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[This corrects the article DOI: 10.3389/fmicb.2023.1131184.].
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Intercropping with Pleurotus ostreatus has been demonstrated to increase the tea yield and alleviate soil acidification in tea gardens. However, the underlying mechanisms remain elusive. Here, high-throughput sequencing and Biolog Eco analysis were performed to identify changes in the community structure and abundance of soil microorganisms in the P. ostreatus intercropped tea garden at different seasons (April and September). The results showed that the soil microbial diversity of rhizosphere decreased in April, while rhizosphere and non-rhizosphere soil microbial diversity increased in September in the P. ostreatus intercropped tea garden. The diversity of tea tree root microorganisms increased in both periods. In addition, the number of fungi associated with organic matter decomposition and nutrient cycling, such as Penicillium, Trichoderma, and Trechispora, was significantly higher in the intercropped group than in the control group. Intercropping with P. ostreatus increased the levels of total nitrogen (TN), total phosphorus (TP), and available phosphorus (AP) in the soil. It also improved the content of secondary metabolites, such as tea catechins, and polysaccharides in tea buds. Microbial network analysis showed that Unclassified_o__Helotiales, and Devosia were positively correlated with soil TN and pH, while Lactobacillus, Acidothermus, and Monascus were positively correlated with flavone, AE, and catechins in tea trees. In conclusion, intercropping with P. ostreatus can improve the physical and chemical properties of soil and the composition and structure of microbial communities in tea gardens, which has significant potential for application in monoculture tea gardens with acidic soils.
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Microbiota , Raíces de Plantas , Pleurotus , Rizosfera , Microbiología del Suelo , Suelo , Té , Pleurotus/crecimiento & desarrollo , Pleurotus/metabolismo , Raíces de Plantas/microbiología , Té/microbiología , Suelo/química , Camellia sinensis/microbiología , Nitrógeno/metabolismo , Nitrógeno/análisis , Fósforo/análisis , Fósforo/metabolismo , Hongos/metabolismo , Bacterias/clasificación , Bacterias/genética , Bacterias/metabolismo , Concentración de Iones de HidrógenoRESUMEN
Cordyceps cicadae (Hypocreales: Cordycipitaceae) is a renowned entomopathogenic fungus used as herbal medicine in China. However, wild C. cicadae resources have been threatened by heavy harvesting. We hypothesised that Bombyx mori L. (Lepidoptera: Bombycidae) could be a new alternative to cultivate C. cicadae due to the low cost of rearing. Bacterial communities are crucial for the formation of Cordyceps and for promoting the production of metabolites. To better understand the bacterial community structure associated with Cordyceps, three Claviciptaceae fungi were used to explore the pathogenicity of the silkworms. Here, fifth-instar silkworms were infected with C. cicadae, Cordyceps cateniannulata (Hypocreales: Cordycipitaceae) and Beauveria bassiana (Hypocreales: Cordycipitaceae). Subsequently, we applied high-throughput sequencing to explore the composition of bacterial communities in silkworms. Our results showed that all three fungi were highly pathogenic to silkworms, which suggests that silkworms have the potential to cultivate Cordyceps. After fungal infection, the diversity of bacterial communities in silkworms decreased significantly, and the abundance of Staphylococcus increased in mummified larvae, which may play a role in the death process when the host suffers infection by entomopathogenic fungi. Furthermore, there were high similarities in the bacterial community composition and function in the C. cicadae and C. cateniannulata infected samples, and the phylogenetic analysis suggested that these similarities may be related to the fungal phylogenetic relationship. Our findings reveal that infection with different entomopathogenic fungi affects the composition and function of bacterial communities in silkworms and that the bacterial species associated with Cordyceps are primarily host dependent, while fungal infection affects bacterial abundance.
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BACKGROUND: Mood swings is linked to a higher risk of cardiovascular diseases (CVDs). However, the causal relationships between them remain unknown. METHODS: We conducted this Mendelian randomization (MR) analysis to evaluate the causal associations between mood swings (n = 373,733) and 5 CVDs, including CAD, MI, HF, AF, and stroke using summary data of large-scale genome-wide association studies (GWAS). FinnGen datasets validated the results. Various MR approaches, sensitivity analyses, multivariable MR (MVMR), and two-step MR mediation analyses were applied. RESULTS: The MR analysis revealed significant causal effects of mood swings on CAD (OR = 1.45, 95 % CI 1.24-1.71; P = 5.52e-6), MI (OR = 1.60, 95 % CI 1.32-1.95; P = 1.77e-6), HF (OR = 1.42, 95 % CI 1.18-1.71; P = 2.32e-4), and stroke (OR = 1.48, 95 % CI 1.19-1.83; P = 3.46e-4), excluding AF (P = 0.16). In the reverse MR analysis, no causal relationships were observed. The results were reproducible using FinnGen data. In the MVMR analysis, the causal effects of mood swings on CAD, MI, HF and stroke still remain significant after adjusting potential confounding factors including BMI, smoking and T2DM, but not for LDL and hypertension. Further mediation analysis indicated hypertension may mediate the causal pathways from mood swings to CAD (18.11 %, 95 % CI: 8.83 %-27.39 %), MI (16.40 %, 95 % CI: 7.93 %-24.87 %), HF (13.06 %, 95 % CI: 6.25 %-19.86 %), and stroke (18.04 %, 95 % CI: 8.73 %-27.34 %). CONCLUSION: Mood swings has a significant causal impact on the development of CAD, MI, HF, and stroke, partly mediated by hypertension.
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Enfermedades Cardiovasculares , Hipertensión , Accidente Cerebrovascular , Humanos , Enfermedades Cardiovasculares/epidemiología , Enfermedades Cardiovasculares/genética , Análisis de la Aleatorización Mendeliana , Estudio de Asociación del Genoma Completo , Accidente Cerebrovascular/epidemiología , Accidente Cerebrovascular/genéticaRESUMEN
BACKGROUND: The presence of type 1 diabetes mellitus (T1DM) has been demonstrated to pose an increased risk for developing cardiovascular diseases (CVDs). However, the causal relationships between T1DM and CVDs remain unclear due to the uncontrolled confounding factors and reverse causation bias of the observational studies. METHODS: Summary statistics of T1DM and seven CVDs from the largest available genome-wide association studies (GWAS) of European ancestry and FinnGen biobank were extracted for the primary MR analysis, and the analysis was replicated using UK biobank (UKBB) for validation. Three complementary methods: inverse variance weighted (IVW), weighted median, and MR-Egger were used for the MR estimates. The potential pleiotropic effects were assessed by MR-Egger intercept and MR-PRESSO global test. Additionally, multivariable MR (MVMR) analysis was performed to examine whether T1DM has independent effects on CVDs with adjustment of potential confounding factors. Moreover, a two-step MR approach was used to assess the potential mediating effects of these factors on the causal effects between T1DM and CVDs. RESULTS: Causal effects of T1DM on peripheral atherosclerosis (odds ratio [OR] = 1.06, 95% confidence interval [CI]: 1.02-1.10; p = 0.002)] and coronary atherosclerosis (OR = 1.03, 95% CI: 1.01-1.05; p = 0.001) were found. The results were less likely to be biased by the horizontal pleiotropic effects (both p values of MR-Egger intercept and MR-PRESSO Global test > 0.05). In the following MVMR analysis, we found the causal effects of T1DM on peripheral atherosclerosis and coronary atherosclerosis remain significant after adjusting for a series of potential confounding factors. Moreover, we found that hypertension partly mediated the causal effects of T1DM on peripheral atherosclerosis (proportion of mediation effect in total effect: 11.47%, 95% CI: 3.23-19.71%) and coronary atherosclerosis (16.84%, 95% CI: 5.35-28.33%). We didn't find significant causal relationships between T1DM and other CVDs, including heart failure (HF), coronary artery disease (CAD), atrial fibrillation (AF), myocardial infarction (MI) and stroke. For the reverse MR from CVD to T1DM, no significant causal relationships were identified. CONCLUSION: This MR study provided evidence supporting the causal effect of T1DM on peripheral atherosclerosis and coronary atherosclerosis, with hypertension partly mediating this effect.
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Aterosclerosis , Enfermedades Cardiovasculares , Enfermedad de la Arteria Coronaria , Diabetes Mellitus Tipo 1 , Hipertensión , Humanos , Enfermedades Cardiovasculares/diagnóstico , Enfermedades Cardiovasculares/epidemiología , Enfermedades Cardiovasculares/genética , Enfermedad de la Arteria Coronaria/diagnóstico , Enfermedad de la Arteria Coronaria/epidemiología , Enfermedad de la Arteria Coronaria/genética , Diabetes Mellitus Tipo 1/diagnóstico , Diabetes Mellitus Tipo 1/epidemiología , Diabetes Mellitus Tipo 1/genética , Estudio de Asociación del Genoma Completo , Análisis de la Aleatorización Mendeliana , NonoxinolRESUMEN
Cryoballoon ablation (CBA) is an effective treatment for drug-refractory atrial fibrillation (AF) patients. Whether CBA as a first-line treatment is superior in the rhythm control of AF than antiarrhythmic drugs (AAD) remains unclear. CBA is superior to AAD as initial therapy for rhythm control of paroxysmal atrial fibrillation (PAF). A comprehensive database search was performed in PubMed, Embase, Cochrane, and Web of Science from inception to March 22, 2023. Treatment efficacy was pooled using risk ratio (RR) and standardized mean difference (SMD) with a 95% confidence interval (CI). This study was registered with Prospero (CRD42023401596). Five randomized-controlled trials involving 923 patients and an observational study were included in this study. The CBA group had a significantly lower overall recurrence rate than the AAD group (CBA vs. AAD: RR = 0.59, 95% CI = 0.49-0.71, p < .05, I2 = 0). The incidence of persistent AF could be better controlled in the CBA group than in the AAD (CBA vs. AAD: RR = 0.17, 95% CI = 0.06-0.49, p < .05, I2 = 0). CBA could improve the quality of life (QoL) of patients better than AAD (CBA vs. AAD: SMD = 0.40, 95% CI = 0.14-0.67, p < .05, I2 = 68.5%). CBA can reduce hospitalization rate significantly than AAD at 36-month follow-up (CBA vs. AAD: RR = 0.29, 95% CI = 0.15-0.58, p < .05, I2 = 0%). Compared to AAD, CBA as first-line therapy could reduce the recurrence rate of atrial arrhythmia and incidence of persistent AF and improve QoL in PAF patients with lower incidences of hospitalization.
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Fibrilación Atrial , Ablación por Catéter , Humanos , Fibrilación Atrial/diagnóstico , Fibrilación Atrial/tratamiento farmacológico , Fibrilación Atrial/cirugía , Antiarrítmicos/uso terapéutico , Calidad de Vida , Resultado del Tratamiento , Hospitalización , Ablación por Catéter/efectos adversos , Recurrencia , Ensayos Clínicos Controlados Aleatorios como Asunto , Estudios Observacionales como AsuntoRESUMEN
Background: Entomopathogenic fungi can live in insects to cause disease and death and are the largest group of entomopathogenic microorganisms. Therefore, these fungi are best known for their microbial control potential. Importantly, they also have other beneficial effects, including promoting plant growth and development by colonizing plant. Here, the study sought to identify specific strains of the entomopathogenic fungus, Cordyceps cateniannulata that would form endophytic associations with tobacco, thus benefiting plant growth and resistance to abiotic stresses, thereby highlighting the application of entomopathogenic fungi in tobacco. Methods: The C. cateniannulata-tobacco symbiont was constructed by root irrigation. The effects of C. cateniannulata on tobacco growth were evaluated by measuring the maximum leaf length, maximum leaf width, number of leaves, plant height, stem thickness, stem circumference, dry and fresh shoot weight 7, 14, 21, and 28 days after colonization. The peroxidase, catalase, superoxide dismutase, and malondialdehyde were measured to observe the impact of C. cateniannulata on tobacco defense enzyme activity. Finally, high-throughput sequencing was used to access microbial communities in the rhizosphere, with data subsequently linked to growth indicators. Results: After tobacco was inoculated with C. cateniannulata X8, which significantly promoted growth and related enzyme activity, malondialdehyde was decreased. The most significant impact was on peroxidase, with its activity being upregulated by 98.20, 154.42, 180.65, and 170.38% in the four time periods, respectively. The high throughput sequencing results indicated that C. cateniannulata had changed the rhizosphere microbial relative abundances, such as increasing Acidobacteria and Ascomycetes, and decreasing Actinomycetes and Basidiomycetes. The redundancy analysis showed that C. cateniannulata significantly boosted tobacco growth by reducing the abundance of specific dominant genera such as Stachybotrys, Cephalotrichum, Streptomyces, Isoptericola, and Microbacterium. Conclusion: Specific strains of C. cateniannulata can be introduced into host plants as endophytes, resulting in promotion of host plant growth and increased resistance to abiotic stress and microbial pathogens. The study provides a foundation for future studies of C. cateniannulata as an ecological agent.
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The incidence, prevalence, and economic burden of heart failure have continued to increase worldwide. It remains unclear whether LCZ696 can ameliorate calcium reuptake in the sarcoplasmic reticulum via the sarcoplasmic endoplasmic reticulum calcium ion-ATPase 2α (SERCA2α)-dependent pathway during cardiac diastole. We investigated whether LCZ696 could ameliorate tachycardia-induced myocardial injury by modulating cardiac SERCA2α levels. A tachycardia-induced myocardial injury model was established by daily intraperitoneal administration of 60 mg/kg isoprenaline (ISO) for 2 weeks. LCZ696 was orally administered for the following 4 weeks. SERCA2α and calcium ion (Ca2+)-related protein expression was assessed by quantitative real-time polymerase chain reaction (qRT-PCR) and western blotting. For additional in vitro studies, HL-1 cardiomyocytes were used. A SERCA2α overexpression vector was constructed and transfected into HL-1 cells. The expression of SERCA2α and Ca2+-related proteins were also measured using qRT-PCR and western blotting. Our in vivo results demonstrated that myocardial injury was successfully induced by intraperitoneal administration of ISO. The expression of both SERCA2α- and Ca2+-related proteins was impaired. Oral administration of LCZ696 increased the expression of SERCA2α, alleviated Ca2+-related protein impairment and cardiac Ca2+ dyshomeostasis, and ameliorated myocardial injury. These results were compared with our in vitro findings. Ca2+-related proteins are affected by the overexpression of SERCA2α. LCZ696 improved tachycardia-induced myocardial injury by increasing SERCA2α expression, which reversed the development of heart failure in ISO-induced mice. These results provide new insights into how sustained LCZ696 treatment in heart failure improves cardiac function through intracellular Ca2+-regulatory mechanisms.
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Calcio , Insuficiencia Cardíaca , Ratones , Animales , Tetrazoles/farmacología , Antagonistas de Receptores de Angiotensina , Compuestos de Bifenilo , Combinación de Medicamentos , Insuficiencia Cardíaca/complicaciones , Insuficiencia Cardíaca/tratamiento farmacológico , Taquicardia/complicaciones , Taquicardia/tratamiento farmacológico , Isoproterenol/farmacologíaRESUMEN
It is always highly desired to have a well-defined relationship between the chemistry in semiconductor processing and the device characteristics. With the shrinkage of technology nodes in the semiconductors roadmap, it becomes more complicated to understand the relation between the device electrical characteristics and the process parameters such as oxidation and wafer cleaning procedures. In this work, we use a novel machine learning approach, i.e., physics-assisted multitask and transfer learning, to construct a relationship between the process conditions and the device capacitance voltage curves. While conventional semiconductor processes and device modeling are based on a physical model, recently, the machine learning-based approach or hybrid approaches have drawn significant attention. In general, a huge amount of data is required to train a machine learning model. Since producing data in the semiconductor industry is not an easy task, physics-assisted artificial intelligence has become an obvious choice to resolve these issues. The predicted C-V uses the hybridization of physics, and machine learning provides improvement while the coefficient of determination (R 2) is 0.9442 for semisupervised multitask learning (SS-MTL) and 0.9253 for transfer learning (TL), referenced to 0.6108 in the pure machine learning model using multilayer perceptrons. The machine learning architecture used in this work is capable of handling data sparsity and promotes the usage of advanced algorithms to model the relationship between complex chemical reactions in semiconductor manufacturing and actual device characteristics. The code is available at https://github.com/albertlin11/moscapssmtl.
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Circulating microRNAs (miRNAs) are promising diagnostic markers in various types of cancers, including papillary thyroid carcinoma (PTC). However, there is sparse information reported with regards to miRNA expression in papillary thyroid microcarcinoma (PTMC) or concerning the role of a combination of miRNAs and ultrasound (US) in the diagnosis of PTMC before surgery. Therefore, we designed a study that aimed to evaluate miRNA expression levels and their potential associations with US findings and determine whether miRNAs could be used as diagnostic and prognostic biomarkers of PTMC. miR222, miR221, miR146b and miR21 levels were determined using reverse transcriptionquantitative polymerase chain reaction (RTqPCR) in serum from 58 patients with PTMC and 47 with PTC, 35 patients with benign thyroid nodules (BTN) and 40 control subjects. Expression levels of the four miRNAs in serum were evaluated before and after surgery. The results indicated that miR222, miR221, miR146b and miR21 expression levels were higher in the PTMC samples than in those from the BTN and control groups and the combination of miRNAs and US had a high sensitivity and specificity for discrimination between BTN and PTMC by receiver operating characteristic (ROC) curve analysis and improved the accuracy of diagnosis of PTMC before surgery. In addition, serum miRNA expression levels were significantly related to poor prognostic factors including metastatic lymph nodules (MLNs), multifocal and bilateral lesions, advanced stage and highrisk PTMC patients. The miRNA expression levels in serum from PTMC patients were rapidly reduced after surgery compared with levels before surgery. In addition, we also analyzed the miRNA expression levels in serum from patients who were divided into two groups according to factors indicating a good or poor prognosis associated with PTMC after surgery. The results suggested that after surgery, the miR222, miR146b and miR21 expression levels were significantly higher in the poor prognosis group compared with these levels in the good prognosis group. Serum miRNA expression levels helped distinguish between benign and malignant nodules and were associated with a poor prognosis in PTMC. Circulating miRNAs may be useful as followup biomarkers and as diagnostic and prognostic tools.
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Biomarcadores de Tumor/sangre , Carcinoma Papilar/sangre , MicroARN Circulante/sangre , ARN Neoplásico/sangre , Neoplasias de la Tiroides/sangre , Adulto , Biomarcadores de Tumor/metabolismo , Carcinoma Papilar/diagnóstico por imagen , Carcinoma Papilar/mortalidad , Carcinoma Papilar/cirugía , Estudios de Casos y Controles , MicroARN Circulante/metabolismo , Diagnóstico Diferencial , Femenino , Estudios de Seguimiento , Voluntarios Sanos , Humanos , Metástasis Linfática , Masculino , Persona de Mediana Edad , Estadificación de Neoplasias , Periodo Posoperatorio , Periodo Preoperatorio , Pronóstico , ARN Neoplásico/metabolismo , Curva ROC , Reacción en Cadena en Tiempo Real de la Polimerasa , Glándula Tiroides/diagnóstico por imagen , Glándula Tiroides/patología , Glándula Tiroides/cirugía , Neoplasias de la Tiroides/diagnóstico por imagen , Neoplasias de la Tiroides/mortalidad , Neoplasias de la Tiroides/cirugía , Tiroidectomía , UltrasonografíaRESUMEN
MicroRNAs (miRNAs/miRs), which are endogenous non-coding single-stranded RNAs 19-25 nucleotides in length, regulate gene expression by blocking translation or transcription repression. The present study revealed that miR-3160-5p was widely expressed in prostate cancer cells by reverse transcription-quantitative polymerase chain reaction. There was a negative association between the expression of miR-3160-5p and F-box and WD repeat domain containing 8 (Fbxw8) in prostate cancer DU145 cells. A luciferase activity assay was used to verify that Fbxw8 is the target of miR-3160-5p. In the present study, using MTT assay and cell cycle analysis, it was demonstrated that DU145 cell proliferation was repressed and the cell cycle was arrested in the G2/M cell cycle phase with upregulation of miR-3160-5p. Subsequent studies demonstrated that miR-3160-5p regulated the progression of the cell cycle in DU145 prostate cancer cells when the expression levels of phosphorylated cell division cycle (CDC)2, CDC25C and cyclin B1 were directly inhibited. Taken together, these findings revealed the mechanism underlying the role of miR-3160-5p in regulating the proliferation of DU145 cells and indicated that miR-3160-5p may serve as a promising novel therapeutic tool for prostate cancer.
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Circulating microRNAs (miRNAs/miRs) are considered to be potential biomarkers for numerous types of cancer. However, previous investigations into the expression of miRNAs in the serum of patients with papillary thyroid carcinoma (PTC) to predict diagnosis, prognosis and recurrence have reported conflicting results, and the role of miRNAs remains unclear. The present study dynamically assessed the circulating miRNA profile in patients with PTC and determined whether miRNAs in the serum could be used as biomarkers for the diagnosis, prognosis and recurrence of PTC. The expression levels of 3 reportedly upregulated miRNAs (miR-222, miR-221 and miR-146b) were analyzed using reverse transcription-quantitative polymerase chain reaction in 106 patients with PTC, 35 patients with benign thyroid nodules (BTN) and 40 paired controls. Patients with either newly diagnosed PTC or BTN who were undergoing thyroidectomies were recruited for a dynamic analysis of preoperative and postoperative serum miRNA levels. The results indicated that the expression levels of serum miR-222, miR-221 and miR-146b were significantly increased in patients with newly diagnosed PTC compared with controls and patients with BTN. Receiver operating characteristic curve analysis indicated that these miRNAs had a high diagnostic sensitivity and specificity for PTC prior to surgery. The expression of these three miRNAs in serum was significantly associated with poorer prognostic variables, including extrathyroidal invasion, metastatic lymph nodes and high-risk or advanced tumor node metastasis stage. More notably, the present study identified 2.36-, 2.69- and 5.39-fold reductions in the serum levels of miR-222, miR-221 and miR-146b, respectively, subsequent to patients undergoing a thyroidectomy. In addition, miR-222, miR-221 and miR-146b were overexpressed in the PTC with recurrence group compared with the PTC without recurrence group. Collectively, dynamic monitoring of circulating miRNAs may serve as a non-invasive biomarker for the diagnosis of PTC and the postoperative monitoring of its progression and recurrence.
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This paper reports a series of novel Ni-based metal-organic framework (Ni-MOFs) prepared by a facile solvothermal process. The synthetic conditions have great effects on the Ni-MOFs morphologies, porous textures, and their electrochemical performance. Improved capacitance performance was successfully realized by the in-situ hybrid of Ni-MOFs with graphene oxide (GO) nanosheets (Ni-MOFs@GO). The pseudocapacitance of ca. 1457.7 F/g for Ni-MOFs obtained at 180 °C with HCl as the modulator was elevated to ca. 2192.4 F/g at a current density of 1 A/g for the Ni-MOFs@GO with GO contents of 3 wt %. Additionally, the capacitance retention was also promoted from ca. 83.5% to 85.1% of its original capacitance at 10 A/g even after 3000 cycles accordingly. These outstanding electrochemical properties of Ni-based MOF materials may be related to their inherent characteristics, such as the unique flower-like architecture and fascinating synergetic effect between the Ni-MOFs and the GO nanosheets.
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Gastric cancer is the fourth most common cancer type and the second leading cause of cancerassociated mortality worldwide. Metastasis is a crucial feature of its progression. DNA methylation provides a key epigenetic signature in the epigenetic regulation pathway, and is implicated in transcriptional regulation. CpG sites, which are associated with gene transcriptional activity, are underrepresented in the mammalian genome and tend to be clustered within CpG islands (CGIs) located in the vicinity of the transcription start sites of the majority of the proteincoding genes in humans. The DNA methylation inhibitor, decitabine (DAC), has been demonstrated to be active in hematological disorders. The majority of previous studies in cancer cells demonstrated that DAC inhibits cell proliferation and the motility of the cells. However, since demethylation across the entire genome alters the expression of a large number of genes, the effects of DAC in different tumor cell types are difficult to accurately predict. Neural precursor cellexpressed, developmentally downregulated (NEDD)41, a member of the NEDD4 family, which belongs to the E3ubiquitin ligase family, was reported to be highly expressed in a wide range of tumor types, and it activates the phosphoinositide 3kinase/Akt pathway by degrading phosphatase and tensin homolog. NEDD41 promotes the migration and invasion of glioma cells via the ubiquitination and subsequent degradation of cyclic nucleotideRas guanine nucleotide exchange factors (CNrasGEFs). In gastric cardia adenocarcinoma, NEDD41 acts as an exceptional prognostic biomarker. In the present study, DAC was revealed to promote the invasive properties of MGC803 gastric cancer cells. NEDD41 targeted the CNrasGEFmediated DAC invasionpromoting activity in MGC803 cells, and CGI methylation in neither the NEDD4 promoter nor the first intron was demonstrated to be associated with this effect. The results of the present study revealed that DAC exerts variable effects in different gastric cancer cell lines and may provide a reference for DAC administration in the clinic.
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Azacitidina/análogos & derivados , Movimiento Celular/efectos de los fármacos , Complejos de Clasificación Endosomal Requeridos para el Transporte/genética , Neoplasias Gástricas/genética , Ubiquitina-Proteína Ligasas/genética , Regulación hacia Arriba , Azacitidina/farmacología , Línea Celular Tumoral , Movimiento Celular/genética , Proliferación Celular/efectos de los fármacos , Proliferación Celular/genética , Metilación de ADN/efectos de los fármacos , Decitabina , Complejos de Clasificación Endosomal Requeridos para el Transporte/metabolismo , Complejos de Clasificación Endosomal Requeridos para el Transporte/fisiología , Humanos , Ubiquitina-Proteína Ligasas Nedd4 , Invasividad Neoplásica/genética , Neoplasias Gástricas/metabolismo , Neoplasias Gástricas/patología , Ubiquitina-Proteína Ligasas/metabolismo , Ubiquitina-Proteína Ligasas/fisiologíaRESUMEN
Sensing and responding to endogenous electrical fields are important abilities for cells engaged in processes such as embryogenesis, regeneration and wound healing. Many types of cultured cells have been induced to migrate directionally within electrical fields in vitro using a process known as galvanotaxis. The underlying mechanism by which cells sense electrical fields is unknown. In this study, we assembled a polydimethylsiloxane (PDMS) galvanotaxis system and found that mouse fibroblasts and human prostate cancer PC3 cells migrated to the cathode. By comparing the effects of a pulsed direct current, a constant direct current and an anion-exchange membrane on the directed migration of mouse fibroblasts, we found that these cells responded to the ionic flow in the electrical fields. Taken together, the observed effects of the calcium content of the medium, the function of the store-operated calcium channels (SOCs) and the intracellular calcium content on galvanotaxis indicated that calcium ionic flow from the anode to the cathode within the culture medium permeated the cells through SOCs at the drift velocity, promoting migration toward the cathode. The RTK-PI3K pathway was involved in this process, but the ROCK and MAPK pathways were not. PC3 cells and mouse fibroblasts utilized the same mechanism of galvanotaxis. Together, these results indicated that the signaling pathway responsible for cathode-directed cellular galvanotaxis involved calcium ionic flow from the anode to the cathode within the culture medium, which permeated the cells through SOCs, causing cytoskeletal reorganization via PI3K signaling.
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Canales de Calcio/metabolismo , Calcio/metabolismo , Electricidad , Animales , Canales de Calcio/química , Canales de Calcio/genética , Línea Celular , Movimiento Celular , Técnicas Electroquímicas/instrumentación , Electrodos , Fibroblastos/citología , Fibroblastos/metabolismo , Humanos , Iones/química , Ratones , Proteína ORAI1 , Fosfatidilinositol 3-Quinasas/metabolismo , Interferencia de ARN , ARN Interferente Pequeño/metabolismo , Proteínas Tirosina Quinasas Receptoras/metabolismo , Transducción de SeñalRESUMEN
OCT4 is an essential transcription factor for maintaining the self-renewal and the pluripotency of embryonic stem cells (ESCs). The human OCT4 gene can generate three mRNA isoforms (OCT4A, OCT4B and OCT4B1) by alternative splicing. OCT4A protein is a transcription factor for the stemness of ESCs, while the function of OCT4B isoforms remains unclear. Most types of cancer express a relatively low level of OCT4 protein, particularly the OCT4B isoforms. In the present study, we found that OCT4A and OCT4B mRNA were co-expressed in several types of tumor cell lines and tumor samples, and we demonstrated that OCT4B functioned as a non-coding RNA, modulating OCT4A expression in an miRNA-dependent manner [competing endogenous RNA (ceRNA) regulation] at the post-transcription level in the tumor cell lines. This is the first time that ceRNA regulation was observed among spliced isoforms of one gene, and may pave the way for identification of new targets for cancer treatment.