RESUMEN
Although more than 9100 plant plastomes have been sequenced, RNA editing sites of the whole plastome have been experimentally verified in only approximately 21 species, which seriously hampers the comprehensive evolutionary study of chloroplast RNA editing. We investigated the evolutionary pattern of chloroplast RNA editing sites in 19 species from all 13 families of gymnosperms based on a combination of genomic and transcriptomic data. We found that the chloroplast C-to-U RNA editing sites of gymnosperms shared many common characteristics with those of other land plants, but also exhibited many unique characteristics. In contrast to that noted in angiosperms, the density of RNA editing sites in ndh genes was not the highest in the sampled gymnosperms, and both loss and gain events at editing sites occurred frequently during the evolution of gymnosperms. In addition, GC content and plastomic size were positively correlated with the number of chloroplast RNA editing sites in gymnosperms, suggesting that the increase in GC content could provide more materials for RNA editing and facilitate the evolution of RNA editing in land plants or vice versa. Interestingly, novel G-to-A RNA editing events were commonly found in all sampled gymnosperm species, and G-to-A RNA editing exhibits many different characteristics from C-to-U RNA editing in gymnosperms. This study revealed a comprehensive evolutionary scenario for chloroplast RNA editing sites in gymnosperms, and reported that a novel type of G-to-A RNA editing is prevalent in gymnosperms.
Asunto(s)
Edición de ARN , ARN del Cloroplasto , Secuencia de Bases , Cloroplastos/genética , Cycadopsida/genética , Evolución Molecular , Filogenia , Edición de ARN/genética , ARN del Cloroplasto/genéticaRESUMEN
The disjunct distribution between East Asia and North America is one of the best established biogeographic patterns. A robust phylogeny is fundamental for understanding the biogeographic histories of taxa with this distribution pattern. Tsuga (hemlock) is a genus of Pinaceae with a typical intercontinental disjunct distribution in East Asia and eastern and western North America, and its phylogeny has not been completely reconstructed in previous studies. In this study, we reconstructed a highly resolved phylogeny of Tsuga using 881 nuclear genes, 60 chloroplast genes and 23 mitochondrial genes and explored its biogeographic and reticulate evolutionary history. The results of phylogenetic analysis, molecular dating and ancestral area reconstruction indicate that Tsuga very likely originated from North America in the late Oligocene and dispersed from America to East Asia via the Bering Land Bridge during the middle Miocene. In particular, we found complex reticulate evolutionary pattern among the East Asian hemlock species. T. sieboldii possibly originated from hybridization with the ancestor of T. chinensis from mainland China and T. forrestii as the paternal donor and the ancestor of T. diversifolia and T. ulleungensis as the maternal donor. T. chinensis (Taiwan) could have originated by hybridization together with T. sieboldii and then evolved independently after dispersal to the Taiwan Island, subsequently experiencing mitochondrial DNA introgression with T. chinensis from mainland China. Moreover, our study found that T. chinensis from western China is more closely related to T. forrestii than to T. chinensis from eastern China. The nonmonophyletic T. chinensis needs taxonomic reconsideration.
Asunto(s)
Filogenia , Filogeografía , Transcriptoma/genética , Tsuga/genética , ADN de Cloroplastos/genética , ADN Mitocondrial/genética , Asia Oriental , Genes Mitocondriales , Hibridación Genética , América del Norte , Factores de Tiempo , Tsuga/anatomía & histología , Estados UnidosRESUMEN
BACKGROUND: Leaves have highly diverse morphologies. However, with an evolutionary history of approximately 200 million years, leaves of the pine family are relatively monotonous and often collectively called "needles", although they vary in length, width and cross-section shapes. It would be of great interest to determine whether Pinaceae leaves share similar morpho-physiological features and even consistent developmental and adaptive mechanisms. RESULTS: Based on a detailed morpho-anatomical study of leaves from all 11 Pinaceae genera, we particularly investigated the expression patterns of adaxial-abaxial polarity genes in two types of leaves (needlelike and flattened) and compared their photosynthetic capacities. We found that the two types of leaves share conserved spatial patterning of vasculatures and genetic networks for adaxial-abaxial polarity, although they display different anatomical structures in the mesophyll tissue differentiation and distribution direction. In addition, the species with needlelike leaves exhibited better photosynthetic capacity than the species with flattened leaves. CONCLUSIONS: Our study provides the first evidence for the existence of a conserved genetic module controlling adaxial-abaxial polarity in the development of different Pinaceae leaves.
Asunto(s)
Adaptación Biológica/genética , Fotosíntesis , Hojas de la Planta/anatomía & histología , Redes Reguladoras de Genes , Pinaceae , Hojas de la Planta/genéticaRESUMEN
BACKGROUND & AIMS: Iron is an essential metal for fundamental metabolic processes, but little is known regarding the involvement of iron in other nutritional disorders. In the present study, we investigated disordered iron metabolism in a murine model of hereditary tyrosinemia type I (HT1), a disease of the tyrosine degradation pathway. METHODS: We analysed the status of iron accumulation following NTBC withdrawal from Fah(-/-) mice, a murine model for HT1. Liver histology and serum parameters were used to assess the extent of liver injury and iron deposition. To determine the physiological significance of iron accumulation, mice were subjected to a low-iron food intake to reduce the iron accumulation. Mechanistic studies were performed on tissues and cells using immunoblotting, qRT-PCR, adenovirus transfection and other assays. RESULTS: Severe iron overload was observed in the murine model of HT1 with dramatically elevated hepatic and serum iron levels. Mechanistic studies revealed that downregulation and dysfunction of Tfr2 decreased hepcidin, leading to iron overload. The Fah(-/-) hepatocytes lost the ability of transferrin-sensitive induction of hepcidin. Forced expression of Tfr2 in the murine liver reduced the iron accumulation. Moreover, transcription factor Sp1 was downregulated and identified as a new regulator of Tfr2 here. Additionally, low-iron food intake effectively reduced the iron deposits, protected the liver and prolonged the survival in these mice. CONCLUSIONS: Iron was severely overloaded in the HT1 mice via the Sp1/Tfr2/Hepcidin axis. The iron overload induced liver injury in the HT1 mice, and reduction of the iron accumulation ameliorated liver injury. LAY SUMMARY: Primary and secondary iron overload is an abnormal status affecting millions of people worldwide. Here, we reported severe iron overload in a murine model of HT1, a disease of the tyrosine degradation pathway, and elucidated the mechanistic basis and the physiological significance of iron overload in HT1. These studies are of general interest not only with respect to secondary iron-induced liver injury in HT1 but also are important to elucidate the crosstalk between the two metabolic pathways.
Asunto(s)
Hígado/lesiones , Tirosinemias , Animales , Hepcidinas , Hierro , Sobrecarga de Hierro , RatonesRESUMEN
UNLABELLED: Sorafenib is a specific adenosine triphosphate-competitive RAF inhibitor used as a first-line treatment of advanced hepatocellular carcinoma (HCC). However, the responses are variable, reflecting heterogeneity of the disease, while the resistance mechanism remains poorly understood. Here, we report that sorafenib treatment can exacerbate disease progression in both patient-derived xenografts and cell line-derived xenografts and that the therapeutic effect of the drug inversely covaries to the ratio of epithelial cell adhesion molecule-positive cells, which may be tumor initiating cells in HCC. The TSC2-AKT cascade mediates this sorafenib resistance. In response to sorafenib treatment, formation of the TSC1/2 complex is enhanced, causing increased phosphorylation of AKT, which contributes to up-regulation of "stemness"-related genes in epithelial cell adhesion molecule-positive cells and enhancement of tumorigenicity. The expression of TSC2 negatively correlated with prognosis in clinical sorafenib therapy. Furthermore, all-trans retinoic acid decreased AKT activity, reduced the epithelial cell adhesion molecule-positive cell population enriched by sorafenib, and potentiated the therapeutic effect of sorafenib in the patient-derived xenograft model. CONCLUSION: Our findings suggest that a subtype of HCC is not suitable for sorafenib therapy; this resistance to sorafenib can be predicted by the status of TSC2, and agents inducing differentiation of tumor initiating cells (e.g., all-trans retinoic acid) should improve the prognosis of this subtype of HCC.
Asunto(s)
Antígenos de Neoplasias/efectos de los fármacos , Antineoplásicos/efectos adversos , Carcinoma Hepatocelular/inducido químicamente , Moléculas de Adhesión Celular/efectos de los fármacos , Neoplasias Hepáticas/inducido químicamente , Células Madre Neoplásicas/efectos de los fármacos , Niacinamida/análogos & derivados , Proteína Oncogénica v-akt/fisiología , Compuestos de Fenilurea/efectos adversos , Proteínas Supresoras de Tumor/fisiología , Animales , Carcinoma Hepatocelular/clasificación , Progresión de la Enfermedad , Molécula de Adhesión Celular Epitelial , Humanos , Neoplasias Hepáticas/clasificación , Ratones , Niacinamida/efectos adversos , Sorafenib , Proteína 2 del Complejo de la Esclerosis TuberosaRESUMEN
The naturally occurring bisexual cone of gymnosperms has long been considered a possible intermediate stage in the origin of flowers, but the mechanisms governing bisexual cone formation remain largely elusive. Here, we employed transcriptomic and DNA methylomic analyses, together with hormone measurement, to investigate the molecular mechanisms underlying bisexual cone development in the conifer Picea crassifolia. Our study reveals a "bisexual" expression profile in bisexual cones, especially in expression patterns of B-class, C-class and LEAFY genes, supporting the out of male model. GGM7 could be essential for initiating bisexual cones. DNA methylation reconfiguration in bisexual cones affects the expression of key genes in cone development, including PcDAL12, PcDAL10, PcNEEDLY, and PcHDG5. Auxin likely plays an important role in the development of female structures of bisexual cones. This study unveils the potential mechanisms responsible for bisexual cone formation in conifers and may shed light on the evolution of bisexuality.
Asunto(s)
Picea , Minorías Sexuales y de Género , Tracheophyta , Humanos , Filogenia , Bisexualidad , Picea/genética , Picea/metabolismo , Metilación de ADN , Tracheophyta/genéticaRESUMEN
The sluggish kinetics of the oxygen evolution reaction (OER) always results in a high overpotential at the anode of water electrolysis and an excessive electric energy consumption, which has been a major obstacle for hydrogen production through water electrolysis. In this study, we present a CoNi-LDH/Fe MOF/NF heterostructure catalyst with nanoneedle array morphology for the OER. In 1.0 M KOH solution, the heterostructure catalyst only required overpotentials of 275 and 305 mV to achieve high current densities of 500 and 1000 mA/cm2 for OER, respectively. The catalytic activities are much higher than those of the reference single-component CoNi-LDH/NF and Fe MOF/NF catalysts. The improved catalytic performance of the heterostructure catalyst can be ascribed to the synergistic effect of CoNi-LDH and Fe MOF. In particular, when the anodic OER is replaced with the urea oxidation reaction (UOR), which has a relatively lower thermodynamic equilibrium potential and is expected to reduce the cell voltage, the overpotentials required to achieve the same current densities can be reduced by 80 and 40 mV, respectively. The cell voltage required to drive overall urea splitting (OUS) is only 1.55 V at 100 mA/cm2 in the Pt/C/NF||CoNi-LDH/Fe MOF/NF two-electrode electrolytic cell. This value is 60 mV lower compared with that required for overall water splitting (OWS). Our results indicate that a reasonable construction of a heterostructure catalyst can significantly give rise to higher electrocatalytic performance, and using UOR to replace the anodic OER of the OWS can greatly reduce the electrolytic energy consumption.
RESUMEN
BACKGROUND & AIMS: Dysregulation of Wnt signaling has been involved in gastric tumorigenesis by mechanisms that are not fully understood. The receptor for activated protein kinase C (RACK1, GNB2L1) is involved in development of different tumor types, but its expression and function have not been investigated in gastric tumors. METHODS: We analyzed expression of RACK1 in gastric tumor samples and their matched normal tissues from 116 patients using immunohistochemistry. Effects of knockdown with small interfering RNAs or overexpression of RACK1 in gastric cancer cell lines were evaluated in cell growth and tumor xenograft. RACK1 signaling pathways were investigated in cells and zebrafish embryos using immunoblot, immunoprecipitation, microinjection, and in situ hybridization assays. RESULTS: Expression of RACK1 was reduced in gastric tumor samples and correlated with depth of tumor infiltration and poor differentiation. Knockdown of RACK1 in gastric cancer cells accelerated their anchorage-independent proliferation in soft agar, whereas overexpression of RACK1 reduced their tumorigenicity in nude mice. RACK1 formed a complex with glycogen synthase kinase Gsk3ß and Axin to promote the interaction between Gsk3ß and ß-catenin and thereby stabilized the ß-catenin destruction complex. On stimulation of Wnt3a, RACK1 repressed Wnt signaling by inhibiting recruitment of Axin by Dishevelled 2 (Dvl2). Moreover, there was an inverse correlation between expression of RACK1 and localization of ß-catenin to the cytoplasm/nucleus in human gastric tumor samples. CONCLUSIONS: RACK1 negatively regulates Wnt signaling pathway by stabilizing the ß-catenin destruction complex and act as a tumor suppressor in gastric cancer cells.
Asunto(s)
Complejo de Señalización de la Axina/metabolismo , Proteínas de Unión al GTP/metabolismo , Proteínas de Neoplasias/metabolismo , Receptores de Superficie Celular/metabolismo , Neoplasias Gástricas/metabolismo , Proteínas Supresoras de Tumor/metabolismo , Vía de Señalización Wnt , Proteínas Adaptadoras Transductoras de Señales/metabolismo , Animales , Complejo de Señalización de la Axina/genética , Estudios de Casos y Controles , Diferenciación Celular , Línea Celular Tumoral , Proliferación Celular , Proteínas Dishevelled , Femenino , Proteínas de Unión al GTP/genética , Regulación Neoplásica de la Expresión Génica , Glucógeno Sintasa Quinasa 3/metabolismo , Glucógeno Sintasa Quinasa 3 beta , Células HEK293 , Humanos , Inmunohistoquímica , Masculino , Ratones , Ratones Desnudos , Persona de Mediana Edad , Invasividad Neoplásica , Proteínas de Neoplasias/genética , Trasplante de Neoplasias , Fosfoproteínas/metabolismo , Interferencia de ARN , Receptores de Cinasa C Activada , Receptores de Superficie Celular/genética , Neoplasias Gástricas/genética , Neoplasias Gástricas/patología , Neoplasias Gástricas/prevención & control , Factores de Tiempo , Transfección , Proteínas Supresoras de Tumor/genética , Vía de Señalización Wnt/genética , Proteína Wnt3A/metabolismo , Pez Cebra/embriología , Pez Cebra/genética , Proteínas de Pez Cebra/genética , Proteínas de Pez Cebra/metabolismo , beta Catenina/metabolismoRESUMEN
[This corrects the article DOI: 10.3389/fmicb.2022.927139.].
RESUMEN
To successfully survive and reproduce, all species constantly modify the structure and expression of their genomes to cope with changing environmental conditions including ultraviolet (UV) radiation. Thus, knowledge of species adaptation to environmental changes is a central theme of evolutionary studies which could have important implication for disease management and social-ecological sustainability in the future but is generally insufficient. Here, we investigated the evolution of UV adaptation in organisms by population genetic analysis of sequence structure, physiochemistry, transcription, and fitness variation in the radiation-sensitive 4 (RAD4) gene of the Irish potato famine pathogen Phytophthora infestans sampled from various altitudes. We found that RAD4 is a key gene determining the resistance of the pathogen to UV stress as indicated by strong phenotype-genotype-geography associations and upregulated transcription after UV exposure. We also found conserved evolution in the RAD4 gene. Only five nucleotide haplotypes corresponding to three protein isoforms generated by point mutations were detected in the 140 sequences analyzed and the mutations were constrained to the N-terminal domain of the protein. Physiochemical changes associated with non-synonymous mutations generate severe fitness penalty to mutants, which are purged out by natural selection, leading to the conserved evolution observed in the gene.
RESUMEN
Quantitative real-time polymerase chain reaction (qRT-PCR) is a sensitive and widely used technique for quantifying gene expression levels, and its accuracy depends on the reference genes used for data normalization. To date, no reference gene has been reported in the nutritious and functional vegetable okra (Abelmoschus esculentus L.). Herein, 11 candidates of reference genes were selected and evaluated for their expression stability in okra in different tissues at different developmental stages by using three software algorithms (geNorm, NormFinder, BestKeeper) and a web-based tool (RefFinder). Among them, eukaryotic initiation factor 4 alpha (eIF4A) and protein phosphatase 2A (PP2A) showed the highest stability, while TUA5 had the lowest stability. The combined usage of these two most stable reference genes was sufficient to normalize gene expression in okra. Then, the above results were further validated by normalizing the expression of the cellulose synthase gene CesA4. This work provides appropriate reference genes for transcript normalization in okra, which will facilitate subsequent functional gene research on this vegetable crop.
Asunto(s)
Abelmoschus , Abelmoschus/genética , Algoritmos , Perfilación de la Expresión Génica , Genes de Plantas , Reacción en Cadena en Tiempo Real de la Polimerasa/métodos , Estándares de Referencia , Programas InformáticosRESUMEN
Pt(m)^Ag nanostructures (m being the atomic Pt/Ag ratio, m = 0.1-0.6) were prepared by reflux citrate reduction of PtCl(6)(2-) ions in aqueous solution containing colloidal Ag (6.3 ± 3.9 nm). A distinct alloying of Pt with Ag was detected due to an involvement of the galvanic replacement reaction between PtCl(6)(2-) and metallic Ag colloids. The nanostructure transformed from a structure with an Ag-core and an alloyed PtAg-shell to a hollow PtAg alloy structure with the increase in m. Compared to a commercial E-TEK Pt/C catalyst, the catalytic performance of Pt in the Pt(m)^Ag/C samples for the cathode oxygen reduction reaction (ORR) strongly correlated with the electronic structure of Pt, as a consequence of varied Pt dispersion and Pt-Ag interaction. With either H(2)SO(4) or KOH as an electrolyte, Pt in the Pt(m)^Ag nanostructures with a relatively high m (≥0.4) showed significantly enhanced intrinsic activity whereas Pt in those catalysts with low m (≤0.2) appeared less active than the Pt/C catalyst. These data are used to discuss the role of electronic structure and geometric effects of Pt toward ORR.
RESUMEN
An electricigenic permeable reactive barrier (EPRB) technology was brought forward for remediation of organic-contaminated groundwater, with a benefit that it overcame the limitations of electron acceptor addition in other groundwater remediation methods. To investigate performances of constructions and materials used in EPRB system, several kinds of reactors were designed and prepared in laboratory. Stainless steel wires, a kind of nontoxic, inexpensive and conductive material, were used as basic material of electrode. In order to improve cathodic oxygen reduction capability, a cathode based on tetramethoxyphenyl porphyrin cobalt (II) (CoTMPP) was prepared and studied in this paper. Results showed that a high catalytic activity for oxygen reduction was exhibited by the CoTMPP based cathode, with an electricity generation 3 times as high as that of the naked stainless steel cathode. Some evidence indicated that by loading on the surface of stainless steel wires and heat-treated under anaerobic conditions, epoxy resin, with its curing agents, might have got a catalytic capability for oxygen reduction.
Asunto(s)
Técnicas de Química Analítica/instrumentación , Técnicas de Química Analítica/métodos , Cobalto/química , Metaloporfirinas/química , Acero Inoxidable/química , Contaminantes Químicos del Agua/análisis , Electricidad , ElectrodosRESUMEN
Two isoforms of human Polycomb-like protein 3 (hPCL3) have been reported as components of the nuclear Polycomb repressive complex 2 (PRC2), with the short isoform (hPCL3s) showing a dominant cytoplasmic localization. The function of cytoplasmic hPCL3s has, however, not been addressed. In this study, we report that hPCL3s is upregulated in clinical hepatocellular carcinoma (HCC) samples and its expression correlated with HCC clinical features. hPCL3s positively regulated the migration, invasion, and metastasis of HCC cells. hPCL3s interacted with components of the cytoplasmic ß-catenin destruction complex, inhibited ß-catenin degradation, and activated ß-catenin/T-cell factor signaling. Downstream of the ß-catenin cascade, IL6 mediated the motility-promoting functions of hPCL3s. Forced expression of hPCL3s in the liver of a HCC mouse model promoted tumorigenesis and metastasis. Taken together, these data show that hPCL3s promotes the metastasis of HCC by activating the ß-catenin/IL6 pathway.Significance: hPCL3s has an oncogenic role in hepatocellular carcinoma by activating the ß-catenin/IL6 signaling axis to promote metastasis. Cancer Res; 78(10); 2536-49. ©2018 AACR.
Asunto(s)
Carcinoma Hepatocelular/patología , Interleucina-6/metabolismo , Neoplasias Hepáticas/patología , Proteínas Nucleares/metabolismo , beta Catenina/metabolismo , Animales , Línea Celular Tumoral , Movimiento Celular/genética , Proliferación Celular/genética , Proteínas de Unión al ADN , Regulación Neoplásica de la Expresión Génica/genética , Células HEK293 , Humanos , Masculino , Ratones , Ratones Endogámicos C57BL , Ratones Noqueados , Ratones Desnudos , Invasividad Neoplásica/genética , Proteínas Nucleares/genética , Isoformas de Proteínas/genética , Isoformas de Proteínas/metabolismo , Factores de Transcripción , Vía de Señalización Wnt/genética , Ensayos Antitumor por Modelo de XenoinjertoRESUMEN
Tumor susceptibility gene 101 (TSG101) is a multi-functional gene involved in cell growth and proliferation in vertebrates. However, its role in the innate immune response of crustaceans remains unclear. Here, a TSG101 gene was identified in crayfish Procambarus clarkii with an open reading frame of 1320 bp that encoded a predicted 48.3-kDa protein highly homologous to those in other invertebrates. TSG101 mRNA was highly expressed in stomach and hepatopancreas, and its expression was induced significantly in different tissues (hemocytes, gills and intestine) by lipopolysaccharide (LPS) and polyinosinic:polycytidylic acid (poly I: C) with various expression patterns. Recombinant TSG101 protein was expressed in Escherichia coli, and a possible protein-protein interaction between TSG101 and hepatocyte growth factor-regulated tyrosine kinase substrate (Hrs) was explored by far-western blotting. RNA interference of TSG101 affected the gene expression of members of the Toll pathway. These results suggest that TSG101 is involved in the innate immune responses of P. clarkii.
Asunto(s)
Proteínas de Artrópodos/metabolismo , Astacoidea/inmunología , Proteínas de Unión al ADN/metabolismo , Complejos de Clasificación Endosomal Requeridos para el Transporte/metabolismo , Hemocitos/inmunología , Hepatopáncreas/inmunología , ARN Mensajero/genética , Estómago/inmunología , Factores de Transcripción/metabolismo , Animales , Proteínas de Artrópodos/genética , Clonación Molecular , Proteínas de Unión al ADN/genética , Complejos de Clasificación Endosomal Requeridos para el Transporte/genética , Factor de Crecimiento de Hepatocito/metabolismo , Inmunidad Innata , Filogenia , Poli I-C/inmunología , ARN Interferente Pequeño/genética , Proteínas Tirosina Quinasas Receptoras/metabolismo , Transducción de Señal , Receptores Toll-Like/metabolismo , Factores de Transcripción/genéticaRESUMEN
OBJECTIVE: To investigate the effect of HBP-A on meniscal injuries and the expressions of genes associated with pathological hypertrophy and calcification of the meniscusinduced by abnormal loading. METHODS: Bovine meniscus explants were subjected to 25% strain at 0.3 Hz for 3 h and treated with 0.6 mg/mL of HBP-A. The cell viability in the meniscus explants after 72 hin culture was determined using live/dead staining and the expression levels of genes associated with pathological hypertrophy and calcification of the meniscus (ANKH, ENPP1, ALP, MMP13, and IL-1) were measured using real-time PCR and Western blotting. The conditioned medium was collected for testing sulfated glycosaminoglycan (GAG) release. RESULTS: The number of dead cells, loss of proteoglycan content, and the expressions of ANKH, ENPP1, ALP and MMP13, and IL-1 at both the mRNA and protein levels were all significantly lower in the meniscus explants treated with 0.6 mg/mL HBP-A than in the explants with only 25% abnormal pressure stimulation (n=3, P<0.05). CONCLUSION: HBP-A can effectively alleviate meniscal injuries induced by abnormal loading and suppress the expressions of genes related with pathological hypertrophy and calcification of the meniscus, and can serve as a potential drug for treatment of knee osteoarthritis.
Asunto(s)
Calcinosis/tratamiento farmacológico , Glucanos/farmacología , Meniscos Tibiales/efectos de los fármacos , Lesiones de Menisco Tibial/tratamiento farmacológico , Animales , Bovinos , Hipertrofia , Osteoartritis de la Rodilla/tratamiento farmacológico , Reacción en Cadena en Tiempo Real de la PolimerasaRESUMEN
OBJECTIVE: To study the influence of curcumin on chemosensitivity of nephroblastoma cells. METHODS: Human nephroblastoma cells line SK-NEP-1 was transplanted to the nude mice subcutaneously to establish the implantation tumor model of human nephroblastoma cells. A total of 30 tumor-bearing mice were divided into three groups of ten randomly. The routine chemotherapy group was given vincristine (0.05 mg/mL·0.2 mL/d) and actinomycin D (15 ng/mL·0.2 mL/d) combined chemotherapy regime. The curcumin chemotherapy group was given the same combined chemotherapy regimens and curcumin (30 mg/kg/d) by intraperitoneal injection. The control group was given normal saline (NS) of the same volume by intraperitoneal injection. Continuous administration would be kept for 4 weeks and 3 days a week. The volumetric changes of every group were recorded. The serum of every group in different time was collected and the VEGF content was detected by ELISA. All mice were cercrificed and the tumor tissues were stripped and weighed after 4 weeks' treatment. The tumor inhibition rate was calculated. The cell proliferation activity and apoptosis rate were detected by MTT and flow cytometry method. All data were statistically analyzed by SPSS 19.0. RESULTS: The tumor volume, serum VEGF content, tumor inhibition rate, cell proliferation activity and apoptosis rate of routine chemotherapy group and curcumin chemotherapy group had significant differences comparing with the control group (P < 0.05) after 4-week's treatment. The cancer growth of curcumin chemotherapy group was obviously decreased and even tended to shrink comparing with routine chemotherapy group (χ(2) = 15.732, P = 0.007). The cell proliferation activity was significantly reduced and the apoptosis rate was significantly higher, (χ(2) = 9.427, P = 0.012) which showing the effect of chemotherapy was enhanced. CONCLUSIONS: The chemosensitivity of nephroblastoma cells could be improved by curcumin, then the effect of preoperative adjuvant chemotherapy scheme would be enhanced, the growth of nephroblastoma cells would be inhibited and the surgical risk of nephroblastoma would be reduced.
RESUMEN
The transcription factor NF-κB plays a pivotal role in innate immunity in response to a variety of stimuli, and the coordinated regulation of this pathway determines the proper host responses to extracellular signals. In this study, we identified RACK1 as a novel negative regulator of NF-κB signaling, NF-κB-mediated cytokine induction and inflammatory reactions. RACK1 physically associates with the IKK complex in a TNF-triggered manner. This interaction interferes with the recruitment of the IKK complex to TRAF2, which is a critical step for IKK phosphorylation and subsequent activation triggered by TNF. By modulating the interaction between TRAF2 and IKK, RACK1 regulates the levels of NF-κB activation in response to different intensities of stimuli. Our findings suggest that RACK1 plays an important role in controlling the sensitivity of TNF-triggered NF-κB signaling by regulating IKK activation and provide new insight into the negative regulation of inflammatory reactions.
Asunto(s)
Proteínas de Unión al GTP/metabolismo , Quinasa I-kappa B/metabolismo , FN-kappa B/metabolismo , Proteínas de Neoplasias/metabolismo , Receptores de Superficie Celular/metabolismo , Factor 2 Asociado a Receptor de TNF/metabolismo , Citocinas/metabolismo , Activación Enzimática/efectos de los fármacos , Proteínas de Unión al GTP/antagonistas & inhibidores , Proteínas de Unión al GTP/química , Células HEK293 , Células HeLa , Humanos , Quinasa I-kappa B/química , Proteínas de Neoplasias/antagonistas & inhibidores , Proteínas de Neoplasias/química , Fosforilación/efectos de los fármacos , Unión Proteica , Estructura Terciaria de Proteína , Interferencia de ARN , ARN Pequeño no Traducido/metabolismo , Receptores de Cinasa C Activada , Receptores de Superficie Celular/antagonistas & inhibidores , Receptores de Superficie Celular/química , Transducción de Señal/efectos de los fármacos , Factor 2 Asociado a Receptor de TNF/química , Factor de Necrosis Tumoral alfa/farmacologíaRESUMEN
A pot culture experiment was carried out to investigate the accumulation properties of mercury (Hg) in rice grain and cabbage grown in seven soil types (Udic Ferrisols, Mollisol, Periudic Argosols, Latosol, Ustic Cambosols, Calcaric Regosols, and Stagnic Anthrosols) spiked with different concentrations of Hg (CK, 0.25, 0.50, 1.00, 2.00, and 4.00 mg/kg). The results of this study showed that Hg accumulation of plants was significantly affected by soil types. Hg concentration in both rice grain and cabbage increased with soil Hg concentrations, but this increase differed among the seven soils. The stepwise multiple regression analysis showed that pH, Mn(II), particle size distribution, and cation exchange capacity have a close relationship with Hg accumulation in plants, which suggested that physicochemical characteristics of soils can affect the Hg accumulation in rice grain and cabbage. Critical Hg concentrations in seven soils were identified for rice grain and cabbage based on the maximum safe level for daily intake of Hg, dietary habits of the population, and Hg accumulation in plants grown in different soil types. Soil Hg limits for rice grain in Udic Ferrisols, Mollisol, Periudic Argosols, Latosol, Ustic Cambosols, Calcaric Regosols, and Stagnic Anthrosols were 1.10, 2.00, 2.60, 2.78, 1.53, 0.63, and 2.17 mg/kg, respectively, and critical soil Hg levels for cabbage are 0.27, 1.35, 1.80, 1.70, 0.69, 1.68, and 2.60 mg/kg, respectively.