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1.
Brain ; 147(6): 2114-2127, 2024 Jun 03.
Artículo en Inglés | MEDLINE | ID: mdl-38227798

RESUMEN

Mutations in the Microrchidia CW-type zinc finger 2 (MORC2) GHKL ATPase module cause a broad range of neuropathies, such as Charcot-Marie-Tooth disease type 2Z; however, the aetiology and therapeutic strategy are not fully understood. Previously, we reported that the Morc2a p.S87L mouse model exhibited neuropathy and muscular dysfunction through DNA damage accumulation. In the present study, we analysed the gene expression of Morc2a p.S87L mice and designated the primary causing factor. We investigated the pathological pathway using Morc2a p.S87L mouse embryonic fibroblasts and human fibroblasts harbouring MORC2 p.R252W. We subsequently assessed the therapeutic effect of gene therapy administered to Morc2a p.S87L mice. This study revealed that Morc2a p.S87L causes a protein synthesis defect, resulting in the loss of function of Morc2a and high cellular apoptosis induced by high hydroxyl radical levels. We considered the Morc2a GHKL ATPase domain as a therapeutic target because it simultaneously complements hydroxyl radical scavenging and ATPase activity. We used the adeno-associated virus (AAV)-PHP.eB serotype, which has a high CNS transduction efficiency, to express Morc2a or Morc2a GHKL ATPase domain protein in vivo. Notably, AAV gene therapy ameliorated neuropathy and muscular dysfunction with a single treatment. Loss-of-function characteristics due to protein synthesis defects in Morc2a p.S87L were also noted in human MORC2 p.S87L or p.R252W variants, indicating the correlation between mouse and human pathogenesis. In summary, CMT2Z is known as an incurable genetic disorder, but the present study demonstrated its mechanisms and treatments based on established animal models. This study demonstrates that the Morc2a p.S87L variant causes hydroxyl radical-mediated neuropathy, which can be rescued through AAV-based gene therapy.


Asunto(s)
Terapia Genética , Animales , Humanos , Ratones , Adenosina Trifosfatasas/genética , Adenosina Trifosfatasas/metabolismo , Enfermedad de Charcot-Marie-Tooth/genética , Enfermedad de Charcot-Marie-Tooth/metabolismo , Enfermedad de Charcot-Marie-Tooth/terapia , Dependovirus/genética , Fibroblastos/metabolismo , Terapia Genética/métodos , Radical Hidroxilo/metabolismo , Factores de Transcripción/genética , Factores de Transcripción/metabolismo
2.
Cancer ; 2024 Jun 28.
Artículo en Inglés | MEDLINE | ID: mdl-38941496

RESUMEN

BACKGROUND: Seasonal variations in systemic immunity have been reported. This study aimed to evaluate whether seasonality affects the efficacy of anticancer immunotherapy. METHODS: A total of 604 patients with lung cancer receiving single anti-programmed cell death (ligand) 1 (anti-PD-[L]1) inhibitors from two prospective observational cohorts were screened. Primary outcomes were progression-free survival (PFS) and overall survival (OS). Patients were classified into two groups according to the season when the treatment started: winter (November-February) and other seasons (March-October). Kaplan-Meier analysis and Cox proportional hazards models were fitted to evaluate the impact of seasonality on survival. For validation, propensity score matching was performed. RESULTS: A total of 484 patients with advanced non-small cell lung cancer were included. In an unmatched population, multivariable analysis demonstrated that the winter group (n = 173) had a significantly lower risk of progression or death from immunotherapy than the other group (n = 311) (PFS: hazard ratio [HR], 0.77 [95% confidence interval (CI), 0.62-0.96]; p = .018; OS: HR, 0.77 [95% CI, 0.1-0.98]; p = .032). In a propensity score-matched population, the winter group (n = 162) showed significantly longer median PFS (2.8 months [95% CI, 1.9-4.1 months] vs. 2.0 months [95% CI, 1.4-2.7 months]; p = .009) than the other group (n = 162). The winter group's median OS was also significantly longer than that of the other group (13.4 months [95% CI, 10.2-18.0 months] vs. 8.0 months [95% CI, 3.6-8.7 months]; p = .012). The trend toward longer survival in the winter group continued in subgroup analyses. CONCLUSIONS: Starting an anti-PD-(L)1 inhibitor in winter was associated with better treatment outcomes in patients with lung cancer compared to other seasons.

3.
Bioorg Chem ; 149: 107504, 2024 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-38850783

RESUMEN

The notable characteristics of recently emerged Antibody-Drug Conjugates (ADCs) encompass the targeting of Human Epidermal growth factor Receptor 2 (HER2) through monoclonal antibodies (mAbs) and a high ratio of drug to antibody (DAR). The achievements of Kadcyla® (T-DM1) and Enhertu® (T-Dxd) have demonstrated that HER2-targeting antibodies, such as trastuzumab, have shown to be competitive in terms of efficacy and price for development. Furthermore, with the arrival of T-Dxd and Trodelvy®, high-DAR (7-8) ADCs, which differ from the moderate DAR (3-4) ADCs that were formerly regarded as conventional, are being acknowledged for their worth. Following this trend of drug development, we endeavored to develop a high-DAR ADC using a straightforward approach involving the utilization of DM1, a highly potent substance, in combination with the widely recognized trastuzumab. To achieve a high DAR, DM1 was conjugated to reduced cysteine through the simple design and synthesis of various dimaleimide linkers with differing lengths. Using LC and MS analysis, we have demonstrated that our synthesis methodology is uncomplicated and efficacious, yielding trastuzumab-based ADCs that exhibit a remarkable degree of uniformity. These ADCs have been experimentally substantiated to exert an inhibitory effect on cancer cells in vitro, thus affirming their value as noteworthy additions to the realm of ADCs.


Asunto(s)
Ado-Trastuzumab Emtansina , Inmunoconjugados , Receptor ErbB-2 , Trastuzumab , Humanos , Inmunoconjugados/química , Inmunoconjugados/farmacología , Receptor ErbB-2/antagonistas & inhibidores , Receptor ErbB-2/metabolismo , Ado-Trastuzumab Emtansina/química , Trastuzumab/química , Trastuzumab/farmacología , Estructura Molecular , Proliferación Celular/efectos de los fármacos , Ensayos de Selección de Medicamentos Antitumorales , Maleimidas/química , Maleimidas/síntesis química , Relación Dosis-Respuesta a Droga , Antineoplásicos/química , Antineoplásicos/farmacología , Antineoplásicos/síntesis química , Relación Estructura-Actividad , Maitansina/química , Maitansina/farmacología , Maitansina/síntesis química , Maitansina/análogos & derivados , Línea Celular Tumoral , Antineoplásicos Inmunológicos/química , Antineoplásicos Inmunológicos/síntesis química , Antineoplásicos Inmunológicos/farmacología
4.
Sensors (Basel) ; 24(8)2024 Apr 17.
Artículo en Inglés | MEDLINE | ID: mdl-38676191

RESUMEN

This paper addresses a joint training approach applied to a pipeline comprising speech enhancement (SE) and automatic speech recognition (ASR) models, where an acoustic tokenizer is included in the pipeline to leverage the linguistic information from the ASR model to the SE model. The acoustic tokenizer takes the outputs of the ASR encoder and provides a pseudo-label through K-means clustering. To transfer the linguistic information, represented by pseudo-labels, from the acoustic tokenizer to the SE model, a cluster-based pairwise contrastive (CBPC) loss function is proposed, which is a self-supervised contrastive loss function, and combined with an information noise contrastive estimation (infoNCE) loss function. This combined loss function prevents the SE model from overfitting to outlier samples and represents the pronunciation variability in samples with the same pseudo-label. The effectiveness of the proposed CBPC loss function is evaluated on a noisy LibriSpeech dataset by measuring both the speech quality scores and the word error rate (WER). The experimental results reveal that the proposed joint training approach using the described CBPC loss function achieves a lower WER than the conventional joint training approaches. In addition, it is demonstrated that the speech quality scores of the SE model trained using the proposed training approach are higher than those of the standalone-SE model and SE models trained using conventional joint training approaches. An ablation study is also conducted to investigate the effects of different combinations of loss functions on the speech quality scores and WER. Here, it is revealed that the proposed CBPC loss function combined with infoNCE contributes to a reduced WER and an increase in most of the speech quality scores.


Asunto(s)
Ruido , Software de Reconocimiento del Habla , Humanos , Análisis por Conglomerados , Algoritmos , Habla/fisiología
5.
Cancer ; 129(3): 405-414, 2023 02 01.
Artículo en Inglés | MEDLINE | ID: mdl-36451343

RESUMEN

BACKGROUND: This study evaluated whether an addition of bevacizumab to erlotinib improves clinical outcomes in patients with advanced EGFR-mutated non-small cell lung cancer (NSCLC). METHODS: This is an open-label, multicenter, randomized Phase 2 study in South Korea. Chemonaïve patients with Stage IIIB/IV NSCLC with EGFR 19 deletion or L858R mutation were eligible. Asymptomatic brain metastasis (BM) was enrolled without local treatment. Patients received either erlotinib plus bevacizumab or erlotinib. RESULTS: Between December 2016 and March 2019, 127 patients were randomly assigned to receive erlotinib plus bevacizumab (n = 64) or erlotinib (n = 63). Fifty-nine (46.5%) patients had baseline BM. Fewer patients in the erlotinib plus bevacizumab arm received radiotherapy for BM than in the erlotinib arm (10.3% vs. 40.0%). A trend toward longer progression-free survival (PFS) was observed in the erlotinib plus bevacizumab arm compared with the erlotinib alone arm; however, it was not statistically significant (median PFS, 17.5 months vs. 12.4 months; hazard ratio [HR], 0.74; 95% CI, 0.51-1.08; p = .119). The unplanned subgroup analysis showed a longer PFS with erlotinib plus bevacizumab in patients with BM (median PFS, 18.6 months vs. 10.3 months; HR, 0.54; 95% CI, 0.31-0.95; p = .032). Grade 3 or worse adverse events occurred in 56.6% of the erlotinib plus bevacizumab arm and 20.6% of the erlotinib arm. CONCLUSIONS: Although it was not statistically significant, a trend to improvement in PFS was observed in patients with erlotinib plus bevacizumab compared to erlotinib alone. PLAIN LANGUAGE SUMMARY: A randomized Phase 2 study compared erlotinib with or without bevacizumab in previously untreated patients with advanced non-small cell lung cancer with EGFR mutation. The erlotinib plus bevacizumab failed to improve median progression-free survival compared with the erlotinib alone. However, the progression-free survival benefit from erlotinib plus bevacizumab was found in patients with brain metastasis with no severe hemorrhagic adverse effects.


Asunto(s)
Carcinoma de Pulmón de Células no Pequeñas , Neoplasias Pulmonares , Humanos , Carcinoma de Pulmón de Células no Pequeñas/tratamiento farmacológico , Carcinoma de Pulmón de Células no Pequeñas/genética , Carcinoma de Pulmón de Células no Pequeñas/patología , Clorhidrato de Erlotinib , Bevacizumab/efectos adversos , Neoplasias Pulmonares/tratamiento farmacológico , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/patología , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Receptores ErbB/genética , Mutación , Inhibidores de Proteínas Quinasas/efectos adversos , Supervivencia sin Enfermedad
6.
Anal Chem ; 95(41): 15302-15310, 2023 Oct 17.
Artículo en Inglés | MEDLINE | ID: mdl-37769202

RESUMEN

The precise investigation and monitoring of the internal structural change within complex layered systems are crucial, as the emergence of undesirable defects or formation of secondary internal structures significantly exerts a profound influence on the overall properties of the system. We demonstrate an advanced sensing platform utilizing terahertz metasurfaces, allowing chemical detection and precise identification within an acrylic paint layer with a noticeable sensitivity, reaching down to several hundreds of nanometers, in nondestructive and noncontact manners. The identification of solid and mixed paint samples was achieved by analyzing their optical properties, including the refractive index and absorption coefficient. Notably, the presence of internal pore defects within the mixed acrylic paint led to geometric distortions, affecting the state of the overall system. Intriguingly, even in cases where acrylic paint exhibited identical colors perceptible under visible light, distinct discrimination and identification of chemical compositions were successfully proposed.

7.
Small ; 19(38): e2301744, 2023 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-37231559

RESUMEN

Application of Si anodes is hindered by severe capacity fading due to pulverization of Si particles during the large volume changes of Si during charge/discharge and repeated formation of the solid-electrolyte interphase. To address these issues, considerable efforts have been devoted to the development of Si composites with conductive carbons (Si/C composites). However, Si/C composites with high C content inevitably show low volumetric capacity because of low electrode density. For practical applications, the volumetric capacity of a Si/C composite electrode is more important than gravimetric capacity, but volumetric capacity in pressed electrodes is rarely reported. Herein, a novel synthesis strategy is demonstrate for a compact Si nanoparticle/graphene microspherical assembly with interfacial stability and mechanical strength achieved by consecutively formed chemical bonds using 3-aminopropyltriethoxysilane and sucrose. The unpressed electrode (density: 0.71 g cm-3 ) shows a reversible specific capacity of 1470 mAh g-1 with a high initial coulombic efficiency of 83.7% at a current density of 1 C-rate. The corresponding pressed electrode (density: 1.32 g cm-3 ) exhibits high reversible volumetric capacity of 1405 mAh cm-3 and gravimetric capacity of 1520 mAh g-1 with a high initial coulombic efficiency of 80.4% and excellent cycling stability of 83% over 100 cycles at 1 C-rate.

8.
Int J Mol Sci ; 24(12)2023 Jun 09.
Artículo en Inglés | MEDLINE | ID: mdl-37373116

RESUMEN

Podocyte damage and renal inflammation are the main features and pathogenesis of diabetic nephropathy (DN). Inhibition of lysophosphatidic acid (LPA) receptor 1 (LPAR1) suppresses glomerular inflammation and improves DN. Herein, we investigated LPA-induced podocyte damage and its underlying mechanisms in DN. We investigated the effects of AM095, a specific LPAR1 inhibitor, on podocytes from streptozotocin (STZ)-induced diabetic mice. E11 cells were treated with LPA in the presence or absence of AM095, and the expression of NLRP3 inflammasome factors and pyroptosis were measured. A chromatin immunoprecipitation assay and Western blotting were performed to elucidate underlying molecular mechanisms. Gene knockdown by transfecting small interfering RNA was used to determine the role of the transcription factor Egr1 (early growth response protein 1) and histone methyltransferase EzH2 (Enhancer of Zeste Homolog 2) in LPA-induced podocyte injury. AM095 administration inhibited podocyte loss, NLRP3 inflammasome factor expression, and cell death in STZ-induced diabetic mice. In E11 cells, LPA increased NLRP3 inflammasome activation and pyroptosis via LPAR1. Egr1 mediated NLRP3 inflammasome activation and pyroptosis in LPA-treated E11 cells. LPA decreased H3K27me3 enrichment at the Egr1 promoter in E11 cells by downregulating EzH2 expression. EzH2 knockdown further increased LPA-induced Egr1 expression. In podocytes from STZ-induced diabetic mice, AM095 suppressed Egr1 expression increase and EzH2/H3K27me3 expression reduction. Collectively, these results demonstrate that LPA induces NLRP3 inflammasome activation by downregulating EzH2/H3K27me3 and upregulating Egr1 expression, resulting in podocyte damage and pyroptosis, which may be a potential mechanism of DN progression.


Asunto(s)
Diabetes Mellitus Experimental , Nefropatías Diabéticas , Podocitos , Ratones , Animales , Nefropatías Diabéticas/metabolismo , Podocitos/metabolismo , Inflamasomas/metabolismo , Regulación hacia Abajo , Piroptosis , Proteína con Dominio Pirina 3 de la Familia NLR/genética , Proteína con Dominio Pirina 3 de la Familia NLR/metabolismo , Histonas/metabolismo , Diabetes Mellitus Experimental/metabolismo , Proteína Potenciadora del Homólogo Zeste 2/genética , Proteína Potenciadora del Homólogo Zeste 2/metabolismo , Proteína 1 de la Respuesta de Crecimiento Precoz/genética , Proteína 1 de la Respuesta de Crecimiento Precoz/metabolismo , Inflamación/metabolismo
9.
Opt Express ; 30(17): 30038-30046, 2022 Aug 15.
Artículo en Inglés | MEDLINE | ID: mdl-36242115

RESUMEN

Critical factors for terahertz polarizers include broadband operation, high transmittance, and a good extinction ratio. In this paper, using a 5 nm-wide metallic slit array with a 200 nm periodicity as a wire grid polarizer, we achieved over 95% transmittance with an average extinction ratio of 40 dB, over the entire spectrum as defined by the terahertz time-domain spectroscopy (0.4 ∼ 2 THz). Theoretical calculations revealed that the slit array can show 100% transmission up to 5 THz, and wider bandwidths with a higher cutoff frequency can be achieved by reducing the slit periodicity. These results provide a novel approach for achieving a broadband THz polarizer and open a new path for seamless integration of the polarizers with nanophotonic applications.

10.
Zoolog Sci ; 39(5): 500-506, 2022 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-36205371

RESUMEN

A new spionid polychaete, Scolelepis (Parascolelepis) brunnea sp. nov., from an intertidal mud flat in Korean waters, is reported. The new species is unique among species of Scolelepis Blainville, 1828 in having conspicuously long, reddish-brown branchiae on the anteriormost chaetigers. The new species is morphologically and genetically most closely related to Scolelepis (Parascolelepis) anterobranchiata Lee and Min, 2022 from Korea. However, the new species differs from the latter by a combination of the following characteristics: presence of reddish-brown pigmentations on anteriormost body, neuropodial hooded hooks appearing from chaetigers 21 to 22, larger size of worms, and three teeth above the main fang of neuropodial hooded hooks. Detailed description and images of the new species, along with three gene regions (cytochrome c oxidase subunit I [COI], 16S ribosomal DNA [16S rDNA], and 18S rDNA), are provided.


Asunto(s)
Anélidos , Poliquetos , Animales , Anélidos/genética , ADN Ribosómico , Complejo IV de Transporte de Electrones/genética , Poliquetos/genética , República de Corea
11.
BMC Pregnancy Childbirth ; 22(1): 113, 2022 Feb 10.
Artículo en Inglés | MEDLINE | ID: mdl-35144573

RESUMEN

BACKGROUND: In twin pregnancies, the cord prolapse of either fetus during the pre-viable period leads to fetal death but can also cause an intrauterine infection, leading to death or prematu-re birth of the remaining fetus. However, there are no validated protocols to prolong the gestational period or decrease the morbidity and mortality of the remaining fetus. CASE PRESENTATION: The present cases were PPROM and cord prolapse very early during the second trimester (around 17 weeks in the first case and 19 weeks in the second case). The first fetus was evacuated, and cervical cerclage was performed at 23 and 20 weeks in the two cases, respectively. After maintaining the pregnancy, the second baby was born around 27 and 39 weeks in the first and second cases, respectively. The delivery interval between the first and second fetuses was 46 days in the first case and 126 days in the second case. CONCLUSION: If cord prolapse is identified at a pre-viable time in twin fetuses, evacuation and cerclage should be performed as soon as possible after the cord prolapse to reduce intrauterine infection and increase the survival chances of the remaining fetus.


Asunto(s)
Cerclaje Cervical/métodos , Parto Obstétrico/métodos , Rotura Prematura de Membranas Fetales/cirugía , Segundo Trimestre del Embarazo , Embarazo Gemelar , Cordón Umbilical/cirugía , Adulto , Femenino , Humanos , Nacimiento Vivo , Embarazo , Resultado del Embarazo , Prolapso
12.
Sensors (Basel) ; 22(14)2022 Jul 19.
Artículo en Inglés | MEDLINE | ID: mdl-35891070

RESUMEN

In this paper, a new two-step joint optimization approach based on the asynchronous subregion optimization method is proposed for training a pipeline model composed of two different models. The first-step processing of the proposed joint optimization approach trains the front-end model only, and the second-step processing trains all the parameters of the combined model together. In the asynchronous subregion optimization method, the first-step processing only supports the goal of the front-end model. However, the first-step processing of the proposed approach works with a new loss function to make the front-end model support the goal of the back-end model. The proposed optimization approach was applied, here, to a pipeline composed of a deep complex convolutional recurrent network (DCCRN)-based speech enhancement model and a conformer-transducer-based ASR model as a front-end and a back-end, respectively. Then, the performance of the proposed two-step joint optimization approach was evaluated on the LibriSpeech automatic speech recognition (ASR) corpus in noisy environments by measuring the character error rate (CER) and word error rate (WER). In addition, an ablation study was carried out to examine the effectiveness of the proposed optimization approach on each of the processing blocks in the conformer-transducer ASR model. Consequently, it was shown from the ablation study that the conformer-transducer-based ASR model with the joint network trained only by the proposed optimization approach achieved the lowest average CER and WER. Moreover, the proposed optimization approach reduced the average CER and WER on the Test-Noisy dataset under matched noise conditions by 0.30% and 0.48%, respectively, compared to the approach of separate optimization of speech enhancement and ASR. Compared to the conventional two-step joint optimization approach, the proposed optimization approach provided average CER and WER reductions of 0.22% and 0.31%, respectively. Moreover, it was revealed that the proposed optimization approach achieved a lower average CER and WER, by 0.32% and 0.43%, respectively, than the conventional optimization approach under mismatched noise conditions.


Asunto(s)
Percepción del Habla , Habla , Ruido , Software de Reconocimiento del Habla
13.
Sensors (Basel) ; 23(1)2022 Dec 25.
Artículo en Inglés | MEDLINE | ID: mdl-36616801

RESUMEN

In this paper, we propose an end-to-end (E2E) neural network model to detect autism spectrum disorder (ASD) from children's voices without explicitly extracting the deterministic features. In order to obtain the decisions for discriminating between the voices of children with ASD and those with typical development (TD), we combined two different feature-extraction models and a bidirectional long short-term memory (BLSTM)-based classifier to obtain the ASD/TD classification in the form of probability. We realized one of the feature extractors as the bottleneck feature from an autoencoder using the extended version of the Geneva minimalistic acoustic parameter set (eGeMAPS) input. The other feature extractor is the context vector from a pretrained wav2vec2.0-based model directly applied to the waveform input. In addition, we optimized the E2E models in two different ways: (1) fine-tuning and (2) joint optimization. To evaluate the performance of the proposed E2E models, we prepared two datasets from video recordings of ASD diagnoses collected between 2016 and 2018 at Seoul National University Bundang Hospital (SNUBH), and between 2019 and 2021 at a Living Lab. According to the experimental results, the proposed wav2vec2.0-based E2E model with joint optimization achieved significant improvements in the accuracy and unweighted average recall, from 64.74% to 71.66% and from 65.04% to 70.81%, respectively, compared with a conventional model using autoencoder-based BLSTM and the deterministic features of the eGeMAPS.


Asunto(s)
Trastorno del Espectro Autista , Niño , Humanos , Lactante , Trastorno del Espectro Autista/diagnóstico , Memoria a Largo Plazo , Grabación en Video/métodos
14.
Int J Mol Sci ; 23(18)2022 Sep 10.
Artículo en Inglés | MEDLINE | ID: mdl-36142408

RESUMEN

The epithelial-mesenchymal transition (EMT) is a differentiation process associated with fibrogenesis in diabetic nephropathy (DN). Lysophosphatidic acid (LPA) is a small, naturally occurring glycerophospholipid implicated in the pathogenesis of DN. In this study, we investigated the role of LPA/LPAR1 signaling in the EMT of tubular cells as well as the underlying mechanisms. We observed a decrease in E-cadherin and an increase in vimentin expression levels in the kidney tubules of diabetic db/db mice, and treatment with ki16425 (LPAR1/3 inhibitor) inhibited the expression of these EMT markers. Ki16425 treatment also decreased the expression levels of the fibrotic factors fibronectin and alpha-smooth muscle actin (α-SMA) in db/db mice. Similarly, we found that LPA decreased E-cadherin expression and increased vimentin expression in HK-2 cells, which was reversed by treatment with ki16425 or AM095 (LPAR1 inhibitor). In addition, the expression levels of fibronectin and α-SMA were increased by LPA, and this effect was reversed by treatment with ki16425 and AM095 or by LPAR1 knockdown. Moreover, LPA induced the expression of the transcription factor, Krüppel-like factor 5 (KLF5), which was decreased by AM095 treatment or LPAR1 knockdown. The expression levels of EMT markers and fibrotic factors induced by LPA were decreased upon KLF5 knockdown in HK-2 cells. Inhibition of the extracellular signal-regulated kinase (ERK), c-Jun N-terminal kinase (JNK), and serine-threonine kinase (AKT) pathways decreased LPA-induced expression of KLF5 and EMT markers. In conclusion, these data suggest that LPA contributes to the pathogenesis of diabetic nephropathy by inducing EMT and renal tubular fibrosis via regulation of KLF5 through the LPAR1.


Asunto(s)
Nefropatías Diabéticas , Actinas/metabolismo , Animales , Cadherinas/metabolismo , Nefropatías Diabéticas/metabolismo , Células Epiteliales/metabolismo , Transición Epitelial-Mesenquimal , Quinasas MAP Reguladas por Señal Extracelular/metabolismo , Factor V , Fibronectinas/metabolismo , Fibrosis , Glicerofosfolípidos/metabolismo , Isoxazoles , Proteínas Quinasas JNK Activadas por Mitógenos/metabolismo , Túbulos Renales/metabolismo , Factores de Transcripción de Tipo Kruppel/genética , Factores de Transcripción de Tipo Kruppel/metabolismo , Lisofosfolípidos , Ratones , Propionatos , Proteínas Serina-Treonina Quinasas , Proteínas Proto-Oncogénicas c-akt/metabolismo , Transducción de Señal , Factores de Transcripción/metabolismo , Vimentina/metabolismo
15.
Pak J Med Sci ; 38(3Part-I): 469-475, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-35480548

RESUMEN

Background and Objective: In 2020, during the coronavirus disease (COVID-19) pandemic, medical students were placed in a learning environment that exposed them to unsafe clinical settings. In this study, using a phenomenological approach, we analyze the experiences of fourth-year students in the Daegu area of South Korea, a region that experienced a high concentration of COVID-19 infections. Methods: The essays of 80 students from four medical schools who agreed to participate in the study were utilized in the final data analysis. The data were analyzed using the proposed phenomenological analysis. Results: Forty-seven condensed meaning units, twelve subthemes, and three essential themes were identified. The main theme includes the following: 1) confusion and stress due to sudden changes in the learning situation 2) learned the medical professionalism of physicians 3) reflection and internal change regarding what it means to be a physician. Conclusions: The COVID-19 pandemic had a significant impact on students who participated in clinical clerkships. This study can provide baseline data for planning educational strategies and establishing a support system for students in response to the changes that they may experience in the event of the reoccurrence of a novel infectious disease in the future.

16.
Br J Cancer ; 124(1): 290-298, 2021 01.
Artículo en Inglés | MEDLINE | ID: mdl-33204025

RESUMEN

BACKGROUND: Recently, fusion variants of the breast cancer anti-oestrogen-resistance 4 (BCAR4) gene were recurrently discovered in lung adenocarcinoma from the genome-wide studies. However, the functional characterisation of BCAR4 fusion has not been investigated. METHODS: Based on the analysis of RNA-sequencing data, we identified a fusion transcript of CD63-BCAR4 in a Korean patient with lung adenocarcinoma who did not harbour any known activating mutations in EGFR and KRAS genes. To investigate the oncogenic effect of CD63-BCAR4, in vitro and in vivo animal experiments were performed. RESULTS: In vitro experiments showed strongly enhanced cell migration and proliferation by the exogenous expression of CD63-BCAR4 protein in bronchial epithelial cells. Cell migration was notably reduced after knockdown of BCAR4 fusion by small-interfering RNA. The tumorigenic and metastatic capability of the CD63-BCAR4 fusion was confirmed by using the mouse xenograft model. Fusion-overexpressed cells result in metastasis to the liver and lung as well as the primary tumours after subcutaneous injection into mice. Cyclin D1, MMP1, Slug and mesenchymal markers were significantly increased after CD63-BCAR4 overexpression in the in vitro and in vivo experiments. CONCLUSIONS: Taken together, our results suggest a newly identified fusion gene, CD63-BCAR4 as a potential novel oncogene in lung adenocarcinoma.


Asunto(s)
Adenocarcinoma del Pulmón/genética , Neoplasias Pulmonares/genética , Fusión de Oncogenes/genética , ARN Largo no Codificante/genética , Tetraspanina 30/genética , Adenocarcinoma del Pulmón/patología , Animales , Carcinogénesis/genética , Movimiento Celular , Xenoinjertos , Humanos , Neoplasias Pulmonares/patología , Ratones , Proteínas de Fusión Oncogénica/genética
17.
Small ; 17(32): e2101930, 2021 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-34216430

RESUMEN

Graphene is extensively investigated for various energy storage systems. However, the very low density (<0.01 g cm-3 ) of graphene nanosheets has hindered its further applications. To solve this issue, a controlled assembly of 2D graphene building blocks should be developed into graphene microspheres with high packing density, and restacking of graphene should be prevented to ensure an electrochemically accessible surface area during the assembly. Furthermore, graphene microspheres should have multiple 1D external conductive architecture to promote contacts with the neighbors. This study reports in situ growth of novel graphene nanostructures in reduced graphene oxide microspherical assembly (denoted as GT/GnS@rGB) with restacking resistance and interparticle contacts, for electrochemical energy storage. The GT/GnS@rGB showed high gravimetric (231.8 F g-1 ) and volumetric (181.5 F cm-3 ) capacitances at 0.2 A g-1 in organic electrolyte with excellent rate capabilities of 94.3% (@ 0.2 vs 10 Ag-1 ). Furthermore, GT/GnS@rGB exhibited excellent cycling stability (96.1% of the initial capacitance after 100 000 charge/discharge cycles at 2 A g-1 ). As demonstrated in the electrochemical evaluation as electrode materials for electrical double-layer capacitors, unique structural and textural features of the GT/GnS@rGB would be beneficial in the use of graphene assembly for energy storage applications.

18.
Int J Mol Sci ; 22(23)2021 Nov 26.
Artículo en Inglés | MEDLINE | ID: mdl-34884579

RESUMEN

This research investigated the capture of nitrate by magnesium ions in plasma-activated water (PAW) and its antifungal effect on the cell viability of the newly emerged mushroom pathogen Cryptococcus pseudolongus. Optical emission spectra of the plasma jet exhibited several emission bands attributable to plasma-generated reactive oxygen and nitrogen species. The plasma was injected directly into deionized water (DW) with and without an immersed magnesium block. Plasma treatment of DW produced acidic PAW. However, plasma-activated magnesium water (PA-Mg-W) tended to be neutralized due to the reduction in plasma-generated hydrogen ions by electrons released from the zero-valent magnesium. Optical absorption and Raman spectra confirmed that nitrate ions were the dominant reactive species in the PAW and PA-Mg-W. Nitrate had a concentration-dependent antifungal effect on the tested fungal cells. We observed that the free nitrate content could be controlled to be lower in the PA-Mg-W than in the PAW due to the formation of nitrate salts by the magnesium ions. Although both the PAW and PA-Mg-W had antifungal effects on C. pseudolongus, their effectiveness differed, with cell viability higher in the PA-Mg-W than in the PAW. This study demonstrates that the antifungal effect of PAW could be manipulated using nitrate capture. The wide use of plasma therapy for problematic fungus control is challenging because fungi have rigid cell wall structures in different fungal groups.


Asunto(s)
Antifúngicos/farmacología , Basidiomycota/efectos de los fármacos , Magnesio/química , Nitratos/química , Gases em Plasma/farmacología , Agua/farmacología , Antifúngicos/química , Concentración de Iones de Hidrógeno , Nitratos/aislamiento & purificación , Gases em Plasma/química , Agua/química
19.
Molecules ; 26(9)2021 May 08.
Artículo en Inglés | MEDLINE | ID: mdl-34066676

RESUMEN

Microcolumns have a stacked structure composed of an electron emitter, electron lens (source lens), einzel lens, and a deflector manufactured using a micro electro-mechanical system process. The electrons emitted from the tungsten field emitter mostly pass through the aperture holes. However, other electrons fail to pass through because of collisions around the aperture hole. We used Raman scattering measurements and X-ray photoelectron spectroscopy analyses to investigate the influence of electron beam bombardment on a Si electron lens irradiated by acceleration voltages of 0, 20, and 30 keV. We confirmed that the crystallinity was degraded, and carbon-related contamination was detected at the surface and edge of the aperture hole of the Si electron lens after electron bombardment for 24 h. Carbon-related contamination on the surface of the Si electron lens was verified by analyzing the Raman spectra of the carbon-deposited Si substrate using DC sputtering and a carbon rod sample. We report the crystallinity and the origin of the carbon-related contamination of electron Si lenses after electron beam bombardment by non-destructive Raman scattering and XPS analysis methods.

20.
J Obstet Gynaecol ; 41(4): 605-611, 2021 May.
Artículo en Inglés | MEDLINE | ID: mdl-32815448

RESUMEN

The lymph node status is the most important prognostic factor for endometrial cancer. This study aimed to assess whether sentinel lymph node mapping (SLNM) is applicable in endometrial cancer. A retrospective review of patients with endometrial cancer who were diagnosed and treated in Asan Medical Centre from September 2015 to December 2017 was conducted. One hundred patients underwent robotic (da Vinci®) or laparoscopic surgical treatment, including SLNM with indocyanine green (ICG) fluorescence detection using the Firefly® and NIR/ICG systems. At least one lymph node area was observed in 100% of SLNM cases. Sentinel node detection and frozen biopsy were performed in all cases, and all patients with metastasis were found on SLNM. The sensitivity and negative predictive value were both 100% in the patient-by-patient and station-by-station analyses. SLNM appears to be a feasible method to reduce the morbidity and increase the detection rate in early-stage endometrial carcinoma.What is already known on this subject? There are studies that it is safe to diagnose the possibility of lymph node metastasis through sentinel lymph node mapping in endometrial cancer.What do the results of this study add? In this study, it is shown that the accuracy of sentinel lymph node mapping is 100% accurate.What are the implications of these findings for clinical practise and/or further research? Therefore, total lymphadenectomy will not be necessary for the future.


Asunto(s)
Colorantes , Neoplasias Endometriales/diagnóstico por imagen , Verde de Indocianina , Metástasis Linfática/diagnóstico por imagen , Imagen Óptica/estadística & datos numéricos , Ganglio Linfático Centinela/diagnóstico por imagen , Adulto , Anciano , Neoplasias Endometriales/patología , Femenino , Humanos , Escisión del Ganglio Linfático , Persona de Mediana Edad , Imagen Óptica/métodos , Valor Predictivo de las Pruebas , Sensibilidad y Especificidad , Biopsia del Ganglio Linfático Centinela
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