RESUMEN
BACKGROUND: MutT homolog 1 (MTH1) sanitizes oxidized dNTP pools to promote the survival of cancer cells and its expression is frequently upregulated in cancers. Polyubiquitination stabilizes MTH1 to facilitate the proliferation of melanoma cells, suggesting the ubiquitin system controls the stability and function of MTH1. However, whether ubiquitination regulates MTH1 in gastric cancers has not been well defined. This study aims to investigate the interaction between MTH1 and a deubiquitinase, USP9X, in regulating the proliferation, survival, migration, and invasion of gastric cancer cells. METHODS: The interaction between USP9X and MTH1 was evaluated by co-immunoprecipitation (co-IP) in HGC-27 gastric cancer cells. siRNAs were used to interfere with USP9X expression in gastric cancer cell lines HGC-27 and MKN-45. MTT assays were carried out to examine the proliferation, propidium iodide (PI) and 7-AAD staining assays were performed to assess the cell cycle, Annexin V/PI staining assays were conducted to examine the apoptosis, and transwell assays were used to determine the migration and invasion of control, USP9X-deficient, and USP9X-deficient plus MTH1-overexpressing HGC-27 and MKN-45 gastric cancer cells. RESULTS: Co-IP data show that USP9X interacts with and deubiquitinates MTH1. Overexpression of USP9X elevates MTH1 protein level by downregulating its ubiquitination, while knockdown of USP9X has the opposite effect on MTH1. USP9X deficiency in HGC-27 and MKN-45 cells causes decreased proliferation, cell cycle arrest, extra apoptosis, and defective migration and invasion, which could be rescued by excessive MTH1. CONCLUSION: USP9X interacts with and stabilizes MTH1 to promote the proliferation, survival, migration and invasion of gastric cancer cells.
Asunto(s)
Movimiento Celular , Proliferación Celular , Enzimas Reparadoras del ADN , Invasividad Neoplásica , Monoéster Fosfórico Hidrolasas , Neoplasias Gástricas , Ubiquitina Tiolesterasa , Humanos , Neoplasias Gástricas/patología , Neoplasias Gástricas/metabolismo , Neoplasias Gástricas/genética , Proliferación Celular/genética , Ubiquitina Tiolesterasa/metabolismo , Ubiquitina Tiolesterasa/genética , Línea Celular Tumoral , Monoéster Fosfórico Hidrolasas/metabolismo , Monoéster Fosfórico Hidrolasas/genética , Enzimas Reparadoras del ADN/metabolismo , Enzimas Reparadoras del ADN/genética , Ubiquitinación , Supervivencia Celular , Apoptosis , ARN Interferente PequeñoRESUMEN
INTRODUCTION: The objective of this research is to explore whether LncRNA RP11 23J9.4 can be used as a targeted marker for the treatment of thyroid cancer (TC), downregulation of LncRNA RP11 23J9.4 and X-ray radiation have synergistic inhibitory effect on TC. METHODS: The expression of LncRNA RP11 23J9.4 in papillary thyroid carcinoma (PTC) cell was downregulated by cell transfection, and its inhibitory effect on PTC cells was proved through proliferation, invasion experiment, apoptosis, and cell cycle analysis. The transfected cells were irradiated with 2 Gy X-ray. The above methods were also used to detect whether they had synergistic inhibitory effect on TC. The expression of Axin2 gene and protein were detected by real-time PCR, Western blotting, and immunohistochemistry. RESULTS: On the one hand, it is proved that downregulating the expression of LncRNA RP11 23J9.4 can inhibit the development of TC through Axin2. On the other hand, it is clear that downregulation of LncRNA RP11 23J9.4 and X-ray radiation have synergistic inhibitory effect on TC. CONCLUSIONS: LncRNA RP11 23J9.4 and X-ray have significant synergistic effect on TC. LncRNA RP11 23J9.4 can be used as a marker for TC targeted therapy.
Asunto(s)
ARN Largo no Codificante , Neoplasias de la Tiroides , Humanos , ARN Largo no Codificante/genética , ARN Largo no Codificante/metabolismo , Línea Celular Tumoral , Proliferación Celular/genética , Regulación Neoplásica de la Expresión Génica , Neoplasias de la Tiroides/genética , Neoplasias de la Tiroides/metabolismo , Cáncer Papilar Tiroideo/genética , Movimiento Celular/genéticaRESUMEN
BACKGROUND: A growing body of research suggests that methylated genes can be used as early diagnostic markers for cancer. Some studies on methylated Syndecan 2 (SDC2) have shown that it has a great diagnostic ability in colorectal cancer. This meta-analysis was aimed to estimate the diagnostic performance of methylated SDC2 as a potential novel biomarker to screen for the colorectal cancer. METHODS: Two independent researchers conducted a comprehensive literature search to identify all relevant studies on SDC2 methylation for the diagnosis of colorectal cancer from inception to March 1, 2021. By using STATA and Revman software, the data were analyzed using a Bivariate mixed model. The quality of each study was also evaluated. RESULTS: A total of 12 studies comprised of 1574 colorectal cancer patients and 1945 healthy people were included in our meta-analysis. Bivariate analysis showed a pooled sensitivity of 0.81 [95% confidence interval (CI) 0.74-0.86], specificity of 0.95 (95% CI 0.93-0.96), positive likelihood ratio of 15.29 (95% CI 10.83-21.60), and negative likelihood ratio of 0.21 (95% CI 0.15-0.27). The diagnostic odds ratio and the area under the summary ROC curve for diagnosing colorectal cancer were 74.42 (95% CI45.44-121.89) and 0.96 (95% CI 0.94-0.97), respectively. For adenomas, the pooled sensitivity and specificity were 0.47 (95% CI 0.34-0.61) and 0.95 (95% CI 0.92-0.97), respectively. CONCLUSIONS: Our analysis revealed that methylated SDC2 could be considered as a potential novel biomarker to screen for colorectal cancer.
Asunto(s)
Neoplasias Colorrectales , Sindecano-2 , Biomarcadores de Tumor/genética , Neoplasias Colorrectales/diagnóstico , Neoplasias Colorrectales/genética , ADN , Metilación de ADN , Detección Precoz del Cáncer , Humanos , Sensibilidad y Especificidad , Sindecano-2/genéticaRESUMEN
BACKGROUND The recurrence of COVID-19 and the continuous escalation of prevention and control policies can lead to an increase in mental health problems. This study aimed to investigate the perceived stress, coping style, resilience, and social support among patients on maintenance hemodialysis (MHD) during the COVID-19 epidemic lockdown in China. MATERIAL AND METHODS This cross-sectional observational study enrolled 197 patients on MHD from the Guangdong Province Traditional Chinese Medical Hospital and the Hedong Hospital of Guangzhou Liwan District People's Hospital during July 2021. AMOS 24.0 and PROCESS Macro 3.1 model 6 were used for analyses of moderating mediating effects. RESULTS Perceived stress was negatively correlated with positive coping style (r=-0.305, P<0.001) and resilience (r=-0.258, P<0.001), whereas resilience (r=0.631, P<0.001) and social support (r=0.300, P<0.001) were positively correlated with positive coping style among patients on MHD. In the moderated mediating model, perceived stress had significant direct predictive effects on positive coping style (95% CI -0.33, -0.07), and perceived stress had significant indirect predictive effects on positive coping styles through resilience (95% CI -0.26, -0.06) or social support (95% CI 0.01, 0.06). Perceived stress had significant indirect predictive effects on positive coping style through both resilience and social support (95% CI -0.04, -0.01). CONCLUSIONS Perceived stress not only predicted coping style directly, but also indirectly predicted coping style through resilience and social support. Coping style was affected by internal and external factors during the COVID-19 pandemic lockdown period.
Asunto(s)
Adaptación Psicológica/fisiología , COVID-19/psicología , Enfermedades Renales/psicología , Adulto , Pueblo Asiatico/psicología , COVID-19/complicaciones , China/epidemiología , Control de Enfermedades Transmisibles , Estudios Transversales , Femenino , Humanos , Enfermedades Renales/complicaciones , Enfermedades Renales/virología , Masculino , Persona de Mediana Edad , Pandemias , Diálisis Renal , Resiliencia Psicológica/fisiología , SARS-CoV-2/patogenicidad , Apoyo Social , Estrés Psicológico/psicología , Encuestas y CuestionariosRESUMEN
Indoor 3D positioning is useful in multistory buildings, such as shopping malls, libraries, and airports. This study focuses on indoor 3D positioning using wireless access points (AP) in an environment without adding additional hardware facilities in large-scale complex places. The integration of a deep learning algorithm into indoor 3D positioning is studied, and a 3D dynamic positioning model based on temporal fingerprints is proposed. In contrast to the traditional positioning models with a single input, the proposed method uses a sliding time window to build a temporal fingerprint chip as the input of the positioning model to provide abundant information for positioning. Temporal information can be used to distinguish locations with similar fingerprint vectors and to improve the accuracy and robustness of positioning. Moreover, deep learning has been applied for the automatic extraction of spatiotemporal features. A temporal convolutional network (TCN) feature extractor is proposed in this paper, which adopts a causal convolution mechanism, dilated convolution mechanism, and residual connection mechanism and is not limited by the size of the convolution kernel. It is capable of learning hidden information and spatiotemporal relationships from the input features and the extracted spatiotemporal features are connected with a deep neural network (DNN) regressor to fit the complex nonlinear mapping relationship between the features and position coordinates to estimate the 3D position coordinates of the target. Finally, an open-source public dataset was used to verify the performance of the localization algorithm. Experimental results demonstrated the effectiveness of the proposed positioning model and a comparison between the proposed model and existing models proved that the proposed model can provide more accurate three-dimensional position coordinates.
Asunto(s)
Algoritmos , Redes Neurales de la ComputaciónRESUMEN
OBJECTIVE: Despite its association with static mesenteric malperfusion, the morphologic characteristics and optimal management of acute type B aortic dissection (ABAD) with superior mesenteric artery (SMA) involvement are poorly understood. We studied the associated risk factors and reported the outcomes of endovascular treatment. METHODS: From May 2016 to May 2018, we examined 212 consecutive patients with ABAD in our center. Those with SMA involvement (SMAI) were included in the present study and divided into those with and without mesenteric malperfusion (MMP) according to the clinical findings. After thoracic endovascular aortic repair (TEVAR) with or without SMA revascularization, we compared the clinical data, imaging results, and outcomes for those with and without MMP. RESULTS: Computed tomography angiography confirmed 44 cases of SMAI: 12 (27.3%) with MMP and 32 (72.7%) without MMP. The patients with MMP had presented more frequently with lower extremity malperfusion (33.3% vs 3.1%; P = .023) than had those without MMP, with an odds ratio of 14.15 (P = .047). Multivariate analysis showed that patients with a low true lumen (TL)/false lumen (FL) diameter ratio of the SMA (TL/FL-SMA <1) had a greater risk of developing MMP than those with a high TL/FL-SMA ratio of >1 (odds ratio, 8.49; 95% confidence interval, 1.24-58.26; P = .029). SMA TL thrombosis was a significant predictor of the requirement for additional SMA revascularization after TEVAR among patients with MMP (P = .045). During a mean 10-month follow-up period, complete FL thrombosis in the SMA was seen in 11 patients (25%; 33.3% with MMP vs 21.9% without MMP; P = .43). The overall mortality rate was 6.82% (16.7% in the MMP group and 3.1% in the non-MMP group; P = .09). CONCLUSIONS: In the present study, limb ischemia and the TL/FL-SMA ratio were two independent predictors for the development of MMP in patients with ABAD and SMAI. We found that TEVAR can be safely performed for these patients, and SMA TL thrombosis predicted for the need for SMA revascularization.
Asunto(s)
Aneurisma de la Aorta Torácica/cirugía , Disección Aórtica/cirugía , Implantación de Prótesis Vascular , Procedimientos Endovasculares , Arteria Mesentérica Superior/cirugía , Enfermedad Aguda , Adulto , Anciano , Disección Aórtica/diagnóstico por imagen , Disección Aórtica/mortalidad , Disección Aórtica/fisiopatología , Aneurisma de la Aorta Torácica/diagnóstico por imagen , Aneurisma de la Aorta Torácica/mortalidad , Aneurisma de la Aorta Torácica/fisiopatología , Aortografía , Implantación de Prótesis Vascular/efectos adversos , Implantación de Prótesis Vascular/mortalidad , Angiografía por Tomografía Computarizada , Procedimientos Endovasculares/efectos adversos , Procedimientos Endovasculares/mortalidad , Femenino , Humanos , Masculino , Arteria Mesentérica Superior/diagnóstico por imagen , Arteria Mesentérica Superior/fisiopatología , Persona de Mediana Edad , Estudios Retrospectivos , Medición de Riesgo , Factores de Riesgo , Circulación Esplácnica , Factores de Tiempo , Resultado del TratamientoRESUMEN
Acoustic impedance sensing based on forward stimulated Brillouin scattering (FSBS) in fiber has attracted the attention of researchers in recent years. Here, we propose a novel, to the best of our knowledge, multipoint sensing scheme based on FSBS, which explores frequency-division multiplexing. Since the resonance center frequencies of the FSBS-invoked acoustic modes are dependent on the fiber diameter, different fiber sections can be differentiated using carefully selected representative peaks in the FSBS spectrum. With a Sagnac loop structure, continuous-wave light is adopted for FSBS excitation, reducing the required fiber length for efficient opto-acoustic interaction. By evaluating the linewidths of representative peaks, simultaneous acoustic impedance sensing at multiple locations is realized with 0.8 m sensor size.
RESUMEN
Tracking operating trains and identifying illegal intruders are two important and critical issues in subway safety management. One challenge is to find a reliable methodology that would enable these two needs to be addressed with high sensitivity and spatial resolution over a long-distance range. This paper proposes a novel monitoring approach based on distributed vibration, which is suitable for both train tracking and incursion detection. For an actual subway system, ultra-weak fiber Bragg grating (FBG) sensing technology was applied to collect the distributed vibration responses from moving trains and intruders. The monitoring data from the subway operation stage were directly utilized to evaluate the feasibility of the proposed method for tracking trains. Moreover, a field simulation experiment was performed to validate the possibility of detecting human intrusion. The results showed that the diagonal signal pattern in the distributed vibration response can be used to reveal the location and speed of the moving loads (e.g., train and intruders). Other train parameters, such as length and the number of compartments, can also be obtained from the vibration responses through cross-correlation and envelope processing. Experimental results in the time and frequency domains within the selected intrusion range indicated that the proposed method can distinguish designed intrusion cases in terms of strength and mode.
RESUMEN
A one-step reduction method was used for the preparation of stable graphitic carbon nitride-gold nanoparticles (g-C3N4-Au) nanocomposites from ultrathin g-C3N4 nanosheets and chloroauric acid by using NaBH4 as a reducing agent under ultrasonication. The nanocomposites were characterized by transmission electron microscopy, X-ray photoelectron spectroscopy, UV-Vis absorption and fluorescence spectroscopy etc. The results revealed that the gold nanoparticles (AuNPs) are uniformly formed on the g-C3N4 nanosheets. It is found that the peroxidase-like catalytic activity of this nanocomposite for the oxidation of 3,3',5,5'-tetramethylbenzidine by H2O2 to form a blue-colored product is strongly enhanced in the presence of Hg(II). Based on this phenomenon, a sensitive "turn-on" colorimetric assay for Hg(II) was developed that works at physiological pH values. Under optimal conditions, the absorption signal at 652 nm increases linearly with Hg(II) concentration in the range from 5 to 500 nM. A detection limit as low as 3.0 nM was achieved. This assay has excellent selectivity over other metal ions. It was successfully applied to the determination of Hg(II) in real water samples. The method is cost-effective, rapid, and allows for visual detection. Graphical abstract The nanocomposite composed of graphitic carbon nitride (g-C3N4) and gold nanoparticles (g-C3N4-AuNPs) can catalyze tetramethylbenzidine (TMB) oxidation by H2O2 to produce light-blue product (oxTMB). The peroxidase-like activity of g-C3N4-AuNPs can be greatly enhanced by Hg2+, thus increases the amount of the blue product formed.
Asunto(s)
Colorimetría/métodos , Oro , Mercurio/análisis , Nanocompuestos/química , Nanopartículas/química , Nitrilos/química , Colorimetría/normas , Grafito/química , Microscopía , Imitación Molecular , Peroxidasa , Análisis EspectralRESUMEN
In this work, uniformly-dispersed platinum nanoparticles (PtNPs) were synthesized by a simple chemical reduction method, in which citric acid and sodium borohydride acted as a stabilizer and reducer, respectively. An ultrasensitive colorimetric sensor for the facile and rapid detection of Ag⺠ions was constructed based on the peroxidase mimetic activities of the obtained PtNPs, which can catalyze the oxidation of 3,3',5,5'-tetramethylbenzidine (TMB) by H2O2 to produce colored products. The introduced Ag⺠would be reduced to Ag° by the capped citric acid, and the deposition of Ag° on the PtNPs surface, can effectively inhibit the peroxidase-mimetic activity of PtNPs. Through measuring the maximum absorption signal of oxidized TMB at 652 nm, ultra-low detection limits (7.8 pM) of Ag⺠can be reached. In addition to such high sensitivity, the colorimetric assay also displays excellent selectivity for other ions of interest and shows great potential for the detection of Ag⺠in real water samples.
RESUMEN
BACKGROUND: Coronary effluent from an isolated perfused heart undergoing ischemic preconditioning can be transferred to precondition another naïve isolated heart. We investigated the effects of this effluent on mitochondrial integrity and function following a global infarct model of ischemia/reperfusion and the role of adenosine in this model of remote preconditioning. METHODS AND RESULTS: Coronary effluent from isolated perfused rabbit hearts was collected prior to (control effluent) and during three cycles of 5-min ischemia and 10-min reperfusion (IPC effluent). Adenosine concentration was significantly increased in IPC effluent (2.6 ± 1.1 µM) versus control effluent (0.21 ± 0.06 µM, P < 0.01). Infarct size (% necrotic LV mass) after 30-min global ischemia and 90-min reperfusion was significantly reduced in hearts preconditioned with IPC effluent (IPC(eff), 23 ± 7 %) and control effluent supplemented with 2.5 µM exogenous adenosine (C(eff)+ 2.5 µM ADO, 25 ± 10 %) when compared to control effluent perfused hearts (C(eff), 41 ± 8 %, P < 0.05). Compared to C(eff) mitochondria, IPC(eff) mitochondria had preserved complex I/State3 and complex IV/State 3 respiration and outer membrane integrity, and reduced cytochrome c release. In contrast, C(eff) + 2.5 µM ADO mitochondria had improved state 2 respiration and coupling to oxidative phosphorylation, reduced reactive oxygen species production and preserved outer membrane integrity. Administration of adenosine receptor blocker 8-(p-sulfophenyl)theophylline abolished the infarct limiting effect (46 ± 7 %) and the mitochondrial integrity and function preservation of IPC effluent. CONCLUSION: Remote cardioprotection by IPC effluent preserves mitochondrial integrity and function in an adenosine receptor dependent mechanism, and although infarct size reduction can be mimicked by adenosine, IPC effluent contains additional factor(s) contributing to modulation of the mitochondrial response to ischemia/reperfusion injury.
Asunto(s)
Precondicionamiento Isquémico Miocárdico/métodos , Infarto del Miocardio/prevención & control , Daño por Reperfusión Miocárdica/fisiopatología , Receptores Purinérgicos P1/metabolismo , Adenosina/metabolismo , Animales , Modelos Animales de Enfermedad , Masculino , Mitocondrias/metabolismo , Infarto del Miocardio/etiología , Infarto del Miocardio/patología , Conejos , Especies Reactivas de Oxígeno/metabolismo , Teofilina/análogos & derivados , Teofilina/farmacologíaRESUMEN
The inhaling of cigarette smoke (CS) causes damage to airway epithelial cells, which is related to chronic obstructive pulmonary disease (COPD). It has been established that CS induces autophagy, but it is still unclear whether excessive or insufficient autophagy results in cell death. This study discovered that CS significantly elevates PSAT1 expression in bronchial epithelial cells. Further studies using autophagy inhibitor, RNA interference, RT-qPCR, western blot, and CCK-8 assay in 16-HBE cells have confirmed that autophagy is temporarily initiated by cigarette smoke extract (CSE), but insufficient autophagy leads to cell death. PSAT1 induced by CSE promotes autophagy and resists insufficient autophagy caused by CSE through Akt/mTOR pathway in human bronchial epithelial cells, playing a protective role.
Asunto(s)
Fumar Cigarrillos , Enfermedad Pulmonar Obstructiva Crónica , Humanos , Autofagia , Muerte Celular , Células Epiteliales/metabolismo , Enfermedad Pulmonar Obstructiva Crónica/genéticaRESUMEN
The microenvironment of diffuse large B-cell lymphoma (DLBCL) is composed of various components, including immune cells and immune checkpoints, some of which have been correlated with the prognosis of DLBCL, but their results remain controversial. Therefore, we conducted a systematic review and meta-analysis to investigate the association between the microenvironment and prognosis in DLBCL. We searched PubMed, Web of Science, and EMBASE for relevant articles between 2001 and 2022. Twenty-five studies involving 4495 patients with DLBCL were included in the analysis. This meta-analysis confirmed that high densities of Foxp3+Tregs and PD-1+T cells are good indicators for overall survival (OS) in DLBCL, while high densities of programmed cell death protein ligand1(PD-L1)-positive expression cells and T-cell immunoglobulin-and mucin domain-3-containing molecule 3 (TIM-3)-positive expression tumor-infiltrating cells (TILs) play a contrary role in OS. Additionally, higher numbers of T-cell intracytoplasmic antigen-1(TIA-1)-positive expression T cells imply better OS and progression-free survival (PFS), while high numbers of lymphocyte activation gene(LAG)-positive expression TILs predict bad OS and PFS. Various non-tumoral cells in the microenvironment play important roles in the prognosis of DLBCL.
Asunto(s)
Biomarcadores de Tumor , Linfoma de Células B Grandes Difuso , Microambiente Tumoral , Humanos , Linfoma de Células B Grandes Difuso/patología , Linfoma de Células B Grandes Difuso/inmunología , Linfoma de Células B Grandes Difuso/metabolismo , Linfoma de Células B Grandes Difuso/mortalidad , Pronóstico , Microambiente Tumoral/inmunología , Biomarcadores de Tumor/metabolismo , Linfocitos Infiltrantes de Tumor/inmunología , Linfocitos Infiltrantes de Tumor/metabolismoRESUMEN
Immune disorder is considered the main pathogenesis of autoimmune diseases, such as rheumatoid arthritis (RA). The balance of the two special subsets of CD4âºT cells, T helper cell 17 (Th17), and Regulator T cell (Treg) is the key factor of maintaining a normal immune response. Dendritic cells (DCs), which are the most powerful antigen-presenting cells, play an important role in regulating the balance of Th17 and Treg. The combination of disease modifying antirheumatic drugs (DMARDs) is an important strategy of RA therapy. In this study, we investigated the effect of MTX and CTX on DC maturation in ovalbumin (OVA) immunized mice. Th17 inflammatory response is stronger, while the level of DCs maturity is higher. In contrast, the immunosuppression of Treg is stronger. We found that MTX combined with CTX significantly inhibited the DCs maturity and downregulated the antigen presenting capacity of DCs. As a result, it reestablished a balance of Th17 and Treg. Our study adds a novel mechanism and therapeutic target of MTX combined with CTX for autoimmune disease treatment.
Asunto(s)
Diferenciación Celular/efectos de los fármacos , Ciclofosfamida/farmacología , Células Dendríticas/citología , Células Dendríticas/efectos de los fármacos , Metotrexato/farmacología , Animales , Antígenos de Superficie/metabolismo , Células Dendríticas/inmunología , Células Dendríticas/metabolismo , Inmunofenotipificación , Activación de Linfocitos , Prueba de Cultivo Mixto de Linfocitos , Masculino , Ratones , Ovalbúmina/inmunología , Fenotipo , Linfocitos T Reguladores/efectos de los fármacos , Linfocitos T Reguladores/inmunología , Linfocitos T Reguladores/metabolismo , Células Th17/efectos de los fármacos , Células Th17/inmunología , Células Th17/metabolismoRESUMEN
Cigarette smoke exposure is a well-recognized causative factor for Chronic obstructive pulmonary disease (COPD), but the molecular mechanisms responsible for this effect need to be further investigated. An expanding number of studies suggest that m6A modification is involved in the progression of various diseases. Nevertheless, evidence on the regulatory function of m6A modification in human bronchial epithelial cells exposed to cigarette smoke is scarce. In this study, we investigated for the first time the effect of cigarette smoke exposure on contributing to high Mettl3 expression in HBE cells in vitro, an essential m6A writer. To investigate the pattern of m6A modification in HBE cells following cigarette smoke exposure, Mettl3 was down-regulated in HBE cells and a MeRIP-seq analysis revealed differences in m6A methylation between wild-type (WT) and Mettl3 knockdown HBE cells exposed to CSE. There were 1584 significantly hypomethylated genes engaged in multicellular organismal developments. We identified 200 differentially expressed genes with hypomethylated m6A peaks in conjunction with Mettl3 knockdown, among four candidate genes (NR1H4, TSPEAR, ACSBG1, and SLC5A5) that could be further explored in COPD. According to the research, cigarette smoke may control the behavior of human bronchial epithelial cells through m6A modification in COPD, providing a unique molecular mechanism.
Asunto(s)
Fumar Cigarrillos , Enfermedad Pulmonar Obstructiva Crónica , Humanos , Metilación , Transcriptoma , Células Epiteliales , Enfermedad Pulmonar Obstructiva Crónica/genética , Enfermedad Pulmonar Obstructiva Crónica/metabolismo , Metiltransferasas/genética , Metiltransferasas/metabolismo , Metiltransferasas/farmacologíaRESUMEN
Due to changes in light intensity, varying degrees of aphid aggregation, and small scales in the climate chamber environment, accurately identifying and counting aphids remains a challenge. In this paper, an improved YOLOv5 aphid detection model based on CNN is proposed to address aphid recognition and counting. First, to reduce the overfitting problem of insufficient data, the proposed YOLOv5 model uses an image enhancement method combining Mosaic and GridMask to expand the aphid dataset. Second, a convolutional block attention mechanism (CBAM) is proposed in the backbone layer to improve the recognition accuracy of aphid small targets. Subsequently, the feature fusion method of bi-directional feature pyramid network (BiFPN) is employed to enhance the YOLOv5 neck, further improving the recognition accuracy and speed of aphids; in addition, a Transformer structure is introduced in front of the detection head to investigate the impact of aphid aggregation and light intensity on recognition accuracy. Experiments have shown that, through the fusion of the proposed methods, the model recognition accuracy and recall rate can reach 99.1%, the value mAP@0.5 can reach 99.3%, and the inference time can reach 9.4 ms, which is significantly better than other YOLO series networks. Moreover, it has strong robustness in actual recognition tasks and can provide a reference for pest prevention and control in climate chambers.
RESUMEN
Purpose: Persistent inflammation and epithelial-mesenchymal transition are essential pathophysiological processes in chronic obstructive pulmonary disease (COPD) and involve airway remodeling. m6A methylation modification was discovered to play an important role in various diseases. Nevertheless, the regulatory role of m6A methylation has not yet been investigated in cigarette smoking-induced COPD. The study aims to explore the regulatory role of m6A methylation in cigarette smoking-induced COPD. Patients and Methods: In this study, two Gene Expression Omnibus (GEO) datasets were first utilized to analyze the expression profiles of m6A RNA methylation regulators in COPD. We then established a cell model of COPD by exposing human bronchial epithelial cells (HBECs) to cigarette smoke extract (CSE) in vitro and detected the expression of m6A writer Mettl3 and EMT phenotype markers. RNA interference, cycloleucine, RT-qPCR, western blot, MeRIP-sequencing, and cell migration assay were performed to investigate the potential effect of Mettl3 on the EMT process in CSE-induced HBECs. Results: Our results showed that Mettl3 expression was significantly elevated in cigarette smoking-induced COPD patients and in a cellular model of COPD. Furthermore, Mettl3 silence and cycloleucine treatment inhibited the EMT process of HBECs caused by CSE. Mechanically, Mettl3 silence weakens the m6A methylation of SOCS3 mRNA to enhance the protein expression of SOCS3, inhibiting CSE-induced SOCS3/STAT3/SNAI1 signaling and EMT processes in HBECs. Conclusion: Our study inferred that Mettl3-mediated m6A RNA methylation modification modulates CSE-induced EMT by targeting SOCS3 mRNA and ultimately serves as a crucial regulator in the emergence of COPD. This conclusion reinforces the regulatory role of m6A methylation in COPD.
Asunto(s)
Fumar Cigarrillos , Enfermedad Pulmonar Obstructiva Crónica , Enfermedad Pulmonar Obstructiva Crónica/genética , Enfermedad Pulmonar Obstructiva Crónica/metabolismo , Enfermedad Pulmonar Obstructiva Crónica/patología , Transición Epitelial-Mesenquimal/efectos de los fármacos , Fumar Cigarrillos/patología , Metiltransferasas/genética , Metiltransferasas/metabolismo , Bronquios/patología , Células Cultivadas , Técnicas de Silenciamiento del Gen , Cicloleucina/farmacologíaRESUMEN
Background: Recent research has suggested that patients with metastatic non-small cell lung cancer (mNSCLC) can achieve ongoing response after discontinuation of immune checkpoint inhibitor (ICI), but the best time to discontinue and the factors influencing efficacy remain unknown. Method: A systematic search was performed for prospective clinical trials in patients with mNSCLC treated with ICIs published up to July 10, 2022. Eligible studies reported treatment-free survival (TFS) after discontinuation of ICI in partial objective responders. We calculated objective response rate (ORR) and TFS using random-effects models with respective 95% confidence intervals (Cis), and performed subgroup analyses to discuss the specific associations between ORR and TFS and the associated influencing factors. Results: Across the 26 cohorts (3833 patients) included, the weighted mean ORR for all patients was 29.30% (95% CI 24.28% to 34.57%), with ICI plus chemotherapy (48.83%, 95% CI 44.36% to 53.30%) significantly higher than monotherapy (23.40%, 95% CI 18.53% to 28.62%). 395 patients were all patients who were complete or partial responders in the study, 194 discontinued ICI treatment, and nearly 35.5% achieved a durable response. No significant differences in TFS were found between subgroups according to the ICI regimen classification. Four cohorts of patients who completed 35 courses of treatment showed high levels of pooled TFS at 6 (80.18%, 95% CI 53.03% to 97.87%) and 12 months (66.98%, 95% CI 46.90% to 84.47%). Three cohorts of patients discontinued ICI treatment due to treatment-related adverse events (TRAEs) with the TFS rates at 6 (76.98%, 95% CI 65.79% to 86.65%) and 12 months (64.79%, 95% CI 50.20% to 78.19%). Conclusion: Patients with mNSCLC were able to achieve ongoing responses after discontinuation of ICI. In conclusion, the results of this meta-analysis indicate that different treatment regimens, different drugs or different treatment durations may have an impact on TFS.
Asunto(s)
Carcinoma de Pulmón de Células no Pequeñas , Neoplasias Pulmonares , Humanos , Inhibidores de Puntos de Control Inmunológico/efectos adversos , Carcinoma de Pulmón de Células no Pequeñas/tratamiento farmacológico , Estudios Prospectivos , Neoplasias Pulmonares/tratamiento farmacológico , Duración de la TerapiaRESUMEN
BACKGROUND: This study investigate the anti-tumor effect of curcumin and whether its mediated by hsa_circ_0136666 through miR-1301-3p/CXCL1 in colorectal carcinoma (CRC). Through multiple experiments, we have drawn the conclusion that curcumin inhibited CRC development through the hsa_circ_0136666/miR-1301-3p/CXCL1 axis, hinting at a novel treatment option for curcumin to prevent CRC development. AIM: To determine whether hsa_circ_0136666 involvement in curcumin-triggered CRC progression was mediated by sponging miR-1301-3p. METHODS: Cell counting kit-8, colony-forming cell, 5-ethynyl-2'-deoxyuridine, and flow cytometry assays were carried out to determine cell proliferation, apoptosis, and cell cycle progression. Real-time quantitative polymerase chain reaction quantified hsa_circ_0136666, miR-1301-3p, and chemokine (C-X-C motif) ligand 1 (CXCL1), and western blot analysis determined CXCL1, B-cell lymphoma-2 (Bcl-2), and Bcl-2 related X protein (Bax) protein levels. CircBank or starbase software was first used for the prediction of miR-1301-3p binding with hsa_circ_0136666 and CXCL1, followed by RNA pull-down, RNA immunoprecipitation, and dual-luciferase reporter assay validation. In vivo experiments were implemented in a murine xenograft model. RESULTS: Curcumin blocked CRC cell proliferation but boosted apoptosis. Moreover, elevated hsa_circ_0136666 Levels were observed in CRC cells, which were reduced by curcumin. In vitro, hsa_circ_0136666 overexpression abolished the antitumor activity of CRC cells. Mechanical analysis revealed the ability of hsa_circ_0136666 to sponge miR-1301-3p to modulate CXCL1 levels. CONCLUSION: Curcumin inhibited CRC development through the hsa_circ_0136666/miR-1301-3p/CXCL1 axis, hinting at a novel treatment option for curcumin to prevent CRC development.
RESUMEN
In the present work, a highly sensitive sandwich-type electrochemical immunosensor of carcinoembryonic antigen (CEA) was developed by preparing N-doped hollow mesoporous nanocarbon spheres/gold hybrids (NHMN/Au) hybridsas sensing platformand Au/ferrocene (Au/Fc) as signal amplifiers. The large surface area and high conductivity as well as good biocompatibility of NHMN/Au can increase the loading of primary antibody (Ab1) and accelerate the electron transport rate of the electrode surface, while Au can carry immobilized secondary antibodies (Ab2) and Fc derivative (Fc-SH).By using Fc-SH as response probe, the experiments show that the peak current of probe could increase after occurring the specific recognition of Ab1-CEA-Ab2, thus a novel sandwich-type immunosensor of CEA was developed. Finally, the proposed method for CEA detection was applied in human serum and the obtained results are satisfactory, indicating the developed method has important clinical applications for CEA determination.