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1.
Pestic Biochem Physiol ; 177: 104884, 2021 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-34301352

RESUMEN

In the present study, a total of 21 natural or synthetic small-molecule organic acids were selected and determined for their activity against postharvest gray mold caused by B. cinerea. Overall, cuminic acid, which was extracted from the seed of Cuminum cyminum L, showed the most promising antifungal activity against B. cinerea both in vitro and in vivo. The study on action mechanism showed that cuminic acid could inhibit the development of sclerotia and the secretion of oxalic acid, destroy the cell membrane integrity, and down regulate the expression of several key genes involved in sclerotia development and pathogenicity of B. cinerea. Furthermore, cuminic acid could potentially reduce the degradation of TSS and TA content, while it had no significant effect on the weight loss, firmness, and VC content of apple and tomato. Importantly, cuminic acid could enhance the antioxidant enzyme activities of the fruits. All these results demonstrate the antifungal activity and highlight the great potential of cuminic acid as an alternative environmental-friendly agent for the control of postharvest gray mold both on fruits and vegetables.


Asunto(s)
Botrytis , Solanum lycopersicum , Frutas , Enfermedades de las Plantas
2.
J Biomech Eng ; 141(11)2019 Nov 01.
Artículo en Inglés | MEDLINE | ID: mdl-31145780

RESUMEN

The impact of left subclavian artery (LSA) coverage during thoracic endovascular aortic repair (TEVAR) on the circulatory system is not fully understood. Here, we coupled a single-phase non-Newtonian model with fluid-structure interaction (FSI) technique to simulate blood flow in an acute type B aortic dissection. Three-element Windkessel model was implemented to reproduce physiological pressure waves, where a new workflow was designed to determine model parameters with the absence of measured data. Simulations were carried out in three geometric models to demonstrate the consequence of TEVAR with the LSA coverage; case A: pre-TEVAR aorta; case B: post-TEVAR aorta with the disappearance of LSA; case C: post-TEVAR aorta with virtually adding LSA. Results show that the blood flow through the compressed true lumen is only 8.43%, which may lead to ischemia in related organs. After TEVAR, the wall pressure on the stented segment increases and blood flow in the supra-aortic branches and true lumen is improved. Meantime, the average deformation of the aorta is obviously reduced due to the implantation of the stent graft. After virtually adding LSA, significant changes in the distribution of blood flow and two indices based on wall shear stress are observed. Moreover, the movement of residual false lumen becomes stable, which could contribute to patient recovery. Overall, this study quantitatively evaluates the efficacy of TEVAR for acute type B aortic dissection and demonstrates that the coverage of LSA has a considerable impact on the important hemodynamic parameters.

3.
Anal Chem ; 86(14): 7001-8, 2014 Jul 15.
Artículo en Inglés | MEDLINE | ID: mdl-24958198

RESUMEN

Despite great improvements in the past decades, the controllable fabrication of metal nanoelectrodes still remains very challenging. In this work, a simple and general way to fabricate metal nanoelectrodes (Ag, Au, and Pt) is developed. On the basis of interfacial reactions at nano-liquid/liquid interfaces supported at nanopipettes, the nanoparticles can be formed in situ and have been used to block the orifices of pipettes to make nanoelectrodes. The effect of the driving force for interfacial reaction at the liquid/liquid interface, the ratio of redox species in organic and aqueous phases, and the surface charge of the inner wall of a pipette have been studied. The fabricated nanoelectrodes have been characterized by scanning electron microscopy (SEM) and electrochemical techniques. A silver electrode with about 10 nm in radius has been employed as the scanning electrochemical microscopy (SECM) probe to explore the thickness of a water/nitrobenzene (W/NB) interface, and this value is equal to 0.8 ± 0.1 nm (n = 5). This method of fabrication of nanoelectrodes can be extended to other metal or semiconductor electrodes.

5.
Biomech Model Mechanobiol ; 22(6): 1953-1964, 2023 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-37481471

RESUMEN

The heat transfer mechanism inside the human aorta may be related to the physiological function and lesion formation of the aortic wall. The objective of this study was to acquire the temperature distribution in the three-dimensional idealized aorta. An idealized healthy aortic geometry and three representative diseased aortas: aortic aneurysm, coarctation of the aorta, and aortic dissection were constructed. Advanced fluid-structure interaction (FSI) computational framework was applied to predict the aortic temperature distribution. The movement of the aortic root due to the heartbeat was also considered. The displacement distribution of the aortic vessel wall was consistent with clinical observation. The lesser curvature of the aortic arch, aneurysm body, coarctation region, and false lumen were all exposed to relatively high temperatures (over 310.006 K). We found that the rigid wall assumption slightly underestimated the magnitude of the whole aortic wall-averaged temperature while the changing trend and local temperature were like the results of the FSI method. Besides, the wall-averaged temperature would increase and the temperature inflection point would advance when the aortic vessel wall was loaded with a high heat flux. This pilot study revealed the aortic heat transfer mechanism and temperature distribution, and the findings may help to understand the physiological characteristics of the aortic vessel wall.


Asunto(s)
Aneurisma de la Aorta , Calor , Humanos , Proyectos Piloto , Simulación por Computador , Aorta/patología , Modelos Cardiovasculares , Hemodinámica/fisiología , Estrés Mecánico
6.
Comput Biol Med ; 166: 107554, 2023 Sep 28.
Artículo en Inglés | MEDLINE | ID: mdl-37839217

RESUMEN

Distal stent graft-induced new entry tear (dSINE) is an important complication of thoracic endovascular aortic repair (TEVAR) for the treatment of type B aortic dissection (TBAD). This study aims to explore whether the aorta distal to the stent plays an important role in the occurrence of dSINE. Sixty-nine patient-specific geometrical models of twenty-three enrolled patients were reconstructed from preoperative, postoperative, and predSINE computed tomography scans. Computational fluid dynamics (CFD) simulations were performed to calculate the von Mises stress in the CFD group. Meanwhile, morphological measurements were performed in all patients, including measurements of the inverted pyramid index at different follow-up time points and the postoperative true lumen volume change rate. In the CFD study, the time-averaged von Mises stress of the true lumen distal to the stent in dSINE patients was significantly higher than that in the CFD controls (20.42 kPa vs. 15.47 kPa). In the morphological study, a special aortic plane (plane A) with an extremely small area distal to the stent was observed in dSINE patients, which resulted in an inverted pyramid structure in the true lumen distal to the stent. This structure in dSINE patients became increasingly obvious during the follow-up period and finally reached the maximum value before dSINE occurred (mean, 3.91 vs. 1.23). At the same time, enlargement of the true lumen distal to the stent occurs before dSINE, manifesting as a continuous increase in the true lumen volume (mean, 0.70 vs. 013). A new theory of what causes dSINE to occur has been proposed: the inverted pyramid structure of the true lumen distal to the stent caused an increase in the von Mises stress in this region and aortic enlargement, which ultimately led to the occurrence of dSINE.

7.
Eur J Med Chem ; 253: 115321, 2023 May 05.
Artículo en Inglés | MEDLINE | ID: mdl-37037137

RESUMEN

Histone lysine specific demethylase 1 (LSD1) is responsible for the demethylation of mono-/dimethylated lysine residue on histone proteins. LSD1 plays an extensive and essential role in the pathogenesis and progression of many human diseases such as cancers, and thus is becoming an attractive therapeutic target for cancer treatment. Tranylcypromine (TCP) is an important chemical template for developing irreversible LSD1 inhibitors, representing a major chemotype of clinical candidates. Here we report a novel pool of TCP derivatives with triazolopyrimidine as a privileged heterocylic motif. Starting from ticagrelor, a clinically available antiplatelet agent, as a hit compound, our medicinal efforts have led to the identification of compound 9j with nanomolar inhibitory potency against LSD1 as well as broad-spectrum antiproliferative activities against tumor cells. Enzyme studies show that compound 9j is selective over MAO-A/B enzymes, and also cellular active to elevate the expression of H3K4me2 by inhibiting LSD1 in cells. Furthermore, in a H1650 xenograft mouse model, oral administration of compound 9j at low 10 and 20 mg/kg dosages could enable a significant reduction in tumor size and a remarkable extension of survival. The current work is expected to provide an additional strategy to achieve new TCP-based LSD1 inhibitors.


Asunto(s)
Antineoplásicos , Tranilcipromina , Humanos , Animales , Ratones , Tranilcipromina/farmacología , Inhibidores Enzimáticos/farmacología , Antineoplásicos/química , Histonas/metabolismo , Lisina , Histona Demetilasas , Relación Estructura-Actividad
8.
Front Physiol ; 13: 867613, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-35547578

RESUMEN

Thrombosis seriously threatens human cardiovascular health and the safe operation of medical devices. The Food and Drug Administration's (FDA) benchmark nozzle model was designed to include the typical structure of medical devices. However, the thrombosis in the FDA nozzle has yet not been investigated. The objective of this study is to predict the thrombus formation process in the idealized medical device by coupling computational fluid dynamics and a macroscopic hemodynamic-based thrombus model. We developed the hemodynamic-based thrombus model by considering the effect of platelet consumption. The thrombus model was quantitatively validated by referring to the latest thrombosis experiment, which was performed in a backward-facing step with human blood flow. The same setup was applied in the FDA nozzle to simulate the thrombus formation process. The thrombus shaped like a ring was firstly observed in the FDA benchmark nozzle. Subsequently, the accuracy of the shear-stress transport turbulence model was confirmed in different turbulent flow conditions. Five scenarios with different Reynolds numbers were carried out. We found that turbulence could change the shape of centrosymmetric thrombus to axisymmetric and high Reynolds number blood flow would delay or even prevent thrombosis. Overall, the present study reports the thrombosis process in the FDA benchmark nozzle using the numerical simulation method, and the primary findings may shed light on the effect of turbulence on thrombosis.

9.
Comput Methods Programs Biomed ; 221: 106826, 2022 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-35526507

RESUMEN

BACKGROUND AND OBJECTIVES: The aorta serves as the main tube of the human blood circulation system. Energy loss (EL) occurs when blood flows through the aorta and there may be a potential correlation between EL and aortic diseases. However, the components of blood flow EL are still not fully understood. This study aims to quantitatively reveal the EL components in healthy and diseased aortas. METHODS: We construct an idealized healthy aorta and three idealized representative diseased aortas: aortic aneurysm, coarctation of the aorta, and aortic dissection. Computational hemodynamic studies are carried out by using the fluid-structure interaction simulation framework. RESULTS: Four kinds of EL components: viscous friction, turbulence dissipation, wall deformation, and local lesion are firstly acquired in healthy and diseased aortas based on the high-resolution blood flow information. Viscous friction contributes most to the EL (45.69%-57.22%). EL caused by the deformation of the aortic wall ranks second (15.18%-33.12%). The proportions of turbulence dissipation and local lesion depend on individual geometric characteristics. Besides, the buffering efficiency of the healthy and diseased aorta is about 80%. CONCLUSIONS: This study quantitatively reports the components of blood flow EL in healthy and diseased aortas, the finding may provide novel insights into the pathogenesis of aortic diseases.


Asunto(s)
Aneurisma de la Aorta , Modelos Cardiovasculares , Aorta , Velocidad del Flujo Sanguíneo/fisiología , Simulación por Computador , Hemodinámica , Humanos , Estrés Mecánico
10.
Biomech Model Mechanobiol ; 21(1): 221-230, 2022 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-34748063

RESUMEN

The human aorta is a high-risk area for vascular diseases, which are commonly restored by thoracic endovascular aortic repair. In this paper, we report a promising shear-activated targeted nanoparticle drug delivery strategy to assist in the treatment of coarctation of the aorta and aortic aneurysm. Idealized three-dimensional geometric models of coarctation of the aorta and aortic aneurysm are designed, respectively. The unique hemodynamic environment of the diseased aorta is used to improve nanoparticle drug delivery. Micro-carriers with nanoparticle drugs would be targeting activated to release nanoparticle drugs by local abnormal shear stress rate (SSR). Coarctation of the aorta provides a high SSR hemodynamic environment, while the aortic aneurysm is exposed to low SSR. We propose a method to calculate the SSR thresholds for the diseased aorta. Results show that the upstream near-wall area of the diseased location is an ideal injection location for the micro-carriers, which could be activated by the abnormal SSR. Released nanoparticle drugs would be successfully targeted delivered to the aortic diseased wall. Besides, the high diffusivity of the micro-carriers and nanoparticle drugs has a significant impact on the surface drug concentrations of the diseased aortic walls, especially for aortic aneurysms. This study preliminary demonstrates the feasibility of shear-activated targeted nanoparticle drug delivery in the treatment of aortic diseases and provides a theoretical basis for developing the drug delivery system and novel therapy.


Asunto(s)
Aneurisma de la Aorta , Coartación Aórtica , Nanopartículas , Aorta Torácica , Sistemas de Liberación de Medicamentos , Hemodinámica , Humanos , Modelos Cardiovasculares , Estrés Mecánico
11.
Biomech Model Mechanobiol ; 21(2): 419-431, 2022 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-34994871

RESUMEN

Thoracic endovascular aortic repair (TEVAR) has become the standard treatment of a variety of aortic pathologies. The objective of this study is to evaluate the hemodynamic effects of stent-graft introducer sheath during TEVAR. Three idealized representative diseased aortas were designed: aortic aneurysm, coarctation of the aorta, and aortic dissection. Computational fluid dynamics studies were performed in the above idealized aortic geometries. An introducer sheath routinely used in the clinic was virtually placed into diseased aortas. Comparative analysis was carried out to evaluate the hemodynamic effects of the introducer sheath. Results show that the blood flow to the supra-aortic branches would increase above 9% due to the obstruction of the introducer sheath. The region exposed to high endothelial cell activation potential (ECAP) expands in the scenarios of coarctation of the aorta and aortic dissection, which indicates that the probability of thrombus formation may increase during TEVAR. The pressure magnitude in peak systole shows an obvious rise, and a similar phenomenon is not observed in early diastole. The blood viscosity in the aortic arch and descending aorta is remarkably altered by the introducer sheath. The uneven viscosity distribution confirms the necessity of using non-Newtonian models, and high-viscosity region with high ECAP further promotes thrombosis. Our results highlight the hemodynamic effects of stent-graft introducer sheath during TEVAR, which may associate with perioperative complications.


Asunto(s)
Aneurisma de la Aorta Torácica , Implantación de Prótesis Vascular , Procedimientos Endovasculares , Aorta Torácica/cirugía , Aneurisma de la Aorta Torácica/cirugía , Prótesis Vascular , Hemodinámica , Humanos , Diseño de Prótesis , Stents , Resultado del Tratamiento
12.
Int J Food Microbiol ; 383: 109939, 2022 Dec 16.
Artículo en Inglés | MEDLINE | ID: mdl-36166914

RESUMEN

Sclerotinia rot infected by cosmopolitan fungi Sclerotinia sclerotiorum is a serious and destructive disease in carrot production, especially during their postharvest storage. Natural products with the advantages of environmentally friendly and safety have been widely concerned. This research estimated the impact of hinokitiol against S. sclerotiorum and on the quality of carrots. In vitro and in vivo tests demonstrated that hinokitiol had promising antifungal activities against both carbendazim-susceptible and -resistant isolates of S. sclerotiorum. Importantly, it effectively kept the quality and prolonged the shelf life of carrot by declining the loss of weight, ascorbic acid, carotenoid, and total phenolics content, preventing the formation of malondialdehyde, and enhancing the activities of antioxidant enzymes. Further study found that hinokitiol inhibited the formation of sclerotia by destroying the morphology and the integrality of cell membrane, reduced the pathogenicity by suppressing the synthesis of oxalic acid and exopolysaccharide, declined the activities of enzymes and the gene expression related to sclerotia development in S. sclerotiorum. These information evidenced the great potential of hinokitiol as a natural fresh-keeping agent for the management of postharvest decay infected by S. sclerotiorum.


Asunto(s)
Ascomicetos , Productos Biológicos , Daucus carota , Antifúngicos/farmacología , Productos Biológicos/farmacología , Productos Biológicos/metabolismo , Antioxidantes/metabolismo , Ácido Oxálico/metabolismo , Ácido Oxálico/farmacología , Ácido Ascórbico/farmacología , Carotenoides/metabolismo , Malondialdehído/metabolismo , Malondialdehído/farmacología
13.
Int J Nanomedicine ; 17: 1323-1341, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-35345783

RESUMEN

Introduction: Cancerous tumors are still a major disease that threatens human life, with tumor multidrug resistance (MDR) being one of the main reasons for the failure of chemotherapy. Thus, reversing tumor MDR has become a research focus of medical scientists. Methods: Here, a reduction-sensitive polymer prodrug micelle, mPEG-DCA-SS-PTX (PDSP), was manufactured with a new polymer inhibitor of drug resistance as a carrier to overcome MDR and improve the anti-tumor effect of PTX. Results: The PDSP micelles display good stability, double-responsive drug release, and excellent biocompatibility. The PDSP micelles reduced the cytotoxicity of PTX to normal HL-7702 cells and enhanced that to SMMC-7721 and MCF-7 cells in vitro. Improved sensitivity of A549/ADR to PDSP was also observed in vitro. Furthermore, in vivo experiments show reduced systemic toxicity and enhanced therapeutic efficacy of PTX to H22 subcutaneous tumor-bearing mice. Conclusion: This work proves that the reduction-sensitive polymer prodrug micelles carried by the new polymer inhibitor can be used as an alternative delivery system to target tumors and reverse MDR for paclitaxel and other tumor-resistant drugs.


Asunto(s)
Micelas , Paclitaxel , Animales , Sistemas de Liberación de Medicamentos , Resistencia a Múltiples Medicamentos , Resistencia a Antineoplásicos , Humanos , Ratones , Paclitaxel/farmacología , Polímeros/farmacología
14.
Front Cardiovasc Med ; 9: 1057195, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-36582736

RESUMEN

Introduction: A contactless multiscale cardiac motion measurement method is proposed using impulse radio ultra-wideband (IR-UWB) radar at a center frequency of 7.29 GHz. Motivation: Electrocardiograph (ECG), heart sound, and ultrasound are traditional state-of-the-art heartbeat signal measurement methods. These methods suffer from defects in contact and the existence of a blind information segment during the cardiogram measurement. Methods: Experiments and analyses were conducted using coarse-to-fine scale. Anteroposterior and along-the-arc measurements were taken from five healthy male subjects (aged 25-43) when lying down or prone. In every measurement, 10 seconds of breath-holding data were recorded with a radar 55 cm away from the body surface, while the ECG was monitored simultaneously as a reference. Results: Cardiac motion detection from the front was superior to that from the back in amplitude. In terms of radar detection angles, the best cardiac motion information was observed at a detection angle of 120°. Finally, in terms of cardiac motion cycles, all the ECG information, as well as short segments of cardiac motion details named blind ECGs segments, were detected. Significance: A contactless and multiscale cardiac motion detection method is proposed with no blind detection of segments during the entire cardiac cycle. This paves the way for a potentially significant method of fast and accurate cardiac disease assessment and diagnosis that exhibits promising application prospects in contactless online cardiac monitoring and in-home healthcare.

15.
J Ethnopharmacol ; 290: 115101, 2022 May 23.
Artículo en Inglés | MEDLINE | ID: mdl-35151834

RESUMEN

ETHNOPHARMACOLOGICAL RELEVANCE: Zexie Tang (ZXT), only two consists with Alismatis Rhizoma (AR) and Atractylodes macrocephala Rhizoma (AM), a classical Chinese medicine formula from Synopsis of the Golden Chamber with a history of 2000 years. Clinical observation in recent years has found that ZXT has excellent lipid-lowering effect. AIM OF THE STUDY: To explore the potential mechanism of ZXT ameliorates hyperlipidemia based on FKBP38/mTOR/SREBPs pathway. MATERIALS AND METHODS: WD-induced hyperlipidemia mice and oleic acid induced cell lipid accumulation model were used to investigate pharmacodynamic. The effect of ZXT on the transcriptional activity of SREBPs was detected by reporter gene assay. Proteins and downstream genes of mTOR/SREBPs pathway were detected in vivo and in vitro. Combined with network pharmacology and HPLC-Q-TOF/MS, the active ingredients were screened and identified. The interaction between active compounds of ZXT and FKBP38 protein were analyzed by docking analysis. RESULTS: ZXT decreased TC, TG and LDL-c levels in blood of WD-induced hyperlipidemia mouse model, and improved insulin resistance in vivo. ZXT also reduced TC, TG and lipid accumulation in cells line, and inhibited SREBPs luciferase activity, protein and its target genes expression such as FASN, HMGCR, etc. Meanwhile, ZXT inhibited protein expression levels of p-mTOR, p-S6K, etc in vitro and in vivo. Combined with network pharmacology and HPLC-Q-TOF/MS, 16 active ingredients were screened and identified. Docking results showed that active compounds of ZXT binding to FKBP38 and formed hydrogen bond. CONCLUSION: Our findings highlighted that ZXT ameliorates hyperlipidemia, in which FKBP/mTOR/SREBPs pathway might be the potential regulatory mechanism.


Asunto(s)
Hiperlipidemias/patología , Lípidos/sangre , Extractos Vegetales/farmacología , Proteínas de Unión a los Elementos Reguladores de Esteroles/efectos de los fármacos , Serina-Treonina Quinasas TOR/efectos de los fármacos , Proteínas de Unión a Tacrolimus/efectos de los fármacos , Alismatales , Animales , Atractylodes , Modelos Animales de Enfermedad , Relación Dosis-Respuesta a Droga , Masculino , Ratones , Ratones Endogámicos C57BL , Simulación del Acoplamiento Molecular , Farmacología en Red
16.
Comput Biol Med ; 136: 104709, 2021 09.
Artículo en Inglés | MEDLINE | ID: mdl-34365279

RESUMEN

Type B aortic dissection is a major aortic catastrophe that can be acutely complicated by rapid expansion, rupture, and malperfusion syndromes. The separation of the intima from aortic walls will form a second blood-filled lumen defined as "false lumen (FL)", where the thrombus is more likely to form due to the local stasis hemodynamic conditions. Complete thrombosis of FL is associated with a beneficial outcome while patency and partial thrombosis will lead to later complications. However, the thrombosis mechanism is still unclear and little is known about the impact of chemical species transported by blood flow on this process. The proteins involved in the coagulation cascade (CC) may play an important role in the process of thrombosis, especially in the activation and stabilization of platelets. Based on this hypothesis, a reduced-order fluid-chemical model was established to simulate CC in an aortic dissection phantom with two tears. A high level of fibrin is continuously observed at the top of the FL and some time-varying areas between two tears, indicating a high likelihood of thrombus formation there. This finding is consistent with the clinical observation. The time evolution of coagulation factors is greatly affected by local hemodynamics, especially in the high disturbance zone where the evolution has characteristics of periodic changes consistent with the flow field. The ability of the proposed model to reproduce the CC response provides a potential application to integrate with a model that can simulate platelet activities, forming a biochemical-based model which would help unveil the mechanisms of thrombosis in FL and the clinical decision of appropriate treatment.


Asunto(s)
Aneurisma de la Aorta Torácica , Disección Aórtica , Procedimientos Endovasculares , Trombosis , Aorta , Hemodinámica , Humanos , Modelos Químicos
17.
Comput Biol Med ; 138: 104882, 2021 11.
Artículo en Inglés | MEDLINE | ID: mdl-34600328

RESUMEN

Thoracic endovascular aortic repair (TEVAR) has developed to be the most effective treatment for aortic diseases. This study aims to evaluate the biomechanical implications of the implanted endograft after TEVAR. We present a novel image-based, patient-specific, fluid-structure computational framework. The geometries of blood, endograft, and aortic wall were reconstructed based on clinical images. Patient-specific measurement data was collected to determine the parameters of the three-element Windkessel. We designed three postoperative scenarios with rigid wall assumption, blood-wall interaction, blood-endograft-wall interplay, respectively, where a two-way fluid-structure interaction (FSI) method was applied to predict the deformation of the composite stent-wall. Computational results were validated with Doppler ultrasound data. Results show that the rigid wall assumption fails to predict the waveforms of blood outflow and energy loss (EL). The complete storage and release process of blood flow energy, which consists of four phases is captured by the FSI method. The endograft implantation would weaken the buffer function of the aorta and reduce mean EL by 19.1%. The closed curve area of wall pressure and aortic volume could indicate the EL caused by the interaction between blood flow and wall deformation, which accounts for 68.8% of the total EL. Both the FSI and endograft have a slight effect on wall shear stress-related-indices. The deformability of the composite stent-wall region is remarkably limited by the endograft. Our results highlight the importance of considering the interaction between blood flow, the implanted endograft, and the aortic wall to acquire physiologically accurate hemodynamics in post-TEVAR computational studies and the deformation of the aortic wall is responsible for the major EL of the blood flow.


Asunto(s)
Aneurisma de la Aorta Torácica , Implantación de Prótesis Vascular , Procedimientos Endovasculares , Aorta Torácica/diagnóstico por imagen , Aorta Torácica/cirugía , Aneurisma de la Aorta Torácica/diagnóstico por imagen , Aneurisma de la Aorta Torácica/cirugía , Prótesis Vascular , Hemodinámica , Humanos , Diseño de Prótesis , Stents , Resultado del Tratamiento
18.
J Nat Med ; 75(3): 540-552, 2021 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-33590347

RESUMEN

The accumulation of iron-dependent lipid peroxides is one of the important causes of NAFLD. The purpose of this study is to explore the effect of dehydroabietic acid (DA) on ferroptosis in nonalcoholic fatty liver disease (NAFLD) mice and its possible mechanisms. DA improved NAFLD and reduced triglycerides (TG), total cholesterol (TC), and lipid peroxidation level and inhibited ferroptosis in the liver of HFD-induced mice. DA binds with Keap1 to form 3 stable hydrogen bonds at VAL512 and LEU557 and increased nuclear factor erythroid 2-related factor 2 (Nrf2)-antioxidant response elemen (ARE) luciferase activity. DA promoted the expression downstream of Nrf2 such as heme oxygenase-1 (HO-1), glutathione (GSH) and its peroxidase 4 (GPX4), so as to eliminate the accumulation of reactive oxygen species (ROS) and reduce lipid peroxides malondialdehyde (MDA) in the liver. DA inhibited ferroptosis and increased the expression of key genes such as ferroptosis suppressor protein 1 (FSP1) in vitro and vivo. In all, DA may bind with Keap1, activate Nrf2-ARE, induce its target gene expression, inhibit ROS accumulation and lipid peroxidation, and reduce HFD-induced NAFLD.


Asunto(s)
Abietanos/uso terapéutico , Ferroptosis/efectos de los fármacos , Enfermedad del Hígado Graso no Alcohólico/tratamiento farmacológico , Transducción de Señal/efectos de los fármacos , Animales , Elementos de Respuesta Antioxidante , Colesterol/sangre , Glutatión/metabolismo , Células HEK293 , Hemo-Oxigenasa 1/metabolismo , Humanos , Proteína 1 Asociada A ECH Tipo Kelch/metabolismo , Peroxidación de Lípido/efectos de los fármacos , Masculino , Malondialdehído/metabolismo , Proteínas de la Membrana , Ratones , Ratones Endogámicos C57BL , Factor 2 Relacionado con NF-E2/metabolismo , Fosfolípido Hidroperóxido Glutatión Peroxidasa/metabolismo , Especies Reactivas de Oxígeno/metabolismo , Proteína de Unión al Calcio S100A4/metabolismo , Triglicéridos/sangre
19.
Int J Pharm ; 600: 120528, 2021 May 01.
Artículo en Inglés | MEDLINE | ID: mdl-33781880

RESUMEN

Tumor multidrug resistance (MDR) is one of the main reasons for the failure of clinical chemotherapy. Here, a bio-responsive anti-drug-resistant polymer micelle that can respond to the reductive GSH in the tumor microenvironment (TME) for delivery of HCPT was designed. A new type of polymer with anti-drug resistance and anti-tumor effect was synthesized and used to encapsulated HCPT to form reduction-sensitive micelles (PDSAH) by a thin-film dispersion method. It is demonstrated that the micelle formulation improves the anti-tumor activity and biosafety of HCPT, and also plays a significant role in reversing the drug resistance, which contributes to inhibiting the tumor growth and prolonging the survival time of H22 tumor-bearing mice. The results indicate that this nanoplatform can serve as a flexible and powerful system for delivery of other drugs that are tolerated by tumors or bacteria.


Asunto(s)
Camptotecina , Micelas , Animales , Camptotecina/análogos & derivados , Línea Celular Tumoral , Sistemas de Liberación de Medicamentos , Resistencia a Múltiples Medicamentos , Resistencia a Antineoplásicos , Ratones , Polímeros
20.
J Biomech ; 99: 109478, 2020 01 23.
Artículo en Inglés | MEDLINE | ID: mdl-31706561

RESUMEN

The inadequate landing zone during thoracic endovascular aortic repair (TEVAR) could be resolved by fenestration technology. The fenestration structure consists of a main endograft and a left subclavian artery (LSA) stent-graft. The purpose of this study is to assess the biomechanical implications of the protruding segment (PS) of the LSA stent-graft after TEVAR with in situ fenestration (ISF-TEVAR). The PS is characterized by the protruding length and centerline angle between the LSA and PS. An idealized three-dimensional geometric model of the human aorta was constructed as the reference benchmark. We designed nine postoperative aortic geometries with different protruding lengths (5, 10, 15 mm) and centerline angles (-20°, 0°, +20°). The blood was assumed to be non-Newtonian and the three-element Windkessel model was applied to reproduce physiological pressure waveforms. The interaction between the blood and vessel wall was captured by a two-way fluid-structure method. We also considered the impact of the fenestration structure on the vessel wall. Long protruding length (15 mm) and the retrograde angle (+20°) result in a markedly reduced LSA flow ratio (1.3%). There is a pressure difference between the inner and outer walls of the PS. The region around the PS is more prone to thrombosis. The flow stability and turbulence intensity of downstream blood of the PS gradually deteriorate. The largest deformed region moves from the aortic arch to the ascending aorta after ISF-TEVAR. The postoperative hemodynamics largely depends on the protruding length and angle of the LSA stent-graft. The configurations should be carefully controlled during ISF-TEVAR.


Asunto(s)
Aorta Torácica/cirugía , Procedimientos Endovasculares , Fenómenos Mecánicos , Anciano , Aorta Torácica/fisiología , Femenino , Hemodinámica , Humanos , Masculino , Persona de Mediana Edad , Diseño de Prótesis , Stents , Resultado del Tratamiento
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