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1.
Porcine Health Manag ; 10(1): 9, 2024 Feb 16.
Artículo en Inglés | MEDLINE | ID: mdl-38365750

RESUMEN

BACKGROUND: Our previous study confirmed that large litter size adversely affects prepartum maternal hormones and behaviour, concurrently with heightened oxidative stress in primiparous sows. The purpose of this study was to examine the effect of large litter size on litter performance, postpartum maternal behaviour, salivary cortisol levels, and colostral immunoglobulin levels in sows, as well as investigate their correlations with the levels of oxidative stress parameters. RESULTS: A total of 24 primiparous sows (Landrace[Formula: see text]Large white) and their offspring were categorised into two groups based on litter size: NORMAL (n = 8) with litter size ranging from 7 to 14 (mean 11.5[Formula: see text]2.7), and LARGE (n=16) with litter size ranging from 15 to 20 (mean 15.9[Formula: see text]1.4). All sows were housed in a group housing system during gestation and transitioned to an adaptable loose housing system (2.4[Formula: see text]2.3 m) during the farrowing and lactation periods. The nursing and carefulness behaviour of the sows was monitored over a 24-h period between 72 and 96 h after parturition. Saliva samples were collected for cortisol assay on 35, 21, and 7 days before parturition (D-35, D-21, and D-7, respectively), as well as on days 1, 7, and 28 after parturition (D1, D7, and D28, respectively). On D1, higher piglet mortality rates were observed among the LARGE group compared to the NORMAL group (p<0.01). The total and successful nursing behaviours of the sows were less frequent in the LARGE group than in the NORMAL group (p<0.05, for both), and the carefulness score of the LARGE group was also lower than that of the NORMAL group (p< 0.01). On D1, cortisol levels in LARGE sows were higher than those in NORMAL sows (p< 0.05), and for other time points (D-21, D-7, D7, and D28), cortisol levels in LARGE sows tended to be higher than those in NORMAL sows (p < 0.10, for all). Successful nursing behaviour displayed negative correlations with levels of salivary cortisol and certain oxidative stress parameters measured on D1. CONCLUSIONS: These findings suggest that the strategy for alleviating physiological and oxidative stress during the peripartum periods could benefit potential postpartum maternal behaviour and litter performance in the sows with large litters.

2.
Antioxidants (Basel) ; 13(2)2024 Feb 07.
Artículo en Inglés | MEDLINE | ID: mdl-38397808

RESUMEN

Hyperprolific sows often experience increased oxidative stress during late gestation and lactation periods, which can adversely affect the farrowing process and overall lactation performance. This study examines the influence of providing a coconut coir mat (CCM; 1 × 1 m) as nesting material, supplementing high-dose vit-C (HVC; 20% vit-C, 10 g/kg feed) as an antioxidant, or both on maternal behavior, the farrowing process, oxidative status, cortisol levels, and preovulatory follicle developments in sows with large litters. In total, 35 sows (Landrace × Yorkshire; litter size 15.43 ± 0.27) were allocated to the following four treatment groups: control (n = 9, basal diet), vit-C (n = 8, basal diet + HVC), mat (n = 10, basal diet + CCM), and mat + vit-C (n = 8, basal diet + HVC + CCM). A post-hoc analysis showed that compared with sows that were not provided CCM, mat and mat + vit-C groups demonstrated increased durations of nest-building behavior during the period from 24 h to 12 h before parturition (p < 0.05 for both), reduced farrowing durations, and decreased intervals from birth to first udder contact (p < 0.01 for both). The mat group exhibited lower advanced oxidation protein product (AOPP) levels during late gestation and lactation periods than the control group (p < 0.05). Sows with HVC supplementation showed longer farrowing durations than those without HVC supplementation (p < 0.0001). The vit-C group had higher salivary cortisol levels on day 1 after farrowing than the other treatment groups (p < 0.05). Furthermore, the follicle diameters on day 3 after weaning in the vit-C group tended to be smaller than those in the control group (p = 0.077). HVC supplementation prolonged farrowing and increased the physiological stress on postpartum, and no advantageous effects on maternal behavior and developmental progression of preovulatory follicles were observed. Hence, alternative solutions beyond nutritional approaches are required to address increased oxidative stress in hyperprolific sows and secure their welfare and reproductive performance. The present results substantiated the positive impact of providing CCM as nesting material for sows with large litters on nest-building behavior and the farrowing process, which could mitigate the deleterious consequences induced by peripartum physiological and oxidative stress.

3.
Dalton Trans ; 53(7): 2922-2928, 2024 Feb 13.
Artículo en Inglés | MEDLINE | ID: mdl-38284239

RESUMEN

The viscoelastic damping of nanocomposites reinforced with BNNTs and CNTs was compared. MD simulations revealed that the interfacial damping of pristine-CNT was superior to that of pristine-BNNT. The contrasting effects of structural defects were elucidated using interfacial adhesion, interphase, and overlapping phonon density of states in the nanotubes and polymers.

4.
Korean J Orthod ; 54(1): 48-58, 2024 Jan 25.
Artículo en Inglés | MEDLINE | ID: mdl-38072448

RESUMEN

Objective: : To quantify the effects of midline-related landmark identification on midline deviation measurements in posteroanterior (PA) cephalograms using a cascaded convolutional neural network (CNN). Methods: : A total of 2,903 PA cephalogram images obtained from 9 university hospitals were divided into training, internal validation, and test sets (n = 2,150, 376, and 377). As the gold standard, 2 orthodontic professors marked the bilateral landmarks, including the frontozygomatic suture point and latero-orbitale (LO), and the midline landmarks, including the crista galli, anterior nasal spine (ANS), upper dental midpoint (UDM), lower dental midpoint (LDM), and menton (Me). For the test, Examiner-1 and Examiner-2 (3-year and 1-year orthodontic residents) and the Cascaded-CNN models marked the landmarks. After point-to-point errors of landmark identification, the successful detection rate (SDR) and distance and direction of the midline landmark deviation from the midsagittal line (ANS-mid, UDM-mid, LDM-mid, and Me-mid) were measured, and statistical analysis was performed. Results: : The cascaded-CNN algorithm showed a clinically acceptable level of point-to-point error (1.26 mm vs. 1.57 mm in Examiner-1 and 1.75 mm in Examiner-2). The average SDR within the 2 mm range was 83.2%, with high accuracy at the LO (right, 96.9%; left, 97.1%), and UDM (96.9%). The absolute measurement errors were less than 1 mm for ANS-mid, UDM-mid, and LDM-mid compared with the gold standard. Conclusions: : The cascaded-CNN model may be considered an effective tool for the auto-identification of midline landmarks and quantification of midline deviation in PA cephalograms of adult patients, regardless of variations in the image acquisition method.

5.
Arch Pharm Res ; 47(1): 20-39, 2024 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-38151648

RESUMEN

Ocular diseases are a growing global concern and have a significant impact on the quality of life. Cataracts, glaucoma, age-related macular degeneration, and diabetic retinopathy are the most prevalent ocular diseases. Their prevalence and the global market size are also increasing. However, the available pharmacotherapy is currently limited. These diseases share common pathophysiological features, including neovascularization, inflammation, and/or neurodegeneration. Histone deacetylases (HDACs) are a class of enzymes that catalyze the removal of acetyl groups from lysine residues of histone and nonhistone proteins. HDACs are crucial for regulating various cellular processes, such as gene expression, protein stability, localization, and function. They have also been studied in various research fields, including cancer, inflammatory diseases, neurological disorders, and vascular diseases. Our study aimed to investigate the relationship between HDACs and ocular diseases, to identify a new strategy for pharmacotherapy. This review article explores the role of HDACs in ocular diseases, specifically focusing on diabetic retinopathy, age-related macular degeneration, and retinopathy of prematurity, as well as optic nerve disorders, such as glaucoma and optic neuropathy. Additionally, we explore the interplay between HDACs and key regulators of fibrosis and angiogenesis, such as TGF-ß and VEGF, highlighting the potential of targeting HDAC as novel therapeutic strategies for ocular diseases.


Asunto(s)
Retinopatía Diabética , Glaucoma , Degeneración Macular , Recién Nacido , Humanos , Retinopatía Diabética/tratamiento farmacológico , Histona Desacetilasas/metabolismo , Calidad de Vida , Glaucoma/tratamiento farmacológico , Inhibidores de Histona Desacetilasas/farmacología , Inhibidores de Histona Desacetilasas/uso terapéutico , Inhibidores de Histona Desacetilasas/química
6.
Comput Methods Programs Biomed ; 242: 107853, 2023 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-37857025

RESUMEN

BACKGROUND AND OBJECTIVE: Despite recent development of AI, prediction of the surgical movement in the maxilla and mandible by OGS might be more difficult than that of tooth movement by orthodontic treatment. To evaluate the prediction accuracy of the surgical movement using pairs of pre-(T0) and post-surgical (T1) lateral cephalograms (lat-ceph) of orthognathic surgery (OGS) patients and dual embedding module-graph convolution neural network (DEM-GCNN) model. METHODS: 599 pairs from 3 institutions were used as training, internal validation, and internal test sets and 201 pairs from other 6 institutions were used as external test set. DEM-GCNN model (IEM, learning the lat-ceph images; LTEM, learning the landmarks) was developed to predict the amount and direction of surgical movement of ANS and PNS in the maxilla and B-point and Md1crown in the mandible. The distance between T1 landmark coordinates actually moved by OGS (ground truth) and predicted by DEM-GCNN model and pre-existed CNN-based Model-C (learning the lat-ceph images) was compared. RESULTS: In both internal and external tests, DEM-GCNN did not exhibit significant difference from ground truth in all landmarks (ANS, PNS, B-point, Md1crown, all P > 0.05). When the accumulated successful detection rate for each landmark was compared, DEM-GCNN showed higher values than Model-C in both the internal and external tests. In violin plots exhibiting the error distribution of the prediction results, both internal and external tests showed that DEM-GCNN had significant performance improvement in PNS, ANS, B-point, Md1crown than Model-C. DEM-GCNN showed significantly lower prediction error values than Model-C (one-jaw surgery, B-point, Md1crown, all P < 0.005; two-jaw surgery, PNS, ANS, all P < 0.05; B point, Md1crown, all P < 0.005). CONCLUSION: We developed a robust OGS planning model with maximized generalizability despite diverse qualities of lat-cephs from 9 institutions.


Asunto(s)
Mandíbula , Procedimientos Quirúrgicos Ortognáticos , Humanos , Cefalometría/métodos , Mandíbula/diagnóstico por imagen , Mandíbula/cirugía , Procedimientos Quirúrgicos Ortognáticos/métodos , Maxilar/diagnóstico por imagen , Maxilar/cirugía
7.
Med Image Anal ; 89: 102894, 2023 10.
Artículo en Inglés | MEDLINE | ID: mdl-37562256

RESUMEN

A major responsibility of radiologists in routine clinical practice is to read follow-up chest radiographs (CXRs) to identify changes in a patient's condition. Diagnosing meaningful changes in follow-up CXRs is challenging because radiologists must differentiate disease changes from natural or benign variations. Here, we suggest using a multi-task Siamese convolutional vision transformer (MuSiC-ViT) with an anatomy-matching module (AMM) to mimic the radiologist's cognitive process for differentiating baseline change from no-change. MuSiC-ViT uses the convolutional neural networks (CNNs) meet vision transformers model that combines CNN and transformer architecture. It has three major components: a Siamese network architecture, an AMM, and multi-task learning. Because the input is a pair of CXRs, a Siamese network was adopted for the encoder. The AMM is an attention module that focuses on related regions in the CXR pairs. To mimic a radiologist's cognitive process, MuSiC-ViT was trained using multi-task learning, normal/abnormal and change/no-change classification, and anatomy-matching. Among 406 K CXRs studied, 88 K change and 115 K no-change pairs were acquired for the training dataset. The internal validation dataset consisted of 1,620 pairs. To demonstrate the robustness of MuSiC-ViT, we verified the results with two other validation datasets. MuSiC-ViT respectively achieved accuracies and area under the receiver operating characteristic curves of 0.728 and 0.797 on the internal validation dataset, 0.614 and 0.784 on the first external validation dataset, and 0.745 and 0.858 on a second temporally separated validation dataset. All code is available at https://github.com/chokyungjin/MuSiC-ViT.


Asunto(s)
Música , Humanos , Estudios de Seguimiento , Aprendizaje , Redes Neurales de la Computación , Curva ROC
8.
Artículo en Inglés | MEDLINE | ID: mdl-37402199

RESUMEN

Reidentification (Re-id) of vehicles in a multicamera system is an essential process for traffic control automation. Previously, there have been efforts to reidentify vehicles based on shots of images with identity (id) labels, where the model training relies on the quality and quantity of the labels. However, labeling vehicle ids is a labor-intensive procedure. Instead of relying on expensive labels, we propose to exploit camera and tracklet ids that are automatically obtainable during a Re-id dataset construction. In this article, we present weakly supervised contrastive learning (WSCL) and domain adaptation (DA) techniques using camera and tracklet ids for unsupervised vehicle Re-id. We define each camera id as a subdomain and tracklet id as a label of a vehicle within each subdomain, i.e., weak label in the Re-id scenario. Within each subdomain, contrastive learning using tracklet ids is applied to learn a representation of vehicles. Then, DA is performed to match vehicle ids across the subdomains. We demonstrate the effectiveness of our method for unsupervised vehicle Re-id using various benchmarks. Experimental results show that the proposed method outperforms the recent state-of-the-art unsupervised Re-id methods. The source code is publicly available on https://github.com/andreYoo/WSCL_VeReid.

9.
PLoS One ; 18(6): e0287512, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-37379287

RESUMEN

The prevalence of dysphagia is increasing, resulting in socioeconomic burden, but previous reports have only been based on a limited populations. Therefore, we aimed to investigate the nationwide incidence and prevalence of dysphagia requiring medical attention to provide adequate information for healthcare planning and resource allocation. In this nationwide retrospective cohort study, the data of adults aged ≥20 years recorded from 2006 to 2016 were sourced from the Korean National Health Insurance Service database. Medical claim codes based on ICD-10-CM were used to define dysphagia and possible causes. The annual incidence and prevalence of dysphagia were calculated. Cox regression was used to estimate dysphagia risk in people with possible dysphagia etiology. Survival analysis was performed to estimate the mortality and hazard ratio of dysphagia. The crude annual incidence of dysphagia increased continuously from 7.14 in 2006 to 15.64 in 2016. The crude annual prevalence of dysphagia in 2006 was 0.09% and increased annually to 0.25% in 2016. Stroke (odds ratio [OR]: 7.86, 95% confidence interval [CI]: 5.76-6.68), neurodegenerative disease (OR: 6.20, 95% CI: 5.76-6.68), cancer (OR: 5.59, 95% CI: 5.17-6.06), and chronic obstructive pulmonary disease (OR: 2.94, 95% CI: 2.71-3.18) were associated with a high risk of dysphagia. The mortality in the dysphagia group was 3.12 times higher than that in the non-dysphagia group (hazard ratio: 3.12, 95% CI: 3.03-3.23). The incidence and prevalence of dysphagia requiring medical attention are increasing annually. The increasing trend was conspicuous in the geriatric population. The presence of stroke, neurodegenerative disease, cancer, and chronic obstructive pulmonary disease is associated with a high risk of dysphagia. Therefore, adequate screening, diagnosis, and management of dysphagia in the older population must be emphasized in geriatric healthcare.


Asunto(s)
Trastornos de Deglución , Neoplasias , Enfermedades Neurodegenerativas , Enfermedad Pulmonar Obstructiva Crónica , Accidente Cerebrovascular , Adulto , Humanos , Anciano , Incidencia , Prevalencia , Estudios Retrospectivos , Trastornos de Deglución/epidemiología , República de Corea/epidemiología
10.
J Craniomaxillofac Surg ; 51(5): 265-271, 2023 May.
Artículo en Inglés | MEDLINE | ID: mdl-37353406

RESUMEN

This study aimed to investigate the difference in facial reanimation surgery using functional gracilis muscle transfer between the masseteric nerve alone and its combined use with cross face nerve graft (CFNG), which has not been explored before. A novel analysis method based on artificial intelligence (AI) was employed to compare the outcomes of the two approaches. Using AI, 3-dimensional facial landmarks were extracted from 2-dimensional photographs, and distance and angular symmetry scores were calculated. The patients were divided into two groups, with Group 1 undergoing one-stage CFNG and masseteric nerve dual innervation, and Group 2 receiving only masseteric nerve. The symmetry scores were obtained before and 1 year after surgery to assess the degree of change. Of the 35 patients, Group 1 included 13 patients, and Group 2 included 22 patients. The analysis revealed that, in the resting state, the change in the symmetry score of the mouth corner showed distance symmetry (2.55 ± 2.94, 0.52 ± 2.75 for Group 1 and Group 2, respectively, p = 0.048) and angle symmetry (1.21 ± 1.43, 0.02 ± 0.22 for Group 1 and Group 2, respectively, p = 0.001), which were significantly improved in Group 1, indicating a more symmetric pattern after surgery. In the smile state, only the angle symmetry was improved more symmetrically in Group 1 (3.20 ± 2.38, 1.49 ± 2.22 for Group 1 and Group 2, respectively, p = 0.041). Within the limitations of the study it seems that this new analysis method enabled a more accurate numerical symmetry score to be obtained, and while the degree of mouth corner excursion was sufficient with only the masseteric nerve, accompanying CFNG led to further improvement in symmetry in the resting state.


Asunto(s)
Parálisis Facial , Transferencia de Nervios , Humanos , Parálisis Facial/cirugía , Estudios Retrospectivos , Inteligencia Artificial , Transferencia de Nervios/métodos , Sonrisa/fisiología , Nervio Facial/cirugía
11.
Artículo en Inglés | MEDLINE | ID: mdl-37159323

RESUMEN

Most deep anomaly detection models are based on learning normality from datasets due to the difficulty of defining abnormality by its diverse and inconsistent nature. Therefore, it has been a common practice to learn normality under the assumption that anomalous data are absent in a training dataset, which we call normality assumption. However, in practice, the normality assumption is often violated due to the nature of real data distributions that includes anomalous tails, i.e., a contaminated dataset. Thereby, the gap between the assumption and actual training data affects detrimentally in learning of an anomaly detection model. In this work, we propose a learning framework to reduce this gap and achieve better normality representation. Our key idea is to identify sample-wise normality and utilize it as an importance weight, which is updated iteratively during the training. Our framework is designed to be model-agnostic and hyperparameter insensitive so that it applies to a wide range of existing methods without careful parameter tuning. We apply our framework to three different representative approaches of deep anomaly detection that are classified into one-class classification-, probabilistic model-, and reconstruction-based approaches. In addition, we address the importance of a termination condition for iterative methods and propose a termination criterion inspired by the anomaly detection objective. We validate that our framework improves the robustness of the anomaly detection models under different levels of contamination ratios on five anomaly detection benchmark datasets and two image datasets. On various contaminated datasets, our framework improves the performance of three representative anomaly detection methods, measured by area under the ROC curve.

12.
J Pathol Transl Med ; 57(2): 113-122, 2023 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-36950813

RESUMEN

BACKGROUND: Gallbladder cancer (GBC) is usually detected in advanced stages with a low 5-year survival rate. Delta-like ligand 4 (DLL4), vascular endothelial growth factor (VEGF), and hypoxia-inducible factor-2alpha (HIF2α) have been studied for their role in tumorigenesis and potential for therapeutic target, and multiple clinical trials of the agents targeting them are ongoing. We investigated the expression of these markers in surgically resected GBC and tried to reveal their association with the clinicopathologic features, mutual correlation of their expression, and prognosis of the GBC patients by their expression. METHODS: We constructed the tissue microarray blocks of 99 surgically resected GBC specimens and performed immunohistochemistry of DLL4, VEGF, and HIF2α. We used the quantitative digital image analysis to evaluate DLL4 and VEGF expression, while the expression of HIF2α was scored manually. RESULTS: The expression of VEGF and HIF2α showed a significant trend with tumor differentiation (p= .028 and p= .006, respectively). We found that the high DLL4 and VEGF expression were significantly correlated with lymph node metastasis (p= .047, both). The expression of VEGF and HIF2α were significantly correlated (p < .001). The GBC patients with low HIF2α expression showed shorter recurrence-free survival than those with high HIF2α expression. CONCLUSIONS: This study suggested the possibility of the usage of DLL4 and VEGF to predict the lymph node metastasis and the possibility of VEGF and HIF2α to predict the expression level mutually. Further studies may be needed to validate our study results and eventually accelerate the introduction of the targeted therapy in GBC.

13.
Sensors (Basel) ; 22(17)2022 Sep 02.
Artículo en Inglés | MEDLINE | ID: mdl-36081094

RESUMEN

Treatment of facial palsy is essential because neglecting this disorder can lead to serious sequelae and further damage. For an objective evaluation and consistent rehabilitation training program of facial palsy patients, a clinician's evaluation must be simultaneously performed alongside quantitative evaluation. Recent research has evaluated facial palsy using 68 facial landmarks as features. However, facial palsy has numerous features, whereas existing studies use relatively few landmarks; moreover, they do not confirm the degree of improvement in the patient. In addition, as the face of a normal person is not perfectly symmetrical, it must be compared with previous images taken at a different time. Therefore, we introduce three methods to numerically approach measuring the degree of facial palsy after extracting 478 3D facial landmarks from 2D RGB images taken at different times. The proposed numerical approach performs registration to compare the same facial palsy patients at different times. We scale landmarks by performing scale matching before global registration. After scale matching, coarse registration is performed with global registration. Point-to-plane ICP is performed using the transformation matrix obtained from global registration as the initial matrix. After registration, the distance symmetry, angular symmetry, and amount of landmark movement are calculated for the left and right sides of the face. The degree of facial palsy at a certain point in time can be approached numerically and can be compared with the degree of palsy at other times. For the same facial expressions, the degree of facial palsy at different times can be measured through distance and angle symmetry. For different facial expressions, the simultaneous degree of facial palsy in the left and right sides can be compared through the amount of landmark movement. Through experiments, the proposed method was tested using the facial palsy patient database at different times. The experiments involved clinicians and confirmed that using the proposed numerical approach can help assess the progression of facial palsy.


Asunto(s)
Parálisis Facial , Bases de Datos Factuales , Humanos , Imagenología Tridimensional/métodos , Movimiento
14.
Comput Biol Med ; 148: 105914, 2022 09.
Artículo en Inglés | MEDLINE | ID: mdl-35961089

RESUMEN

Landmark detection in flatfoot radiographs is crucial in analyzing foot deformity. Here, we evaluated the accuracy and efficiency of the automated identification of flatfoot landmarks using a newly developed cascade convolutional neural network (CNN) algorithm, Flatfoot Landmarks AnnoTating Network (FlatNet). A total of 1200 consecutive weight-bearing lateral radiographs of the foot were acquired. The first 1050 radiographs were used as the training and tuning, and the following 150 radiographs were used as the test sets, respectively. An expert orthopedic surgeon (A) manually labeled ground truths for twenty-five anatomical landmarks. Two orthopedic surgeons (A and B, each with eight years of clinical experience) and a general physician (GP) independently identified the landmarks of the test sets using the same method. After two weeks, observers B and GP independently identified the landmarks once again using the developed deep learning CNN model (DLm). The X- and Y-coordinates and the mean absolute distance were evaluated. The average differences (mm) from the ground truth were 0.60 ± 0.57, 1.37 ± 1.28, and 1.05 ± 1.23 for the X-coordinate, and 0.46 ± 0.59, 0.97 ± 0.98, and 0.73 ± 0.90 for the Y-coordinate in DLm, B, and GP, respectively. The average differences (mm) from the ground truth were 0.84 ± 0.73, 1.90 ± 1.34, and 1.42 ± 1.40 for the absolute distance in DLm, B, and GP, respectively. Under the guidance of the DLm, the overall differences (mm) from the ground truth were enhanced to 0.87 ± 1.21, 0.69 ± 0.74, and 1.24 ± 1.31 for the X-coordinate, Y-coordinate, and absolute distance, respectively, for observer B. The differences were also enhanced to 0.74 ± 0.73, 0.57 ± 0.63, and 1.04 ± 0.85 for observer GP. The newly developed FlatNet exhibited better accuracy and reliability than the observers. Furthermore, under the FlatNet guidance, the accuracy and reliability of the human observers generally improved.


Asunto(s)
Pie Plano , Pie , Humanos , Redes Neurales de la Computación , Reproducibilidad de los Resultados , Soporte de Peso
15.
J Extracell Vesicles ; 11(1): e12179, 2022 01.
Artículo en Inglés | MEDLINE | ID: mdl-34982509

RESUMEN

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) entry is mediated by the interaction of the viral spike (S) protein with angiotensin-converting enzyme 2 (ACE2) on the host cell surface. Although a clinical trial testing soluble ACE2 (sACE2) for COVID-19 is currently ongoing, our understanding of the delivery of sACE2 via small extracellular vesicles (sEVs) is still rudimentary. With excellent biocompatibility allowing for the effective delivery of molecular cargos, sEVs are broadly studied as nanoscale protein carriers. In order to exploit the potential of sEVs, we design truncated CD9 scaffolds to display sACE2 on the sEV surface as a decoy receptor for the S protein of SARS-CoV-2. Moreover, to enhance the sACE2-S binding interaction, we employ sACE2 variants. sACE2-loaded sEVs exhibit typical sEVs characteristics and bind to the S protein. Furthermore, engineered sEVs inhibit the entry of wild-type (WT), the globally dominant D614G variant, Beta (K417N-E484K-N501Y) variant, and Delta (L452R-T478K-D614G) variant SARS-CoV-2 pseudovirus, and protect against authentic SARS-CoV-2 and Delta variant infection. Of note, sACE2 variants harbouring sEVs show superior antiviral efficacy than WT sACE2 loaded sEVs. Therapeutic efficacy of the engineered sEVs against SARS-CoV-2 challenge was confirmed using K18-hACE2 mice. The current findings provide opportunities for the development of new sEVs-based antiviral therapeutics.


Asunto(s)
Enzima Convertidora de Angiotensina 2/inmunología , COVID-19/inmunología , Vesículas Extracelulares/inmunología , Glicoproteína de la Espiga del Coronavirus/inmunología , Animales , Femenino , Células HEK293 , Humanos , Ratones , Unión Proteica , Dominios y Motivos de Interacción de Proteínas
16.
Anticancer Res ; 41(11): 5489-5498, 2021 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-34732419

RESUMEN

BACKGROUND/AIM: Pressurized intraperitoneal aerosol chemotherapy (PIPAC) is known to show uneven distribution and penetration of agents based on the nozzle position. Thus, this study aimed to investigate the ideal nozzle position for maximizing drug delivery during PIPAC. MATERIALS AND METHODS: We created 2 cm-, 4 cm- and 8 cm-ex vivo models according to the distance from the bottom to the nozzle using 21×15×16 cm-sized sealable plastic boxes. After each set of eight normal peritoneal tissues from swine were placed at eight different points (A to H), we performed PIPAC, compared the methylene blue staining areas to investigate the distribution, and estimated the depth of concentrated diffusion (DCD) and the depth of maximal diffusion (DMD) of doxorubicin. RESULTS: In terms of distribution, the 4 cm- and 8 cm-ex vivo models showed more stained faces than the 2 cm-ex vivo model. Regarding the penetration depth, the 4 cm- ex vivo model showed the highest DCD (mean; 244.1 µm, C; 105.1 µm, D; 80.9 µm, E; 250.2 µm, G; 250.2 µm, H) and DMD (mean; 174.8 µm, D; 162.7 µm, E; 511.7 µm, F; 522.2 µm, G; 528.1 µm, H) in the most points corresponding to 62.5%. CONCLUSION: The ideal nozzle position during PIPAC might be halfway between the nozzle inlet and the bottom in the ex vivo model.


Asunto(s)
Antibióticos Antineoplásicos/administración & dosificación , Antineoplásicos/administración & dosificación , Doxorrubicina/administración & dosificación , Sistemas de Liberación de Medicamentos/instrumentación , Neoplasias Peritoneales/tratamiento farmacológico , Peritoneo/metabolismo , Aerosoles , Animales , Antibióticos Antineoplásicos/metabolismo , Antineoplásicos/metabolismo , Difusión , Doxorrubicina/metabolismo , Diseño de Equipo , Presión , Sus scrofa , Distribución Tisular
17.
Front Plant Sci ; 12: 693854, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-34489997

RESUMEN

Dietary supplements of anthocyanin-rich vegetables have been known to increase potential health benefits for humans. The optimization of environmental conditions to increase the level of anthocyanin accumulations in vegetables during the cultivation periods is particularly important in terms of the improvement of agricultural values in the indoor farm using artificial light and climate controlling systems. This study reports on the measurement of variations in anthocyanin accumulations in leaf tissues of four different cultivars in Brassica rapa var. chinensis (bok choy) grown under the different environmental conditions of the indoor farm using hyperspectral imaging. Anthocyanin accumulations estimated by hyperspectral imaging were compared with the measured anthocyanin accumulation obtained by destructive analysis. Between hyperspectral imaging and destructive analysis values, no significant differences in anthocyanin accumulation were observed across four bok choy cultivars grown under the anthocyanin stimulation environmental condition, whereas the estimated anthocyanin accumulations displayed cultivar-dependent significant differences, suggesting that hyperspectral imaging can be employed to measure variations in anthocyanin accumulations of different bok choy cultivars. Increased accumulation of anthocyanin under the stimulation condition for anthocyanin accumulation was observed in "purple magic" and "red stem" by both hyperspectral imaging and destructive analysis. In the different growth stages, no significant differences in anthocyanin accumulation were found in each cultivar by both hyperspectral imaging and destructive analysis. These results suggest that hyperspectral imaging can provide comparable analytic capability with destructive analysis to measure variations in anthocyanin accumulation that occurred under the different light and temperature conditions of the indoor farm. Leaf image analysis measuring the percentage of purple color area in the total leaf area displayed successful classification of anthocyanin accumulation in four bok choy cultivars in comparison to hyperspectral imaging and destructive analysis, but it also showed limitation to reflect the level of color saturation caused by anthocyanin accumulation under different environmental conditions in "red stem," "white stem," and "green stem." Finally, our hyperspectral imaging system was modified to be applied onto the high-throughput plant phenotyping system, and its test to analyze the variation of anthocyanin accumulation in four cultivars showed comparable results with the result of the destructive analysis.

18.
Theranostics ; 11(18): 8855-8873, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-34522215

RESUMEN

Mitochondrial dysfunction and oxidative stress are frequently observed in the early stages of Alzheimer's disease (AD). Studies have shown that presenilin-1 (PS1), the catalytic subunit of γ-secretase whose mutation is linked to familial AD (FAD), localizes to the mitochondrial membrane and regulates its homeostasis. Thus, we investigated how five PS1 mutations (A431E, E280A, H163R, M146V, and Δexon9) observed in FAD affect mitochondrial functions. Methods: We used H4 glioblastoma cell lines genetically engineered to inducibly express either the wild-type PS1 or one of the five PS1 mutants in order to examine mitochondrial morphology, dynamics, membrane potential, ATP production, mitochondria-associated endoplasmic reticulum (ER) membranes (MAMs), oxidative stress, and bioenergetics. Furthermore, we used brains of PS1M146V knock-in mice, 3xTg-AD mice, and human AD patients in order to investigate the role of PS1 in regulating MAMs formation. Results: Each PS1 mutant exhibited slightly different mitochondrial dysfunction. Δexon9 mutant induced mitochondrial fragmentation while A431E, E280A, H163R, and M146V mutants increased MAMs formation. A431E, E280A, M146V, and Δexon9 mutants also induced mitochondrial ROS production. A431E mutant impaired both complex I and peroxidase activity while M146V mutant only impaired peroxidase activity. All PS1 mutants compromised mitochondrial membrane potential and cellular ATP levels were reduced by A431E, M146V, and Δexon9 mutants. Through comparative profiling of hippocampal gene expression in PS1M146V knock-in mice, we found that PS1M146V upregulates Atlastin 2 (ATL2) expression level, which increases ER-mitochondria contacts. Down-regulation of ATL2 after PS1 mutant induction rescued abnormally elevated ER-mitochondria interactions back to the normal level. Moreover, ATL2 expression levels were significantly elevated in the brains of 3xTg-AD mice and AD patients. Conclusions: Overall, our findings suggest that each of the five FAD-linked PS1 mutations has a deleterious effect on mitochondrial functions in a variety of ways. The adverse effects of PS1 mutations on mitochondria may contribute to MAMs formation and oxidative stress resulting in an accelerated age of disease onset in people harboring mutant PS1.


Asunto(s)
Enfermedad de Alzheimer/fisiopatología , Mitocondrias/fisiología , Presenilina-1/genética , Adenosina Trifosfato/metabolismo , Enfermedad de Alzheimer/genética , Animales , Línea Celular Tumoral , Retículo Endoplásmico/metabolismo , Técnicas de Sustitución del Gen/métodos , Humanos , Potencial de la Membrana Mitocondrial/fisiología , Ratones , Ratones Endogámicos C57BL , Ratones Transgénicos , Mutación , Estrés Oxidativo/fisiología , Presenilina-1/metabolismo
19.
Sci Rep ; 11(1): 17512, 2021 09 01.
Artículo en Inglés | MEDLINE | ID: mdl-34471219

RESUMEN

This study aimed to evaluate the biocompatibility and patency of our newly developed titanium vascular anastomotic device (TVAD) in a pig jugular vein. TVAD was made of commercially pure grade 2 titanium. The patency and anastomotic time were simultaneously confirmed in an ex-vivo system developed by the authors and in vivo using pig jugular veins. Five 8-month-old pigs, with body weights of 50-60 kg, underwent anastomosis of both jugular veins using the device. Graft patency was evaluated for 12 weeks by biplane angiography and sonography. All tissue biopsy samples were analysed by histology. In all 10 cases, the anastomosis was completed in < 5 min. The vessel lumen was not damaged, and the inner vessel wall was completely endothelialised at the anastomotic site. No foreign body reactions were observed at the vessel lumen, vessels, and outer vessel walls by histopathologic analysis. Patency and absence of leakage at the anastomotic site of the follow-up period were confirmed clearly by angiography and sonography. This preliminary animal study proved that our newly developed device is a very promising tool for intima-to-intima contact anastomosis. TVAD can be used as a feasible and safe medical tool for vessel anastomosis.


Asunto(s)
Anastomosis Quirúrgica/instrumentación , Implantación de Prótesis Vascular/instrumentación , Venas Yugulares/cirugía , Ensayo de Materiales/métodos , Titanio/química , Grado de Desobstrucción Vascular , Anastomosis Quirúrgica/métodos , Animales , Venas Yugulares/patología , Modelos Animales , Porcinos
20.
In Vivo ; 35(5): 2703-2710, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-34410959

RESUMEN

AIM: To establish an experimental system for comparing different methods of intraperitoneal chemotherapy in a rat model. MATERIALS AND METHODS: We used six-week-old Sprague-Dawley rats, and created an early postoperative intraperitoneal chemotherapy (EPIC) system using 18-gauge syringes and evacuators, and a hyperthermic intraperitoneal chemotherapy (HIPEC) system using two peristaltic pumps which controlled the flow rate and temperature. Pressurized intraperitoneal aerosol chemotherapy (PIPAC) was achieved using a nozzle for dispersing aerosols at a flow rate up to 41.5 ml/min. The distribution and intensity of 0.2% trypan blue dye was compared among three methods. RESULTS: The distribution was limited and the intensity was weak after EPIC, and the dye stained moderately in gravity-dependent regions after HIPEC. On the other hand, the distribution was the most comprehensive, and the intensity was the greatest after PIPAC. CONCLUSION: This experimental system in a rat model may reflect the comparative effect among EPIC, HIPEC and PIPAC in humans.


Asunto(s)
Quimioterapia Intraperitoneal Hipertérmica , Aerosoles , Animales , Ratas , Ratas Sprague-Dawley
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