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1.
J Exp Med ; 219(2)2022 02 07.
Artigo em Inglês | MEDLINE | ID: mdl-35015026

RESUMO

Inflammatory monocytes are key mediators of acute and chronic inflammation; yet, their functional diversity remains obscure. Single-cell transcriptome analyses of human inflammatory monocytes from COVID-19 and rheumatoid arthritis patients revealed a subset of cells positive for CD127, an IL-7 receptor subunit, and such positivity rendered otherwise inert monocytes responsive to IL-7. Active IL-7 signaling engaged epigenetically coupled, STAT5-coordinated transcriptional programs to restrain inflammatory gene expression, resulting in inverse correlation between CD127 expression and inflammatory phenotypes in a seemingly homogeneous monocyte population. In COVID-19 and rheumatoid arthritis, CD127 marked a subset of monocytes/macrophages that retained hypoinflammatory phenotypes within the highly inflammatory tissue environments. Furthermore, generation of an integrated expression atlas revealed unified features of human inflammatory monocytes across different diseases and different tissues, exemplified by those of the CD127high subset. Overall, we phenotypically and molecularly characterized CD127-imprinted functional heterogeneity of human inflammatory monocytes with direct relevance for inflammatory diseases.


Assuntos
Artrite Reumatoide/imunologia , COVID-19/imunologia , Epigênese Genética/imunologia , Subunidade alfa de Receptor de Interleucina-7/imunologia , Monócitos/imunologia , SARS-CoV-2/imunologia , Feminino , Humanos , Inflamação/imunologia , Interleucina-7/imunologia , Masculino
2.
J Mech Behav Biomed Mater ; 125: 104906, 2022 01.
Artigo em Inglês | MEDLINE | ID: mdl-34736024

RESUMO

BACKGROUND: Quantification of subject-specific residual stress field remains a challenge that prohibits accurate stress analysis and refined understanding of the biomechanical behavior of the aortic wall. METHOD: This study presents a framework combining experiments, constitutive modeling, and computer simulation to quantify the subject-specific three-dimensional residual stress field of the aortic wall. The material properties and residual deformations were acquired from the same porcine aortic sample, so that the subject-specific residual stress field was quantified analytically. Consequently, a novel stress-driven tissue growth model was developed and incorporated in a finite element aortic model to recover the subject-specific residual stress with the help of analytical solution. We then evaluated the framework's efficacy by simulating the residual stress distribution in the aortic dissection (AD). RESULT: Subject-specific residual stress field of the aortic sample was quantified analytically. No appreciable discrepancy was observed between the numerically simulated and analytically derived residual stress distributions, indicating the effectiveness of the tissue growth model. Errors arising from the numerically simulated circumferential opening angle and axial bending angle were within 5% relative to experimental results, highlighting that the framework was accurate in terms of subject-specific residual stress estimation. Finally, numerical simulations recovered the buckling behavior of the intimal flap of the dissected aorta and revealed the expansion of the false lumen and compression of the true lumen as the tear propagates circumferentially. CONCLUSION: The proposed framework is effective in quantifying the three-dimensional subject-specific residual stress field and it is potentially applicable in more sophisticated scenarios involving residual stress.


Assuntos
Aneurisma Dissecante , Aorta , Animais , Simulação por Computador , Suínos , Túnica Íntima
4.
J Ethnopharmacol ; 281: 114562, 2021 Dec 05.
Artigo em Inglês | MEDLINE | ID: mdl-34438027

RESUMO

ETHNOPHARMACOLOGICAL RELEVANCE: The traditional Chinese medicine formula Danggui-Shaoyao-San (DSS) has been reported to show therapeutic effect on dementia. AIM OF THE STUDY: The present study aims to investigate whether DSS treatment could alleviate diabetes-induced cognitive dysfunction, and explores its neuroprotective mechanism on db/db mice. MATERIALS AND METHODS: The female db/db mice were randomly divided into model group, DSS low-dose group and DSS high-dose group. Homologous female db/m mice were used as the control group. DSS was intragastric administrated for 15 weeks. Glucose tolerance, insulin tolerance, blood glucose and blood lipid levels were measured. Morris water maze was used to measure spatial learning and memory ability in mice. Nissl staining and Tunel staining were used to measure the changes of brain neurons, and ELISA kits were used to measure levels of inflammatory mediators (PGE2, TXB2 and LTB4). The kits detected oxidative stress (MDA, SOD, CAT, GSH-PX), nitrosative stress (NO, iNOS, TNOS) and glucose metabolism (LDH, PK, HK) levels. Western blot and immunofluorescence detected neurotrophic factors (PSD95, BDNF, NGF and SYN), apoptosis (Bcl-2, Bax, Bcl-xl, Caspase-3) and changes of ERα, O-GlcNAc, OGT, OGA levels. RESULTS: Morris water maze results showed that DSS could improve the learning and memory abilities of female db/db mice. Nissl staining showed that DSS could relieve hippocampal neurons damage of db/db mice. In addition, the serological tests showed that DSS could improve the impaired glucose tolerance and insulin resistance, while reduce hyperlipemia in db/db mice. Besides, DSS treatment increased the activities of SOD, GSH-PX, and CAT, and reduced MDA, NO, iNOs, tNOS, PGE2, TXB2 and LTB4 levels. Western blot and immunofluorescence results of PSD95, BDNF, NGF, and SYN showed that DSS could improve the expressions of neurotrophic factors. Meanwhile, Tunel staning and Western blot (Bcl-2, Bax, Bcl-xl, Caspase-3) results indicated that DSS could reduce neuronal apoptosis. Finally, Western blot (ERα, O-GlcNAc, OGA, and OGT) and immunofluorescence (ERα and O-GlcNAc) results indicated that DSS could increase the levels of ERα and OGA, decrease the levels of O-GlcNAc and OGT. CONCLUSION: DSS alleviate DE might be related to improve the abnormal O-GlcNAc-modification of ERα.

5.
Cell ; 184(7): 1895-1913.e19, 2021 04 01.
Artigo em Inglês | MEDLINE | ID: mdl-33657410

RESUMO

A dysfunctional immune response in coronavirus disease 2019 (COVID-19) patients is a recurrent theme impacting symptoms and mortality, yet a detailed understanding of pertinent immune cells is not complete. We applied single-cell RNA sequencing to 284 samples from 196 COVID-19 patients and controls and created a comprehensive immune landscape with 1.46 million cells. The large dataset enabled us to identify that different peripheral immune subtype changes are associated with distinct clinical features, including age, sex, severity, and disease stages of COVID-19. Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) RNA was found in diverse epithelial and immune cell types, accompanied by dramatic transcriptomic changes within virus-positive cells. Systemic upregulation of S100A8/A9, mainly by megakaryocytes and monocytes in the peripheral blood, may contribute to the cytokine storms frequently observed in severe patients. Our data provide a rich resource for understanding the pathogenesis of and developing effective therapeutic strategies for COVID-19.


Assuntos
COVID-19/imunologia , Megacariócitos/imunologia , Monócitos/imunologia , RNA Viral , SARS-CoV-2/genética , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Criança , China , Estudos de Coortes , Citocinas/metabolismo , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , RNA Viral/sangue , RNA Viral/isolamento & purificação , Análise de Célula Única , Transcriptoma/imunologia , Adulto Jovem
7.
bioRxiv ; 2020 Nov 10.
Artigo em Inglês | MEDLINE | ID: mdl-33200127

RESUMO

Studies on human monocytes historically focused on characterization of bulk responses, whereas functional heterogeneity is largely unknown. Here, we identified an inducible population of CD127-expressing human monocytes under inflammatory conditions and named the subset M127. M127 is nearly absent in healthy individuals yet abundantly present in patients with infectious and inflammatory conditions such as COVID-19 and rheumatoid arthritis. Multiple genomic and functional approaches revealed unique gene signatures of M127 and unified anti-inflammatory properties imposed by the CD127-STAT5 axis. M127 expansion correlated with mild COVID-19 disease outcomes. Thereby, we phenotypically and molecularly characterized a human monocyte subset marked by CD127 that retained anti-inflammatory properties within the pro-inflammatory environments, uncovering remarkable functional diversity among monocytes and signifying M127 as a potential therapeutic target for human inflammatory disorders.

8.
Science ; 369(6506): 984-988, 2020 08 21.
Artigo em Inglês | MEDLINE | ID: mdl-32820125

RESUMO

Germinal center (GC) responses potentiate the generation of follicular regulatory T (TFR) cells. However, the molecular cues driving TFR cell formation remain unknown. Here, we show that sclerostin domain-containing protein 1 (SOSTDC1), secreted by a subpopulation of follicular helper T (TFH) cells and T-B cell border-enriched fibroblastic reticular cells, is developmentally required for TFR cell generation. Fate tracking and transcriptome assessment in reporter mice establishes SOSTDC1-expressing TFH cells as a distinct T cell population that develops after SOSTDC1- TFH cells and loses the ability to help B cells for antibody production. Notably, Sostdc1 ablation in TFH cells results in substantially reduced TFR cell numbers and consequently elevated GC responses. Mechanistically, SOSTDC1 blocks the WNT-ß-catenin axis and facilitates TFR cell differentiation.


Assuntos
Proteínas Adaptadoras de Transdução de Sinal/metabolismo , Linfócitos T Auxiliares-Indutores/imunologia , Linfócitos T Reguladores/imunologia , Proteínas Adaptadoras de Transdução de Sinal/genética , Animais , Linfócitos B/imunologia , Diferenciação Celular/genética , Diferenciação Celular/imunologia , Centro Germinativo/imunologia , Ativação Linfocitária/genética , Ativação Linfocitária/imunologia , Contagem de Linfócitos , Camundongos , Camundongos Mutantes , Proteínas Wnt/metabolismo , beta Catenina/metabolismo
9.
Aging (Albany NY) ; 12(7): 6401-6414, 2020 04 08.
Artigo em Inglês | MEDLINE | ID: mdl-32268299

RESUMO

The natural polyamine spermidine and spermine have been reported to ameliorate aging and aging-induced dementia. However, the mechanism is still confused. An aging model, the senescence accelerated mouse-8 (SAMP8), was used in this study. Novel object recognition and the open field test results showed that oral administration of spermidine, spermine and rapamycin increased discrimination index, modified number, inner squares distance and times. Spermidine and spermine increased the activity of SOD, and decreased the level of MDA in the aging brain. Spermidine and spermine phosphorylate AMPK and regulate autophagy proteins (LC3, Beclin 1 and p62). Spermidine and spermine balanced mitochondrial and maintain energy for neuron, with the regulation of MFN1, MFN2, DRP1, COX IV and ATP. In addition, western blot results (Bcl-2, Bax and Caspase-3, NLRP3, IL-18, IL-1ß) showed that spermidine and spermine prevented apoptosis and inflammation, and elevate the expression of neurotrophic factors, including NGF, PSD95and PSD93 and BDNF in neurons of SAMP8 mice. These results indicated that the effect of spermidine and spermine on anti-aging is related with improving autophagy and mitochondrial function.


Assuntos
Autofagia , Encéfalo/metabolismo , Senescência Celular , Mitocôndrias , Espermidina , Espermina , Animais , Autofagia/efeitos dos fármacos , Autofagia/fisiologia , Senescência Celular/efeitos dos fármacos , Senescência Celular/fisiologia , Demência/metabolismo , Modelos Animais de Doenças , Camundongos , Mitocôndrias/efeitos dos fármacos , Mitocôndrias/fisiologia , Estresse Oxidativo , Espermidina/metabolismo , Espermidina/farmacologia , Espermina/metabolismo , Espermina/farmacologia
11.
Food Funct ; 11(3): 2489-2497, 2020 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-32134423

RESUMO

Dementia is a kind of age-related neurodegenerative disease. Carnosine, an endogenous dipeptide consisting of ß-alanine and l-histidine, has been shown to have neuroprotective effects. However, the exact mechanism is still obscure. In this study, senescence-accelerated mouse prone 8 (SAMP8) mice, an age-related animal model, were used. Carnosine (100 and 200 mg kg-1 day-1) was orally administered to the mice once daily for six weeks. Behavioral tests, western blotting, and detection kits were used to evaluate the potential effects of carnosine on SAMP8 mice. Open-field and new object recognition experiments have shown that carnosine improved cognitive deficits in SAMP8 mice. Carnosine decreased the levels of malondialdehyde (MDA) and reactive oxygen species (ROS), increased the activity of superoxide dismutase (SOD) and the level of adenosine triphosphate (ATP) in SAMP8 mice. Concomitantly, western blotting results proved that carnosine increased the protein expressions of Mitofusin-1, Mitofusin-2, and Bcl-2 and reduced the protein expressions of P-Drp1, Bax, cleaved Caspase-3 and NLRP3 inflammasomes in the hippocampus of SAMP8 mice. The present data provided evidence that carnosine might improve cognitive impairment in SAMP8 mice through modulating mitochondrial dysfunction.


Assuntos
Envelhecimento/efeitos dos fármacos , Carnosina/farmacologia , Demência/tratamento farmacológico , Memória/efeitos dos fármacos , Doenças Mitocondriais/tratamento farmacológico , Animais , Apoptose/efeitos dos fármacos , Hipocampo/efeitos dos fármacos , Hipocampo/fisiopatologia , Inflamação/tratamento farmacológico , Inflamação/fisiopatologia , Masculino , Camundongos , Neurônios/efeitos dos fármacos , Estresse Oxidativo/efeitos dos fármacos
12.
Aging (Albany NY) ; 12(4): 3175-3189, 2020 02 16.
Artigo em Inglês | MEDLINE | ID: mdl-32065782

RESUMO

Alzheimer's disease (AD) is an age-related neurodegenerative disease. The main active component in Angelica sinensis, ligustilide, has been reported to have the protective effect on AD. Whether ligustilide could protect against age-induced dementia is still unknown. In this study, we used an aging model, SAMP8 mice to investigate the neuroprotective effect of ligustilide. The behavioral tests (Morris water maze, object recognition task, open field test and elevated plus maze) results showed that ligustilide could improve the memory deficit in SAMP8 mice. For mechanism study, we found that the protein level of P-Drp1 (fission) was decreased and the levels of Mfn1 and Mfn2 (fusion) were increased after ligustilide treatment in animals and cells. Ligustilide increased P-AMPK and ATP levels. Malondialdehyde and superoxide dismutase activity results indicated that ligustilide exerts antioxidant effects by reducing the level of oxidative stress markers. In addition, ligustilide improved neural function and alieved apoptosis and neuroinflammation. These findings have shown that ligustilide treatment improves mitochondrial function in SAMP8 mice, and improves memory loss.


Assuntos
4-Butirolactona/análogos & derivados , Envelhecimento/metabolismo , Inflamação/tratamento farmacológico , Aprendizagem em Labirinto/efeitos dos fármacos , Transtornos da Memória/tratamento farmacológico , Mitocôndrias/efeitos dos fármacos , Fármacos Neuroprotetores/farmacologia , 4-Butirolactona/farmacologia , 4-Butirolactona/uso terapêutico , Animais , Apoptose/efeitos dos fármacos , Encéfalo/efeitos dos fármacos , Encéfalo/metabolismo , Inflamação/metabolismo , Masculino , Transtornos da Memória/metabolismo , Camundongos , Mitocôndrias/metabolismo , Fármacos Neuroprotetores/uso terapêutico , Estresse Oxidativo/efeitos dos fármacos , Memória Espacial/efeitos dos fármacos
13.
Int J Biol Macromol ; 151: 47-55, 2020 May 15.
Artigo em Inglês | MEDLINE | ID: mdl-32035959

RESUMO

ß-Amyloid (Aß) plays an important role in the pathogenesis of Alzheimer's disease (AD). However, there is still no effective Aß-targeting drugs for AD treatment. In this study, we explored the effect and mechanism of Sodium Tanshinone IIA Sulfonate (STS) on AD. Aß-treated HT22 cells, an immortalized mouse hippocampal neuronal cell line, were employed. Different dosages of STS (0.1, 1 and 10 µM) were selected. STS improved cell viability and protected against Aß-induced apoptosis in a dose-dependent manner. Furthermore, the levels of reactive oxygen species (ROS) and malondialdehyde (MDA) were decreased, while the activities of superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px) were significantly increased after STS treatment. STS decreased the levels of phosphorylate PKR-like (p-PERK), phosphorylate eukaryotic initiation factor 2 (p-eIF2α), phosphorylate inositol-requiring enzyme (p-IRE1α), X-box binding protein 1 (XBP1) and binding immunoglobulin heavy chain protein (Bip), while increased protein disulfide isomerase (PDI) levels in Aß-treated HT22 cells. In addition, the levels of insulin degrading enzymes (IDE) and Nepterrilysin (NEP) (or call it CD10) were significantly increased after STS treatment. Taken together, these results indicated that STS might be effective in treating AD via increasing the levels of Aß-degrading enzymes.


Assuntos
Peptídeos beta-Amiloides/efeitos adversos , Peptídeos beta-Amiloides/metabolismo , Inibidores Enzimáticos/farmacologia , Fragmentos de Peptídeos/efeitos adversos , Fragmentos de Peptídeos/metabolismo , Fenantrenos/farmacologia , Substâncias Protetoras/farmacologia , Linhagem Celular , Sobrevivência Celular/efeitos dos fármacos , Inibidores Enzimáticos/química , Peroxidação de Lipídeos/efeitos dos fármacos , Estrutura Molecular , Fenantrenos/química , Substâncias Protetoras/química , Proteólise/efeitos dos fármacos , Espécies Reativas de Oxigênio/metabolismo
14.
Cardiovasc Eng Technol ; 11(1): 24-35, 2020 02.
Artigo em Inglês | MEDLINE | ID: mdl-31820352

RESUMO

PURPOSE: Multiple overlapping uncovered stents (MOUS) are employed to promote false lumen thrombosis in the aortic dissections (AD), when the tears are in close vicinity to the branch vessels. However, the overall rate of false lumen thrombosis remains unsatisfactory. This study was performed to investigate the hemodynamic influence of MOUS on aortic dissection to shed some light on the mechanism of post-stenting false lumen thrombosis. METHODS: An anatomically accurate computational fluid dynamics model was developed to investigate the hemodynamics of AD. A parametric study was carried out to demonstrate the hemodynamic influence of MOUS in various post-surgery scenarios featuring the representative surgical strategies involving MOUS. RESULTS: The use of reduced-porosity MOUS slowed the blood flow in the false lumen and decreased the wall shear stress. MOUS depressed the false lumen and enlarged the true lumen, without significantly altering the blood outflow distribution among the branch vessels. Compared with MOUS-alone and stent graft-alone scenarios, the combination of MOUS and stent graft generated a substantially large region of stagnant flow. The active flow was confined to an area in close vicinity to the tears covered by the MOUS, which perfuse the right renal artery in the false lumen. CONCLUSIONS: MOUS helps to generate a favored hemodynamic environment for thrombus formation in the false lumen. Application of MOUS along with covered stent grafts may represent a more effective treatment for AD than utilizing MOUS or stent graft alone.


Assuntos
Aneurisma Dissecante/cirurgia , Aorta/cirurgia , Aneurisma Aórtico/cirurgia , Implante de Prótese Vascular/instrumentação , Procedimentos Endovasculares/instrumentação , Hemodinâmica , Stents , Trombose/fisiopatologia , Aneurisma Dissecante/diagnóstico por imagem , Aneurisma Dissecante/fisiopatologia , Aorta/diagnóstico por imagem , Aorta/fisiopatologia , Aneurisma Aórtico/diagnóstico por imagem , Aneurisma Aórtico/fisiopatologia , Aortografia , Velocidade do Fluxo Sanguíneo , Angiografia por Tomografia Computadorizada , Simulação por Computador , Humanos , Hidrodinâmica , Modelos Cardiovasculares , Porosidade , Desenho de Prótese , Fluxo Pulsátil , Trombose/diagnóstico por imagem , Resultado do Tratamento
15.
Med Sci Monit ; 25: 4169-4175, 2019 Jun 04.
Artigo em Inglês | MEDLINE | ID: mdl-31163019

RESUMO

BACKGROUND The finite element analysis (FEA) was used to explore the effect of different graft heights on adjacent segment and graft segment stress after C4/5 anterior cervical discectomy and fusion (ACDF). MATERIAL AND METHODS A detailed, geometrically accurate 3-dimensional cervical spine model was successfully built from computed tomography (CT) scanning of a healthy adult male. We changed the graft height in C4-C5 to be 90%, 150%, 175%, and 200% of the preoperative disc height and simulated the postoperative scenarios with different bone graft height, respectively. A stress analysis was conducted on the adjacent segment and graft segment. RESULTS The maximum von Mises stress on C3-C4 showed that when the graft height was 200%, the values were 0.99 MPa, 0.85 MPa, 0.91 MPa, and 0.89 MPa in different loading conditions. For C5-C6, the maximum von Mises stress was 0.77 MPa, 0.83 MPa, 0.91 MPa, and 0.81 MPa, observed when the graft height was 175%, except in extension condition. With regard to graft segment (C4-C5), the biggest von Mises stress was 1.25 MPa, 1.77 MPa, 1.75 MPa, and 1.81 MPa observed at 200% graft height. For these 3 segments, the smallest von Mises stress was found at 150% graft height under the 4 loading conditions. CONCLUSIONS The graft height makes an important difference on the stress on the adjacent segment and the graft segment after anterior cervical discectomy and fusion. A 150% graft height was considered the proper graft height in C4/C5 ACDF, with the lowest stress on the adjacent segment and the graft segment.


Assuntos
Transplante Ósseo/métodos , Discotomia/métodos , Adulto , Fenômenos Biomecânicos , Vértebras Cervicais/cirurgia , Simulação por Computador , Análise de Elementos Finitos , Humanos , Disco Intervertebral/cirurgia , Degeneração do Disco Intervertebral/cirurgia , Masculino , Amplitude de Movimento Articular , Fusão Vertebral/métodos , Tomografia Computadorizada por Raios X , Suporte de Carga
16.
Anat Rec (Hoboken) ; 302(10): 1800-1807, 2019 10.
Artigo em Inglês | MEDLINE | ID: mdl-30809953

RESUMO

Gut mucosal immune responses are known to act as the first line of defense against invasion of pathogenic microorganisms. Piglets have an incompletely developed gut mucosal immune system, making them sensitive to intestinal infections. Promoting the development of the mucosal immune system will increase the pathogen resistance of piglets. The aim of the present study was to investigate the effect of carotenoid (4,4'-diaponeurosporene)-producing Bacillus subtilis (B.s-Dia) on intestinal mucosal immunity in piglets. We showed that oral administration to piglets of B.s-Dia remarkably improved the development of Peyer's patches (PPs) (P < 0.01), and increased villus height (P < 0.01) and colon crypt depth (P < 0.01). In addition, B.s-Dia also increased the number of intraepithelial lymphocytes (P < 0.01), while Bacillus subtilis (B.s) had no significant influence on it (P > 0.05). Moreover, B.s-Dia also increased the number of SIgA+ cells (P < 0.01). Oral administration of either B.s or B.s-Dia increased the number of CD4+ and CD8+ cells in ileum lamina propria (P < 0.01). These results indicate that B.s-Dia contributes to a higher extent to porcine mucosal immune system development than B.s, and might serve as an immunopotentiator candidate. Anat Rec, 302:1800-1807, 2019. © 2019 American Association for Anatomy.


Assuntos
Bacillus subtilis/imunologia , Carotenoides/metabolismo , Imunidade nas Mucosas , Probióticos/administração & dosagem , Suínos/crescimento & desenvolvimento , Triterpenos/metabolismo , Administração Oral , Ração Animal/microbiologia , Criação de Animais Domésticos/métodos , Animais , Bacillus subtilis/metabolismo , Carotenoides/imunologia , Íleo/crescimento & desenvolvimento , Íleo/imunologia , Mucosa Intestinal/crescimento & desenvolvimento , Mucosa Intestinal/imunologia , Nódulos Linfáticos Agregados/crescimento & desenvolvimento , Nódulos Linfáticos Agregados/imunologia , Suínos/imunologia , Triterpenos/imunologia
17.
J Mech Behav Biomed Mater ; 92: 188-196, 2019 04.
Artigo em Inglês | MEDLINE | ID: mdl-30738379

RESUMO

Residual stress is believed to play a significant role in the in vivo stress state of the arterial wall, but quantifying residual stress in vivo is challenging. Based on the well-known assumptions that residual stress is a result of heterogeneous arterial growth and that it homogenizes the transmural distribution of arterial wall stress, we propose a new anisotropic tissue growth model for the aorta to recover the three-dimensional residual stress field in a bi-layer human aortic wall. Finite element simulations showed that the predicted residual stress magnitude with this method are within the documented range for human aorta. Particularly, the homeostatic inter-layer stress difference is identified as a key parameter to quantify the opening angle. To the authors' knowledge, this is the first finite element study employing anisotropic growth of aortic tissue in a bi-layer model to generate three-dimensional residual stress field, and the resultant opening angle can match with the experiments. A parametric study found that inter-layer stress homogeneity, arterial blood pressure, axial pre-stretch, and material stiffness strongly affect the residual stress field.


Assuntos
Aorta , Análise de Elementos Finitos , Modelos Biológicos , Estresse Mecânico , Anisotropia , Aorta/fisiologia , Fenômenos Biomecânicos , Pressão Sanguínea
18.
Biomech Model Mechanobiol ; 18(2): 387-398, 2019 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-30413984

RESUMO

It is well known that residual deformations/stresses alter the mechanical behavior of arteries, e.g., the pressure-diameter curves. In an effort to enable personalized analysis of the aortic wall stress, approaches have been developed to incorporate experimentally derived residual deformations into in vivo loaded geometries in finite element simulations using thick-walled models. Solid elements are typically used to account for "bending-like" residual deformations. Yet, the difficulty in obtaining patient-specific residual deformations and material properties has become one of the biggest challenges of these thick-walled models. In thin-walled models, fortunately, static determinacy offers an appealing prospect that allows for the calculation of the thin-walled membrane stress without patient-specific material properties. The membrane stress can be computed using forward analysis by enforcing an extremely stiff material property as penalty treatment, which is referred to as the forward penalty approach. However, thin-walled membrane elements, which have zero bending stiffness, are incompatible with the residual deformations, and therefore, it is often stated as a limitation of thin-walled models. In this paper, by comparing the predicted stresses from thin-walled models and thick-walled models, we demonstrate that the transmural mean stress is approximately the same for the two models and can be readily obtained from in vivo clinical images without knowing the patient-specific material properties and residual deformations. Computation of patient-specific mean stress can be greatly simplified by using the forward penalty approach, which may be clinically valuable.


Assuntos
Aorta/patologia , Modelos Cardiovasculares , Estresse Mecânico , Análise de Elementos Finitos , Humanos , Probabilidade
19.
Zhongguo Ying Yong Sheng Li Xue Za Zhi ; 34(1): 69-73, 2018 Jan 08.
Artigo em Chinês | MEDLINE | ID: mdl-29926663

RESUMO

OBJECTIVE: To investigate the effects of centella asiatica (CA) granule on the expression of transform growth factor-ß1(TGF-ß1) and related down-stream signals in rats with early diabetic nephropathy(DN) and to clarify the molecular mechanisms of CA molecular mechanism of on preventing and curing early diabetic kidney disease DN by studying the effects of centella asiatica on TGF-ß1 expression and related down-stream signals. METHODS: Sixty male SD rats were divided into control group(n=10) and DN model group(n=50). The model rats were made a right nephrectomy. One week later, diabetic nephropathy was induced by intraperitoneal injection of streptocozin(30 mg/kg) for three consecutive days. High blood glucose level of Tail vein (fasting glucose ≥ 16.7 mmol/L) and high urinary protein level(total protein level in DN group was more than twice higher than the control group) were measured to confirm early DN in rats. In the sham operation group, the right renal capsule was damaged and the corresponding amount of saline was injected. The model rats were administrated by the means of intragastric administration. The DN model group were divided into DN group, DN+fosinopril group(1.6 mg/kg·d), DN+high CA group(16.8 mg/kg·d), DN+medium CA group(11.2 mg/kg·d) and DN+low CA group(5.6 mg/kg·d), and each group was intragastric administration one time every morning last for 16 weeks. The expressions of mRNA and protein of TGF-ß1, TßR1, TßR2, Smad2/3, Smad7 and the level of Smad2/3 phosphorylation were detected by using real time quantitative polymerase chain reaction and Western blot. RESULTS: The expressions of mRNA and protein of TGF-ß1, TßR1, TßR2, Smad2/3 and the level of Smad2/3 phosphorylation were significantly increased, the expressions of mRNA and protein of Smad7 were dramatically decreased. The fosinopril and high dosage CA could reverse the effects of DN. CONCLUSIONS: CA plays an important role in preventing and curing DN through regulating the TGF-ß1/Smad signaling pathways.


Assuntos
Centella/química , Nefropatias Diabéticas/tratamento farmacológico , Medicamentos de Ervas Chinesas/farmacologia , Fator de Crescimento Transformador beta1/metabolismo , Animais , Diabetes Mellitus Experimental , Nefropatias Diabéticas/induzido quimicamente , Nefropatias Diabéticas/metabolismo , Rim/fisiopatologia , Masculino , Ratos , Ratos Sprague-Dawley , Receptor do Fator de Crescimento Transformador beta Tipo I/metabolismo , Receptor do Fator de Crescimento Transformador beta Tipo II/metabolismo , Transdução de Sinais , Proteína Smad2/metabolismo , Proteína Smad3/metabolismo , Proteína Smad7/metabolismo
20.
Zhongguo Ying Yong Sheng Li Xue Za Zhi ; 34(2): 122-125, 2018 Feb 08.
Artigo em Chinês | MEDLINE | ID: mdl-29926674

RESUMO

OBJECTIVES: Stably expressed transforming growth factor -beta 1(TGF-ß1)MCs were obtained and the effects of centellaasiatica (CA) granule on the expressions of Smad 2/3, Smad 7 and collagen Ⅳ and the level of Smad 2/3 phosphorylation were observed. METHODS: Lipofectin method was used to transfect TGF-ß1 vector into MC, and the stably expressed TGF-ß1 cell lines were selected by G418. The cells were divided into three groups. Control group:normal MC + RPMI 1640 + 10% normal rat serum; TGF-ß1 group:stably expressed TGF-ß1 MC + RPMI 1640 + 10% normal rat serum; CA group:stably expressed TGF-ß1 MC + RPMI 1640 + 10% rat serum containing high CA. The experiments were repeated for five times. The contents of TGF-ß1 and collagen Ⅳ in the culture medium were detected with ELISA, the expressions of mRNA and protein of TGF-ß1, Smad 2/3, Smad 7 and the level of Smad 2/3 phosphorylation were detected by using real time quantitative polymerase chain reaction and Western blot. RESULTS: The contents of TGF-ß1 and collagen Ⅳ in the culture medium of stably-expressed TGF-ß1 MC were increased significantly, and the CA could reverse the effects of TGF-ß1. The expressions of mRNA and protein of TGF-ß1, Smad 2/3 and the level of Smad 2/3 phosphorylation were increased significantly in TGF-ß1 transfected MC, and CA could dramatically reduce the expressions of mRNA and protein of TGF-ß1, Smad 2/3 and the level of Smad 2/3 phosphorylation. The high expression of TGF-ß1 decreased the expression of Smad 7 mRNA and protein, and the CA could antagonize the effect of mRNA expression. CONCLUSIONS: The MCs stably-expressed TGF-ß1 can activate the TGF-ß1/Smad signal pathway and increase the expression of collagen Ⅳ. CA can decrease the occurrence of diabetic nephropathy(DN) by reducing the production of collagen Ⅳ through inhibiting the TGF-ß1/Smad signal pathway.


Assuntos
Centella/química , Colágeno Tipo IV/metabolismo , Medicamentos de Ervas Chinesas/farmacologia , Células Mesangiais/efeitos dos fármacos , Proteínas Smad/metabolismo , Fator de Crescimento Transformador beta1/metabolismo , Animais , Células Cultivadas , Células Mesangiais/metabolismo , Ratos , Transdução de Sinais , Proteína Smad2/metabolismo , Proteína Smad3/metabolismo , Proteína Smad7/metabolismo
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