RESUMEN
BACKGROUND AND AIMS: Myofibroblasts are considered the major effector cell type of liver fibrosis and primarily derived from hepatic stellate cells (HSCs). In the present study, we investigated the contribution of C-C motif chemokine (CCL11) to HSC-myofibroblast trans -differentiation and its implication in liver fibrosis. APPROACH AND RESULTS: We report that CCL11 levels were elevated in HSCs, but not in hepatocytes or Kupffer cells, isolated from mice with liver fibrosis compared with the control mice. CCL11 levels were also up-regulated by 2 pro-fibrogenic growth factors TGF-ß and platelet derived growth factor in cultured HSCs. Mechanistically, zinc finger factor 281 bound to the CCL11 promoter and mediated CCL11 trans -activation in HSCs. Depletion of CCL11 attenuated whereas treatment with recombinant CCL11 promoted HSC activation. Further, global CCL11 deletion ( CCL11-/- ) or HSC/myofibroblast-specific CCL11 knockdown mitigated fibrogenesis in mice. RNA-sequencing revealed that CCL11 might regulate HSC activation by stimulating the transcription of Jagged 1. Reconstitution of Jagged 1 restored the fibrogenic response in CCL11-/- mice. Finally, several targeting strategies that aimed at blockading CCL11 signaling, either by administration of an antagonist to its receptor C-C motif chemokine receptor 3 or neutralizing antibodies against CCL11/C-C motif chemokine receptor 3, ameliorated liver fibrosis in mice. CONCLUSIONS: Our data unveil a previously unrecognized role for CCL11 in liver fibrosis and provide proof-of-concept evidence that targeting CCL11 can be considered as an effective therapeutic approach.
Asunto(s)
Hepatocitos , Cirrosis Hepática , Animales , Ratones , Células Cultivadas , Células Estrelladas Hepáticas/metabolismo , Hepatocitos/metabolismo , Proteína Jagged-1/metabolismo , Hígado/patología , Cirrosis Hepática/patología , Receptores de Quimiocina/metabolismoRESUMEN
BACKGROUND: The lncRNA TRG-AS1 and its co-expressed gene P2RY10 are important for colorectal cancer (CRC) occurrence and development. The purpose of our research was to explore the roles of TRG-AS1 and P2RY10 in CRC progression. METHODS: The abundance of TRG-AS1 and P2RY10 in CRC cell lines (HT-29 and LoVo) and normal colon cells FHC was determined and difference between CRC cells and normal cells was compared. LoVo cells were transfected with si-TRG-AS1 and si-P2RY10 constructs. Subsequently, the viability, colony formation, and migration of the transfected cells were analyzed using cell counting kit-8, clonogenicity, and scratch-wound/Transwell® assays, respectively. Cells overexpressing GNA13 were used to further explore the relationship between TRG-AS1 and P2RY10 along with their downstream functions. Finally, nude mice were injected with different transfected cell types to observe tumor formation in vivo. RESULTS: TRG-AS1 and P2RY10 were significantly upregulated in HT-29 and LoVo compared to FHC cells. TRG-AS1 knockdown and P2RY10 silencing suppressed the viability, colony formation, and migration of LoVo cells. TRG-AS1 knockdown downregulated the expression of P2RY10, GNA12, and GNA13, while P2RY10 silencing downregulated the expression of TRG-AS1, GNA12, and GNA13. Additionally, GNA13 overexpression reversed the cell growth and gene expression changes in LoVo cells induced by TRG-AS1 knockdown or P2RY10 silencing. In vivo experiments revealed that CRC tumor growth was suppressed by TRG-AS1 knockdown and P2RY10 silencing. CONCLUSIONS: TRG-AS1 knockdown repressed the growth of HT-29 and LoVo by regulating P2RY10 and GNA13 expression.
Asunto(s)
Movimiento Celular , Proliferación Celular , Neoplasias Colorrectales , Regulación Neoplásica de la Expresión Génica , Ratones Desnudos , ARN Largo no Codificante , Animales , Humanos , Ratones , Línea Celular Tumoral , Movimiento Celular/genética , Proliferación Celular/genética , Neoplasias Colorrectales/genética , Neoplasias Colorrectales/patología , Subunidades alfa de la Proteína de Unión al GTP G12-G13/genética , Subunidades alfa de la Proteína de Unión al GTP G12-G13/metabolismo , Células HT29 , ARN Largo no Codificante/genética , ARN Largo no Codificante/metabolismo , Regulación hacia ArribaRESUMEN
OBJECTIVE: Our study aimed to assess the ability of high-sensitivity modified Glasgow prognostic Score (HS-mGPS) predicting survival in patients undergoing radical surgery for hepatocellular carcinoma (HCC) and to compare the impact with other Inflammation-Based prognostic scoring systems including Glasgow prognostic Score (GPS) and modified GPS (mGPS). METHODS: Our study evaluated 293 patients with HCC who had undergone hepatectomy at the Third Affiliated Hospital of Soochow University between 2010 and 2018. The HS-mGPS, mGPS, and GPS were calculated based on particular cut-off values of preoperative C-reactive protein and albumin, and the correlations between HS-mGPS and clinicopathological parameters were evaluated. Univariate and multivariate survival analyses were conducted by Kaplan-Meier method and Cox proportional hazards model. To evaluate the discrimination ability of each prognostic score, the receiver operating characteristic (ROC) curve were generated and the areas under the curve (AUC) were measured and compared. RESULT: The study results indicated a correlation between elevated HS-mGPS scores and adverse clinical factors, including higher BCLC stage, C-P grade, multiple tumors, and larger tumor diameter. Kaplan-Meier and univariate survival analyses revealed that higher scores of HS-mGPS, GPS, and mGPS were all associated with significantly reduced overall survival (OS) (all p < 0.001). In multivariate survival analysis, HS-mGPS emerged as an independent risk factor for poor OS in patients undergoing hepatectomy for HCC (p = 0.010), along with factors including maximal tumor diameter (p < 0.001), microvascular invasion (MVI) (p = 0.008), and BCLC stage (p = 0.001). The analysis of ROC curves and the AUC values indicated that HS-mGPS outperforms GPS and mGPS in predicting the long-term prognosis of patients with resectable HCC. CONCLUSION: Preoperative HS-mGPS proves superior in predicting adverse long-term outcomes in HCC patients undergoing radical surgery.
Asunto(s)
Carcinoma Hepatocelular , Hepatectomía , Neoplasias Hepáticas , Humanos , Neoplasias Hepáticas/cirugía , Neoplasias Hepáticas/mortalidad , Neoplasias Hepáticas/patología , Neoplasias Hepáticas/sangre , Carcinoma Hepatocelular/cirugía , Carcinoma Hepatocelular/mortalidad , Carcinoma Hepatocelular/patología , Carcinoma Hepatocelular/sangre , Masculino , Femenino , Persona de Mediana Edad , Pronóstico , Anciano , Estudios Retrospectivos , Adulto , Estimación de Kaplan-Meier , Tasa de Supervivencia , Proteína C-Reactiva/análisisRESUMEN
OBJECTIVE: This study aimed to investigate the underlying molecular mechanisms of Withaferin A (WA) in hepatocellular carcinoma (HCC). MATERIALS AND METHODS: The gene and protein expression were analyzed using RT-qPCR and western blot, respectively. The proliferation of HCC cells was evaluated by CCK-8 assays. The migrative ability of HCC cells was measured by transwell assays. RESULTS: We revealed that WA suppressed the proliferation and migration of HCC cells and inhibited IGF2BP3 (insulin like growth factor 2 mRNA binding protein 3) expression. IGF2BP3 abundance reversed the reactive oxygen species (ROS) accumulation and suppression of HCC cell proliferation and migration induced by WA. Besides, IGF2BP3 suppressed ROS production to promote the growth and migration of HCC cells. Furthermore, we found that IGF2BP3 exerted its tumor-promotive and ROS-suppressive effect on HCC cells by regulating the expression of FOXO1 (forkhead box O1). In addition, IGF2BP3-stimulated activation of JAK2 (Janus kinase 2)/STAT3 (signal transducer and activator of transcription 3) phosphorylation effectively decreased the transcription of FOXO1. FOXO1 abundance decreased the phosphorylation of JAK2 and STAT3 by increasing ROS level, forming a feedback loop for the inhibition of JAK2/STAT3 signaling activated by IGF2BP3. CONCLUSIONS: WA-induced ROS inhibited HCC cell growth and migration through the inhibition of IGF2BP3 to deactivate JAK2/STAT3 signaling, resulting in increased FOXO1 expression to further stimulate ROS production and inhibit JAK2/STAT3 signaling.
Asunto(s)
Carcinoma Hepatocelular , Neoplasias Hepáticas , Witanólidos , Humanos , Carcinoma Hepatocelular/patología , Janus Quinasa 2/metabolismo , Especies Reactivas de Oxígeno/metabolismo , Neoplasias Hepáticas/patología , Factor de Transcripción STAT3/metabolismo , Proliferación Celular , Línea Celular Tumoral , Apoptosis , Proteína Forkhead Box O1/genética , Proteína Forkhead Box O1/metabolismoRESUMEN
The red imported fire ant (Solenopsis invicta Buren) is a social pest species with a robust reproductive ability that causes extensive damage. Identification of the genes involved in queen fertility is critical in order to better understand the reproductive biology and screening for the potential molecular targets in S. invicta. Here, we used the mRNA deep sequencing (RNA-seq) approach to identify differentially expressed genes (DEGs) in the transcriptomes of three reproductive caste types of S. invicta, including queen (QA) and winged female (FA) and male (MA) ants. The genes that were specific to and highly expressed in the queens were then screened, and the Vg2 and Vg3 genes were chosen as targets to explore their functions in oogenesis and fertility. A minimum of 6.08 giga bases (Gb) of clean reads was obtained from all samples, with a mapping rate > 89.78%. There were 7524, 7133, and 977 DEGs identified in the MA vs. QA, MA vs. FA, and FA vs. QA comparisons, respectively. qRT-PCR was used to validate 10 randomly selected DEGs, including vitellogenin 2 (Vg2) and 3 (Vg3), and their expression patterns were mostly consistent with the RNA-seq data. The S. invicta Vgs included conserved domains and motifs that are commonly found in most insect Vgs. SiVg2 and SiVg3 were highly expressed in queens and winged females and were most highly expressed in the thorax, followed by the fat body, head, and epidermis. Evaluation based on a loss-of-function-based knockdown analysis showed that the downregulation of either or both of these genes resulted in smaller ovaries, less oogenesis, and less egg production. The results of transcriptional sequencing provide a foundation for clarifying the regulators of queen fertility in S. invicta. The functions of SiVg2 and SiVg3 as regulators of oogenesis highlight their importance in queen fecundity and their potential as targets of reproductive disruption in S. invicta control.
Asunto(s)
Hormigas , Vitelogeninas , Animales , Femenino , Masculino , Vitelogeninas/genética , Vitelogeninas/metabolismo , Hormigas de Fuego , Reproducción/genética , Fertilidad/genética , Hormigas/genéticaRESUMEN
BACKGROUND: This study was aimed at comparing the safety and effectiveness of endoscopic ultrasound-guided hepaticogastrostomy (EUS-HGS) and EUS-HGS combined with antegrade stenting (EUS-HGAS) in patients with malignant biliary obstruction (MBO) after failed endoscopic retrograde cholangiopancreatography (ERCP). METHODS: Patients diagnosed with MBO and receiving EUS-HGS or EUS-HGAS from September 2015 to October 2020 were enrolled in this study. Clinical success, complications, reintervention rate, post-operative hospital stay, time to stent dysfunction, and patient death were compared. RESULTS: A total of 45 patients (21 in the EUS-HGAS group and 24 in the EUS-HGS group) were enrolled in this study. In the EUS-HGAS group, 21 patients all achieved clinical success (100%); in the EUS-HGS group, 24 patients also achieved technical success (100%) (P > 0.05). The differences between pre- and post-operative TB and ALT and AST levels were greater in the single-step EUS-HGAS group (P < 0.05). The incidence of complications was 2 of 21 (9.5%) in the EUS-HGAS group and 5 of 24 (20.8%) in the EUS-HGS group (P > 0.05). The reintervention rate was 0 in the EUS-HGAS group and 1 (4.2%) in the EUS-HGS group (P > 0.05). Time to stent dysfunction or patient death was longer in the EUS-HGAS group (P < 0.05). The post-operative hospital stay was longer and the total cost was higher in the EUS-HGAS group. CONCLUSION: EUS-HGAS was superior to EUS-HGS in terms of biliary drainage effectiveness and time to stent dysfunction or patient death in patients with MBO after failed ERCP. Furthermore, two-step EUS-HGAS may be safer in some patients.
Asunto(s)
Colangiopancreatografia Retrógrada Endoscópica , Colestasis , Colangiopancreatografia Retrógrada Endoscópica/efectos adversos , Colestasis/etiología , Colestasis/cirugía , Drenaje/efectos adversos , Endosonografía/efectos adversos , Humanos , Stents/efectos adversos , Ultrasonografía Intervencional/efectos adversosRESUMEN
Although the diagnosis and therapy approach developed, techniques for the early diagnosis of HCC remain insufficient which results in poor prognosis of patients. The traditional biomarker AFP, however, has been proved with low specificity. Circulating exosomal ncRNAs revealed different profiles reflecting the characteristics of tumour. In this study, we mainly focused on circulating exosomal ncRNAs which might be the fingerprint for HCC, especially for the diagnosis or metastasis prediction. A high throughput lncRNA microarray in exosomes extracted from cell-free plasma was applied. The risk score analysis was employed to screen the potential exosome-derived lncRNAs in two independent sets based on different clinical parameters in 200 paired HCC patients. After a multi-stage validation, we finally revealed three lncRNAs, ENSG00000248932.1, ENST00000440688.1 and ENST00000457302.2, increased in HCC comparing with the both chronic hepatitis (CH) patients and cancer-free controls. ROC curve revealed a higher sensitivity and specificity in predicting the occurrence of HCC from cancer-free controls and CH patients with the area under curve (AUC) of 0.905 and 0.879 by combining AFP. The three lncRNA panel combined with AFP also indicted a fingerprint function in predicting the metastasis of HCC with the AUC of 0.870. In conclusion, ENSG00000248932.1, ENST00000440688.1 and ENST00000457302.2 might be the potential biomarker for the tumorigenesis prediction from CH patients or healthy controls and may also be applied for dynamic monitoring the metastasis of HCC.
Asunto(s)
Biomarcadores de Tumor/genética , Carcinoma Hepatocelular/secundario , Exosomas/genética , Neoplasias Hepáticas/patología , ARN Largo no Codificante/genética , Biomarcadores de Tumor/sangre , Carcinogénesis , Carcinoma Hepatocelular/sangre , Carcinoma Hepatocelular/genética , Estudios de Casos y Controles , Estudios de Seguimiento , Humanos , Neoplasias Hepáticas/sangre , Neoplasias Hepáticas/genética , Metástasis de la Neoplasia , Pronóstico , ARN Largo no Codificante/sangre , Curva ROCRESUMEN
This study aimed to determine long non-coding RNA (lncRNA) small nucleolar RNA host gene 14 (SNHG14) expression in pancreatic cancer and to explore the potential molecular actions of SNHG14 in mediating pancreatic cancer progression. Gene expression was detected by quantitative real-time PCR. Cell proliferation, growth and invasion were detected by respective CCK-8, colony formation, and transwell invasion assays. Protein levels were measured by Western blotting. Cell apoptosis and caspase-3 activity were detected by flow cytometry and caspase-3 activity assay. The link between miR-613 and its targets was evaluated by luciferase reporter assay. In vivo tumour growth was evaluated using a xenograft model of nude mice. SNHG14 expression was up-regulated in cancerous tissues from pancreatic cancer patients. High expression of SNHG14 was associated with poor tumour differentiation, advanced TNM stage and nodal metastasis. SNHG14 overexpression enhanced cell proliferative, growth and invasive abilities, and suppressed apoptotic rates and caspase-3 activity in pancreatic cancer cells, while SNHG14 knockdown exerted opposite effects. Mechanistic studies revealed that miR-613 was targeted by SNHG14, and Annexin A2 (ANXA2) was targeted and inversely regulated by miR-613 in pancreatic cancer cells. In vivo studies showed that SNHG14 knockdown attenuated tumour growth. MiR-613 was down-regulated and ANXA2 was up-regulated in the pancreatic cancer tissues, and SNHG14 expression levels were inversely correlated with miR-613 expression levels and positively correlated with the ANXA2 mRNA expression levels. Collectively, our results suggest that SNHG14 potentiates pancreatic cancer progression through modulation of annexin A2 expression via acting as a competing endogenous RNA for miR-613.
Asunto(s)
Anexina A2/metabolismo , Biomarcadores de Tumor/metabolismo , Neoplasias Pancreáticas/patología , ARN Largo no Codificante/genética , Animales , Anexina A2/genética , Apoptosis , Biomarcadores de Tumor/genética , Proliferación Celular , Progresión de la Enfermedad , Femenino , Regulación Neoplásica de la Expresión Génica , Humanos , Masculino , Ratones , Ratones Endogámicos BALB C , Ratones Desnudos , Persona de Mediana Edad , Neoplasias Pancreáticas/genética , Neoplasias Pancreáticas/metabolismo , Pronóstico , Células Tumorales Cultivadas , Ensayos Antitumor por Modelo de XenoinjertoRESUMEN
PURPOSE: Laparoscopic common bile duct exploration (LCBDE) has been widely used to remove common bile duct (CBD) stones. However, surgery is not considered as the first treatment choice for elderly patients with CBD stones because of the potential risk of postoperative complications. This study aims to evaluate the safety and efficiency of LCBDE for elderly patients. METHODS: From April 2011 to October 2016, 265 consecutive patients underwent LCBDE. We performed a retrospective study and divided these patients into 2 groups. The younger group was younger than 70 years old (n = 179), and the elderly group was 70 years old or older (n = 86). We compared patient demographics, clinical characteristics, intraoperative parameters, postoperative complications, and incidence of recurrent stone between the 2 groups. RESULTS: The elderly patients had higher preoperative morbidity of chronic diseases, such as pulmonary diseases, heart diseases, arterial hypertension, and abdominal operation history ( P < .05). There were no significant differences between the 2 groups in terms of operation time, intraoperative blood loss, conversion rate to open surgery, total cost, overall complications, and incidence of recurrent stone ( P > .05). CONCLUSION: LCBDE can also be carried out as a safe and effective approach to remove CBD stones in elderly patients, although they have higher risk of chronic diseases.
Asunto(s)
Procedimientos Quirúrgicos del Sistema Biliar , Coledocolitiasis/cirugía , Conducto Colédoco/cirugía , Laparoscopía , Adulto , Anciano , Procedimientos Quirúrgicos del Sistema Biliar/efectos adversos , Procedimientos Quirúrgicos del Sistema Biliar/métodos , Femenino , Humanos , Laparoscopía/efectos adversos , Laparoscopía/métodos , Masculino , Persona de Mediana Edad , Complicaciones Posoperatorias , Estudios Retrospectivos , Adulto JovenRESUMEN
Tea green leafhoppers (Empoasca spp.) are considered one of the major pests in tea plantations in Asia. They are, however, difficult to monitor due to their size and flying and jumping abilities. In this study, we clarified the identification of the leafhopper species encountered in our study plantations and examined the impacts of sampling methods in estimating population abundance and sex ratio. The natural sex ratio of eggs, nymphs, and adults of tea green leafhopper and the differences between male and female were tested. Despite previous reports that Empoasca vitis (Goethe) was the major leafhopper present in our study area, our results showed that only Empoasca onukii Matsuda was found. Variation in population size over time and bias in sex ratio depending on the sampling methods were found in our monitoring experiments. In general, adult males were more attracted to yellow sticky cards than females. We believe that because female leafhoppers should be the target in pest control, yellow sticky cards may not be the most suitable monitoring or effective control of tea green leafhopper. We demonstrate the importance of understanding the implications of sampling techniques for population estimation and sex ratio bias as well as how temporal variation may affect monitoring results. Precise monitoring should take into consideration the different life histories of male and female.
Asunto(s)
Hemípteros/fisiología , Control de Insectos/métodos , Animales , Camellia sinensis/crecimiento & desarrollo , China , Femenino , Hemípteros/clasificación , Hemípteros/crecimiento & desarrollo , Masculino , Ninfa/crecimiento & desarrollo , Ninfa/fisiología , Óvulo/crecimiento & desarrollo , Óvulo/fisiología , Dinámica PoblacionalRESUMEN
When Chinese coal mines are mining Carboniferous Permian coal seams, the mechanism of water inrush from the roof of the working face usually conforms to the "Upper Three Zones" or "Upper Four Zones" theory. The water inrush passageway is water-conducting fracture zone, and the water inrush position is located in the goaf. However, when mining Jurassic coal seams in Chinese coal mines, the location of water inrush often appears at the head-on working face, above the coal mining machine. Due to the support of the fully mechanized mining support, the roof rock layer cannot collapse and therefore cannot form water-conducting fracture zone. Therefore, the water inrush mechanism cannot be explained by the above two theories. This paper is guided by the Practical Mine Pressure Control Theory, and based on the explanation of the motion forms of bending (pulling) failure movement and shearing (cutting) failure movement, and combined with on-site examples, it is revealed that the passageways leading to from the head-on working face roof in a Jurassic coal seam in the Ordos Basin are splitting zones type, fracture line type and structural fracture type, respectively. Taking the changes in water inflow during the mining process of the 3301 and 3302 working faces in Zhujiamao Coal Mine as examples, this paper reveals the mechanism of water inrush from the head-on working face roof caused by splitting zones type, and proves the existence of this passageway through on-site 3D high-density electrical detection and tracing experiments. Taking two catastrophic water inrush accidents that occurred head-on in the 1309 working face of Guojiahe Coal Industry Co., Ltd. as examples, the water inrush mechanism of the fracture line type and the water inrush mechanism of the structural fracture type were respectively revealed. Based on mechanism of water inrush from head-on roof of working face and the analysis of the on-site water inrush process, a method for distinguishing the type of water inrush passageway from the front roof of the working face is proposed. The results indicate that the Jurassic coal seam mining in the Ordos Basin is prone to shearing (cutting) failure movement, resulting in the frequent formation of the three types of water inrush passageways mentioned above.
RESUMEN
Although circular RNAs (circRNA) have been demonstrated to modulate tumor initiation and progression, their roles in the proliferation of hepatocellular carcinoma (HCC) are still poorly understood. Based on the analysis of GEO data (GSE12174), hsa-circRNA-0015004 (circ-0015004) was screened and validated in 80 sets of HCC specimens. Subcellular fractionation analysis was designed to determine the cellular location of circ-0015004. Colony formation and cell counting kit-8 were performed to investigate the role of circ-0015004 in HCC. Dual-luciferase reporter gene assays, RNA immunoprecipitation and chromatin immunoprecipitation were employed to verify the interaction among circ-0015004, miR-330-3p and regulator of chromatin condensation 2 (RCC2). The expression level of circ-0015004 was significantly upregulated in HCC cell lines and HCC tissues. HCC patients with higher circ-0015004 levels displayed shorter overall survival, and higher tumor size and TNM stage. Moreover, knockdown of circ-0015004 significantly reduced HCC cell proliferation in vitro and inhibited the growth of HCC in nude mice. Mechanistic studies revealed that circ-0015004 could upregulate the expression of RCC2 by sponging miR-330-3p, thereby promoting HCC cell proliferation. Furthermore, we identified that Ying Yang 1 (YY1) could function as an important regulator of circ-0015004 transcription. This study systematically demonstrated the novel regulatory signaling of circ-0015004/miR-330-3p/RCC2 axis in promoting HCC progression, providing insight into HCC diagnosis and treatment from bench to clinic.
Asunto(s)
Carcinoma Hepatocelular , Proliferación Celular , Regulación Neoplásica de la Expresión Génica , Factores de Intercambio de Guanina Nucleótido , Neoplasias Hepáticas , MicroARNs , ARN Circular , Humanos , Carcinoma Hepatocelular/genética , Carcinoma Hepatocelular/patología , Carcinoma Hepatocelular/metabolismo , ARN Circular/genética , ARN Circular/metabolismo , Neoplasias Hepáticas/genética , Neoplasias Hepáticas/patología , Neoplasias Hepáticas/metabolismo , Animales , MicroARNs/genética , MicroARNs/metabolismo , Proliferación Celular/genética , Ratones , Línea Celular Tumoral , Masculino , Femenino , Factores de Intercambio de Guanina Nucleótido/genética , Factores de Intercambio de Guanina Nucleótido/metabolismo , Proteínas de Ciclo Celular/genética , Proteínas de Ciclo Celular/metabolismo , Ratones Desnudos , Persona de Mediana Edad , Factor de Transcripción YY1/metabolismo , Factor de Transcripción YY1/genética , Regulación hacia Arriba , ARN Endógeno Competitivo , Proteínas Cromosómicas no HistonaRESUMEN
PURPOSE: Long noncoding RNAs (lncRNAs) exert a significant influence on various cancer-related processes through their intricate interactions with RNAs. Among these, lncRNA ZFAS1 has been implicated in oncogenic roles in multiple cancer types. Nevertheless, the intricate biological significance and underlying mechanism of ZFAS1 in the initiation and progression of hepatocellular carcinoma (HCC) remain largely unexplored. METHODS: Analysis of The Cancer Genome Atlas Program (TCGA) database revealed a notable upregulation of lncRNA ZFAS1 in HCC tissues. To explore its function, we investigated colony formation and performed CCK-8 assays to gauge cellular proliferation and wound healing, Transwell assays to assess cellular migration, and an in vivo study employing a nude mouse model to scrutinize tumor growth and metastasis. Luciferase reporter assay was used to confirm the implicated interactions. Rescue experiments were conducted to unravel the plausible mechanism underlying the activation of the PI3K/AKT pathway by lncRNAs ZFAS1 and ATIC. RESULTS: ZFAS1 and ATIC were significantly upregulated in the HCC tissues and cells. ZFAS1 knockdown inhibited cell proliferation and migration. We observed a direct interaction between the lncRNA ZFAS1 and ATIC. ATIC knockdown also suppressed cell proliferation and migration. SC79, an activator of AKT, partially restores the effects of lncRNA ZFAS1/ATIC knockdown on cell proliferation and migration. Knockdown of lncRNA ZFAS1/ATIC inhibited tumor growth and lung metastasis in vivo. CONCLUSION: Overall, lncRNA ZFAS1 regulates ATIC transcription and contributes to the growth and migration of HCC cells through the PI3K/AKT signaling pathway.
Asunto(s)
Carcinoma Hepatocelular , Movimiento Celular , Proliferación Celular , Neoplasias Hepáticas , Fosfatidilinositol 3-Quinasas , Proteínas Proto-Oncogénicas c-akt , ARN Largo no Codificante , Transducción de Señal , Animales , Femenino , Humanos , Masculino , Ratones , Factores de Transcripción con Motivo Hélice-Asa-Hélice Básico/genética , Factores de Transcripción con Motivo Hélice-Asa-Hélice Básico/metabolismo , Carcinoma Hepatocelular/genética , Carcinoma Hepatocelular/patología , Carcinoma Hepatocelular/metabolismo , Línea Celular Tumoral , Movimiento Celular/genética , Proliferación Celular/genética , Regulación Neoplásica de la Expresión Génica , Neoplasias Hepáticas/genética , Neoplasias Hepáticas/patología , Neoplasias Hepáticas/metabolismo , Ratones Endogámicos BALB C , Ratones Desnudos , Fosfatidilinositol 3-Quinasas/metabolismo , Fosfatidilinositol 3-Quinasas/genética , Proteínas Proto-Oncogénicas c-akt/metabolismo , Proteínas Proto-Oncogénicas c-akt/genética , ARN Largo no Codificante/genética , Transducción de Señal/genéticaRESUMEN
Background: Liver cancer remains to be one of the leading causes of cancer worldwide. The treatment options face several challenges and nanomaterials have proven to improve the bioavailability of several drug candidates and their applications in nanomedicine. Specifically, chitosan nanoparticles (CNPs) are extremely biodegradable, pose enhanced biocompatibility and are considered safe for use in medicine. Methods: CNPs were synthesized by ionic gelation, loaded with rutin (rCNPs) and characterized by ultraviolet-visible spectroscopy (UV-Vis), Fourier-transform infrared spectroscopy (FTIR), dynamic light scattering (DLS) and transmission electron microscopy (TEM). The rCNPs were tested for their cytotoxic effects on human hepatoma Hep3B cells, and experiments were conducted to determine the mechanism of such effects. Further, the biocompatibility of the rCNPs was tested on L929 fibroblasts, and their hemocompatibility was determined. Results: Initially, UV-vis and FTIR analyses indicated the possible loading of rutin on rCNPs. Further, the rutin load was quantitatively measured using Ultra-Performance Liquid Chromatography (UPLC) and the concentration was 88 µg/mL for 0.22 micron filtered rCNPs. The drug loading capacity (LC%) of the rCNPs was observed to be 13.29 ± 0.68%, and encapsulation efficiency (EE%) was 19.55 ± 1.01%. The drug release was pH-responsive as 88.58% of the drug was released after 24 hrs at the lysosomal pH 5.5, whereas 91.44% of the drug was released at physiological pH 7.4 after 102 hrs. The cytotoxic effects were prominent in 0.22 micron filtered samples of 5 mg/mL rutin precursor. The particle size for the rCNPs at this concentration was 144.1 nm and the polydispersity index (PDI) was 0.244, which is deemed to be ideal for tumor targeting. A zeta potential (ζ-potential) value of 16.4 mV indicated rCNPs with good stability. The IC50 value for the cytotoxic effects of rCNPs on human hepatoma Hep3B cells was 9.7 ± 0.19 µg/mL of rutin load. In addition, the increased production of reactive oxygen species (ROS) and changes in mitochondrial membrane potential (MMP) were observed. Gene expression studies indicated that the mechanism for cytotoxic effects of rCNPs on Hep3B cells was due to the activation of Unc-51-like autophagy-activating kinase (ULK1) mediated autophagy and nuclear factor kappa B (NF-κB) signaling besides inhibiting the epithelial-mesenchymal Transition (EMT). In addition, the rCNPs were less toxic on NCTC clone 929 (L929) fibroblasts in comparison to the Hep3B cells and possessed excellent hemocompatibility (less than 2% of hemolysis). Conclusion: The synthesized rCNPs were pH-responsive and possessed the physicochemical properties suitable for tumor targeting. The particles were effectively cytotoxic on Hep3B cells in comparison to normal cells and possessed excellent hemocompatibility. The very low hemolytic profile of rCNPs indicates that the drug could be administered intravenously for cancer therapy.
Asunto(s)
Autofagia , Carcinoma Hepatocelular , Quitosano , Neoplasias Hepáticas , FN-kappa B , Nanopartículas , Rutina , Transducción de Señal , Rutina/farmacología , Rutina/química , Rutina/administración & dosificación , Rutina/farmacocinética , Quitosano/química , Quitosano/farmacología , Humanos , FN-kappa B/metabolismo , Carcinoma Hepatocelular/tratamiento farmacológico , Carcinoma Hepatocelular/patología , Carcinoma Hepatocelular/metabolismo , Nanopartículas/química , Neoplasias Hepáticas/tratamiento farmacológico , Neoplasias Hepáticas/patología , Autofagia/efectos de los fármacos , Línea Celular Tumoral , Transducción de Señal/efectos de los fármacos , Transición Epitelial-Mesenquimal/efectos de los fármacos , Ratones , Animales , Portadores de Fármacos/química , Portadores de Fármacos/farmacología , Supervivencia Celular/efectos de los fármacosRESUMEN
OBJECTIVE: To investigate the safety and application value of combining Laennec extracapsular occlusion with ICG fluorescence imaging in laparoscopic anatomic hepatectomy. METHODS: Complete laparoscopic dissection was performed outside the Laennec sheath, blocking Glisson's pedicle of the corresponding liver segment or lobe. An appropriate amount of indocyanine green (ICG) dye was intravenously injected, and the boundary line between the pre-cut liver segment and liver lobe was identified using fluorescence laparoscopy. Complete resection of the liver segment or lobe was performed based on anatomical markers. Clinical data, including operation time, intraoperative blood loss, postoperative hospital stay, and postoperative complications, were collected. RESULTS: A total of 14 cases were included in the study, including seven cases of primary liver cancer, three cases of metastatic liver cancer, three cases of intrahepatic bile duct calculi, and one case of hepatic hemangioma. All 14 patients underwent anatomic hepatectomy under fluorescent laparoscopy, with four cases involving the right liver, seven cases involving the left liver, two cases involving the right anterior lobe, and one case involving the right posterior lobe. CONCLUSION: Combining laparoscopic follow-up of the Laennec membrane with Glisson outer sheath block and intraoperative ICG fluorescence imaging provides real-time guidance for locating the resection boundaries during anatomic hepatectomy. This approach helps in controlling intraoperative bleeding, reducing operation time, and ensuring high safety. It holds significant value in clinical application.
Asunto(s)
Laparoscopía , Neoplasias Hepáticas , Humanos , Hepatectomía/métodos , Verde de Indocianina , Laparoscopía/métodos , Neoplasias Hepáticas/diagnóstico por imagen , Neoplasias Hepáticas/cirugía , Neoplasias Hepáticas/patología , Imagen Óptica/métodosRESUMEN
The red imported fire ant (Solenopsis invicta Buren) is a highly adaptable invasive species that can nest and reproduce in different habitat soils. We aimed to explore the adaptability of red imported fire ants in different habitats by analyzing changes in the physicochemical properties of nest soils and bacterial communities. Five habitat types (forest, tea plantation, rice field, lawn, and brassica field) were selected. The results showed that the pH of the nest soils increased significantly in all five habitats compared to the control soils of the same habitat. A significant increase in nitrogen content was detected in the nests. The Cr, Pb, Cu, and Ni levels were significantly reduced in the soils of the five habitats, due to nesting activities. Analysis of the composition and diversity of the soil microbial community showed that, although the richness and diversity of bacteria in the nest soils of red imported fire ants in the five habitats varied, the relative abundance of Actinobacteria significantly increased and it emerged as the dominant bacterial group. These results indicate that red imported fire ants modify the physicochemical properties of nest soils and bacterial communities to create a suitable habitat for survival and reproduction.
RESUMEN
In the view of the situation where great economic loss often occurs during mining deep coal seams in Feicheng coal field due to water inrush from the floor Ordovician limestone aquifer, the floor "lower four-zone" theory was used as a guide. 81006 working face of Caozhuang Coalmine in Feicheng coal field was taken as the research background, and paste filling technology was proposed to inhibit or reduce the damaged floor depth caused by mine ground pressure in order to prevent water inrush from the floor Ordovician limestone aquifer. Glue material, coal gangue powder, and fly ash were selected as filling material, and a ground filling system, including a material production system, storage material system, power supply and water supply system, automatic control and measurement system, monitoring and control communications system, emergency response system, and underground filling system, including pipe conveyor system and working face blocking grout loss system, were established to achieve effective filling goaf. Field stress monitoring and floor damaged depth measurement showed that when reaching a steady state after a period of time, paste filling working face not only restored to the original stress state but also significantly reduced the floor's damaged depth caused by mine ground pressure. This verifies that working face with paste-like backfill technology is a very effective measure to prevent water-inrush from the floor.
RESUMEN
BACKGROUND: Light stimulation at a specific wavelength triggers various responses in insects and can be used for pest control. To develop efficient and ecofriendly photophysical pest control methods, the effects of green light on locomotion, growth (molting and eclosion) and reproduction in Nilaparvata lugens (Stål) (BPH), a major rice pest, were studied. Transcriptomics and transmission electron microscopy (TEM) were used to investigate the mechanisms involved. RESULTS: BPH adults showed disrupted daily locomotion patterns following green light treatment at night and exhibited abnormal locomotion peaks. Total 6-day locomotion of brachypterous adults was significantly greater than in the control group. The durations of growth stages 1-4 were all shorter under green light treatment than in the control, whereas the time from fourth molting to eclosion (stage 5) was significantly longer. When BPH adults under green light treatment began laying eggs, the egg hatching ratio (36.69%) was significantly lower than in the control (47.49%). Moreover, in contrast to the control, BPH molting and eclosion events tended to happen more at night. Transcriptome analysis proved that green light significantly affected the expression of genes involved in cuticular proteins, chitin deacetylase and chitinase, which are related to cuticular development. TEM observations confirmed abnormal cuticular development in nymph and adult BPHs (endocuticle, exocuticle and pore canals) under green light treatment. CONCLUSION: Green light treatment at night notably affected locomotion, growth and reproduction in BPH, thus providing a novel idea for controlling this pest. © 2023 Society of Chemical Industry.
Asunto(s)
Hemípteros , Oryza , Animales , Hemípteros/fisiología , Ninfa , ReproducciónRESUMEN
The diversity of root endophytic microorganisms, which is closely related to plant life activities, is known to vary with the plant growth stage. This study on the ratooning rice Jiafuzhan explored the diversity of the root endophytic bacteria and fungi and their dynamics during the plant life cycle. By sequencing the 16S ribosomal ribonucleic acid (16S rRNA) and internal transcribed spacer (ITS) genes, 12,154 operational taxonomic units (OTUs) and 497 amplicon sequence variants (ASVs) were obtained, respectively. The root endophytic microorganisms of rice in the seedling, tillering, jointing, heading, and mature stages of the first crop and at 13, 25, and 60 days after regeneration (at the heading, full heading, and mature stages of the second crop, respectively) were analyzed using diversity and correlation analyses. There were significant differences in the α-diversity and ß-diversity of root endophytic bacteria and fungi in the growth stage. Additionally, linear discriminant analysis (LDA) effect size (LEfSe) analysis revealed biomarker bacteria for each growth stage, but biomarker fungi did not exist in every stage. Moreover, the correlation analysis showed that the bacterial and fungal biomarkers interacted with each other. Furthermore, the nitrogen-fixing genus Bradyrhizobium existed in all growth stages. These findings indicate the pattern of root endophytic microorganisms of ratooning rice at different growth stages, and they provide new insights into the high yield of the second crop of ratooning rice (in light of the abundance of various bacteria and fungi).
RESUMEN
CD8+Tregs are important immunoregulatory cells that participate in immunopathological processes in many diseases. Rapamycin (Rapa) is a macrolide immunosuppressant that inhibits the mammalian target of rapamycin (mTOR) and has been shown to improve CD4+-induced Tregs (iTregs) generation. This study aimed to evaluate the role of Rapa in the generation and function of CD8+iTregs. Human CD8 + CD25-CD45RA + T cells were divided into two groups, one with Rapa and the other without Rapa, and both groups were cultured under Treg-induced conditions. Rapa significantly improved Foxp3 expression and the suppressive function of CD8+iTregs in vitro. Further studies showed that Rapa suppressed inflammatory cytokine expression and enhanced anti-inflammatory cytokine expression. Under inflammatory conditions in vitro, Rapa-CD8 + iTregs sustained Foxp3 and anti-inflammatory cytokine expression. An in-depth study showed that Rapa regulated CpG demethylation in the Foxp3 region and STAT1 and STAT3 phosphorylation in CD8+iTregs. Finally, we compared the regulatory ability of Rapa and all-trans retinoic acid, another reagent that stimulates CD4+ iTreg generation in vitro, which showed that Rapa, but not all-trans retinoic acid, improved CD8+ iTreg induction and suppressed CD4+T cell expansion in vitro and protected against graft-versus-host disease in a humanized murine model in vivo. These results strongly suggest that CD8+iTregs initiated by Rapa may represent a new therapeutic strategy for inflammatory and autoimmune diseases.