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1.
Plant Biotechnol J ; 22(4): 802-818, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38217351

RESUMO

The microphenotype plays a key role in bridging the gap between the genotype and the complex macro phenotype. In this article, we review the advances in data acquisition and the intelligent analysis of plant microphenotyping and present applications of microphenotyping in plant science over the past two decades. We then point out several challenges in this field and suggest that cross-scale image acquisition strategies, powerful artificial intelligence algorithms, advanced genetic analysis, and computational phenotyping need to be established and performed to better understand interactions among genotype, environment, and management. Microphenotyping has entered the era of Microphenotyping 3.0 and will largely advance functional genomics and plant science.


Assuntos
Inteligência Artificial , Genômica , Fenótipo , Genômica/métodos , Genótipo , Plantas/genética
2.
J Plant Res ; 2024 Aug 07.
Artigo em Inglês | MEDLINE | ID: mdl-39112806

RESUMO

The vascular bundle in the ear-internode of maize is a key conduit for transporting photosynthetic materials between "source" and "sink", making it critically important to examine its micro-phenotypes and genetic architecture to identify advantageous characteristics and cultivate high-yielding and high-quality varieties. Unfortunately, the limited observation methods and scope of study precludes any comprehensive and systematic investigations into the microscopic phenotypes and genetic mechanisms of vascular bundle in maize ear-internode. In this study, 47 phenotypic traits were extracted in 495 maize inbred lines using micro computed tomography (Micro-CT) scanning technology and a deep learning-based phenotype acquisition method for stem vascular bundle, which included stem slice-related, epidermis zone-related, periphery zone-related, inner zone-related and vascular bundles-related traits. Phenotypic analysis indicated that there was extensive phenotypic variation of vascular bundle traits in ear-internode, especially that in the inner zone. Of these, 30 phenotypic traits with heritability greater than 0.70 were conducted for GWAS, and a total of 4,225 significant SNPs and 416 candidate genes with detailed functional annotations were identified. Furthermore, 20 genes were highly expressed in stem-related tissues, especially in maize internodes. Functional analysis of candidate genes indicated that the pathways obtained for candidate genes of different trait groups were distinct, mainly involved in vitamin synthesis and metabolism, transport of substances, carbohydrate derivative catabolic process, protein transport and localization, and anatomical structure development. The results of this study will help to further understand the phenotypic traits of stem vascular bundles and provide a reference for revealing the genetic mechanism of maize ear-internode vascular bundles.

3.
BMC Genomics ; 22(1): 134, 2021 Feb 25.
Artigo em Inglês | MEDLINE | ID: mdl-33632121

RESUMO

BACKGROUND: Bone marrow mesenchymal stem cells are a potential resource for the clinical therapy of certain diseases. Canine, as a companion animal, living in the same space with human, is an ideal new model for human diseases research. Because of the high prevalence of diabetes, alternative transplantation islets resource (i.e. insulin producing cells) for diabetes treatment will be in urgent need, which makes our research on the transdifferentiation of Bone marrow mesenchymal stem cells into insulin producing cells become more important. RESULT: In this study, we completed the transdifferentiation process and achieved the transcriptome profiling of five samples with two biological duplicates, namely, "BMSCs", "islets", "stage 1", "stage 2" and "stage 3", and the latter three samples were achieved on the second, fifth and eighth day of induction. A total of 11,530 differentially expressed transcripts were revealed in the profiling data. The enrichment analysis of differentially expressed genes revealed several signaling pathways that are essential for regulating proliferation and transdifferentiation, including focal adhesion, ECM-receptor interaction, tight junction, protein digestion and absorption, and the Rap1 signaling pathway. Meanwhile, the obtained protein-protein interaction network and functional identification indicating involvement of three genes, SSTR2, RPS6KA6, and VIP could act as a foundation for further research. CONCLUSION: In conclusion, to the best of our knowledge, this is the first survey of the transdifferentiation of canine BMSCs into insulin-producing cells according with the timeline using next-generation sequencing technology. The three key genes we pick out may regulate decisive genes during the development of transdifferentiation of insulin producing cells.


Assuntos
Insulinas , Células-Tronco Mesenquimais , Animais , Células da Medula Óssea , Transdiferenciação Celular/genética , Cães , Perfilação da Expressão Gênica , Humanos
4.
Plant Biotechnol J ; 19(1): 35-50, 2021 01.
Artigo em Inglês | MEDLINE | ID: mdl-32569428

RESUMO

High-throughput phenotyping is increasingly becoming an important tool for rapid advancement of genetic gain in breeding programmes. Manual phenotyping of vascular bundles is tedious and time-consuming, which lags behind the rapid development of functional genomics in maize. More robust and automated techniques of phenotyping vascular bundles traits at high-throughput are urgently needed for large crop populations. In this study, we developed a standard process for stem micro-CT data acquisition and an automatic CT image process pipeline to obtain vascular bundle traits of stems including geometry-related, morphology-related and distribution-related traits. Next, we analysed the phenotypic variation of stem vascular bundles between natural population subgroup (480 inbred lines) based on 48 comprehensively phenotypic information. Also, the first database for stem micro-phenotypes, MaizeSPD, was established, storing 554 pieces of basic information of maize inbred lines, 523 pieces of experimental information, 1008 pieces of CT scanning images and processed images, and 24 192 pieces of phenotypic data. Combined with genome-wide association studies (GWASs), a total of 1562 significant single nucleotide polymorphism (SNPs) were identified for 30 stem micro-phenotypic traits, and 84 unique genes of 20 traits such as VBNum, VBAvArea and PZVBDensity were detected. Candidate genes identified by GWAS mainly encode enzymes involved in cell wall metabolism, transcription factors, protein kinase and protein related to plant signal transduction and stress response. The results presented here will advance our knowledge about phenotypic trait components of stem vascular bundles and provide useful information for understanding the genetic controls of vascular bundle formation and development.


Assuntos
Feixe Vascular de Plantas , Zea mays , Estudos de Associação Genética , Fenótipo , Melhoramento Vegetal , Polimorfismo de Nucleotídeo Único , Zea mays/genética
5.
FASEB J ; 33(5): 5990-6000, 2019 05.
Artigo em Inglês | MEDLINE | ID: mdl-30726104

RESUMO

Despite surgical and chemotherapeutic advances over the past few decades, the prognosis for ovarian cancer remains very poor. Although cyclin-dependent kinase (CDK) 9 has an established pathogenic role in various cancers, its function in ovarian cancer remains poorly defined. The purpose of this study was to evaluate the expression of CDK9 and its therapeutic potential in ovarian cancer. CDK9 expression was determined by immunohistochemistry in a unique ovarian cancer tissue microarray constructed with paired primary, metastatic, and recurrent tumor tissues from 26 ovarian cancer patients. CDK9 was highly expressed in human ovarian cancer cell lines and was also elevated in metastatic and recurrent ovarian tumor tissue compared with patient-matched primary ovarian tumor tissue. In addition, increased CDK9 significantly correlated with poor patient prognosis. Inhibition of CDK9 by small interfering RNA or CDK9 inhibitor functionally suppressed RNA transcription elongation, induced apoptosis, and reduced proliferation of ovarian cancer cells. Inhibition of CDK9 also suppressed ovarian cancer cell spheroid growth, clonogenicity formation, and migration activity. Our results reveal CDK9 as a novel prognostic biomarker and a promising therapeutic target for preventing metastasis and recurrence while also improving the overall clinical outcome for ovarian cancer patients.-Wang, J., Dean, D. C., Hornicek, F. J., Shi, H., Duan, Z. Cyclin-dependent kinase 9 (CDK9) is a novel prognostic marker and therapeutic target in ovarian cancer.


Assuntos
Biomarcadores Tumorais/metabolismo , Quinase 9 Dependente de Ciclina/genética , Quinase 9 Dependente de Ciclina/metabolismo , Neoplasias Ovarianas/metabolismo , Apoptose , Biomarcadores Tumorais/genética , Linhagem Celular Tumoral , Movimento Celular , Proliferação de Células , Feminino , Humanos , Imuno-Histoquímica , Metástase Neoplásica , Recidiva Local de Neoplasia , Neoplasias Ovarianas/diagnóstico , Neoplasias Ovarianas/patologia , Prognóstico , RNA Interferente Pequeno/metabolismo , Transdução de Sinais , Análise Serial de Tecidos
6.
Int J Mol Sci ; 21(15)2020 Aug 03.
Artigo em Inglês | MEDLINE | ID: mdl-32756402

RESUMO

Long noncoding RNAs (lncRNAs) have been extensively explored over the past decade, including mice and humans. However, their impact on the transdifferentiation of canine bone marrow mesenchymal stem cells (cBMSCs) into insulin-producing cells (IPCs) is largely unknown. In this study, we used a three-step induction procedure to induce cBMSCs into IPCs, and samples (two biological replicates each) were obtained after each step; the samples consisted of "BMSCs" (B), "stage 1" (S1), "stage 2" (S2), "stage 3" (S3), and "islets" (I). After sequencing, 15,091 lncRNAs were identified, and we screened 110, 41, 23, and 686 differentially expressed lncRNAs (padjusted < 0.05) in B vs. S1, S1 vs. S2, S2 vs. S3, and I vs. S3 pairwise comparisons, respectively. In lncRNA target prediction, there were 166,623 colocalized targets and 2,976,362 correlated targets. Gene Ontology (GO) analysis showed that binding represented the main molecular functions of both the cis- and trans-modes. Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis suggested that the insulin signaling pathway, Rap1 signaling pathway, tight junctions, MAPK signaling pathway, and cell cycle were enriched for these relative genes. The expression of lncRNAs was verified using qRT-PCR. This study provides a lncRNA catalog for future research concerning the mechanism of the transdifferentiation of cBMSCs into IPCs.


Assuntos
Genoma/genética , Células Secretoras de Insulina/metabolismo , Insulinas/genética , RNA Longo não Codificante/genética , Animais , Diferenciação Celular/genética , Biologia Computacional , Cães , Perfilação da Expressão Gênica , Regulação da Expressão Gênica/genética , Humanos , Insulinas/metabolismo , Células-Tronco Mesenquimais , Camundongos , Transdução de Sinais/genética
7.
Clin Sci (Lond) ; 133(14): 1567-1579, 2019 07 31.
Artigo em Inglês | MEDLINE | ID: mdl-31292221

RESUMO

Long non-coding RNAs (lncRNAs) are known to be potential factors in promoting tumor progression. However, the function and mechanism of lncRNA XIST in non-small cell lung cancer (NSCLC) remains poorly understood. The expression levels of lncRNA XIST in NSCLC tissues and cell lines were detected with real-time PCR, and the correlation of the expression level of XIST with histopathological characteristics and prognosis was analyzed. The biological function of lncRNA XIST was validated through assays in vivo and in vitro The expression of lncRNA XIST was significantly up-regulated in NSCLC tissues. In addition, overexpression of XIST was positively correlated with the advanced clinical status of tumors, as well as poor overall survival and DFS. A tumor suppressive effect was presented via functional knockdown of lncRNA XIST. Up-regulation of XIST enhanced the proliferation, migration, and invasion ability of NSCLC cells both in vivo and in vitro Mechanically, it was indicated that XIST could serve as an endogenous competitive RNA modulating miR-744, leading to the miR-744/RING1 signaling pathway inhibition and Wnt/ß-catenin signaling pathway activation. Taken together, it was confirmed here that XIST overexpression is associated with tumor progression phenotype and the newly discovered XIST/miR-744/RING1 axis, which could serve as a potential biomarker and therapeutic target for NSCLC.


Assuntos
Carcinoma Pulmonar de Células não Pequenas/genética , Proliferação de Células , Neoplasias Pulmonares/genética , MicroRNAs/genética , Complexo Repressor Polycomb 1/genética , RNA Longo não Codificante/metabolismo , Células A549 , Carcinoma Pulmonar de Células não Pequenas/metabolismo , Carcinoma Pulmonar de Células não Pequenas/fisiopatologia , Linhagem Celular Tumoral , Regulação Neoplásica da Expressão Gênica , Humanos , Neoplasias Pulmonares/metabolismo , Neoplasias Pulmonares/fisiopatologia , MicroRNAs/metabolismo , Complexo Repressor Polycomb 1/metabolismo , RNA Longo não Codificante/genética , Via de Sinalização Wnt
8.
Gynecol Oncol ; 152(1): 194-201, 2019 01.
Artigo em Inglês | MEDLINE | ID: mdl-30297273

RESUMO

Despite the surgical and chemotherapeutic advances over the past few decades, ovarian cancer remains the leading cause of gynecological cancer-related mortality. The absence of biomarkers in early detection and the development of drug resistance are principal causes of treatment failure in ovarian cancer. Recent progress in RNA sequencing (RNA-Seq) with Next Generation Sequencing technology has expanded the understanding of the molecular pathogenesis of ovarian cancer. As compared to previous hybridization-based microarray and Sanger sequence-based methods, RNA-Seq provides multiple layers of resolutions and transcriptome complexity, with less background noise and a broader dynamic range of RNA expression. Beyond quantifying gene expression, the data generated by RNA-Seq accelerates the identification of alternatively spliced genes, fusion genes, mutations/SNPs, allele-specific expression, novel transcripts and non-coding RNAs. RNA-Seq has been successfully applied in ovarian cancer research for earlier detection, ascertaining pathological origin, and defining the aberrant genes and dysregulated molecular pathways across patient groups. This review outlines the distinct advantages of RNA-Seq compared to other transcriptomics methods and its recent applications in ovarian cancer.


Assuntos
Neoplasias Ovarianas/genética , Análise de Sequência de RNA/métodos , Biomarcadores Tumorais/análise , Resistência a Múltiplos Medicamentos , Detecção Precoce de Câncer , Feminino , Sequenciamento de Nucleotídeos em Larga Escala , Humanos , Neoplasias Ovarianas/diagnóstico , Neoplasias Ovarianas/patologia , Transcriptoma
9.
Oncology ; 95(1): 52-60, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-29617702

RESUMO

PURPOSE: Recent studies highlight the role of autophagy in cancer tumorigenesis, recurrence, metastasis, and chemoresistance. p62 is an adapter protein that is crucial for the autophagy pathway. In this study, we will describe the expression of p62 and its correlation with clinic prognosis in osteosarcoma. METHODS: Western blot was used to test the expression of p62 in osteosarcoma cell lines (U2OS, KHOS, MG63, Saos-2, U2OSR2, KHOSR2, and 143B). A tissue microarray (TMA) was analyzed by immunohistochemistry to determine the expression levels of p62 in osteosarcoma patients and evaluate any correlation between p62 and clinical characteristics in osteosarcoma patients. RESULTS: p62 was expressed differently in all cell lines. The TMA also showed differential expression in osteosarcoma tissues. Seventy-five of 79 (94.9%) patient tissues exhibited p62 immunostaining, ranging from no staining (4 of 97, 5.1%) to 1+ staining (40 of 79, 50.6%), 2+ staining (17 of 79, 21.5%), and 3+ staining (18 of 79, 22.8%). The low staining (1+) was classified as the p62 weak group (50.6%), the medium staining (2+) and intense staining (3+) were classified as the p62 strong group (44.3%). Analyzing the clinical data of the osteosarcoma TMA, we found that the 5-year survival rate of patients with weak p62 expression was significantly lower than that of the patients with strong p62 expression (p = 0.0165). Furthermore, the decreased p62 expression may be associated with higher metastatic and chemoresistant rates in osteosarcoma patients. CONCLUSION: Our results suggest that p62 may be an effective predictor of prognosis and a potential target for therapy in osteosarcoma.


Assuntos
Autofagia/fisiologia , Neoplasias Ósseas/patologia , Osteossarcoma/patologia , Proteínas de Ligação a RNA/biossíntese , Adolescente , Autofagia/genética , Biomarcadores Tumorais/metabolismo , Neoplasias Ósseas/genética , Carcinogênese/genética , Linhagem Celular Tumoral , Proliferação de Células , Intervalo Livre de Doença , Feminino , Regulação Neoplásica da Expressão Gênica/genética , Humanos , Masculino , Recidiva Local de Neoplasia/patologia , Osteossarcoma/genética , Proteínas de Ligação a RNA/genética , Taxa de Sobrevida
10.
Gynecol Oncol ; 150(1): 143-150, 2018 07.
Artigo em Inglês | MEDLINE | ID: mdl-29699801

RESUMO

OBJECTIVE: Multidrug resistance is the major cause of treatment failure in ovarian cancer. p62 (SQSTM1) is a multifunctional protein involved in multiple cellular processes including proliferation, drug sensitivity and autophagy-associated cancer cell growth. However, the role of p62 in drug resistance remains controversial. METHODS: In this study, we examined p62 expression by immunohistochemistry in a unique ovarian cancer tissue microarray (TMA), which was constructed with paired primary, metastatic, and recurrent tumor tissues. The expression levels of p62 and autophagy related proteins were evaluated in two panels of human cancer cell lines by western blot. Cell viabilities were determined by MTT assay after exposure ovarian cancer cells to different concentrations of paclitaxel alone or in combination with autophagy inhibitors. RESULTS: Both the metastatic and recurrent tumor tissues expressed less p62 than the patient-matched primary tumor. A significant inverse correlation has been found between p62 expression and both the disease-free survival and overall survival. Additionally, multidrug resistant cancer cell lines expressed lower levels of p62 as compared with their parental drug sensitive cell lines. Importantly, inhibition of autophagy enhanced paclitaxel sensitivity in drug resistant ovarian cancer cells. Furthermore, the wound healing assay exhibited that the inhibition of autophagy significantly decreased resistant ovarian cancer cell migration in vitro. CONCLUSION: Our findings highlight the potential of p62 as a new prognostic marker for ovarian cancer patients and p62's associated autophagy pathway may be a promising therapeutic target to prevent metastasis, recurrence and to reverse drug resistance in ovarian cancer.


Assuntos
Neoplasias Ovarianas/metabolismo , Proteína Sequestossoma-1/biossíntese , Adenina/administração & dosagem , Adenina/análogos & derivados , Protocolos de Quimioterapia Combinada Antineoplásica/farmacologia , Autofagia , Linhagem Celular Tumoral , Movimento Celular/fisiologia , Resistencia a Medicamentos Antineoplásicos , Feminino , Humanos , Hidroxicloroquina/administração & dosagem , Imuno-Histoquímica , Recidiva Local de Neoplasia/genética , Recidiva Local de Neoplasia/metabolismo , Recidiva Local de Neoplasia/patologia , Neoplasias Ovarianas/tratamento farmacológico , Neoplasias Ovarianas/genética , Neoplasias Ovarianas/patologia , Paclitaxel/administração & dosagem , Proteína Sequestossoma-1/genética , Proteína Sequestossoma-1/metabolismo
11.
Genome ; 61(7): 505-513, 2018 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-29800531

RESUMO

Although many gene expression profiling studies of maize leaves infected with Ustilago maydis have been published, heterogeneity of the results, caused by various data processing methods and pathogenic strains in different data sets, remains strong. Hence, we conducted a combined analysis of six genome-wide expression data sets of maize leaves infected with five different U. maydis strains by using the same pre-processing and quality control procedures. Six data sets were regrouped into five groups according to pathogenic strain used. Subsequently, each group of data set was processed by Multi-array Average for pre-processing and by pair-wise Pearson correlation for quality control. The differentially expressed genes were calculated by a standard linear mixed-effect model and then validated by various sensitivity analysis and multiple evidences. Finally, 44 unique differentially expressed genes were identified. Pathway enrichment analysis indicated that these genes related to response to fungus, oxidation-reduction, transferase activity, and several carbohydrate metabolic and catabolic processes. In addition, the hub genes within protein-protein interaction networks showed high relevance with the basic pathogenesis. We report a highly credible differentially expressed list, and the genes with multiple validations may denote a common signature of U. maydis in maize, which provides a new window for disease-resistant protection of maize plants.


Assuntos
Perfilação da Expressão Gênica , Regulação da Expressão Gênica de Plantas , Doenças das Plantas/genética , Zea mays/genética , Redes Reguladoras de Genes/genética , Genes de Plantas/genética , Interações Hospedeiro-Patógeno , Doenças das Plantas/microbiologia , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismo , Mapas de Interação de Proteínas/genética , Ustilago/fisiologia , Zea mays/microbiologia
12.
Biol Res ; 51(1): 40, 2018 Oct 27.
Artigo em Inglês | MEDLINE | ID: mdl-30368254

RESUMO

BACKGROUND: The biomechanical properties of maize stalks largely determine their lodging resistance, which affects crop yield per unit area. However, the quantitative and qualitative relationship between micro-phenotypes and the biomechanics of maize stalks is still under examined. In particular, the roles of the number, geometry, and distribution of vascular bundles of stalks in maize lodging resistance remain unclear. Research on these biomechanical properties will benefit from high-resolution micro-phenotypic image acquisition capabilities, which have been improved by modern X-ray imaging devices such as micro-CT and the development of micro-phenotyping analysis software. Hence, high-throughput image analysis and accurate quantification of anatomical phenotypes of stalks are necessary. RESULTS: We have updated VesselParser version 1.0 to version 2.0 and have improved its performance, accuracy, and computation strategies. Anatomical characteristics of the second and third stalk internodes of the cultivars 'Jingke968' and 'Jingdan38' were analyzed using VesselParser 2.0. The relationships between lodging resistance and anatomical phenotypes of stalks between the two different maize varieties were investigated. The total area of vascular bundles in the peripheral layer, auxiliary axis diameter, and total area of vascular bundles were revealed to have the highest correlation with mechanical properties, and anatomical phenotypes of maize stalk were better predictors of mechanical properties than macro features observed optically from direct measurement, such as diameter and perimeter. CONCLUSIONS: This study demonstrates the utility of VesselParser 2.0 in assessing stalk mechanical properties. The combination of anatomical phenotypes and mechanical behavior research provides unique insights into the problem of stalk lodging, showing that micro phenotypes of vascular bundles are good predictors of maize stalk mechanical properties that may be important indices for the evaluation and identification of the biomechanical properties to improve lodging resistance of future maize varieties.


Assuntos
Ensaios de Triagem em Larga Escala/métodos , Fenótipo , Caules de Planta/anatomia & histologia , Feixe Vascular de Plantas/anatomia & histologia , Zea mays/anatomia & histologia , Processamento de Imagem Assistida por Computador , Caules de Planta/genética , Valores de Referência , Reprodutibilidade dos Testes , Microtomografia por Raio-X/métodos , Zea mays/genética
13.
BMC Cancer ; 17(1): 851, 2017 Dec 14.
Artigo em Inglês | MEDLINE | ID: mdl-29241458

RESUMO

BACKGROUND: This study was aimed at investigating whether metformin can reverse the resistance of ovarian cancer cells to cisplatin and exploring the underlying mechanism. METHODS: Ovarian cancer cell proliferation in vitro was evaluated using a CCK-8 assay. The resistance index of platinum-resistant ovarian cancer cells was determined and cell cycle and apoptosis rate determined by annexin V/propidium iodide double-staining in CP70 cells. Western blotting was used to determine IGF1, IGF1R, AKT, p-IGF1, p-IGF1R, p-AKT, and MRP2 levels in cells treated with different concentrations of metformin and LY29400, an inhibitor of the insulin-like growth factor pathway. Changes in gene expression levels of MRP2, IGF1, IGF1R, and AKT were determined by fluorescence real-time quantitative PCR assay of CP70 cells treated with metformin. Tumors of human ovarian cancer cell lines CP70 and A2780 were established by subcutaneous transplantation of cells in nude mice and the effect of metformin on MRP2 expression and tumor inhibition assessed. RESULTS: The IC50 value of cisplatin in CP70 cells decreased significantly as metformin concentration increased (P < 0.05). The cell cycle distribution in CP70 cells changed with metformin treatment; the percentage of cells in the G0/G1 phase, as well as the natural apoptosis rate was significantly increased with metformin treatment (P < 0.05). IGF1, IGF1R, AKT p-IGF1, p-IGF1R, and p-Akt protein expression was enhanced dose-dependently with metformin, and was also significantly changed by treatment of CP70 cells with 0 mM metformin +10 mM LY294002. Moreover, changes in the expression of MRP2, IGF1, IGF1R, and AKT was metformin-concentration dependent, and was significantly different from that in the untreated control group (P < 0.05). In nude mice, the tumor volumes of the cisplatin-treated groups were significantly less than in the control group, and was further suppressed by co-treatment with cisplatin and metformin (P < 0.05), indicating that these 2 drugs had a synergistic effect on tumor inhibition. CONCLUSION: Metformin can improve the sensitivity of ovarian cancer CP70 cells to cisplatin in a concentration-dependent manner by activating the AKT signaling pathway, inhibiting the IGF1R signaling pathway, and reducing MRP2 expression.


Assuntos
Antineoplásicos/farmacologia , Protocolos de Quimioterapia Combinada Antineoplásica/farmacologia , Resistencia a Medicamentos Antineoplásicos/efeitos dos fármacos , Neoplasias Ovarianas/tratamento farmacológico , Transdução de Sinais/efeitos dos fármacos , Animais , Antineoplásicos/uso terapêutico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Linhagem Celular Tumoral , Cromonas/farmacologia , Cisplatino/farmacologia , Cisplatino/uso terapêutico , Relação Dose-Resposta a Droga , Sinergismo Farmacológico , Feminino , Concentração Inibidora 50 , Metformina/farmacologia , Metformina/uso terapêutico , Camundongos , Camundongos Nus , Morfolinas/farmacologia , Proteína 2 Associada à Farmacorresistência Múltipla , Proteínas Associadas à Resistência a Múltiplos Medicamentos/metabolismo , Neoplasias Ovarianas/patologia , Proteínas Proto-Oncogênicas c-akt/metabolismo , Receptor IGF Tipo 1 , Receptores de Somatomedina/metabolismo , Ensaios Antitumorais Modelo de Xenoenxerto
14.
J Cell Biochem ; 117(4): 844-52, 2016 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-26365432

RESUMO

Previous studies have shown that promyelocytic leukemia zinc finger (PLZF), chemokine (C-X-C motif) receptor 4 (CXCR4) and mir146a were associated with the self-renewal of mouse spermatogonial stem cells (SSCs); however, there is little information on their effects on the fate of livestock SSCs. Here, we have identified a regulatory pathway in dairy goat mGSCs, involving PLZF, mir146a and the SDF-1 receptor CXCR4. PLZF overexpression downregulated mir146a and simultaneously upregulated the expression of CXCR4 protein, whereas PLZF knockdown (siPLZF) induced the specifically opposite effects. The in vitro assays demonstrated that PLZF specifically interacts with and suppresses the mir146a promoter, and mir146a targets CXCR4 to impede its translation. The levels of ERK1/2 phosphorylation in the mGSCs overexpressed CXCR4 and PLZF were upregulated, respectively, whereas mir146a expression was decreased and CXCR4 protein was increased. Mir146a overexpression and siPLZF impaired mGSC proliferation and differentiation, however, Mir146a knockdown induced the opposite effects. The effects of PLZF and mir146a were mediated regulation by mir146a and CXCR4, respectively. Overexpression of CXCR4 or addition of CXCL12 in cultures of dairy goat mGSCs resulted in the upregulation of their signaling, and the phosphorylation of ERK1/2 was increased. Collectively, these findings indicate that PLZF is an important transcription factor in the regulation of the expression of CXCR4 to promote dairy goat mGSC proliferation by targeting mir146a.


Assuntos
Células-Tronco Adultas/metabolismo , Fatores de Transcrição Kruppel-Like/genética , MicroRNAs/genética , Receptores CXCR4/genética , Espermatogônias/metabolismo , Células-Tronco Adultas/citologia , Animais , Diferenciação Celular , Proliferação de Células , Quimiocina CXCL12/genética , Quimiocina CXCL12/metabolismo , Indústria de Laticínios , Feminino , Regulação da Expressão Gênica , Cabras , Fatores de Transcrição Kruppel-Like/antagonistas & inibidores , Fatores de Transcrição Kruppel-Like/metabolismo , Masculino , MicroRNAs/antagonistas & inibidores , MicroRNAs/metabolismo , Proteína Quinase 1 Ativada por Mitógeno/genética , Proteína Quinase 1 Ativada por Mitógeno/metabolismo , Proteína Quinase 3 Ativada por Mitógeno/genética , Proteína Quinase 3 Ativada por Mitógeno/metabolismo , Fosforilação , Regiões Promotoras Genéticas , Biossíntese de Proteínas , RNA Interferente Pequeno/genética , RNA Interferente Pequeno/metabolismo , Receptores CXCR4/metabolismo , Transdução de Sinais , Espermatogônias/citologia
15.
Zhonghua Fu Chan Ke Za Zhi ; 50(9): 685-91, 2015 Sep.
Artigo em Chinês | MEDLINE | ID: mdl-26675396

RESUMO

OBJECTIVE: To investigate the effects of metformin on cell proliferation in differentiation degree of endometrial carcinoma cells and related mechanisms. METHODS: The endometrial cancer cell lines Ishikawa and AN3CA were used. Cell proliferation was assessed after exposure to metformin with or without epithelial growth factor receptor (EGFR) inhibitor AG1478 by cell counting kit-8 (CCK-8) method. EGFR mRNA was determined by reverse transcription (RT)-PCR. The expression of phosphorylation EGFR (p-EGFR) and total EGFR (t-EGFR) and phosphorylation extracellular signal-regulated kinase 1/2 (p-ERK1/2) and total ERK1/2 (t-ERK1/2) were examined by western blot. RESULTS: (1) CCK-8 experiment showed that metformin could inhibit the proliferation of endometrial cancer cells in a time-dependent manner and a dose-dependent manner (P < 0.05), but the inhibition of well differentiated cell line Ishikawa was lower than that in poorly differentiated cells AN3CA (P < 0.05). AG1478 also could inhibit the proliferation of endometrial cancer cells in a time-dependent manner and in a dose-dependent manner (P < 0.05), but the inhibition rate of well differentiated cell line Ishikawa was higher than that in poorly differentiated cells AN3CA (P < 0.05). Metformin + AG1478 also could inhibit the proliferation of endometrial cancer cells in a time-dependent manner and in a dose-dependent manner (P < 0.05), and the inhibition of combined with metformin and AG1478 was stronger than that with a single application of drugs, but the inhibition rate of Ishikawa was higher than that in AN3CA (P < 0.05). (2) RT-PCR method showed that different concentrations of metformin (0.01, 0.1, 1, 5, 10 mmol/L, respectively) for 24 hours, the expression level of EGFR mRNA in Ishikawa cells were respectively 0.74 ± 0.03, 0.61 ± 0.04, 0.46 ± 0.03, 0.31 ± 0.03 and 0.23 ± 0.03, the expression level of EGFR mRNA in AN3CA cells were respectively 0.79 ± 0.20, 0.61 ± 0.03, 0.50 ± 0.05, 0.32 ± 0.03 and 0.26 ± 0.04, the inhibition effect showed a significant concentration-dependent manner (all P < 0.01). (3) Western blot method displayed that the effect of metformin treated respectively 2, 4, 6 or 8 hours, there were not significant difference in the expression levels of t-EGFR protein and t-ERK1/2 between Ishikawa and AN3CA cells (all P > 0.05). But the expression levels of p-EGFR and p-ERK1/2 protein were significantly lower between two groups (P < 0.01), which showed a time-dependent manner (P < 0.01). CONCLUSION: Metformin could inhibit the proliferation of endometrial cancer cells, the inhibition is associated with the differentiation degree of cancer cells. Metformin could enhance the EGFR signaling pathway inhibitor AG1478 inhibition of endometrial cancer cells, which may inhibit EGFR expression of phosphorylated proteins to inhibit the phosphorylation of ERK1/2 proteins and then inhibit proliferation of endometrial cancer cells.


Assuntos
Diferenciação Celular/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Endométrio/efeitos dos fármacos , Hipoglicemiantes/farmacologia , Metformina/farmacologia , Antineoplásicos , Regulação para Baixo , Neoplasias do Endométrio/genética , Neoplasias do Endométrio/metabolismo , Neoplasias do Endométrio/prevenção & controle , Endométrio/metabolismo , Feminino , Humanos , Proteína Quinase 3 Ativada por Mitógeno , Fosforilação , Quinazolinas , Transdução de Sinais , Tirfostinas
16.
Biochem Biophys Res Commun ; 449(4): 432-7, 2014 Jul 11.
Artigo em Inglês | MEDLINE | ID: mdl-24858688

RESUMO

Ovarian cancer is the leading cause of death from gynecological malignancies worldwide. Understanding the molecular mechanism underlying ovarian cancer progression facilitates the development of promising strategy for ovarian cancer therapy. Previously, we observed frequent down-regulation of miR-497 expression in ovarian cancer tissues. In this study, we investigated the role of miR-497 in ovarian cancer metastasis. We found that endogenous miR-497 expression was down-regulated in the more aggressive ovarian cancer cell lines compared with the less aggressive cells. Exogenous expression of miR-497 suppressed ovarian cancer cell migration and invasion, whereas reduction of endogenous miR-497 expression induced tumor cell migration and invasion. Mechanistic investigations confirmed pro-metastatic factor SMURF1 as a direct target of miR-497 through which miR-497 ablated tumor cell migration and invasion. Further studies revealed that lower levels of miR-497 expression were associated with shorter overall survival as well as increased SMURF1 expression in ovarian cancer patients. Our results indicate that down-regulation of miR-497 in ovarian cancer may facilitate tumor metastasis. Restoration of miR-497 expression may be a promising strategy for ovarian cancer therapy.


Assuntos
MicroRNAs/fisiologia , Neoplasias Ovarianas/patologia , Ubiquitina-Proteína Ligases/antagonistas & inibidores , Linhagem Celular Tumoral , Movimento Celular/efeitos dos fármacos , Regulação para Baixo , Feminino , Humanos , MicroRNAs/biossíntese , Invasividade Neoplásica/fisiopatologia , Prognóstico
17.
Plant Phenomics ; 6: 0225, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-39108845

RESUMO

Marked variations in the 3-dimensional (3D) shape of corn leaves can be discerned as a function of various influences, including genetics, environmental factors, and the management of cultivation processes. However, the causes of these variations remain unclear, primarily due to the absence of quantitative methods to describe the 3D spatial morphology of leaves. To address this issue, this study acquired 3D digitized data of ear-position leaves from 478 corn inbred lines during the grain-filling stage. We propose quantitative calculation methods for 13 3D leaf shape features, such as the leaf length, 3D leaf area, leaf inclination angle, blade-included angle, blade self-twisting, blade planarity, and margin amplitude. Correlation analysis, cluster analysis, and heritability analysis were conducted among the 13 leaf traits. Leaf morphology differences among subpopulations of the inbred lines were also analyzed. The results revealed that the 3D leaf traits are capable of revealing the morphological differences among different leaf surfaces, and the genetic analysis revealed that 84.62% of the 3D phenotypic traits of ear-position leaves had a heritability greater than 0.3. However, the majority of 3D leaf shape traits were strongly affected by environmental conditions. Overall, this study quantitatively investigated 3D leaf shape in corn, providing a reliable basis for further research on the genetic regulation of corn leaf morphology and advancing the understanding of the complex interplay among crop genetics, phenotypes, and the environment.

18.
Nanomaterials (Basel) ; 13(16)2023 Aug 08.
Artigo em Inglês | MEDLINE | ID: mdl-37630867

RESUMO

The emergence of the Internet of things stimulates the pursuit of flexible and miniaturized supercapacitors. As an advanced technology, screen printing displays vigor and tremendous potential in fabricating supercapacitors, but the adoption of high-performance ink is a great challenge. Here, hierarchical V3O7 with rodlike texture was prepared via a facile template-solvothermal route; and the morphology, component, and valence bond information are characterized meticulously. Then, the screen-printed inks composed of V3O7, acetylene black, and PVDF are formulated, and the rheological behaviors are studied detailedly. Benefitting from the orderly aligned ink, the optimal screen-printed electrode can exhibit an excellent specific capacitance of 274.5 F/g at 0.3 A/g and capacitance retention of 81.9% after 5000 cycles. In addition, a flexible V3O7 symmetrical supercapacitor (SSC) is screen-printed and assembled on the Ag current collector, exhibiting a decent areal specific capacitance of 322.5 mF/cm2 at 0.5 mA/cm2, outstanding cycling stability of 90.8% even after 5000 cycles, satisfactory maximum energy density of 129.45 µWh/cm2 at a power density of 0.42 mW/cm2, and remarkable flexibility and durability. Furthermore, a single SSC enables the showing of an actual voltage of 1.70 V after charging, and no obvious self-discharge phenomenon is found, revealing the great applied value in supply power. Therefore, this work provides a facile and low-cost reference of screen-printed ink for large-scale fabrication of flexible supercapacitors.

19.
Poult Sci ; 102(2): 102335, 2023 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-36470031

RESUMO

Hexavalent chromium (Cr(Ⅵ)) is considered to be a common environmental pollutant, which widely exists in industrial effluents and wastes and then potentially noxious effects to the health of the poultry. Studies have reported that selenium (Se), which is one of the essential trace elements of the poultry and participates in the oxidative metabolism, can alleviate Cr(Ⅵ)-induced organ damage by inhibiting oxidative stress, but its specific molecular mechanism remains unclear. Herein, animal models of Cr(Ⅵ)- and Se-exposure were constructed using broilers to investigate the antagonistic mechanism of Se to Cr(Ⅵ)-induced hepatotoxicity. In this experiment, the four groups of broiler models were used as the research objects: control, Se, Se plus Cr, and Cr groups. Histopathology and ultrastructure liver changes were observed. Liver-somatic index, serum biochemistry, oxidative stress, Nrf2 pathway related factors, and autophagy-related genes were also determined. Overall, Se was found to ameliorate the disorganized structure, hepatic insufficiency, and oxidative damage caused by Cr(Ⅵ) exposure. Electron microscopy analysis further showed that the number of autophagosomes was obviously decreased after Se treatment compared to Cr group. Furthermore, gene and protein expression analyses illustrated that the levels of Nrf2, glutathione peroxidase 1 (GPx-1), NAD(P)H: quinone oxidoreductase 1 (NQO1), and mechanistic target of rapamycin (mTOR) in the Se&Cr group was upregulated, along with decreased expression of Beclin 1, ATG5 and LC3 compared to the Cr group. These suggest that Se can repair the oxidative lesion and autophagy induced by Cr(Ⅵ) exposure in broiler livers by upregulating the Nrf2 signaling pathway.


Assuntos
Doença Hepática Induzida por Substâncias e Drogas , Selênio , Animais , Selênio/farmacologia , Selênio/metabolismo , Galinhas/metabolismo , Fator 2 Relacionado a NF-E2/genética , Fator 2 Relacionado a NF-E2/metabolismo , Cromo/toxicidade , Cromo/metabolismo , Estresse Oxidativo , Doença Hepática Induzida por Substâncias e Drogas/prevenção & controle , Doença Hepática Induzida por Substâncias e Drogas/veterinária , Transdução de Sinais
20.
Artigo em Inglês | MEDLINE | ID: mdl-38090851

RESUMO

Video object removal aims at erasing a target object in the entire video and filling holes with plausible contents, given an object mask in the first frame as input. Existing solutions mostly break down the task into (supervised) mask tracking and (self-supervised) video completion, and then separately tackle them with tailored designs. In this paper, we introduce a new setup, coined as unified video object removal, where mask tracking and completion are addressed within a unified framework. Despite introducing more challenges, the setup is promising for future practical usage. We embrace the observation that these two sub-tasks have strong inherent connections in terms of pixel-level temporal correspondence. Making full use of the connections could be beneficial considering the complexity of both algorithm and deployment. We propose a single network linking the two sub-tasks by inferring temporal correspondences across multiple frames, i.e., correspondences between valid-valid (V-V) pixel pairs for mask tracking and correspondences between valid-hole (V-H) pixel pairs for video completion. Thanks to the unified setup, the network can be learned end-to-end in a totally unsupervised fashion without any annotations. We demonstrate that our method can generate visually pleasing results and perform favorably against existing separate solutions in realistic test cases.

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