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An efficient interfacial heating system composed of a light-absorbing material and a hydrophilic porous support is developed through eco-friendly and energy-effective fabrication processes. Lignin nanoparticles (NPs) and cellulose nanofibers (CNFs) are harnessed as biorenewable light absorbers and hydrophilic supports, respectively. Lignin NPs are prepared using a solvent exchange process of the fractionated lignin with organic solvents to improve its π-π stacking and light-absorbing property for efficient photothermal conversion. Then, the lignin NPs are mixed with CNFs and lyophilized to obtain a light-absorbing porous hydrogel (LAPH), and the resulting LAPHs are covalently cross-linked and hybridized with Au NPs through a seed-mediated growth to further enhance their mechanical stability, hydrophilicity, and photothermal conversion properties. The resulting LAPHs exhibit an outstanding and prolonged performance as a solar steam generator such as high salt and pH tolerance, evaporation rate (3.17 kg m-2 h-1), and solar steam generation efficiency (83.4%) under 1 sun irradiation.
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Semiconductor-based photocatalysis is one of the favorable techniques for the wastewater treatment. Herein, we synthesized the activated carbon-decorated cerium dioxide (AC-CeO2) nanocomposites via the facile ultrasonication method by using the biomass-derived AC nanoflakes and the sonochemically-synthesized CeO2 nanoparticles. The AC-CeO2 nanocomposites exhibited the aggregated morphology with the AC nanoflakes-anchored CeO2 nanoparticles. Since the hybridization of conductive AC and semiconductive CeO2 would lead to the increased photocarrier transport and the reduced photocarrier recombination, during the photocatalytic reaction, the AC-CeO2 nanocomposites showed the enhanced crystal violet dye-degradation efficiency up to 97.9 % within 135 min. The results suggest that the AC-CeO2 nanocomposites hold promise as a prominent photocatalyst for future green environmental technology.
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Violeta Genciana , Nanocompostos , Nanocompostos/química , CatáliseRESUMO
BACKGROUND AND PURPOSE: Achieving favorable postoperative outcomes in patients with drug-resistant epilepsy (DRE) requires early referrals for preoperative examinations. The purpose of this study was to investigate the possibility of a user-friendly early DRE prediction model that is easy for nonexperts to utilize. METHODS: A two-step genotype analysis was performed, by applying 1) whole-exome sequencing (WES) to the initial test set (n=243) and 2) target sequencing to the validation set (n=311). Based on a multicenter case-control study design using the WES data set, 11 genetic and 2 clinical predictors were selected to develop the DRE risk prediction model. The early prediction scores for DRE (EPS-DRE) was calculated for each group of the selected genetic predictors (EPS-DREgen), clinical predictors (EPS-DREcln), and two types of predictor mix (EPS-DREmix) in both the initial test set and the validation set. RESULTS: The multidimensional EPS-DREmix of the predictor mix group provided a better match to the outcome data than did the unidimensional EPS-DREgen or EPS-DREcln. Unlike previous studies, the EPS-DREmix model was developed using only 11 genetic and 2 clinical predictors, but it exhibited good discrimination ability in distinguishing DRE from drug-responsive epilepsy. These results were verified using an unrelated validation set. CONCLUSIONS: Our results suggest that EPS-DREmix has good performance in early DRE prediction and is a user-friendly tool that is easy to apply in real clinical trials, especially by nonexperts who do not have detailed knowledge or equipment for assessing DRE. Further studies are needed to improve the performance of the EPS-DREmix model.
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Drug administration should be considered a risk factor for venous thromboembolism (VTE) in younger healthy patients. We present a case of new-onset pulmonary embolism (PE), possibly associated with excessive creatine supplement intake. A 24-year-old non-smoker male presented to the emergency department with sudden-onset dyspnoea and chest discomfort. Computed tomography pulmonary angiography and venography confirmed PE in the left and right pulmonary artery branches and a thrombus in the left popliteal vein. The patient had no family history of VTE, and other causes of thrombophilia were unlikely. He reported a recent increase in the intensity of his workouts and the dose of his creatine supplements in preparation for a bodybuilding competition. The creatine supplements likely promoted dehydration during intense workouts and profuse sweating. He received anticoagulation therapy, and the creatine supplements were discontinued. Creatine supplements should be used cautiously when there is a higher risk of becoming dehydrated.
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Alexander disease (AxD) is a neurodegenerative astrogliopathy caused by mutation in the glial fibrillary acidic protein (GFAP) gene. A 42-year-old Korean man presented with temporary gait disturbance and psychiatric regression after a minor head trauma in the absence of bulbar symptoms and signs. Magnetic resonance images of the brain and spinal cord showed significant atrophy of the medulla oblongata and the entire spinal cord as well as contrast-enhanced T2 hypointensity in the basal ganglia. DNA sequencing revealed a novel 33-bp in-frame deletion mutation (p.Glu138_Leu148del) within the 1B rod domain of GFAP, which was predicted to be deleterious by PROVEAN analysis. To test whether the deletion mutant is disease-causing, we performed in vitro GFAP assembly and sedimentation assays, and GFAP aggregation assays in human adrenal carcinoma SW13 (Vim-) cells and rat primary astrocytes. All the assays revealed that GFAP p.Glu138_Leu148del is aggregation prone. Based on these findings, we diagnosed the patient with Type II AxD. This is a report that demonstrates the pathogenicity of InDel mutation of GFAP through functional studies. This patient's atypical presentation as well as the discrepancy between clinical symptoms and radiologic findings may extend the scope of AxD.
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Doença de Alexander , Doença de Alexander/diagnóstico , Doença de Alexander/genética , Doença de Alexander/patologia , Animais , Encéfalo/metabolismo , Proteína Glial Fibrilar Ácida/genética , Humanos , Mutação , Fenótipo , RatosRESUMO
The high-performance room-temperature-operating Si single-electron transistors (SETs) were devised in the form of the multiple quantum-dot (MQD) multiple tunnel junction (MTJ) system. The key device architecture of the Si MQD MTJ system was self-formed along the volumetrically undulated [110] Si nanowire that was fabricated by isotropic wet etching and subsequent oxidation of the e-beam-lithographically patterned [110] Si nanowire. The strong subband modulation in the volumetrically undulated [110] Si nanowire could create both the large quantum level spacings and the high tunnel barriers in the Si MQD MTJ system. Such a device scheme can not only decrease the cotunneling effect, but also reduce the effective electron temperature. These eventually led to the energetic stability for both the Coulomb blockade and the negative differential conductance characteristics at room temperature. The results suggest that the present device scheme (i.e., [110] Si MQD MTJ) holds great promise for the room-temperature demonstration of the high-performance Si SETs.
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Vaccination is currently the most effective strategy to control porcine reproductive and respiratory syndrome (PRRS). New-generation PRRS vaccines are required to be safe and broadly cross-protective. We have recently created the chimeric PRRS virus K418DM which proved to be a good vaccine candidate under field conditions. In the present study, we designed safety and efficacy tests under experimental and field conditions for further evaluation of K418DM1.1, a plaque-purified K418DM. In the homologous challenge study, K418DM1.1 induced high serum virus neutralization (SVN) antibody titers (i.e., 4.2 log2 ± 1.7) at 21 days post-challenge (dpc) and provided protection as demonstrated by the significantly lower levels of viremia at 3 and 7 dpc and significantly lower microscopic lung lesion scores compared to the unvaccinated group. K418DM1.1 was also protective in the heterologous challenge study, with vaccinated pigs showing significantly lower levels of viremia at 14 dpc compared to the unvaccinated pigs. A field study was performed to evaluate the efficacy of K418DM1.1 against heterologous exposure and vaccinated pigs presented significantly lower viremia than unvaccinated pigs. According to the safety test for the examination of virulence reversion, no infectivity was observed in tissue homogenate filtrate both in the vaccinated and comingled groups. Thus, the risk of virulence, as well as transmission, appeared negligible. These overall results indicate that K418DM1.1 is a good vaccine candidate based on its safety and protective efficacy.
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Síndrome Respiratória e Reprodutiva Suína/imunologia , Vírus da Síndrome Respiratória e Reprodutiva Suína/imunologia , Vacinação/veterinária , Vacinas Virais/efeitos adversos , Viremia/veterinária , Animais , Sus scrofa , Suínos , Viremia/imunologiaRESUMO
Ependymal cells (ECs) are multiciliated neuroepithelial cells that line the ventricles of the brain and the central canal of the spinal cord (SC). How ependymal motile cilia are maintained remains largely unexplored. Here we show that zebrafish embryos deficient in Wnt signaling have defective motile cilia, yet harbor intact basal bodies. With respect to maintenance of ependymal motile cilia, plcδ3a is a target gene of Wnt signaling. Lack of Connexin43 (Cx43), especially its channel function, decreases motile cilia and intercellular Ca2+ wave (ICW) propagation. Genetic ablation of cx43 in zebrafish and mice diminished motile cilia. Finally, Cx43 is also expressed in ECs of the human SC. Taken together, our findings indicate that gap junction mediated ICWs play an important role in the maintenance of ependymal motile cilia, and suggest that the enhancement of functional gap junctions by pharmacological or genetic manipulations may be adopted to ameliorate motile ciliopathy.
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Cílios/metabolismo , Conexina 43/metabolismo , Conexinas/metabolismo , Epêndima/metabolismo , Medula Espinal/metabolismo , Peixe-Zebra/embriologia , Animais , Diferenciação Celular , Cílios/genética , Conexina 43/genética , Epêndima/patologia , Junções Comunicantes , Regulação da Expressão Gênica no Desenvolvimento , Técnicas de Inativação de Genes , Humanos , Masculino , Camundongos , Camundongos Knockout , Transdução de Sinais/genética , Via de Sinalização Wnt/genética , Proteínas de Peixe-Zebra/genética , Proteínas de Peixe-Zebra/metabolismoRESUMO
Nondystrophic myotonias are disorders of Na+ (Nav1.4 or SCN4A) and Cl- (CLCN1) channels in skeletal muscles, and frequently show phenotype heterogeneity. The molecular mechanism underlying their pathophysiology and phenotype heterogeneity remains unclear. As zebrafish models have been recently exploited for studies of the pathophysiology and phenotype heterogeneity of various human genetic diseases, a zebrafish model may be useful for delineating nondystrophic myotonias. Here, we generated transgenic zebrafish expressing a human mutant allele of SCN4A, referred to as Tg(mylpfa:N440K), and needle electromyography revealed increased number of myotonic discharges and positive sharp waves in the muscles of Tg(mylpfa:N440K) than in controls. In addition, forced exercise test at a water temperature of 24⯰C showed a decrease in the distance moved, time spent in and number of visits to the zone with stronger swimming resistance. Finally, a forced exercise test at a water temperature of 18⯰C exhibited a higher number of dive-bombing periods and drifting-down behavior than in controls. These findings indicate that Tg(mylpfa:N440K) is a good vertebrate model of exercise- and cold-induced human nondystrophic myotonias. This zebrafish model may contribute to provide insight into the pathophysiology of myotonia in sodium channelopathy and could be used to explore a new therapeutic avenue.
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Temperatura Baixa , Modelos Animais de Doenças , Músculo Esquelético/fisiopatologia , Miotonia Congênita/genética , Canal de Sódio Disparado por Voltagem NAV1.4/genética , Esforço Físico , Peixe-Zebra , Animais , Animais Geneticamente Modificados , Eletromiografia , Mutação de Sentido Incorreto , Miotonia/genética , Miotonia/fisiopatologia , Miotonia Congênita/fisiopatologia , Transtornos Miotônicos/genética , Transtornos Miotônicos/fisiopatologia , Paralisia Periódica Hiperpotassêmica/genética , Paralisia Periódica Hiperpotassêmica/fisiopatologiaRESUMO
BACKGROUND: Knowledge of the genetic etiology of epilepsy can provide essential prognostic information and influence decisions regarding treatment and management, leading us into the era of precision medicine. However, the genetic basis underlying epileptogenesis or epilepsy pharmacoresistance is not well-understood, particularly in non-familial epilepsies with heterogeneous phenotypes that last until or start in adulthood. METHODS: We sought to determine the contribution of known epilepsy-associated genes (EAGs) to the causation of non-familial epilepsies with heterogeneous phenotypes and to the genetic basis underlying epilepsy pharmacoresistance. We performed a multi-center study for whole exome sequencing-based screening of 178 selected EAGs in 243 non-familial adult patients with primarily focal epilepsy (122 drug-resistant and 121 drug-responsive epilepsies). The pathogenicity of each variant was assessed through a customized stringent filtering process and classified according to the American College of Medical Genetics and Genomics guidelines. RESULTS: Possible causal genetic variants of epilepsy were uncovered in 13.2% of non-familial patients with primarily focal epilepsy. The diagnostic yield according to the seizure onset age was 25% (2/8) in the neonatal and infantile period, 11.1% (14/126) in childhood and 14.7% (16/109) in adulthood. The higher diagnostic yields were from ion channel-related genes and mTOR pathway-related genes, which does not significantly differ from the results of previous studies on familial or early-onset epilepsies. These potentially pathogenic variants, which were identified in genes that have been mainly associated with early-onset epilepsies with severe phenotypes, were also linked to epilepsies that start in or last until adulthood in this study. This finding suggested the presence of one or more disease-modifying factors that regulate the onset time or severity of epileptogenesis. The target hypothesis of epilepsy pharmacoresistance was not verified in our study. Instead, neurodevelopment-associated epilepsy genes, such as TSC2 or RELN, or structural brain lesions were more strongly associated with epilepsy pharmacoresistance. CONCLUSIONS: We revealed a fraction of possible causal genetic variants of non-familial epilepsies in which genetic testing is usually overlooked. In this study, we highlight the importance of earlier identification of the genetic etiology of non-familial epilepsies, which leads us to the best treatment options in terms of precision medicine and to future neurobiological research for novel drug development. This should be considered a justification for physicians determining the hidden genetics of non-familial epilepsies that last until or start in adulthood.
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Laser surgery (LS) or radiotherapy (RT) is normally recommended in early glottic cancer. The objective of this study was to perform a comprehensive meta-analysis of acoustic and perceptual outcomes to compare voice quality of LS or RT in early-stage glottic cancer. Data sources were obtained after searching PubMed, Google Scholar, EBSCO, and RISS using the following search terms: glottic cancer, glottic carcinoma, endoscopic surgery, laser surgery, radiotherapy, radiation, voice, voice quality, and grade, roughness, breathiness, asthenia, and strain (GRBAS) scale. Articles that compared voice outcomes between LS and RT were identified. This meta-analysis included 15 articles with 744 patients, including 400 in the LS group and 344 in the RT group. Random effects models were selected. Forest plots included standardized mean differences, standard errors, variance, 95% confidence intervals (lower limit to upper limit), z-values, and P-values. In perceptual analysis, grade (G) and asthenia (A) of RT were significantly better than LS. There was no statistically significant difference in roughness (R), breath (B), or strain (S) between LS and RT groups. Jitter, shimmer, and noise to harmonic ratio measurements showed significant differences, resulting in enhanced posttreatment effect of RT compared to LS. Results of our meta-analysis suggested that RT might lead to superior voice quality than LS in early glottic cancer.
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PURPOSE: Recurrence and chemoresistance (CR) are the leading causes of death in patients with high-grade serous carcinoma (HGSC) of the ovary. The aim of this study was to identify genetic changes associated with CR mechanisms using a patient-derived xenograft (PDX) mouse model and genetic sequencing. MATERIALS AND METHODS: To generate a CR HGSC PDX tumor, mice bearing subcutaneously implanted HGSC PDX tumors were treated with paclitaxel and carboplatin. We compared gene expression and mutations between chemosensitive (CS) and CR PDX tumors with whole exome and RNA sequencing and selected candidate genes. Correlations between candidate gene expression and clinicopathological variables were explored using the Cancer Genome Atlas (TCGA) database and the Human Protein Atlas (THPA). RESULTS: Three CR and four CS HGSC PDX tumor models were successfully established. RNA sequencing analysis of the PDX tumors revealed that 146 genes were significantly up-regulated and 54 genes down-regulated in the CR group compared with the CS group. Whole exome sequencing analysis showed 39 mutation sites were identified which only occurred in CR group. Differential expression of SAP25, HLA-DPA1, AKT3, and PIK3R5 genes and mutation of TMEM205 and POLR2A may have important functions in the progression of ovarian cancer chemoresistance. According to TCGA data analysis, patients with high HLA-DPA1 expression were more resistant to initial chemotherapy (p=0.030; odds ratio, 1.845). CONCLUSION: We successfully established CR ovarian cancer PDX mouse models. PDX-based genetic profiling study could be used to select some candidate genes that could be targeted to overcome chemoresistance of ovarian cancer.
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Cisplatino/farmacologia , Cistadenocarcinoma Seroso/genética , Resistencia a Medicamentos Antineoplásicos , Sequenciamento do Exoma/métodos , Perfilação da Expressão Gênica/métodos , Neoplasias Ovarianas/genética , Paclitaxel/farmacologia , Animais , Linhagem Celular Tumoral , Cisplatino/uso terapêutico , Cistadenocarcinoma Seroso/tratamento farmacológico , Feminino , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Redes Reguladoras de Genes , Cadeias alfa de HLA-DP/genética , Humanos , Camundongos , Mutação , Transplante de Neoplasias , Neoplasias Ovarianas/tratamento farmacológico , Paclitaxel/uso terapêutico , Análise de Sequência de RNARESUMO
BACKGROUND: Foot-and-mouth disease (FMD) can be controlled by either stamping out or vaccination, a choice which depends on both the economic importance of the livestock sector as well as the disease status. In FMD-free countries with vaccination, such as Korea, vaccination programs should guarantee prevention against transmission of FMD. Monitoring of vaccination programs is also essential for ensuring sufficient coverage that will limit the transmission of FMDV. There are several methods to screen FMD virus (FMDV) structural protein (SP) antibodies including SPCE (Solid-phase competitive ELISA), LPBE (Liquid-phase blocking ELISA), and VNT (Virus neutralization test). Among these, SPCE is widely used for serological monitoring since VNT-the gold standard method-has certain practical limitations, such as high costs in terms of time and labor. However, whether SPCE can ensure the vaccination status of individual animals and whole farms is unclear. In this study, SPCE, LPBE and VNT were compared with respect to correlation with each other and sensitivity at commercial pig farms. RESULTS: The positive results obtained by PrioCHECK SPCE differed from those obtained by LPBE and VNT. The sensitivity of SPCE relative to those of the other tests was fairly low. The raw data of SPCE were most highly correlated with those of VNT with XJ strain, while their positivity and negativity were most highly correlated with LPBE. The results of ROC analysis proposed new cut-off for PrioCHECK SPCE higher than the previous 50% inhibition. CONCLUSIONS: The high false positive rate of PrioCHECK SPCE suggested that high seropositivity by SPCE may not guarantee a true vaccination coverage. Adjusting the cut-off percentage (%) inhibition value for SPCE is needed to address this problem, and it is highly recommended that routine FMDV serological monitoring programs using PrioCHECK SPCE should be combined with alternative methods such as LPBE or VNT.
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Anticorpos Antivirais/sangue , Febre Aftosa/prevenção & controle , Monitorização Imunológica/métodos , Testes Sorológicos/veterinária , Vacinação/veterinária , Animais , Ensaio de Imunoadsorção Enzimática/veterinária , Febre Aftosa/sangue , Vírus da Febre Aftosa/imunologia , Testes de Neutralização/veterinária , República da Coreia , Proteínas Estruturais Virais/imunologia , Vacinas Virais/normasRESUMO
The greater sciatic notch is an effective indicator for sexual estimation, which is the initial process to identify unknown skeleton. Visual assessment is the mainstream of analysis methods; however, the subjectivity of researchers is also questioned. Metric method using three-dimensional models reconstructed from radiographic images can ensure reproducible and stable measurement of the greater sciatic notch. In this study, the greater sciatic notch was analyzed in various manners, including distances, angles, and dimensions, with the aid of an automatic measurement program and a landmark verification system. Among 28 items, 15 measurements showed more than 85% accuracy. Measurements related to the posterior part of the greater sciatic notch near the posterior inferior iliac spine particularly showed higher accuracy (93.1%). To test this observation, "arithmetic posterior angle of the greater sciatic notch", a generalized form of partial angle of the greater sciatic notch, was designed. It showed more than 90% accuracy. When the results of the three-dimensional measurements were applied to classify dry bones, it proved to be valid in contemporary Korean population. The method and results of this study can be referenced in wider use of the greater sciatic notch analysis.
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Ílio/anatomia & histologia , Imageamento Tridimensional , Ossos Pélvicos/anatomia & histologia , Determinação do Sexo pelo Esqueleto/métodos , Tomografia Computadorizada por Raios X , Adulto , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Adulto JovemRESUMO
MicroRNA-630 (miR-630) has been implicated in the development and progression of multiple cancers. The current study aimed to investigate the role of miR-630 in chemoresistant epithelial ovarian cancer. MiR-630 expression levels were detected in ovarian cancer cell line SKOV3 and paclitaxel-resistant SKOV3 (SKOV3-TR) via microarray and qRT-PCR. MiR-630 inhibitors and negative controls were transfected into SKOV3 and SKOV3-TR cells. Wound healing, invasion, chemosensitivity, and cell apoptosis assays were performed to determine proliferation and migration rates. Chemoresistant patient-derived xenograft (PDX) models were established and utilized to verify the effect of miR-630 on chemoresistant ovarian cancer. Inhibition of miR-630 decreased cell proliferation and enhanced the sensitivity of SKOV3-TR and SKOV3 cells to paclitaxel. In the chemosensitivity assay, we observed that the miR-630 inhibitor exhibited a synergistic effect with paclitaxel on SKOV3-TR cells. Inhibition was correlated with enhanced expression of apoptosis-related proteins. APAF-1 was predicted to be a potential target of miR-630. An in vivo PDX study showed that the miR-630 inhibitor sensitized chemoresistant ovarian cancer to paclitaxel. Thus, miR-630 inhibitor sensitizes chemoresistant epithelial ovarian cancer to chemotherapy by enhancing apoptosis. Our findings suggest that miR-630 might be a potential therapeutic target for chemotherapy-resistant ovarian cancer.
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Antineoplásicos Fitogênicos/farmacologia , Apoptose/efeitos dos fármacos , Resistencia a Medicamentos Antineoplásicos/efeitos dos fármacos , MicroRNAs/antagonistas & inibidores , Neoplasias Ovarianas/tratamento farmacológico , Paclitaxel/farmacologia , Animais , Fator Apoptótico 1 Ativador de Proteases/genética , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Feminino , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Humanos , Camundongos , MicroRNAs/genética , Neoplasias Ovarianas/genética , Neoplasias Ovarianas/patologia , Ovário/efeitos dos fármacos , Ovário/metabolismo , Ovário/patologiaRESUMO
PURPOSE: Although the use of xenograft models is increasing, few studies have compared the clinical features or outcomes of epithelial ovarian cancer (EOC) patients according to the tumorigenicity of engrafted specimens. The purpose of this study was to evaluate whether tumorigenicity was associated with the clinical features and outcomes of EOC patients. MATERIALS AND METHODS: Eighty-eight EOC patients who underwent primary or interval debulking surgery from June 2014 to December 2015 were included. Fresh tumor specimens were implanted subcutaneously on each flank of immunodeficient mice. Patient characteristics, progression-free survival (PFS), and germline mutation spectra were compared according to tumorigenicity. RESULTS: Xenografts were established successfully from 49 of 88 specimens. Tumorigenicity was associated with lymphovascular invasion and there was a propensity to engraft successfully with high-grade tumors. Tumors from patientswho underwent non-optimal (residual disease ≥ 1 cm) primary orinterval debulking surgery had a significantly greater propensity to achieve tumorigenicity than those who received optimal surgery. In addition, patients whose tumors became engrafted seemed to have a shorter PFS and more frequent germline mutations than patients whose tumors failed to engraft. Tumorigenicity was a significant factor for predicting PFS with advanced International Federation of Gynecology and Obstetrics stage and high-grade cancers. CONCLUSIONS: Tumorigenicity in a xenograft model was a strong prognostic factor and was associated with more aggressive tumors in EOC patients. Xenograft models can be useful as a preclinical tool to predict prognosis and could be applied to further pharmacologic and genomic studies on personalized treatments.
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Proteína BRCA1/genética , Proteína BRCA2/genética , Mutação em Linhagem Germinativa , Neoplasias Epiteliais e Glandulares/patologia , Neoplasias Epiteliais e Glandulares/cirurgia , Neoplasias Ovarianas/patologia , Neoplasias Ovarianas/cirurgia , Adulto , Idoso , Idoso de 80 Anos ou mais , Animais , Carcinoma Epitelial do Ovário , Procedimentos Cirúrgicos de Citorredução , Intervalo Livre de Doença , Feminino , Humanos , Camundongos , Pessoa de Meia-Idade , Invasividade Neoplásica , Transplante de Neoplasias , Neoplasias Epiteliais e Glandulares/genética , Neoplasias Ovarianas/genética , Análise de SobrevidaRESUMO
BACKGROUND: To develop surrogate insulin-producing cells for diabetes therapy, adult stem cells have been identified in various tissues and studied for their conversion into ß-cells. Pancreatic progenitor cells are derived from the endodermal epithelium and formed in a manner similar to gut progenitor cells. Here, we generated insulin-producing cells from the intestinal epithelial cells that induced many of the specific pancreatic transcription factors using adenoviral vectors carrying three genes: PMB (pancreatic and duodenal homeobox 1 [Pdx1], V-maf musculoaponeurotic fibrosarcoma oncogene homolog A [MafA], and BETA2/NeuroD). METHODS: By direct injection into the intestine through the cranial mesenteric artery, adenoviruses (Ad) were successfully delivered to the entire intestine. After virus injection, we could confirm that the small intestine of the mouse was appropriately infected with the Ad-Pdx1 and triple Ad-PMB. RESULTS: Four weeks after the injection, insulin mRNA was expressed in the small intestine, and the insulin gene expression was induced in Ad-Pdx1 and Ad-PMB compared to control Ad-green fluorescent protein. In addition, the conversion of intestinal cells into insulin-expressing cells was detected in parts of the crypts and villi located in the small intestine. CONCLUSION: These data indicated that PMB facilitate the differentiation of mouse intestinal cells into insulin-expressing cells. In conclusion, the small intestine is an accessible and abundant source of surrogate insulin-producing cells.
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BACKGROUND: Alexander disease (AxD) is an astrogliopathy that predominantly affects the white matter of the central nervous system (CNS), and is caused by a mutation in the gene encoding the glial fibrillary acidic protein (GFAP), an intermediate filament primarily expressed in astrocytes and ependymal cells. The main pathologic feature of AxD is the presence of Rosenthal fibers (RFs), homogeneous eosinophilic inclusions found in astrocytes. Because of difficulties in procuring patient' CNS tissues and the presence of RFs in other pathologic conditions, there is a need to develop an in vivo assay that can determine whether a mutation in the GFAP results in aggregation and is thus disease-causing. METHODS: We found a GFAP mutation (c.382G > A, p.Asp128Asn) in a 68-year-old man with slowly progressive gait disturbance with tendency to fall. The patient was tentatively diagnosed with AxD based on clinical and radiological findings. To develop a vertebrate model to assess the aggregation tendency of GFAP, we expressed several previously reported mutant GFAPs and p.Asp128Asn GFAP in zebrafish embryos. RESULTS: The most common GFAP mutations in AxD, p.Arg79Cys, p.Arg79His, p.Arg239Cys and p.Arg239His, and p.Asp128Asn induced a significantly higher number of GFAP aggregates in zebrafish embryos than wild-type GFAP. CONCLUSIONS: The p.Asp128Asn GFAP mutation is likely to be a disease-causing mutation. Although it needs to be tested more extensively in larger case series, the zebrafish assay system presented here would help clinicians determine whether GFAP mutations identified in putative AxD patients are disease-causing.
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Doença de Alexander/genética , Proteína Glial Fibrilar Ácida/genética , Idoso , Animais , Astrócitos , Proteína Glial Fibrilar Ácida/metabolismo , Humanos , Masculino , Mutação , Peixe-ZebraRESUMO
COACH syndrome is an autosomal recessive developmental disorder, a subtype of Joubert syndrome and related disorders, characterized by cerebellar vermis hypoplasia, oligophrenia, ataxia, coloboma, and hepatic fibrosis. Although mutations in TMEM67 (transmembrane protein 67)/MKS3 (Meckel-Gruber syndrome, type 3) were reported to cause COACH syndrome, this causality has not verified by functional studies. In a 20-year-old Korean man, we found cerebellar ataxia, isolated elevation in serum γ-glutamyl transpeptidase (γ-GTP) activity, oligophrenia, the molar tooth sign (MTS) in the brain MR images and congenital hepatic fibrosis (CHF). Two novel compound heterozygous mutations were found in TMEM67 in the patient: i) missense mutation (c.395 G > C and p.Gly132Ala) in exon 3, and ii) deletion in exon 26 (c.2758delT and p.Tyr920ThrfsX40). Western blotting showed that the p.Tyr920ThrfsX40 mutation accelerates turnover of the TMEM67 protein. Although wild-type human TMEM67 RNA rescued phenotypes of zebrafish embryos injected with anti-sense oligonucleotide morpholinos against tmem67, the two human TMEM67 RNAs individually harboring the two mutations did not. Finally, Wnt signaling, but not Hedgehog signaling, was suppressed in tmem67 morphants. To the best of our knowledge, this is the first report verifying the causality between COACH syndrome and TMEM67, which will further our understanding of molecular pathogenesis of the syndrome.
Assuntos
Anormalidades Múltiplas/genética , Ataxia/genética , Encéfalo/anormalidades , Colestase/genética , Coloboma/genética , Hepatopatias/genética , Proteínas de Membrana/genética , Proteínas de Membrana/metabolismo , Mutação , Anormalidades Múltiplas/tratamento farmacológico , Anormalidades Múltiplas/metabolismo , Animais , Ataxia/tratamento farmacológico , Ataxia/metabolismo , Encéfalo/metabolismo , Colestase/tratamento farmacológico , Colestase/metabolismo , Coloboma/tratamento farmacológico , Coloboma/metabolismo , Modelos Animais de Doenças , Células HEK293 , Humanos , Hepatopatias/tratamento farmacológico , Hepatopatias/metabolismo , Masculino , Morfolinos/administração & dosagem , Morfolinos/farmacologia , Mutação de Sentido Incorreto , Deleção de Sequência , Via de Sinalização Wnt , Adulto Jovem , Peixe-ZebraRESUMO
Non-focused ultrasound and high-intensity focused ultrasound (HIFU) devices induce lipolysis by generating acoustic cavitation and coagulation necrosis in targeted tissues. We aimed to investigate the morphometric characteristics of immediate tissue reactions induced by 2 MHz, 13-mm focused HIFU via two-dimensional ultrasound images and histologic evaluation of cadaveric skin from the abdomen and thigh. Acoustic fields of a 2 MHz, 38-mm HIFU transducer were characterized by reconstruction of the fields using acoustic intensity measurement. Additionally, abdominal and thigh tissues from a fresh cadaver were treated with a HIFU device for a single, two, and three pulses at the pulse energy of 130 J/cm2 and a penetration depth of 13 mm. Acoustic intensity measurement revealed characteristic focal zones of significant thermal injury at the depth of 38 mm. In both the abdomen and thigh tissue, round to oval ablative thermal injury zones (TIZs) were visualized in subcutaneous fat layers upon treatment with a single pulse of HIFU treatment. Two to three HIFU pulses generated larger and more remarkable ablative zones throughout subcutaneous fat layers. Finally, experimental treatment in a tumescent infiltration-like setting induced larger HIFU-induced TIZs of an oval or columnar shape, compared to non-tumescent settings. Although neither acoustic intensity measurement nor cadaveric tissue exactly reflects in vivo HIFU-induced reactions in human tissue, we believe that our data will help guide further in vivo studies in investigating the therapeutic efficacy and safety of HIFU-induced lipolysis.