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1.
J Sep Sci ; 47(13): e2400157, 2024 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-38982555

RESUMEN

Capillary electrophoresis (CE) is a powerful separation technique offering quick and efficient analyses in various fields of bioanalytical chemistry. It is characterized by many well-known advantages, but one, which is perhaps the most important for this application field, is somewhat overlooked. It is the possibility to perform chemical and biochemical reactions at the nL scale inside the separation capillary. There are two basic formats applicable for this purpose, heterogeneous and homogeneous. In the former, one reactant is immobilized onto a particle or monolithic support or directly on the capillary wall, and the other is injected. In the latter, the reactant mixing inside a capillary is based on electromigration or diffusion. One of the diffusion-based methodologies, termed Transverse Diffusion of Laminar Flow Profiles, is the subject of this review. Since most studies utilizing in-capillary reactions in CE focus on enzymes, which are being continuously and exhaustively reviewed, this review covers the atypical applications of this methodology, but still in the bioanalytical field. As can be seen from the demonstrated applications, they are not limited to reactions, but can also be utilized for other biochemical systems.

2.
AAPS PharmSciTech ; 25(7): 243, 2024 Oct 15.
Artículo en Inglés | MEDLINE | ID: mdl-39406951

RESUMEN

This study explored, for the first time the role of different designs of the Flow-Through-Cell (FTC, USP IV) dissolution Tester in predicting the in-vivo performance of Pentoxifylline (PTX) sustained-release (SR) market product, under fed & fasting conditions. Release studies of Trental® SR 400 mg (Sanofi, Egypt), were carried-out in the FTC under different conditions, including: different volumes / compositions of release media, variable FTC flow patterns as well as applying open / closed loop configuration setups. Pharmacokinetic (PK) data, obtained from literature, were converted to in-vivo fraction-absorbed [FA] using Wagner-Nelson (WN) method. A 1:1 IVIVC was investigated by comparing PTX fraction-dissolved [FD] under different FTC release designs versus calculated [FA]. Predicted PK parameters were evaluated, and compared with actual data, with estimation of prediction-error (PE%). The suggested FTC design; a closed-loop setup, with turbulent-flow pattern of the dissolution medium; provided the most acceptable PTX release according to USP labeled limits (USP 27). Also, results showed that PTX release was pronouncedly increased in a finite-volume of gradient-buffer system rather than water, which guarantee complete resemblance to GIT environment. This release design presented the most predictive IVIVC model with PTX in-vivo performance under fasting / fed states, with acceptable PE% values in terms of Cmax and AUCs. A suggested FTC design is proposed as an alternative dissolution model in the official USP-monograph for PTX SR products.


Asunto(s)
Preparaciones de Acción Retardada , Ayuno , Pentoxifilina , Solubilidad , Pentoxifilina/farmacocinética , Pentoxifilina/administración & dosificación , Pentoxifilina/química , Ayuno/metabolismo , Preparaciones de Acción Retardada/farmacocinética , Liberación de Fármacos , Humanos , Química Farmacéutica/métodos
3.
Build Environ ; 256: None, 2024 May 15.
Artículo en Inglés | MEDLINE | ID: mdl-38983757

RESUMEN

Ultra-Clean-Air (UCA) operating theatres aim to minimise surgical instrument contamination and wound infection through high flow rates of ultra-clean air, reducing the presence of Microbe Carrying Particles (MCPs). This study investigates the airflow patterns and ventilation characteristics of a UCA operating theatre (OT) under standard ventilation system operating conditions, considering both empty and partially occupied scenarios. Utilising a precise computational model, quasi-Direct Numerical Simulations (qDNS) were conducted to delineate flow velocity profiles, energy spectra, distributions of turbulent kinetic energy, energy dissipation rate, local Kolmogorov scales, and pressure-based coherent structures. These results were also complemented by a tracer gas decay analysis following ASHRAE standard guidelines. Simulations showed that contrary to the intended laminar regime, the OT's geometry inherently fosters a predominantly turbulent airflow, sustained until evacuation through the exhaust vents, and facilitating recirculation zones irrespective of occupancy level. Notably, the occupied scenario demonstrated superior ventilation efficiency, a phenomenon attributed to enhanced kinetic energy induced by the additional obstructions. The findings underscore the critical role of UCA-OT design in mitigating MCP dissemination, highlighting the potential to augment the design to optimise airflow across a broader theatre spectrum, thereby diminishing recirculation zones and consequently reducing the propensity for Surgical Site Infections (SSIs). The study advocates for design refinements to harness the turbulent dynamics beneficially, steering towards a safer surgical environment.

4.
J Biol Chem ; 298(10): 102404, 2022 10.
Artículo en Inglés | MEDLINE | ID: mdl-35988646

RESUMEN

Endothelial cells (ECs) are the primary cellular constituent of blood vessels that are in direct contact with hemodynamic forces over their lifetime. Throughout the body, vessels experience different blood flow patterns and rates that alter vascular architecture and cellular behavior. Because of the complexities of studying blood flow in an intact organism, particularly during development, the field has increasingly relied on in vitro modeling of blood flow as a powerful technique for studying hemodynamic-dependent signaling mechanisms in ECs. While commercial flow systems that recirculate fluids exist, many commercially available pumps are peristaltic and best model pulsatile flow conditions. However, there are many important situations in which ECs experience laminar flow conditions in vivo, such as along long straight stretches of the vasculature. To understand EC function under these contexts, it is important to be able to reproducibly model laminar flow conditions in vitro. Here, we outline a method to reliably adapt commercially available peristaltic pumps to study laminar flow conditions. Our proof-of-concept study focuses on 2D models but could be further adapted to 3D environments to better model in vivo scenarios, such as organ development. Our studies make significant inroads into solving technical challenges associated with flow modeling and allow us to conduct functional studies toward understanding the mechanistic role of shear forces on vascular architecture, cellular behavior, and remodeling in diverse physiological contexts.


Asunto(s)
Adaptación Fisiológica , Células Endoteliales , Células Endoteliales/fisiología , Estrés Mecánico , Células Cultivadas
5.
Glycobiology ; 33(8): 637-650, 2023 10 06.
Artículo en Inglés | MEDLINE | ID: mdl-37486674

RESUMEN

One critical step of metastasis formation is the extravasation of circulating tumor cells from the bloodstream. This process requires the dynamic interaction of cell adhesion molecules like E-selectin on endothelial cells with carbohydrate ligands on tumor cells. To characterize these glycans in a comprehensible approach, the rolling, tethering, and firm adhesion of nine human tumor cell lines on human umbilical vein endothelial cells was analyzed using laminar flow adhesion assays. The tumor cell lines were grouped into three subsets by their canonical E-selectin ligand status (sialyl-Lewis A and X +/+, -/+, -/-) and their adhesiveness was compared after enzymatic, pharmacologic, chemical treatment or antibody blockade of the tumor cells or endothelial cells, respectively. Tumor cells were also screened regarding their glycosyltransferase expression profile. We found that although E-selectin and terminal α2,3-sialic acid largely determined firm adhesion, adhesive events did not exclusively depend on the presence of sialyl-Lewis A and/or sialyl-Lewis X. Nevertheless, two of the three sialyl-Lewis A/X-/- tumor cells additionally or fully depended on vascular cell adhesion molecule-1 for firm adhesion. The significance of O-GalNAc- and N-glycans for adhesion varied remarkably among the tumor cells. The sialyl-Lewis A/X+/+ subset showed glycoprotein-independent adhesion, suggesting a role of glycolipids as well. All sialyl-Lewis A/X-/- tumor cells lacked FUT3 and FUT7 expression as opposed to sialyl-Lewis A/X+/+ or -/+ cell lines. In summary, the glycans on tumor cells mediating endothelial adhesion are not as much restricted to sialyl-Lewis A /X as previously assumed. The present study specifically suggests α2,3-linked sialic acid, O-GalNAc glycans, glycosphingolipids, and FUT3/FUT7 products as promising targets for future studies.


Asunto(s)
Selectina E , Células Endoteliales , Humanos , Selectina E/metabolismo , Células Endoteliales/metabolismo , Adhesión Celular , Ácido N-Acetilneuramínico , Antígeno Sialil Lewis X , Polisacáridos , Oligosacáridos/química
6.
Electrophoresis ; 2023 Nov 30.
Artículo en Inglés | MEDLINE | ID: mdl-38037281

RESUMEN

A careful analysis of the typical devices and conditions used during hydrodynamic injection in capillary electrophoresis shows that the Hagen-Poiseuille model for the laminar flow is valid, even during the transitions of pressure. Therefore, the monitoring of pressure becomes a reliable approach to evaluate the effective injected volume, because the volume is proportional to the integral of pressure (IoP) over time. A piezoresistive sensor was used to monitor the air pressure at headspace of the sample vial. A set of 18 injections at 50 mbar and different times were used to evaluate the use of the normalization of the peak areas of the analytes by the IoP to compensate for imperfection during the injection. There was a significant decrease in relative standard deviation (RSD), and the proposed approach presented results similar to the use of internal standard. In addition, a microcontroller was used not only to monitor the pressure but also to command a peristaltic pump and a solenoid valve creating a system that dynamically controls the applied pressure and stops the injection when the desired value of IoP is reached. The system was used in a proof of concept in which different combinations of pressure and time were used: 10 mbar × 50 s, 25 mbar × 20 s, 50 mbar × 10 s, 125 mbar × 4 s, and 250 mbar × 2 s. Despite the constraints posed by the flowrates of the peristaltic pump and the solenoid valve, the microcontroller effectively conducted the injections across this extensive range of conditions, resulting in an IoP RSD of 2.7%.

7.
Eur Biophys J ; 52(4-5): 459-471, 2023 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-36583735

RESUMEN

Within the complex milieu of a cell, which comprises a large number of different biomolecules, interactions are critical for function. In this post-reductionist era of biochemical research, the 'holy grail' for studying biomolecular interactions is to be able to characterize them in native environments. While there are a limited number of in situ experimental techniques currently available, there is a continuing need to develop new methods for the analysis of biomolecular complexes that can cope with the additional complexities introduced by native-like solutions. We think approaches that use microfluidics allow researchers to access native-like environments for studying biological problems. This review begins with a brief overview of the importance of studying biomolecular interactions and currently available methods for doing so. Basic principles of diffusion and microfluidics are introduced and this is followed by a review of previous studies that have used microfluidics to measure molecular diffusion and a discussion of the advantages and challenges of this technique.


Asunto(s)
Microfluídica , Proteínas , Microfluídica/métodos , Difusión
8.
J Fish Biol ; 103(6): 1556-1559, 2023 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-37635640

RESUMEN

During an escape from predators, many animals need to evaluate and choose a refuge within seconds. We investigated refuge choice in the amphibious blackspotted rockskipper, Entomacrodus striatus, in Moorea, French Polynesia. Rockskippers are small combtooth blennies that inhabit rocky beaches and jetties at the aquatic/terrestrial interface. They are conspicuous for their eponymous jumping to/from refugia among rocks when threatened. We have observed refugia with both multiple conspecifics and solitary fish in the field, and here tested whether fish choose refugia that are occupied by conspecifics in the laboratory. E. striatus chose unoccupied refugia on the opposite side of the experimental tank in 11/14 trials, a significantly greater number of times than they chose occupied refugia. In 3/14 trials, fish chose occupied refugia, indicating that refuge occupation does not prohibit their use by conspecifics. We hypothesize that chemical stress signals from the occupying fish deter most fish from choosing the same refuge.


Asunto(s)
Perciformes , Animales , Peces , Polinesia
9.
Biol Proced Online ; 24(1): 5, 2022 Apr 28.
Artículo en Inglés | MEDLINE | ID: mdl-35484481

RESUMEN

Numerous cancer-associated deaths are owing to a lack of effective diagnostic and therapeutic approaches. Microfluidic systems for analyzing a low volume of samples offer a precise, quick, and user-friendly technique for cancer diagnosis and treatment. Microfluidic devices can detect many cancer-diagnostic factors from biological fluids and also generate appropriate nanoparticles for drug delivery. Thus, microfluidics may be valuable in the cancer field due to its high sensitivity, high throughput, and low cost. In the present article, we aim to review recent achievements in the application of microfluidic systems for the diagnosis and treatment of various cancers. Although microfluidic platforms are not yet used in the clinic, they are expected to become the main technology for cancer diagnosis and treatment. Microfluidic systems are proving to be more sensitive and accurate for the detection of cancer biomarkers and therapeutic strategies than common assays. Microfluidic lab-on-a-chip platforms have shown remarkable potential in the designing of novel procedures for cancer detection, therapy, and disease follow-up as well as the development of new drug delivery systems for cancer treatment.

10.
Environ Res ; 215(Pt 3): 114347, 2022 12.
Artículo en Inglés | MEDLINE | ID: mdl-36116490

RESUMEN

Laminar-flow microfluidic microbial fuel cell (LMMFC) has attracted attention due to the advantage of the liquid-liquid interface between anolyte and catholyte without the use of membrane as a separator resulting in less fabrication cost. Unlike previous studies of LMMFC using syringe pumps, this study proposes the use of osmotic pumps to feed anolyte and catholyte in the microchannel without any additional power supply. The osmotic pump was constructed with two cylindrical chambers separated by a forward osmosis membrane, with the initial draw solution concentration of 90 g l-1 NaCl. We have, for the first time, demonstrated using the osmotic pumps to deliver both anolyte and catholyte and create co-laminar flow in LMMFC. Under the catholyte and anolyte flow rates of 18 ml/h and 40 ml/h respectively, LMMFC cultivated with Shewanella oneidensis produced the maximum power density of 87 mW m-2 and current density of 747 mA m-2 with the internal resistance of 1660 Ω. Further studies are warranted to develop osmotic pumps-fed LMMFC into a potential platform for portable biosensors.


Asunto(s)
Fuentes de Energía Bioeléctrica , Empleo , Microfluídica , Ósmosis , Cloruro de Sodio
11.
Sensors (Basel) ; 22(8)2022 Apr 14.
Artículo en Inglés | MEDLINE | ID: mdl-35459009

RESUMEN

For intelligence brakes in the electronic pneumatic brake system of commercial vehicles, the pressure change rate is used as the key control parameter and evaluation index. This can improve the brake safety, stability, and ride comfort of the vehicle. The real-time detection of the brake pressure change rate for commercial vehicles is the premise for realizing the accurate control of brake pressure change rate. Based on Poiseuille's law, an efficient measurement method of brake pressure change rate is proposed for commercial vehicles, and a new measuring device with an isothermal container and laminar flow resistance tube as the core components is designed. Through thermal insulation performance tests, flow resistance tests and measurement accuracy tests, combined with simulations, the effects of structural parameters and copper wire filling density on the performance of the isothermal container are analyzed, and these key parameters are optimized to improve the thermal insulation performance. A tubular laminar flow resistance tube composed of 304 stainless steel capillaries in parallel is designed. The influence mechanism of core parameters such as the number, radius, and length of laminar flow channels on its performance is studied, and the optimal parameter array is selected to optimize its performance. The experimental platform for measuring brake pressure change rate is constructed. By comparing the measurement curve of brake pressure change rate under simulation and experiment, the correctness and effectiveness of the pressure change rate measurement principle and the key components for electronically controlled pneumatic brakes of commercial vehicles are verified to meet engineering requirements.

12.
Environ Monit Assess ; 195(1): 15, 2022 Oct 22.
Artículo en Inglés | MEDLINE | ID: mdl-36271202

RESUMEN

Retrieval of glacier ice thickness is extremely important for monitoring water resources and predicting glacier dynamics and changes. The inter-annual glacier ice thickness observations (more than 5 years) exploit the glacier mass changes. Ice thickness is one of the important parameters to predict the future sea-level rise. Without adequate knowledge and precise information of glacier ice thickness distribution, future sea-level changes cannot be accurately assessed. In this study, we use an existing flow model to estimate the ice thickness of the High Mountain Asia (HMA) glaciers, using remote sensing techniques. The glacier ice velocity is one of the significant parameters in the Laminar flow model to retrieve the ice thickness. The glacier ice velocity is derived by utilizing the Differential SAR Interferometry (DInSAR) technique. The most optimum DInSAR data (ALOS-2/PALSAR-2) is used for estimating the ice velocity of the HMA glaciers. The ice thickness is mainly estimated for five different states in the HMA region, namely Himachal Pradesh, Uttarakhand, Sikkim, Bhutan, and Arunachal Pradesh. Most of the states are observed with a mean ice thickness of 100 m. Five benchmark glaciers (Samudra Tapu, Bara Shigri, Chhota Shigri, Sakchum, and Gangotri glaciers) are also selected for validating our results with the existing thickness information. The issues related to velocity-based ice thickness inversion are also emphasized in this study. The high-velocity rate due to the influx of melting water from adjacent glaciers causes an increment in the flow rate. This abnormal velocity derives erroneous ice thickness measurements. This is one of the major problems to be considered in the velocity-based thickness-derived procedures. Finally, the investigation suggests the inclusion of the velocity influencing parameters in the physical-based models for an accurate ice thickness inversion.

13.
Electrophoresis ; 42(11): 1229-1237, 2021 06.
Artículo en Inglés | MEDLINE | ID: mdl-33650106

RESUMEN

For their characterization and quality control, monoclonal antibodies are frequently analyzed at the bottom-up level to generate specific fingerprints that can be used to tackle post-translational modifications or ensure production consistency between lots. To circumvent time-consuming and labor-intensive off-line sample preparation steps, the implementation of integrated methodologies from sample preparation to separation and detection is highly valuable. In this perspective, capillary zone electrophoresis appears as a choice technique since the capillary can subsequently be used as a vessel for sample preparation and electrophoretic discrimination/detection of the reaction products. Here, a fast in-line methodology for the routine quality control of mAbs at the bottom-up level is reported. Simultaneous denaturation and reduction (pretreatment step) were conducted with RapiGest® surfactant and dithiothreitol before in-line tryptic digestion. Reactant mixing was realized by transverse diffusion of laminar flow profile under controlled temperature. In-line digestion was carried out with a resistant trypsin to autolysis. The main parameters affecting the digestion efficiency (trypsin concentration and incubation conditions) were optimized to generate mAb electrophoretic profiles free from trypsin interferences. An acidic MS-compatible BGE was used to obtain high resolution separation of released peptides and in-line surfactant cleavage. The whole methodology was performed in less than two hours with good repeatability of migration times (RSD = 0.91%, n = 5) and corrected peak areas (RSD = 9.6%, n = 5). CE-fingerprints were successfully established for different mAbs and an antibody-drug conjugate.


Asunto(s)
Anticuerpos Monoclonales , Anticuerpos Monoclonales/análisis , Electroforesis Capilar , Tensoactivos , Tripsina
14.
Chem Rec ; 21(9): 2164-2177, 2021 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-33734573

RESUMEN

Electrosynthesis and microflow synthesis have become essential tools in their own rights in modern organic synthesis. In this personal account, we summarize our works on the integrated use of these techniques, i. e., electrosynthesis in a flow microreactor. Our group has developed an electrochemical microflow system composed of a pair of electrodes that face each other to form a micrometer-scale gap for the flow path, through which solution passes in laminar flow. By the aid of laminar flow, unprecedented chemo- and electrochemical selectivity has been observed, which is not achievable with conventional batch-type electrochemical cells. In addition, we showcase various unique electrochemical systems and reactions achieved with the flow microreactor, including self-supported electrolysis, efficient paired electrolysis, in situ generation of active species and its flash use, the spaciotemporal control of electropolymerization, and combinatorial screening of the reaction conditions.

15.
Surgeon ; 19(5): e112-e116, 2021 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-33051110

RESUMEN

INTRODUCTION: Recent years have seen a large increase in the proportion and number of sling-assisted, implant-based breast reconstructions. These are associated with significant rates of loss of the reconstruction. Various methods have been suggested to reduce this loss rate. One such method is the use of operating theatres with laminar flow. The majority of cases of sling-assisted, implant-based breast reconstruction in south-east Scotland are performed in two adjacent theatres, one with laminar flow and one without. This provided the opportunity to assess whether there was any difference in outcome potentially attributable to laminar flow. METHODS: Patients undergoing sling-assisted, implant-based breast reconstruction between August 2013 and December 2018 were studied with follow up for at least 6 months. RESULTS: 307 patients underwent a total of 470 procedures. 247 procedures were performed with laminar flow and 223 without. There was no difference in the indications for mastectomy, incision used or rates of smoking or radiotherapy between the two groups. Implant loss occurred in 15.8% of procedures with laminar flow and 14.3% of those without (p = 0.66). Wound problems occurred in 27.5% of procedures with laminar flow and 27.8% of those without (p = 0.97). There was no significant difference in loss rates between surgeons, mastectomy indication, sling materials or with chemotherapy use. Increased loss rates were observed in smokers, with radiotherapy, with incisions other than transverse, with larger breasts and with increasing patient weight. CONCLUSION: This study finds no evidence of benefit for laminar flow in theatre for sling-assisted, implant-based breast reconstruction.


Asunto(s)
Implantes de Mama , Neoplasias de la Mama , Mamoplastia , Mama , Neoplasias de la Mama/cirugía , Femenino , Humanos , Mastectomía , Complicaciones Posoperatorias/epidemiología , Estudios Retrospectivos , Resultado del Tratamiento
16.
J Shoulder Elbow Surg ; 30(3): 580-586, 2021 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-32949760

RESUMEN

BACKGROUND: Although the rate of periprosthetic joint infection following shoulder arthroplasty is low, it is a morbid and costly complication. Airborne particulates have long been recognized as a potential source of wound contamination, and operating room-mounted and smaller localized laminar airflow devices have been developed to minimize airborne particulates. This randomized controlled trial evaluated the effectiveness of a localized laminar flow device in reducing the intrusion of ambient airborne particles and bacteria into the surgery site during shoulder arthroplasty as measured by overall particle counts and colony-forming units (CFUs). METHODS: Patients undergoing primary anatomic or reverse shoulder arthroplasty were eligible for participation. After providing informed consent, patients were randomly assigned to the Air Barrier System (ABS) group or control group. For all patients, the ABS was placed on the surgical field; however, it was only turned on by the technician for those randomized to the ABS. Study participants, surgeons, and surgical staff were blinded to group assignment. Bacterial CFUs were collected from within 5 cm of the surgical wound every 10 minutes, whereas airborne particulates were collected every minute. Poisson regression models were used to determine whether differences existed in CFUs and particulate counts between the ABS and control groups. RESULTS: A total of 43 patients were randomized into the ABS (n = 21) or control (n = 22) group. Surgical time (P = .53) and the average staff count (P = .16) in the operating room did not differ between groups. Poisson regression showed that the ABS group had significantly lower CFUs (ß = -0.583, P < .001) along with surgical time and particulates with a diameter ≥ 5 µm. Staff count and particulates with a diameter < 5 µm were not significant predictors of CFUs. Infection was not a primary outcome; however, no postoperative infections have been reported in either study group with a minimum of 1-year follow-up for all patients. DISCUSSION: This double-blinded, randomized trial demonstrated that a localized laminar flow device dramatically reduced the count of CFUs in the air directly above the wound and beneath the ABS (adjusted for the number of operating room personnel and surgical time). The use of the device was not associated with a longer case duration; however, some additional setup time was required prior to surgical incision to place the device. Further study is required to determine the clinical implications of this finding-specifically, whether such devices result in lower rates of periprosthetic joint infection after shoulder arthroplasty.


Asunto(s)
Artroplastía de Reemplazo de Hombro , Microbiología del Aire , Artroplastia , Artroplastía de Reemplazo de Hombro/efectos adversos , Humanos , Quirófanos , Infección de la Herida Quirúrgica/etiología , Infección de la Herida Quirúrgica/prevención & control
17.
Eur Heart J ; 40(30): 2523-2533, 2019 08 07.
Artículo en Inglés | MEDLINE | ID: mdl-31222221

RESUMEN

AIMS: To assess the functional relevance and therapeutic potential of the pro-angiogenic long non-coding RNA MANTIS in vascular disease development. METHODS AND RESULTS: RNA sequencing, CRISPR activation, overexpression, and RNAi demonstrated that MANTIS, especially its Alu-element, limits endothelial ICAM-1 expression in different types of endothelial cells. Loss of MANTIS increased endothelial monocyte adhesion in an ICAM-1-dependent manner. MANTIS reduced the binding of the SWI/SNF chromatin remodelling factor BRG1 at the ICAM-1 promoter. The expression of MANTIS was induced by laminar flow and HMG-CoA-reductase inhibitors (statins) through mechanisms involving epigenetic rearrangements and the transcription factors KLF2 and KLF4. Mutation of the KLF binding motifs in the MANTIS promoter blocked the flow-induced MANTIS expression. Importantly, the expression of MANTIS in human carotid artery endarterectomy material was lower compared with healthy vessels and this effect was prevented by statin therapy. Interestingly, the protective effects of statins were mediated in part through MANTIS, which was required to facilitate the atorvastatin-induced changes in endothelial gene expression. Moreover, the beneficial endothelial effects of statins in culture models (spheroid outgrowth, proliferation, telomerase activity, and vascular organ culture) were lost upon knockdown of MANTIS. CONCLUSION: MANTIS is tightly regulated by the transcription factors KLF2 and KLF4 and limits the ICAM-1 mediated monocyte adhesion to endothelial cells and thus potentially atherosclerosis development in humans. The beneficial effects of statin treatment and laminar flow are dependent on MANTIS.


Asunto(s)
Velocidad del Flujo Sanguíneo/fisiología , Inhibidores de Hidroximetilglutaril-CoA Reductasas/farmacología , Factores de Transcripción de Tipo Kruppel/metabolismo , ARN Largo no Codificante/metabolismo , Inductores de la Angiogénesis/metabolismo , Estenosis Carotídea/metabolismo , Adhesión Celular/efectos de los fármacos , Adhesión Celular/fisiología , Células Cultivadas , Células Endoteliales de la Vena Umbilical Humana , Humanos , Molécula 1 de Adhesión Intercelular/metabolismo , Factor 4 Similar a Kruppel
18.
Sensors (Basel) ; 20(7)2020 Apr 10.
Artículo en Inglés | MEDLINE | ID: mdl-32290329

RESUMEN

The actual fluid form of an electrolyte in a molecular electronic converter is an important factor that causes a decrease in the accuracy of a molecular electronic transducer (MET) liquid motion sensor. To study the actual fluid morphology of an inertial electrolyte in molecular electron transducers, an inlet effect is defined according to the fluid morphology of turbulent-laminar flow, and a numerical simulation model of turbulent-laminar flow is proposed. Based on the turbulent-laminar flow model, this paper studies the variation of the inlet effect intensity when the thickness of the outermost insulating layer is 50 µm and 100 µm, respectively. Meanwhile, the changes of the inlet effect intensity and the error rate of central axial velocity field are also analyzed when the input signal intensity is different. Through the numerical experiment, it verifies that the thickness of the outermost insulating layer and the amplitude of the input signal are two important factors which can affect the inlet effect intensity and also the accuracy of the MET. Therefore, this study can provide a theoretical basis for the quantitative study on the performance optimization of a MET liquid sensor.

19.
Int J Mol Sci ; 21(22)2020 Nov 20.
Artículo en Inglés | MEDLINE | ID: mdl-33233811

RESUMEN

Calciprotein particles (CPPs), which increasingly arise in the circulation during the disorders of mineral homeostasis, represent a double-edged sword protecting the human organism from extraskeletal calcification but potentially causing endothelial dysfunction. Existing models, however, failed to demonstrate the detrimental action of CPPs on endothelial cells (ECs) under flow. Here, we applied a flow culture system, where human arterial ECs were co-incubated with CPPs for 4 h, and a normolipidemic and normotensive rat model (10 daily intravenous injections of CPPs) to simulate the scenario occurring in vivo in the absence of confounding cardiovascular risk factors. Pathogenic effects of CPPs were investigated by RT-qPCR and Western blotting profiling of the endothelial lysate. CPPs were internalised within 1 h of circulation, inducing adhesion of peripheral blood mononuclear cells to ECs. Molecular profiling revealed that CPPs stimulated the expression of pro-inflammatory cell adhesion molecules VCAM1 and ICAM1 and upregulated transcription factors of endothelial-to-mesenchymal transition (Snail, Slug and Twist1). Furthermore, exposure to CPPs reduced the production of atheroprotective transcription factors KLF2 and KLF4 and led to YAP1 hypophosphorylation, potentially disturbing the mechanisms responsible for the proper endothelial mechanotransduction. Taken together, our results suggest the ability of CPPs to initiate endothelial dysfunction at physiological flow conditions.


Asunto(s)
Nanopartículas Calcificantes/efectos adversos , Células Endoteliales/patología , Mecanotransducción Celular , Animales , Calcio/química , Células Cultivadas , Humanos , Factor 4 Similar a Kruppel , Masculino , Ratas , Ratas Wistar , Estrés Mecánico , Enfermedades Vasculares/metabolismo
20.
J Med Ultrasound ; 28(4): 219-224, 2020.
Artículo en Inglés | MEDLINE | ID: mdl-33659160

RESUMEN

BACKGROUND: Doppler technique is a technology that can raise the predictive, diagnostic, and monitoring abilities in blood flow and suitable for researchers. The application depends on Doppler shift (shift frequencies), wherein the movement of red blood cells away from the probe is determined by the decrease or increase in the ultrasound (US) frequency. METHODS: In this experiment, the clinical US (Hitachi Avious [HI] model) system was used as a primary instrument for data acquisition and test the compatibility, efficacy, and validation of artificial blood (blood-mimicking fluid [BMF]) by color- and motion-mode. This BMF was prepared for use in the Doppler flow phantom. RESULTS: The motion of BMF through the vessel-mimicking material (VMM) was parallel and the flow was laminar and in the straight form (regular flow of BMF inside the VMM). Moreover, the scale of color velocity in the normal range at that flow rate was in the normal range. CONCLUSION: The new BMF that is being valid and effective in utilizing for US in vitro research applications. In addition, the clinical US ([HI] model) system can be used as a suitable instrument for data acquisition and test the compatibility, efficacy, and validation at in vitro applications (BMF, flow phantom components).

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