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Two-dimensional (2D) van der Waals magnets comprise rich physics that can be exploited for spintronic applications. We investigate the interplay between spin-phonon coupling and spin textures in a 2D van der Waals magnet by combining magneto-Raman spectroscopy with cryogenic Lorentz transmission electron microscopy. We find that when stable skyrmion bubbles are formed in the 2D magnet, a field-dependent Raman shift can be observed, and this shift is absent for the 2D magnet prepared in its ferromagnetic state. Correlating these observations with numerical simulations that take into account field-dependent magnetic textures and spin--phonon coupling in the 2D magnet, we associate the Raman shift to field-induced modulations of the skyrmion bubbles and derive the existence of inhomogeneity in the skyrmion textures over the film thickness.
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INTRODUCTION: The correlation between serum angiopoietin-2 levels and acute kidney injury (AKI) is a topic of significant clinical interest. This meta-analysis aims to provide a comprehensive evaluation of this relationship. CONTENT: A systematic search was conducted in PubMed, Embase, Web of Science, and Cochrane databases up to October 11, 2023. The included studies were evaluated using the Newcastle-Ottawa Scale (NOS) and Methodological Index for Non-Randomized Studies (MINORS). Weighted mean differences (WMD) and odds ratios (OR) were calculated using random-effects models. Sensitivity analysis, funnel plots, and Egger's test were used to assess the robustness and publication bias of the findings. Subgroup analyses were performed to explore potential variations between adults and children. SUMMARY: Eighteen studies encompassing a total of 7,453 participants were included. The analysis revealed a significant elevation in serum angiopoietin-2 levels in patients with AKI compared to those without (WMD: 4.85; 95â¯% CI: 0.75 to 0.27; I²=93.2â¯%, p<0.001). Subgroup analysis indicated significantly higher angiopoietin-2 levels in adults with AKI (WMD: 5.17; 95â¯% CI: 3.51 to 6.83; I²=82.6â¯%, p<0.001), but not in children. Additionally, high serum angiopoietin-2 levels were associated with an increased risk of AKI (OR: 1.58; 95â¯% CI: 1.39 to 1.8; I²=89.1â¯%, p<0.001). Sensitivity analysis validated the robustness of these results, showing no substantial change in the overall effect size upon the exclusion of individual studies. OUTLOOK: This meta-analysis supports a significant association between elevated serum angiopoietin-2 levels and increased risk of AKI. The observed differential association between adults and children highlights the need for further targeted research to understand these age-specific variations.
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Aberrant energy metabolism not only endows tumor cells with unlimited proliferative capacity but also contributes to the establishment of the glucose-deficient/lactate-rich immunosuppressive tumor microenvironment (ITM) impairing antitumor immunity. Herein, a novel metabolic nanoregulator (D/B/CQ@ZIF-8@CS) was developed by enveloping 2-deoxy-d-glucose (2-DG), BAY-876, and chloroquine (CQ) into zeolitic imidazolate framework-8 (ZIF-8) to simultaneously deprive the energy/nutrition supply of tumor cells and relieve the ITM for synergetic tumor starvation-immunotherapy. Aerobic glycolysis, glucose uptake, and autophagy flux could be concurrently blocked by D/B/CQ@ZIF-8@CS, cutting off the nutrition/energy supply and the source of lactate. Furthermore, inhibition of glucose uptake and aerobic glycolysis could effectively reverse the glucose-deficient/lactate-rich ITM, thus functionally inactivating regulatory T cells and augmenting anti-CTLA-4 immunotherapy. Such a two-pronged strategy would provide new insights for the design of metabolic intervention-based synergistic cancer therapy.
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Glicólise , Neoplasias , Linhagem Celular Tumoral , Metabolismo Energético , Glucose/metabolismo , Humanos , Terapia de Imunossupressão , Lactatos , Neoplasias/tratamento farmacológico , Microambiente TumoralRESUMO
We demonstrate that reflectionless propagation of electromagnetic waves between two different materials can be achieved by designing an intermediate temporal medium, which can work in an ultra-wide frequency band. Such a temporal medium is designed with consideration of a multi-stage variation of the material's permittivity in the time domain. The multi-stage temporal permittivity is formed by a cascaded quarter-wave temporal coating, which is an extension of the antireflection temporal coating by Pacheco-Peña et al. [Optica7, 323 (2020)10.1364/OPTICA.381175]. The strategy to render ultra-wideband antireflection temporal medium is discussed analytically and verified numerically. In-depth analysis shows that the multi-stage design of the temporal media implies a continuously temporal variation of the material's constitutive parameters, thus an ultra-wideband antireflection temporal medium is reasonably obtained. As an illustrative example for application, the proposed temporal medium is adopted to realize impedance matching between a dielectric slab and free space, which validates our new findings.
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Lensless cameras are characterized by several advantages (e.g., miniaturization, ease of manufacture, and low cost) as compared with conventional cameras. However, they have not been extensively employed due to their poor image clarity and low image resolution, especially for tasks that have high requirements on image quality and details such as text detection and text recognition. To address the problem, a framework of deep-learning-based pipeline structure was built to recognize text with three steps from raw data captured by employing lensless cameras. This pipeline structure consisted of the lensless imaging model U-Net, the text detection model connectionist text proposal network (CTPN), and the text recognition model convolutional recurrent neural network (CRNN). Compared with the method focusing only on image reconstruction, U-Net in the pipeline was able to supplement the imaging details by enhancing factors related to character categories in the reconstruction process, so the textual information can be more effectively detected and recognized by CTPN and CRNN with fewer artifacts and high-clarity reconstructed lensless images. By performing experiments on datasets of different complexities, the applicability to text detection and recognition on lensless cameras was verified. This study reasonably demonstrates text detection and recognition tasks in the lensless camera system, and develops a basic method for novel applications.
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Artefatos , Redes Neurais de ComputaçãoRESUMO
Purpose: Using the gastric cancer cell line SGC7901 and gastric cancer stem cell (CSC-G), we conducted this study to investigate the role of cancer stem cells in invasion, metastasis and tumor angiogenesis. Methods: Stem cell markers (OCT4, SOX2, C-Myc and Klf4) expression was detected by RT-PCR and Western blotting. The proliferation, migration, invasion abilities, L-OHP and 5-FU resistance, angiogenesis were assessed using in vitro spherical clone formation assays, plate cloning experiments, transwell migration, transwell invasion, drug resistance, scratch-wound migration, ring formation assay, and their tumorigenic and ability were assessed using a tumor formation experiment in mice. Results: Compared with the SGC7901, the expression of Oct4, Sox2, Klf4 and CD44 mRNA was significantly higher in CSC-G, the mRNA relative expression of E-cadherin in CSC-G was lower than SGC7901, while the expression of c-Myc did not significantly change. The proliferation, drug resistance, migration, and invasion abilities were significantly higher in CSC-G, and the tumorigenic ability in mice was also significantly higher. Conclusion: The proliferation, drug resistance, migration, invasion, and tumorigenic abilities of CSC-G significantly were higher than SGC7901. CSC-G plays important roles in proliferation, migration, invasion, and tumorigenicity.
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Resistencia a Medicamentos Antineoplásicos/efeitos dos fármacos , Células-Tronco Neoplásicas/patologia , Neovascularização Patológica/patologia , Neoplasias Gástricas/patologia , Animais , Antígenos CD/genética , Antineoplásicos/farmacologia , Caderinas/genética , Linhagem Celular Tumoral , Movimento Celular , Feminino , Regulação Neoplásica da Expressão Gênica , Humanos , Receptores de Hialuronatos/genética , Fator 4 Semelhante a Kruppel , Camundongos Endogâmicos NOD , Células-Tronco Neoplásicas/efeitos dos fármacos , Fator 3 de Transcrição de Octâmero/metabolismo , Reação em Cadeia da Polimerase em Tempo Real , Fatores de Transcrição SOXB1/metabolismo , Neoplasias Gástricas/irrigação sanguínea , Neoplasias Gástricas/tratamento farmacológico , Ensaios Antitumorais Modelo de XenoenxertoRESUMO
BACKGROUND: Additional studies comparing laparoscopic gastrectomy (LG) versus open gastrectomy (OG) for advanced gastric cancer (AGC) have been published, and it is necessary to update the systematic review of this subject. OBJECTIVE: We conducted the meta-analysis to find some proof for the use of LG in AGC and evaluate whether LG is an alternative treatment for AGC. METHOD: Randomized controlled trials (RCT) and high-quality retrospective studies (NRCT) compared LG and OG for AGC, which were published in English between January 2010 and May 2019, were search in PubMed, Embase, and Web of Knowledge by three authors independently and thoroughly. Some primary endpoints were compared between the two groups, including intraoperative time, intraoperative blood loss, harvested lymph nodes, first flatus, first oral intake, first out of bed, post-operative hospital stay, postoperative morbidity and mortality, rate of disease recurrence, and 5-year over survival (5-y OS). Besides, considering for this 10-year dramatical surgical material development between 2010 and 2019, we furtherly make the same analysis based on recent studies published between 2016 and 2019. RESULT: Thirty-six studies were enrolled in this systematic review and meta-analysis, including 5714 cases in LAG and 6094 cases in OG. LG showed longer intraoperative time, less intraoperative blood loss, and quicker recovery after operations. The number of harvested lymph nodes, hospital mortality, and tumor recurrence were similar. Postoperative morbidity and 5-y OS favored LG. Furthermore, the systemic analysis of recent studies published between 2016 and 2019 revealed similar result. CONCLUSION: A positive trend was indicated towards LG. LG can be performed as an alternative to OG for AGC.
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Gastrectomia/métodos , Recidiva Local de Neoplasia/cirurgia , Neoplasias Gástricas/cirurgia , Perda Sanguínea Cirúrgica/estatística & dados numéricos , Mortalidade Hospitalar , Humanos , Laparoscopia/métodos , Tempo de Internação/estatística & dados numéricos , Linfonodos/patologia , Recidiva Local de Neoplasia/patologia , Período Pós-Operatório , Ensaios Clínicos Controlados Aleatórios como Assunto , Estudos Retrospectivos , Neoplasias Gástricas/patologia , Resultado do TratamentoRESUMO
BACKGROUND: Zinc-finger E-box binding homeobox 1 (ZEB-1) plays crucial roles in epithelial-to-mesenchymal transition during tumor carcinogenesis. Published studies have examined the potential value of ZEB-1 as a biomarker for the prognosis of cancer. Nevertheless, the prognostic significance of ZEB-1 in human solid tumor remains inconclusive. Therefore, we performed the present meta-analysis to evaluate the prognostic value of ZEB-1 in patients with solid tumors. METHODS: The 13 included studies (1616 patients) were exact electronic searched from Web of Science, PubMed and EBSCO until September 2018. Pooled hazard ratios (HR) and the corresponding 95% confidence intervals (CI) for overall survival (OS) were analyzed through random or fixed effects models. Univariate and multivariate analyses were independently performed. Subgroup analyses, heterogeneity and publication bias were investigated to further enhance reliability. RESULTS: This research indicated that elevated expression of ZEB-1 significantly predicted worse OS in patients with solid tumors. In the univariate analysis, the pooled HR for OS was 1.66 (95% CI: 1.45-1.90; P < 0.01). Meanwhile, in multivariate analysis, the pooled HR for OS was 2.28 (95% CI: 1.58-3.30; P < 0.01). Begg's funnel plot and Begg's test did not show evidence of significant publication bias, both in univariate analysis and multivariate analysis. CONCLUSIONS: High expression of ZEB-1 was associated with poorer OS, suggesting that ZEB-1 may be a potential biomarker for the prediction of prognosis, and a novel therapeutic target in human solid tumors.
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Biomarcadores Tumorais/genética , Neoplasias/diagnóstico , Neoplasias/genética , Homeobox 1 de Ligação a E-box em Dedo de Zinco/genética , Biomarcadores Tumorais/normas , Feminino , Humanos , Masculino , Neoplasias/mortalidade , Prognóstico , Análise de Sobrevida , Regulação para CimaRESUMO
Extracellular matrix protein periostin is highly expressed in various tumors and plays a critical role in tumor development and progression. Periostin is mainly secreted by stromal cells such as cancer-associated fibroblasts, myofibroblasts, osteoblasts and bone marrow-derived mesenchymal stromal cells. But in some cases, tumor cells, especially cancer stem cells, can also produce periostin. Periostin has been shown to regulate multiple biological behaviors of tumor cells, including proliferation, survival, invasion, angiogenesis, metastasis and chemoresistance. Moreover, an excessive periostin deposition exerts a pivotal role in remodeling various tumor microenvironments, such as cancer stem cell niche, perivascular niche, premetastatic niche, immunosuppressive microenvironment, bone marrow microenvironment and other tumor growth-supportive microenvironments. In this review, we provide an update understanding of the multifaceted functions and mechanisms of periostin in tumor development and progression.
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Moléculas de Adesão Celular/fisiologia , Neoplasias/patologia , Células-Tronco Neoplásicas , Células Estromais , Microambiente Tumoral , Humanos , Nicho de Células-TroncoRESUMO
BACKGROUND: Acinetobacter baumannii (AB) is critical for healthcare-associated infections (HAI) with significant regional differences in the resistance rate, but its risk factors and infection trends has not been well studied. We aimed to explore the risk factors, epidemiological characteristics and resistance of multidrug-resistant Acinetobacter baumannii (MDR-AB) in intensive care unit inpatients. METHODS: Data of patients with MDR-AB (195 cases), and with antibiotic-sensitive AB infection (294 cases, control) during January to December, 2015 in three medical centers in Xiamen, China were conducted and analyzed in the present retrospective study. RESULTS: Lower respiratory tract infection with AB accounted for 68.71%. MDR-AB was detected in 39.88% of all cases. Univariate analysis suggested that mechanical ventilation, indwelling catheter, cancer patients, length of hospitalization in intensive care unit (ICU) ≥15 d, Acute Physiology and Chronic Health Evaluation (APACHE) II score, combined using antibiotic before isolation of AB and use of third-lines cephalosporins were associated with the development of MDR-AB healthcare-associated infections. Dose-response relationship analysis suggested that the age and the days of mechanical ventilation were associated with increased infection with MDR-AB. Logistic regression analysis suggested that, mechanical ventilation, combined using antibiotic before isolation of AB, and indwelling catheter, were associated with MDR-AB infection, with odds ratios (OR) and 95% confidence intervals (CI) of 3.93 (1.52-10.14), 4.11 (1.58-10.73), and 4.15 (1.32-12.99), respectively. CONCLUSIONS: MDR-AB infection was associated with mechanical ventilation, combined using antibiotic before isolation of AB, and indwelling catheter. Furthermore, the age and the days of mechanical ventilation were associated with increased infection with MDR-AB.
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Infecções por Acinetobacter/tratamento farmacológico , Infecções por Acinetobacter/microbiologia , Acinetobacter baumannii/efeitos dos fármacos , Farmacorresistência Bacteriana Múltipla/efeitos dos fármacos , Infecções por Acinetobacter/epidemiologia , Acinetobacter baumannii/patogenicidade , Adulto , Idoso , Idoso de 80 Anos ou mais , Antibacterianos/administração & dosagem , Antibacterianos/uso terapêutico , Infecções Relacionadas a Cateter/tratamento farmacológico , Infecções Relacionadas a Cateter/epidemiologia , Infecções Relacionadas a Cateter/microbiologia , Cefalosporinas/uso terapêutico , China/epidemiologia , Infecção Hospitalar/tratamento farmacológico , Infecção Hospitalar/epidemiologia , Relação Dose-Resposta a Droga , Feminino , Humanos , Unidades de Terapia Intensiva/estatística & dados numéricos , Masculino , Pessoa de Meia-Idade , Respiração Artificial/efeitos adversos , Estudos Retrospectivos , Fatores de RiscoRESUMO
Tumor microenvironment consists of tumor cells, stromal cells, extracellular matrix and a plethora of soluble components. The complex array of interactions between tumor cells and their surrounding tumor microenvironments contribute to the determination of the fate of tumor cells during tumorigenesis and metastasis. Matricellular protein periostin is generally absent in most adult tissues but is highly expressed in tumor microenvironments. Current evidence reveals that periostin plays a critical role in establishing and remodeling tumor microenvironments such as the metastatic niche, cancer stem cell niche, perivascular niche, pre-metastatic niche, fibrotic microenvironment and bone marrow microenvironment. Here, we summarize the current knowledge of the multifaceted role of periostin in the tumor microenvironments.
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Moléculas de Adesão Celular/genética , Regulação Neoplásica da Expressão Gênica , Proteínas de Neoplasias/genética , Neoplasias/genética , Microambiente Tumoral/genética , Medula Óssea/metabolismo , Medula Óssea/patologia , Moléculas de Adesão Celular/metabolismo , Comunicação Celular , Progressão da Doença , Matriz Extracelular/metabolismo , Matriz Extracelular/patologia , Fibroblastos/metabolismo , Fibroblastos/patologia , Humanos , Metástase Neoplásica , Proteínas de Neoplasias/metabolismo , Neoplasias/metabolismo , Neoplasias/patologia , Células-Tronco Neoplásicas/metabolismo , Células-Tronco Neoplásicas/patologia , Nicho de Células-Tronco/genética , Células Estromais/metabolismo , Células Estromais/patologiaRESUMO
In the past decades, the oncogenic role of fibroblast growth factor receptor 2 has been demonstrated in a number of cancer types. However, studies have reported contradictory findings concerning the correlation between fibroblast growth factor receptor 2 expression and prognosis in solid tumors. To address this discrepancy, we performed a meta-analysis with 18 published studies (2975 patients) retrieved from PubMed, EMBASE, and Web of science. Data were extracted and computed into odds ratios. The results showed that fibroblast growth factor receptor 2 overexpression was significantly associated with decreased 3-year overall survival (odds ratio = 1.93, 95% confidence interval: 1.30-2.85, p = 0.001) and 5-year overall survival (odds ratio = 1.62, 95% confidence interval: 1.07-2.44, p = 0.02) in patients with solid tumors. Subgroup analysis revealed that high fibroblast growth factor receptor 2 expression was also associated with poor prognosis of gastric cancer, hepatocellular carcinoma, and esophageal cancer, but not correlated with pancreatic cancer. In conclusion, fibroblast growth factor receptor 2 overexpression is correlated with decreased survival in most solid tumors, suggesting that the expression status of fibroblast growth factor receptor 2 is a valuable prognostic biomarker and a novel therapeutic target in human solid tumors.
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Biomarcadores Tumorais/biossíntese , Neoplasias/genética , Prognóstico , Receptor Tipo 2 de Fator de Crescimento de Fibroblastos/biossíntese , Biomarcadores Tumorais/genética , Intervalo Livre de Doença , Regulação Neoplásica da Expressão Gênica , Humanos , Neoplasias/patologia , PubMed , Receptor Tipo 2 de Fator de Crescimento de Fibroblastos/genéticaRESUMO
Periostin (POSTN) is a limiting factor in the metastatic colonization of disseminated tumour cells. However, the role of POSTN in regulating the immunosuppressive function of immature myeloid cells in tumour metastasis has not been documented. Here, we demonstrate that POSTN promotes the pulmonary accumulation of myeloid-derived suppressor cells (MDSCs) during the early stage of breast tumour metastasis. Postn deletion decreases neutrophil and monocytic cell populations in the bone marrow of mice and suppresses the accumulation of MDSCs to premetastatic sites. We also found that POSTN-deficient MDSCs display reduced activation of ERK, AKT and STAT3 and that POSTN deficiency decreases the immunosuppressive functions of MDSCs during tumour progression. Moreover, the pro-metastatic role of POSTN is largely limited to ER-negative breast cancer patients. Lysyl oxidase contributes to POSTN-promoted premetastatic niche formation and tumour metastasis. Our findings indicate that POSTN is essential for immunosuppressive premetastatic niche formation in the lungs during breast tumour metastasis and is a potential target for the prevention and treatment of breast tumour metastasis. Copyright © 2016 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.
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Neoplasias da Mama/patologia , Moléculas de Adesão Celular/metabolismo , Tolerância Imunológica/genética , Células Supressoras Mieloides/patologia , Metástase Neoplásica/patologia , Animais , Neoplasias da Mama/genética , Neoplasias da Mama/metabolismo , Moléculas de Adesão Celular/genética , Camundongos , Camundongos Knockout , Células Supressoras Mieloides/metabolismo , Metástase Neoplásica/genética , Transdução de Sinais/fisiologiaRESUMO
miR-411-5p (previously called miR-411) is severely involved in human diseases, however, the relationship between miR-411-5p and breast cancer has not been investigated thoroughly. Here, we found that the expression of miR-411-5p was downregulated in breast cancer tissues compared with their matched adjacent non-neoplastic tissues. In addition, the expression of miR-411-5p was also lower in breast cancer cell lines in contrast with MCF-10A. Moreover, we investigated the target and mechanism of miR-411-5p in breast cancer using mimic and inhibitor, and demonstrated the involvement of GRB2 and Ras activation. Ectopic expression of miR-411-5p suppressed the breast cancer cell proliferation, migration and invasion while low expression of miR-411-5p exhibited the opposite effect. Furthermore, GRB2 was demonstrated to be significantly overexpressed in breast cancer tissues compared with normal tissues, and low expression of GRB2 had a longer overall survival compared with high expression of GRB2 in breast cancer. In general, our study shed light on the miR-411-5p related mechanism in the progression of breast cancer and, miR-411-5p/GRB2/Ras axis is potential to be molecular target for breast cancer therapy.
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Neoplasias da Mama/genética , Neoplasias da Mama/patologia , Proteína Adaptadora GRB2/genética , MicroRNAs/genética , Regiões 3' não Traduzidas , Neoplasias da Mama/metabolismo , Linhagem Celular Tumoral , Movimento Celular/genética , Proliferação de Células/genética , Progressão da Doença , Regulação para Baixo , Feminino , Proteína Adaptadora GRB2/metabolismo , Expressão Gênica , Inativação Gênica , Humanos , Células MCF-7 , Invasividade Neoplásica/genética , Metástase Neoplásica/genética , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , RNA Neoplásico/genética , RNA Neoplásico/metabolismo , Transdução de Sinais/genética , Proteínas ras/metabolismoRESUMO
Periostin actively contributes to tissue injury, fibrosis, atherosclerosis, and inflammatory diseases; however, its role in hepatic fibrosis is unclear. Herein, we revealed that periostin expression was significantly up-regulated in carbon tetrachloride- and bile duct ligation-induced mice with acute and chronic liver fibrosis. Deficiency in periostin abrogated the development of liver fibrosis in mice. Carbon tetrachloride treatment significantly increased α-smooth muscle actin, fibronectin, and collagen I levels in wild-type mice, which were unaffected in periostin-knockout mice. Periostin-deficient mice showed a significantly reduced area of collagen deposition and decreased levels of serum alanine aminotransferase and aspartate aminotransferase compared with wild-type mice after 2 weeks of carbon tetrachloride administration. Chemokine ligand 2, IL-6, IL-1ß, tumor necrosis factor-α, and tissue inhibitor of metalloproteinases 1 mRNA levels were significantly lower in periostin-deficient mice than in wild-type mice after carbon tetrachloride treatment. Periostin colocalized with hepatic stellate cell-derived collagen I and α-smooth muscle actin in mouse acute and chronic fibrotic liver tissues. Transforming growth factor (TGF)-ß1 markedly induced periostin expression in primary mouse hepatic stellate cells. Periostin-deficient mice showed significantly lower levels of TGF-ß1 and TGF-ß2 compared with wild-type mice after carbon tetrachloride treatment. High levels of periostin in patients with acute or chronic hepatitis correlated with TGF-ß1 and TGF-ß2 expression in serum from patients with hepatitis. Data indicate that periostin is a novel mediator of hepatic fibrosis development.
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Moléculas de Adesão Celular/metabolismo , Doença Hepática Induzida por Substâncias e Drogas/metabolismo , Hepatite/metabolismo , Inflamação/metabolismo , Cirrose Hepática/metabolismo , Fígado/metabolismo , Animais , Moléculas de Adesão Celular/genética , Doença Hepática Induzida por Substâncias e Drogas/patologia , Colágeno/metabolismo , Células Estreladas do Fígado/metabolismo , Células Estreladas do Fígado/patologia , Hepatite/patologia , Humanos , Inflamação/patologia , Fígado/patologia , Cirrose Hepática/patologia , Camundongos , Camundongos Knockout , Fator de Crescimento Transformador beta/metabolismoRESUMO
Twist2 is a highly conserved basic helix-loop-helix transcription factor that plays a critical role in embryogenesis. Recent evidence has revealed that aberrant Twist2 expression contributes to tumor progression; however, the role of Twist2 in human hepatocellular carcinoma (HCC) and its underlying mechanisms remain undefined. In this report, we demonstrate that Twist2 is overexpressed in human HCC tumors. We show that ectopic expression of Twist2 induces epithelial-mesenchymal transition phenotypes, augments cell migration and invasion and colony-forming abilities in human HCC cells in vitro, and promotes tumor growth in vivo. Moreover, we found a higher percentage of CD24(+) liver cancer stem-like cells in Twist2-transduced HCC cells. Twist2-expressing cells exhibited an increased expression of stem cell markers Bmi-1, Sox2, CD24 and Nanog and an increased capacity for self-renewal. Knockdown of CD24 in HepG2/Twist2 cells decreased the levels of Sox2, pSTAT3 and Nanog, and reversed the cancer stem-like cell phenotypes induced by ectopic expression of Twist2. Furthermore, Twist2 regulated the CD24 expression by directly binding to the E-box region in CD24 promoter. Therefore, our data demonstrated that Twist2 augments liver cancer stem-like cell self-renewal in a CD24-dependent manner. Twist2-CD24-STAT3-Nanog pathway may play a critical role in regulating liver cancer stem-like cell self-renewal. The identification of the Twist2-CD24 signaling pathway provides a potential therapeutic approach to target cancer stem cells in HCCs.
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Antígeno CD24/fisiologia , Divisão Celular/fisiologia , Neoplasias Hepáticas/patologia , Células-Tronco Neoplásicas/patologia , Proteínas Repressoras/fisiologia , Proteína 1 Relacionada a Twist/fisiologia , Sequência de Bases , Linhagem Celular Tumoral , Primers do DNA , Transição Epitelial-Mesenquimal , Citometria de Fluxo , Humanos , Reação em Cadeia da PolimeraseRESUMO
Genistein, the predominant isoflavone found in soy products, has exerted its anticarcinogenic effect in many different tumor types in vitro and in vivo. Accumulating evidence in recent years has strongly indicated the existence of cancer stem cells in gastric cancer. Here, we showed that low doses of genistein (15 µM), extracted from Millettia nitida Benth var hirsutissima Z Wei, inhibit tumor cell self-renewal in two types of gastric cancer cells by colony formation assay and tumor sphere formation assay. Treatment of gastric cancer cells with genistein reduced its chemoresistance to 5-Fu (fluorouracil) and ciplatin. Further results indicated that the reduced chemoresistance may be associated with the inhibition of ABCG2 expression and ERK 1/2 activity. Furthermore, genistein reduced tumor mass in the xenograft model. Together, genistein inhibited gastric cancer stem cell-like properties and reduced its chemoresistance. Our results provide a further rationale and experimental basis for using the genistein to improve treatment of patients with gastric cancer.
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Resistencia a Medicamentos Antineoplásicos/efeitos dos fármacos , Genisteína/farmacologia , Células-Tronco Neoplásicas/efeitos dos fármacos , Neoplasias Gástricas/tratamento farmacológico , Ensaios Antitumorais Modelo de Xenoenxerto , Membro 2 da Subfamília G de Transportadores de Cassetes de Ligação de ATP , Transportadores de Cassetes de Ligação de ATP/genética , Animais , Antineoplásicos/farmacologia , Western Blotting , Linhagem Celular Tumoral , Sobrevivência Celular/efeitos dos fármacos , Cisplatino/farmacologia , Relação Dose-Resposta a Droga , Feminino , Fluoruracila/farmacologia , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Genisteína/química , Humanos , Camundongos Nus , Proteína Quinase 1 Ativada por Mitógeno/metabolismo , Proteína Quinase 3 Ativada por Mitógeno/metabolismo , Estrutura Molecular , Proteínas de Neoplasias/genética , Células-Tronco Neoplásicas/metabolismo , Células-Tronco Neoplásicas/patologia , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Neoplasias Gástricas/genética , Neoplasias Gástricas/metabolismo , Ensaio Tumoral de Célula-TroncoRESUMO
OBJECTIVE: To explore the analgesic effects and postoperative recovery of ropivacaine incision infiltration in elderly patients after total laparoscopic radical gastrectomy. METHODS: The clinical data were obtained prospectively from 61 elderly patients ( ≥ 65y) undergoing traditional total laparoscopic radical gastrectomy under standard general anesthesia at our department during January 2012 and September 2013. After surgery, they were randomly double-blindly divided into 3 groups: local infiltration of ropivacaine group (0.5% ropivacaine incision infiltration, 40 ml, n = 22), local infiltration of sodium chloride group (0.9% sodium chloride injection incision infiltration, 40 ml, n = 20) and control group (no analgesic, n = 19). The intensity of postoperative pain was evaluated by numeric rating scale (NRS). And 10 mg of morphine was administered intramuscularly as rescue medication when NRS exceeded 4.NRS, cases on remedy analgesia and associated side effects were observed and recorded after 6 h postoperatively. A comparative study was made for postoperative first ambulation time, intestinal function recovery time, complication incidence, postoperative hospital stay and medical expenses among three groups. RESULTS: Significant postoperative difference existed in NRS at 6, 12, 24, 48 h among ropivacaine, sodium and control groups respectively (6 h: 2.65 ± 0.25 vs 5.47 ± 0.12 vs 5.63 ± 0.27, 12 h: 2.42 ± 0.34 vs 5.82 ± 0.63 vs 5.67 ± 0.49, 24 h: 2.27 ± 0.83 vs 3.95 ± 0.51 vs 3.84 ± 0.60, 48 h: 2.05 ± 0.90 vs 3.75 ± 0.72 vs 3.74 ± 0.56, P < 0.05) . The patients with ropivacaine local infiltration had a lower rate of remedy analgesia than those with sodium chloride injection incision infiltration or without analgesic (both P < 0.05). There was no obvious adverse effect of ropivacaine infiltration at 48 h postoperatively. Both postoperative first ambulation and peristalsis recovery time were shorter (P < 0.05) in ropivacaine group ((53 ± 9) and (80 ± 6) h) than sodium group ((91 ± 11) and (105 ± 9) h) and control group ((93 ± 11) and (109 ± 10) h) . Meanwhile, ropivacaine group had significance decreased postoperative hospital stay and medical expenses than that in local infiltration of sodium group and control group ((10.2 ± 1.3) vs (12.6 ± 1.3), (12.9 ± 1.6) days, (57 000 ± 5 000) vs (63 000 ± 6 000), (65 000 ± 6 000) yuan) (all P < 0.05). Occurrence of complications significantly differed among three groups (local infiltration of ropivacaine group 9.10% (2/22), local infiltration of sodium chloride group 25.00% (5/20) and control group 21.05% (4/19), P < 0.05). CONCLUSION: Ropivacaine infiltration may reduce postoperative pain after total laparoscopic radical gastrectomy, enable faster recovery and provide an alternative analgesia in elderly patients.
Assuntos
Amidas/uso terapêutico , Analgésicos/uso terapêutico , Dor Pós-Operatória/tratamento farmacológico , Idoso , Amidas/administração & dosagem , Analgesia , Analgésicos/administração & dosagem , Gastrectomia , Humanos , Laparoscopia , Manejo da Dor , Medição da Dor , Ropivacaina , Resultado do TratamentoRESUMO
OBJECTIVE: To study the impact of preoperative enteral immune nutrition on patients with malignant gastrointestinal tumors. METHODS: 82 patients with malignant gastrointestinal tumors were divided equally into 2 groups:enteral nutrition group (EN) and normal diet group (Control). Enteral Nutritional Emulsion (TPF-T) served as nasogastically-fed liquid diet for the patients in EN group over a period of 7 days prior to surgery. Normal diet was given to the patients in control group under the same condition as those in EN group in terms of calories and nitrogen contents. Enzyme linked immunosorbent assay (ELISA) was performed to determine the quantity of serum albumin (ALB), transferrin protein (TRF), pre-albumin (PA) and retinol binding protein (RBP). Flow cytometry (FCM) was performed to determine T cell subsets. Postoperative complications, resumption of peristalsis, length of hospital stay, and nutritional costs were also recorded. RESULTS: TRF, PA and RBP increased significantly in the patients in EN group compared with those in control group (P < 0.05). The patients in EN group had significantly higher proportions of CD3+, CD4+/CD8+ higher than those of control (P < 0.05). No serious complications (eg. death or gastrointestinal fistula) were found in the patients. The total nutritional cost for the patients in EN group was similar to that of the controls (P > 0.05). The patients in EN group had less postoperative complications, quicker resumption of peristalsis, shorter hospital stay and lower level of postoperative nutrition cost compared with those of controls (P < 0.05). CONCLUSION: Enteral nutrition support can improve the nutritional status and immunity of patients with malignant gastrointestinal tumors, which has both pre-operative and post-operative benefits for the patients.
Assuntos
Nutrição Enteral , Neoplasias Gastrointestinais/terapia , Cuidados Pré-Operatórios , Humanos , Tempo de Internação , Estado Nutricional , Complicações Pós-Operatórias , Proteínas de Ligação ao Retinol , Albumina Sérica , Subpopulações de Linfócitos T , TransferrinaRESUMO
Transformation optics (TO) provides an unprecedented technique to control electromagnetic (EM) waves by engineering the constitutive parameters of the surrounding medium through a proper spatial transformation. In general, ideal transformation optical devices require simultaneous electric and magnetic responses along all three dimensions. To ease the practical implementation, previous studies usually made use of reduced parameters or other simplified approaches, which inevitably introduce extra reflection or unwanted phase shift. Up to today, experimental realizations of full-parameter transformation optical devices in free space are still quite limited. Here, a general design strategy is proposed to solve this problem. As a specific example, a full-parameter spatial-compression TO medium with constitutive parameters taking the diagonal form diag(a, a, 1/a) for the TM wave incidence was designed and realized experimentally. Such spatial-compression TO media were then applied to the implementation of an ideal omnidirectional invisibility cloak capable of concealing a large-scale object over a wide range of illumination angles. Both the simulation and experiment confirm that the cloak allows for nearly unity transmission of EM waves in the forward direction without introducing extra scattering or phase shift. This work constitutes an important stepping stone for future practical implementation of arbitrary full-parameter omnidirectional transformation optical devices.