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1.
Int J Mol Sci ; 24(3)2023 Jan 18.
Artigo em Inglês | MEDLINE | ID: mdl-36768233

RESUMO

Correlating gene expression patterns with biomechanical properties of connective tissues provides insights into the molecular processes underlying the tissue growth and repair. Cadaveric specimens such as human knees are widely considered suitable for biomechanical studies, but their usefulness for gene expression experiments is potentially limited by the unavoidable, nuclease-mediated degradation of RNA. Here, we tested whether valid gene expression profiles can be obtained using degraded RNA from human anterior cruciate ligaments (ACLs). Human ACL RNA (N = 6) degraded in vitro by limited ribonuclease digestion resemble highly degraded RNA isolated from cadaveric tissue. PCR threshold cycle (Ct) values for 90 transcripts (84 extracellular matrix, 6 housekeeping) in degraded RNAs variably ranged higher than values obtained from their corresponding non-degraded RNAs, reflecting both the expected loss of target templates in the degraded preparations as well as differences in the extent of degradation. Relative Ct values obtained for mRNAs in degraded preparations strongly correlated with the corresponding levels in non-degraded RNA, both for each ACL as well as for the pooled results from all six ACLs. Nuclease-mediated degradation produced similar, strongly correlated losses of housekeeping and non-housekeeping gene mRNAs. RNA degraded in situ yielded comparable results, confirming that in vitro digestion effectively modeled degradation by endogenous ribonucleases in frozen and thawed ACL. We conclude that, contrary to conventional wisdom, PCR-based expression analyses can yield valid mRNA profiles even from RNA preparations that are more than 90% degraded, such as those obtained from connective tissues subjected to biomechanical studies. Furthermore, legitimate quantitative comparisons between variably degraded tissues can be made by normalizing data to appropriate housekeeping transcripts.


Assuntos
Lesões do Ligamento Cruzado Anterior , Ligamento Cruzado Anterior , Humanos , Articulação do Joelho , Transcriptoma , RNA/genética , Cadáver , Fenômenos Biomecânicos
2.
Exp Cell Res ; 405(2): 112667, 2021 08 15.
Artigo em Inglês | MEDLINE | ID: mdl-34107273

RESUMO

This study aimed toengineer a pancreatic tissue. Intact rat pancreases were successfully decellularized, and were reseeded with human-induced pluripotent stem cells using different 2D and 3D culture growth factors. The differentiation process was assessed for the presence of a pancreas-like tissue. The histology and SEM analysis revealed cell attachment in all samples, except for the Exp4, and the Flow-cytometry provided 87% viability for the differentiated cells. In Exp1, PDX1 with the positive expression of 2.87±0.06 was dramatically higher than Exp2 with a 2.44±0.06 reaction. NGN3-reactions were 8±0.1 and 6.6±0.2 in Exp1 and Exp2 at P < 0.05, respectively. C-peptide with the expression of 7.5±0.7 in Exp3 was almost equal to that in Exp1 and Exp2. Glucagon (5.1±1) and PDX1 (3.2±0.82) in Exp3 indicated no significant difference. The significant upregulations of pancreatic endocrine markers (PDX1 and NGN3), and the cell-specific glucose transporter (GLUT2) were observed in the differentiated IPCs in the 3D culture of Exp2 after 21 days. The highest insulin and C-peptide concentrations were observed in Exp2. In Exp3, insulin secretion in response to high glucose and 10 mM arginine was 42.43 ±6.34 µU/ml. A decellularized pancreas in the presence of hiPSCs and growth factors could be efficiently used as a natural scaffold.


Assuntos
Diferenciação Celular/fisiologia , Células-Tronco Pluripotentes Induzidas/citologia , Células Secretoras de Insulina/citologia , Pâncreas/citologia , Animais , Ilhotas Pancreáticas/citologia , Carioferinas/metabolismo , Ratos Wistar , Receptores Citoplasmáticos e Nucleares/metabolismo , Regulação para Cima/fisiologia , Proteína Exportina 1
3.
Biotechnol Appl Biochem ; 69(4): 1712-1722, 2022 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-34415072

RESUMO

Oxidative damage by free radicals has a negative effect on blood quality during storage. Antioxidant nanoparticles can prevent oxidative stress. We use SOD-CAT-Alb-PEG-PLGA- nanoparticles to reduce the effects of oxidative stress in blood storage. Electrospray was employed to prepare nanoparticles. Nanoparticles entered the test bags and were kept for 35 days from the time of donation under standard conditions. On target days, experiments were performed on the samples taken. The examination included blood smear, red blood cells count, hemoglobin, hematocrit, K, Fe, glutathione peroxidase, glutathion reductase, glucose-6-phosphate dehydrogenase, prooxidant-antioxidant balance, malondialdehyde, and flow cytometric assay for phosphatidylserine. The repeated measures analysis was performed on samples every week. Morphological changes were less in the test group compared to the control. The quantitative hemolysis profile test showed significant changes in the test and control groups (p < 0.05) in consecutive weeks except for K and Fe. Oxidative stress parameters too showed a significant change during the target days of the examination (p < 0.05). Also, the phosphatidylserine expression was increased in control groups more than test in consecutive weeks (p < 0.05). It seems that the use of antioxidant nanoparticles improves the quality of stored red blood cells and can prevent posttransfusion complications and blood loss by reducing oxidative stress.


Assuntos
Antioxidantes , Nanopartículas , Antioxidantes/metabolismo , Antioxidantes/farmacologia , Preservação de Sangue , Catalase/metabolismo , Glutationa Peroxidase/metabolismo , Estresse Oxidativo , Fosfatidilserinas , Superóxido Dismutase/metabolismo
4.
Differentiation ; 121: 25-34, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34454348

RESUMO

The native extracellular matrix (ECM) provides a matrix to hold tissue/organ, defines the cellular fate and function, and retains growth factors. Such a matrix is considered as a most biomimetic scaffold for tissue engineering due to the biochemical and biological components, 3D hierarchical structure, and physicomechanical properties. Several attempts have been performed to decellularize allo- or xeno-graft tissues and used them for bone repairing and regeneration. Decellularized ECM (dECM) technology has been developed to create an in vivo-like microenvironment to promote cell adhesion, growth, and differentiation for tissue repair and regeneration. Decellularization is mediated through physical, chemical, and enzymatic methods. In this review, we describe the recent progress in bone decellularization and their applications as a scaffold, hydrogel, bioink, or particles in bone tissue engineering. Furthermore, we address the native dECM limitations and the potential of non-bone dECM, cell-based ECM, and engineered ECM (eECM) for in vitro osteogenic differentiation and in vivo bone regeneration.


Assuntos
Engenharia Tecidual , Alicerces Teciduais , Matriz Extracelular Descelularizada , Matriz Extracelular , Osteogênese , Tecnologia
5.
Cell Tissue Bank ; 23(2): 301-312, 2022 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-34414549

RESUMO

To produce an esophageal scaffold with suitable features and evaluate the result of in vivo cell seeding after its implantation in the omentum and near its original anatomical position in the rat model. The esophagus of twelve rats were resected, cannulated, and decellularized via a peristaltic pump. After confirmation of decellularization and preservation of extracellular matrix, decellularized scaffolds were implanted either in the abdominal cavity (group I, n = 6) or cervical area (group II, n = 6). Histological evaluations were performed after 3 and 6 months of implantation. The results of histological evaluations, scanning electron microscopy, and the tensile test confirmed the maintenance of extracellular matrix and removal of all cellular constituents. At the time of biopsy, no evidence of inflammation was detected and the implanted scaffolds appeared normal. Histopathological evaluations of implanted tissues revealed that undifferentiated cells were seen in scaffolds of all follow-ups in both groups. Epithelial cell seeding was more advanced in biopsies of group II obtained after 6 months of operation and was accompanied by angiogenesis in surrounding adventitia. It seems that the implantation of scaffold near its original place may have an important role in further cell seeding. This method may be surpassing in comparison with traditional implantation techniques for perfecting esophageal transplantation.


Assuntos
Engenharia Tecidual , Alicerces Teciduais , Animais , Células Epiteliais , Esôfago , Matriz Extracelular , Ratos , Engenharia Tecidual/métodos
6.
Mater Des ; 2172022 May.
Artigo em Inglês | MEDLINE | ID: mdl-35935127

RESUMO

The gastrointestinal (GI) tract is a continuous channel through the body that consists of the esophagus, the stomach, the small intestine, the large intestine, and the rectum. Its primary functions are to move the intake of food for digestion before storing and ultimately expulsion of feces. The mechanical behavior of GI tissues thus plays a crucial role for GI function in health and disease. The mechanical properties are characterized by a biomechanical constitutive model, which is a mathematical representation of the relation between load and deformation in a tissue. Hence, validated biomechanical constitutive models are essential to characterize and simulate the mechanical behavior of the GI tract. Here, a systematic review of these constitutive models is provided. This review is limited to studies where a model of the strain energy function is proposed to characterize the stress-strain relation of a GI tissue. Several needs are identified for more advanced modeling including: 1) Microstructural models that provide actual structure-function relations; 2) Validation of coupled electro-mechanical models accounting for active muscle contractions; 3) Human data to develop and validate models. The findings from this review provide guidelines for using existing constitutive models as well as perspective and directions for future studies.

7.
Europace ; 21(3): 492-501, 2019 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-30481301

RESUMO

AIMS: Substrate based catheter ablation strategies are widely employed for treatment of scar-related ventricular tachycardia (VT). We analysed intracardiac electrograms (EGMs) from close-coupled paced extrastimuli extracted from the EnSite Precision mapping system. We sought to characterize EGM responses of ventricular myocardium to varying coupling intervals from the right ventricular apex (RVA) in both healthy individuals and patients presenting with VT for catheter ablation. METHODS AND RESULTS: Extrastimuli were delivered from the RVA after estimation of the ventricular effective refractory period. Electrograms were recorded from high-density mapping catheters in the left ventricle and exported for analysis to MATLAB. Observational data were collected from 14 patients with ischaemic VT (mean age 72.4 ± 6.3 years, one female) and five controls (mean age 59.4 ± 7.4 years, one female). These derived data were used to inform an interventional strategy on a further 10 patients (mean age 64.7 ± 10.0 years; two female). Significant differences were observed in EGM duration (ED) and latency (LT) at all coupling intervals between VT patients and controls. Significant increases in ED and LT with decreased RVA coupling interval were observed at VT isthmuses. Abnormal responses derived from control subject data were used to classify four types of ventricular EGM response. Targeting sites with abnormal LT and ED significantly reduced VT inducibility (5/14 derivation patients to 0/10 intervention patients; P = 0.03). CONCLUSION: Paced electrogram feature analysis is a novel tool to characterize the ischaemic substrate. Association with VT isthmuses and early ablation results suggest a possible role in substrate ablation for ischaemic VT.


Assuntos
Potenciais de Ação , Estimulação Cardíaca Artificial , Técnicas Eletrofisiológicas Cardíacas , Frequência Cardíaca , Ventrículos do Coração/fisiopatologia , Taquicardia Ventricular/diagnóstico , Função Ventricular Esquerda , Idoso , Estudos de Casos e Controles , Ablação por Cateter , Feminino , Ventrículos do Coração/cirurgia , Humanos , Masculino , Valor Preditivo dos Testes , Período Refratário Eletrofisiológico , Taquicardia Ventricular/fisiopatologia , Taquicardia Ventricular/cirurgia , Fatores de Tempo
8.
Ann Noninvasive Electrocardiol ; 24(3): e12629, 2019 05.
Artigo em Inglês | MEDLINE | ID: mdl-30688396

RESUMO

BACKGROUND: Current noninvasive risk stratification methods offer limited prediction of arrhythmic events when selecting patients for ICD implantation. Our laboratory has recently developed a signal processing metric called Layered Symbolic Decomposition frequency (LSDf) that quantifies the percentage of hidden QRS wave frequency components in signal-averaged ECG (SAECG) recordings. The purpose of this pilot study was to determine whether LSDf can be predictive of ventricular arrhythmia or death in an ICD patient cohort. METHODS AND RESULTS: Fifty-two ICD patients were recruited from 2008 to 2009. These were followed for a mean of 8.5 ± 0.4 years for the primary outcome of first appropriately treated ventricular arrhythmia (VT/VF) or death. Thirty-four subjects met the primary outcome. LSDf was significantly lower, and 12-lead QRS duration was significantly greater in patients meeting the primary outcome (12.14 ± 3.97% vs. 16.45 ± 3.73%; p = 0.001) and (111.59 ± 14.96 ms vs. 97.69 ± 13.51 ms; p = 0.012) respectively. A 13.25% LSDf threshold (0.74 sensitivity and 0.85 specificity) was selected based on an ROC curve. Kaplan-Meier survival analysis was conducted; patients above the 13.25% threshold demonstrated significantly better survival outcomes (log-rank p < 0.001). In Cox multivariate regression analysis, the LSDf threshold (13.25%) was compared to LVEF (28.5%), 12-lead QRSd (100 ms), age, % male sex, NYHA classification, and antiarrhythmic usage. LSDf was a predictor of the primary outcome (p = 0.005) and an independent predictor for solely ventricular arrhythmia (p = 0.002). CONCLUSION: Layered Symbolic Decomposition frequency analysis in SAECG recordings may be a viable predictor of negative ICD survival outcomes.


Assuntos
Morte Súbita Cardíaca/etiologia , Desfibriladores Implantáveis/efeitos adversos , Eletrocardiografia/métodos , Processamento de Imagem Assistida por Computador , Taquicardia Ventricular/diagnóstico por imagem , Taquicardia Ventricular/terapia , Idoso , Área Sob a Curva , Estudos de Coortes , Feminino , Seguimentos , Humanos , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Seleção de Pacientes , Projetos Piloto , Valor Preditivo dos Testes , Prognóstico , Estudos Prospectivos , Curva ROC , Medição de Risco , Volume Sistólico , Análise de Sobrevida , Taquicardia Ventricular/mortalidade
9.
J Cell Physiol ; 233(5): 3805-3816, 2018 05.
Artigo em Inglês | MEDLINE | ID: mdl-28500662

RESUMO

Type 1 diabetes is characterized by autoimmune destruction of pancreatic cells. Organ transplantation is an acceptable treatment for native organ failure. However, it is associated with several problems due to a number of reasons, such as the lack of appropriate donors and immunosuppression. In our present study, a novel model is presented for in vivo recellularization of acellular pancreas by implanting between the host pancreas and the adjacent omental flap. In this study, the pancreases were harvested and cannulated via the common bile duct and then, the scaffolds were acellularized by a detergent-based protocol. After that, the abdomens of 35 rats were opened and the spleen was extracted with the adjacent omentum, and placed outside the abdomen. The acellularized scaffold was stretched over the host pancreas and the omentum was wrapped around it to make a sandwich-like structure, which was then fixed with Chromic Sutures 6-0 and marked with Prolene 4-0 on four sides. All samples were biopsied at 14, 30, 60, 90, and 120 days post-transplantation. The result showed marked recellularization of acellularized pancreas with visible neovascularization and neoß-cells with minimal inflammatory response. This study provides a new approach to produces a normal-like pancreas by allograft transplantation for pancreas tissue engineering. We observed that in vivo transplantation of acellularized pancreas can promote recellularization, proliferation, and differentiation by blood circulation. These findings support that in vivo studies can contribute to finding faster solutions for the treatment of diabetes.


Assuntos
Reatores Biológicos , Pâncreas/citologia , Engenharia Tecidual , Alicerces Teciduais , Animais , Diferenciação Celular/fisiologia , Matriz Extracelular/metabolismo , Ratos Sprague-Dawley , Engenharia Tecidual/métodos , Transplante Homólogo/métodos
10.
Apoptosis ; 23(11-12): 616-625, 2018 12.
Artigo em Inglês | MEDLINE | ID: mdl-30101359

RESUMO

Strong 14-3-3 zeta protein expression plays an important role in tumorigenesis, including in the maintenance of cell growth, resistance increase, and the prevention of apoptosis. In this study, we focus on two targets: (1) the expression of 14-3-3 zeta in the different grades of human astrocytoma (II-IV), (2) suppression of 14-3-3 zeta protein expression in glioblastoma derived astrocytes by 14-3-3 zeta shRNA lentiviral particles. The tissues of human astrocytoma were provided from 30 patients (ten of each grade of astrocytoma). Control tissues were obtained from the peritumoral brain zone of those patients with glioblastoma. The protein and mRNA expression levels of each astrocytoma grade were assessed via western blotting and RT-PCR, respectively. Results indicated that 14-3-3 zeta was significantly expressed in glioblastoma multiforme (grade IV) and 14-3-3 zeta expression levels enhanced according to the increase of astrocytoma malignancy. In the cellular study for knock down of the 14-3-3 zeta protein, surgical biopsy of glioblastoma was used to isolate primary astrocyte. Astrocytes were transduced with 14-3-3 zeta shRNA or non-targeted shRNA lentiviral particles. Furthermore, reduction of the 14-3-3 zeta protein expression in the astrocytes evaluated through qRT-PCR and western blot after transduction of 14-3-3 zeta shRNA lentiviral particles. Moreover, apoptosis properties, including DNA fragmentation and ratio increase of Bax/Bcl-2 were observed in astrocytes following reduction of 14-3-3 zeta protein expression. Further observation indicated that the mitochondrial pathway through release of cytochorome c and caspase-3 activity was involved in the apoptosis induction. Hence, this study demonstrates a key role of the 14-3-3 zeta protein in tumorigenesis but also indicates that 14-3-3 zeta can be considered as a target for the astrocytoma treatment specially glioblastoma.


Assuntos
Proteínas 14-3-3/genética , Apoptose/genética , Neoplasias Encefálicas/patologia , Regulação para Baixo/genética , Glioblastoma/patologia , Proteínas 14-3-3/antagonistas & inibidores , Proteínas 14-3-3/metabolismo , Astrócitos/metabolismo , Astrócitos/patologia , Astrocitoma/genética , Astrocitoma/patologia , Encéfalo/patologia , Neoplasias Encefálicas/genética , Carcinogênese/genética , Feminino , Técnicas de Silenciamento de Genes , Glioblastoma/genética , Humanos , Masculino , Pessoa de Meia-Idade , Mitocôndrias/metabolismo , RNA Mensageiro/metabolismo , RNA Interferente Pequeno/metabolismo , Células Tumorais Cultivadas
11.
Cells Tissues Organs ; 205(2): 72-84, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-29742511

RESUMO

INTRODUCTION: Diabetes is known as a worldwide disease with a great burden on society. Since therapeutic options cover a limited number of target points, new therapeutic strategies in the field of regenerative medicine are considered. Bioscaffolds along with islet cells would provide bioengineered tissue as a substitute for ß-cells. The perfusion-decellularization technique is considered to create such scaffolds since they mimic the compositional, architectural, and biomechanical nature of a native organ. In this study, we investigated 2 decellularization methods preserving tissue microarchitecture. METHODS: Procured pancreas from Sprague-Dawley rats was exposed to different percentages of detergent for 2, 4, and 6 h after cannulation via the common bile duct or aorta. RESULTS: High concentrations of sodium dodecyl sulfate (SDS), i.e., > 0.05%, resulted in tissue disruption or incomplete cell removal depending on the duration of exposure. In both methods, 6-h exposure to 0.05% SDS created a bioscaffold with intact extracellular matrices and proper biomechanical characteristics. Tissue-specific stainings revealed that elastic, reticular, and collagen fiber concentrations were well preserved. Quantitative findings showed that glycosaminoglycan content was slightly different, but hydroxyproline was in the range of native pancreas tissue. Dye infusion through ductal and vascular cannulation proved that the vascular network was intact, and scanning electron microscopy indicated a homogeneous porous structure. CONCLUSIONS: Using the detergent-based method, an effective and time-efficient procedure, a whole pancreas extracellular matrix bioscaffold can be developed that can be used as a 3D structure for pancreas tissue engineering-based studies and regenerative medicine applications.


Assuntos
Artérias/fisiologia , Cateterismo , Matriz Extracelular/metabolismo , Ductos Pancreáticos/fisiologia , Engenharia Tecidual/métodos , Alicerces Teciduais/química , Animais , Fenômenos Biomecânicos , Vasos Sanguíneos/fisiologia , Sobrevivência Celular , Colágeno/metabolismo , Glicosaminoglicanos/metabolismo , Hidroxiprolina/metabolismo , Ductos Pancreáticos/ultraestrutura , Ratos Sprague-Dawley
12.
Mol Biol Rep ; 45(6): 2263-2273, 2018 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-30242665

RESUMO

The potential of herpes simplex virus type 1 thymidine kinase (HSV-tk)-expressing olfactory ensheathing cells (OEC) treated with ganciclovir (GCV) to induce cell death in adjacent HSV-tk-negative cells (bystander effect) has been well demonstrated. Although it has been shown that bystander effect occurs through the delivery of phosphorylated GCV, the bystander effect mechanism and the role of gap junctions for human OECs mediated suicide gene therapy in primary astrocytes of human glioblastma remain obscure. In the present study, the efficacy of a new method for the transfer of phosphorylated GCV from OECs into primary astrocytes was evaluated. Surgical biopsy of glioblastoma was used to isolate primary astrocyte. Biopsy of olfactory mucosa was applied to isolate olfactory ensheathing cell. Expression of S100-beta antigen was confirmed immunocytochemically in astrocytes and OECs. OECs were transduced to lentiviral containing thymidine kinase gene (TK) and co-cultured with astrocytes. Fluorescent dye transfer and western blot analysis indicated the expression of connexin43 between olfactory ensheathing cells and astrocytes whereas, expression of the gap junction protein connexin43 was inhibited by the gap junction inhibitor 18α-glycyrrhethinic acid (AGA, 20 µg/ml). Furthermore, co-culture of astrocytes with OEC-TK in the presence of concentration of 30 µg/ml GCV led to a decrease in astrocytes survival rate. Also, apoptosis hallmarks, including DNA fragmentation in cell nuclear, expression increase of Bax to Bcl-2 ratio and increase of caspase3 activation were observed in this study. Our findings suggest that human olfactory ensheathing cells can deliver phosphorylated GCV into the glioblastoma derived astrocytes through gap junction communication for apoptosis induction.


Assuntos
Astrócitos/efeitos dos fármacos , Ganciclovir/administração & dosagem , Glioblastoma/tratamento farmacológico , Adulto , Antivirais , Efeito Espectador , Técnicas de Cocultura , Conexina 43/efeitos dos fármacos , Ganciclovir/farmacologia , Junções Comunicantes/efeitos dos fármacos , Genes Reporter , Terapia Genética , Vetores Genéticos , Herpesvirus Humano 1 , Humanos , Mucosa Olfatória , Cultura Primária de Células , Timidina Quinase/uso terapêutico , Células Tumorais Cultivadas
13.
J Pediatr Hematol Oncol ; 40(8): 609-615, 2018 11.
Artigo em Inglês | MEDLINE | ID: mdl-29734214

RESUMO

In this study, we investigated the effects of pomegranate on alleviating cyclophosphamide-induced hemorrhagic cystitis (HC). Initially, 16 Sprague-Dawley rats were allocated into 4 groups: group 1 (control), group 2 (CP) in which HC was induced by cyclophosphamide; group 3 (CP+M), HC-induced rats that received Mesna regimen, and group 4 (CP+P), which compromised rats that had been on a 14-day diet of pomegranate juice before HC induction. Cystometry was performed a few hours before euthanasia; after euthanasia, aortic blood samples and bladder tissue samples were obtained to perform TUNEL assay, and histopathologic and biochemical assessments. Urodynamic findings revealed that mean detrusor pressure in CP+P was significantly lower compared with that in CP and CP+M (P<0.05). Histopathologically, urothelium destruction and inflammation were lower in CP+P and CP+M compared with that in CP. Collagen destruction was less prominent in CP+P compared with that in CP and CP+M. Tissue and plasma levels of malondialdehyde were significantly lower in CP+P versus CP (P<0.05). Catalase activity and total protein thiol group levels in plasma and bladder tissue were higher in CP+P versus CP (P<0.05). The TUNEL positivity in CP+P was significantly weaker than that in CP, indicating less DNA fragmentation and apoptosis. Pomegranate's characteristics could significantly affect the inflammatory and destructive process of hemorrhagic cystitis.


Assuntos
Ciclofosfamida/efeitos adversos , Cistite , Hemorragia , Lythraceae/química , Mesna/farmacologia , Extratos Vegetais/farmacologia , Urotélio , Animais , Ciclofosfamida/farmacologia , Cistite/induzido quimicamente , Cistite/tratamento farmacológico , Cistite/metabolismo , Cistite/patologia , Hemorragia/induzido quimicamente , Hemorragia/tratamento farmacológico , Hemorragia/metabolismo , Hemorragia/patologia , Masculino , Extratos Vegetais/química , Ratos , Ratos Sprague-Dawley , Urodinâmica/efeitos dos fármacos , Urotélio/metabolismo , Urotélio/patologia
14.
Phys Chem Chem Phys ; 17(16): 10849-55, 2015 Apr 28.
Artigo em Inglês | MEDLINE | ID: mdl-25820573

RESUMO

Adsorption geometry of dye molecules can have a substantial impact on the efficiency and functional lifespan of a dye-sensitised solar cell (DSSC) and therefore, its reliable assessment is an important step in engineering more efficient DSSCs. X-ray photoelectron spectroscopy (XPS) of oxygen is empirically proved to be the most efficient technique in distinguishing between the two most occurring adsorption geometries, i.e. monodentate and bidentate. In this computational study, we provide a comprehensive analysis of XPS and X-ray absorption spectroscopy (XAS) of carbon and oxygen for these binding modes in a perylene-sensitised TiO2. We confirm that O 1s XPS has an excellent sensitivity in mode identification. Moreover, we show that adsorption has a great impact on the XPS binding energies and reduces them by ∼4 eV, and using this effect, we extend the XPS usage to study dye desorption in the cell. Finally, our results for XAS indicate that although less sensitive, the spectra from carbon can be used in mode detection.

15.
IEEE J Biomed Health Inform ; 28(2): 789-800, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-37948139

RESUMO

This paper presents a systematic investigation into the effectiveness of Self-Supervised Learning (SSL) methods for Electrocardiogram (ECG) arrhythmia detection. We begin by conducting a novel analysis of the data distributions on three popular ECG-based arrhythmia datasets: PTB-XL, Chapman, and Ribeiro. To the best of our knowledge, our study is the first to quantitatively explore and characterize these distributions in the area. We then perform a comprehensive set of experiments using different augmentations and parameters to evaluate the effectiveness of various SSL methods, namely SimCRL, BYOL, and SwAV, for ECG representation learning, where we observe the best performance achieved by SwAV. Furthermore, our analysis shows that SSL methods achieve highly competitive results to those achieved by supervised state-of-the-art methods. To further assess the performance of these methods on both In-Distribution (ID) and Out-of-Distribution (OOD) ECG data, we conduct cross-dataset training and testing experiments. Our comprehensive experiments show almost identical results when comparing ID and OOD schemes, indicating that SSL techniques can learn highly effective representations that generalize well across different OOD datasets. This finding can have major implications for ECG-based arrhythmia detection. Lastly, to further analyze our results, we perform detailed per-disease studies on the performance of the SSL methods on the three datasets.


Assuntos
Eletrocardiografia , Autogestão , Humanos , Arritmias Cardíacas/diagnóstico , Conhecimento
16.
Res Sq ; 2023 Jan 23.
Artigo em Inglês | MEDLINE | ID: mdl-36747669

RESUMO

A non-invasive risk assessment tool capable of stratifying coronary artery stenosis into high and low risk would reduce the number of patients who undergo invasive FFR, the current gold standard procedure for assessing coronary artery disease. Current statistic-based models that predict if FFR is above or below the threshold for physiological significance rely completely on anatomical parameters, such as percent diameter stenosis (%DS), resulting in models not accurate enough for clinical application. The inclusion of coronary artery flow rate (CFR) was added to an anatomical-only logistic regression model to quantify added predictive value. Initial hypothesis testing on a cohort of 96 coronary artery segments with some degree of stenosis found higher mean CFR in a group with low FFR < 0.8 (µ = 2.37 ml/s) compared to a group with high FFR > 0.8 (µ = 1.85 ml/s) (p-value = 0.046). Logistic regression modeling using both %DS and CFR (AUC = 0.78) outperformed logistic regression models using either only %DS (AUC = 0.71) or only CFR (AUC = 0.62). Including physiological parameters in addition to anatomical parameters are necessary to improve statistical based models for assessing high or low FFR.

17.
Sci Rep ; 13(1): 10201, 2023 06 23.
Artigo em Inglês | MEDLINE | ID: mdl-37353535

RESUMO

Conduits are commonly used for treating lesions in arteries and veins. The conventional stents are cylindrical in shape, which increases flow resistance with length. This study presents a design of stents and conduits where the conduit caliber expands gradually to reduce resistance while avoiding flow separation. Inflow was provided from a header tank at two different pressures (i.e., 10 and 25 mm Hg pressure) into a cylindrical or expanding conduit. The initial conduit calibers were 2-, 3-, 4-, and 5-mm and 160-, 310-, and 620-mm lengths in each case. The flow rates of expanding caliber conduits (at a rate of r4-6/cm where r is the initial conduit radius) were compared to traditional cylindrical conduits of constant radius. The expanded caliber yields a significantly increased flow of 16-55% for R4/L expansion, 9-44% for R5/L expansion, and 1-28% for R6/L expansion. Simulated flow models using computational fluid dynamics (CFD) were used to validate and expand the experimental findings. Flow separation was detected for certain simulations by flow pathlines and wall shear stress (WSS) calculations. The results showed that a caliber expansion rate of r6/cm is the optimal rate of expansion for most potential applications with minimum flow separation, lower resistance, and increased flow.


Assuntos
Artérias , Stents , Velocidade do Fluxo Sanguíneo , Veias , Modelos Cardiovasculares , Hemodinâmica
18.
Front Digit Health ; 5: 1193467, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37588022

RESUMO

Introduction: The SARS-CoV-2 (COVID-19) pandemic has created substantial health and economic burdens in the US and worldwide. As new variants continuously emerge, predicting critical clinical events in the context of relevant individual risks is a promising option for reducing the overall burden of COVID-19. This study aims to train an AI-driven decision support system that helps build a model to understand the most important features that predict the "mortality" of patients hospitalized with COVID-19. Methods: We conducted a retrospective analysis of "5,371" patients hospitalized for COVID-19-related symptoms from the South Florida Memorial Health Care System between March 14th, 2020, and January 16th, 2021. A data set comprising patients' sociodemographic characteristics, pre-existing health information, and medication was analyzed. We trained Random Forest classifier to predict "mortality" for patients hospitalized with COVID-19. Results: Based on the interpretability of the model, age emerged as the primary predictor of "mortality", followed by diarrhea, diabetes, hypertension, BMI, early stages of kidney disease, smoking status, sex, pneumonia, and race in descending order of importance. Notably, individuals aged over 65 years (referred to as "older adults"), males, Whites, Hispanics, and current smokers were identified as being at higher risk of death. Additionally, BMI, specifically in the overweight and obese categories, significantly predicted "mortality". These findings indicated that the model effectively learned from various categories, such as patients' sociodemographic characteristics, pre-hospital comorbidities, and medications, with a predominant focus on characterizing pre-hospital comorbidities. Consequently, the model demonstrated the ability to predict "mortality" with transparency and reliability. Conclusion: AI can potentially provide healthcare workers with the ability to stratify patients and streamline optimal care solutions when time is of the essence and resources are limited. This work sets the platform for future work that forecasts patient responses to treatments at various levels of disease severity and assesses health disparities and patient conditions that promote improved health care in a broader context. This study contributed to one of the first predictive analyses applying AI/ML techniques to COVID-19 data using a vast sample from South Florida.

19.
Curr Med Chem ; 30(12): 1406-1419, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-36065926

RESUMO

Given the importance of COVID-19-induced ARDS, recently, researchers have strived to determine underlying mechanisms involved in the inflammatory responses. In this regard, inflammasomes possess a distinct priority for cytokine storm occurrence and, subsequently, ARDS progression in ill patients with SARS-CoV-2 infection. In this minireview, the characteristics of known inflammasome inhibitors and designed research in this field were concretely deciphered.


Assuntos
COVID-19 , Síndrome do Desconforto Respiratório , Humanos , COVID-19/complicações , Inflamassomos , SARS-CoV-2 , Proteína 3 que Contém Domínio de Pirina da Família NLR , Síndrome do Desconforto Respiratório/tratamento farmacológico
20.
Comput Methods Programs Biomed ; 216: 106674, 2022 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-35134596

RESUMO

BACKGROUND AND OBJECTIVES: Fractional flow reserve (FFR) is the gold standard for quantification of coronary stenosis and pressure wire is the gold standard for measuring FFR. Recently, computational fluid dynamics (CFD) methods have been used to compute FFR less invasively using images obtained from coronary angiography. This approach is, however, computationally intensive and solutions to reduce computation time are clearly required. METHODS: We hypothesized that FFR can be calculated instantly using a reduced order model (ROM) derived using response surface method (RSM) for simulation modeling in lieu of the computationally intensive CFD. Specifically, eleven physiological and anatomical factors known to affect FFR were selected as input variables, and Plackett-Burman analysis was performed in conjunction with CFD on model arteries to identify set of variables affecting FFR the most. Based on the Box-Behnken design, a mathematical model was developed to compute FFR using the retained set of variables. RESULTS: The model fidelity was tested on a cohort of 90 patients (100 coronary arteries) with known pressure-wire FFR. FFR derived from this ROM had a strong correlation with pressure-wire FFR with sensitivity of 89.4%, specificity of 100% and area under curve of 0.947 (p < 0.05). CONCLUSIONS: The ROM method can be used to reliably calculate FFR in patients with coronary stenosis and able to replace time-consuming CFD-based FFR estimation and provide instead a real-time calculation method.


Assuntos
Estenose Coronária , Reserva Fracionada de Fluxo Miocárdico , Angiografia Coronária/métodos , Estenose Coronária/diagnóstico por imagem , Vasos Coronários/diagnóstico por imagem , Humanos , Valor Preditivo dos Testes , Índice de Gravidade de Doença
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