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Circular RNA (circRNA) is thought to mediate the occurrence and development of human cancer and usually acts as a tiny RNA (miRNA) sponge to regulate downstream gene expression. However, it is not clear whether and how circACVR2A (hsa_circ_0001073) is involved in the progression of HCC. The purpose of this study is to clarify the potential role and molecular mechanism of circACVR2A in regulating the progression of hepatocellular carcinoma cells (HCC). The abundance of related proteins in circACVR2A, microRNA (miR511-5p) and PI3K-Akt signaling pathway was determined by quantitative reverse transcriptase polymerase chain reaction (RT-PCR) or Western blotting. Cell viability, invasion and apoptosis were analyzed by CCK-8, Transwell analysis and Tunel staining, respectively. The interaction between circACVR2A and microRNA was evaluated by double luciferase reporter gene assay. The results showed that circACVR2A was highly expressed in hepatocellular carcinoma cell lines. Our in vivo and in vitro data showed that circACVR2A promoted the proliferation, migration and invasion of HCC. In terms of mechanism, we found that circACVR2A can directly interact with miR511-5p and act as a miRNA sponge to regulate the expression of related proteins in PI3K-Akt signaling pathway.In HCC, circACVR2A can mediate miR-511-5p/mRNA network to activate PI3K signal pathway. This shows that the molecular regulatory network with circACVR2A as the core is a new potential target for diagnosis and treatment of hepatocellular carcinoma.
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Carcinoma Hepatocelular , Movimiento Celular , Proliferación Celular , Regulación Neoplásica de la Expresión Génica , Neoplasias Hepáticas , MicroARNs , Fosfatidilinositol 3-Quinasas , Proteínas Proto-Oncogénicas c-akt , ARN Circular , Transducción de Señal , Carcinoma Hepatocelular/genética , Carcinoma Hepatocelular/patología , Carcinoma Hepatocelular/metabolismo , MicroARNs/genética , Humanos , Neoplasias Hepáticas/genética , Neoplasias Hepáticas/patología , Neoplasias Hepáticas/metabolismo , ARN Circular/genética , Proteínas Proto-Oncogénicas c-akt/metabolismo , Fosfatidilinositol 3-Quinasas/metabolismo , Movimiento Celular/genética , Animales , Línea Celular Tumoral , Ratones , Apoptosis/genética , Progresión de la Enfermedad , MasculinoRESUMEN
Acute lung injury (ALI) is a common disease with complex pathogenesis. However, the treatment is mainly symptomatic with limited clinical options. Asiaticoside (AS), a Chinese herbal extract, has protective effects against LPS-induced ALI in mice and inhibits nitric oxide and prostaglandin E2 synthesis; however, the specific mechanism of AS in the prevention and treatment of LPS-induced ALI needs further study. Sema4D/CD72 pathway, mitochondrial dysfunction, and miRNA-21 are closely associated with inflammation. Therefore, the present study aimed to explore whether AS exerts its therapeutic effect on ALI by influencing Sema4D/CD72 pathway and mitochondrial dysfunction, restoring the balance of inflammatory factors, and influencing miRNA-21 expression. Cell and animal experiments were performed to investigate the effect of AS on ALI. Lipopolysaccharide (LPS) was used to establish the ALI model. CCK8 and flow cytometry were used to detect the cell viability and apoptosis rate. HE staining and wet-to-dry weight ratio (W/D) of lung tissue were determined. The expressions of Sema4D, CD72, NF-κB p65, Bax, Bcl2, and caspase 3 in RAW264.7 cells and lung tissues were detected by western blot, and the levels of IL-10 and IL-1ß induced by LPS in supernatant of RAW264.7 cells and BALF were measured by ELISA. And the expression of miRNA-21 in cells and lung tissues was detected by fluorescence quantitative PCR. The result shows that AS treatment suppressed LPS-induced cell damage and lung injury in mice. AS treatment could alleviate the pathological changes such as inflammatory infiltration and histopathological changes in the lungs caused by LPS, and reduce the ratio of W/D. AS significantly alleviated the decrease of mitochondrial membrane potential induced by LPS, inhibited the increase of ROS production, and reduced the expression of mitochondrial fission proteins Drp1 and Fis1. The high-dose AS group significantly downregulated the expression of Sema4D, CD72, phosphorylated NF-κB p65, and apoptosis-related proteins, decreased the pro-inflammatory factor IL-1ß, and enhanced the level of anti-inflammatory factor IL-10. In addition, AS promoted miRNA-21 expression. These effects inhibited apoptosis and restored the balance between anti- and pro-inflammatory factors. This represents the inaugural report elucidating the mechanism by which AS inhibits the Sema4D/CD72 signaling pathway. These findings offer novel insights into the potential application of AS in both preventing and treating ALI.
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INTRODUCTION: Adductor spasmodic dysphonia (ADSD) is characterized by involuntary laryngeal muscle spasms. Due to the lack of a quantitative evaluation method, most measurements have demonstrated difficulty in validity and reliability for diagnosing ADSD. This study aimed to establish a novel indicator for ADSD and determine its diagnostic effects. METHODS: We investigated 98 voice samples from 49 patients with ADSD and 49 healthy subjects. A sustained vowel was recorded by a high-definition audio recorder. Voice samples underwent regular acoustic evaluation and a novel global dimension method. Global dimension (GD), Jitter, Shimmer, HNR, Frequency shift, and CPPS were measured for both groups. RESULTS: Statistical analysis revealed that the global dimension method effectively differentiated ADSD patients from healthy subjects (P<0.001, D'>0.8). Subsequent multiclass receiver operating characteristic analysis demonstrated that GD possessed the most significant classification accuracy (AUC = 0.988) compared with other acoustic parameters. CONCLUSION: GD was an effective metric for objective differentiation between ADSD patients and healthy subjects. This metric could assist clinicians in the diagnosis of ADSD patients.
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The "universal target" region of the gene encoding the 60 kDa chaperonin protein (cpn60, also known as groEL or hsp60) is a proven sequence barcode for bacteria and a useful target for marker gene amplicon-based studies of complex microbial communities. To date, identification of cpn60 sequence variants from microbiome studies has been accomplished by alignment of queries to a reference database. Naïve Bayesian classifiers offer an alternative identification method that provides variable rank classification and shorter analysis times. We curated a set of cpn60 barcode sequences to train the RDP classifier and tested its performance on data from previous human microbiome studies. Results showed that sequences accounting for 79%, 86% and 92% of the observations (read counts) in saliva, vagina and infant stool microbiome data sets were classified to the species rank. We also trained the QIIME 2 q2-feature-classifier on cpn60 sequence data and demonstrated that it gives results consistent with the standalone RDP classifier. Successful implementation of a naïve Bayesian classifier for cpn60 sequences will facilitate future microbiome studies and open opportunities to integrate cpn60 amplicon sequence identification into existing analysis pipelines.
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OBJECTIVE: Little is known about the efficacy of using artificial intelligence (AI) to identify laryngeal carcinoma from images of vocal lesions taken in different hospitals with multiple laryngoscope systems. This multicentre study aimed to establish an AI system and provide a reliable auxiliary tool to screen for laryngeal carcinoma. STUDY DESIGN: Multicentre case-control study. SETTING: Six tertiary care centres. PARTICIPANTS: Laryngoscopy images were collected from 2179 patients with vocal fold lesions. OUTCOME MEASURES: An automatic detection system of laryngeal carcinoma was established and used to distinguish malignant and benign vocal lesions in 2179 laryngoscopy images acquired from 6 hospitals with 5 types of laryngoscopy systems. Pathological examination was the gold standard for identifying malignant and benign vocal lesions. RESULTS: Out of 89 cases in the malignant group, the classifier was able to correctly identify laryngeal carcinoma in 66 patients (74.16%, sensitivity). Out of 640 cases in the benign group, the classifier was able to accurately assess the laryngeal lesion in 503 cases (78.59%, specificity). Furthermore, the region-based convolutional neural network (R-CNN) classifier achieved an overall accuracy of 78.05%, with a 95.63% negative predictive value and a 32.51% positive predictive value for the testing data set. CONCLUSION: This automatic diagnostic system has the potential to assist clinical laryngeal carcinoma diagnosis which may improve and standardise the diagnostic capacity of laryngologists using different laryngoscopes.
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Carcinoma , Neoplasias Laríngeas , Laringoscopía , Pliegues Vocales , Inteligencia Artificial , Humanos , Neoplasias Laríngeas/diagnóstico , Carcinoma/patología , Laringoscopios , Laringoscopía/métodos , Estudios de Casos y Controles , Pliegues Vocales/diagnóstico por imagenRESUMEN
OBJECTIVE: The objective of this study was to examine the perceptual structure and acoustic characteristics of speech of patients with adductor spasmodic dysphonia (ADSD) in Mandarin. STUDY DESIGN: Case-Control Study MATERIALS AND METHODS: For the estimation of dysphonia level, perceptual and acoustic analysis were used for patients with ADSD (N = 20) and the control group (N = 20) that are Mandarin-Chinese speakers. For both subgroups, a sustained vowel and connected speech samples were obtained. The difference of perceptual and acoustic parameters between the two subgroups was assessed and analyzed. RESULTS: For acoustic assessment, the percentage of phonatory breaks (PBs) of connected reading and the percentage of aperiodic segments and frequency shifts (FS) of vowel and reading in patients with ADSD were significantly worse than controls, the mean harmonics-to-noise ratio and the fundamental frequency standard deviation of vowel as well. For perceptual evaluation, the rating of speech and vowel in patients with ADSD are significantly higher than controls. The percentage of aberrant acoustic events (PB, frequency shift, and aperiodic segment) and the fundamental frequency standard deviation and mean harmonics-to-noise ratio were significantly correlated with the perceptual rating in the vowel and reading productions. CONCLUSIONS: The perceptual and acoustic parameters of connected vowel and reading in patients with ADSD are worse than those in normal controls, and could validly and reliably estimate dysphonia of ADSD in Mandarin-speaking Chinese.
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Acústica , Disfonía/diagnóstico , Acústica del Lenguaje , Percepción del Habla , Medición de la Producción del Habla , Calidad de la Voz , Adulto , Estudios de Casos y Controles , China , Disfonía/fisiopatología , Femenino , Humanos , Juicio , Masculino , Persona de Mediana Edad , Fonación , Valor Predictivo de las Pruebas , Lectura , Reproducibilidad de los Resultados , Índice de Severidad de la Enfermedad , Factores de Tiempo , Adulto JovenRESUMEN
OBJECTIVE: To investigate the characteristics of adductor spasmodic dysphonia phonatory break in mandarin Chinese and select the stimuli phrases. METHOD: Thirty-eight patients with adductor spasmodic dysphonia were involved in this study. Standard phrase " fù mu xin" and a speech corpus in mandarin Chinese with 229 syllables covering all vowel and constant of mandarin Chinese were selected. Every patient read the phrases above twice in normal speed and comfortable voice. Two auditory perpetual speech pathologists marked phonatory break syllables respectively. The frequency of phonatory break syllables and their located phrases were calculated, rated and described. The phrases including the most phonatory break syllables were selected as stimuli phrases, the phonatory break frequency of which was also higher than that of standard phrase "fù mu xin". RESULT: Phonatory break happened in the reading of all patients. The average number of phonatory break syllables was 14 (3-33). Phonatroy break occurred when saying 177 (77.3%) syllables in the speech corpus. The syllables "guo, rén, zang, diàn, che, gè, guan, a, ba, ne, de" broke in 23.1%-41.0% patients. These syllables belonged to the phrases "ping guo, huo che, shì de, ni shì gè hao rén, wo mén shì you zong shì ba qin shì nong dé hen zang, wo mén nà bian you wang qiú yùn dong chang, can guan, jiu ba hé yi gè miàn bao dìan, ta shì duo me kang kai a,wo ying gai zài xìn li xie yi xie shén me ne?". Thirty-seven patients (97.3%) had phonatory break in above mentioned words. Ratios of these words phonatory break also were more than "fù mu xin". CONCLUSION: Adductor spasmodic dysphonic patients exhibited different degrees of phonatory break in mandarine Chinese. The phrases" shì de, ping guo, huo che, ni shì gè hao rén, wo mén nà bian you wang qiú yùn dong chang, can guan, jiu ba hé yi gè miàn bao dìan, ta shì duo me kang kai a" were recommended as stimuli phrases for adductor spasmodic dysphonia evaluation.