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1.
Proc Natl Acad Sci U S A ; 121(34): e2405632121, 2024 Aug 20.
Artículo en Inglés | MEDLINE | ID: mdl-39150783

RESUMEN

Transcription of eukaryotic protein-coding genes generates immature mRNAs that are subjected to a series of processing events, including capping, splicing, cleavage, and polyadenylation (CPA), and chemical modifications of bases. Alternative polyadenylation (APA) greatly contributes to mRNA diversity in the cell. By determining the length of the 3' untranslated region, APA generates transcripts with different regulatory elements, such as miRNA and RBP binding sites, which can influence mRNA stability, turnover, and translation. In the model plant Arabidopsis thaliana, APA is involved in the control of seed dormancy and flowering. In view of the physiological importance of APA in plants, we decided to investigate the effects of light/dark conditions and compare the underlying mechanisms to those elucidated for alternative splicing (AS). We found that light controls APA in approximately 30% of Arabidopsis genes. Similar to AS, the effect of light on APA requires functional chloroplasts, is not affected in mutants of the phytochrome and cryptochrome photoreceptor pathways, and is observed in roots only when the communication with the photosynthetic tissues is not interrupted. Furthermore, mitochondrial and TOR kinase activities are necessary for the effect of light. However, unlike AS, coupling with transcriptional elongation does not seem to be involved since light-dependent APA regulation is neither abolished in mutants of the TFIIS transcript elongation factor nor universally affected by chromatin relaxation caused by histone deacetylase inhibition. Instead, regulation seems to correlate with changes in the abundance of constitutive CPA factors, also mediated by the chloroplast.


Asunto(s)
Arabidopsis , Cloroplastos , Regulación de la Expresión Génica de las Plantas , Luz , Poliadenilación , Arabidopsis/genética , Arabidopsis/metabolismo , Cloroplastos/metabolismo , Cloroplastos/genética , Empalme Alternativo , Proteínas de Arabidopsis/metabolismo , Proteínas de Arabidopsis/genética , ARN Mensajero/genética , ARN Mensajero/metabolismo
2.
BMC Pulm Med ; 24(1): 374, 2024 Aug 01.
Artículo en Inglés | MEDLINE | ID: mdl-39085818

RESUMEN

BACKGROUND: Previous studies have reported reduced acute exacerbation rates and improved symptom control in asthma patients treated using inhaled corticosteroids plus formoterol maintenance and reliever therapy (MART). Fluticasone furoate (FF) and vilanterol (VIL) also provide rapid bronchodilation and sustained anti-inflammatory effects, however no studies have investigated FF/VIL as MART for asthma control. METHODS: From October 1, 2021 to September 30, 2023, this retrospective study included asthma patients classified as step 3 or 4 according to the Global Initiative for Asthma guidelines, who were then divided into two groups. One group received BUD/FOR as MART, while the other received FF/VIL as MART. Pulmonary function tests, exacerbation rates, Asthma Control Test (ACT), fractional exhaled nitric oxide (FeNO) levels, and blood eosinophil counts were measured before and after 12 months of treatment. RESULTS: A total of 161 patients were included, of whom 36 received BUD/FOR twice daily as MART, and 125 received FF/VIL once daily as MART. After 12 months of treatment, the FF/VIL group showed a significant increase in ACT scores by 1.57 (p < 0.001), while the BUD/FOR group had an increase of 0.88 (p = 0.11). In terms of FeNO levels, the BUD/FOR group experienced a decline of -0.2 ppb (p = 0.98), whereas the FF/VIL group had a mild increase of + 0.8 ppb (p = 0.7). Notably, there was a significant difference in the change of FeNO between the two groups (∆ FeNO: -0.2 ppb in BUD/FOR; + 0.8 ppb in FF/VIL, p < 0.001). There were no significant alterations observed in FEV1, blood eosinophil count, or acute exacerbation decline in either group. CONCLUSIONS: In the current study, patients treated with FF/VIL as MART showed improvements in ACT scores, while those treated with BUD/FOR as MART exhibited a reduction in FeNO levels. However, the difference between the two treatment groups did not reach clinical significance. Thus, FF/VIL as MART showed similar effectiveness to BUD/FOR as MART.


Asunto(s)
Asma , Alcoholes Bencílicos , Clorobencenos , Combinación de Medicamentos , Humanos , Masculino , Femenino , Alcoholes Bencílicos/administración & dosificación , Alcoholes Bencílicos/uso terapéutico , Estudios Retrospectivos , Asma/tratamiento farmacológico , Persona de Mediana Edad , Clorobencenos/administración & dosificación , Clorobencenos/uso terapéutico , Adulto , Broncodilatadores/administración & dosificación , Broncodilatadores/uso terapéutico , Administración por Inhalación , Androstadienos/administración & dosificación , Androstadienos/uso terapéutico , Budesonida/administración & dosificación , Budesonida/uso terapéutico , Antiasmáticos/uso terapéutico , Antiasmáticos/administración & dosificación , Anciano , Fumarato de Formoterol/administración & dosificación , Resultado del Tratamiento , Óxido Nítrico/análisis , Óxido Nítrico/metabolismo , Combinación Budesonida y Fumarato de Formoterol/administración & dosificación , Combinación Budesonida y Fumarato de Formoterol/uso terapéutico , Pruebas de Función Respiratoria , Eosinófilos/efectos de los fármacos
3.
FASEB J ; 36(1): e22110, 2022 01.
Artículo en Inglés | MEDLINE | ID: mdl-34918393

RESUMEN

Dengue virus (DENV) is a cause of vascular endothelial dysfunction and vascular leakage, which are characterized as hallmarks of dengue hemorrhagic fever or dengue shock syndrome, which become a severe global health emergency with substantial morbidity and mortality. Currently, there are still no promising therapeutics to alleviate the dengue-associated vascular hemorrhage in a clinical setting. In the present study, we first observed that heme oxygenase-1 (HO-1) expression level was highly suppressed in severe DENV-infected patients. In contrast, the overexpression of HO-1 could attenuate DENV-induced pathogenesis, including plasma leakage and thrombocytopenia, in an AG129 mouse model. Our data indicate that overexpression of HO-1 or its metabolite biliverdin can maintain endothelial integrity upon DENV infection in vitro and in vivo. We further characterized the positive regulatory effect of HO-1 on the endothelial adhesion factor vascular endothelial-cadherin to decrease DENV-induced endothelial hyperpermeability. Subsequently, we confirmed that two medicinal plant-derived compounds, andrographolide, and celastrol, widely used as a nutritional or medicinal supplement are useful to attenuate DENV-induced plasma leakage through induction of the HO-1 expression in DENV-infected AG129 mice. In conclusion, our findings reveal that induction of the HO-1 signal pathway is a promising option for the treatment of DENV-induced vascular pathologies.


Asunto(s)
Permeabilidad Capilar , Virus del Dengue/metabolismo , Endotelio Vascular/enzimología , Hemo-Oxigenasa 1/metabolismo , Proteínas de la Membrana/metabolismo , Dengue Grave/enzimología , Animales , Línea Celular , Virus del Dengue/genética , Modelos Animales de Enfermedad , Hemo-Oxigenasa 1/genética , Humanos , Proteínas de la Membrana/genética , Ratones , Ratones Mutantes , Dengue Grave/genética
4.
BMC Pulm Med ; 23(1): 331, 2023 Sep 08.
Artículo en Inglés | MEDLINE | ID: mdl-37684581

RESUMEN

BACKGROUND: We conducted a retrospective observational study to explore the potential application of impulse oscillometry (IOS) as an alternative to high-resolution computed tomography (HRCT) for detecting pulmonary involvement in patients with rheumatoid arthritis (RA) because clinically evident interstitial lung disease (ILD) and airway involvement are common in this population. METHODS: We enrolled 72 patients with RA who underwent pulmonary function tests (PFTs) and IOS between September 2021 and September 2022. We aimed to identify the PFT and IOS variables associated with lung diseases shown on HRCT images. RESULTS: In our cohort of 72 patients, 48 underwent HRCT; of these, 35 had airway disease or ILD and 13 showed no obvious abnormalities on HRCT. Abnormal IOS and PFT parameters were observed in 34 and 23 patients, respectively, with abnormal HRCT images. The predicted percentages for forced vital capacity, the ratio of forced expiratory volume in the first one second to forced vital capacity, and forced mid-expiratory flow value were significantly lower in patients with abnormal HRCT. Lung resistance at 5 Hz, difference in resistance between 5 and 20 Hz, resonant frequency (Fres), and reactance area were higher in these patients and reactance at 5 Hz was lower. Compared to other parameters, Fres > 14.14 was significantly associated with alterations in HRCT and may be used as an indicator for monitoring disease. CONCLUSION: Fres > 14.14 is significantly associated with lung involvement in RA patients. Performance of spirometry with IOS is more beneficial than spirometry alone for evaluating lung involvement in RA patients.


Asunto(s)
Artritis Reumatoide , Enfermedades Pulmonares Intersticiales , Trastornos Respiratorios , Humanos , Adulto , Oscilometría , Enfermedades Pulmonares Intersticiales/diagnóstico , Pruebas de Función Respiratoria , Artritis Reumatoide/complicaciones
5.
Int J Mol Sci ; 24(11)2023 Jun 05.
Artículo en Inglés | MEDLINE | ID: mdl-37298699

RESUMEN

This study investigated miRNA and cytokine expression changes in peritoneal fluid samples of patients with advanced ovarian cancer (OVCA) after receiving hyperthermic intraperitoneal chemotherapy (HIPEC) during cytoreduction surgery (CRS). We collected samples prior to HIPEC, immediately after HIPEC, and 24/48/72 h after CRS from a total of 6 patients. Cytokine levels were assessed using a multiplex cytokine array, and a miRNA PanelChip Analysis System was used for miRNA detection. Following HIPEC, miR-320a-3p, and miR-663-a were found to be immediately down-regulated but increased after 24 h. Further, significant upregulation post-HIPEC and sustained increases in expression were detected in six other miRNAs, including miR-1290, miR-1972, miR-1254, miR-483-5p, miR-574-3p, and miR-574-5p. We also found significantly increased expression of cytokines, including MCP-1, IL-6, IL-6sR, TIMP-1, RANTES, and G-CSF. The changing expression pattern throughout the study duration included a negative correlation in miR-320a-3p and miR-663-a to cytokines including RANTES, TIMP-1, and IL-6 but a positive correlation in miRNAs to cytokines including MCP-1, IL-6sR, and G-CSF. Our study found miRNAs and cytokines in the peritoneal fluid of OVCA patients demonstrated different expression characteristics following CRS and HIPEC. Both changes in expression demonstrated correlations, but the role of HIPEC remains unknown, prompting the need for research in the future.


Asunto(s)
Hipertermia Inducida , MicroARNs , Neoplasias Ováricas , Neoplasias Peritoneales , Humanos , Femenino , Quimioterapia Intraperitoneal Hipertérmica , Quimiocina CCL5 , Inhibidor Tisular de Metaloproteinasa-1 , Neoplasias Peritoneales/tratamiento farmacológico , Neoplasias Peritoneales/genética , Líquido Ascítico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Interleucina-6/genética , Neoplasias Ováricas/tratamiento farmacológico , Neoplasias Ováricas/genética , Carcinoma Epitelial de Ovario/tratamiento farmacológico , Citocinas/uso terapéutico , MicroARNs/genética , MicroARNs/uso terapéutico , Factor Estimulante de Colonias de Granulocitos/uso terapéutico , Terapia Combinada , Tasa de Supervivencia , Estudios Retrospectivos
6.
Environ Res ; 206: 112610, 2022 04 15.
Artículo en Inglés | MEDLINE | ID: mdl-34953885

RESUMEN

To not only optimize the hyper-parameters of the classification layer of dense convolutional network with 201 convolutional layers (DenseNet-201) but also use data augmentation processes could enhance the performance of DenseNet-201, and DenseNet-201 is rarely applied to the identifications of the environmental microorganism (EM) images. Hence, this study was to propose the optimally fine-tuned DenseNet-201 (OFTD) with data augmentation to better classify the EM images on Environmental Microorganism Dataset (EMDS). The training dataset was composed of 70% Environmental Microorganism Dataset (EMDS) images and so was mainly used to fit the parameters of convolutional layers of optimally fine-tuned DenseNet-201 (OFTD). Meanwhile, the other EMDS images were considered as the testing dataset and used to qualify the performance of the OFTD. Also, gradient-weighted class activation mapping method (Grad-CAM) was adopted to visually illustrate the dominant features of the EM images. Based on the results, the OFTD model with data augmentation achieved the highest classification accuracy of 98.4%. In this case, so its stability and accuracy were guaranteed. Besides, the optimally fine-tuned classification layer is considered a more efficient method than the data augmentation technique adopted in this study when it comes to the improvement of the performance in DenseNet-201 implemented on EMDS. Grad-CAM highlighted the coarse EM features identified effectively by the OFTD; for example, foot and stalk were considered as the dominated features of Rotifera and Vorticella, respectively. In summary, the proposed OFTD with data augmentation could provide an efficient solution for the EM detection in digital microscope.


Asunto(s)
Redes Neurales de la Computación
7.
J Formos Med Assoc ; 121(9): 1728-1738, 2022 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-35168836

RESUMEN

BACKGROUND: The need is growing to create medical big data based on the electronic health records collected from different hospitals. Errors for sure occur and how to correct them should be explored. METHODS: Electronic health records of 9,197,817 patients and 53,081,148 visits, totaling about 500 million records for 2006-2016, were transmitted from eight hospitals into an integrated database. We randomly selected 10% of patients, accumulated the primary keys for their tabulated data, and compared the key numbers in the transmitted data with those of the raw data. Errors were identified based on statistical testing and clinical reasoning. RESULTS: Data were recorded in 1573 tables. Among these, 58 (3.7%) had different key numbers, with the maximum of 16.34/1000. Statistical differences (P < 0.05) were found in 34 (58.6%), of which 15 were caused by changes in diagnostic codes, wrong accounts, or modified orders. For the rest, the differences were related to accumulation of hospital visits over time. In the remaining 24 tables (41.4%) without significant differences, three were revised because of incorrect computer programming or wrong accounts. For the rest, the programming was correct and absolute differences were negligible. The applicability was confirmed using the data of 2,730,883 patients and 15,647,468 patient-visits transmitted during 2017-2018, in which 10 (3.5%) tables were corrected. CONCLUSION: Significant magnitude of inconsistent data does exist during the transmission of big data from diverse sources. Systematic validation is essential. Comparing the number of data tabulated using the primary keys allow us to rapidly identify and correct these scattered errors.


Asunto(s)
Macrodatos , Investigación Biomédica , Bases de Datos Factuales , Registros Electrónicos de Salud , Humanos , Sistemas Multiinstitucionales
8.
Int J Cancer ; 148(3): 665-672, 2021 02 01.
Artículo en Inglés | MEDLINE | ID: mdl-32781482

RESUMEN

Human papillomavirus (HPV) is the well-established etiologic factor for cervical neoplasia. Cervical conization constitutes an effective treatment for high-grade cervical intraepithelial neoplasia (HG-CIN). We conducted an observational study for long-term outcomes and HPV genotype changes after conization for HG-CIN. Between 2008 and 2014, patients with newly diagnosed HG-CIN before conization (surveillance new [SN] group) and those who had undergone conization without hysterectomy (surveillance previous [SP] group) were enrolled. HPV testing and Pap smear were performed periodically for the SN and SP (collectively S) groups. All other patients receiving conization for HG-CIN during the study period were identified from our hospital database. Those eligible but not enrolled into our study were assigned to the non-surveillance (non-S) group. For the S group (n = 493), the median follow-up period was 74.3 months. Eighty-four cases had recurrent CIN Grade 2 or worse (CIN2+) (5-year cumulative rate: 14.8%), of which six had invasive cancer. Among the 84 patients, 65 (77.4%) exhibited type-specific persistence in the paired HPV results, whereas only 7 (8.3%) harbored new HPV types that belonged to the 9-valent vaccine types. Among the 7397 non-S patients, 789 demonstrated recurrent CIN2+, of which 57 had invasive cancer. The stages distribution of those progressed to invasive cancer in the non-S group were more advanced than the S group (P = .033). Active surveillance might reduce the severity of those progressed to cancer. Because a majority of the patients with recurrent CIN2+ had persistent type-specific HPV infections, effective therapeutic vaccines are an unmet medical need.


Asunto(s)
Alphapapillomavirus/genética , Infecciones por Papillomavirus/diagnóstico , Displasia del Cuello del Útero/patología , Displasia del Cuello del Útero/cirugía , Neoplasias del Cuello Uterino/patología , Neoplasias del Cuello Uterino/cirugía , Adulto , Anciano , Alphapapillomavirus/patogenicidad , Conización , Progresión de la Enfermedad , Femenino , Genotipo , Humanos , Persona de Mediana Edad , Clasificación del Tumor , Prueba de Papanicolaou , Estudios Prospectivos , Taiwán , Resultado del Tratamiento , Neoplasias del Cuello Uterino/virología , Adulto Joven , Displasia del Cuello del Útero/virología
9.
J Ultrasound Med ; 40(1): 49-58, 2021 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-32562435

RESUMEN

OBJECTIVES: We hypothesized that specific endobronchial ultrasound (EBUS) features may differentiate sarcoidosis from other causes of lymphadenopathy. METHODS: We conducted this retrospective observational study from January 2014 to January 2019 to analyze patients with intrathoracic lymphadenopathy who underwent EBUS-guided transbronchial needle aspiration. Ultrasound features, including nodal size, margin, echogenicity, the presence or absence of calcification, a central hilar structure, the coagulation necrosis sign, nodal conglomeration, and the septal vessel sign in the color Doppler mode were recorded and compared between 3 groups. RESULTS: Of the 90 included patients, 15 had a diagnosis of tuberculosis; 56 had a diagnosis of sarcoidosis; and 19 had a diagnosis of malignant lymph nodes by EBUS-guided transbronchial needle aspiration. The presence of nodal conglomeration (94.6% versus 60.0% versus 5.3%; P < .001), the septal vessel sign in the color Doppler mode (55.4% versus 13.3% versus 15.8%; P = .002), and a distinct margin (73.2% versus 13.3% versus 47.4%; P < .001) were significantly higher in the sarcoidosis group than in the tuberculosis lymphadenopathy and malignant lymph node groups. The presence of the coagulation necrosis sign (8.9% versus 93.3% versus 31.6%; P < .001) was significantly lower in the sarcoidosis group than in tuberculosis lymphadenopathy and malignant lymph node groups. A multivariate analysis showed that the presence of nodal conglomeration, the absence of coagulation necrosis, and the presence of the septal vessel sign in the color Doppler mode were independent predictive factors for the diagnosis of sarcoidosis. CONCLUSIONS: The presence of nodal conglomeration, the absence of coagulation necrosis, and the presence of the septal vessel sign in the color Doppler mode in lymph nodes on EBUS are predictive of sarcoidosis.


Asunto(s)
Linfadenopatía , Sarcoidosis , Biopsia por Aspiración con Aguja Fina Guiada por Ultrasonido Endoscópico , Endosonografía , Humanos , Ganglios Linfáticos/diagnóstico por imagen , Linfadenopatía/diagnóstico por imagen , Estudios Retrospectivos , Sarcoidosis/diagnóstico por imagen , Ultrasonografía
10.
J Viral Hepat ; 26(6): 655-665, 2019 06.
Artículo en Inglés | MEDLINE | ID: mdl-30706605

RESUMEN

MicroRNAs are small noncoding RNAs that are central factors between hepatitis C virus (HCV) and host cellular factors for viral replication and liver disease progression, including liver fibrosis, cirrhosis and hepatocellular carcinoma. In the present study, we found that overexpressing miR-let-7c markedly reduced HCV replication because it induced haem oxygenase-1 (HO-1) expression by targeting HO-1 transcriptional repressor Bach1, ultimately leading to stimulating an antiviral interferon response and blockade of HCV viral protease activity. In contrast, the antiviral actions of miR-let-7c were attenuated by miR-let-7c inhibitor treatment, exogenously expressing Bach1 or suppressing HO-1 activity and expression. A proposed model indicates a key role for miR-let-7c targeting Bach1 to transactivate HO-1-mediated antiviral actions against HCV. miR-let-7c may serve as an attractive target for antiviral development.


Asunto(s)
Factores de Transcripción con Cremalleras de Leucina de Carácter Básico/genética , Hemo-Oxigenasa 1/genética , Hepacivirus/fisiología , Interacciones Microbiota-Huesped , MicroARNs/genética , Replicación Viral , Factores de Transcripción con Cremalleras de Leucina de Carácter Básico/inmunología , Línea Celular , Hepacivirus/inmunología , Humanos , Interferones/inmunología
11.
J Formos Med Assoc ; 118(4): 821-827, 2019 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-30293927

RESUMEN

BACKGROUND: Carbon monoxide (CO), a colorless and odorless gas, is one of the common causes of poisoning-related deaths worldwide. CO poisoning can result in hypoxic brain damage and death, but intensive care can improve the likely outcome for critically ill patients. However, there is a paucity of clinical data regarding the prognostic factors and association between organ dysfunction and clinical outcome of patients treated for CO poisoning in the intensive care unit (ICU). METHODS: We performed a retrospective study of patients admitted to a university affiliated hospital ICU between July 2001 and December 2010 following CO poisoning. Outcomes were survival to ICU discharge and to hospital discharge. RESULTS: Seven hundred and eighty-seven patients were admitted to the university hospital following CO poisoning, of which 140 (17.8%) were admitted to the hospital ICU. The overall mortality rate of the patients admitted to the ICU was 14.3% (20/140). Univariate analysis indicated that non-surviving patients with CO poisoning were more likely to have initial blood carboxyhemoglobin (COHb) level > 30%, shock, acute respiratory failure, Acute Physiology and Chronic Health Evaluation II (APACHE II) score ≥ 25, Glasgow coma scale (GCS) score of 3, acute renal failure, dysfunction or failure of more than 3 organs, low blood pH, low HCO3- level, high potassium level, and high glucose level. They were also more likely to have not received hyperbaric oxygen (HBO) intervention. Multivariate logistical regression analysis indicated that the mortality rate of patients treated in the ICU for CO poisoning was higher if their initial APACHE II score was ≥25, GCS was 3, and more than 3 organs were dysfunctional. Moreover, HBO intervention in ICU significantly decreased patients' risk of mortality due to CO poisoning. CONCLUSION: In conclusion, we observed that APACHE II score >25, GCS 3, and dysfunction of more than 3 organ systems on admission to emergency department was associated with a significant mortality risk in patients treated in the ICU for CO poisoning. Moreover, HBO therapy could reduce the risk of mortality in patients with CO poisoning in ICU.


Asunto(s)
Intoxicación por Monóxido de Carbono/mortalidad , Mortalidad Hospitalaria , Unidades de Cuidados Intensivos/estadística & datos numéricos , APACHE , Lesión Renal Aguda/etiología , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Intoxicación por Monóxido de Carbono/terapia , Carboxihemoglobina/análisis , Femenino , Escala de Coma de Glasgow , Hospitales Universitarios , Humanos , Oxigenoterapia Hiperbárica , Modelos Logísticos , Masculino , Persona de Mediana Edad , Insuficiencia Multiorgánica/etiología , Análisis Multivariante , Pronóstico , Estudios Retrospectivos , Taiwán/epidemiología , Adulto Joven
12.
Int J Mol Sci ; 20(18)2019 Sep 14.
Artículo en Inglés | MEDLINE | ID: mdl-31540136

RESUMEN

Insulin resistance and diabetes are both associated with chronic hepatitis C virus (HCV) infection, and the glucagon-like peptide-1(GLP-1) receptor agonist, liraglutide, is a common therapy for diabetes. Our aim was to investigate whether liraglutide treatment can inhibit HCV replication. A cell culture-produced HCV infectious system was generated by transfection of in vitro-transcribed genomic JFH-1 ribonucleic acid (RNA) into Huh-7.5 cells. Total RNA samples were extracted to determine the efficiency of HCV replication. The Ava5 cells were treated with liraglutide and cell viability was calculated. A Western blot analysis of the protein expression was performed. The immunoreactive blot signals were also detected. Liraglutide activated GLP-1 receptors in the HCV infectious system, and inhibited subgenomic HCV RNA replication in the HuH-7.5 cells. The Western blot analysis revealed both HCV protein and replicon RNA were reduced after treatment with liraglutide in a dose-dependent manner. Liraglutide decreased the cell viability of HCV RNA at an optimum concentration of 120 µg/mL, activated the 5' adenosine monophosphate-activated protein kinase (AMPK) and the phosphorylated- transducer of regulated cyclic adenosine monophosphate (CAMP) response element-binding protein 2 (TORC2), thereby decreasing the cell viability of phosphoenolpyruvate carboxykinase (PEPCK) and G6pase RNA Therefore, we conclude that liraglutide can inhibit HCV replication via an AMPK/TORC2-dependent pathway.


Asunto(s)
Proteínas Quinasas Activadas por AMP/metabolismo , Hepacivirus/efectos de los fármacos , Hepatocitos/enzimología , Liraglutida/farmacología , Replicación Viral/efectos de los fármacos , Proteínas Quinasas Activadas por AMP/antagonistas & inhibidores , Línea Celular Tumoral , Supervivencia Celular/efectos de los fármacos , Péptido 1 Similar al Glucagón/agonistas , Péptido 1 Similar al Glucagón/farmacología , Receptor del Péptido 1 Similar al Glucagón/agonistas , Receptor del Péptido 1 Similar al Glucagón/metabolismo , Hepacivirus/fisiología , Hepatocitos/metabolismo , Hepatocitos/virología , Humanos , Diana Mecanicista del Complejo 2 de la Rapamicina/metabolismo , Fosfoenolpiruvato Carboxiquinasa (ATP)/metabolismo , Fosforilación/efectos de los fármacos , Transducción de Señal/efectos de los fármacos
13.
J Biomed Inform ; 81: 61-73, 2018 05.
Artículo en Inglés | MEDLINE | ID: mdl-29550394

RESUMEN

A microarray analysis generally contains expression data of thousands of genes, but most of them are irrelevant to the disease of interest, making analyzing the genes concerning specific diseases complicated. Therefore, filtering out a few essential genes as well as their regulatory networks is critical, and a disease can be easily diagnosed just depending on the expression profiles of a few critical genes. In this study, a target gene screening (TGS) system, which is a microarray-based information system that integrates F-statistics, pattern recognition matching, a two-layer K-means classifier, a Parameter Detection Genetic Algorithm (PDGA), a genetic-based gene selector (GBG selector) and the association rule, was developed to screen out a small subset of genes that can discriminate malignant stages of cancers. During the first stage, F-statistic, pattern recognition matching, and a two-layer K-means classifier were applied in the system to filter out the 20 critical genes most relevant to ovarian cancer from 9600 genes, and the PDGA was used to decide the fittest values of the parameters for these critical genes. Among the 20 critical genes, 15 are associated with cancer progression. In the second stage, we further employed a GBG selector and the association rule to screen out seven target gene sets, each with only four to six genes, and each of which can precisely identify the malignancy stage of ovarian cancer based on their expression profiles. We further deduced the gene regulatory networks of the 20 critical genes by applying the Pearson correlation coefficient to evaluate the correlationship between the expression of each gene at the same stages and at different stages. Correlationships between gene pairs were calculated, and then, three regulatory networks were deduced. Their correlationships were further confirmed by the Ingenuity pathway analysis. The prognostic significances of the genes identified via regulatory networks were examined using online tools, and most represented biomarker candidates. In summary, our proposed system provides a new strategy to identify critical genes or biomarkers, as well as their regulatory networks, from microarray data.


Asunto(s)
Biomarcadores de Tumor/genética , Perfilación de la Expresión Génica , Redes Reguladoras de Genes , Estadificación de Neoplasias/métodos , Análisis de Secuencia por Matrices de Oligonucleótidos , Neoplasias Ováricas/genética , Algoritmos , Bases de Datos Genéticas , Femenino , Humanos , Estimación de Kaplan-Meier , Neoplasias Ováricas/diagnóstico , Reconocimiento de Normas Patrones Automatizadas , Pronóstico
14.
Proc Natl Acad Sci U S A ; 112(8): 2575-80, 2015 Feb 24.
Artículo en Inglés | MEDLINE | ID: mdl-25675481

RESUMEN

The developmental rehearsal for the debut of hearing is marked by massive changes in the membrane properties of hair cells (HCs) and spiral ganglion neurons (SGNs). Whereas the underlying mechanisms for the developing HC transition to mature stage are understood in detail, the maturation of SGNs from hyperexcitable prehearing to quiescent posthearing neurons with broad dynamic range is unknown. Here, we demonstrated using pharmacological approaches, caged-Ca(2+) photolysis, and gramicidin patch recordings that the prehearing SGN uses Ca(2+)-activated Cl(-) conductance to depolarize the resting membrane potential and to prime the neurons in a hyperexcitable state. Immunostaining of the cochlea preparation revealed the identity and expression of the Ca(2+)-activated Cl(-) channel transmembrane member 16A (TMEM16A) in SGNs. Moreover, null deletion of TMEM16A reduced the Ca(2+)-activated Cl(-) currents and action potential firing in SGNs. To determine whether Cl(-) ions and TMEM16A are involved in the transition between pre- and posthearing features of SGNs we measured the intracellular Cl(-) concentration [Cl(-)]i in SGNs. Surprisingly, [Cl(-)]i in SGNs from prehearing mice was ∼90 mM, which was significantly higher than posthearing neurons, ∼20 mM, demonstrating discernible altered roles of Cl(-) channels in the developing neuron. The switch in [Cl(-)]i stems from delayed expression of the development of intracellular Cl(-) regulating mechanisms. Because the Cl(-) channel is the only active ion-selective conductance with a reversal potential that lies within the dynamic range of SGN action potentials, developmental alteration of [Cl(-)]i, and hence the equilibrium potential for Cl(-) (ECl), transforms pre- to posthearing phenotype.


Asunto(s)
Canales de Cloruro/metabolismo , Potenciales de la Membrana , Neuronas/fisiología , Ganglio Espiral de la Cóclea/fisiología , Potenciales de Acción/efectos de los fármacos , Animales , Anoctamina-1 , Anoctaminas , Calcio/farmacología , Membrana Celular/efectos de los fármacos , Membrana Celular/fisiología , Canales de Cloruro/antagonistas & inhibidores , Cloruros/metabolismo , Femenino , Audición/fisiología , Masculino , Potenciales de la Membrana/efectos de los fármacos , Ratones Noqueados , Neuronas/efectos de los fármacos , Fenotipo , Miembro 2 de la Familia de Transportadores de Soluto 12/metabolismo , Ganglio Espiral de la Cóclea/efectos de los fármacos , Simportadores/metabolismo , Cotransportadores de K Cl
15.
Anal Chem ; 89(7): 3973-3980, 2017 04 04.
Artículo en Inglés | MEDLINE | ID: mdl-28323416

RESUMEN

We report a one-pot two-nanoprobe approach coupled to mass spectrometry for simultaneous quantification and post-translational modification (PTM) profiling of targeted protein in biofluid. Using N-glycoprotein as model, the assay employs two nanoprobes, antibody-conjugated SiO2 nanoparticles and lectin-conjugated magnetic Fe3O4 nanoparticles, to achieve target glycoprotein isolation from biofluid and subsequent glycopeptide enrichment in a single tube. As demonstrated on α-fetoprotein (AFP), a serum biomarker for hepatocellular carcinoma (HCC), the assay has high purification specificity (20 glycopeptides) with 2-fold and 10-fold superior total glycopeptide intensity compared to non-one-pot method (9 glycopeptides) or without enrichment (6 glycopeptides), respectively. By multiple reaction monitoring mass spectrometry (MRM-MS) analysis of the nonglycopeptides, the assay can quantify low abundant AFP expression (0.5 ng) with good correlation with conventional ELISA method (Pearson's r = 0.987). Furthermore, we present the first study revealing AFP glycopeptide signatures of individual HCC patients, comprised of 23 heterogeneous glycoforms of bi- and triantennary, core and terminal fucosylation, and mono- to trisialylation. In addition to 12 novel AFP glycoforms, our quantification result uncovers five abundant glycoforms in HCC, including 3 core-fucosylated (CF) forms. These identified CF forms may be evaluated in future studies as potential targets in a glycopeptide biomarker panel to further improve accuracy of conventional AFP-L3 tests. Through this one-pot assay, a comprehensive target protein profile comprised of protein expression and glycosylation pattern was achieved in simple protocol with high sensitivity, reduced analysis time, and minute starting material. This assay can be extended to other PTM biosignatures by conjugation of other affinity ligands on the nanoprobe.


Asunto(s)
Biomarcadores de Tumor/sangre , Carcinoma Hepatocelular/sangre , Glicoproteínas/sangre , Neoplasias Hepáticas/sangre , Nanopartículas/química , Anticuerpos/química , Anticuerpos/metabolismo , Biomarcadores de Tumor/metabolismo , Cromatografía Liquida , Ensayo de Inmunoadsorción Enzimática , Glicoproteínas/metabolismo , Humanos , Lectinas/química , Lectinas/metabolismo , Nanopartículas de Magnetita/química , Procesamiento Proteico-Postraduccional , Dióxido de Silicio/química , Dióxido de Silicio/metabolismo , Espectrometría de Masas en Tándem
16.
Micromachines (Basel) ; 15(7)2024 Jun 28.
Artículo en Inglés | MEDLINE | ID: mdl-39064352

RESUMEN

The following study involved the utilization of dispersion polymerization to synthesize micron/nano-sized polystyrene (PS) spheres, which were then deposited onto a silicon substrate using the floating assembly method to form a long-range monolayer. Subsequently, dry etching techniques were utilized to create subwavelength structures. The adjustment of the stabilizer polyvinylpyrrolidone (PVP), together with changes in the monomer concentration, yielded PS spheres ranging from 500 nm to 5.6 µm in diameter. These PS spheres were suspended in a mixture of alcohol and deionized water before being arranged using the floating assembly method. The resulting tightly packed particle arrangement is attributed to van der Waals forces, Coulomb electrostatic forces between the PS spheres, and surface tension effects. The interplay of these forces was analyzed to comprehend the resulting structure. Dry etching, utilizing the PS spheres as masks, enabled the exploration of the effects of etching parameters on the resultant structures. Unlike traditional dry etching methods controlling RF power and etching gases, in the present study, we focused on adjusting the oxygen flow rate to achieve cylindrical, conical, and parabolic etched structures.

17.
Head Neck ; 46(6): E61-E66, 2024 06.
Artículo en Inglés | MEDLINE | ID: mdl-38469981

RESUMEN

BACKGROUND: Extrathyroid implantation or dissemination of thyroid tissue secondary to a thyroid procedure is rare. Most of these belonged to thyroid carcinoma with metastatic potential and uncommon for benign pathologies. METHODS: We report the case of a 31-year-old female who was identified to have multiple subcutaneous implantation of thyroid tissue 5 years after transoral endoscopic thyroidectomy vestibular approach. A comprehensive literature search on implantation of thyroid tissue secondary to thyroid procedures was performed. RESULTS: Accidental tearing of the capsule during previous surgery may lead to the subcutaneous implantation. Through literature review, a total 29 articles with 47 patients were identified. 33.3% were benign lesions, and implantation was mostly secondary to fine needle aspiration biopsy (46.5%). CONCLUSIONS: Subcutaneous or port site implantation after endoscopic thyroid surgery may occur in benign thyroid pathologies and therefore, oncologic principles must be strictly followed during surgery regardless of its histopathological nature.


Asunto(s)
Bocio Nodular , Tiroidectomía , Humanos , Femenino , Tiroidectomía/métodos , Tiroidectomía/efectos adversos , Adulto , Bocio Nodular/cirugía , Bocio Nodular/patología , Cirugía Endoscópica por Orificios Naturales/métodos , Cirugía Endoscópica por Orificios Naturales/efectos adversos , Endoscopía/métodos
18.
Vaccines (Basel) ; 12(6)2024 Jun 14.
Artículo en Inglés | MEDLINE | ID: mdl-38932387

RESUMEN

BACKGROUND: The impact of mRNA COVID-19 vaccines on the immunological profiles of pregnant women remains a crucial area of study. This research aims to explore the specific immunological changes triggered by these vaccines in this demographic. METHODS: In a focused investigation, we examined the effects of mRNA COVID-19 vaccination on microRNA expression in pregnant women. Key microRNAs, including miR-451a, miR-23a-3p, and miR-21-5p, were analyzed for expression changes post-vaccination. Additionally, we assessed variations in S1RBD IgG levels and specific cytokines to gauge the broader immunological response. RESULTS: Post-vaccination, significant expression shifts in the targeted microRNAs were observed. Alongside these changes, we noted alterations in S1RBD IgG and various cytokines, indicating an adapted inflammatory response. Notably, these immunological markers displayed no direct correlation with S1RBD IgG concentrations, suggesting a complex interaction between the vaccine and the immune system in pregnant women. CONCLUSIONS: Our pilot study provides valuable insights into the nuanced effects of the mRNA COVID-19 vaccine on immune dynamics in pregnant women, particularly emphasizing the role of microRNAs. The findings illuminate the intricate interplay between vaccines, microRNAs, and immune responses, enhancing our understanding of these relationships in the context of pregnancy. This research contributes significantly to the growing body of knowledge regarding mRNA COVID-19 vaccines and their specific impact on maternal immunology, offering a foundation for further studies in this vital area.

19.
Front Cell Infect Microbiol ; 14: 1358967, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38572318

RESUMEN

Introduction: The aim of this study is to investigate changes in TNF-related apoptosis-inducing ligand (TRAIL) and gamma interferon-induced protein 10 (IP-10) after COVID-19 vaccination in pregnant women and to explore their association with neutralizing antibody (Nab) inhibition. Methods: The study evaluated 93 pregnant women who had previously received two (n=21), three (n=55) or four (n=17) doses of COVID-19 vaccine. Also we evaluated maternal blood samples that were collected during childbirth. The levels of TRAIL, IP-10 and Nab inhibition were measured using enzyme-linked immunosorbent assays (ELISA). Results and discussion: Our study revealed four-dose group resulted in lower TRAIL levels when compared to the two-dose and three-dose groups (4.78 vs. 16.07 vs. 21.61 pg/ml, p = 0.014). The two-dose group had reduced IP-10 levels than the three-dose cohort (111.49 vs. 147.89 pg/ml, p=0.013), with no significant variation compared to the four-dose group. In addition, the four-dose group showed stronger Nab inhibition against specific strains (BA.2 and BA.5) than the three-dose group. A positive correlation was observed between TRAIL and IP-10 in the two-dose group, while this relationship was not found in other dose groups or between TRAIL/IP-10 and Nab inhibition. As the doses of the COVID-19 vaccine increase, the levels of TRAIL and IP-10 generally increase, only by the fourth dose, the group previously vaccinated with AZD1222 showed lower TRAIL but higher IP-10. Despite these changes, more doses of the vaccine consistently reinforced Nab inhibition, apparently without any relation to TRAIL and IP-10 levels. The variation may indicate the induction of immunological memory in vaccinated mothers, which justifies further research in the future.


Asunto(s)
COVID-19 , Interferones , Embarazo , Humanos , Femenino , Vacunas contra la COVID-19 , Quimiocina CXCL10 , Ligando Inductor de Apoptosis Relacionado con TNF , Mujeres Embarazadas , ChAdOx1 nCoV-19 , COVID-19/prevención & control , Vacunación , Anticuerpos Neutralizantes , Anticuerpos Antivirales
20.
Vaccines (Basel) ; 12(3)2024 Mar 15.
Artículo en Inglés | MEDLINE | ID: mdl-38543946

RESUMEN

This study assessed IgG levels to influenza/pertussis and neutralizing antibody (Nab) responses of COVID-19 vaccines in blood of pregnant women following immunization with pertussis (Tdap), influenza, and COVID-19 vaccines. We prospectively collected 71 participants categorized by the following vaccine combinations: 3TI, 4TI, 3T, and 4T groups (three and four doses of COVID-19 vaccines plus Tdap/influenza or Tdap vaccines alone). Our findings have indicated that the 3TI group exhibited elevated IgG levels for influenza B compared to the 3T group (12.90 vs. 7.75 U, p = 0.001); this pattern was not observed for influenza A. Pertussis IgG levels remained uniform across all groups. The 4TI group demonstrated a greater Nab inhibition rate from COVID-19 vaccines compared to both the 3TI and 3T groups (61.34% vs. 22.5% and 15.16%, respectively, p = 0.001). We observed no correlation between Nab inhibition rate and IgG levels for Tdap/influenza, with the exception of a moderate correlation with influenza B in the 3TI group. The efficacy of Tdap vaccine in pregnant women remained consistent, regardless of the administration of COVID-19 or influenza vaccines. Interestingly, without the influenza vaccine, both three and four doses of the COVID-19 vaccine still offered protection against influenza A, but not B. Hence, co-administering COVID-19, influenza, and Tdap vaccines during prenatal care maintains immunogenicity and is highly advised to safeguard pregnant women fully.

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