage proliferative diabetic retinopathy (PDR) group (30 cases) and intermediate to late stage PDR group (30 cases). Thirty non-diabetic healthy volunteers were included in the control group. The central cornea was observed with an in vivo laser confocal microscope. The corneal nerve fiber density, nerve fiber length, nerve branch density, and nerve fiber tortuosity were compared between groups. The corneal Langerhans cells, epithelial cells, stromal cells and endothelial cells were also compared. Results: There were more nerve fibers and branches in the control group than the other three diabetic groups. The nerve fiber length in the control group, NPDR group, early stage PDR group and intermediate to late stage PDR group was (21.55±2.57), (14.73±1.56), (11.23±1.40) and (8.02±1.33) mm/mm2, respectively, and there were statistically significant differences between the groups (F=316.17, P=0.00). In the nerve fiber density, nerve branch density and curvature, there were statistically significant differences between the groups (F=345.72, 479.46, 167.00, all P=0.00). The basal cell density in the control group, NPDR group, and two PDR groups was (5 761±303), (5 336±367), (4 146±379) and (3 658±365) cells/mm2, respectively, and there were statistically significant differences between the groups (F=234.94, P=0.00). The anterior stromal cell density in the four groups was (836±30), (727±57), (544±59) and (360±47) cells/mm2, respectively, and there were statistically significant differences between the groups (F=535.08, P=0.00). The hexagonal endothelium cell rate in the four groups was 62.0%±5.5%, 51.1%±3.7%, 40.2%±4.0% and 27.8%±3.9%, respectively, and the Langerhans cell density was (1.5±0.6), (4.2±1.3), (6.8±2.1) and (10.9±2.1) cells/mm2, respectively; there were statistically significant differences between the groups (F=342.28, 179.78, all P=0.00). There was no statistically significant difference between the groups in the corneal endothelial cell density (F=1.58, P=0.20). Conclusions: In type 2 diabetes patients with diabetic retinopathy, the corneal nerve fiber and branch density can be significantly reduced, and the density of the hexagonal corneal endothelial cells, epithelial basal cells and anterior stromal cells can also decrease. Langerhans cells may be involved in the development diabetic keratopathy. (Chin J Ophthalmol, 2020, 56: 754-760).


Assuntos
Diabetes Mellitus Tipo 2 , Retinopatia Diabética , Estudos de Casos e Controles , Diabetes Mellitus Tipo 2/complicações , Retinopatia Diabética/diagnóstico por imagem , Células Endoteliais , Humanos , Microscopia Confocal
17.
Drugs Today (Barc) ; 56(9): 599-608, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-33025953

RESUMO

Ripasudil (K-115) is a novel Rho-associated protein kinase (ROCK) inhibitor. The Rho-ROCK pathway regulates key downstream effectors involved in many cellular functions, in particular in the actin cytoskeleton activity. The clinical effects of ripasudil expected on the eye include an intraocular pressure-lowering effect and a wound-healing activity on corneal endothelial cells, but many other functions are currently under investigation. To date, ripasudil has been approved in Japan (2014) for the treatment of glaucoma and ocular hypertension, and several clinical trials are currently investigating its role in the treatment of Fuchs' corneal dystrophy. In this review, we will discuss its pharmacokinetics, pharmacodynamics and clinical efficacy, focusing also on its safety and tolerability profile.


Assuntos
Glaucoma/tratamento farmacológico , Isoquinolinas/uso terapêutico , Hipertensão Ocular/tratamento farmacológico , Sulfonamidas/uso terapêutico , Ensaios Clínicos como Assunto , Células Endoteliais , Humanos , Japão , Quinases Associadas a rho/antagonistas & inibidores
18.
Sheng Li Xue Bao ; 72(5): 541-550, 2020 Oct 25.
Artigo em Chinês | MEDLINE | ID: mdl-33106824

RESUMO

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.


Assuntos
Receptores de Proteínas Morfogenéticas Ósseas Tipo II , Hipertensão Pulmonar , Animais , Regulação para Baixo , Células Endoteliais/metabolismo , Humanos , Hipertensão Pulmonar/induzido quimicamente , Hipertensão Pulmonar/tratamento farmacológico , Lipopolissacarídeos , NF-kappa B/metabolismo , Ratos , Ratos Sprague-Dawley , Remodelação Vascular
19.
Zhonghua Wei Zhong Bing Ji Jiu Yi Xue ; 32(9): 1131-1134, 2020 Sep.
Artigo em Chinês | MEDLINE | ID: mdl-33081905

RESUMO

According to the world epidemic report, the mortality of patients with severe coronavirus disease 2019 (COVID-19) is high. Diabetic patients are more susceptible to COVID-19. Since the mortality of COVID-19 patients with diabetes is on the top of list, hyperglycemia is considered an independent risk factor for severe COVID-19. Up to now, there is few effective treatment for severe patients infected with 2019 novel coronavirus (2019-nCoV). Clinical studies observed that cytokine storms existed in patients with severe COVID-19. Sustained high levels of cytokines cause diffuse damage to pulmonary capillary endothelial cells and alveolar epithelial cells, resulting in acute respiratory distress syndrome (ARDS). ARDS is the main cause of death in COVID-19 patients. Host-directed therapy (HDT) is an emerging therapeutic method in the field of anti-infection, which can activate the self-protective immune response, suppress excessive inflammatory response, and be used to assist the treatment of traditional drugs to shorten the course of disease. Metformin has been shown to be effective in HDT and can assist in the treatment of the viral and bacterial infectious disease. This paper discusses the rationality and potential therapeutic mechanism of metformin in the treatment of severe COVID-19. It was speculated that the use of metformin for controlling blood glucose in severe COVID-19 patients with diabetes may prevent or inhibit the occurrence of ARDS, thereby reducing the mortality of COVID-19 patients. The possible mechanism is that metformin could inhibit cytokine storm via suppressing interleukin-6 (IL-6) signaling, prevent the process of lung fibrosis, suppress endocytosis, thereby elevating angiotensin converting enzyme 2 (ACE2) expression.


Assuntos
Betacoronavirus , Infecções por Coronavirus , Metformina/uso terapêutico , Pandemias , Pneumonia Viral , Infecções por Coronavirus/tratamento farmacológico , Células Endoteliais , Pneumonia Viral/tratamento farmacológico
20.
Zhong Nan Da Xue Xue Bao Yi Xue Ban ; 45(9): 1024-1034, 2020.
Artigo em Inglês, Chinês | MEDLINE | ID: mdl-33051415

RESUMO

OBJECTIVES: There is a significant increase of high-mobility group protein B1 (HMGB1) in plasma levels of patients with pulmonary hypertension, but the biological significance is still unclear. Anti-proliferative protein 1 (prohibitin 1, PHB1) is an important protein that maintains the homeostasis of vascular cells. This study aimed to investigate the effect of HMGB1 on pulmonary artery endothelial cells and the role of PHB1. METHODS: In vivo experiment: A rat model of pulmonary hypertension induced by monocrotaline (MCT) was constructed. The right ventricular systolic pressure (RVSP), and the weight ratio of right ventricle to left ventricle plus ventricular septum were used to evaluate the success of model. ELISA was used to detect the level of HMGB1 in rat's plasma. Western blotting was used to detect the level of PHB1 in rat's lung tissues. CD31 immunofluorescence was used to detect the integrity of pulmonary vascular endothelium. In vitro experiments: Pulmonary artery endothelial cell (PAEC) was incubated with HMGB1 to observe the effect of HMGB1 on PAEC injury. Overexpression and knockdown of PHB1 were conducted, and the role of PHB1 was investigated by detecting the levels of reative oxygen species and cytochrome c (cyto-c), and the activation of caspase-3. RESULTS: Compared with the control group, the level of HMGB1 in the plasma of rats with pulmonary hypertension was significantly increased (P<0.05), and the expression of PHB1 in the lung tissue was decreased accompanied with endothelial dysfunction (P<0.05); HMGB1 incubation damaged the pulmonary artery endothelium and down-regulated PHB1 expression (P<0.05), while overexpression of PHB1 reduced the PAEC damage and oxidative stress induced by HMGB1 (P<0.05). Meanwhile, PHB1 reduced HMGB1-induced cyto-c expression and caspase-3 cleavage by inhibiting oxidative stress (P<0.05). CONCLUSIONS: The down-regulation of PHB1 expression mediates HMGB1-induced PAEC injury, which is related to the induction of oxidative stress, the increase of cyto-c release, and the promotion of caspase-3 cleavage.


Assuntos
Proteína HMGB1 , Proteínas Repressoras , Animais , Células Endoteliais , Proteína HMGB1/genética , Humanos , Artéria Pulmonar , Ratos , Proteínas Repressoras/genética
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