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1.
Semin Thromb Hemost ; 2024 Sep 18.
Artigo em Inglês | MEDLINE | ID: mdl-39293485

RESUMO

Portal vein thrombosis (PVT) is commonly encountered in patients with cirrhosis, challenging our understanding of its development, particularly the ambiguous contribution of inflammation. This study utilized Mendelian randomization (MR) to explore the causal impact of circulating inflammatory markers on PVT.Employing a two-sample MR framework, we merged genome-wide association study (GWAS) meta-analysis findings of 91 inflammation-associated proteins with independent PVT data from the FinnGen consortium's R10 release. A replication analysis was performed using a distinct GWAS dataset from the UK Biobank. Inverse variance weighting, MR-Egger regression, weighted median estimator, and Mendelian Randomization Pleiotropy RESidual Sum and Outlier were used for analysis, supplemented by multivariable MR (MVMR) to adjust for cirrhosis effects.Findings indicate a significant inverse association between the genetically inferred concentration of eukaryotic translation initiation factor 4E-binding protein 1 (4E-BP1) and PVT risk, evidenced by an odds ratio (OR) of 0.37 (95% confidence interval [CI]: 0.21-0.67; p = 9.2 × 10-4; adjusted for multiple testing p = 0.084). This association was corroborated in the replication phase (OR = 0.39, 95% CI: 0.17-0.93; p = 0.03) and through MVMR analysis (OR = 0.34, 95% CI: 0.15-0.79; p = 0.012). Sensitivity analyses disclosed no evidence of heterogeneity or pleiotropy.Our investigation emphasizes the 4E-BP1 as a protective factor against PVT, underscoring its potential relevance in understanding PVT pathogenesis and its implications for diagnosis and therapy.

2.
J Vasc Interv Radiol ; 35(9): 1332-1339, 2024 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-38499268

RESUMO

PURPOSE: To assess the feasibility and effectiveness of percutaneous transluminal renal angioplasty (PTRA) for pediatric renovascular hypertension (RVH) secondary to total renal artery occlusion (RAO). MATERIALS AND METHODS: From 2011 to 2021, 13 pediatric patients with RVH confirmed with 14 renal artery occlusions were reviewed. The mean age was 11.2 years (range, 4-16 years). Nine occlusions involved main artery occlusion, and 5 involved branch occlusion. Blood pressure ratio (BPR) was defined as the ratio of the actual measured blood pressure (BP) value to the 95th percentile value adjusted for age, sex, and height. RESULTS: PTRA was performed in 9 patients (9/13, 69%). Technical success was achieved in 5 patients (5/9, 56%), with stent placement in 2 children (2/9, 22%). During the 12-month follow-up, restenosis was identified in both of the stent-receiving patients at the 12-month follow-up visit (2/9, 22%). Mean systolic BPR decreased from 1.20 (SD ± 0.07) to 0.96 (SD ± 0.06; P = .003), mean diastolic BPR decreased from 1.19 (SD ± 0.07) to 0.95 (SD ± 0.08; P = .005), and the number of medications required decreased from 3.8 (SD ± 0.8) to 2.4 (SD ± 0.9; P = .052) after PTRA. Subsequent to PTRA, the mean glomerular filtration rate of the occluded kidney improved from 19.5 mL/min (SD ± 12.3) to 36.3 mL/min (SD ± 10.8; P = .007), and the mean longitudinal dimension of the affected kidneys significantly increased from 8.2 cm (SD ± 1.5) to 9.2 cm (SD ± 1.7; P = .006). CONCLUSIONS: Endovascular treatment is often feasible for pediatric patients with RAO, results in acceptable BP control, and preserves renal function.


Assuntos
Estudos de Viabilidade , Hipertensão Renovascular , Obstrução da Artéria Renal , Stents , Humanos , Criança , Feminino , Masculino , Adolescente , Obstrução da Artéria Renal/fisiopatologia , Obstrução da Artéria Renal/terapia , Obstrução da Artéria Renal/diagnóstico por imagem , Obstrução da Artéria Renal/etiologia , Resultado do Tratamento , Pré-Escolar , Hipertensão Renovascular/fisiopatologia , Hipertensão Renovascular/terapia , Hipertensão Renovascular/etiologia , Hipertensão Renovascular/diagnóstico , Estudos Retrospectivos , Fatores de Tempo , Pressão Sanguínea , Angioplastia com Balão/instrumentação , Angioplastia com Balão/efeitos adversos , Recidiva , Fatores Etários , Angioplastia/efeitos adversos
3.
Acta Biochim Biophys Sin (Shanghai) ; 56(4): 621-633, 2024 04 25.
Artigo em Inglês | MEDLINE | ID: mdl-38516704

RESUMO

Non-alcoholic fatty liver disease (NAFLD) is the most common chronic liver disease, with a global prevalence of 25%. Patients with NAFLD are more likely to suffer from advanced liver disease, cardiovascular disease, or type II diabetes. However, unfortunately, there is still a shortage of FDA-approved therapeutic agents for NAFLD. Lian-Mei-Yin (LMY) is a traditional Chinese medicine formula used for decades to treat liver disorders. It has recently been applied to type II diabetes which is closely related to insulin resistance. Given that NAFLD is another disease involved in insulin resistance, we hypothesize that LMY might be a promising formula for NAFLD therapy. Herein, we verify that the LMY formula effectively reduces hepatic steatosis in diet-induced zebrafish and NAFLD model mice in a time- and dose-dependent manner. Mechanistically, LMY suppresses Yap1-mediated Foxm1 activation, which is crucial for the occurrence and development of NAFLD. Consequently, lipogenesis is ameliorated by LMY administration. In summary, the LMY formula alleviates diet-induced NAFLD in zebrafish and mice by inhibiting Yap1/Foxm1 signaling-mediated NAFLD pathology.


Assuntos
Diabetes Mellitus Tipo 2 , Resistência à Insulina , Hepatopatia Gordurosa não Alcoólica , Humanos , Camundongos , Animais , Hepatopatia Gordurosa não Alcoólica/tratamento farmacológico , Hepatopatia Gordurosa não Alcoólica/etiologia , Hepatopatia Gordurosa não Alcoólica/metabolismo , Lipogênese , Peixe-Zebra , Diabetes Mellitus Tipo 2/metabolismo , Fígado/metabolismo , Dieta Hiperlipídica , Fatores de Transcrição/metabolismo , Proteínas Adaptadoras de Transdução de Sinal/metabolismo , Lipídeos , Camundongos Endogâmicos C57BL , Proteína Forkhead Box M1/metabolismo
4.
J Nanobiotechnology ; 21(1): 55, 2023 Feb 17.
Artigo em Inglês | MEDLINE | ID: mdl-36803994

RESUMO

Acne is a chronic skin condition that has serious consequences for mental and social well-being because it frequently occurs on the face. Several acne treatment approaches have commonly been used but have been hampered by side effects or weak activity. Thus, the investigation of the safety and efficacy of anti-acne compounds is of considerable medical importance. Herein, an endogenous peptide (P5) derived from fibroblast growth factors 2 (FGF2) was conjugated to the polysaccharide hyaluronic acid (HA) to generate the bioconjugate nanoparticle HA-P5, which suppresses fibroblast growth factor receptors (FGFRs) to significantly rehabilitate acne lesions and reduce sebum accumulation in vivo and in vitro. Moreover, our results show that HA-P5 inhibits both fibroblast growth factor receptor 2 (FGFR2) and androgen receptor (AR) signalling in SZ95 cells, reverses the acne-prone transcriptome, and decreases sebum secretion. Furthermore, the cosuppression mechanism revealed that HA-P5 blocks FGFR2 activation, as well as the YTH N6-methyladenosine RNA binding protein F3 (YTHDF3) downstream molecules, including an N6-methyladenosine (m6A) reader that facilitates AR translation. More importantly, a significant difference between HA-P5 and the commercial FGFR inhibitor AZD4547 is that HA-P5 does not trigger the overexpression of aldo-keto reductase family 1 member C3 (AKR1C3), which blocks acne treatment by catalyzing the synthesis of testosterone. Overall, we demonstrate that a polysaccharide-conjugated and naturally derived oligopeptide HA-P5 can alleviate acne and act as an optimal FGFR2 inhibitor and reveal that YTHDF3 plays a crucial role in signalling between FGFR2 and AR.


Assuntos
Acne Vulgar , Receptor Tipo 2 de Fator de Crescimento de Fibroblastos , Humanos , Receptor Tipo 2 de Fator de Crescimento de Fibroblastos/genética , Receptor Tipo 2 de Fator de Crescimento de Fibroblastos/metabolismo , Receptor Tipo 2 de Fator de Crescimento de Fibroblastos/uso terapêutico , Fator 2 de Crescimento de Fibroblastos , Ácido Hialurônico/uso terapêutico , Acne Vulgar/tratamento farmacológico , Peptídeos/uso terapêutico
5.
J Nanobiotechnology ; 21(1): 57, 2023 Feb 21.
Artigo em Inglês | MEDLINE | ID: mdl-36803772

RESUMO

BACKGROUND: Globally, millions of patients suffer from regenerative deficiencies, such as refractory wound healing, which is characterized by excessive inflammation and abnormal angiogenesis. Growth factors and stem cells are currently employed to accelerate tissue repair and regeneration; however, they are complex and costly. Thus, the exploration of new regeneration accelerators is of considerable medical interest. This study developed a plain nanoparticle that accelerates tissue regeneration with the involvement of angiogenesis and inflammatory regulation. METHODS: Grey selenium and sublimed sulphur were thermalized in PEG-200 and isothermally recrystallised to composite nanoparticles (Nano-Se@S). The tissue regeneration accelerating activities of Nano-Se@S were evaluated in mice, zebrafish, chick embryos, and human cells. Transcriptomic analysis was performed to investigate the potential mechanisms involved during tissue regeneration. RESULTS: Through the cooperation of sulphur, which is inert to tissue regeneration, Nano-Se@S demonstrated improved tissue regeneration acceleration activity compared to Nano-Se. Transcriptome analysis revealed that Nano-Se@S improved biosynthesis and ROS scavenging but suppressed inflammation. The ROS scavenging and angiogenesis-promoting activities of Nano-Se@S were further confirmed in transgenic zebrafish and chick embryos. Interestingly, we found that Nano-Se@S recruits leukocytes to the wound surface at the early stage of regeneration, which contributes to sterilization during regeneration. CONCLUSION: Our study highlights Nano-Se@S as a tissue regeneration accelerator, and Nano-Se@S may provide new inspiration for therapeutics for regenerative-deficient diseases.


Assuntos
Nanocompostos , Nanopartículas , Selênio , Embrião de Galinha , Humanos , Camundongos , Animais , Selênio/farmacologia , Selênio/química , Peixe-Zebra/metabolismo , Espécies Reativas de Oxigênio , Cicatrização , Nanopartículas/química , Inflamação , Enxofre
6.
Acta Biochim Biophys Sin (Shanghai) ; 55(10): 1630-1639, 2023 10 25.
Artigo em Inglês | MEDLINE | ID: mdl-37381672

RESUMO

Umbilical cord blood (UCB) is an advantageous source for hematopoietic stem/progenitor cell (HSPC) transplantation, yet the current strategies for large-scale and cost-effective UCB-HSPC preparation are still unavailable. To overcome these obstacles, we systematically evaluate the feasibility of our newly identified CH02 peptide for ex vivo expansion of CD34 + UCB-HSPCs. We herein report that the CH02 peptide is specifically enriched in HSPC proliferation via activating the FLT3 signaling. Notably, the CH02-based cocktails are adequate for boosting 12-fold ex vivo expansion of UCB-HSPCs. Meanwhile, CH02-preconditioned UCB-HSPCs manifest preferable efficacy upon wound healing in diabetic mice via bidirectional orchestration of proinflammatory and anti-inflammatory factors. Together, our data indicate the advantages of the CH02-based strategy for ex vivo expansion of CD34 + UCB-HSPCs, which will provide new strategies for further development of large-scale HSPC preparation for clinical purposes.


Assuntos
Diabetes Mellitus Experimental , Transplante de Células-Tronco Hematopoéticas , Animais , Camundongos , Sangue Fetal , Células-Tronco Hematopoéticas , Antígenos CD34 , Moléculas de Adesão Celular , Peptídeos/farmacologia , Células Cultivadas
7.
Cancer Cell Int ; 21(1): 251, 2021 May 07.
Artigo em Inglês | MEDLINE | ID: mdl-33962639

RESUMO

BACKGROUND: Bladder cancer is the leading causes of cancer-associated mortality and seriously affects population health. Hypoxia plays a key role in tumor development and immune escape, which contributes to malignant behaviors. METHODS: In this study, we analyzed the RNA-seq and clinical information of bladder cancer patients from The Cancer Genome Atlas (TCGA) database. To investigate the hypoxia-related prognostic and immune microenvironment in bladder cancer, we constructed a hypoxia-related risk model for overall survival (OS). The RNA-seq and clinical data of bladder cancer patients from the Gene Expression Omnibus (GEO) database were used as validation sets. RESULTS: The hypoxia-related risk signature was significantly correlated with clinical outcomes and could independently predict OS outcomes. Furthermore, the hypoxia-related risk signature could effectively reflected the levels of immune cell type fractions and the expression of critical immune checkpoint genes were higher in the high-risk group compared to the low-risk group. We also validated the expression levels of the prognostic genes in bladder cancer and paracancerous tissue samples through qRT-PCR analysis. CONCLUSION: We established a 7 hypoxia-related gene (HRG) signature that can be used as an independent clinical predictor and provided a potential mechanism in bladder cancer immunotherapy.

8.
BMC Cardiovasc Disord ; 21(1): 326, 2021 07 03.
Artigo em Inglês | MEDLINE | ID: mdl-34217209

RESUMO

BACKGROUND: Drug-coated balloons (DCBs) have shown superiority in the endovascular treatment of short femoropopliteal artery disease. Few studies have focused on outcomes in long lesions. This study aimed to evaluate the safety and effectiveness of Orchid® DCBs in long lesions over 1 year of follow-up. METHODS: This study is a multicentre cohort and real-world study. The patients had lesions longer than or equal to 150 mm of the femoropopliteal artery and were revascularized with DCBs. The primary endpoints were primary patency, freedom from clinically driven target lesion revascularization (TLR) at 12 months and major adverse events (all-cause death and major target limb amputation). The secondary endpoints were the changes in Rutherford classification and the ankle brachial index (ABI). RESULTS: One hundred fifteen lesions in 109 patients (mean age 67 ± 11 years, male proportion 71.6%) were included in this study. The mean lesion length was 252.3 ± 55.4 mm, and 78.3% of the lesions were chronic total occlusion (CTO). Primary patency by Kaplan-Meier estimation was 98.1% at 6 months and 82.1% at 12 months. The rate of freedom from TLR by Kaplan-Meier estimation was 88.4% through 12 months. There were no procedure- or device-related deaths through 12 months. The rate of all-cause death was 2.8%. Cox regression analysis suggested that renal failure and critical limb ischaemia (CLI) were statistically significant predictors of the primary patency endpoint. CONCLUSION: In our real-world study, DCBs were safe and effective when used in long femoropopliteal lesions, and the primary patency rate at 12 months by Kaplan-Meier estimation was 82.1%.


Assuntos
Angioplastia com Balão/instrumentação , Materiais Revestidos Biocompatíveis , Artéria Femoral , Doença Arterial Periférica/terapia , Artéria Poplítea , Dispositivos de Acesso Vascular , Idoso , Angioplastia com Balão/efeitos adversos , Angioplastia com Balão/mortalidade , Pequim , Feminino , Artéria Femoral/diagnóstico por imagem , Artéria Femoral/fisiopatologia , Humanos , Masculino , Pessoa de Meia-Idade , Doença Arterial Periférica/diagnóstico por imagem , Doença Arterial Periférica/mortalidade , Doença Arterial Periférica/fisiopatologia , Artéria Poplítea/diagnóstico por imagem , Artéria Poplítea/fisiopatologia , Fatores de Tempo , Resultado do Tratamento , Grau de Desobstrução Vascular
9.
Eur J Vasc Endovasc Surg ; 59(5): 834-842, 2020 May.
Artigo em Inglês | MEDLINE | ID: mdl-31874808

RESUMO

OBJECTIVE: The aim was to identify the change in gene expression between mesenchymal stem cells (MSCs) and induced endothelial cells (ECs) and to investigate the potential mechanism of endothelial differentiation based on ribonucleic acid sequencing (RNA-Seq) analysis. METHODS: MSCs were isolated from bone marrow and exposed to inducing medium. The dynamic transcription profiles of MSCs were identified and ECs were induced through RNA-seq. Differentially expressed genes (DEGs) were identified. Enrichment of functions and signalling pathways analysis were performed based on Gene Ontology (GO) and the Kyoto Encyclopedia of Genes and Genomes (KEGG) database. Quantitative real time polymerase chain reaction (qRT-PCR) was used to validate the genes selected from RNA-Seq. RESULTS: In total, 2769 DEGs were identified, of which 1117 genes were upregulated and 1652 genes were downregulated. GO and KEGG pathway analyses identified significantly enriched pathways in DEGs, including extracellular matrix organisation, blood vessel morphogenesis, angiogenesis, extracellular matrix binding, growth factor binding and glycosaminoglycan binding extracellular matrix-receptor interaction pathway, cytokine-receptor interaction pathway and transforming growth factor (TGF)-ß signalling pathway. All genes found to be associated with the TGF-ß pathway were significantly downregulated. Eleven novel genes were also identified that most likely are involved in endothelial differentiation and were upregulated with more than 10 fold change, which were further validated by qRT-PCR. CONCLUSION: The GO and KEGG analysis revealed that extracellular matrix, cytokines and the TGF-ß pathway play an important role in the process of endothelial differentiation. Furthermore, 11 genes were found that may be involved in the differentiation of MSCs into ECs and contribute to current understanding of the differentiation mechanism.


Assuntos
Diferenciação Celular/genética , Células Endoteliais/citologia , Células-Tronco Mesenquimais/citologia , RNA-Seq , Humanos
10.
J Magn Reson Imaging ; 50(3): 719-724, 2019 09.
Artigo em Inglês | MEDLINE | ID: mdl-30635951

RESUMO

BACKGROUND: Early diagnosis of acute kidney injury (AKI) has clinical importance. Current methods are neither adequately sensitive nor specific. Blood oxygen level-dependent (BOLD) imaging and diffusion-weighted imaging (DWI) may help to assess AKI in the early phase. PURPOSE: To investigate the feasibility of BOLD imaging and DWI in the assessment of AKI and compare the sensitivities of both techniques in early detection of renal damage. STUDY TYPE: Prospective animal study. ANIMAL MODEL: Thirty New Zealand white rabbits. FIELD STRENGTH/SEQUENCE: 3 T clinical MRI/BOLD and DWI. ASSESSMENT: Thirty rabbits were divided into three groups (severe AKI group, mild AKI group, and control group). Transarterial renal embolization with different doses of microspheres was performed to create severe and mild AKI disease models. All the MRI scans of kidneys were conducted within 2 hours after the embolization procedure. Histological examinations with hematoxylin and eosin staining were performed to validate renal damage. STATISTICAL TESTS: Analysis of variance (ANOVA) for comparisons between groups, and paired t-test for tests within the same group. P < 0.05 was considered statistically significant. RESULTS: Both R2* and apparent diffusion coefficient (ADC) showed significant differences between the severe AKI group (56.34 ± 3.45 s-1 for R2*, 1.14 ± 0.23 mm2 /s for ADC) and the control group (28.24 ± 2.26 s-1 for R2*, 1.94 ± 0.33 mm2 /s for ADC, both P < 0.01). However, the ADC values did not show significant differences (P = 0.41) between mild AKI group (1.88 ± 0.31 mm2 /s for ADC) and the control group (1.94 ± 0.33 mm2 /s for ADC), while R2* was still useful in differentiating the two groups (52.32 ± 4.1 s-1 vs. 28.24 ± 2.26 s-1 for R2*, P < 0.01). The histopathologic results were found to be correlated with MRI findings. DATA CONCLUSION: BOLD contrast and DW images are both effective in detecting AKI noninvasively, but BOLD imaging is more sensitive in early detection of mild ischemia than DWI. LEVEL OF EVIDENCE: 1 Technical Efficacy: Stage 2 J. Magn. Reson. Imaging 2019;50:719-724.


Assuntos
Injúria Renal Aguda/diagnóstico por imagem , Imageamento por Ressonância Magnética/métodos , Injúria Renal Aguda/fisiopatologia , Animais , Imagem de Difusão por Ressonância Magnética/métodos , Modelos Animais de Doenças , Diagnóstico Precoce , Estudos de Viabilidade , Rim/diagnóstico por imagem , Rim/fisiopatologia , Masculino , Estudos Prospectivos , Coelhos , Reprodutibilidade dos Testes , Sensibilidade e Especificidade
12.
Ann Vasc Surg ; 59: 5-11, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31009728

RESUMO

BACKGROUND: To evaluate the unclear cerebral hemodynamic variations in patients with and without near occlusion (NO) in hours after carotid artery stenting (CAS) by transcranial Doppler (TCD). METHODS: Data of 56 patients (11 patients with carotid artery NO and 45 patients with severe stenosis without NO) who underwent unilateral CAS were analyzed. All patients underwent TCD or transcranial color-code Doppler monitoring before CAS and again at one and three hours after the procedure. We compared bilateral middle cerebral artery peak systolic velocity (MCA-PSV), pulsatility index (PI), and blood pressure (BP) data between the two groups. RESULTS: Ipsilateral MCA-PSV increased relative to baseline in the stenosis group at one hour (97 ± 30 vs. 84 ± 23 cm/s, 16%, P < 0.001) and three hours (96 ± 28 vs. 84 ± 23 cm/s, 15%, P < 0.001) after CAS. Corresponding increases were distinctly higher in the NO group than in the stenosis group at one hour (116 ± 37 vs. 80 ± 29 cm/s, 51%, P < 0.001) and three hours (113 ± 39 vs. 80 ± 29 cm/s, 46%, P = 0.001) after CAS, whereas BP decreased similarly between the two groups. The ipsilateral PI increased postsurgically in both groups, whereas contralateral MCA-PSV was unaltered. CONCLUSIONS: CAS can induce a significant increase in PSV and PI in ipsilateral MCA within three hours in patients with NO or severe stenosis but absent NO. The increment of ipsilateral MCA-PSV was greater in patients with NO. TCD can facilitate BP control in the early stage after CAS in patients with NO.


Assuntos
Angioplastia com Balão/instrumentação , Estenose das Carótidas/terapia , Circulação Cerebrovascular , Hemodinâmica , Artéria Cerebral Média/fisiopatologia , Stents , Idoso , Angioplastia com Balão/efeitos adversos , Velocidade do Fluxo Sanguíneo , Estenose das Carótidas/diagnóstico por imagem , Estenose das Carótidas/fisiopatologia , Feminino , Humanos , Masculino , Artéria Cerebral Média/diagnóstico por imagem , Fluxo Pulsátil , Índice de Gravidade de Doença , Fatores de Tempo , Resultado do Tratamento , Ultrassonografia Doppler em Cores , Ultrassonografia Doppler Transcraniana/métodos
13.
Cell Physiol Biochem ; 49(3): 1033-1048, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30196288

RESUMO

BACKGROUND/AIMS: How to aid recovery from severe skin injuries, such as burns, chronic or radiation ulcers, and trauma, is a critical clinical problem. Current treatment methods remain limited, and the discovery of ideal wound-healing therapeutics has been a focus of research. Functional recombinant proteins such as basic fibroblast growth factor (bFGF) and epidermal growth factor (EGF) have been developed for skin repair, however, some disadvantages in their use remain. This study reports the discovery of a novel small peptide targeting fibroblast growth factor receptor 2 IIIc (FGFR2IIIc) as a potential candidate for skin wound healing. METHODS: A phage-displayed peptide library was used for biopanning FGFR2IIIc-targeting small peptides. The selected small peptides binding to FGFR2IIIc were qualitatively evaluated by an enzyme-linked immunosorbent assay. Their biological function was detected by a cell proliferation assay. Among them, an optimized small peptide named H1 was selected for further study. The affinity of the H1 peptide and FGFR2IIIc was determined by an isothermal titration calorimetry device. The ability of theH1 peptide to promote skin wound repair was investigated using an endothelial cell tube formation assay and wound healing scratch assay in vitro. Subsequently, the H1 peptide was assessed using a rat skin full-thickness wound model and chorioallantoic membrane (CAM) assays in vivo. To explore its molecular mechanisms, RNA-Seq, quantitative real-time PCR, and western blot assays were performed. Computer molecular simulations were also conducted to analyze the binding model. RESULTS: We identified a novel FGFR2IIIc-targeting small peptide, called H1, with 7 amino acid residues using phage display. H1 had high binding affinity with FGFR2IIIc. The H1 peptide promoted the proliferation and motility of fibroblasts and vascular endothelial cells in vitro. In addition, the H1 peptide enhanced angiogenesis in the chick chorioallantoic membrane and accelerated wound healing in a rat full-thickness wound model in vivo. The H1 peptide activated both the PI3K-AKT and MAPK-ERK1/2 pathways and simultaneously increased the secretion of vascular endothelial growth factor. Computer analysis demonstrated that the model of H1 peptide binding to FGFR2IIIc was similar to that of FGF2 and FGFR2IIIc. CONCLUSION: The H1 peptide has a high affinity for FGFR2IIIc and shows potential as a wound healing agent. As a substitute for bFGF, it could be developed into a novel therapeutic candidate for skin wound repair in the future.


Assuntos
Peptídeos/farmacologia , Receptor Tipo 2 de Fator de Crescimento de Fibroblastos/metabolismo , Pele/patologia , Cicatrização/efeitos dos fármacos , Animais , Linhagem Celular , Movimento Celular/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Células Endoteliais da Veia Umbilical Humana , Humanos , Ligantes , Masculino , Camundongos , Neovascularização Fisiológica/efeitos dos fármacos , Biblioteca de Peptídeos , Peptídeos/química , Peptídeos/metabolismo , Ligação Proteica , Ratos , Ratos Sprague-Dawley , Receptor Tipo 2 de Fator de Crescimento de Fibroblastos/antagonistas & inibidores , Transdução de Sinais/efeitos dos fármacos , Pele/metabolismo , Fator A de Crescimento do Endotélio Vascular/metabolismo
15.
Eur J Vasc Endovasc Surg ; 55(2): 257-265, 2018 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-29208350

RESUMO

OBJECTIVE: Endothelial cells (ECs) play an important role in neovascularisation, but are too limited in number for adequate therapeutic applications. Mesenchymal stem cells (MSCs) have the potential to differentiate into endothelial lineage cells, which makes them attractive candidates for therapeutic angiogenesis. The aim of this study was to investigate efficient differentiation of MSCs into ECs by inducing medium in vitro. METHODS: MSCs were isolated from bone marrow by density gradient centrifugation. The characterisation of the MSCs was determined by their cluster of differentiation (CD) marker profile. Inducing medium containing vascular endothelial growth factor (VEGF), basic fibroblast growth factor (bFGF), insulin like growth factor (IGF), epidermal growth factor (EGF), ascorbic acid, and heparin was applied to differentiate the MSCs into ECs. Endothelial differentiation was quantitatively evaluated using flow cytometry. Real time quantitative PCR (qRT-PCR) was used to analyse mRNA expression of endothelial markers. Tube formation assay was further performed to examine the functional status of the differentiated MSCs. RESULTS: Flow cytometry analysis demonstrated that CD31+ and CD34+ cells increased steadily from 12% at 3 days, to 40% at 7 days, and to 60% at 14 days. Immunofluorescence staining further confirmed the expression of CD31 and CD34. qRT-PCR showed that expression of von Willebrand factor (vWF), vascular endothelial cadherin (VE-cadherin) and vascular endothelial growth factor receptor-2 (VEGFR-2) were significantly higher in the induced MSCs group compared with the uninduced MSCs group. The functional behavior of the differentiated cells was tested by tube formation assay in vitro on matrigel. Induced MSCs were capable of developing capillary networks, and progressive formation of vessel like structures was associated with increased EC population. CONCLUSIONS: These results provide a method to efficiently promote differentiation of MSCs into ECs in vitro for potential application in the treatment of peripheral arterial disease.


Assuntos
Diferenciação Celular/fisiologia , Citocinas/metabolismo , Células Endoteliais/fisiologia , Células-Tronco Mesenquimais/fisiologia , Doença Arterial Periférica/terapia , Biomarcadores/metabolismo , Separação Celular/métodos , Células Cultivadas/fisiologia , Células Cultivadas/transplante , Centrifugação com Gradiente de Concentração/métodos , Meios de Cultura/metabolismo , Células Endoteliais/transplante , Citometria de Fluxo , Humanos , Neovascularização Fisiológica/fisiologia , RNA Mensageiro/metabolismo , Reação em Cadeia da Polimerase em Tempo Real , Fator A de Crescimento do Endotélio Vascular
17.
Clin Invest Med ; 40(6): E228-E234, 2017 Dec 17.
Artigo em Inglês | MEDLINE | ID: mdl-29256388

RESUMO

PURPOSE: The aim of this study was to observe the exact plaque distribution at the common femoral artery bifurcation by multi-slice computed tomography angiography and to examine the relationship between plaque distribution and carina location. METHODS: Symptomatic outpatients who underwent multi-slice computed tomography angiography between May 2013 and February 2015 were enrolled in this study. The presence and distribution of atherosclerotic plaques were assessed in cross section views of vessel lumen. Each vessel lumen cross section was divided into four equal quadrants for the common femoral, superficial femoral and profunda femoral arteries. The quadrant of the superficial femoral artery in which the carina was located was also recorded. RESULTS: In total, 184 common femoral artery bifurcations in 92 patients were analyzed. Normal arteries were more common in profunda femoral arteries than in common femoral arteries and superficial femoral arteries (both P< 0.001). Plaques were found more medial and posterior quadrants in common femoral arteries. In superficial femoral arteries, plaques were found most frequently in anterior quadrants (78.3%, n=144) and least frequently in posterior quadrants (49.5%, n=91). The carina was located in the posterior quadrant in 160 bifurcations (87.0%) of superficial femoral arteries. Quadrants opposite the carina contained plaque most proportionally (77.2%) and quadrants of carina were affected least proportionally (52.7%) in superficial femoral arteries (P.


Assuntos
Doença da Artéria Coronariana/diagnóstico por imagem , Artéria Femoral/diagnóstico por imagem , Tomografia Computadorizada por Raios X/métodos , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Placa Aterosclerótica/diagnóstico por imagem
19.
J Environ Sci (China) ; 32: 168-79, 2015 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-26040743

RESUMO

The effects of different Planetary Boundary Layer (PBL) structures on pollutant dispersion processes within two idealized street canyon configurations and a realistic urban area were numerically examined by a Computational Fluid Dynamics (CFD) model. The boundary conditions of different PBL structures/conditions were provided by simulations of the Weather Researching and Forecasting model. The simulated results of the idealized 2D and 3D street canyon experiments showed that the increment of PBL instability favored the downward transport of momentum from the upper flow above the roof to the pedestrian level within the street canyon. As a result, the flow and turbulent fields within the street canyon under the more unstable PBL condition are stronger. Therefore, more pollutants within the street canyon would be removed by the stronger advection and turbulent diffusion processes under the unstable PBL condition. On the contrary, more pollutants would be concentrated in the street canyon under the stable PBL condition. In addition, the simulations of the realistic building cluster experiments showed that the density of buildings was a crucial factor determining the dynamic effects of the PBL structure on the flow patterns. The momentum field within a denser building configuration was mostly transported from the upper flow, and was more sensitive to the PBL structures than that of the sparser building configuration. Finally, it was recommended to use the Mellor-Yamada-Nakanishi-Niino (MYNN) PBL scheme, which can explicitly output the needed turbulent variables, to provide the boundary conditions to the CFD simulation.


Assuntos
Movimentos do Ar , Poluentes Atmosféricos/análise , Atmosfera/análise , Monitoramento Ambiental/métodos , Urbanização , Arquitetura , China , Simulação por Computador , Modelos Teóricos , Tempo (Meteorologia)
20.
Huan Jing Ke Xue ; 45(1): 71-80, 2024 Jan 08.
Artigo em Zh | MEDLINE | ID: mdl-38216459

RESUMO

Based on air quality monitoring, surface meteorological data, wind profile radar observation, and the HYSPLIT model, the characteristics and causes of O3 pollution in eastern China during the period of the typhoons BAVI, MAYSAK, and HAISHEN from August 26 to September 8, 2020 were analyzed. The results showed that during the succession of the three landfall typhoons, the O3 pollution sites in Beijing Tianjin Hebei and its surrounding areas (BTHS) and the Yangtze River Delta (YRD) exceeded 50%. During the HAISHEN period, O3 pollution days in the two regions reached 2.22 d and 2.97 d, respectively, with significant persistence characteristics. The location of the typhoon had an obvious influence on O3 concentration. When the typhoons were located within the 24h warning line, the O3 concentrations in BTHS and YRD were relatively low. When the typhoons were located between the 24 h and 48 h warning lines, the O3 concentration in BTHS was the highest. When the typhoons moved north of 34°N, the YRD was most prone to regional O3 pollution. O3 pollution in Shanghai mainly occurred under the control of the northward air flow to the west side of the typhoons, and the regional transport from the upstream area had a significant impact on the increase in O3 and its precursor concentrations. The downdraft below 1 000 m maintained O3 at a high concentration at night. In Jinan, O3 pollution mainly occurred under the control of the subtropical high and typhoon periphery. The downdraft prevailed in the middle and lower levels during the O3 pollution. From August 28 to 30, under the control of the subtropical high, the pollutants were mainly accumulated locally, and some of them were transmitted within the province, showing a "double high" phenomenon of O3 and PM2.5. From September 5 to 8, under the influence of HAISHEN peripheral circulation, the regional transport was obvious, and the O3 concentration increased earlier than that of PM2.5.

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