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BACKGROUND: Drought stress is a prevalent abiotic stress that significantly hinders the growth and development of plants. According to studies, ß-aminobutyric acid (BABA) can influence the ABA pathway through the AtIBI1 receptor gene to enhance cold resistance in Arabidopsis. However, the Aspartate tRNA-synthetase (AspRS) gene family, which acts as the receptor for BABA, has not yet been investigated in poplar. Particularly, it is uncertain how the AspRS gene family (PtrIBIs)r can resist drought stress after administering various concentrations of BABA to poplar. RESULTS: In this study, we have identified 12 AspRS family genes and noted that poplar acquired four PtrIBI pairs through whole genome duplication (WGD). We conducted cis-action element analysis and found a significant number of stress-related action elements on different PtrIBI genes promoters. The expression of most PtrIBI genes was up-regulated under beetle and mechanical damage stresses, indicating their potential role in responding to leaf damage stress. Our results suggest that a 50 mM BABA treatment can alleviate the damage caused by drought stress in plants. Additionally, via transcriptome sequencing, we observed that the partial up-regulation of BABA receptor genes, PtrIBI2/4/6/8/11, in poplars after drought treatment. We hypothesize that poplar responds to drought stress through the BABA-PtrIBIs-PtrVOZ coordinated ABA signaling pathway. Our research provides molecular evidence for understanding how plants respond to drought stress through external application of BABA. CONCLUSIONS: In summary, our study conducted genome-wide analysis of the AspRS family of P. trichocarpa and identified 12 PtrIBI genes. We utilized genomics and bioinformatics to determine various characteristics of PtrIBIs such as chromosomal localization, evolutionary tree, gene structure, gene doubling, promoter cis-elements, and expression profiles. Our study found that certain PtrIBI genes are regulated by drought, beetle, and mechanical damage implying their crucial role in enhancing poplar stress tolerance. Additionally, we observed that external application of low concentrations of BABA increased plant drought resistance under drought stress. Through the BABA-PtrIBIs-PtrVOZ signaling module, poplar plants were able to transduce ABA signaling and regulate their response to drought stress. These results suggest that the PtrIBI genes in poplar have the potential to improve drought tolerance in plants through the topical application of low concentrations of BABA.
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Arabidopsis , Aspartato-ARNt Ligasa , Escarabajos , Animales , Resistencia a la Sequía , Transducción de Señal/genética , Arabidopsis/genética , ARN de Transferencia/genéticaRESUMEN
BACKGROUND: Functional lung volume (FLV) obtained from computed tomography images was a breakthrough for lung imaging and functional assessment. We compared the accuracy of the FLV measurement method and the segment-counting (SC) method in predicting postoperative pulmonary function. METHODS: A total of 113 patients who underwent two thoracoscopic surgeries were enrolled in our study. We predicted postoperative pulmonary function by the FLV measurement method and the SC method. Novel formulas based on the FLV measurement method were established using linear regression equations between the factors affecting pulmonary function and the measured values. RESULTS: The predicted postoperative forced vital capacity (ppoFVC) and forced expiratory volume in 1 s (ppoFEV1) measured by the 2 methods showed high concordance between the actual postoperative forced vital capacity (postFVC) and the forced expiratory volume in 1 s (postFEV1) [r = 0.762, P < 0.001 (FLV method) and r = 0.759, P < 0.001 (SC method) for FVC; r = 0.790, P < 0.001 (FLV method) and r = 0.795, P < 0.001 (SC method) for FEV1]. Regression analysis showed that the measured preoperative pulmonary function parameters (FVC, FEV1) and the ratio of reduced FLV to preoperative FLV were significantly associated with the actual postoperative values and could predict these parameters (all P < 0.001). The feasibility of using these equations [postFVC = 0.8 × FVC - 0.784 × ΔFLV/FLV + 0.283 (R2 = 0.677, RSD = 0.338), postFEV1 = 0.766 × FEV1 - 0.694 × ΔFLV/FLV + 0.22 (R2 = 0.743, RSD = 0.265)] to predict the pulmonary function parameters after wedge resection was also verified. CONCLUSIONS: The new FLV measurement method is valuable for predicting postoperative pulmonary function in patients undergoing lung resection surgery, with accuracy and consistency similar to those of the conventional SC method.
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Neoplasias Pulmonares , Pulmón , Humanos , Neoplasias Pulmonares/cirugía , Mediciones del Volumen Pulmonar , Capacidad Vital , Volumen Espiratorio ForzadoRESUMEN
OBJECTIVE: Chest tube management plays a key role in minimising erioperative period. We have improved the knotless method to chest tube wounds. In this article, we demonstrate the clinical bility and safety of this method. METHOD: From 13 October 2018-3 January 2019, patients were ecutively included in our study at the First Affiliated Hospital of n Medical University, Dalian, China. They were separated into approximately equally sized groups-the knotless group and the entional group. Our improved knotless method was performed ose the chest tube wounds of patients in the knotless group, and onventional method using the pre-existing U-shaped string to the chest tube wounds of patients in the conventional group. Patient clinical information, tube-related complications, retreatment s and cosmetic scores were compared between the groups. RESULTS: The cohort comprised 102 patients; 47 in the knotless group and 55 in the conventional group. There were no statistically significant differences in patient clinical information or tube-related complications between the two groups (p>0.05; both comparisons). In the knotless group, retreatment times were shorter (p<0.001) and cosmetic scores were higher (p<0.001). CONCLUSION: This study showed that our new knotless method is safe and has wide clinical feasibility. The new method also improved patient cosmetic scores. Furthermore, it decreased the patients' economic burdens.
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Tubos Torácicos , Técnicas de Sutura , Humanos , Estudios Prospectivos , Estudios de Factibilidad , ChinaRESUMEN
Nuclear accidents and the improper disposal of nuclear wastes have led to serious environmental radioactive pollutions. The rational design of adsorbents for the highly efficient separation of strontium(II) is essential in treating nuclear waste and recovering radioactive strontium resources. Metal-organic frameworks (MOFs) are potential materials for the separation of aqueous metal ions owing to their designable structure and tunable functionality. Herein, a novel 3D MOF material MOF-18Cr6, in which 1D channels are formed using 18-crown-6-ether-containing ligands as channel walls, is fabricated for strontium(II) separation. In contrast to traditional MOFs designed by grafting functional groups in the framework pores, MOF-18Cr6 possesses regular 18-crown-6-ether cavities on the channel walls, which not only can transport and intake strontium(II) via the channels, but also prevent blockage of the channels after the binding of strontium(II). Consequently, the functional sites are fully utilized to achieve a high strontium(II) removal rate of 99.73 % in simulated nuclear wastewater. This study fabricates a highly promising adsorbent for the separation of aqueous radioactive strontium(II), and more importantly, can provide a new strategy for the rational design of high-performance MOF adsorbents for separating target substances from complex aqueous environments.
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The origination of new genes contributes to phenotypic evolution in humans. Two major challenges in the study of new genes are the inference of gene ages and annotation of their protein-coding potential. To tackle these challenges, we created GenTree, an integrated online database that compiles age inferences from three major methods together with functional genomic data for new genes. Genome-wide comparison of the age inference methods revealed that the synteny-based pipeline (SBP) is most suited for recently duplicated genes, whereas the protein-family-based methods are useful for ancient genes. For SBP-dated primate-specific protein-coding genes (PSGs), we performed manual evaluation based on published PSG lists and showed that SBP generated a conservative data set of PSGs by masking less reliable syntenic regions. After assessing the coding potential based on evolutionary constraint and peptide evidence from proteomic data, we curated a list of 254 PSGs with different levels of protein evidence. This list also includes 41 candidate misannotated pseudogenes that encode primate-specific short proteins. Coexpression analysis showed that PSGs are preferentially recruited into organs with rapidly evolving pathways such as spermatogenesis, immune response, mother-fetus interaction, and brain development. For brain development, primate-specific KRAB zinc-finger proteins (KZNFs) are specifically up-regulated in the mid-fetal stage, which may have contributed to the evolution of this critical stage. Altogether, hundreds of PSGs are either recruited to processes under strong selection pressure or to processes supporting an evolving novel organ.
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Evolución Molecular , Primates/genética , Proteoma/genética , Análisis de Secuencia de ADN/métodos , Programas Informáticos , Animales , Encéfalo/metabolismo , Humanos , Sistemas de Lectura Abierta , Proteoma/metabolismo , SinteníaRESUMEN
The detection of environmental uranyl is attracting increasing attention. However, the available detection strategies mainly depend on the selective recognition of uranyl, which is subject to severe interference by coexisting metal ions. Herein, based on the unique uranyl-triggered photocleavage property, the protein BSA is labelled with fluorescent molecules that exhibit an aggregation-induced emission effect for uranyl detection. Uranyl-triggered photocleavage causes the separation of the fluorescent-molecule-labelled protein fragments, leading to attenuation of the emission fluorescence, which is used as a signal for uranyl detection. This detection strategy shows high selectivity for uranyl and an ultralow detection limit of 24â pM with a broad detection range covering five orders of magnitude. The detection method also shows high reliability and stability, making it a promising technique for practical applications in diverse environments.
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Fluorescencia , Colorantes Fluorescentes/química , Albúmina Sérica Bovina/química , Uranio/análisis , Contaminantes Químicos del Agua/análisis , Animales , BovinosRESUMEN
Background: Teashirt homolog 2 (TSHZ2) is essential for maintaining cellular homeostasis and regulating transcription on neoplasia development. However, the regulation of TSHZ2 in lung tumorigenesis and the underlying mechanisms remain unclear. Objective: To evaluate the relationship between TSHZ2 expression in patients' tumor tissue and prognosis in lung adenocarcinoma. Methods: TSHZ2 expression in different lung adenocarcinoma cell lines and human tissue were detected by Western blotting. The effect of TSHZ2 on cell proliferation, apoptosis and migration in lung adenocarcinoma cells was measured by CCK8, colony formation, flowcytometric analyses and wound-healing, respectively. TSHZ2 expression in different lung adenocarcinoma cell lines and human tissue from patients was detected using Western blotting and immunohistochemical staining. We also retrospectively analyzed 226 lung adenocarcinoma patients after surgical resection using immunohistochemical staining, and the association of TSHZ2 expression with the patient survival was evaluated. Results: TSHZ2 was lowly expressed in certain lung adenocarcinoma cell lines (PC9 and B203L), but other cells showed a high expression. Low expression of TSHZ2 was also observed in most lung adenocarcinoma tissues compared with adjacent tissues. Furthermore, we found that the overexpression of TSHZ2 plasmids led to the dramatic inhibition of cell proliferation, colony formation ability, migration and apoptosis induction in PC9 lung adenocarcinoma cells. In contrast, no obvious effect was found when the TSHZ2 expression was down-regulated by si-TSHZ2. An elevated TSHZ2 expression was observed in 155(68.6%) tumor tissues samples of lung adenocarcinoma patients. Notably, the lung adenocarcinoma patients with a high TSHZ2 expression tended to have EGFR mutations less frequently and a preferable prognosis to those with a lower expression. Conclusion: A high TSHZ2 expression inhabited cell proliferation and predicted a better prognosis of lung adenocarcinoma, possibly representing a useful therapeutic target for lung adenocarcinoma.
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Adenocarcinoma del Pulmón/genética , Regulación Neoplásica de la Expresión Génica , Proteínas de Homeodominio/metabolismo , Neoplasias Pulmonares/genética , Adenocarcinoma del Pulmón/mortalidad , Adenocarcinoma del Pulmón/patología , Adenocarcinoma del Pulmón/cirugía , Adulto , Anciano , Anciano de 80 o más Años , Línea Celular Tumoral , Proliferación Celular/genética , Regulación hacia Abajo , Femenino , Estudios de Seguimiento , Proteínas de Homeodominio/análisis , Humanos , Estimación de Kaplan-Meier , Pulmón/patología , Pulmón/cirugía , Neoplasias Pulmonares/mortalidad , Neoplasias Pulmonares/patología , Neoplasias Pulmonares/cirugía , Masculino , Persona de Mediana Edad , Neumonectomía , PronósticoRESUMEN
Attachment of conceptus to the endometrial luminal epithelium (LE) is a critical event for early placentation in Eutheria. Since the attachment occurs at a particular site within the uterus, a coordinated communication between three spatially distinct compartments (conceptus and endometrial LE from two anatomical regions of the uterus to which conceptus attaches and does not attach) is essential but remains to be fully characterized. Using the laser capture microdissection (LCM) technique, we firstly developed an approach that can allow us to pair the pig conceptus sample with its nearby endometrial epithelium sample without losing the native spatial information. Then, a comprehensive spatio-temporal transcriptomic profile without losing the original conceptus-endometrium coordinates was constructed. The analysis shows that an apparent difference in transcriptional responses to the conceptus exists between the endometrial LE from the two anatomically distinct regions in the uterus. In addition, we identified the communication pathways that link the conceptus and endometrial LE and found that these pathways have important roles in conceptus attachment. Furthermore, a number of genes whose expression is spatially restricted in the two different anatomical regions within the uterus were characterized for the first time and two of them (SULT2A1 and MEP1B) may cooperatively contribute to establish conceptus attachment in pigs. The results from our study have implications in understanding of conceptus/embryo attachment in pigs and other large polytocous species.
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Comunicación Celular/genética , Endometrio/metabolismo , Porcinos/genética , Transcriptoma/genética , Animales , Implantación del Embrión/genética , Embrión de Mamíferos , Endometrio/crecimiento & desarrollo , Epitelio/metabolismo , Femenino , Captura por Microdisección con Láser , Embarazo , Porcinos/crecimiento & desarrollo , Útero/crecimiento & desarrollo , Útero/metabolismoRESUMEN
We present a method that jointly analyzes the polymorphism and divergence sites in genomic sequences of multiple species to identify the genes under natural selection and pinpoint the occurrence time of selection to a specific lineage of the species phylogeny. This method integrates population genetics models using a Bayesian Poisson random field framework and combines information over all gene loci to boost the power for detecting selection. The method provides posterior distributions of the fitness effects of each gene along with parameters associated with the evolutionary history, including the species divergence time and effective population size of external species. The results of simulations demonstrate that our method achieves a high power to identify genes under positive selection for a wide range of selection intensity and provides reasonably accurate estimates of the population genetic parameters. The proposed method is applied to genomic sequences of humans, chimpanzees, gorillas, and orangutans and identifies a list of lineage-specific targets of positive selection. The positively selected genes in the human lineage are enriched in pathways of gene expression regulation, immune system and metabolism, etc. Our analysis provides insights into natural evolution in the coding regions of humans and great apes and thus serves as a basis for further molecular and functional studies.
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Evolución Biológica , Modelos Genéticos , Selección Genética , Animales , Teorema de Bayes , Simulación por Computador , Genoma , Hominidae/genética , Humanos , Polimorfismo GenéticoRESUMEN
Background: Histological heterogeneity of lung adenocarcinoma may result in different prognosis among patients with the same TNM pathological stage. However, no objective evaluation system of lung adenocarcinoma based on pathological features has been widely accepted for assessing the prognosis. Methods: We retrospectively analyzed 179 patients with stage I lung adenocarcinoma after complete surgical resection. The pathological classification was according to the IASLC/ATS/ERS adenocarcinoma classifications, and the detailed abundance ratio using HE staining of primary tumor specimens was recorded. A new additional scoring formula on the pathological features (ASP) was established. The association of the ASP score with the patients' survival was examined. Results: The ASP scoring was significantly associated with smoking history (p=0.004), lymphatic vessel invasion (p<0.001), vascular invasion, differentiation (p<0.001) and Ki67 (p<0.001). The patients in the high-ASP-score group tended to have vascular invasion (odds ratio [OR]: 1.637, 95% confidence interval [CI]: 1.923-13.745, p=0.001) and high Ki67 expression (OR: 2.625, 95%CI: 1.328-5.190, p=0.006) by logistic regression analyses. The prognosis differed significantly in the Kaplan-Meier survival curves, and the 5-year survival rates in the low and high ASP score groups were 97.8% and 89.6%, respectively (p=0.018). Based on the univariate analysis, female (OR: 0.111, 95%CI: 0.014-0.906, p=0.040), long smoking history (OR: 7.250, 95%CI: 1.452-36.195, p=0.016), poor differentiation characteristics correlation (OR: 12.691, 95%CI: 1.557-103.453, p=0.018), and high ASP score (OR: 5.788, 95%CI: 1.138-29.423, p=0.034) were shown to be independently associated with an unfavorable prognosis. Conclusion: The ASP score can effectively screen high-risk patients for complete surgical resection of stage I lung adenocarcinoma.
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Adenocarcinoma del Pulmón/epidemiología , Recurrencia Local de Neoplasia/epidemiología , Pronóstico , Adenocarcinoma del Pulmón/diagnóstico , Adenocarcinoma del Pulmón/patología , Anciano , Supervivencia sin Enfermedad , Femenino , Humanos , Estimación de Kaplan-Meier , Masculino , Persona de Mediana Edad , Recurrencia Local de Neoplasia/diagnóstico , Recurrencia Local de Neoplasia/patología , Estadificación de NeoplasiasRESUMEN
Human skin color diversity is considered an adaptation to environmental conditions such as UV radiation. Investigations into the genetic bases of such adaptation have identified a group of pigmentation genes contributing to skin color diversity in African and non-African populations. Here, we present a population analysis of the pigmentation gene KITLG with previously reported signal of Darwinian positive selection in both European and East Asian populations. We demonstrated that there had been recurrent selective events in the upstream and the downstream regions of KITLG in Eurasian populations. More importantly, besides the expected selection on the KITLG variants favoring light skin in coping with the weak UV radiation at high latitude, we observed a KITLG variant showing adaptation to winter temperature. In particular, compared with UV radiation, winter temperature showed a much stronger correlation with the prevalence of the presumably adaptive KITLG allele in Asian populations. This observation was further supported by the in vitro functional test at low temperature. Consequently, the pleiotropic effects of KITLG, that is, pigmentation and thermogenesis were both targeted by natural selection that acted on different KITLG sequence variants, contributing to the adaptation of Eurasians to both UV radiation and winter temperature at high latitude areas.
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Aclimatación/genética , Pueblo Asiatico/genética , Selección Genética , Pigmentación de la Piel/genética , Factor de Células Madre/genética , Frío , Femenino , Humanos , Masculino , Rayos UltravioletaRESUMEN
Ancestry informative markers play an important role in medical genetics and forensic analyses. Several ancestry informative SNP panels have been developed and validated that can differentiate global populations into continental or major regional groups. These global panels have served as good first-tier genetic markers; however, their performance in discriminating populations within regions appears unsatisfactory. To boost ancestry inference for regional populations, second-tier panels with more refined discrimination power among subpopulations within each of the regions need to be developed. In East Asia, Han Chinese, Japanese, and Korean show highly similar externally visible characteristics and are genetically closely related. Reliable ancestry informative genetic markers appear invaluable in discriminating these populations. In the present study, we compiled a genome-wide SNP dataset composing of 317,439 clean SNPs for a total of 1101 unrelated individuals from Han Chinese (817), Koreans (184), and Japanese (100). From this starting dataset, we developed a set of four nested ancestry informative SNP panels including 36, 59, 98, and 142 SNPs, respectively. The results of cross-validation tests indicate that these panels can discriminate the Chinese Han, Japanese, and Korean populations with overall average accuracies ranging from 90% to 99%. In the further performance assessments, these panels also manifested high sensitivity and specificity. In combination with the first-tier global panels, these second-tier panels would contribute to medical genetics and forensic research in East Asia.
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Pueblo Asiatico/genética , Genética de Población , Polimorfismo de Nucleótido Simple , China , Humanos , Japón , República de CoreaRESUMEN
By chemical cross-linking the amidoxime group onto dual-surfaces of natural ore materials, namely halloysite nanotubes (HNTs), an efficient adsorbent, AO-HNTs, is developed. AO-HNTs show high uranium adsorption capacity of 456.24â mg g-1 in 32â ppm uranium-spiked simulated seawater. In natural seawater, AO-HNTs reach the high uranium extraction capacity of 9.01â mg g-1 after 30â days' field test. The dual-surface amidoximated hollow nanotubular AO-HNTs exhibit more coordination active sites for uranium adsorption, which is attributed to the high and fast uranium adsorption capacity. Because of the stable natural ore structure, AO-HNTs also show long service life. Benefiting from the low cost of HNTs, the cost for uranium extraction from seawater is close to the uranium price in the spot uranium market, suggesting that AO-HNTs could be used for economical extraction of uranium from the oceans.
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BACKGROUND/AIMS: Activator protein-2 (AP-2) transcription factors have been proved to be essential in maintaining cellular homeostasis and regulating the transformation from normal growth to neoplasia. However, the role of AP-2ß, a key member of AP-2 family, in breast cancer is rarely reported. METHODS: The effect of AP-2 on cell growth, migration and invasion in breast cancer cells were measured by MTT, colony formation, wound-healing and transwell assays, respectively. The expression levels of AP-2ß and other specific markers in breast cancer cell lines and tissue microarrays from the patients were detected using RT-PCR, Western blot and immunohistochemical staining. The regulation of AP-2ß on tumor growth in vivo was analyzed in a mouse xenograft model. RESULTS: We demonstrated the tumor-promoting function of AP-2ß in breast cancer. AP-2ß was found to be highly expressed in breast cancer cell lines and tumor tissues of breast cancer patients. The shRNA-mediated silencing of AP-2ß led to the dramatic inhibition of cell proliferation, colony formation ability, migration and invasiveness in breast cancer cells accompanied by the down-regulated expression of some key proteins involved in cancer progression, including p75, MMP-2, MMP-9, C-Jun, p-ERK and STAT3. Overexpression of AP-2ß markedly up-regulated the levels of these proteins. Consistent with the in vitro study, the silencing or overexpression of AP-2ß blocked or promoted tumor growth in the mice with xenografts of breast cancers. Notably, the high AP-2ß expression levels was correlated with poor prognosis and advanced malignancy in patients with breast cancer. CONCLUSIONS: Our study demonstrates that AP-2ß promotes tumor growth and predicts poor prognosis, and may represent a potential therapeutic target for breast cancer.
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Neoplasias de la Mama/metabolismo , Proliferación Celular , Proteínas de Neoplasias/metabolismo , Factor de Transcripción AP-2/metabolismo , Animales , Neoplasias de la Mama/diagnóstico , Neoplasias de la Mama/patología , Femenino , Xenoinjertos , Humanos , Células MCF-7 , Ratones , Ratones Endogámicos BALB C , Ratones Desnudos , Trasplante de Neoplasias , PronósticoRESUMEN
BACKGROUND/AIMS: ß-catenin is an integral component of the canonical Wnt signaling pathway, and its mutations are an autosomal recessive cause of colorectal cancer (CRC), medulloblastoma (MDB), and ovarian cancer. Nevertheless, little is known about its function in lung cancers. METHODS: We first knocked down ß-catenin by siRNA to investigate its effects on lung cancer cell proliferation, migration and apoptosis. Then we verified the interaction between ß-catenin and CREB binding protein (CBP) by immunofluoresence and co-immunoprecipition assays. Finally, the expression of ß-catenin and CBP in human lung adenocarcinoma specimens were analyzed by immunohistochemistry assay. RESULTS: ß-catenin knockdown inhibited cell proliferation, promoted apoptosis and suppressed cell migration in A549 and H460 cells accompanied by the decreased expression of Myc, PCNA, VEGF, CD44, MMP-9, MMP-13 and activated bax/caspase-3 pathway. Furthermore, co-immunoprecipition and immunofluoresence analyses revealed that CBP interacted with ß-catenin and contributed to ß-catenin-mediated lung cancer cell growth. Abolishment of their interaction by the Wnt/ß-catenin inhibitor ICG-001 remarkably suppressed cell proliferation. Immunohistochemistry assay of tissue microarrays from patients with lung cancer indicated that both CBP and ß-catenin were highly expressed in tumor tissues and predicted poor prognosis in lung adenocarcinoma patients. CONCLUSIONS: Our study has provided new evidence for the role of ß-catenin in promoting the growth of lung cancer cells through cooperation with CBP, and suggested that dual targeting of ß-catenin and CBP could be a potential therapeutic strategy in lung cancer treatment.
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Adenocarcinoma/patología , Proteína de Unión a CREB/metabolismo , Neoplasias Pulmonares/patología , beta Catenina/metabolismo , Células A549 , Adenocarcinoma/metabolismo , Adenocarcinoma/mortalidad , Anciano , Apoptosis/efectos de los fármacos , Compuestos Bicíclicos Heterocíclicos con Puentes/toxicidad , Proteína de Unión a CREB/antagonistas & inhibidores , Proteína de Unión a CREB/genética , Caspasa 3/metabolismo , Línea Celular Tumoral , Movimiento Celular/efectos de los fármacos , Proliferación Celular/efectos de los fármacos , Femenino , Humanos , Inmunohistoquímica , Estimación de Kaplan-Meier , Neoplasias Pulmonares/metabolismo , Neoplasias Pulmonares/mortalidad , Masculino , Metaloproteinasa 13 de la Matriz/metabolismo , Metaloproteinasa 9 de la Matriz/metabolismo , Microscopía Fluorescente , Persona de Mediana Edad , Estadificación de Neoplasias , Proteínas Proto-Oncogénicas c-bcl-2/metabolismo , Pirimidinonas/toxicidad , Interferencia de ARN , ARN Interferente Pequeño/metabolismo , Factor A de Crecimiento Endotelial Vascular/metabolismo , Vía de Señalización Wnt/efectos de los fármacos , Proteína X Asociada a bcl-2/metabolismo , beta Catenina/antagonistas & inhibidores , beta Catenina/genéticaRESUMEN
Aberrant overexpression of the transcription/translation factor Y-box-binding protein-1 (YBX1) is associated with non-small cell lung cancer (NSCLC) aggressiveness. Cancer stem cells (CSCs) contribute to the tumorigenesis and metastasis of NSCLC. Hitherto, the mechanism by which YBX1 regulates CSCs and metastasis in NSCLC remains unclear. Here, we demonstrated that YBX1 levels were elevated in NSCLC tissues and cell lines. Enforced expression of YBX1 promoted NSCLC cells invasion, sphere forming ability and ALDH1+ population. Conversely, reduced YBX1 impaired CSC properties of NSCLC cells in vitro and tumor-initiating frequencies, as well as metastasis in vivo. Importantly, we described a mechanism whereby YBX1 directly promoted NANOG, a transcription factor, transcriptional activation. Depletion of NANOG abolished the enhanced ability of invasion and sphere formation in YBX1 elevated-A549 cells. Collectively, these findings demonstrate a novel role of YBX1 in maintaining the stemness of CSCs and metastasis, unveiling YBX1 as promising therapeutic target for NSCLC treatments.
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Neoplasias Pulmonares/genética , Neoplasias Pulmonares/secundario , Proteína Homeótica Nanog/genética , Células Madre Neoplásicas/patología , Células Madre Neoplásicas/fisiología , Proteína 1 de Unión a la Caja Y/genética , Carcinogénesis/genética , Diferenciación Celular , Línea Celular Tumoral , Regulación Neoplásica de la Expresión Génica , Humanos , Neoplasias Pulmonares/patología , Invasividad Neoplásica , Activación Transcripcional/genéticaRESUMEN
BACKGROUND: M-type phospholipase A2 receptor (PLA2R) has been identified as the major target antigen in idiopathic membranous nephropathy (IMN). However, the role of glomerular PLA2R (gPLA2R) and the associations of serum anti-PLA2R antibody (sPLA2R-Ab) titre with diagnosis, treatment and prognosis in IMN need to be further investigated. METHODS: We screened 148 consecutive patients with biopsy-proven membranous nephropathy (MN; 113 with IMN and 35 with secondary MN (SMN)) who were followed up for ≤20 months. Serum and urine samples were simultaneously collected at different time points. The levels of sPLA2R-Ab were detected using immunofluorescence and enzyme-linked immunosorbent assay. gPLA2R was assessed by immunofluorescence. RESULTS: Most patients with IMN displayed both gPLA2R and sPLA2R-Ab positive (85.8 and 82.3%, respectively). In contrast, very few patients with SMN showed either gPLA2R or sPLA2R-Ab positive. The sPLA2R-Ab titre, not gPLA2R, was significantly correlated with proteinuria. Surprisingly, changes in sPLA2R-Ab titre occurred earlier and faster than proteinuria in patients who were followed up for ≤20 months during the whole period of observation. Survival analysis of IMN patients indicated a significant association between sPLA2R-Ab titre and outcome, whereas, no significant difference was observed between the gPLA2R intensity and outcome. CONCLUSIONS: These data indicate that sPLA2R-Ab might be a better biomarker for IMN diagnosis and treatment outcome. In addition, monitoring sPLA2R-Ab titre may assist in determining when to initiate the administration of immunosuppressive agents and in evaluating treatment efficacy.
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Anticuerpos/sangre , Glomerulonefritis Membranosa/inmunología , Glomerulonefritis Membranosa/metabolismo , Glomérulos Renales/química , Receptores de Fosfolipasa A2/análisis , Receptores de Fosfolipasa A2/inmunología , Adulto , Biomarcadores/sangre , Femenino , Humanos , Masculino , Persona de Mediana Edad , Tasa de SupervivenciaRESUMEN
The stripe rust pathogen Puccinia striiformis f. sp. tritici frequently causes significant yield losses in China, due to rapid development of new races that overcome resistance in wheat cultivars. Indirect evidence suggests that sexual reproduction occurs in the P. striiformis f. sp. tritici population in China but direct evidence was still lacking. In this study, a large-scale survey of barberry (Berberis spp.) was conducted in Gansu, Shaanxi, Tibet, and Xinjiang provinces in western China. In total, 9,297 single-aecial (SA) samples were used to inoculate a susceptible wheat cultivar to identify samples of P. striiformis f. sp. tritici. Sixteen of the SA samples were identified as P. striiformis f. sp. tritici. When tested on the wheat differentials for identifying P. striiformis f. sp. tritici races, 15 of the 16 SA samples had different virulence patterns, indicating that they were sexually produced through barberry. From the 16 SA samples, 118 single-uredinium (SU) isolates were obtained, from which 88 virulence patterns were identified when tested on 17 Yr single-gene lines. The virulence patterns had relatively narrow virulence spectra, ranging from 0 to 9, with a mean of four virulences per SU isolates. Of the 17 Yr genes, no virulences were detected for Yr5, Yr10, and Yr15; virulences to YrTr1, Yr24, and Yr27 were extremely low (<3%); those to YrSP, Yr9, Yr28, and Yr2 were low (13.6 to 28.0%); those to Yr7, Yr17, Yr8, and YrExp2 were moderate (33.1 to 48.3%); and those to Yr6, Yr44, and Yr25 were high (52.5 to 72.9%). This study provides direct evidence that natural sexual reproduction occurs in the P. striiformis f. sp. tritici population in China, but the frequency appears to be very low. The sexual reproduction on alternate host plants can generate a great virulence diversity, which may have contributed to the high variation in the P. striiformis f. sp. tritici population in China.
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Previous studies on the relationship of barberry (Berberis spp.) and wheat stem rust suggested that, although some barberry species can serve as alternate hosts for the stem rust fungus Puccinia graminis f. sp. tritici, barberry plants play no role in wheat stem rust development and virulence variation of P. graminis f. sp. tritici in China. In the present study, severe rust infections on Berberis shensiana, B. brachypoda, B. potaninii, B. soulieana, and B. aggregata were observed during field surveys in 2011 and 2012. Through artificial inoculation of wheat seedlings ('Mingxian 169') under greenhouse conditions with aeciospores from naturally infected barberry plants, 185 isolates of P. graminis f. sp. tritici were obtained. From the 27 selected isolates that were tested on a set of wheat genotypes used to differentiate P. graminis f. sp. tritici races in China, 18 races were identified, of which 8 races were new and others were of Chinese 21 and 34 race groups. In addition to the information of virulence or avirulence patterns on the Chinese differentials, none of the races were virulent to resistance gene Sr31. The virulence frequencies based on individual Sr genes or differentials ranged from 0 to 96%. Using molecular markers for P. graminis f. sp. tritici, 75 of 4,036 samples of single aecia were identified as P. graminis f. sp. tritici. The low detectable rate of P. graminis f. sp. tritici was verified based on both infection and molecular marker tests. This observation may be correlated with the low levels of wheat stem rust in the surveyed regions. This study shows that P. graminis f. sp. tritici can produce new races through sexual reproduction on Berberis spp. in China.
RESUMEN
BACKGROUND/PURPOSE: Understanding the mechanisms of protecting the kidneys from injury is of great importance because there are no effective therapies that promote repair and the kidneys frequently do not repair adequately. Evidence has shown that erythropoietin (EPO) has a vital renoprotective role, independent of its erythropoietic effect. However, whether EPO can contribute to kidney repair after injury and the potential mechanisms are not fully understood. METHODS: To investigate the renoprotective mechanism of EPO, a kidney ischemia/reperfusion injury (IRI) model was induced in adult male Sprague-Dawley rats. The rats were subsequently randomly treated with EPO or a vehicle 6 hours after the kidney IRI. The rats were sacrificed on Day 3, Day 5, and Day 7 post kidney IRI. Renal function and histological alterations were examined. Renal interstitial macrophage infiltration, cell proliferation, apoptosis, and angiogenesis were evaluated by immunostaining. Furthermore, the effects of EPO on the Wnt/ß-catenin pathway and IRI-related micro-RNAs were investigated. RESULTS: The administration of EPO significantly improved renal function and reduced tubular injury. Furthermore, EPO treatment significantly prevented tubular cell apoptosis and promoted cell proliferation after IRI. Erythropoietin significantly suppressed macrophage infiltration, compared to the vehicle. In addition, treatment with EPO markedly prevented the loss of microvasculature. We have also demonstrated that, compared to the vehicle, EPO administration enhanced the expression of Wnt7b and ß-catenin, and downregulated miR-21, -214, -210, and -199a. CONCLUSION: Erythropoietin protects the kidneys against IRI by attenuating injury of the renal microvasculature and tubule epithelial cells, by promoting Wnt/ß-catenin pathway activation, and by regulating miRNA expression.