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Transcriptome sequencing was employed to mine the simple sequence repeat(SSR) locus information of Saposhnikovia divaricata and design specific primers, which aimed to provide a basis for the research on the genetic diversity of S. divaricata germplasm resources. The seed purity, 1 000-seed weight, germination rate, and seed vigor were determined. MISA was used to obtain the SSR locus information from 12 606 unigene longer than 1 kb in the transcriptome database. Forty-three pairs of SSR primers designed in Primer 3 were used to analyze the polymorphism of 28 S. divaricata samples of different sources. The results showed that there were differences in the seed purity, 1 000-seed weight, germination rate, vigor, and seed length and width among S. divaricata samples of different sources. Particularly, the germination rate and seed vigor had significant differences, and HB-ZJK1, NMG-CF4, NMG-BT, NMG-HLE1, and NMG-CF2 had significantly higher 1 000-seed weight, germination rate, and seed vigor than the samples of other sources. Among the 86 233 unigene, 12 606(14.62%) unigene contained 15 958 SSR loci, with one SSR locus every 5 009 bp on average. The SSR loci were mainly single nucleotide and dinucleotide repeats, which were dominated by G/C and TC/AG, respectively. All the primers were screened by using 28 S. divaricata sample from different habitats, and the primers corresponding to the amplification products with clear bands and stable polymorphism were obtained. The clustering results of the biological characteristics and genetic diversity of the 28 S. divaricata samples were basically consistent, and the samples of the same origin(HB-AG1, HB-AG2, HB-ZJK1, and HB-ZJK2) generally gathered together and had close genetic relationship. The SSRs in S. divaricata transcriptome has high frequency, rich types, and high polymorphism, which provides candidate molecular markers for the germplasm identification, genetic map construction, and molecular-assisted breeding.
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Apiaceae , Transcriptoma , Polimorfismo Genético , Repeticiones de Microsatélite/genética , Apiaceae/genética , Etiquetas de Secuencia ExpresadaRESUMEN
In this work, we utilized the molecular hybridization strategy to design and synthesize novel 1,2,3-triazole benzothiazole derivatives K1-26. The antiproliferative activities against MGC-803, Kyse30 and HCT-116 cells were explored, and their structure-activity relationship were preliminarily conducted and summarized. Among them, compound K18, exhibited the strongest proliferation inhibitory activity, with esophageal cancer cells Kyse30 and EC-109 being the most sensitive to its effects (IC50 values were 0.042 and 0.038 µM, respectively). Compound K18 effectively inhibited tubulin polymerization (IC50 = 0.446 µM), thereby hindering tubulin polymerize into filamentous microtubules in Kyse30 and EC-109 cells. Additionally, compound K18 induced the degradation of oncogenic protein YAP via the UPS pathway. Based on these dual molecular-level effects, compound K18 could induce G2/M phase arrest and cell apoptosis in Kyse30 and EC-109 cells, as well as regulate the expression levels of cell cycle and apoptosis-related proteins. In summary, our findings highlight a novel 1,2,3-triazole benzothiazole derivative K18, which possesses significant potential for treating esophageal cancers.
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Antineoplásicos , Neoplasias Esofágicas , Melfalán , gammaglobulinas , Humanos , Moduladores de Tubulina , Tubulina (Proteína)/metabolismo , Línea Celular Tumoral , Ensayos de Selección de Medicamentos Antitumorales , Proliferación Celular , Relación Estructura-Actividad , Benzotiazoles/farmacología , Triazoles/farmacología , Neoplasias Esofágicas/tratamiento farmacológico , Polimerizacion , Estructura MolecularRESUMEN
Vascular remodeling plays a vital role in hypertensive diseases and is an important target for hypertension treatment. Irisin, a newly discovered myokine and adipokine, has been found to have beneficial effects on various cardiovascular diseases. However, the pharmacological effect of irisin in antagonizing hypertension-induced vascular remodeling is not well understood. In the present study, we investigated the protection and mechanisms of irisin against hypertension and vascular remodeling induced by angiotensin II (Ang II). Adult male mice of wild-type, FNDC5 (irisin-precursor) knockout, and FNDC5 overexpression were used to develop hypertension by challenging them with Ang II subcutaneously in the back using a microosmotic pump for 4 weeks. Similar to the attenuation of irisin on Ang II-induced VSMCs remodeling, endogenous FNDC5 ablation exacerbated, and exogenous FNDC5 overexpression alleviated Ang II-induced hypertension and vascular remodeling. Aortic RNA sequencing showed that irisin deficiency exacerbated intracellular calcium imbalance and increased vasoconstriction, which was parallel to the deterioration in both ER calcium dysmetabolism and ER stress. FNDC5 overexpression/exogenous irisin supplementation protected VSMCs from Ang II-induced remodeling by improving endoplasmic reticulum (ER) homeostasis. This improvement includes inhibiting Ca2+ release from the ER and promoting the re-absorption of Ca2+ into the ER, thus relieving Ca2+-dependent ER stress. Furthermore, irisin was confirmed to bind to its receptors, αV/ß5 integrins, to further activate the AMPK pathway and inhibit the p38 pathway, leading to vasoprotection in Ang II-insulted VSMCs. These results indicate that irisin protects against hypertension and vascular remodeling in Ang II-challenged mice by restoring calcium homeostasis and attenuating ER stress in VSMCs via activating AMPK and suppressing p38 signaling.
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Angiotensina II , Hipertensión , Ratones , Masculino , Animales , Angiotensina II/metabolismo , Fibronectinas/metabolismo , Proteínas Quinasas Activadas por AMP/metabolismo , Remodelación Vascular , Calcio/metabolismo , Músculo Liso Vascular/metabolismo , Estrés del Retículo EndoplásmicoRESUMEN
Colorectal cancer (CRC), classified as a lethal form of cancer, substantially threatens human well-being. Cancer stem cells (CSCs) reflect subsets for cancerous cells having basic stem-cell type properties, being significantly involved in the development of chemoresistance and tumor relapsing. The aberrant TRIM27 expression in various types of cancer indicates its potential involvement in cancer growth and progression. The current understanding of the TRIM27 involvement in CRC remains limited. In current study indicated that TRIM27 can potentially promote CSC-type phenotype of Cisplatin (DDP)-resistant CRC cells. YTHDF1 recruitment onto m6A-amended TRIM27 was crucial for facilitating the TRIM27 translating process in DDP-resistant CRC cells. The present research proposes that TRIM27 exhibits an oncogenic role by enhancing the CSC-type properties in DDP-resistant CRC via the m6A-modified pathway. The potential therapy for combating the relapse of CRC may include TRIM27 and YTHDF1, as they have been found to have significant roles in promoting CSC-type phenotypic characteristics.
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Nowadays, great uncertainty still exists on the urban- and regional-scale anthropogenic CO2 emission estimation based on emission inventories. In order to achieve the carbon peaking and neutrality targets for China, it is urgent to accurately estimate anthropogenic CO2 emissions at regional scales, especially in large urban agglomerations. Using two inventories (EDGAR v6.0 inventory and a modified inventory combining EDGAR v6.0 with GCG v1.0) as prior anthropogenic CO2 emission datasets andtaking themas input data respectively, this study utilized the WRF-STILT atmospheric transport model to simulate atmospheric CO2 concentration in the Yangtze River Delta region from December 2017 to February 2018. The simulated atmospheric CO2 concentrations were further improved by referencing atmospheric CO2 concentration observation at a tall tower in Quanjiao County of Anhui Province and using the scaling factors obtained from the Bayesian inversion method. An estimation of anthropogenic CO2 emission flux in the Yangtze River Delta regionwas finally accomplished. The results indicated that:â in winter, in comparison to the atmospheric CO2 concentration simulated based on EDGAR v6.0, the atmospheric CO2 concentration simulated based on the modified inventory was more consistent with observed values. â¡The simulated atmospheric CO2 concentration was higher than observation at night and lower than observation during the daytime. The CO2 emission data of emission inventories could not fully reflect the diurnal variation in anthropogenic emissions, andtheoverestimation, caused by the simulated low-atmospheric boundary layer height at night, of the contribution from point sources with higher emission height near the observation station were the main reasons. â¢The simulation performance on atmospheric CO2 concentration was greatly affected by the emission bias of the EDGAR grid points that significantly contributed to concentrations of the observation station, and this indicated that the uncertainty in the spatial distribution in EDGAR emission was the main factor influencing the simulation accuracy. â£The posterior anthropogenic CO2 emission flux in the Yangtze River Delta from December 2017 to February 2018 was around (0.184±0.006) mg·(m2·s)-1and (0.183±0.007) mg·(m2·s)-1 based on EDGAR and the modified inventory, respectively. It is suggested that the inventories with higher temporal and spatial resolutions and more accurate spatial emission distribution should be selected as the prior emissions to obtain a more accurate estimation of the regional anthropogenic CO2 emissions.
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OBJECTIVE: As a high-efficiency demanding department in a hospital, the outpatient pharmacy has a great need for quality improvement to provide superior medical service for patients. Little is known about the application of 5S management in a hospital pharmacy department. The aim of this study was to evaluate the impacts of 5S management on pharmaceutical service quality and staff capacity in the outpatient-emergency pharmacy. METHODS: We carried out a 5S project in the outpatient-emergency pharmacy at a local hospital that involved processes including waste elimination, workplace standardisation, and optimisation of workflow and staff quality, and then evaluated the effects of the project. RESULTS: The equipment and items in the outpatient-emergency pharmacy were sorted. All the drugs were categorised and put in order. The redesigned workspace and standardised workflow during the project improved the accuracy and efficiency of drug dispensing. The satisfaction rate of patients regarding the pharmaceutical service quality in the outpatient-emergency pharmacy was elevated, as well as the satisfaction rate of pharmacists about their work experiences. The optimisation of objective conditions also stimulated a positive working attitude and professional ability promotion of pharmacists in the outpatient-emergency pharmacy. CONCLUSIONS: In this study, the 5S management method has proven useful for quality and efficiency improvement in the outpatient-emergency pharmacy, and could be generalised to other departments in a hospital, which provides further evidence of the advantages of the Lean tool in healthcare system management.
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BACKGROUND: Liver dysfunction and liver failure are serious complications of sepsis, directly leading to septic progression and death. Now, there is no specific therapeutics available for sepsis-related liver dysfunction. Prim-O-glucosylcimifugin (POG), a chromone richest in the roots of Saposhnikovia divaricata (Turcz.) Schischk, is usually used to treat headache, rheumatoid arthritis and tetanus. While, the underlying mechanisms of POG against sepsis-induced liver damage and dysfunction are still not clear. PURPOSE: To study the anti-sepsis effect of POG, and its pharmacological mechanism to protect liver injury by weakening the function of macrophages in septic livers through inhibiting NOD-like receptor protein 3 (NLRP3) inflammasome pathway. METHOD: In vivo experiments, septic mouse model was induced by cecal ligation and puncture (CLP), and then the mortality was detected, liver inflammatory damages and plasma biomarkers of liver injury were evaluated by histopathological staining and biochemical assays, respectively. In vitro experiments, mouse primary peritoneal macrophages were treated with lipopolysaccharide (LPS) and ATP, and then the activated-inflammasomes, macrophage migration and polarization were detected by ASC immunofluorescence staining, transwell and flow cytometry assays, respectively. NLRP3 inflammasome components NLRP3, caspase-1, IL-1ß and IL-18 protein expressions were detected using western blot assays, and the contents of IL-1ß and IL-18 were measured by ELISA assays. RESULTS: POG treatment significantly decreased the mortality, liver inflammatory damages, hepatocyte apoptosis and plasma biomarkers of liver injury in CLP-challenged male WT mice, which were comparable to those in ibuprofen (a putative anti-inflammatory drug)-supplemented septic male WT mice and septic NLRP3 deficient-male mice. POG supplementation significantly suppressed NLRP3 inflammasome activation in septic liver tissues and cultured macrophages, by significantly reducing NLRP3, cleaved-caspase-1, IL-1ß and IL-18 levels, the activated-inflammasome ASC specks, and macrophage infiltration and migration, as well as M1-like polarization, but significantly increasing M2-like polarization. These findings were similar to the pharmacological effects of ibuprofen, NLRP3 deficiency, and a special NLRP3 inhibitor, MCC950. CONCLUSION: POG protected against sepsis by inhibiting NLRP3 inflammasome-mediated macrophage activation in septic liver and attenuating liver inflammatory injury, indicating that it may be a potential anti-sepsis drug candidate.
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Inflamasomas , Sepsis , Adenosina Trifosfato , Animales , Caspasa 1/metabolismo , Cromonas , Ibuprofeno , Interleucina-18 , Lipopolisacáridos , Hígado/metabolismo , Macrófagos/metabolismo , Masculino , Ratones , Proteína con Dominio Pirina 3 de la Familia NLR/metabolismo , Proteínas NLR , Sepsis/complicaciones , Sepsis/tratamiento farmacológico , Sepsis/metabolismoRESUMEN
Saposhnikovia divaricata is a commonly used bulk medicinal plant. To explore the key enzyme genes and their expression in the biosynthesis of chromone and coumarin, the key active components, we carried out transcriptome sequencing(Illumina HiSeq) and bioinformatics analysis for the 1-year-old(S1) and 2-year-old(S2) plants of S. divaricata. A total of 40.8 Gb data was obtained. After the sequence assembly via Trinity, 110 732 transcripts and 86 233 unigenes were obtained, which were aligned and annotated with NR, Swiss-Prot, GO, KEGG, and PFAM. Daucus carota and S. divaricata had the highest sequence homology. KEGG pathway enrichment showed that the differentially expressed genes were mainly enriched in plant hormone signal transduction, phenylpropanoid biosynthesis, and flavonoid biosynthesis pathways. A total of 27 differentially expressed unigenes, including 13 enzyme genes, were identified in the pathways related to the synthesis of active ingredients in S. divaricata. Compared with S1 plant, S2 plant showed up-regulated expression of PAL, BGL, C4H, 4CL, CYP98A, CSE, REF, and CCoAOMT and down-regulated expression of CHS, CAD, and COMT. HCT and POD had both up-regulated and down-regulated unigenes. Among them, PAL, C4H, 4CL, BGL, and CHS can be used as candidate genes for the synthesis of the active ingredients in S. divaricata. The four key enzyme genes were verified by RT-qPCR, which showed the results consistent with transcriptome sequencing. This study enriches the genetic information of S. divaricata and provides support for the identification of candidate genes in the biosynthesis of secondary metabolites.
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Apiaceae , Transcriptoma , Apiaceae/genética , Cromonas , Cumarinas , Flavonoides , Perfilación de la Expresión Génica , Regulación de la Expresión Génica de las Plantas , Secuenciación de Nucleótidos de Alto Rendimiento/métodos , Reguladores del Crecimiento de las PlantasRESUMEN
Lung carcinoma is the leading cause of cancer-related death worldwide. Chemotherapy remains the cornerstone of lung cancer treatment. Unfortunately, most types of cancer will develop resistance to chemotherapies over the time. One of the efforts to prevent the chemotherapy resistance is to find alternative chemotherapy drugs. Mogrol has been found to have antitumor activity. However, little is known about the pharmacological mechanisms underlying the suppression of mogrol on lung cancers. In this study, we observed that mogrol exposure significantly reduced the tumor volume and weight in tumor-bearing nude mice without obvious effect on body weight and cardiac function. Mogrol also significantly inhibited the proliferation and migration of lung cancer cells, including non-small-cell lung carcinoma cells, A549, H1299, H1975 and SK-MES-1 cells, with no obvious effect on control human bronchial epithelial cells (HBE). Further studies revealed that mogrol stirred excessive autophagy and autophagic flux, and finally, autophagic cell death, in lung cancer cells, which could be attenuated by autophagy inhibitors, 3-MA and chloroquine. Furthermore, mogrol significantly activated AMPK to induce autophagy and autophagic cell death, which could be abrogated by Compound C, an AMPK inhibitor. In addition, mogrol induced a significant increase in p53 activity in lung cancer cells, accompanied with cell cycle arrest and apoptosis, which could be weakened by p53 silence. Our results indicated that mogrol effectively suppressed lung cancer cells in vivo and in vitro by inducing the excessive autophagy and autophagic cell death via activating AMPK signaling pathway, as well as cell cycle arrest and apoptosis via activating p53 pathway.
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Muerte Celular Autofágica , Carcinoma de Pulmón de Células no Pequeñas , Neoplasias Pulmonares , Proteínas Quinasas Activadas por AMP/metabolismo , Animales , Apoptosis , Autofagia , Carcinoma de Pulmón de Células no Pequeñas/tratamiento farmacológico , Puntos de Control del Ciclo Celular , Línea Celular Tumoral , Proliferación Celular , Pulmón/patología , Neoplasias Pulmonares/metabolismo , Ratones , Ratones Desnudos , Proteína p53 Supresora de Tumor/metabolismoRESUMEN
The PHLDA3 gene encodes a small 127 amino acid protein with a pleckstrin homology (PH)-only domain. The expression and significance of PHLDA3 in lung cancer remain unclear. Here, we investigated the role of PHLDA3 in tumor proliferation and invasion in lung adenocarcinoma. Immunohistochemistry and immunoblotting analyses were used to assess PHLDA3 expression in lung cancer tissues, and its correlation with clinicopathological factors in lung cancer. Plasmids encoding PHLDA3 and small interfering RNA against PHLDA3 were used to regulate the expression of PHLDA3 in lung cancer cells. Furthermore, the effects of PHLDA3 on lung cancer cell proliferation and invasion were investigated using the MTS, colony formation, Matrigel invasion, and wound healing assays. Co-immunoprecipitation analysis and inhibitors of both the Wnt signaling pathway and GSK3ß were used to explore the regulatory mechanisms underlying the role of PHLDA3 in lung cancer cells. PHLDA3 was found to be overexpressed in lung cancer tissues, and its expression was correlated with poor outcomes in lung adenocarcinoma patients. PHLDA3 expression promoted the proliferation, invasion, and migration of lung cancer cells. Overexpression of PHLDA3 activated the Wnt signaling pathway and facilitated epithelial-mesenchymal transition. Inhibition of Wnt signaling pathway activity, using XAV-939, reversed the effects of PHLDA3 overexpression in lung cancer cells; moreover, PHLDA3 could bind to GSK3ß. Inhibition of GSK3ß activity, using CHIR-99021, restored the proliferative and invasive abilities of PHLDA3 knockdown cells. Our findings demonstrate that PHLDA3 is highly expressed in lung adenocarcinomas and is correlated with poor outcomes. Furthermore, it promotes the proliferation and invasion of lung cancer cells by activating the Wnt signaling pathway.
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Adenocarcinoma del Pulmón , Neoplasias Pulmonares , Proteínas Nucleares , Vía de Señalización Wnt/genética , Adenocarcinoma del Pulmón/genética , Adenocarcinoma del Pulmón/metabolismo , Adenocarcinoma del Pulmón/patología , Línea Celular Tumoral , Proliferación Celular , Femenino , Humanos , Pulmón/patología , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/metabolismo , Neoplasias Pulmonares/patología , Masculino , Persona de Mediana Edad , Invasividad Neoplásica/genética , Proteínas Nucleares/genética , Proteínas Nucleares/metabolismoRESUMEN
Intelligent identification of black tea fermentation quality is becoming a bottleneck to industrial automation. This study presents at-line rapid detection of black tea fermentation quality at industrial scale based on low-cost micro-near-infrared spectroscopy (NIRS) and laboratory-made computer vision system (CVS). High-performance liquid chromatography and a spectrophotometer were used for determining the content of catechins and theaflavins, and the color of tea samples, respectively. Hierarchical cluster analysis combined with sensory evaluation was used to group samples through different fermentation degrees. A principal component analysis-support vector machine (SVM) model was developed to discriminate the black tea fermentation degree using color, spectral, and data fusion information; high accuracy (calibration = 95.89%, prediction = 89.19%) was achieved using mid-level data fusion. In addition, SVM model for theaflavins content prediction was established. The results indicated that the micro-NIRS combined with CVS proved a portable and low-cost tool for evaluating the black tea fermentation quality.
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Análisis de los Alimentos/métodos , Industria de Procesamiento de Alimentos/métodos , Espectroscopía Infrarroja Corta/métodos , Té , Biflavonoides/análisis , Calibración , Camellia sinensis/química , Catequina/análisis , Cromatografía Líquida de Alta Presión , Color , Fermentación , Análisis de los Alimentos/instrumentación , Análisis de Componente Principal , Espectroscopía Infrarroja Corta/instrumentación , Máquina de Vectores de Soporte , Té/química , Té/microbiologíaRESUMEN
DEK proto-oncogene (DEK) has been demonstrated as an oncogene and is associated with the development of many types of tumor; however, the expression and role of DEK in breast cancer remain unknown. The present study aimed to determine the role of DEK in the progression of breast cancer. The expression of DEK in 110 breast cancer tissues and 50 adjacent normal breast tissues was examined using immunohistochemistry. Furthermore, DEK expression was upregulated by DEK transfection or downregulated by DEK shRNA interference in MCF7 cells. Proliferative and invasive abilities were examined in MCF7 cells using MTT assay, colony-formation assay and transwell invasion assays. The results demonstrated that DEK expression level was significantly increased in breast cancer tissues compared with normal breast tissues. Furthermore, high DEK expression was associated with high histological grade, lymph node metastasis, advanced Tumor-Node-Metastasis stage and high Ki-67 index; however, DEK expression was not associated with the expression level of estrogen receptor, progesterone receptor, and human epidermal growth factor receptor 2. High DEK expression indicated poor prognosis in patients with breast cancer. DEK overexpression upregulated the protein expression of ß-catenin and Wnt and increased the proliferative and invasive abilities of breast cancer cells. DEK downregulation had the opposite effect. Taken together, the results from the present study demonstrated that high expression of DEK was common in patients with breast cancer and was associated with progression of the disease and poor prognosis, and that DEK overexpression promoted the proliferative and invasive abilities of breast cancer cells.
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Iron (Fe) is an essential element for plant growth, development and metabolism. Due to its lack of solubility and low bioavailability in soil, Fe levels are usually far below the optimum amount for most plants' growth and development. In apple production, excessive use of nitrogen fertilizer may cause iron chlorosis symptoms in the newly growing leaves, but the regulatory mechanisms underlying this phenomenon are unclear. In this study, low nitrate (NO3- , LN) application alleviated the symptoms of Fe deficiency and promoted lower rhizosphere pH, which was beneficial for root Fe acquisition. At the same time, LN treatment increased citrate and abscisic acid accumulation in roots, which promoted Fe transport from root to shoot and maintained Fe homeostasis. Moreover, qRT-PCR analysis showed that nitrate application caused differential expression of genes related to Fe uptake and transport, as well as transcriptional regulators. In summary, our data reveal that low nitrate alleviated Fe deficiency through multiple pathways, demonstrating a new option for minimizing Fe deficiency by regulating the balance between nutrients.
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Hierro/metabolismo , Malus/metabolismo , Nitratos/metabolismo , Ácido Abscísico/metabolismo , Ácido Abscísico/farmacología , Arabidopsis/efectos de los fármacos , Arabidopsis/metabolismo , Ácido Cítrico/farmacología , Regulación de la Expresión Génica de las Plantas , Homeostasis , Concentración de Iones de Hidrógeno , Malus/efectos de los fármacos , Malus/genética , Nitratos/farmacología , Hojas de la Planta/crecimiento & desarrollo , Hojas de la Planta/metabolismo , Raíces de Plantas/metabolismo , Brotes de la Planta/metabolismo , RizosferaRESUMEN
Aberrantly activated Hedgehog (Hh) pathway is critical for driving the initiation and progression of multiple types of cancers, including medulloblastoma (MB) and basal cellular carcinoma (BCC). The majority of current Hh antagonist function by targeting the transmembrane domain of the oncoprotein Smoothened (Smo), a G-protein-coupled receptor-like receptor of Hh pathway. However, the primary and acquired resistance to current Smo inhibitors raise a critical need to develop next-generation of Smo inhibitors to improve their clinical efficacy. In this study, we identify that FDA approved drug ABT-199 significantly and selectively inhibits the Hh pathway. Mechanistically, ABT-199 acts as a competitive inhibitor of oxysterol by potentially targeting the cysteine rich domain (CRD) of Smo, rather as a BH3 mimetic. ABT-199 obviously inhibits the growth of Hh-driven tumors and possesses capacity of combating the primary and acquired resistance to Smo inhibitors caused by Smo mutations. Our data reposition ABT-199 as a Smo inhibitor for treating Hh-driven tumors, especially for those bearing Smo mutations and resistant to current Smo inhibitors. Meanwhile, our findings strengthen the argument that the CRD of Smo is a promising target for developing novel Smo inhibitors with capacity of combating the resistance to Smo inhibitors.
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Antineoplásicos/uso terapéutico , Compuestos Bicíclicos Heterocíclicos con Puentes/uso terapéutico , Neoplasias/tratamiento farmacológico , Transducción de Señal/efectos de los fármacos , Receptor Smoothened/antagonistas & inhibidores , Sulfonamidas/uso terapéutico , Animales , Antineoplásicos/metabolismo , Sitios de Unión , Compuestos Bicíclicos Heterocíclicos con Puentes/metabolismo , Línea Celular Tumoral , Resistencia a Antineoplásicos/efectos de los fármacos , Proteínas Hedgehog/metabolismo , Humanos , Hidroxicolesteroles/metabolismo , Masculino , Ratones , Ratones Endogámicos NOD , Ratones SCID , Células 3T3 NIH , Neoplasias/metabolismo , Unión Proteica , Receptor Smoothened/química , Receptor Smoothened/metabolismo , Sulfonamidas/metabolismoRESUMEN
Thyroid hormone receptor interactor 13 (TRIP13) is an ATPase that has been found to be overexpressed in many tumors. The aim of this study was to investigate the role of TRIP13 and its mechanism of action in lung cancer. The expression of TRIP13 was examined in lung cancer tissues and corresponding normal lung tissues by western blotting. TRIP13 was overexpressed or knocked down by transient transfection or siRNA interference in lung cancer cells, respectively. The expression of key proteins associated with the Wnt signaling pathway and epithelial-mesenchymal transition (EMT) was assessed. The interaction between TRIP13 and low-density lipoprotein receptor-related protein 6 (LRP6) was examined by co-immunoprecipitation and laser confocal immunofluorescence. Moreover, this study determined the proliferative and invasive ability of cells through colony formation, cell proliferation, and Matrigel invasion assays. The expression of TRIP13 was higher in lung cancer tissues than in normal lung tissues (p = 0.002), and this correlated with poor patient prognosis (p < 0.001). In addition, overexpression of TRIP13 enhanced the levels of active ß-catenin and target proteins of the Wnt signaling pathways (p < 0.05). This study found that TRIP13 can co-localize and bind with LRP6. Furthermore, overexpression of TRIP13 caused the upregulation of N-cadherin, Snail, and vimentin, and the downregulation of E-cadherin (p < 0.05). The aforementioned results were reversed after knocking down the expression of TRIP13 (p < 0.05). TRIP13 is highly expressed in lung cancers, indicating poor prognosis. overexpression of TRIP13 promotes the proliferative and invasive ability of lung cancer cells via the activation of Wnt signaling pathway and EMT.
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ATPasas Asociadas con Actividades Celulares Diversas/metabolismo , Proteínas de Ciclo Celular/metabolismo , Transición Epitelial-Mesenquimal , Neoplasias Pulmonares/metabolismo , Neoplasias Pulmonares/patología , Vía de Señalización Wnt , Línea Celular Tumoral , Proliferación Celular , Humanos , Proteína-6 Relacionada a Receptor de Lipoproteína de Baja Densidad/metabolismo , Invasividad Neoplásica , Estadificación de Neoplasias , Análisis de Supervivencia , Ensayo de Tumor de Célula MadreRESUMEN
RATIONALE: Thymic carcinoma with adenoid cystic carcinoma-like features is a special subtype of thymic adenocarcinoma, and the occurrence of this condition is extremely rare. Herein, we report a case of primary thymic carcinoma with adenoid cystic carcinoma-like features in a young man. PATIENT CONCERNS: A 38-year-old man had an incidental finding of space-occupying lesion in the anterior mediastinum during a routine health examination. The patient complained of occasional mild chest tightness during hot weather but had no obvious cough, sputum, chest pain, or fever. Contrast-enhanced computed tomography scan of the chest revealed a space-occupying lesion in the anterior mediastinum, which is likely benign. DIAGNOSIS: The lesion was diagnosed as a primary thymic carcinoma with adenoid cystic carcinoma-like features. INTERVENTION: The patient underwent thoracoscopic resection of left anterior mediastinal mass and enlarged resection of thymectomy and mediastinal fat in our hospital. OUTCOMES: The postoperative course was uneventful. LESSONS: The tissue characteristic of this tumor was extremely similar to that of adenoid cystic carcinoma. A precise pathological examination is extremely important to prevent misdiagnoses of the lesion as adenoid cystic carcinoma or other thymic tumors. Immunohistochemical staining is extremely useful for the pathological and differential diagnoses of this tumor.
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Timoma/patología , Neoplasias del Timo/patología , Adulto , Carcinoma Adenoide Quístico/patología , Diagnóstico Diferencial , Humanos , Masculino , Mediastino/patología , Timoma/diagnóstico , Neoplasias del Timo/diagnósticoRESUMEN
FAM83A (family with sequence similarity 83, member A) has been found to be highly expressed in cancers. The purpose of this study was to clarify the role and mechanism of FAM83A in lung cancers. The expression of FAM83A in lung cancer cells was enhanced by gene transfection or knocked down by small interfering RNA interference. The key proteins of the Wnt signaling pathway, the Hippo signaling pathway, and epithelial-mesenchymal transition (EMT) were examined using Western blot. The proliferation and invasion of lung cancer cells were examined using cell proliferation, colony formation, and invasion assays. The expression of FAM83A in lung cancer tissues was significantly increased and was correlated with advanced tumor-node-metastasis (TNM) stage and poor prognosis. Overexpression of FAM83A enhanced the proliferation, colony formation, and invasion of lung cancer cells. Meanwhile, FAM83A overexpression increased the expression of active ß-catenin and Wnt target genes and the activity of EMT. Furthermore, in FAM83A-overexpressed cells, the activity of Hippo pathway was downregulated, whereas the expression of yes-associated protein (YAP) and its downstream targets cyclin E and CTGF were upregulated. The inhibitor of the Wnt signaling pathway, XAV-939, reversed the promoting effect of FAM83A on YAP, cyclin E, and CTGF. On knocking down the expression of FAM83A, we obtained the opposite results. However, the inhibitor of GSK3ß, CHIR-99021, restored the expression of YAP, cyclin E, and CTGF after FAM83A was knocked down. FAM83A is highly expressed in lung cancers and correlated with advanced TNM stage and poor prognosis. FAM83A promotes the proliferation and invasion of lung cancer cells by regulating the Wnt and Hippo signaling pathways and EMT process.
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DEK has been revealed to be overexpressed in many cancers and associated with cancer progression. The aim of the present study was to elucidate the role of DEK with a specific focus on its underlying mechanism in lung cancers. DEK expression in lung cancers and normal lung tissues and the correlations between DEK expression and clinicopathological parameters of lung cancers were investigated using the data from The Cancer Genome Atlas (TCGA). DEK expression was upregulated by DEK transfection or downregulated by DEK shRNA interference in A549 and H1299 cells. The effects of DEK on the Wnt signaling pathway and epithelialmesenchymal transition (EMT) were examined using western blotting. Proliferative and invasive abilities were observed in A549 and H1299 cells treated with DEK using an MTT assay, colony formation assay, and Transwell migration and invasion assays. The expression of DEK was higher in lung cancer tissues than that in normal lung tissues. DEK expression was positively correlated with the expression of epidermal growth factor receptor (EGFR) and KRAS in lung adenocarcinomas. High expression of DEK indicated poor prognosis in lung adenocarcinomas (P=0.018). Enhanced expression of DEK upregulated the levels of activeßcatenin and Wnt target genes, such as cyclin D1, cMyc and MMP7 and increased the proliferative and invasive abilities of lung cancer cells. Enhanced expression of DEK in A549 and H1299 cells also increased the levels of EGFR, KRAS, vimentin, Snail, and Ncadherin, and decreased the level of Ecadherin. The opposite results were obtained with knockdown of DEK expression. DEK was highly expressed in lung cancers and indicated poor prognosis in lung adenocarcinomas. DEK expression activated the Wnt signaling pathway and EMT process and promoted the proliferation and invasion of lung cancers.
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Adenocarcinoma del Pulmón/genética , Biomarcadores de Tumor/genética , Proteínas Cromosómicas no Histona/genética , Invasividad Neoplásica/genética , Proteínas Oncogénicas/genética , Proteínas de Unión a Poli-ADP-Ribosa/genética , Células A549 , Adenocarcinoma del Pulmón/patología , Movimiento Celular/genética , Proliferación Celular/genética , Ciclina D1/genética , Transición Epitelial-Mesenquimal/genética , Receptores ErbB/genética , Regulación Neoplásica de la Expresión Génica/genética , Humanos , Invasividad Neoplásica/patología , Proteínas Proto-Oncogénicas p21(ras)/genética , Interferencia de ARN , Vía de Señalización Wnt/genética , beta Catenina/genéticaRESUMEN
BACKGROUND: Diabetic kidney disease (DKD) is the main cause of end-stage kidney disease and has become a heavy economic and social burden due to its high prevalence and morbidity. The most effective strategy is that patients with DKD should be diagnosed and treated early. Preliminary studies showed that the Chinese herbal Tangshen Formula (TSF) may delay the progression of DKD, reducing microalbuminuria and macroalbuminuria and improving renal function. We designed a randomized, double-blind, placebo-controlled trial to evaluate the efficacy of TSF in patients with DKD. METHODS/DESIGN: This trial is a 13-center, randomized, double-blind, placebo-controlled study. A total of 632 participants will be randomized in a 1:1 ratio to an experiment group (TSF plus losartan) and a control group (placebo plus losartan). The trial cycle will last 24 weeks. The primary outcome will be the change in the urine microalbumin-creatinine ratio from baseline to week 24. The secondary outcome will be the change in the rate of progression to the clinical proteinuria period after intervention, the rate of urine microalbumin negative conversion, the rate of normal urinary microalbumin, the doubling rate of the baseline creatinine value and the glomerular filtration rate between the two groups. Safety in medication will also be evaluated. DISCUSSION: We hypothesize that patients with type 2 diabetes in the early stage of DKD will benefit from TSF. If successful, this study will provide evidence-based recommendations for clinicians. TRIAL REGISTRATION: ClinicalTrials.gov, NCT03009864. Registered January 2017.
Asunto(s)
Albuminuria/tratamiento farmacológico , Nefropatías Diabéticas/tratamiento farmacológico , Medicamentos Herbarios Chinos/uso terapéutico , Proteinuria/tratamiento farmacológico , Adulto , Anciano , Antihipertensivos/uso terapéutico , Estudios de Casos y Controles , China/epidemiología , Nefropatías Diabéticas/epidemiología , Método Doble Ciego , Medicamentos Herbarios Chinos/efectos adversos , Diagnóstico Precoz , Femenino , Tasa de Filtración Glomerular/efectos de los fármacos , Humanos , Riñón/fisiopatología , Losartán/uso terapéutico , Masculino , Medicina Tradicional China , Persona de Mediana Edad , Placebos/administración & dosificación , Prevalencia , Resultado del TratamientoRESUMEN
With digital satellite remote sensing image data of GF-1,in 2018 the object-oriented classification method was used to extract Zizyphus jujuba planting area in Jia county of Shaanxi province. The results showed that the remote sensing classification method based on rule set could extract and reckon Z. jujube planting area in the study area effectively. The planting area of Z. jujube in Jia county was about 5. 34×104 hm2 and the area of consistent accuracy was 97. 92%. The method used in this study could provide a technical reference for the area extraction of the same type of medicinal materials. And it is of great significance to provide decision support for the protection and utilization of Z. jujube resources.