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1.
Sci Rep ; 13(1): 19380, 2023 11 08.
Artigo em Inglês | MEDLINE | ID: mdl-37938623

RESUMO

Coats' disease is an idiopathic retinal vascular disorder, known to usually occur unilaterally; however, recent studies have highlighted vascular abnormalities in the fellow unaffected eyes. This retrospective study investigated the peripheral vascular features and macular vascular structure of unaffected fellow eyes in patients with unilateral Coats' disease using multimodal imaging tools. We analysed images of patients, including bilateral ultra-widefield imaging, fluorescein angiography (FA), ultra-widefield FA, or standard fundus photography. Available bilateral optical coherence tomography angiography (OCT-A) images were used for macular vascular structure analysis. OCT-A parameters, including foveal avascular zone (FAZ), perfusion index, and vessel density (VD) in the superficial and deep capillary plexuses (SCP, DCP), were calculated using Image J software. The mean age at diagnosis was 34.5 ± 17.9 years. The mean final best-corrected visual acuity of the affected eyes was logMAR 0.78 ± 0.79, while that of the fellow eyes was logMAR 0.04 ± 0.12. Ten fellow eyes had microaneurysms (47.6%), two had tortuous vessel abnormalities (9.5%), and 11(52.4%) had abnormal vascular findings on FA. Although there was a trend towards larger DCP FAZ (1.201 ± 0.086 vs. 1.072 ± 0.226), and lower DCP VD (8.593 ± 1.583 vs. 10.827 ± 3.392) in the affected eyes as measured by the Cirrus machine, the difference was not statistically significant between affected and fellow eyes when measured using the Zeiss Cirrus machine (P = 0.686, P = 0.343, respectively). However, when measured with the Spectralis machine, DCP FAZ was larger in affected eyes (0.828 ± 0.426 vs. 0.254 ± 0.092, P = 0.002) and DCP VD was lower in affected eyes (6.901 ± 2.634 vs. 17.451 ± 7.207, P = 0.002) compared to the fellow eyes, while other parameters showed no significant variations. These findings indicate that there may be subtle vascular abnormalities primarily located in the peripheral regions of the unaffected fellow eyes in patients with unilateral Coats' disease, while the macular microvasculature remains unaffected.


Assuntos
Macula Lutea , Telangiectasia Retiniana , Humanos , Adolescente , Adulto Jovem , Adulto , Pessoa de Meia-Idade , Telangiectasia Retiniana/diagnóstico por imagem , Estudos Retrospectivos , Tomografia de Coerência Óptica , Angiofluoresceinografia
2.
Korean J Ophthalmol ; 37(5): 373-379, 2023 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-37562438

RESUMO

PURPOSE: Although the popularity of Descemet membrane endothelial keratoplasty (DMEK) is increased, there is still few clinical studies in Korea. In this study, we aimed to report the initial clinical outcomes of DMEK in patients followed up for more than 6 months. METHODS: A total of 96 eyes that underwent DMEK by a single surgeon for Fuchs endothelial corneal dystrophy, pseudophakic bullous keratopathy, or other indications were evaluated for best-corrected visual acuity (BCVA), endothelial cell density (ECD), central corneal thickness (CCT), postoperative complications, and graft survival. RESULTS: The postoperative BCVA significantly increased compared to the preoperative BCVA by 59.4% (1.00 ± 0.77 logarithm of the minimum angle of resolution vs. 0.67 ± 0.76 logarithm of the minimum angle of resolution, p < 0.001). The average preoperative ECD was 754 ± 382 cells/mm2, increasing to 1,333 ± 562 cells/mm2 at 3 months (76.8%, p < 0.001), 1,334 ± 632 cells/mm2 at 6 months (76.9%, p < 0.001), 1,121 ± 474 cells/mm2 at 12 months (48.7%, p = 0.024), and 972 ± 458 cells/mm2 at 24 months postoperatively (28.9%, p = 0.445). Compared to 3 months, the ECD declined by 15.9% at 12 months (p = 0.009) and 27.1% at 24 months postoperatively (p = 0.158). The average CCT was 675 ± 113 µm preoperatively, decreasing to 581 ± 102, 574 ± 101, and 594 ± 94 µm at 6, 12, and 24 months after DMEK, respectively (p < 0.001 between all follow-up time points). Allograft rejection was detected in three (3.1%) and 14 eyes (14.6%) underwent retransplantation at an average of 10.1 ± 8.4 months after DMEK. CONCLUSIONS: DMEK is promising for maintaining corneal clarity, low postoperative complication rates, and stable graft longevity.

3.
Materials (Basel) ; 16(13)2023 Jun 21.
Artigo em Inglês | MEDLINE | ID: mdl-37444829

RESUMO

A one-step hybrid bending/diffusion bonding process (HB/DBP) was developed for application to Ti-6Al-4V sheets to effectively improve buy-to-fly (BTF) ratio of aircraft parts, integrating sequential diffusion bonding followed by a bending process. The resulting bonding characteristics of these titanium alloy sheets were analyzed. Microstructural analysis and mechanical lap shear tests were performed to estimate the bonding quality. Additionally, bonding ratio, thickness strain, and shear strength were evaluated in relation to pressure under increasing temperature. When the applied pressure was lower than 0.5 MPa, early failure occurred at the joint of the specimens. However, when high pressure was applied, early failure occurred near the joint. To discuss the phenomenon, time-dependent viscoplastic material properties were characterized, and a numerical simulation analysis was performed. Viscoplastic deformation was observed around the bending area, which caused weakness around the bond under high-pressure conditions. A prototype of a Y-shaped heat shield was manufactured and the buy-to-fly ratio was effectively improved using the newly developed process. This study demonstrates the potential of applying the developed process for producing aircraft parts and the importance of viscoplastic behavior for the analysis of final product reliability.

4.
J Clin Med ; 11(11)2022 May 24.
Artigo em Inglês | MEDLINE | ID: mdl-35683353

RESUMO

Background and Aims: The utility of clinical information from esophagogastroduodenoscopy (EGD) reports has been limited because of its unstructured narrative format. We developed a natural language processing (NLP) pipeline that automatically extracts information about gastric diseases from unstructured EGD reports and demonstrated its applicability in clinical research. Methods: An NLP pipeline was developed using 2000 EGD and associated pathology reports that were retrieved from a single healthcare center. The pipeline extracted clinical information, including the presence, location, and size, for 10 gastric diseases from the EGD reports. It was validated with 1000 EGD reports by evaluating sensitivity, positive predictive value (PPV), accuracy, and F1 score. The pipeline was applied to 248,966 EGD reports from 2010-2019 to identify patient demographics and clinical information for 10 gastric diseases. Results: For gastritis information extraction, we achieved an overall sensitivity, PPV, accuracy, and F1 score of 0.966, 0.972, 0.996, and 0.967, respectively. Other gastric diseases, such as ulcers, and neoplastic diseases achieved an overall sensitivity, PPV, accuracy, and F1 score of 0.975, 0.982, 0.999, and 0.978, respectively. The study of EGD data of over 10 years revealed the demographics of patients with gastric diseases by sex and age. In addition, the study identified the extent and locations of gastritis and other gastric diseases, respectively. Conclusions: We demonstrated the feasibility of the NLP pipeline providing an automated extraction of gastric disease information from EGD reports. Incorporating the pipeline can facilitate large-scale clinical research to better understand gastric diseases.

5.
Biomaterials ; 283: 121460, 2022 04.
Artigo em Inglês | MEDLINE | ID: mdl-35286852

RESUMO

The palatine tonsils (hereinafter referred to as "tonsils") serve as a reservoir for viral infections and play roles in the immune system's first line of defense. The aims of this study were to establish tonsil epithelial cell-derived organoids and examine their feasibility as an ex vivo model for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. The tonsil organoids successfully recapitulated the key characteristics of the tonsil epithelium, including cellular composition, histologic properties, and biomarker distribution. Notably, the basal layer cells of the organoids express molecules essential for SARS-CoV-2 entry, such as angiotensin-converting enzyme 2 (ACE2), transmembrane serine protease 2 (TMPRSS2) and furin, being susceptible to the viral infection. Changes in the gene expression profile in tonsil organoids revealed that 395 genes associated with oncostatin M signaling and lipid metabolism were highly upregulated within 72 h after SARS-CoV-2 infection. Notably, remdesivir suppressed the viral RNA copy number in organoid culture supernatants and intracellular viral protein levels in a dose-dependent manner. Here, we suggest that tonsil epithelial organoids could provide a preclinical and translational research platform for investigating SARS-CoV-2 infectivity and transmissibility or for evaluating antiviral candidates.


Assuntos
COVID-19 , Organoides , Humanos , Tonsila Palatina , SARS-CoV-2 , Internalização do Vírus
6.
J Cell Mol Med ; 26(7): 2104-2118, 2022 04.
Artigo em Inglês | MEDLINE | ID: mdl-35178859

RESUMO

Damage to normal tissue can occur over a long period after cancer radiotherapy. Free radical by radiation can initiate or accelerate chronic inflammation, which can lead to atherosclerosis. However, the underlying mechanisms remain unclear. Vascular smooth muscle cells (VSMCs) proliferate in response to JAK/STAT3 signalling. C-reactive protein (CRP) can induce VSMCs apoptosis via triggering NADPH oxidase (NOX). Apoptotic VSMCs promote instability and inflammation of atherosclerotic lesions. Herein, we identified a VSMCs that switched from proliferation to apoptosis through was enhanced by radiation-induced CRP. NOX inhibition using lentiviral sh-p22phox prevented apoptosis upon radiation-induced CRP. CRP overexpression reduced the amount of STAT3/Ref-1 complex, decreased JAK/STAT phosphorylation and formed a new complex of Ref-1/CRP in VSMC. Apoptosis of VSMCs was further increased by CRP co-overexpressed with Ref-1. Functional inhibition of NOX or p53 also prevented apoptotic activity of the CRP-Ref-1 complex. Immunofluorescence showed co-localization of CRP, Ref-1 and p53 with α-actin-positive VSMC in human atherosclerotic plaques. In conclusion, radiation-induced CRP increased the VSMCs apoptosis through Ref-1, which dissociated the STAT3/Ref-1 complex, interfered with JAK/STAT3 activity, and interacted with CRP-Ref-1, thus resulting in transcription-independent cell death via p53. Targeting CRP as a vascular side effect of radiotherapy could be exploited to improve curability.


Assuntos
Proteína C-Reativa , Músculo Liso Vascular , Apoptose , Proteína C-Reativa/genética , Proteína C-Reativa/metabolismo , Células Cultivadas , Humanos , Músculo Liso Vascular/metabolismo , Miócitos de Músculo Liso/metabolismo , Espécies Reativas de Oxigênio/metabolismo , Fator de Transcrição STAT3/metabolismo
7.
Tissue Eng Regen Med ; 18(3): 467-478, 2021 06.
Artigo em Inglês | MEDLINE | ID: mdl-33515168

RESUMO

BACKGROUND: Schwann cells (SCs) secrete neurotrophic factors and provide structural support and guidance during axonal regeneration. However, nearby nerves may be damaged to obtain primary SCs, and there is a lack of nervous tissue donors. We investigated the potential of Wharton's Jelly-derived mesenchymal stem cells (WJ-MSCs) in differentiating into Schwann cell-like cells (WJ-SCLCs) as an alternative to SCs. We also examined whether implantation of WJ-SCLCs-laden acellular nerve grafts (ANGs) are effective in inducing functional recovery and nerve regeneration in an animal model of peripheral nerve injury. METHODS: The differentiation of WJ-MSCs into WJ-SCLCs was determined by analyzing SC-specific markers. The secretion of neurotrophic factors was assessed by the Neuro Discovery antibody array. Neurite outgrowth and myelination of axons were found in a co-culture system involving motor neuron cell lines. The effects of ANGs on repairing sciatic nerves were evaluated using video gait angle test, isometric tetanic force analysis, and toluidine blue staining. RESULTS: Compared with undifferentiated WJ-MSCs, WJ-SCLCs showed higher expression levels of SC-specific markers such as S100ß, GFAP, KROX20, and NGFR. WJ-SCLCs also showed higher secreted amounts of brain-derived neurotrophic factor, glial cell-derived neurotrophic factor, and granulocyte-colony stimulating factor than did WJ-MSCs. WJ-SCLCs effectively promoted the outgrowth and myelination of neurites in motor neuron cells, and WJ-SCLCs laden ANGs significantly facilitated peripheral nerve regeneration in an animal model of sciatic nerve injury. CONCLUSION: WJ-MSCs were readily differentiated into WJ-SCLCs, which effectively promoted the regeneration of peripheral nerves. Transplantation of WJ-SCLCs with ANGs might be useful for assisting peripheral nerve regeneration.


Assuntos
Células-Tronco Mesenquimais , Geleia de Wharton , Animais , Fator Neurotrófico Derivado de Linhagem de Célula Glial , Regeneração Nervosa , Células de Schwann , Nervo Isquiático
8.
RSC Adv ; 11(3): 1517-1523, 2021 Jan 04.
Artigo em Inglês | MEDLINE | ID: mdl-35424089

RESUMO

A highly fluorinated alternating polymer, P(RFMi-St), possessing improved thermal properties and patterning capabilities over perfluoroalkyl polymethacrylates under high energy radiation was achieved with semi-perfluorododecyl maleimide (RFMi) and styrene (St). RFMi could be synthesised efficiently via a Mitsunobu reaction condition and copolymerised with St by free radical and reversible-deactivation radical polymerisation protocols. P(RFMi-St) showed a satisfactory glass-transition temperature (108 °C) and intermolecular cross-linking behaviour under electron-beam and commercially more important extreme UV (λ = 13.5 nm) irradiation. The exposed regions lost their solubility, resulting in the successful formation of mechanically non-deteriorated negative-tone images down to 50 nm. In addition, P(RFMi-St) could be solution-processed with chemically non-damaging fluorous liquids, which enabled the polymer to be applied effectively on top of an organic semiconductor layer as a dielectric material (dielectric constant 2.7) for the organic field-effect transistor fabrication.

9.
Reprod Sci ; 28(2): 479-487, 2021 02.
Artigo em Inglês | MEDLINE | ID: mdl-33037561

RESUMO

Evidence is growing that phthalate esters play an important role in the pathogenesis of estrogen-dependent gynecologic diseases, especially uterine fibroids. We aimed to investigate whether in vitro treatment with di-(2-ethylhexyl)-phthalate (DEHP) affects angiogenesis, proliferation, and apoptosis in uterine fibroids. To ascertain this, we evaluated vascular endothelial growth factor (VEGF) expression and AKT/ERT phosphorylation and compared the fibroid volume between nonobese diabetic/severe combined immunodeficiency (NOD/SCID) mice fed with and without DEHP. VEGF expression was measured using enzyme-linked immunosorbent assay, and AKT/ERK phosphorylation was analyzed by western blot analysis in human myometrial and fibroid cells. The volume of the fibroid tissues implanted to NOD/SCID mice was measured, and the expression of collagen type I protein, Ki-67, proliferating cell nuclear antigen, and B cell lymphoma 2 were analyzed using immunohistochemistry. We could see significant increases in VEGF expression and AKT phosphorylation in human myometrial and fibroid cells treated with DEHP. The volume of the fibroid tissues was significantly increased in NOD/SCID mice fed with DEHP, which was accompanied by increased expression of collagen type I and AKT phosphorylation. Taken together, these results suggest that exposure to phthalate esters may influence uterine fibroid pathogenesis by increasing VEGF and collagen expression and upregulating AKT phosphorylation.


Assuntos
Dietilexilftalato/toxicidade , Ésteres/toxicidade , Leiomioma/patologia , Miométrio/efeitos dos fármacos , Neoplasias Uterinas/patologia , Animais , Apoptose/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Colágeno Tipo I/metabolismo , Progressão da Doença , MAP Quinases Reguladas por Sinal Extracelular/metabolismo , Feminino , Humanos , Leiomioma/metabolismo , Camundongos Endogâmicos NOD , Camundongos SCID , Miométrio/metabolismo , Miométrio/patologia , Neovascularização Patológica , Fosforilação , Proteínas Proto-Oncogênicas c-akt/metabolismo , Transdução de Sinais , Células Tumorais Cultivadas , Neoplasias Uterinas/metabolismo , Fator A de Crescimento do Endotélio Vascular/metabolismo
10.
Int J Mol Sci ; 21(19)2020 Oct 03.
Artigo em Inglês | MEDLINE | ID: mdl-33023023

RESUMO

Anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis is an autoimmune disorder which affects small- and, to a lesser degree, medium-sized vessels. ANCA-associated vasculitis encompasses three disease phenotypes: granulomatosis with polyangiitis (GPA), microscopic polyangiitis (MPA), and eosinophilic granulomatosis with polyangiitis (EGPA). This classification is largely based on clinical presentations and has several limitations. Recent research provided evidence that genetic background, risk of relapse, prognosis, and co-morbidities are more closely related to the ANCA serotype, proteinase 3 (PR3)-ANCA and myeloperoxidase (MPO)-ANCA, compared to the disease phenotypes GPA or MPA. This finding has been extended to the investigation of biomarkers predicting disease activity, which again more closely relate to the ANCA serotype. Discoveries related to the immunopathogenesis translated into clinical practice as targeted therapies are on the rise. This review will summarize the current understanding of the immunopathogenesis of ANCA-associated vasculitis and the interplay between ANCA serotype and proposed disease biomarkers and illustrate how the extending knowledge of the immunopathogenesis will likely translate into development of a personalized medicine approach in the management of ANCA-associated vasculitis.


Assuntos
Vasculite Associada a Anticorpo Anticitoplasma de Neutrófilos/genética , Anticorpos Anticitoplasma de Neutrófilos/genética , Mieloblastina/genética , Peroxidase/genética , Vasculite Associada a Anticorpo Anticitoplasma de Neutrófilos/sangue , Vasculite Associada a Anticorpo Anticitoplasma de Neutrófilos/classificação , Vasculite Associada a Anticorpo Anticitoplasma de Neutrófilos/patologia , Anticorpos Anticitoplasma de Neutrófilos/sangue , Biomarcadores/sangue , Síndrome de Churg-Strauss/sangue , Síndrome de Churg-Strauss/genética , Síndrome de Churg-Strauss/patologia , Granulomatose com Poliangiite/sangue , Granulomatose com Poliangiite/genética , Granulomatose com Poliangiite/patologia , Humanos , Poliangiite Microscópica/sangue , Poliangiite Microscópica/genética , Poliangiite Microscópica/patologia , Prognóstico , Sorogrupo
11.
ACS Appl Mater Interfaces ; 12(40): 45590-45601, 2020 Oct 07.
Artigo em Inglês | MEDLINE | ID: mdl-32914629

RESUMO

Despite their extraordinary mechanosensitivities, most channel-like crack-based strain sensors are limited by their poor levels of stretchability and linearity. This work presents a simple yet efficient way of modulating the cracking structure of thin metal films on elastomers to facilitate the development of high-performance wearable strain sensors. A net-shaped crack structure based on a thin platinum (Pt) film can be produced by coating an elastomer surface with M13 bacteriophages (phages) and consequently engineering the surface strain upon stretching. This process produces a Pt-on-phage (PoP) strain sensor that simultaneously exhibits high levels of stretchability (24%), sensitivity (maximum gauge factor ≈ 845.6 for 20-24%), and linearity (R2 ≈ 0.988 up to 20%). In addition, the sensor performance can be further modulated by either changing the phage coating volume or adding a silver nanowire coating to the PoP sensor film. The balanced strain-sensing performance, combined with fast response times and high levels of mechanical flexibility and operational stability, enables the devices to detect a wide range of human motions in real time after being attached to various body parts. Furthermore, PoP-based strain sensors can be usefully extended to detect more complex multidimensional strains through further strain engineering on a cross-patterned PoP film.

12.
Breast Cancer Res Treat ; 182(3): 591-600, 2020 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-32529408

RESUMO

PURPOSE: This study evaluates the oncogenic role of PIBF1 in triple-negative breast cancer (TNBC). TNBC is considered to have a poorer prognosis than other types of breast cancer and is associated with high risk of recurrence and distant metastasis. Currently, there are no effective therapies for the TNBC patients with distant metastasis due to the lack of targeted therapeutic options. METHODS: The effects of PIBF1 knockdown on the cell viability and motility of TNBC cell lines were investigated. Effects of PIBF1 overexpression on tumorigenicity and cell motility were confirmed using Ba/F3 cell line and xenograft study on BALB/c nude mice. RESULTS: In TNBC cell lines that highly express PIBF1, knockdown of PIBF1 induces apoptosis and suppresses cell viability and motility with activation of the ATR/CHK1 signaling pathway. Moreover, the oncogenic function of PIBF1 was confirmed using the Ba/F3 cell line. CONCLUSION: For the first time, these findings clarify the role of PIBF1 in regulating ATR/CHK1 signaling pathway and inhibiting the proliferation and migration of TNBC cell lines. These results demonstrate the oncogenic roles of PIBF1 and provide new insights into the function and the molecular mechanism of PIBF1 in malignant TNBC.


Assuntos
Proteínas Mutadas de Ataxia Telangiectasia/antagonistas & inibidores , Quinase 1 do Ponto de Checagem/antagonistas & inibidores , Proteínas da Gravidez/metabolismo , Fatores Supressores Imunológicos/metabolismo , Neoplasias de Mama Triplo Negativas/metabolismo , Animais , Apoptose/fisiologia , Proteínas Mutadas de Ataxia Telangiectasia/metabolismo , Biomarcadores Tumorais/genética , Biomarcadores Tumorais/metabolismo , Movimento Celular/fisiologia , Proliferação de Células/fisiologia , Quinase 1 do Ponto de Checagem/metabolismo , Feminino , Técnicas de Silenciamento de Genes , Xenoenxertos , Humanos , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Nus , Proteínas da Gravidez/biossíntese , Proteínas da Gravidez/genética , Transdução de Sinais , Fatores Supressores Imunológicos/biossíntese , Fatores Supressores Imunológicos/genética , Neoplasias de Mama Triplo Negativas/genética , Neoplasias de Mama Triplo Negativas/patologia , Células Tumorais Cultivadas
13.
Pancreatology ; 20(2): 247-253, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-31889624

RESUMO

BACKGROUND: Although several studies have focused on the oncologic impact of the preoperative prognostic nutritional index (PNI), there is no study correlating the preoperative PNI changes with the oncologic outcome of resected pancreatic cancer following neoadjuvant chemotherapy (NAC). METHODS: We retrospectively analyzed 107 pancreatic ductal adenocarcinoma patients who underwent NAC followed by surgical resection. ΔPNI was defined as post-NAC PNI subtracted from pre-NAC PNI. Patients were divided into high (≥-1.94, n = 54) and low ΔPNI groups (<-1.94, n = 53). Long-term oncologic outcomes, such as overall survival (OS) and disease-free survival (DFS), were compared. Univariate and multivariate analysis were used to identify independent prognostic factors. RESULTS: The high ΔPNI group correlated with lower pre-NAC PNI (46.96 ± 4.68 vs. 51.77 ± 5.63, p < 0.001) and higher post-NAC PNI (50.05 ± 4.80 vs. 42.56 ± 7.44, p < 0.001) more than the low ΔPNI group. The high ΔPNI group was also associated with longer OS compared with the low ΔPNI group (mean OS: 63.97 months [95% CI: 49.95-77.99] vs. 41.16 months [95% CI: 27.66-54.66], p = 0.003); there was no significant difference in DFS (p > 0.05). Multivariate analysis revealed that low ΔPNI was an independent risk factor for OS (HR, 3.516; 95% CI, 1.885-6.558; p < 0.001), but not for DFS (p > 0.05). CONCLUSIONS: Low ΔPNI (<-1.94) was an independent risk factor for the overall survival of resected pancreatic cancer patients following NAC. In the preoperative setting, improving the PNI can better the long-term oncologic outcome of this condition.


Assuntos
Carcinoma Ductal Pancreático/tratamento farmacológico , Carcinoma Ductal Pancreático/cirurgia , Terapia Neoadjuvante/métodos , Avaliação Nutricional , Neoplasias Pancreáticas/tratamento farmacológico , Neoplasias Pancreáticas/cirurgia , Idoso , Intervalo Livre de Doença , Feminino , Humanos , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Período Pré-Operatório , Prognóstico , Fatores de Risco , Análise de Sobrevida , Resultado do Tratamento
14.
Radiat Res ; 191(3): 262-270, 2019 03.
Artigo em Inglês | MEDLINE | ID: mdl-30702968

RESUMO

In the event of a mass casualty radiation scenario, biodosimetry has the potential to quantify individual exposures for triaging and providing dose-appropriate medical intervention. Structural maintenance of chromosomes 1 (SMC1) is phosphorylated in response to ionizing radiation. The goal of this study was to develop a new biodosimetry method using SMC1 phosphorylation as a measure of exposure to radiation. In the initial experiments, two normal human cell lines (WI-38VA-13 and HaCaT) and four lymphoblastoid cell lines were irradiated, and the levels of SMC1 phosphorylation at Ser-360 and Ser-957 were assessed using Western blotting. Subsequently, similar experiments were performed using peripheral blood mononuclear cells (PBMCs) obtained from 20 healthy adults. Phosphorylation of SMC1 at Ser-957 and Ser-360 was increased by exposure in a dose-dependent manner, peaked at 1-3 h postirradiation and then decreased gradually. Ser-360 was identified as a new phosphorylation site and was more sensitive to radiation than Ser-957, especially at doses below 1 Gy. Our results demonstrate a robust ex vivo response of phospho-SMC1-(Ser-360) to ionizing radiation in human PBMCs. Detection of phosphorylation at Ser-360 in SMC1 could be used as a marker of radiation exposure. Our findings suggest that it is feasible to measure blood cell-based changes in the phosphorylation level of a protein as an ex vivo radiation exposure detection method, even after low-dose exposure.


Assuntos
Proteínas de Ciclo Celular/química , Proteínas de Ciclo Celular/metabolismo , Proteínas Cromossômicas não Histona/química , Proteínas Cromossômicas não Histona/metabolismo , Leucócitos Mononucleares/metabolismo , Leucócitos Mononucleares/efeitos da radiação , Serina/metabolismo , Linhagem Celular , Cromatina/metabolismo , Relação Dose-Resposta à Radiação , Humanos , Fosforilação/efeitos da radiação , Fatores de Tempo
15.
Hum Reprod ; 33(5): 807-816, 2018 05 01.
Artigo em Inglês | MEDLINE | ID: mdl-29562285

RESUMO

STUDY QUESTION: Does interleukin-32 (IL-32) play a role in the pathogenesis of endometriosis? SUMMARY ANSWER: IL-32 might be involved in the pathogenesis of endometriosis through increased viability, proliferation and invasion of endometrial cells. WHAT IS KNOWN ALREADY: Endometriosis is characterized as a chronic inflammatory disease and several proinflammatory cytokines are suggested to be involved in its pathogenesis and pathophysiology. IL-32, recognized as a new proinflammatory cytokine and a strong inducer of other proinflammatory cytokines, has been shown to serve as a key modulator in several chronic inflammatory diseases. STUDY DESIGN, SIZE, DURATION: This study included comparison of IL-32 levels in the peritoneal fluids between women with and without endometriosis, in-vitro experiments using Ishikawa cells and endometrial stromal cells (ESCs), and experiments on IL-32 transgenic mice and wild-type mice with induced endometriosis. PARTICIPANTS/MATERIALS, SETTING, METHODS: IL-32 levels in the peritoneal fluids were measured using enzyme-linked immunosorbent assays. Cell viability, expression of proliferating cell nuclear antigen (PCNA), and cellular invasiveness were analyzed following in-vitro treatment of Ishikawa cells and ESCs with recombinant IL-32 alpha (α) and gamma (γ). Ectopic endometriotic lesions were compared between IL-32 transgenic mice and wild-type mice after autologous endometrial transplantation with immunohistochemistry for Ki-67 antigen and PCNA. MAIN RESULTS AND THE ROLE OF CHANCE: The peritoneal fluid concentration of IL-32 was significantly higher in patients with advanced stage endometriosis compared with the controls. In-vitro treatment with IL-32 α and γ caused significant increases in cellular viability, PCNA expression, and invasiveness in Ishikawa cells and ESCs. The IL-32 transgenic mice had a significantly larger size of the ectopic endometrial lesions with higher expression of Ki-67 antigen and PCNA compared with wild-type mice. LARGE SCALE DATA: N/A. LIMITATIONS, REASONS FOR CAUTION: It is still unclear whether IL-32 is a main regulator, or one of several downstream proinflammatory cytokines, causing establishment and/or progression of endometriosis. WIDER IMPLICATIONS OF THE FINDINGS: Further investigation on IL-32 signaling pathways may contribute to development a more effective treatment of endometriosis. STUDY FUNDING/COMPETING INTEREST(S): This research was supported by a grant of the Korea Health Technology R&D Project through the Korea Health Industry Development Institute (KHIDI), funded by the Ministry of Health & Welfare, Republic of Korea (Grant number: HI16C1682). None of the authors has anything to disclose.


Assuntos
Líquido Ascítico/metabolismo , Endometriose/metabolismo , Endométrio/metabolismo , Interleucinas/metabolismo , Adulto , Animais , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Feminino , Humanos , Inflamação/metabolismo , Interleucinas/farmacologia , Camundongos , Camundongos Transgênicos , Células Estromais/metabolismo
16.
Small ; 14(14): e1704232, 2018 04.
Artigo em Inglês | MEDLINE | ID: mdl-29473293

RESUMO

High sensitivity and high stretchability are two conflicting characteristics that are difficult to achieve simultaneously in elastic strain sensors. A highly sensitive and stretchable strain sensor comprising a microstructured metal nanowire (mNW)/elastomer composite film is presented. The surface structure is easily prepared by combining an mNW coating and soft-lithographic replication processes in a simple and reproducible manner. The densely packed microprism-array architecture of the composite film leads to a large morphological change in the mNW percolation network by efficiently concentrating the strain in the valley regions upon stretching. Meanwhile, the percolation network comprising mNWs with a high aspect ratio is stable enough to prevent electrical failure, even under high strains. This enables the sensor to simultaneously satisfy high sensitivity (gauge factor ≈81 at >130% strain) and high stretchability (150%) while ensuring long-term reliability (10 000 cycles at 150% strain). The sensor can also detect strain induced by bending and pressure, thus demonstrating its potential as a versatile sensing tool. The sensor is successfully utilized to monitor a wide range of human motions in real time. Furthermore, the unique sensing mechanism is easily extended to detect more complex multiaxial strains by optimizing the surface morphology of the device.

17.
ACS Appl Mater Interfaces ; 9(46): 40905-40913, 2017 Nov 22.
Artigo em Inglês | MEDLINE | ID: mdl-29099584

RESUMO

This work presents a new template-assisted fabrication method to obtain stretchable metal grids for high-performance stretchable transparent conducting electrodes (TCEs). Readily accessible metal woven mesh (MWM) is used as a template to make the fabrication process simple, cost-effective, reproducible, and potentially scalable by combining it with silver nanowire (AgNW) coating and elastomer filling processes. Stretchable TCEs are made with the AgNW-coated MWM and show remarkable optoelectronic performance with a sheet resistance of ∼3.2 Ω/sq and optical transmittance of >80%, large maximum stretchability of 40%, and electrical and mechanical robustness even under repeated stretching and bending deformations (1000 cycles). The device is demonstrated in a highly flexible touch screen panel that can operate well even in a bent state.

18.
ACS Appl Mater Interfaces ; 9(23): 19612-19621, 2017 Jun 14.
Artigo em Inglês | MEDLINE | ID: mdl-28534393

RESUMO

Recent efforts to develop stretchable resistive heaters open up the possibility for their use in wearable thermotherapy applications. Such heaters should have high electrothermal performance and stability to be used practically, and the fabrication must be simple, economic, reproducible, and scalable. Here we present a simple yet highly efficient way of producing high-performance stretchable heaters, which is based on a facile kirigami pattering (the art of cutting and folding paper) of a highly conductive paper for practical wearable thermotherapy. The resulting kirigami heater exhibits high heating performance at low voltage (>40 °C at 1.2 V) and fast thermal response (<60 s). The simple kirigami patterning approach enables the heater to be extremely stretchable (>400%) while stably retaining its excellent performance. Furthermore, the heater shows the uniform spatial distribution of heat over the whole heating area and is highly durable (1000 cycles at 300% strain). The heater attached to curvilinear body parts shows stable heating performance even under large motions while maintaining intimate conformal contact with the skin thanks to the high stretchability and sufficient restoring force. The usability of the heater as a wearable thermotherapy device is demonstrated by increased blood flow at the wrist during operation.


Assuntos
Dispositivos Eletrônicos Vestíveis , Calefação , Temperatura Alta , Hipertermia Induzida
19.
ACS Appl Mater Interfaces ; 9(20): 17499-17507, 2017 May 24.
Artigo em Inglês | MEDLINE | ID: mdl-28471157

RESUMO

Wearable pressure sensors are crucial building blocks for potential applications in real-time health monitoring, artificial electronic skins, and human-to-machine interfaces. Here we present a highly sensitive, simple-architectured wearable resistive pressure sensor based on highly compliant yet robust carbon composite conductors made of a vertically aligned carbon nanotube (VACNT) forest embedded in a polydimethylsiloxane (PDMS) matrix with irregular surface morphology. A roughened surface of the VACNT/PDMS composite conductor is simply formed using a sandblasted silicon master in a low-cost and potentially scalable manner and plays an important role in improving the sensitivity of resistive pressure sensor. After assembling two of the roughened composite conductors, our sensor shows considerable pressure sensitivity of ∼0.3 kPa-1 up to 0.7 kPa as well as stable steady-state responses under various pressures, a wide detectable range of up to 5 kPa before saturation, a relatively fast response time of ∼162 ms, and good reproducibility over 5000 cycles of pressure loading/unloading. The fabricated pressure sensor can be used to detect a wide range of human motions ranging from subtle blood pulses to dynamic joint movements, and it can also be used to map spatial pressure distribution in a multipixel platform (in a 4 × 4 pixel array).

20.
Exp Mol Med ; 49(4): e316, 2017 04 14.
Artigo em Inglês | MEDLINE | ID: mdl-28408748

RESUMO

Chronic obstructive pulmonary disease (COPD) is a chronic inflammatory disease, and bacterial infection plays a role in its pathogenesis. Bacteria secrete nanometer-sized extracellular vesicles (EVs), which may induce more immune dysfunction and inflammation than the bacteria themselves. We hypothesized that the microbiome of lung EVs might have distinct characteristics depending on the presence of COPD and smoking status. We analyzed and compared the microbiomes of 13 nonsmokers with normal spirometry, 13 smokers with normal spirometry (healthy smokers) and 13 patients with COPD by using 16S ribosomal RNA gene sequencing of surgical lung tissue and lung EVs. Subjects were matched for age and sex in all groups and for smoking levels in the COPD and healthy smoker groups. Each group included 12 men and 1 woman with the same mean age of 65.5 years. In all groups, EVs consistently showed more operational taxonomic units (OTUs) than lung tissue. In the healthy smoker and COPD groups, EVs had a higher Shannon index and a lower Simpson index than lung tissue and this trend was more prominent in the COPD group. Principal component analysis (PCA) showed clusters based on sample type rather than participants' clinical characteristics. Stenotrophomonas, Propionibacterium and Alicyclobacillus were the most commonly found genera. Firmicutes were highly present in the EVs of the COPD group compared with other samples or groups. Our analysis of the lung microbiome revealed that the bacterial communities present in the EVs and in the COPD group possessed distinct characteristics with differences in the OTUs, diversity indexes and PCA clustering.


Assuntos
Vesículas Extracelulares/microbiologia , Pulmão/microbiologia , Microbiota , Doença Pulmonar Obstrutiva Crônica/microbiologia , Fumar/efeitos adversos , Idoso , Estudos de Casos e Controles , Feminino , Humanos , Masculino , Pessoa de Meia-Idade
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