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To evaluate the potential ecotoxicity of ethiprole and early warning to earthworms (Eisenia fetida), different concentrations (0 mg·kg-1, 416 mg·kg-1, 625 mg·kg-1, and 1000 mg·kg-1) of ethiprole were added to artificial soil. The key bioindicators were measured and screened at 3 days, 7 days, 14 days, 21 days, and 28 days. The results show that the activity of catalase (CAT) was inhibited for all treatments during the whole exposure period. Besides, the olive tail moment (OTM) value increased gradually as the concentration got higher, which exhibited a dose-time-dependent relationship. Superoxide dismutase (SOD) gene reached the maximum on the 7th day. Mitochondrial large ribosomal RNA (l-rRNA) subunit gene was always in a downregulated state as the concentration increased. Our results show that different concentrations of ethiprole induced certain oxidative stress, DNA damage, and genotoxicity in earthworms. The CAT activity, OTM, and SOD gene could be the most sensitive biomarkers to monitor the toxicity of ethiprole in the soil.
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Dano ao DNA , Oligoquetos , Estresse Oxidativo , Animais , Oligoquetos/efeitos dos fármacos , Oligoquetos/genética , Estresse Oxidativo/efeitos dos fármacos , Expressão Gênica/efeitos dos fármacos , Poluentes do Solo/toxicidade , Superóxido Dismutase/metabolismo , Catalase/metabolismoRESUMO
The extent of immune-mediated hepatic damage (such as in viral hepatitis) is characterised by the downregulation of cytochrome P450s (CYPs), a class of drug-metabolising enzymes. However, whether this downregulation aids liver cells in maintaining their homeostasis or whether the damage is aggravated remains largely unexplored. Herein, we evaluated the effects of phosphorylation mediated by the protein kinase C (PKC)/cAMP-response element binding protein (CREB) and nitration mediated by inducible nitric oxide synthase (iNOS) on the downregulation of CYP2E1 during immune-mediated liver injury. Additionally, we investigated the regulatory mechanism mediated by the nuclear factor κB (NF-κB). The rat model of immune-mediated liver injury was replicated by administering a single i.v. injection of Bacillus Calmette-Guerin (BCG, 125 mg/kg) vaccine and three i.p. injections of ammonium pyrrolidine dithiocarbamate (25, 50, 100 mg/kg/d, days 11, 12, and 13); blood was then collected on day 14. Subsequently, the livers were extracted to identify the different pharmacokinetic and biochemical indicators involved in the process. Our study reports new findings on the dependence between PKC-mediated CREB phosphorylation in the anti-inflammatory pathway and nitration emergency induced by iNOS in pro-inflammatory pathways in the NF-κB pathway. The interaction of these two pathways leads to the downregulation and recovery of CYP2E1, thus alleviating inflammation and nitration stress. Our results confirm that BCG-mediated downregulation of CYP2E1 is linked to iNOS-induced nitration and PKC/NF-κB-mediated CREB phosphorylation, and that NF-κB is an important molecular target in this process. These findings suggest that the downregulation of CYP2E1 may be an autonomous process characteristic of liver cells, helping them adapt to environmental changes, alleviate further hypoxia in inflamed tissues, and minimise exposure to toxic and harmful metabolites.
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In this study, we investigated the effect of Hippophae rhamnoides L. (HRP) on the activity of CYP2D6 via the CAMP/PKA/NF-κB pathway in rats with Bacille Calmette-Guerin (BCG)-induced immunological liver injury. BCG (125 mg/kg) was injected to establish the rat model of liver injury. HRP was administered intragastrically for one week as the intervention drug. Proteomics techniques were used to analyze protein expression levels, obtaining a comprehensive understanding of the liver injury process. ELISA or western blotting was used to detect specific protein levels. Dextromethorphan was detected using high-performance liquid chromatography to reflect the metabolic activity of CYP2D6. BCG downregulated the expression of CYP2D6, cAMP, PKA, IκB, and P-CREB and upregulated that of NF-κB, IL-1ß, TNF-α, and CREB in the liver; HRP administration reversed these effects. Therefore, HRP may restore the metabolic function of the liver by reversing the downregulation of CYP2D6 through inhibition of NF-κB signal transduction and regulation of the cAMP/PKA/CREB/CYP2D6 pathway. These findings highlight the role of HRP as an alternative clinical drug for treating hepatitis B and other immune-related liver diseases.
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Doença Hepática Crônica Induzida por Substâncias e Drogas , Hippophae , Ratos , Animais , NF-kappa B/metabolismo , Hippophae/metabolismo , Citocromo P-450 CYP2D6RESUMO
BaNi2As2 is a structural analog of the pnictide superconductor BaFe2As2, which, like the iron-based superconductors, hosts a variety of ordered phases including charge density waves (CDWs), electronic nematicity, and superconductivity. Upon isovalent Sr substitution on the Ba site, the charge and nematic orders are suppressed, followed by a sixfold enhancement of the superconducting transition temperature (Tc). To understand the mechanisms responsible for enhancement of Tc, we present high-resolution angle-resolved photoemission spectroscopy (ARPES) measurements of the Ba1-xSrxNi2As2 series, which agree well with our density functional theory (DFT) calculations throughout the substitution range. Analysis of our ARPES-validated DFT results indicates a Lifshitz transition and reasonably nested electron and hole Fermi pockets near optimal substitution where Tc is maximum. These nested pockets host Ni dxz/dyz orbital compositions, which we associate with the enhancement of nematic fluctuations, revealing unexpected connections to the iron-pnictide superconductors. This gives credence to a scenario in which nematic fluctuations drive an enhanced Tc.
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Glioma is regarded as a prevalent form of cancer that affects the Central Nervous System (CNS), with an aggressive growth pattern and a low clinical cure rate. Despite the advancement of the treatment strategy of surgical resection, chemoradiotherapy and immunotherapy in the last decade, the clinical outcome is still grim, which is ascribed to the low immunogenicity and tumor microenvironment (TME) of glioma. The multifunctional molecule, called ceruloplasmin (CP) is involved in iron metabolism. Its expression pattern, prognostic significance, and association with the immune cells in gliomas have not been thoroughly investigated. Studies using a variety of databases, including Chinese Glioma Genome Atlas (CGGA), The Cancer Genome Atlas (TCGA), and Gliovis, showed that the mRNA and protein expression levels of CP in patients suffering from glioma increased significantly with an increasing glioma grade. Kaplan-Meier (KM) curves and statistical tests highlighted a significant reduction in survival time of patients with elevated CP expression levels. According to Cox regression analysis, CP can be utilized as a stand-alone predictive biomarker in patients suffering from glioma. A significant association between CP expression and numerous immune-related pathways was found after analyzing the data using the Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG), and Gene Set Enrichment Analysis (GSEA). Tumor Immune Estimation Resource (TIMER) and CIBERSORT analyses indicated a substantial correlation between the CP expression and infiltration of immunocytes in the TME. Additionally, immune checkpoints and CP expression in gliomas showed a favorable correlation. According to these results, patients with glioma have better prognoses and levels of tumor immune cell infiltration when their CP expression is low. As a result, CP could be used as a probable therapeutic target for gliomas and potentially anticipate the effectiveness of immunotherapy.
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Bird songs are considered a sexually selected trait that can reflect the individual health of males as well as the vitality of potential mates and their competitors. Vocalization features should, therefore, be related to parasite load and body condition. Here, we performed a thorough acoustic analysis of the display calls of 9-month-old sub-adults and 18-month-old adults of pasture-raised red junglefowls Gallus gallus. We investigated whether the calls of pasture-raised red junglefowls can indicate body size and body condition, in addition to the influence of parasitic infection intensity on the expression of sexual traits. We found that frequency-related syllable parameters were significantly positively correlated with wing length in adults, whereas body weight was independent of both the frequency and temporal parameters of calls. In addition, we correlated parasitic load with the expression of sexually selected traits and discovered a positive association between the intensity of parasite infection and wing length in sub-adults, independent of vocal parameters. Overall, the results suggest that the vocalization of red junglefowls may convey reliable body size information, which will facilitate further studies of different vocal parameters in the transmission of bird vocalizations.
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The ubiquitin-dependent proteolytic pathway is crucial for cellular regulation, including control of the cell cycle, differentiation, and apoptosis. Proteasome 26S Subunit Ubiquitin Receptor, Non-ATPase 4, (PSMD4) is a member of the ubiquitin proteasome family that is upregulated in multiple solid tumors, including hepatocellular carcinoma (HCC), and the existence of PSMD4 is associated with unfavorable prognosis. In this study, transcriptome sequencing of HCC tissues and non-tumor hepatic tissues from the public database Cancer Genome Atlas (TGCA) revealed a high expression of PSMD4. Additionally, PSMD4 loss in HCC cells suppressed the tumor development in mouse xenograft model. PSMD4, which is maintained by inflammatory factors secreted from tumor matrix cells, positively mediates cell growth and is associated with Akt/GSK-3ß/ cyclooxygenase2 (COX2) pathway activation, inhibition of p53 promoter activity, and increased p53 degradation. However, the domain without the C-terminus (VWA+UIM1/2) sustained the activation of p53 transcription. Thus, our findings suggest that PSMD4 is involved in HCC tumor growth through COX2 expression and p53 downregulation. Therapeutic strategies targeting PSMD4 and its downstream effectors could be used for the treatment of PSMD4-abundant HCC patients.
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Carcinoma Hepatocelular , Neoplasias Hepáticas , Humanos , Animais , Camundongos , Carcinoma Hepatocelular/patologia , Neoplasias Hepáticas/patologia , Proteínas Proto-Oncogênicas c-akt/metabolismo , Proteína Supressora de Tumor p53/genética , Proteína Supressora de Tumor p53/metabolismo , Ciclo-Oxigenase 2/genética , Ciclo-Oxigenase 2/metabolismo , Complexo de Endopeptidases do Proteassoma/genética , Complexo de Endopeptidases do Proteassoma/metabolismo , Glicogênio Sintase Quinase 3 beta/metabolismo , Linhagem Celular Tumoral , Apoptose/genética , Proliferação de Células , Modelos Animais de Doenças , Ubiquitinas/genética , Regulação Neoplásica da Expressão Gênica/genética , Proteínas de Ligação a RNA/genéticaRESUMO
OBJECTIVES: To observe the protective effects of dexmedetomidine (Dex) postconditioning on myocardial ischemia/reperfusion injury (IRI) and to explore its potential molecular mechanisms. METHODS: One-hundred forty-seven male Sprague-Dawley rats were randomly divided into five groups receiving the different treatments: Sham, ischemia/reperfusion (I/R), Dex, Brusatol, Dex + Brusatol. By the in vivo rat model of myocardial IRI, cardioprotective effects of Dex postconditioning were evaluated by assessing serum CK-MB and cTnI levels, myocardial HE and Tunel staining and infarct size. Furthermore, the oxidative stress-related markers including intracellular ROS level, myocardial tissue MDA level, SOD and GSH-PX activities were determined. RESULTS: Dex postconditioning significantly alleviated myocardial IRI, decreased intracellular ROS and myocardial tissue MDA level, increased SOD and GSH-PX activities. Dex postconditioning significantly up-regulated myocardial expression of Bcl-2, down-regulated Bax and cleaved caspase-3 and decreased cardiomyocyte apoptosis rate. furthermores, Dex postconditioning promoted Nrf2 nuclear translocation, increased myocardial expression of Sirt3 and SOD2 and decreased Ac-SOD2. However, brusatol reversed cardioprotective benefits of Dex postconditioning, significantly decreased Dex-induced Nrf2 nuclear translocation and reduced myocardial expression of Sirt3 and SOD2. CONCLUSIONS: Dex postconditioning can alleviate myocardial IRI by suppressing oxidative stress and apoptosis, and these beneficial effects are at least partly mediated by activating the Nrf2/Sirt3/SOD2 signaling pathway.
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Dexmedetomidina , Traumatismo por Reperfusão Miocárdica , Traumatismo por Reperfusão , Sirtuína 3 , Animais , Masculino , Ratos , Apoptose , Dexmedetomidina/uso terapêutico , Dexmedetomidina/farmacologia , Traumatismo por Reperfusão Miocárdica/tratamento farmacológico , Traumatismo por Reperfusão Miocárdica/metabolismo , Fator 2 Relacionado a NF-E2/metabolismo , Ratos Sprague-Dawley , Espécies Reativas de Oxigênio , Transdução de Sinais , Sirtuína 3/metabolismo , Sirtuína 3/farmacologia , Superóxido Dismutase/metabolismoRESUMO
The discovery of superconductivity in planar nickelates raises the question of how the electronic structure and correlations of Ni1+ compounds compare to those of the Cu2+ cuprate superconductors. Here, we present an angle-resolved photoemission spectroscopy (ARPES) study of the trilayer nickelate Pr4Ni3O8, revealing a Fermi surface resembling that of the hole-doped cuprates but with critical differences. Specifically, the main portions of the Fermi surface are extremely similar to that of the bilayer cuprates, with an additional piece that can accommodate additional hole doping. We find that the electronic correlations are about twice as strong in the nickelates and are almost k-independent, indicating that they originate from a local effect, likely the Mott interaction, whereas cuprate interactions are somewhat less local. Nevertheless, the nickelates still demonstrate the strange-metal behavior in the electron scattering rates. Understanding the similarities and differences between these two families of strongly correlated superconductors is an important challenge.
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Peripheral blood mononuclear cells (PBMCs) of a 38-year-old healthy female were isolated and reprogrammed into the induced pluripotent stem cells (iPSCs). The established iPSC line expressed various pluripotency stem cell markers and potential of differentiating into three germ layers, meanwhile maintained normal karyotype.
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Células-Tronco Pluripotentes Induzidas , Feminino , Humanos , Adulto , Células-Tronco Pluripotentes Induzidas/metabolismo , Leucócitos Mononucleares/metabolismo , Camadas Germinativas/metabolismo , Biomarcadores/metabolismo , Diferenciação CelularRESUMO
Peripheral blood mononuclear cells derived from a 35-year-old healthy male were reprogrammed into induced pluripotent stem cells (iPSCs). The iPSCs maintained a normal karyotype, expressed various pluripotency stem cell markers, and showed potential of differentiating into three germ layers. This iPSCs could be differentiated into multiple cell subtypes for drug discovery and investigation of mechanisms.
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Células-Tronco Pluripotentes Induzidas , Células-Tronco Pluripotentes , Masculino , Humanos , Adulto , Células-Tronco Pluripotentes Induzidas/metabolismo , Leucócitos Mononucleares , Diferenciação Celular , Camadas GerminativasRESUMO
Cancer stem cells (CSCs) are involved in cancer recurrence and metastasis owing to their self-renewal properties and drug-resistance capacity. Lipocalin-2 (Lcn2) of the lipocalin superfamily is highly expressed in pancreatic cancer. Nevertheless, reports on the involvement of Lcn2 in the regulation of pancreatic CSC properties are scant. This study is purposed to investigate whether Lcn2 plays a crucial role in CSC renewal and stemness maintenance in pancreatic carcinoma. Immunohistochemistry results of tumor tissue chips together with Gene Expression Omnibus sequencing files confirmed that Lcn2 is highly expressed in pancreatic carcinoma compared with that in normal tissues. The exogenous expression of Lcn2 attenuated CSC-associated SOX2, CD44, and EpCAM expression and suppressed sarcosphere formation and tumorigenesis in the pancreatic carcinoma cell line PANC-1, which showed low expression of Lcn2. However, Lcn2 knockout in BxPC-3 cell line, which presented high Lcn2 expression, promoted CSC stemness, further enhancing sarcosphere formation and tumorigenesis. Moreover, Lcn2 was found to regulate stemness in pancreatic cancer depending on the activation of AKT and c-Jun. Lcn2 suppresses stemness properties in pancreatic carcinoma by activating the AKT-c-Jun pathway, and thus, it may be a novel candidate to suppress the stemness of pancreatic cancer. This study provides a new insight into disease progression.
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Neoplasias Pancreáticas , Proteínas Proto-Oncogênicas c-akt , Carcinogênese/genética , Linhagem Celular Tumoral , Regulação Neoplásica da Expressão Gênica , Humanos , Lipocalina-2/genética , Lipocalina-2/metabolismo , Células-Tronco Neoplásicas/patologia , Neoplasias Pancreáticas/patologia , Proteínas Proto-Oncogênicas c-akt/metabolismo , Proteínas Proto-Oncogênicas c-jun , Neoplasias PancreáticasRESUMO
BACKGROUND: Available literature indicates that long-term drinkers demand a higher dose of propofol for induction of anesthesia than non-drinkers. However, there is no study having assessed the influence of long-term high-risk drinking (LTHRD) on the effective doses of propofol for successful insertion of gastroscope with sedation. This study was designed to compare the effective doses of propofol for successful insertion of gastroscope between LTHRD and non-drinking (ND) Chinese male patients. METHODS: Thirty-one LTHRD patients and 29 ND male patients undergoing elective gastroscopy with propofol sedation were enrolled. The modified Dixon's up-and-down method was applied to determine the calculated median effective dose (ED50) of propofol for successful insertion of gastroscope. Furthermore, the isotonic regression analysis was used to establish the dose-response curve of propofol and assess the effective doses of propofol where 50% (ED50) and 95% (ED95) of gastroscope insertions were successful. RESULTS: The calculated ED50 of propofol for successful insertion of gastroscope was 1.55 ± 0.10 mg/kg and 1.44 ± 0.11 mg/kg in the LTHRD and ND patients. The isotonic regression analysis further showed that ED50 and ED95 of propofol for successful insertion of gastroscope was 1.50 mg/kg (95%CI, 1.40-1.63) and 1.80 mg/kg (95%CI, 1.74-1.90) in the LTHRD patients, respectively; 1.40 mg/kg (95% CI, 1.27-1.57) and 1.60 mg/kg (95%CI, 1.56-1.65) in the ND patients. The ED50 of propofol for successful insertion of gastroscope was not significantly different between LTHRD and ND patients. CONCLUSIONS: This study demonstrates that the difference in the estimated ED50 of propofol for successful insertion of gastroscope between LTHRD and ND Chinese male patients was not statistically significant. TRIAL REGISTRATION: The study was registered on November 28, 2020 ( ChiCTR2000040382 ) in the Chinese Clinical Trial Registry.
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Anestésicos Intravenosos , Propofol , China , Relação Dose-Resposta a Droga , Gastroscópios , Humanos , Intubação Intratraqueal/métodos , MasculinoRESUMO
Objective: Myocardial ischemia/reperfusion injury (IRI) is a common and serious complication in clinical practice. Sevoflurane conditionings have been identified to provide a protection against myocardial IRI in animal experiments, but their true clinical benefits remain controversial. Here, we aimed to analyze the preclinical evidences obtained in animal models of myocardial IRI and explore the possible reasons for controversial clinical benefits. Methods: Our primary outcome was the difference in mean infarct size between the sevoflurane and control groups in animal models of myocardial IRI. After searching the databases of PubMed, Embase, Web of Science, and the Cochrane Library, a systematic review retrieved 37 eligible studies, from which 28 studies controlled comparisons of sevoflurane preconditioning (SPreC) and 40 studies controlled comparisons of sevoflurane postconditioning (SPostC) that were made in a pooled random-effects meta-analysis. In total, this analysis included data from 313 control animals and 536 animals subject to sevoflurane conditionings. Results: Pooled estimates for primary outcome demonstrated that sevoflurane could significantly reduce the infarct size after myocardial IRI whether preconditioning [weighted mean difference (WMD): -18.56, 95% CI: -23.27 to -13.85, P < 0.01; I 2 = 94.1%, P < 0.01] or postconditioning (WMD: -18.35, 95% CI: -20.88 to -15.83, P < 0.01; I 2 = 90.5%, P < 0.01) was performed. Interestingly, there was significant heterogeneity in effect size that could not be explained by any of the prespecified variables by meta-regression and stratified analysis. However, sensitivity analysis still identified the cardioprotective benefits of sevoflurane conditionings with robust results. Conclusion: Sevoflurane conditionings can significantly reduce infarct size in in-vivo models of myocardial IRI. Given the fact that there is a lack of consistency in the quality and design of included studies, more well-performed in-vivo studies with the detailed characterization of sevoflurane protocols, especially studies in larger animals regarding cardioprotection effects of sevoflurane, are still required.
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Background: The use of police breath alcohol detectors in rat breath alcohol detection experiments has always been a challenge because of the small lung capacity and inability of rats to actively inhale. However, the method of using gas chromatography to detect blood alcohol concentration is time-consuming, complex, relatively expensive, and cannot achieve on-site detection and multi-point unlimited non-invasive detection. Objectives: In this study, a laboratory method was validated for rat breath ethanol concentration (BrAC) measurement to estimate blood ethanol concentration (BAC) in rats. Methods: The rats were placed in a gas collection bottle, the breath sample was drawn out with a syringe, and injected into the mouthpiece of the breath alcohol detector through a rubber tube. The results were immediately detected and automatically converted to BAC. Male rats were randomly divided into three groups. The control group received an intraperitoneal injection of normal saline, the liver injury group received an intraperitoneal injection of 50% Carbon tetrachloride (CCL4 1 mL.kg-1), and the induction group received an intraperitoneal injection of phenobarbital sodium (75 mg.kg-1). Western blot analysis was used to detect the protein expression of CYP2E1. Similar grouping and experimental methods were used for female rats. Results: This method was reproducible. The metabolic activity of CYP2E1 was downregulated in the injury group and upregulated in the induction group, which was consistent with the results obtained for CYP2E1 protein expression. Conclusions: Our results confirmed that the rat gas cylinder breath alcohol assay can be used for multiple detections with immediate and non-invasive determination of alcohol metabolizing capacity. This is important for studies that require repeated assessment of blood alcohol levels.
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Agriculture soil plays a crucial role in sustainable development of human society. Unfortunately, soil quality is continuing degradation due to industrial and agricultural activities. Among them, agriculture soil contamination by heavy metals has become a serious threat to global food safety and human health. Because of low-cost, easy to implement, and fast effects, in situ chemical stabilization strategy has drawn great attention in soil remediation fields. However, since heavy metals are not removed from soil, it is still a great challenge to develop the cost-effective stabilizers with strong and long-term immobilization ability. Layered double hydroxides (LDHs) have been extensively applied in environmental fields owing to their unique structure. Very recently, LDHs have been used as amendment in in situ soil remediation for immobilization of heavy metals, exhibiting excellent long-term stability in practice application through trapping heavy metal ions into the lattice of LDHs layer. Given that the super-stable mineralization effect of LDHs for heavy metals, we summarize the structure of LDHs, key points of super-stable mineralization, practical challenges, and potential applications in other heavy metals pollution scenarios in this article, wishing that could provide new strategies and insights into rational designing of amendments for soil remediation.
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Lipocalin2 (Lcn2) has been shown to be a vital regulator of tumorigenesis in a variety of different cancers. However, its expression patterns and possible roles in ovarian cancer remain obscure. The aim of this study was to investigate the expression of Lcn2 in ovarian cancer cells and to determine any potential association between Lcn2 and ovarian tumor development and cancer progression. Our results indicated that Lcn2 was upregulated in tumor tissue from ovarian cancer patients as well as in three ovarian cancer cell lines compared to normal tissues and cells. Overexpression of Lcn2 promoted both cell proliferation and migration in ovarian cancer cells. Conversely, knockdown of Lcn2 in cell lines suppressed both migration and proliferation. Moreover, upregulation of Lcn2 contributed to tumor growth in nude mice in vivo. Mechanistically, Lcn2 was found to lead to tumor progression in ovarian cancer cells through activation of the ERK/GSK3ß/ß-catenin signaling pathway. In summary, Lcn2 promotes cell proliferation and migration in ovarian cancer through activation of the ERK/GSK3ß/ß-catenin signaling pathway, suggesting that Lcn2 might be a novel therapeutic target for ovarian cancer.
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Movimento Celular/genética , Proliferação de Células/genética , Lipocalina-2/genética , Neoplasias Ovarianas/patologia , Animais , Linhagem Celular Tumoral , Progressão da Doença , Feminino , Regulação Neoplásica da Expressão Gênica , Técnicas de Silenciamento de Genes , Glicogênio Sintase Quinase 3 beta/metabolismo , Humanos , Sistema de Sinalização das MAP Quinases/genética , Camundongos , Camundongos Nus , Neoplasias Ovarianas/genética , Via de Sinalização Wnt/genéticaRESUMO
AIMS: Liver cancer is one of the leading causes of cancer death worldwide owing to its delayed diagnosis and absence of efficient treatment at advanced TNM stages. Increasing evidence demonstrated that microRNAs are implicated in tumorgenesis and cancer development by regulating cancer-related proteins. This study aimed to explore the effect of miR-3619-5p on cell growth in liver cancer. MAIN METHODS: The effect of miR-3619-5p on cell proliferation was measured by quantitative real-time PCR, MTT assay, flow cytometry, and Immunofluorescence assay. The interaction between miR-3619-5p and PSMD10 was validated using dual-luciferase. The expression of PSMD10 and Ki67 was further determined by immunohistochemistry. KEY FINDINGS: MiR-3619-5p over-expression remarkably inhibited cell proliferation and induced G1 phase arrest, accompanied with reduced expression of proliferating cell nuclear antigen. The expression of miR-3619-5p was negatively correlated to that of PSMD10, and PSMD10 was validated to be a downstream target of miR-3619-5p. Moreover, miR-3619-5p induced suppressed proliferation and G1 phase arrest were abrogated by elevated the expression of PSMD10 in liver cancer cells. PSMD10 over-expression also induced phosphorylation of signal transducer and activator of transcription 3 (STAT3) and retinoblastoma protein (Rb1). Besides, elevated cyclin A, cyclin D1 and cyclin E expression supported that PSMD10 promoted the progress of cell cycle. In addition, miR-3619-5p inhibited tumor growth in vivo by targeting PSMD10, accompanied with blocked cell cycle. SIGNIFICANCE: In conclusion, our findings revealed that miR-3619-5p inhibits cancer cell proliferation by targeting PSMD10, and miR-3619-5p as a potential therapeutic target for the treatment of liver cancer.
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Neoplasias Hepáticas/patologia , MicroRNAs/fisiologia , Complexo de Endopeptidases do Proteassoma/fisiologia , Proteínas Proto-Oncogênicas/fisiologia , Linhagem Celular Tumoral , Proliferação de Células , Humanos , Técnicas In VitroRESUMO
Magnetic topological insulators (TI) provide an important material platform to explore quantum phenomena such as quantized anomalous Hall effect and Majorana modes, etc. Their successful material realization is thus essential for our fundamental understanding and potential technical revolutions. By realizing a bulk van der Waals material MnBi4Te7 with alternating septuple [MnBi2Te4] and quintuple [Bi2Te3] layers, we show that it is ferromagnetic in plane but antiferromagnetic along the c axis with an out-of-plane saturation field of ~0.22 T at 2 K. Our angle-resolved photoemission spectroscopy measurements and first-principles calculations further demonstrate that MnBi4Te7 is a Z2 antiferromagnetic TI with two types of surface states associated with the [MnBi2Te4] or [Bi2Te3] termination, respectively. Additionally, its superlattice nature may make various heterostructures of [MnBi2Te4] and [Bi2Te3] layers possible by exfoliation. Therefore, the low saturation field and the superlattice nature of MnBi4Te7 make it an ideal system to investigate rich emergent phenomena.