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Soil salinity has negative impacts on food security and sustainable agriculture. Ion homeostasis, osmotic adjustment and reactive oxygen species scavenging are the main approaches utilized by rice to resist salt stress. Breeding rice cultivars with high salt tolerance (ST) and yield is a significant challenge due to the lack of elite alleles conferring ST. Here, we report that the elite allele LEA12OR, which encodes a late embryogenesis abundant (LEA) protein from the wild rice Oryza rufipogon Griff., improves osmotic adjustment and increases yield under salt stress. Mechanistically, LEA12OR, as the early regulator of the LEA12OR-OsSAPK10-OsbZIP86-OsNCED3 functional module, maintains the kinase stability of OsSAPK10 under salt stress, thereby conferring ST by promoting abscisic acid biosynthesis and accumulation in rice. The superior allele LEA12OR provides a new avenue for improving ST and yield via the application of LEA12OR in current rice through molecular breeding and genome editing.
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A multimode detection system has stringent requirements in terms of electromagnetic characteristic control and electromagnetic compatibility. To meet these requirements, we designed and manufactured a type of transparent electromagnetic-wave-absorbing optical window based on a random grid (EAOWRG) in this study. Owing to the design and regulation of the materials of the random grid and the structures of the metasurface, the optical window has excellent multispectral transparency, electromagnetic wave absorption, and electromagnetic shielding performance. The experimental results showed that the transmissivity of the EAOWRG in the optical spectral ranges of 460-800â nm and 8-12 µm is above 89.77%, the electromagnetic reflectivity in the frequency ranges of 3.6-7.2â GHz and 14.3-17.7â GHz is not more than - 5â dB, the bandwidth at which the electromagnetic reflectivity is not more than -10â dB is 4.4â GHz, the electromagnetic shielding effectiveness in the frequency range of 2-18â GHz is above 31â dB. The average radar cross section of the detection system using the EAOWRG in the ± 60° angle domain at 6â GHz is 8.79â dB lower than that before processing. The detection system has a good imaging effect in the visible and infrared bands, meeting the requirements of the electromagnetic characteristic control and electromagnetic compatibility, and has good application prospects.
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Salt stress is a major threat to crop quality and yield. Most experiments on salt stress-related genes have been conducted at the laboratory or greenhouse scale. Consequently, there is a lack of research demonstrating the merit of exploring these genes in field crops. Here, we found that the R2R3-MYB transcription factor SiMYB19 from foxtail millet is expressed mainly in the roots and is induced by various abiotic stressors such as salt, drought, low nitrogen, and abscisic acid. SiMYB19 is tentatively localized to the nucleus and activates transcription. It enhances salt tolerance in transgenic rice at the germination and seedling stages. SiMYB19 overexpression increased shoot height, grain yield, and salt tolerance in field- and salt pond-grown transgenic rice. SiMYB19 overexpression promotes abscisic acid (ABA) accumulation in transgenic rice and upregulates the ABA synthesis gene OsNCED3 and the ABA signal transduction pathway-related genes OsPK1 and OsABF2. Thus, SiMYB19 improves salt tolerance in transgenic rice by regulating ABA synthesis and signal transduction. Using rice heterologous expression analysis, the present study introduced a novel candidate gene for improving salt tolerance and increasing yield in crops grown in saline-alkali soil.
Assuntos
Oryza/genética , Oryza/metabolismo , Oryza/microbiologia , Plantas Geneticamente Modificadas , Tolerância ao Sal/genética , Setaria (Planta)/genética , Fatores de Transcrição/genética , Secas , Regulação da Expressão Gênica de Plantas , Oryza/classificação , Fenótipo , Filogenia , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismo , Estresse Salino , Plântula/genética , Plântula/crescimento & desenvolvimentoRESUMO
KEY MESSAGE: We found GmNAC06 plays an important role in salt stress responses through the phenotypic, physiological and molecular analyses of OE, VC, and Mutant composite soybean. Salinization affects 20% of all cultivated land worldwide because of the high salinity of irrigation water and the excessive use of water, and this amount is increasing daily. NAC (NAM, ATAF, and CUC) have been found to be involved in salt stress. In this study, a soybean NAC gene, GmNAC06 (Glyma06g21020.1), was cloned and functionally characterized. The results of expression analysis suggested that salt stress could influence the expression level of GmNAC06. The subcellular localization analysis results suggested that GmNAC06 may function as a transcription factor. Under salt stress, the overexpression technology combined with CRISPR-Cas9 system found that GmNAC06 could cause the accumulation of proline and glycine betaine to alleviate or avoid the negative effects of ROS; similarly, it could control the Na+/K+ ratios in hairy roots to maintain ionic homeostasis. The fresh weight of the transgenic hairy roots and the histochemical ROS staining of wild leaves suggested that transgenic hairy roots influence the function of wild leaves under salt stress conditions. Moreover, the expression levels of GmUBC2 and GmHKT1 were higher in the GmNAC06 hairy roots than in the control. Thus, the overexpression of GmNAC06 in hairy roots notably causes an entire composite plant to exhibit salt tolerance. The phenotype of composite soybean plants and transgenic Arabidopsis plants suggest that GmNAC06 plays a role in response to salt stress and could be useful in generating salt tolerant transgenic crops.
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Glycine max/fisiologia , Proteínas de Plantas/química , Proteínas de Plantas/metabolismo , Estresse Salino , Tolerância ao Sal , Fatores de Transcrição/química , Fatores de Transcrição/metabolismo , Arabidopsis/genética , Regulação da Expressão Gênica de Plantas , Fenótipo , Raízes de Plantas/genética , Plantas Geneticamente Modificadas , Domínios Proteicos , Espécies Reativas de Oxigênio/metabolismo , Glycine max/genética , Frações Subcelulares/metabolismo , Ativação Transcricional/genéticaRESUMO
BACKGROUND: Despite an enormous research effort, patients diagnosed with advanced colorectal cancer (CRC) still have low prognosis after surgical resection and chemotherapy. The major obstacle for CRC treatment is chemoresistance to front line anti-cancer drugs, such as 5-fluorouracil (5-FU) and oxaliplatin. However, the mechanism of chemoresistance to these drugs remains unclear. METHODS: Cell viability to 5-FU and oxaliplatin was measured by the CellTiter-Glo® 2.0 Cell Viability Assay. The endogenous REV7 protein in CRC cells was detected by western blotting. The translesion synthesis (TLS) events were measured by plasmid-based TLS efficiency assay. Cell apoptosis was evaluated by caspase3/7 activity assay. The in vivo tumor progression was analyzed by HT29 xenograft mice model. RESULTS: In this study, we found that expression of REV7, which is a key component of translesion synthesis (TLS) polymerase ζ (POL ζ), is significantly increased in both 5-FU and oxaliplatin resistant CRC cells. TLS efficiency analysis revealed that upregulated REV7 protein level results in enhanced TLS in response to 5-FU and oxaliplatin. Importantly, inhibition of REV7 by CRISPR/Cas9 knockout exhibited significant synergy with 5-FU and oxaliplatin in cell culture and murine xenograft model. CONCLUSION: These results suggest that combination of REV7 deficiency and 5-FU or oxaliplatin has strong inhibitory effects on CRC cells and identified REV7 as a promising target for chemoresistant CRC treatment.
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BACKGROUND: Environmental stimuli can activate a series of physiological and biochemical responses in plants accompanied by extensive transcriptional reprogramming. Long non-coding RNAs (lncRNAs), as versatile regulators, control gene expression in multiple ways and participate in the adaptation to biotic and abiotic stresses. RESULTS: In this study, soybean seedlings were continuously cultured for 15 days with high salinity solutions started from seed germination. Strand-specific whole transcriptome sequencing and stringent bioinformatic analysis led to the identification of 3030 long intergenic non-coding RNAs (lincRNAs) and 275 natural antisense transcripts (lncNATs) in soybean roots. In contrast to mRNAs, newly identified lncRNAs exhibited less exons, similar AU content to UTRs, even distribution across the genome and low evolutionary conservation. Remarkably, more than 75% of discovered lncRNAs that were activated or up-regulated by continuous salt stress mainly targeted proteins with binding and catalytic activities. Furthermore, two DNA methylation maps with single-base resolution were generated by using reduced representation bisulfite sequencing, offering a genome-wide perspective and important clues for epigenetic regulation of stress-associated lncRNAs and protein-coding genes. CONCLUSIONS: Taken together, our findings systematically demonstrated the characteristics of continuous salt stress-induced lncRNAs and extended the knowledge of corresponding methylation profiling, providing valuable evidence for a better understanding of how plants cope with long-term salt stress circumstances.
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Metilação de DNA , Glycine max/crescimento & desenvolvimento , RNA Longo não Codificante/genética , Estresse Salino , Epigênese Genética , Perfilação da Expressão Gênica , Regulação da Expressão Gênica no Desenvolvimento , Regulação da Expressão Gênica de Plantas , Raízes de Plantas/genética , RNA de Plantas/genética , Glycine max/genética , Sequenciamento do ExomaRESUMO
Clinical application of oxaliplatin, a platinum-based chemotherapeutic agent, in cancer, especially colorectal cancer, is widely used. However, oxaliplatin-induced peripheral neurotoxicity (OIPN) has a high incidence, and to date, there have been few detailed studies on pathogenesis and treatment mechanisms. The present study was performed by using a proteomic approach to explore protein expression profiling of rats treated with oxaliplatin by multiplex isobaric tags for relative and absolute quantification labeling and two-dimensional liquid chromatography-tandem mass spectrometry. There were 74 proteins that showed different expression in sciatic nerve between control rats and OIPN model rats, with 53 upregulated proteins and 21 downregulated proteins detected in OIPN groups compared with control groups. On the basis of Gene Ontology clustering, these proteins were associated with biological processes (eg, muscle contraction, muscle system process, and skeletal muscle contraction), cellular component (eg, myofibril, contractile fiber, and contractile fiber part) and molecular function (structural constituent of muscle, hydro-lyase activity, and calcium ion binding). On the basis of Kyoto Encyclopedia of Genes and Genomes pathway database, these proteins were associated with African trypanosomiasis, malaria, nitrogen metabolism, etc. Real-time polymerase chain reaction, Western blot as well as immunohistochemistry analysis was performed to examine the expression of partially differential protein. In conclusion, our study establishes a protein expression profile of oxaliplatin-induced rats and mechanisms leading to OIPN development, and will be useful for developing novel diagnostic biomarkers and aiding in the prevention and control of OIPN.
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Cromatografia Líquida/métodos , Síndromes Neurotóxicas/metabolismo , Oxaliplatina/efeitos adversos , Proteoma/metabolismo , Proteômica/métodos , Espectrometria de Massas em Tandem/métodos , Animais , Antineoplásicos/efeitos adversos , Antineoplásicos/uso terapêutico , Western Blotting , Perfilação da Expressão Gênica/métodos , Ontologia Genética , Imuno-Histoquímica , Marcação por Isótopo/métodos , Masculino , Neoplasias/tratamento farmacológico , Neoplasias/genética , Neoplasias/metabolismo , Síndromes Neurotóxicas/etiologia , Síndromes Neurotóxicas/genética , Oxaliplatina/uso terapêutico , Proteoma/genética , Ratos Sprague-Dawley , Reação em Cadeia da Polimerase Via Transcriptase ReversaRESUMO
Small guide RNA (sgRNA) is an important component of the CRISPR/Cas9 system. The gene editing efficiency of the CRISPR/Cas9 system could be enhanced by using highly active U6 promoters to drive the expression of sgRNA. Therefore, we constructed various expression vectors based on the 11 GmU6 promoters predicted and cloned in the whole soybean genome. The expression of truncated GUS driven by 11 GmU6 promoters was tested in hairy roots and by Arabidopsis thaliana transformation. The results indicated that higher transcriptional levels were driven by 5 GmU6 promoters (GmU6-4, GmU6-7, GmU6-8, GmU6-10 and GmU6-11) in both soybean hairy roots and Arabidopsis thaliana. In addition, three genes, Glyma03g36470, Glyma14g04180 and Glyma06g136900, were selected as targets to detect the transcriptional levels of multiple GmU6 promoters. Mutations in these three genes were detected in soybean hairy roots after Agrobacterium rhizogenes infection, indicating efficient target gene editing, including nucleotide insertion, deletion, and substitution. Mutation efficiencies differed among the 11 GmU6 promoters, ranging from 2.8% to 20.6%, and markedly higher efficiencies were obtained with all three genes using the GmU6-8 (20.3%) and GmU6-10 (20.6%) promoters. These two GmU6 promoters also showed higher ability to drive truncated GUS transcription in both soybean hairy roots and transformed Arabidopsis thaliana. These results will help to construct an efficient CRISPR-Cas9 gene editing system and promote the application of the CRISPR-Cas9 genome editing system in soybean molecular breeding.
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Sistemas CRISPR-Cas/genética , Glycine max/genética , Regiões Promotoras Genéticas/genética , Edição de Genes , Glycine max/metabolismoRESUMO
Cholangiocarcinoma (CCA) is a lethal cancer associated with chronic inflammation that has increased in prevalence in recent decades. The dysregulated expression of microRNAs (miRNAs) has been detected in various types of malignancies, and depending on the target genes this can result in miRNAs functioning as tumor suppressors or oncogenes. In this study, we investigated the role of miR-124 in cholangiocarcinoma (CCA) and found that its expression was significantly downregulated in the tumor tissue of patients and in CCA cell lines. Our results provided evidence that miR-124 induces apoptotic cell death and triggers the autophagic flux in CCA cells. EZH2 and STAT3 were identified as direct targets of miR-124. The effect of miR-124 on EZH2 expression in CCA cells was evaluated using cell transfection, xenotransplantation into nude mice and a luciferase reporter assay. Silencing of EZH2 restored the effects of miR-124, whereas overexpression of EZH2 abrogated the effects of miR-124. Silencing of Beclin1 or ATG5 abrogated the effects of miR-124 or siEZH2. In vivo, overexpression of miR-124 dramatically induced autophagy-related cell death and suppressed tumorigenicity. Taken together, our findings indicated that downregulation of miR-124 expression was associated with disease progression in human CCA and we revealed that miR-124 exerts a tumor suppressive function in CCA by inducing autophagy-related cell death via direct targeting of the EZH2-STAT3 signaling axis.
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Autofagia , Neoplasias dos Ductos Biliares/patologia , Biomarcadores Tumorais/metabolismo , Colangiocarcinoma/patologia , Proteína Potenciadora do Homólogo 2 de Zeste/metabolismo , MicroRNAs/genética , Fator de Transcrição STAT3/metabolismo , Animais , Apoptose , Neoplasias dos Ductos Biliares/genética , Neoplasias dos Ductos Biliares/metabolismo , Biomarcadores Tumorais/genética , Estudos de Casos e Controles , Proliferação de Células , Colangiocarcinoma/genética , Colangiocarcinoma/metabolismo , Proteína Potenciadora do Homólogo 2 de Zeste/genética , Feminino , Seguimentos , Regulação Neoplásica da Expressão Gênica , Humanos , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Nus , Pessoa de Meia-Idade , Prognóstico , Fator de Transcrição STAT3/genética , Transdução de Sinais , Taxa de Sobrevida , Células Tumorais Cultivadas , Ensaios Antitumorais Modelo de XenoenxertoRESUMO
The traditional Chinese medicine "Fuzi" (Aconiti Lateralis Radix Praeparata) and its three representative alkaloids, aconitine (AC), benzoylaconine (BAC), and aconine, have been shown to increase mitochondrial mass. Whether Fuzi has effect on mitochondrial biogenesis and the underlying mechanisms remain unclear. In the present study, we focused on the effect of BAC on mitochondrial biogenesis and the underlying mechanisms. We demonstrated that Fuzi extract and its three components AC, BAC, and aconine at a concentration of 50 µM significantly increased mitochondrial mass in HepG2 cells. BAC (25, 50, 75 µM) dose-dependently promoted mitochondrial mass, mtDNA copy number, cellular ATP production, and the expression of proteins related to the oxidative phosphorylation (OXPHOS) complexes in HepG2 cells. Moreover, BAC dose-dependently increased the expression of proteins involved in AMPK signaling cascade; blocking AMPK signaling abolished BAC-induced mitochondrial biogenesis. We further revealed that BAC treatment increased the cell viability but not the cell proliferation in HepG2 cells. These in vitro results were verified in mice treated with BAC (10 mg/kg per day, ip) for 7 days. We showed that BAC administration increased oxygen consumption rate in mice, but had no significant effect on intrascapular temperature. Meanwhile, BAC administration increased mtDNA copy number and OXPHOS-related protein expression and activated AMPK signaling in the heart, liver, and muscle. These results suggest that BAC induces mitochondrial biogenesis in mice through activating AMPK signaling cascade. BAC may have the potential to be developed as a novel remedy for some diseases associated with mitochondrial dysfunction.
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Aconitina/análogos & derivados , Mitocôndrias/efeitos dos fármacos , Biogênese de Organelas , Transdução de Sinais/efeitos dos fármacos , Proteínas Quinases Ativadas por AMP/metabolismo , Aconitina/farmacologia , Animais , Sobrevivência Celular/efeitos dos fármacos , Diterpenos , Medicamentos de Ervas Chinesas , Células Hep G2 , Humanos , Masculino , Camundongos Endogâmicos BALB C , Mitocôndrias/metabolismo , Oxigênio/metabolismo , Extratos Vegetais/farmacologiaRESUMO
Salinity is a major abiotic stress that affects plant growth and development. Plant roots are the sites of salt uptake. Here, an isobaric tag for a relative and absolute quantitation based proteomic technique was employed to identify the differentially expressed proteins (DEPs) from seedling roots of the salt-tolerant genotype Han 12 and the salt-sensitive genotype Jimai 19 in response to salt treatment. A total of 121 NaCl-responsive DEPs were observed in Han 12 and Jimai 19. The main DEPs were ubiquitination-related proteins, transcription factors, pathogen-related proteins, membrane intrinsic protein transporters and antioxidant enzymes, which may work together to obtain cellular homeostasis in roots and to determine the overall salt tolerance of different wheat varieties in response to salt stress. Functional analysis of three salt-responsive proteins was performed in transgenic plants as a case study to confirm the salt-related functions of the detected proteins. Taken together, the results of this study may be helpful in further elucidating salt tolerance mechanisms in wheat.
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Proteínas de Plantas/metabolismo , Raízes de Plantas/metabolismo , Proteômica/métodos , Estresse Fisiológico , Triticum/metabolismo , Arabidopsis/genética , Regulação da Expressão Gênica de Plantas , Proteínas de Plantas/análise , Proteínas de Plantas/genética , Plantas Geneticamente Modificadas , Salinidade , Tolerância ao Sal , Glycine max/genética , Triticum/efeitos dos fármacos , Triticum/genéticaRESUMO
BACKGROUND/AIMS: Phosphoserine aminotransferase 1 (PSAT1) is over-expressed in many carcinoma tissues, however little is known regarding its expression and function in esophageal carcinogenesis. This study investigated the expression of PSAT1 in human esophageal squamous cell carcinoma (ESCC) tissues to determine the relationship between PSAT1 expression and clinicopathological factors. METHODS: The expression of PSAT1 in 64 surgical resections from esophageal carcinogenesis patients was examined by quantitative RT-PCR and immunohistochemistry and the results were compared with clinicopathological factors. In vitro experiments were performed in ESCC cells overexpressing PSAT1 to measure cell viability and invasion. Tumor formation in vivowas examined by injection of tumor cells into immunocompromised mice subcutaneously. RESULTS: PSAT1 expression was elevated in ESCC tissues compared to normal esophageal tissues. Increased PSAT1 expression was significantly associated with stage of disease, lymph node metastasis, distant metastasis and poor prognosis. In vitro, PSAT1 overexpression promoted ESCC cell proliferation and matrigel invasion. In vivo, injection of mice with ECSS cells overexpressing PSAT1 enhanced tumor formation. Western blot analysis revealed that PSAT1 upregulated the expression and/or activity of GSK3ß/Snail. CONCLUSION: PSAT1 plays a crucial role in the development of ESCC and predicts poor survival. Therefore, PSAT1 may be a promising novel anticancer therapeutic target.
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Carcinoma de Células Escamosas/genética , Neoplasias Esofágicas/genética , Regulação Enzimológica da Expressão Gênica , Regulação Neoplásica da Expressão Gênica , Transaminases/genética , Adulto , Idoso , Animais , Carcinoma de Células Escamosas/enzimologia , Carcinoma de Células Escamosas/patologia , Linhagem Celular , Linhagem Celular Tumoral , Proliferação de Células/genética , Progressão da Doença , Neoplasias Esofágicas/enzimologia , Neoplasias Esofágicas/patologia , Feminino , Células HEK293 , Humanos , Imuno-Histoquímica , Masculino , Camundongos Endogâmicos BALB C , Camundongos Nus , Pessoa de Meia-Idade , Prognóstico , Interferência de RNA , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Transaminases/metabolismo , Transplante HeterólogoRESUMO
Pancreatic cancer is an aggressive malignancy with a high metastatic potential that results in a high mortality rate worldwide. Although macrophages have the potential to kill tumor cells and elicit immune responses against tumors, there is evidence that tumor-associated macrophages (TAMs) promote tumor progression and suppress T-cell responses. CC-chemokine ligand 20 (CCL20) and its unique receptor CC-chemokine receptor 6 (CCR6) are exploited by cancer cells for migration and metastasis and play important roles in the development and progression of cancer. Recent studies have shown that the expression of CCL20 is upregulated in pancreatic cancer; however, the mechanism of action of CCL20 remains to be fully elucidated. In this study, the aberrant expression of CCL20 in TAMs of pancreatic cancer tissue, including metastatic pancreatic cancer tissue, was detected. CCL20 expression was considerably higher in macrophages than in pancreatic cancer cell lines, particularly in interleukin-4-treated (M2) macrophages. Using Boyden chamber assays of pancreatic cancer cells, we found that CCL20 secreted by M2 macrophages promoted the migration, epithelial-mesenchymal transition, and invasion of pancreatic cancer cells. RNA interference results showed that CCR6 is a receptor for CCL20 in pancreatic cancer cells, mediating the increased invasive properties of these cells promoted by CCL20. Using a mouse model, we confirmed the roles of CCR6/CCL20 in promoting pancreatic cancer growth and liver metastasis in vivo Our findings provide insight into the important role of macrophage-secreted CCL20 in pancreatic cancer and implicate CCR6/CCL20 as potential therapeutic targets.
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Proliferação de Células/fisiologia , Quimiocina CCL20/fisiologia , Macrófagos/metabolismo , Metástase Neoplásica , Neoplasias Pancreáticas/patologia , Animais , Linhagem Celular Tumoral , Quimiocina CCL20/metabolismo , Transição Epitelial-Mesenquimal , Xenoenxertos , Humanos , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Nus , Neoplasias Pancreáticas/metabolismoRESUMO
BACKGROUND/AIMS: The microRNA (miR) 29 family has been studied extensively for its involvement in several diseases, and aberrant expression of its members is associated with tumorigenesis and cancer progression. Here, we examined the role of miR-29a in pancreatic cancer and the involvement of tristetraprolin (TTP). METHODS: We monitored miR-29a and TTP expression in pancreatic cancer by qRT-PCR and western blotting. The effect of miR-29a on pancreatic cancer was determined through MTT assay and migration assay. The results were validated in the tumorigenesis model. RESULTS: We found that miR-29a was up regulated in pancreatic tumor tissues and cell lines and positively correlated with metastasis. Ectopic expression of miR-29a increased the expression of pro-inflammatory factors and epithelial-mesenchymal transition (EMT) markers, through down regulating TTP. TTP was down regulated in tumor tissues, and its ectopic expression decreased cell viability and migration in vitro, inhibited tumor growth and the EMT phenotype in vivo, and reversed the effect of miR-29a on tumor cell proliferation and invasion in vitro and in vivo. CONCLUSION: Our results suggest that miR-29a acts as an oncogene by down regulating TTP and provide the basis for further studies exploring the potential of miR-29a and TTP as biomarkers and targets for the treatment of pancreatic cancer.
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MicroRNAs/genética , Neoplasias Pancreáticas/genética , Neoplasias Pancreáticas/patologia , Tristetraprolina/genética , Animais , Linhagem Celular Tumoral , Movimento Celular , Proliferação de Células , Sobrevivência Celular , Regulação Neoplásica da Expressão Gênica , Humanos , Camundongos , Camundongos Nus , Neoplasias ExperimentaisRESUMO
BACKGROUND/AIMS: Emerging evidence indicates that microRNA (miR)-340 is downregulated in various human cancers, suggesting that it acts as a tumor suppressor. The aim of the present study was to evaluate the expression and role of miR-340 in human esophageal squamous cell carcinoma (ESCC). METHODS: The expression of miR-340 was examined in 64 paired ESCC and adjacent non-tumor tissues by quantitative real time PCR. The effects of miR-340 on ESCC cell proliferation and metastasis were examined by MTT and Matrigel invasion assays. Tumor growth was assessed by subcutaneous inoculation of cells into BALB/c nude mice. Targets of miR-340 were identified by bioinformatics and verified by luciferase reporter assays, quantitative real-time PCR, and western blotting. RESULTS: MiR-340 was significantly downregulated in ESCC tumor tissues compared to adjacent non-tumor tissues and in ESCC cell lines compared to esophageal endothelial cells. Overexpression of miR-340 inhibited ESCC cell growth, colony formation, and invasion, and tumor growth in a xenograft mouse model. PSAT1 was identified as a direct target of miR-340 and its ectopic expression partially reversed the miR-340 mediated inhibition of viability, invasion and EMT in ESCC cells. The expression of miR-340 was negatively correlated with that of PSAT1 in human ESCC samples. CONCLUSION: MiR-340 functions as a tumor suppressor by modulating the expression of PSAT1 and may contribute to the progression and invasiveness of ESCC.
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Carcinoma de Células Escamosas/genética , Proliferação de Células/genética , Neoplasias Esofágicas/genética , MicroRNAs/genética , Transaminases/genética , Animais , Carcinoma de Células Escamosas/patologia , Linhagem Celular , Linhagem Celular Tumoral , Movimento Celular/genética , Regulação para Baixo/genética , Células Endoteliais/patologia , Neoplasias Esofágicas/patologia , Carcinoma de Células Escamosas do Esôfago , Perfilação da Expressão Gênica/métodos , Regulação Neoplásica da Expressão Gênica/genética , Genes Supressores de Tumor/fisiologia , Células HEK293 , Humanos , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Nus , Invasividade Neoplásica/genética , Invasividade Neoplásica/patologiaRESUMO
Severe pain and obstructive jaundice resulting from invasive cholangiocarcinoma or pancreatic carcinoma can be alleviated by implantation of biliary and duodenal stents. However, stents may cause local inflammation to have an adverse effect on the patients' condition and survival. So far, no efficient approaches have been applied to prevent the occurrence of stents-related inflammation. Here, we reported significantly higher levels of serum stromal cell-derived factor 1 (SDF-1) in the patients that developed stents-associated inflammation. A higher number of inflammatory cells have been detected in the cancer close to stent in the patients with high serum SDF-1. Since chemokine plays a pivotal role in the development of inflammation, we implanted an Alzet osmotic pump with the stents to gradually release AMD3100, a specific inhibitor binding of SDF-1 and its receptor C-X-C chemokine receptor 4 (CXCR4), at the site of stents in mice that had developed pancreatic cancer. We found that AMD3100 significantly reduced local inflammation and significantly inhibited cancer cell growth, resulting in improved survival of the mice that bore cancer. Moreover, the suppression of cancer growth may be conducted through modulation of CyclinD1, p21, and p27 in the cancer cells. Together, these data suggest that inhibition of chemokine signaling at the site of stents may substantially improve survival through suppression of stent-related inflammation and tumor growth.
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Quimiocina CXCL12/genética , Inflamação/tratamento farmacológico , Neoplasias Pancreáticas/tratamento farmacológico , Receptores CXCR4/genética , Stents/efeitos adversos , Animais , Benzilaminas , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Quimiocina CXCL12/antagonistas & inibidores , Ciclamos , Compostos Heterocíclicos/administração & dosagem , Humanos , Inflamação/induzido quimicamente , Inflamação/genética , Camundongos , Neoplasias Experimentais/tratamento farmacológico , Neoplasias Experimentais/genética , Neoplasias Experimentais/patologia , Neoplasias Pancreáticas/genética , Neoplasias Pancreáticas/patologia , Receptores CXCR4/metabolismo , Transdução de Sinais/efeitos dos fármacos , Ensaios Antitumorais Modelo de XenoenxertoRESUMO
OBJECTIVE: To investigate the expression of osteopontin (OPN) splice variant mRNA, including the three isoforms OPN-A, OPN-B, and OPN-C, to explore its correlation with clinicopathologic features in gastric cancer, and to elucidate their role in tumor invasion and distant metastasis of gastric cancer. METHODS: The expression of OPN-A, OPN-B and OPN-C mRNA were detected by real-time reverse transcriptase-polymerase chain reaction in 66 gastric cancer tissues. The relationship between the expression of OPN-A, OPN-B and OPN-C mRNA and clinicopathologic features of gastric cancer was analyzed. RESULTS: The expression of OPN-C mRNA in the gastric cancer tissue was 3.21-fold higher than that in peritumoral mucosal tissue, showing a significant difference between them (P < 0.001). OPN-C mRNA expression was correlated with the depth of tumor invasion, tumor diameter, lymph node meatastasis, distant meatastasis and had no correlation with differentiation grades. The low expression of OPN-C mRNA was correlated with long survival benefit (P = 0.03). The expression of OPN-A and OPN-B mRNA had no significant relationship with clinicopathologic features of gastric cancer. CONCLUSIONS: One of the isoform of osteopontin (OPN) OPN-C mRNA is overexpressed in gastric cancer. The overexpression of OPN-C mRNA may reflect the progression and is associated with the prognosis of gastric cancer. OPN-C mRNA may have value as a prognostic biomarker in gastric cancer. However, the expression of OPN-A and OPN-B are not correlated with the progression and metastasis of gastric cancer.
Assuntos
Proteínas de Neoplasias/genética , Osteopontina/genética , RNA Mensageiro/metabolismo , Neoplasias Gástricas/genética , Progressão da Doença , Mucosa Gástrica/metabolismo , Humanos , Linfonodos , Metástase Linfática , Invasividade Neoplásica , Prognóstico , Isoformas de Proteínas/genética , Reação em Cadeia da Polimerase em Tempo Real , Neoplasias Gástricas/mortalidade , Neoplasias Gástricas/patologiaRESUMO
OBJECTIVE: To discuss arterial infusion chemotherapy as second-line treatment for advanced pancreatic carcinoma salvage after failed vein chemotherapy. METHODS: 35 cases with IV stage pancreatic carcinoma, all cases are failed first-line chemotherapy of Gemcitabine. Via femoral artery puncture, gastroduodenal artery, the dorsal pancreatic artery, pancreatic artery, pancreatic tail artery, the rib waist artery, superior mesenteric artery and tumor related to blood supply artery intubation and chemical drug perfusion. Plan: Cisplatin 30 mg/m², Gemcitabine 1 000 mg/m². Treatment for every 3-4 weeks, there is no limit on the total number. RESULTS: 35 cases were local chemotherapy for 217 cycles, at least 1 cycle, a maximum of 9 cycles, 6.2 cycles on average. Among which: CR 1 case, PR 6 cases, SD 15 cases, effective rate (CR+PR) is 20%, disease control rate (DCR) is 68.75%. The median survival time was 9.6 months. The median TTP was 3.7 months. Total effective rate of CBR , the stability rate of CBR and inefficiency rate of CBR were 51.4%, 25.7% and 22.9% respectively. Pain score improvement 88.57% (31/35), 42.86% (15/35) Pain relief last for 3-20 days ( median time 11 days). 17.14% (6/35) Pain relief last for more than 20 days. Pain relief maintain the most elderly 160 days. Half of the patients have different degree of side reaction, III, IV degree leukopenia accounted for 17.14% (6/35), 8.57% (3/35). CONCLUSION: The arterial perfusion chemotherapy as second-line treatment of advanced pancreatic cancer salvage is of clinical value, with better disease control rate and the rate of pain relief.
Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias Pancreáticas/tratamento farmacológico , Cisplatino , Desoxicitidina/análogos & derivados , Humanos , Estadiamento de Neoplasias , Neoplasias Pancreáticas/patologia , Terapia de Salvação , Gencitabina , Neoplasias PancreáticasRESUMO
OBJECTIVE: To evaluate the feasibility and safety of a simple noncystoscopic method previously applied in children for removing double-J stents applied in women by comparing the hospitalization time, operation time, costs, complications, and success rate. METHODS: One hundred eighty women who underwent either cystoscopic or noncystoscopic double-J stent removal in a randomized manner. They were randomly assigned 1:1 to groups of cystoscopic double-J stent removal (n = 90) or noncystoscopic double-J stent removal (n = 90). The age ranged from 19 to 72years. After the removal of the double-J stent, the operation time, costs, complications, and success rate were compared between the two groups. RESULTS: The operation time of the noncystoscopic group was lower than that of the cystoscopic group (6.0(5.0,7.0) minutes vs 2.0(2.0,3.0) minutes, P < .001). The hospitalization costs of the noncystoscopic group were significantly shorter than that of the cystoscopic group (1361.2(1331.4,1379.2) Yuan vs 873.9(868.5,896.1) Yuan, P < .001). There were no complications such as infection and massive bleeding in the two groups during and after the operation. Most noncystoscopic double-J stent removal can succeed in less than three attempts (88/90). All patients in the noncystoscopic group used this technique to remove the double-J stent. CONCLUSION: Noncystoscopic removal of double-J stent has the advantages of short operation time and low hospitalization costs. It is a safe and feasible minimally invasive method to replace cystoscopic removal of the double-J stent.
Assuntos
Hospitalização , Stents , Adulto , Idoso , Feminino , Humanos , Pessoa de Meia-Idade , Adulto Jovem , Estudos de Viabilidade , Duração da CirurgiaRESUMO
AIM: Aging and age-related diseases are an ever-increasing social and public health problem. Allostatic load (AL) shows great potential as an interdisciplinary tool for assessing the aging of human beings but as yet lacks investigation in animal models which is our study focus at. METHODS: Here a continuous study of AL was conducted on naturally aging rats. Blood samples were collected from the rats at ages of 5, 8, 14, 18, and 21 months. Dozens of blood biochemical indicators, including serum corticosterone, total cholesterol, low-density lipoprotein cholesterol, high-density lipoprotein cholesterol, triglycerides, C-reactive protein, interleukin-6, 25-hydroxyvitamin D, free fatty acid, CD3+ T cell count, CD4+/CD3+ T cell ratio, CD8+/CD3+ T cell ratio, and CD3/4/8+ T cell apoptosis, were determined. RESULTS: AL was scored from those indicators, and we found that AL score gradually increased with age. CONCLUSIONS: AL can reliably reveal the cumulative and systemic changes in aging. Geriatr Gerontol Int 2024; â¢â¢: â¢â¢-â¢â¢.