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1.
Int J Mol Sci ; 24(22)2023 Nov 17.
Artigo em Inglês | MEDLINE | ID: mdl-38003661

RESUMO

This study is designed to formulate and characterize chitosan-based nanogels that provide the controlled delivery of anesthetic drugs, such as bupivacaine (BPV), for effective postoperative pain management over prolonged periods of time. Drug carriers of chitosan/poly (MMA-co-HEMA-cl-EGDMA) (CsPMH) nanogels were prepared by varying the composition of comonomers such as MMA, HEMA, and redox initiator CAN. The nanogels were then characterized using FTIR, TGA, SEM, and TEM. The CsPMH nanogels showed greater encapsulation efficiencies from 43.20-91.77%. Computational studies were also conducted to evaluate the interaction between the drug and CsPMH nanoparticles. Finally, BPV-loaded nanoparticles were used to examine their in vitro release behavior. At pH 7.4, all the drug carriers displayed the "n" value around 0.7, thus the BPV release follows anomalous diffusion. Drug carrier 7 demonstrated a steady and sustained release of BPV for approximately 24 h and released about 91% of BPV, following the K-P mechanism of drug release. On the other hand, drug carrier 6 exhibited controlled release for approximately 12 h and released only 62% of BPV.


Assuntos
Quitosana , Nanopartículas , Nanogéis , Quitosana/química , Bupivacaína , Portadores de Fármacos/química , Concentração de Íons de Hidrogênio
2.
Chemosphere ; 313: 137388, 2023 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-36455658

RESUMO

The interactions between the microbes and the surface of an anode play an important role in capturing the respiratory electrons from bacteria in a microbial fuel cell (MFC). The chemical and electrochemical characteristics of the carbon material affect biofilm growth and direct electron transfer in MFCs. This study examined the electrodeposition of polydopamine (PDA) and polypyrrole (PPY) on graphite felt electrode (GF). The MFC with the modified PDA/PPY-GF reached 920 mW/m2, which was 1.5, 1.17, and 1.18 times higher than those of the GF, PDA-GF, and PPY-GF, respectively. PDA has superior hydrophilicity and adhesive force biofilm formation, while PPY provides electrochemically active sites for microbial electron transfer. Raman spectroscopy, Fourier transform infrared spectroscopy, Brunauer-Emmett-Teller surface area measurements, and contact angle analysis revealed the enhanced physicochemical properties of the carbon electrode. These results show that co-doped PDA/PPY provides a strategy for electroactive biofilm development and improves the bioelectrochemical performance in realistic MFC reactors.


Assuntos
Fontes de Energia Bioelétrica , Grafite , Fontes de Energia Bioelétrica/microbiologia , Polímeros/química , Grafite/química , Pirróis/química , Bactérias , Carbono , Eletrodos
3.
Appl Neuropsychol Adult ; : 1-15, 2022 Nov 22.
Artigo em Inglês | MEDLINE | ID: mdl-36412487

RESUMO

Since Parkinson's disease (PD) is a heterogeneous disorder with symptoms, such as tremors, gait and speech disturbances, or memory loss, individualized diagnostics are needed to optimize treatment. In their current form, the typical paper-pencil methods traditionally used to track disease progression are too coarse to capture the subtleties of clinical phenomena. For this reason, digital biomarkers that capture, for example, motor function, cognition, and behavior using apps, wearables, and tracking systems are becoming increasingly established. However, given the high prevalence of cognitive impairment in PD, digital cognitive biomarkers to predict mental progression are important in clinical practice. This pilot study aimed to identify those components of our digital version of the TMT (dTMT) that allow discrimination between PD patients with and without cognitive deficits. A total of 30 healthy control (age 66.3 ± 8.61) and 30 participants with PD (age 68.3 ± 9.66) performed the dTMT using a touch-sensitive tablet to capture enhanced performance metrics, such as the speed between and inside circles. The decomposition of cognitive abilities based on integrating additional variables in the dTMT revealed that the Parkinson's disease group was significantly more sensitive to parameters of inhibitory control. In contrast, the mild cognitive impairment group was sensitive to parameters of cognitive flexibility and working memory. The dTMT allows objective, ecologically valid, and long-term cognitive and fine-motor performance tracking, suggesting its potential as a digital biomarker in neurodegenerative disorders.

4.
J Integr Neurosci ; 21(4): 122, 2022 Jun 30.
Artigo em Inglês | MEDLINE | ID: mdl-35864773

RESUMO

BACKGROUND: Although an extensive body of literature is trying to verify the acute effects of exercise, findings are highly contradictory due to many different study protocols. The number of studies using an intermittent exercise (IE) protocol is limited, especially with regard to comparison across the life span. We examined whether the effects of a HIIE protocol on performance in a perceptual-cognitive task (NeuroTracker® (NT)) differed between children, young adults, and older adults to address this gap. METHODS: A total of 36 participants participated in the present study: 12 children (CH, 6 females, 9.83 ± 1.19 years), 12 young adults (YA, 6 females, 23.5 ± 3.55 years), and 12 older adults (OA, 4 females, 66.92 ± 4.08 years). The IE treadmill protocol used in the present study consisted of eleven 30-second intervals at 90% VO2max, interspersed with 2-minute active recovery periods at 50% VO2max. Before and during this exercise protocol, three series of the NeuroTracker® task were performed after 5, 15, and 25 minutes. RESULTS: We observed a significant main effect time and a significant main effect group regarding absolute NT scores and progression during IE. YA had significantly higher absolute NT scores than CH and OA. The normalized perceptual-cognitive task progression was observed in OA and YA but not in CH. YA, in particular, showed progression in the NT performance during IE. CONCLUSIONS: The present study confirmed previous findings on age-related differences in NT performance. Based on these findings, the effects of different exercise protocols (e.g., continuous vs. intermittent) seem to be a worthwhile subject for future investigations. Normalized speed thresholds should best capture improvement differences between groups to compare results across studies better, as pre-test values are taken as the baseline.


Assuntos
Exercício Físico , Idoso , Criança , Exercício Físico/psicologia , Feminino , Humanos , Projetos Piloto , Adulto Jovem
5.
J Integr Neurosci ; 21(3): 98, 2022 May 17.
Artigo em Inglês | MEDLINE | ID: mdl-35633179

RESUMO

BACKGROUND: Several studies have shown that acute exercise has a small positive effect on cognitive performance. However, it is still unclear what type of exercise has a sustained impact on cognitive performance during post-exercise recovery. Therefore, the purpose of our study was to investigate cognitive performance at the behavioral level, and their neural correlates after a 10-minute post-exercise recovery period with two different types of exercise intervention (high-intensity interval exercise (HIIE) vs. Moderate-intensity continuous exercise (MCE)). METHODS: A total of 29 healthy young adults (7 women) between the ages of 19 and 33 with fair to good cardiovascular fitness were submitted to two different exercise protocols and a recovery session. Cognitive function was assessed using a digital Trail-Making-Test (dTMT). Cortical activity in the prefrontal and the motor cortex using functional near-infrared spectroscopy (fNIRS) was measured before, after acute exercise, and during recovery. The statistical analysis of fNIRS data was performed by comparing the slope and mean of the hemodynamic response. RESULTS: High levels of hemodynamic responses were observed in the prefrontal and motor cortex on the brain during performing the dTMT while walking from pre- to post-exercise and decreased again in post-recovery, accompanied by improvement and maintenance of cognitive performance. Notably, a high hemodynamic response in the left motor area of the brain was maintained by HIIE in post-recovery compared with MCE. CONCLUSIONS: The high cortical activation in the left motor area from post-exercise to recovery for the HIIE group may be due to the additional availability of neural resources for fine motor and postural control by high-intensity exercise-induced fatigue. Additionally, the improved cognitive performance may have effectively utilized the available neural resources in the frontal lobe, depending on the condition (sitting and walking) and the two types of exercise protocol (HIIE and MCE).


Assuntos
Função Executiva , Espectroscopia de Luz Próxima ao Infravermelho , Adulto , Cognição , Função Executiva/fisiologia , Exercício Físico/fisiologia , Exercício Físico/psicologia , Feminino , Hemodinâmica , Humanos , Adulto Jovem
6.
Appl Neuropsychol Adult ; 29(5): 1208-1220, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-33397159

RESUMO

One of the key challenges in assessing cognitive performance is to detect not only apparent impairment but to also pick up on subtle differences. Computerized tests benefit especially from the acquisition of fine-grained outcome measures. However, the equivalency of paper-based and computerized tests cannot be assumed. The Trail-Making-Test is a paper-pencil cognitive assessment tool (ppTMT) that has been used in many research studies to evaluate visuomotor abilities and mental flexibility. A digital version of the extended TMT (including a condition measuring fine motor speed) called the dTMT has been developed. This study aims to test (1) reliability, (2) equivalence, and (3) agreement of the ppTMT and dTMT. A total of 53 healthy individuals aged 19 to 82 years of age (22 men, 31 women; mean age 42.2, SD = 22.8) completed three trials per ppTMT and dTMT condition. Part M involves following a predefined path, Part A links numbers randomly distributed in space, in ascending order, and Part B alternates between linking numbers and letters. dTMT scores were highly reproducible, correlated strongly with paper-pencil administered durations, and discriminated young from older adults. Measures of reliability, sensitivity, and clinical meaning for dTMT scores were favorable compared with ppTMT-based testing. Our findings support the comparability of TMT-indices in computerized assessments. While many digital biomarker efforts are in progress (e.g., neurodegenerative disorders), the dTMT sets itself apart through its high sensitivity, the alternate forms, and the additional component measures. In this light, it could serve as a starting point for an early diagnostic tool.


Assuntos
Teste de Sequência Alfanumérica , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Reprodutibilidade dos Testes , Adulto Jovem
7.
Polymers (Basel) ; 13(22)2021 Nov 16.
Artigo em Inglês | MEDLINE | ID: mdl-34833263

RESUMO

Biodegradable triblock copolymers based on poly(ε-caprolactone) (PCL) and poly(lactic acid) (PLA) were synthesized via ring-opening polymerization of L-lactide followed by reversible addition-fragmentation chain-transfer (RAFT) polymerization of poly(methyl vinyl ketone) (PMVK) as a photodegradable block, and characterized by FT-IR and 1H NMR spectroscopy for structural analyses, and by differential scanning calorimetry (DSC) and thermogravimetric analysis (TGA) for their thermal properties. Porous, biodegradable PCL-b-PLA microspheres were fabricated via the oil/water (O/W) emulsion evaporation method, followed by photodegradation of PMVK blocks by UV irradiation. The macro-chain transfer agent (CTA) synthesized by reacting a carboxylic-acid-terminated CTA-S-1-dodecyl-S'-(a,a'-dimethyl-a''-acetic acid)trithiocarbonate (DDMAT)-with a hydroxyl-terminated PCL-b-PLA block copolymer was used to synthesize well-defined triblock copolymers with methyl vinyl ketone via RAFT polymerization with controlled molecular weights and narrow polydispersity. Gel permeation chromatography traces indicated that the molecular weight of the triblock copolymer decreased with UV irradiation time because of the photodegradation of the PMVK blocks. The morphology of the microspheres before and after UV irradiation was investigated using SEM and videos of three-dimensional confocal laser microscopy, showing a change in their surface texture from smooth to rough, with high porosity owing to the photodegradation of the PMVK blocks to become porous templates.

8.
Artigo em Inglês | MEDLINE | ID: mdl-34063304

RESUMO

The ability to process goal-related visual information while ignoring goal-irrelevant information is essential for the human attention system. The study aimed to investigate how perceptual-cognitive performance was affected during high-intensity interval training (HIIT) using a 3D-multiple object tracking (3D-MOT) task called Neurotracker (NT). In an experimental design, 42 healthy adults (age M = 23.3 SD = 2.94, VO2max 52.8 ± 5.66 mL·kg-1·min-1) were randomly assigned to an intervention (HIIT + NT, NT, HIIT) or control group. NT performance (20 trials per session) was measured pre-and post-test (at 5, 15, and 25 min while running on the treadmill). The participants trained twice a week for a 4-week intervention period. There was a significant interaction effect between pre/post-test and groups regarding perceptual-cognitive performance, indicating similar enhancements in the HIIT + NT and the NT group during exercise. HIIT influences physical fitness but did not show any impact on perceptual-cognitive performance. Due to the specific NT task characteristics, improved physical abilities may not directly impact sport-specific perceptual-cognitive performance. Our findings suggest that training resulted in substantial task-specific gains. Therefore, combination training may be proposed as a training program to improve perceptual-cognitive, and physical performance in a time-efficient way.


Assuntos
Treinamento Intervalado de Alta Intensidade , Adulto , Cognição , Exercício Físico , Teste de Esforço , Humanos , Aptidão Física
9.
Eur J Neurosci ; 54(12): 8225-8248, 2021 12.
Artigo em Inglês | MEDLINE | ID: mdl-33876859

RESUMO

Studies on the effects of acute exercises on cognitive functions vary greatly and depend on the duration and intensity of exercise and the type of cognitive tasks. This study aimed to investigate the neural correlates that underpin the acute effects of high-intensity interval (HIIE) versus moderate-intensity continuous exercise (MCE) on fine motor-cognitive performance while walking (dual-task, DT) in healthy young adults. Twenty-nine healthy right-handers (mean age: 25.1 years ± 4.04; 7 female) performed the digital trail-making-test (dTMT) while walking (5 km/h) before and after acute exercise. During task performance, the hemodynamic activation of the frontopolar area (FPA), dorsolateral prefrontal (DLPFC), and motor cortex (M1) was recorded using functional near-infrared spectroscopy (fNIRS). Both HIIE and MCE resulted in improved dTMT performance, as reflected by an increase in the number of completed circles and a reduction in the time within and between circuits (reflecting improvements in working memory, inhibition, and decision making). Notably, HIIE evoked higher cortical activity on all brain areas measured in the present study than the MCE group. To our knowledge, these results provide the first empirical evidence using a mobile neuroimaging approach that both HIIE and MCE improve executive function during walking, likely mediated by increased activation of the task-related area of the prefrontal cortex and the ability to effectively use, among other things, high fitness levels as neural enrichment resources.


Assuntos
Espectroscopia de Luz Próxima ao Infravermelho , Análise e Desempenho de Tarefas , Adulto , Cognição , Exercício Físico/fisiologia , Feminino , Humanos , Córtex Pré-Frontal/diagnóstico por imagem , Córtex Pré-Frontal/fisiologia , Espectroscopia de Luz Próxima ao Infravermelho/métodos , Caminhada/fisiologia , Adulto Jovem
10.
Pharmaceuticals (Basel) ; 15(1)2021 Dec 24.
Artigo em Inglês | MEDLINE | ID: mdl-35056074

RESUMO

Gene therapy is a suitable alternative to chemotherapy due to the complications of drug resistance and toxicity of drugs, and is also known to reduce the occurrence of cellular mutation through the use of gene carriers. In this study, gene carrier nanoparticles with minimal toxicity and high transfection efficiency were fabricated from a biocompatible and biodegradable polymer, l-tyrosine polyurethane (LTU), which was polymerized from presynthesized desaminotyrosyl tyrosine hexyl ester (DTH) and polyethylene glycol (PEG), by using double emulsion and solvent evaporation techniques, resulting in the formation of porous nanoparticles, and then used to evaluate their potential biological activities through molecular controlled release and transfection studies. To assess cellular uptake and transfection efficiency, two model drugs, fluorescently labeled bovine serum albumin (FITC-BSA) and plasmid DNA-linear polyethylenimine (LPEI) complex, were successfully encapsulated in nanoparticles, and their transfection properties and cytotoxicities were evaluated in LX2 as a normal cell and in HepG2 and MCF7 as cancer cells. The morphology and average diameter of the LTU nanoparticles were confirmed using light microscopy, transmission electron microscopy, and dynamic light scattering, while confocal microscopy was used to validate the cellular uptake of FITC-BSA-encapsulated LTU nanoparticles. Moreover, the successful cellular uptake of LTU nanoparticles encapsulated with pDNA-LPEI and the high transfection efficiency, confirmed by gel electrophoresis and X-gal assay transfection, indicated that LTU nanoparticles had excellent cell adsorption ability, facilitated gene encapsulation, and showed the sustained release tendency of genes through transfection experiments, with an optimal concentration ratio of pDNA and LPEI of 1:10. All the above characteristics are ideal for gene carriers designed to transport and release drugs into the cytoplasm, thus facilitating effective gene therapy.

11.
Elife ; 92020 06 23.
Artigo em Inglês | MEDLINE | ID: mdl-32571478

RESUMO

Generation of autologous human motor neurons holds great promise for cell replacement therapy to treat spinal cord injury (SCI). Direct conversion allows generation of target cells from somatic cells, however, current protocols are not practicable for therapeutic purposes since converted cells are post-mitotic that are not scalable. Therefore, therapeutic effects of directly converted neurons have not been elucidated yet. Here, we show that human fibroblasts can be converted into induced motor neurons (iMNs) by sequentially inducing POU5F1(OCT4) and LHX3. Our strategy enables scalable production of pure iMNs because of the transient acquisition of proliferative iMN-intermediate cell stage which is distinct from neural progenitors. iMNs exhibited hallmarks of spinal motor neurons including transcriptional profiles, electrophysiological property, synaptic activity, and neuromuscular junction formation. Remarkably, transplantation of iMNs showed therapeutic effects, promoting locomotor functional recovery in rodent SCI model. Together, our advanced strategy will provide tools to acquire sufficient human iMNs that may represent a promising cell source for personalized cell therapy.


Assuntos
Fibroblastos/fisiologia , Regulação da Expressão Gênica , Proteínas com Homeodomínio LIM/genética , Locomoção/fisiologia , Neurônios Motores/transplante , Fator 3 de Transcrição de Octâmero/genética , Recuperação de Função Fisiológica/fisiologia , Traumatismos da Medula Espinal/terapia , Fatores de Transcrição/genética , Animais , Transplante de Células , Modelos Animais de Doenças , Feminino , Humanos , Proteínas com Homeodomínio LIM/metabolismo , Masculino , Camundongos , Camundongos Nus , Neurônios Motores/fisiologia , Fator 3 de Transcrição de Octâmero/metabolismo , Traumatismos da Medula Espinal/fisiopatologia , Fatores de Transcrição/metabolismo
12.
Cells ; 9(5)2020 05 21.
Artigo em Inglês | MEDLINE | ID: mdl-32455709

RESUMO

Alzheimer's disease (AD) is a complex, age-related neurodegenerative disease that is the most common form of dementia. However, the cure for AD has not yet been founded. The accumulation of amyloid beta (Aß) is considered to be a hallmark of AD. Beta-site amyloid precursor protein cleaving enzyme 1 (BACE1), also known as beta secretase is the initiating enzyme in the amyloidogenic pathway. Blocking BACE1 could reduce the amount of Aß, but this would also prohibit the other functions of BACE1 in brain physiological activity. SPONDIN1 (SPON1) is known to bind to the BACE1 binding site of the amyloid precursor protein (APP) and blocks the initiating amyloidogenesis. Here, we show the effect of SPON1 in Aß reduction in vitro in neural cells and in an in vivo AD mouse model. We engineered mouse induced neural stem cells (iNSCs) to express Spon1. iNSCs harboring mouse Spon1 secreted SPON1 protein and reduced the quantity of Aß when co-cultured with Aß-secreting Neuro 2a cells. The human SPON1 gene itself also reduced Aß in HEK 293T cells expressing the human APP transgene with AD-linked mutations through lentiviral-mediated delivery. We also demonstrated that injecting SPON1 reduced the amount of Aß and ameliorated cognitive dysfunction and memory impairment in 5xFAD mice expressing human APP and PSEN1 transgenes with five AD-linked mutations.


Assuntos
Doença de Alzheimer/complicações , Doença de Alzheimer/metabolismo , Peptídeos beta-Amiloides/metabolismo , Disfunção Cognitiva/complicações , Disfunção Cognitiva/metabolismo , Proteínas da Matriz Extracelular/metabolismo , Transtornos da Memória/complicações , Transtornos da Memória/metabolismo , Animais , Efeito Espectador , Modelos Animais de Doenças , Feminino , Humanos , Camundongos Endogâmicos C57BL , Células-Tronco Neurais/metabolismo
13.
Pharmaceutics ; 12(3)2020 Mar 21.
Artigo em Inglês | MEDLINE | ID: mdl-32245172

RESUMO

Biodegradable polyfumarateurethane (PFU) for use as a bupivacaine delivery vehicle, synthesized using di-(2-hydroxypropyl fumarate) (DHPF), polyethylene glycol (PEG) and 1,6-hexamethylene diisocyanate (HMDI), was designed to be degradable through the hydrolysis and enzymatic degradation of the ester bonds in its polymer backbone. Using a water-in-oil-in-water double emulsion techniques, nanoparticles encapsulating water or fluorescein isothiocyanate (FITC) were fabricated to avoid the immune system owing to the presence of PEG on their surface. The morphologies of these nanoparticles were characterized by DLS, TEM, FE-SEM, and fluorescent microscopies. The present study explored the encapsulation, loading efficiency and in vitro drug release of bupivacaine encapsulated with biodegradable PFU nanoparticles for the treatment of local anesthesia. Various concentrations of bupivacaine were encapsulated into nanoparticles and their encapsulation efficiencies and drug loading were investigated. Encapsulation efficiency was highest when 2.5% bupivacaine was encapsulated. Drug release behavior from the bupivacaine-loaded PFU nanoparticles followed a sustained release profile.

14.
Arterioscler Thromb Vasc Biol ; 40(4): e105-e113, 2020 04.
Artigo em Inglês | MEDLINE | ID: mdl-32075417

RESUMO

OBJECTIVE: Vascular progenitor cells (VPCs), which are able to differentiate into both endothelial cells and smooth muscle cells, have the potential for treatment of ischemic diseases. Generated by pluripotent stem cells, VPCs carry the risk of tumorigenicity in clinical application. This issue could be resolved by direct lineage conversion, the induction of functional cells from another lineage by using only lineage-restricted transcription factors. Here, we show that induced VPCs (iVPCs) can be generated from fibroblasts by ETS (E-twenty six) transcription factors, Etv2 and Fli1. Approach and Results: Mouse fibroblasts were infected with lentivirus encoding Etv2 and Fli1. Cell colonies appeared in Fli1- and Etv2/Fli1-infected groups and were mechanically picked. The identity of cell colonies was confirmed by proliferation assay and reverse-transcription polymerase chain reaction with vascular markers. Etv2/Fli1- infected cell colonies were sorted by CD144 (also known as CDH5, VE-cadherin). We defined that CD144-positive iVPCs maintained its own population and expanded stably at multiple passages. iVPCs could differentiate into functional endothelial cells and smooth muscle cells by a defined medium. The functionalities of iVPC-derived endothelial cells and smooth muscle cells were confirmed by analyzing LDL (low-density lipoprotein) uptake, carbachol-induced contraction, and tube formation in vitro. Transplantation of iVPCs into the ischemic hindlimb model enhanced blood flow without tumor formation in vivo. Human iVPCs were generated by human ETS transcription factors ETV2 and FLI1. CONCLUSIONS: We demonstrate that ischemic disease curable iVPCs, which have self-renewal and bipotency, can be generated from mouse fibroblasts by enforced ETS family transcription factors, Etv2 and Fli1 expression. Our simple strategy opens insights into stem cell-based ischemic disease therapy.


Assuntos
Fibroblastos/citologia , Isquemia/fisiopatologia , Proteína Proto-Oncogênica c-fli-1/fisiologia , Células-Tronco/fisiologia , Fatores de Transcrição/fisiologia , Animais , Antígenos CD , Caderinas , Diferenciação Celular , Linhagem Celular , Proliferação de Células , Modelos Animais de Doenças , Células Endoteliais/citologia , Membro Posterior/irrigação sanguínea , Isquemia/terapia , Miócitos de Músculo Liso/citologia , Transplante de Células-Tronco , Células-Tronco/imunologia
15.
Acute Crit Care ; 34(1): 86-91, 2019 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31723910

RESUMO

The Jackson table has minimal effects on cardiac function because it does not elevate abdominal and thoracic pressures. In addition, it decreases venous congestion and increases exposure of the surgical field. However, the hips and knees are flexed with inappropriate padding, and venostasis is promoted and increased. Pulmonary thromboembolism (PTE) is fatal; thus immediate diagnosis and treatment are essential. However, clinical signs of intraoperative PTE are difficult to discern. Thrombolytic therapy can be considered as first-line therapy, but bleeding limits its use. The authors report a case of PTE resulting from patient positional change after spine surgery, and the use of immediate postoperative recombinant tissue-type plasminogen activator.

16.
PLoS One ; 14(8): e0221085, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31404112

RESUMO

Direct conversion from fibroblasts to generate hepatocyte like-cells (iHeps) bypassing the pluripotent state has been described in previous reports as an attractive method acquiring hepatocytes for cell-based therapy. The limited proliferation of iHeps, however, has hampered it uses in cell-based therapy. Since hepatic stem cells (HepSCs) possess self-renewal and bipotency with the capacity to differentiate into both hepatocytes and cholangiocytes, they have therapeutic potential for treating liver disease. Here, we investigated the therapeutic effects of induced HepSCs (iHepSCs) on a carbon tetrachloride (CCl4)-induced liver fibrosis model. We demonstrate that Oct4 and Hnf4a are sufficient to convert fibroblasts into expandable iHepSCs. Hepatocyte-like cells derived from iHepSCs (iHepSC-HEPs) exhibit the typical morphology of hepatocytes and hepatic functions, including glycogen storage, low-density lipoprotein (LDL) uptake, Indocyanine green (ICG) detoxification, drug metabolism, urea production, and albumin secretion. iHepSCs-derived cholangiocyte-like cells (iHepSC-CLCs) expressed cholangiocyte-specific markers and formed cysts and tubule-like structures with apical-basal polarity and secretory function in three-dimensional culture condition. Furthermore, iHepSCs showed anti-inflammatory and anti-fibrotic effects in CCl4-induced liver fibrosis. This study demonstrates that Oct4 and Hnf4α-induced HepSCs show typical hepatic and biliary functionality in vitro. It also presents the therapeutic effect of iHepSCs in liver fibrosis. Therefore, directly converting iHepSCs from somatic cells may facilitate the development of patient-specific cell-based therapy for chronic liver damage.


Assuntos
Intoxicação por Tetracloreto de Carbono , Fator 4 Nuclear de Hepatócito , Células-Tronco Pluripotentes Induzidas , Cirrose Hepática , Fígado , Lesão Pulmonar , Fator 3 de Transcrição de Octâmero , Transplante de Células-Tronco , Animais , Intoxicação por Tetracloreto de Carbono/genética , Intoxicação por Tetracloreto de Carbono/metabolismo , Intoxicação por Tetracloreto de Carbono/terapia , Fator 4 Nuclear de Hepatócito/genética , Fator 4 Nuclear de Hepatócito/metabolismo , Células-Tronco Pluripotentes Induzidas/metabolismo , Células-Tronco Pluripotentes Induzidas/patologia , Células-Tronco Pluripotentes Induzidas/transplante , Fígado/metabolismo , Fígado/patologia , Cirrose Hepática/induzido quimicamente , Cirrose Hepática/genética , Cirrose Hepática/metabolismo , Cirrose Hepática/terapia , Lesão Pulmonar/induzido quimicamente , Lesão Pulmonar/genética , Lesão Pulmonar/metabolismo , Masculino , Camundongos , Fator 3 de Transcrição de Octâmero/genética , Fator 3 de Transcrição de Octâmero/metabolismo
17.
Int J Mol Sci ; 19(11)2018 Oct 31.
Artigo em Inglês | MEDLINE | ID: mdl-30384504

RESUMO

Bisphenol A (BPA) is synthetic organic compound that exhibits estrogen-like properties and it induces mitochondrial superoxide production. Melatonin (Mela) protects against BPA-mediated cell damage and apoptosis. However, the antioxidative effects of Mela against BPA-induced superoxide production in porcine oocytes are still not known. In this study, we investigated the antioxidative effects of Mela against BPA-derived superoxide on oocyte maturation in pigs. To investigate the effects of the superoxide specific scavenger, Mito-TEMPO, on porcine oocyte maturation in response to BPA exposure apoptosis proteins, we treated the oocytes with Mito-TEMPO (0.1 µM) after pre-treating them with BPA (75 µM) for 22 h. As expected, the reduction in meiotic maturation and cumulus cell expansion of cumulus-oocyte-complexes (COCs) in the BPA (75 µM) treated group was recovered (p < 0.01) by treatment with Mito-TEMPO (0.1 µM). An increase in the levels of mitochondrial apoptotic proteins (AIF, cleaved Cas 3 and cleaved Parp1) in response to BPA-induced damage was also reduced by Mito-TEMPO treatment in porcine COCs. Interestingly, we confirmed the positive effects of Mela with respect to superoxide production upon BPA exposure during oocyte maturation and also confirmed the reduction in mitochondrial apoptosis in Mela (0.1 µM)-treated porcine COCs. These results provide evidence for the first time that antioxidative effects of Mela on BPA-derived superoxide improve porcine oocyte maturation.


Assuntos
Antioxidantes/farmacologia , Compostos Benzidrílicos/farmacologia , Melatonina/farmacologia , Mitocôndrias/metabolismo , Oócitos/metabolismo , Fenóis/farmacologia , Superóxidos/metabolismo , Animais , Feminino , Proteínas Mitocondriais/metabolismo , Suínos
18.
NMC Case Rep J ; 5(4): 115-117, 2018 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-30327754

RESUMO

The objective of this study is to present a rare case of an invaginated inferior vena cava (IVC) aneurysm in the lumbar intradiscal space. A 73-year-old woman with lower back pain and bilateral lower extremity swelling presented to the clinic. She had undergone spinal surgery performed thrice at the same site (L4-L5) in another hospital and a separate posterolateral fusion surgery procedure 3 years previously. On plain radiography, pseudarthrosis was observed at L4-L5 segment. Contrast computed tomography (CT) imaging revealed a dilatation of the IVC in the intradiscal space of L4-L5. On the anterior side, anterior discectomy was performed. Following insertion of the allograft bone chip and cage, the invaginated IVC aneurysm was repositioned. Implant removal and screw fixation were performed posteriorly. Post-surgery, the patient's lower back pain improved, and the start of anticoagulation treatment after vascular evaluation was planned. Although there have been numerous case reports of patients with intradiscal cysts or gas requiring surgical treatment, there have not yet been any reports of those with invaginated IVC in an intradiscal space. It is important to provide the appropriate treatment based on a thorough prior understanding of the patient's anatomy.

19.
Mitochondrion ; 35: 80-86, 2017 07.
Artigo em Inglês | MEDLINE | ID: mdl-28552593

RESUMO

Mitochondrial dynamics are associated with the development of porcine embryos. However, little is known about the effects of mitochondrial dynamics-related genes (Drp1 and pDrp1-Ser616) on early porcine embryo development. Here, we investigated the effect of Drp1-dependent mitochondrial fission signaling on the development of porcine embryos using the mitochondrial fission inducer, tyrphostin A9 (TA9). We determined that TA9 (1µM) treated embryos were increased the mitochondrial functions, blastocyst development rate and quality, as well as decreased mitochondria-specific superoxide and mitochondrial apoptosis. Thus, TA9-induced appropriate mitochondrial fission improved the developmental competence via maintenance of a balance in mitochondrial dynamics in porcine embryo.


Assuntos
Blastocisto/efeitos dos fármacos , Dinaminas/metabolismo , Dinâmica Mitocondrial , Suínos/embriologia , Tirfostinas/metabolismo , Animais , Feminino
20.
Korean J Anesthesiol ; 69(2): 167-70, 2016 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-27064682

RESUMO

Encountering a patient with unanticipated laryngotracheal stenosis (LTS) during anesthetic induction is challenging for an anesthesiologist. Because routine history taking and pre-anesthetic evaluation cannot rule out the possibility of LTS, other measures should be taken. Perioperative airway maintenance is considered crucial for avoiding complications such as airway edema, bleeding, obstruction, collapse, and ultimately respiratory failure and arrest. We report an unanticipated tracheal stenosis discovered during anesthetic induction that hindered endotracheal intubation. Because airway maintenance was difficult, we postponed surgery until determining the cause of the difficult entry, considered possible therapeutic approaches (both anesthetic and surgical), and provided successful surgery with a continuous epidural block.

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