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This study aims to examine the clinical characteristics and outcomes of clinical myocarditis in pediatric patients in China. This is a multicenter retrospective study. Children diagnosed with clinical myocarditis from 20 hospitals in China and admitted between January 1, 2015, and December 30, 2021, were enrolled. The clinical myocarditis was diagnosed based on the "Diagnostic Recommendation for Myocarditis in Children (Version 2018)". The clinical data were collected from their medical records. A total of 1210 patients were finally enrolled in this study. Among them, 45.6% had a history of respiratory tract infection. An abnormal electrocardiogram was observed in 74.2% of patients. Echocardiography revealed that 32.3% of patients had a left ventricular ejection fraction of less than 50%. Cardiac MRI was performed in 4.9% of children with clinical myocarditis, of which 61% showed localized or diffuse hypersignal on T2-weighted images. Serum levels of cardiac troponin I (cTnI), creatine kinase-MB (CK-MB), and N-terminal B-type natriuretic peptide (NT-proBNP) were higher in patients with fulminant myocarditis than in patients with myocarditis, making them potential risk factors for fulminant myocarditis. Following active treatment, 12.1% of patients were cured, and 79.1% were discharged with improvement. CONCLUSION: Clinical myocarditis in children often presents with symptoms outside the cardiovascular system. CK-MB, cTnI, and NT-proBNP are important indicators for assessing clinical myocarditis. The electrocardiogram and echocardiogram findings in children with clinical myocarditis exhibit significant variability but lack specificity. Cardiac MRI can be a useful tool for screening clinical myocarditis. Most children with clinical myocarditis have a favorable prognosis. WHAT IS KNOWN: ⢠Pediatric myocarditis presents complex clinical manifestations and exhibits varying degrees of severity. Children with mild myocarditis generally have a favorable prognosis, while a small number of children with critically ill myocarditis experience sudden onset, hemodynamic disorders, and fatal arrhythmias. Therefore, early diagnosis and timely treatment of myocarditis are imperative. WHAT IS NEW: ⢠To the best of our knowledge, this multicenter retrospective study is the largest ever reported in China, aiming to reveal the clinical characteristics and outcomes of pediatric clinical myocarditis in China. We provided an extensive analysis of the clinical characteristics, diagnosis, treatment, prognosis, and factors impacting disease severity in pediatric clinical myocarditis in China, which provides insights into the epidemiological characteristics of pediatric clinical myocarditis.
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Miocardite , Criança , Humanos , Miocardite/diagnóstico , Miocardite/terapia , Estudos Retrospectivos , Volume Sistólico , Função Ventricular Esquerda , Creatina Quinase Forma MB , Arritmias Cardíacas , China/epidemiologiaRESUMO
Many current microRNA (miRNA) expression datasets for renal cell carcinoma (RCC) often show inconsistent analysis results, so a shift to comprehensive analysis of multiple datasets can effectively accelerate molecular screening for precision medicine and translational medicine research. MicroRNA (miR)-188-5p is a clinically noteworthy miRNA whose aberrant expression was previously observed in a variety of cancers, but its role in RCC is unclear. In this study, we undertook a comprehensive analysis of four RCC miRNA expression datasets and validated the results using The Cancer Genome Atlas (TCGA) dataset and a cohort of collected clinical samples. Fifteen miRNAs were identified as potential diagnostic markers by the analysis of four RCC miRNAs datasets. Analysis of the TCGA kidney renal clear cell carcinoma dataset showed significantly shorter survival in RCC patients with reduced miR-188-5p expression levels, and our collection of RCC clinical samples showed low miR-188-5p expression in the tumors. Overexpression of miR-188-5p in Caki-1 and 786-O cells inhibited cell growth, colony formation, invasion, and migration. In contrast, miR-188-5p inhibitors reversed these cell phenotypes. We identified a binding site for miR-188-5p in the 3'-UTR region of myristoylated alanine-rich C-kinase substrate (MARCKS) mRNA and demonstrated an interaction between these two molecules. Quantitative RT-PCR and western blot analysis revealed that miR-188-5p could regulate the AKT/mTOR signaling pathway through MARCKS. Mouse transplantation tumor assay indicated that miR-188-5p reduced the tumorigenicity of RCC in vivo. MicroRNA-188-5p could be a valuable new molecule for RCC diagnosis and prognosis.
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Carcinoma de Células Renais , Neoplasias Renais , MicroRNAs , Animais , Camundongos , Carcinoma de Células Renais/patologia , Proteínas Proto-Oncogênicas c-akt/genética , Proteínas Proto-Oncogênicas c-akt/metabolismo , Neoplasias Renais/patologia , MicroRNAs/genética , MicroRNAs/metabolismo , Serina-Treonina Quinases TOR/genética , Serina-Treonina Quinases TOR/metabolismo , Proliferação de Células/genética , Regulação Neoplásica da Expressão Gênica/genética , Linhagem Celular TumoralRESUMO
A fast and effective determination method of different species of vegetable seeds oil is vital in the plant oil industry. The near-infrared reflectance spectroscopy (NIRS) method was developed in this study to analyze the oil and moisture contents of Camelliagauchowensis Chang and C.semiserrata Chi seeds kernels. Calibration and validation models were established using principal component analysis (PCA) and partial least squares (PLS) regression methods. In the prediction models of NIRS, the levels of accuracy obtained were sufficient for C.gauchowensis Chang and C.semiserrata Chi, the correlation coefficients of which for oil were 0.98 and 0.95, respectively, and those for moisture were 0.92 and 0.89, respectively. The near infrared spectrum of crush seeds kernels was more precise compared to intact kernels. Based on the calibration models of the two Camellia species, the NIRS predictive oil contents of C.gauchowensis Chang and C.semiserrata Chi seeds kernels were 48.71 ± 8.94% and 58.37 ± 7.39%, and the NIRS predictive moisture contents were 4.39 ± 1.08% and 3.49 ± 0.71%, respectively. The NIRS technique could determine successfully the oil and moisture contents of C.gauchowensis Chang and C.semiserrata Chi seeds kernels.
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Camellia/química , Óleos de Plantas/análise , Água/análise , Análise dos Mínimos Quadrados , Análise de Componente Principal , Controle de Qualidade , Sementes/química , Espectroscopia de Luz Próxima ao InfravermelhoRESUMO
The lung is one of several moderately radiosensitive organs. Radiation-induced lung injury (RILI), including acute radiation pneumonitis and chronic radiation-induced pulmonary fibrosis, occurs most often in radiotherapy of lung cancer, esophageal cancer, and other thoracic cancers. Clinical symptoms of RILI include dry cough, shortness of breath, chest pain, fever, and even severe respiratory failure and death. The occurrence of RILI is a complex process that includes a variety of cellular and molecular interactions which ultimately leads to large fibroblast accumulation, proliferation, and differentiation, resulting in excessive extracellular matrix deposits, causing pulmonary fibrosis. The progress that has been made in recent years in the understanding of cellular and molecular mechanisms of RILI is summarized in this review.
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Pulmão/efeitos da radiação , Lesões por Radiação/tratamento farmacológico , Pneumonite por Radiação/metabolismo , Anormalidades Induzidas por Radiação/metabolismo , Células Epiteliais Alveolares/efeitos da radiação , Citocinas/efeitos da radiação , Células Endoteliais/efeitos da radiação , Fibroblastos/efeitos da radiação , Humanos , Pulmão/metabolismo , Pulmão/fisiologia , Lesão Pulmonar/metabolismo , Neoplasias Pulmonares/complicações , Macrófagos/efeitos da radiação , Fibrose Pulmonar/etiologiaAssuntos
Proteínas Mutadas de Ataxia Telangiectasia/metabolismo , Resistencia a Medicamentos Antineoplásicos/genética , Neoplasias Pulmonares/genética , RNA Longo não Codificante/genética , Reparo de DNA por Recombinação/genética , Animais , Xenoenxertos , Humanos , Neoplasias Pulmonares/metabolismo , Camundongos , Estabilidade Proteica , RNA Longo não Codificante/metabolismoRESUMO
Recent studies showed that hydrogen can be used as an effective radioprotective agent through scavenging free radicals. This study was undertaken to evaluate the radioprotective effects of hydrogen on immune system in mice. H(2) was dissolved in physiological saline using an apparatus produced by our department. Spleen index and histological analysis were used to evaluate the splenic structural damage. Spleen superoxide dismutase, GSH, MDA were measured to appraise the antioxidant capacity and a DCF assay for the measurement of radical oxygen species. Cell apoptosis was evaluated by an Annexin V-FITC and propidium iodide staining method as well as the apoptotic proteins such as Bcl-2, Bax, caspase-3 and c-caspase-3. CD4+ and CD8+ T cells subtypes were detected by flow cytometry with FITC-labelled antimouse CD4 and PE antimouse CD8 staining. Real-time PCR was utilized to determine the CD4+ T cell subtypes and related cytokines. Our study demonstrated that pre-treatment with H(2) could increase the spleen index and attenuate the radiation damage on splenic structure. Radical oxygen species level was also reduced by H(2) treatment. H(2) also inhibited radiation-induced apoptosis in splenocytes and down-regulated pro-apoptotic proteins in living mice. Radiation-induced imbalance of T cells was attenuated by H(2). Finally, we found that H(2) could regulate the polarization of CD4+ T cells and the level of related cytokines. This study suggests H(2) as an effective radioprotective agent on immune system by scavenging reactive oxygen species.
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Hidrogênio/farmacologia , Substâncias Protetoras/uso terapêutico , Lesões por Radiação/tratamento farmacológico , Lesões por Radiação/imunologia , Cloreto de Sódio/uso terapêutico , Animais , Antioxidantes/farmacologia , Apoptose/efeitos dos fármacos , Citocinas/genética , Citocinas/metabolismo , Raios gama , Masculino , Camundongos Endogâmicos C57BL , Estresse Oxidativo/efeitos dos fármacos , Estresse Oxidativo/efeitos da radiação , Substâncias Protetoras/farmacologia , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Lesões por Radiação/fisiopatologia , Reação em Cadeia da Polimerase em Tempo Real , Cloreto de Sódio/farmacologia , Baço/efeitos dos fármacos , Baço/patologia , Baço/efeitos da radiação , Linfócitos T/efeitos dos fármacos , Linfócitos T/efeitos da radiaçãoRESUMO
Radiation-induced lung injury (RILI) is a potentially fatal and dose-limiting complication of thoracic radiotherapy. This study was to investigate the protective effects of grape seed pro-anthocyanidins (GSPs), an efficient antioxidant and anti-carcinogenic agent, on RILI. In our study, it was demonstrated that acute and late RILI was ameliorated after GSPs treatment possibly through suppressing TGF-ß1/Smad3/Snail signalling pathway and modulating the levels of cytokines (interferon-γ, IL-4 and IL-13) derived from Th1/Th2 cells. In addition, a sustained high level of PGE2 was also maintained by GSPs treatment to limited fibroblast functions. As shown by electron spin resonance spectrometry, GSPs could scavenge hydroxyl radical (â¢OH) in a dose-dependent manner, which might account for the mitigation of lipid peroxidation and consequent apoptosis of lung cells. In vitro, GSPs radiosensitized lung cancer cell A549 while mitigating radiation injury on normal alveolar epithelial cell RLE-6TN. In conclusion, the results showed that GSPs protects mice from RILI through scavenging free radicals and modulating RILI-associated cytokines, suggesting GSPs as a novel protective agent in RILI.
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Raios gama/efeitos adversos , Lesão Pulmonar/etiologia , Lesão Pulmonar/prevenção & controle , Extratos Vegetais/farmacologia , Lesões Experimentais por Radiação/prevenção & controle , Protetores contra Radiação/farmacologia , Vitis/química , Animais , Western Blotting , Citocinas/genética , Citocinas/metabolismo , Espectroscopia de Ressonância de Spin Eletrônica , Feminino , Humanos , Técnicas Imunoenzimáticas , Lesão Pulmonar/metabolismo , Camundongos , Camundongos Endogâmicos C57BL , RNA Mensageiro/genética , Lesões Experimentais por Radiação/etiologia , Lesões Experimentais por Radiação/metabolismo , Reação em Cadeia da Polimerase em Tempo Real , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Sementes/químicaRESUMO
Radiotherapy is an effective treatment method for lung cancer, particularly when the disease is at an advanced stage. However, previous researchers have observed that the majority of patients with conventional radiation therapy develop distant metastases and succumb to the disease. Thus, identifying and understanding novel pathways for the development of new therapeutic targets is a major goal in research on pulmonary neoplasms. Recent studies suggest that epithelial-mesenchymal transition (EMT) is the most important contributor to cancer metastasis. Induction of this complex process requires endogenously produced microRNAs; specifically, downregulation of the miRNA-200c causes an induction of EMT. We recently identified the tank-binding kinase-1 (TBK1) as a downstream effector of the miR-200c-driven pathway, but the biological function of TBK1 in EMT remains unknown. In this study, we tested whether TBK1 has a role in radiation-induced EMT and identified associated potential mechanisms. Human alveolar type II epithelial carcinoma A549 cells were irradiated with (60)Co γ-rays. Western blotting revealed a time- and dose-dependent decrease in E-cadherin with a concomitant increase in vimentin after radiation, suggesting that the epithelial cells acquired a mesenchymal-like morphology. TBK1 siRNA significantly inhibited radiation-induced suppression of the epithelial marker E-cadherin and upregulation of the mesenchymal marker vimentin. The invasion and migratory potential of lung cancer cells upon radiation treatment was also reduced by TBK1 knockdown. Furthermore, radiation-induced EMT attenuated by TBK1 depletion was partially dependent on transcriptional factor ZEB1 expression. Finally, we found glycogen synthase kinase-3ß (GSK-3ß) is involved in regulation of radiation-induced EMT by TBK1. Thus, our findings reveal that TBK1 signaling regulates radiation-induced EMT by controlling GSK-3ß phosphorylation and ZEB1 expression. TBK1 may therefore constitute a useful target for treatment of radiotherapy-induced metastasis diseases.
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Transição Epitelial-Mesenquimal , Quinase 3 da Glicogênio Sintase/metabolismo , Proteínas de Homeodomínio/metabolismo , Proteínas Serina-Treonina Quinases/metabolismo , Radioterapia/efeitos adversos , Fatores de Transcrição/metabolismo , Linhagem Celular Tumoral , Raios gama/efeitos adversos , Glicogênio Sintase Quinase 3 beta , Humanos , NF-kappa B/metabolismo , Metástase Neoplásica , Neoplasias/etiologia , Proteínas Serina-Treonina Quinases/antagonistas & inibidores , Proteínas Smad/metabolismo , Fator de Crescimento Transformador beta/metabolismo , Homeobox 1 de Ligação a E-box em Dedo de ZincoRESUMO
BACKGROUND/AIMS: The ionizing radiation (IR) has been applied in clinical treatment for many years and the radiosensitivity is crucial to the treatment. Radiosensitivity of cells is subjected to many environmental factors, such as hypoxia and temperature. Hyperosmolality as a common environmental factor has been demonstrated to be associated with survival and apoptosis of cells in many studies. Thus we investigated the influence of hyperosmolality on cells radiosensitivity. METHODS: We examined the viability and surviving fraction of L-O2 cells of irradiated L-O2 cells, and detected the effect on AHH-1 cells by flow cytometry, in order to investigate the effect of short-term hyperosmolality pretreatment on cells radiosensitivity. Comet assay was used to assess the DNA strand breaks. Then the detection of Akt1 by western blot and the process of regulatory volume increase by CYSY-TT were involved in the mechanism. RESULT: We demonstrated that a short-term hyperosmolality pretreatment on cells could reduce their radiosensitivity. Further research indicated that the short-term hypertonic condition could induce regulatory volume increase (RVI), which activated Akt1 and degenerated the IκB-α. This process was associated with reduced cells radiosensitivity. Finally, we used the flufenamic acid (FFA), a blocker to cation channels (HICCs) to inhabit RVI and consequently inhabit the protective effect of hyperosmolality on irradiated cells. CONCLUSION: a short-term hyperosmolality pretreatment could reduce the cells radiosensitivity by RVI and following activation of Akt1.
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Concentração Osmolar , Proteínas Proto-Oncogênicas c-akt/metabolismo , Tolerância a Radiação/fisiologia , Linhagem Celular/efeitos da radiação , Tamanho Celular/efeitos da radiação , Sobrevivência Celular/efeitos da radiação , Ensaio Cometa , Quebras de DNA de Cadeia Dupla/efeitos da radiação , Humanos , Radiação IonizanteRESUMO
BACKGROUND: Effect of ionizing radiation on cutaneous dendritic cells (cDC) is critical to its influence on immune status of the skin, which plays an important role in the progression and recovery of radiation skin sickness. This study was to study the influence of whole body irradiation (WBI) on the cDC. METHODS: Density of epidermal and dermal DC was determined with a fluorescent microscopy and the DC numbers in lymph node were measured by flow cytometry. A FITC induced migration assay was also used to study the migration of DC. The expressions of cytokines and chemokines were evaluated by Realtime PCR, and the protein level of was measured by Western blot. RESULTS: WBI caused depletion of cDC in epidermal as well as dermal and augmented FITC-induced migration of DC to the draining lymph node (LN). The number of DC migrated from ear explants to the CCL19-containing medium also increased after exposure to WBI. It was also found that WBI increased mRNA level of CCL19/CCL21 as well as CCR7 in LN and skin tissue. The expressions of TNFα, IL-1α, IL-1ß, and IL-6 in skin tissues were also greatly induced by WBI in a dose dependent manner. Finally, we found that WBI induced translocation of nuclear factor κB (NF-κB) and that the radiation-induced migration of DC was blocked by NF-κB inhibitor or TLR4 knockout. CONCLUSION: WBI caused cDC depletion through induction of DC migration to the draining LN, which might result from the activation of NF-κB and the induction of inflammatory microenvironment within the skin.
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Células Dendríticas/efeitos da radiação , NF-kappa B/metabolismo , Irradiação Corporal Total , Animais , Movimento Celular/efeitos da radiação , Quimiocinas/genética , Quimiocinas/metabolismo , Citocinas/genética , Citocinas/metabolismo , Células Dendríticas/efeitos dos fármacos , Células Dendríticas/metabolismo , Feminino , Linfonodos/citologia , Linfonodos/efeitos da radiação , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , NF-kappa B/antagonistas & inibidores , Prolina/análogos & derivados , Prolina/farmacologia , Pele/efeitos dos fármacos , Pele/imunologia , Tiocarbamatos/farmacologia , Receptor 4 Toll-Like/deficiência , Receptor 4 Toll-Like/genética , Receptor 4 Toll-Like/metabolismo , Regulação para CimaRESUMO
BACKGROUND: Aplasitc anemia (AA) is a bone marrow failure syndrome characterized by an immune-mediated destruction of hematopoietic stem cells. Though clinical symptoms could be ameliorated by bone marrow transplantation and/or immunosuppressive therapy, frequent recurrence and especially evolution of clonal hematologic diseases remains problematic clinically. Cytokines such as interferon-γ (INF-γ), tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6) secreted by autologous T cells are closely related with the development of AA. Hydrogen-rich solution was reported to inhibit the levels of cytokines including INF-γ, TNF-α and IL-6 in vivo in recent studies. This study was to investigate the potential therapeutic effects of hydrogen-rich solution on AA in vivo. METHODS: AA model was determined in vivo by mice and body weights of the mice were used as the basic physiological index. Peripheral blood cells were calculated to evaluate the hematologic recovery degree. Bone marrow nucleated cells (BMNCs), tissue histology, as well as CFU-S and CFU-GM forming units were used to evaluate the recovery of bone marrow microenvironment. The ratio of CD4(+) and CD8(+) cells were examined along with cytokine levels in serum to determine the efficacy of H2-rich solution on the affected immunological functions. RESULTS: Body weight and number of peripheral blood cells were significantly improved for mice in the H2-rich solution treated groups as compared with those with AA. The number of BMNCs and CFUs increased markedly and the bone marrow microenvironment was also improved significantly. The experimental group restrained the cell apoptosis, relieved hyperemia and accelerated tissue repair. The number of CD4(+) and CD8(+) cells as well as the ratio of CD4/CD8 increased to normal gradually, while the levels of TNF-α, IFN-γ, and IL-6 in serum decreased after H2-rich solution treatment. CONCLUSION: Our study firstly showed that hydrogen-rich solution accelerated the recovery of either hematological or immunological recovery on aplastic anemia mice. This finding suggests hydrogen-rich solution as a potential clinical therapeutic agent for AA.
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Anemia Aplástica/terapia , Hidrogênio/uso terapêutico , Solução Salina Hipertônica/química , Animais , Células Sanguíneas/citologia , Peso Corporal/efeitos dos fármacos , Medula Óssea/patologia , Células da Medula Óssea/citologia , Linfócitos T CD4-Positivos/citologia , Linfócitos T CD4-Positivos/imunologia , Linfócitos T CD8-Positivos/citologia , Linfócitos T CD8-Positivos/imunologia , Modelos Animais de Doenças , Hidrogênio/química , Hidrogênio/farmacologia , Interferon gama/sangue , Interleucina-6/sangue , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Fator de Necrose Tumoral alfa/sangueRESUMO
Dysregulation of adipogenesis is related to diabetic peripheral neuropathy (DPN) pathogenesis, which may be mediated by immune infiltration. Nevertheless, the expression patterns of multiple adipogenesis-related genes and the differences of immune infiltration in different lipid metabolism levels remain unknown. GSE95849, a gene expression matrix containing DPN patients and healthy participants, was downloaded from Gene Expression Omnibus (GEO) database. Differentially expressed adipogenesis-related genes (DEARGs) were screened by overlapping the adipogenesis-related genes with differentially expressed genes (DEGs). DPN patients from GSE24290 and GSE148059 were divided into two adipogenesis subgroups according to the expression of DEARGs. The single-sample gene set enrichment analysis (ssGSEA) was used to estimate the abundance of the immune cells between two subgroups. The analysis of immune infiltration suggested that a variety of immune cells and immune processes were elevated in the high expression group of DEARGs. The differentially expressed genes of the two subgroups were mainly enriched in biological processes and signaling pathways related to lipid metabolism. PPARG, FABP4, LIPE, FASN, SCD, DGAT2, PNPLA2, ADIPOQ, LEP, and CEBPA were identified as the hub genes of the two subgroups, whose related transcription factors (TFs) and miRNAs were predicted. An immunohistochemical assay was used to verify the expression of hub genes in DPN nerve tissues. Our comprehensive analysis of adipogenesis subgroups in DPN illustrated that different expression patterns of DEARGs may lead to different immune and inflammatory states. The identification of DEARGs may help to further distinguish the different characteristics of DPN patients and lay the foundation for targeted treatment. Our findings may bring a novel perspective to the diagnosis and treatment of DPN patients.
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Diabetes Mellitus , Neuropatias Diabéticas , MicroRNAs , Humanos , Adipogenia/genética , Bases de Dados FactuaisRESUMO
The testes and intestines are highly sensitive to ionizing radiation. Low-dose radiation can cause infertility and enteritis. However, there is a lack of safe and efficient radioprotective agents. This study aims to investigate the radioprotective effects of grape seed proanthocyanidins (GSPs) on testicular and intestinal damage induced by ionizing radiation. In vitro, GSPs reduced the apoptosis and proliferation inhibition of mouse testicular stromal cells TM3 and human small intestinal crypt epithelial cells HIEC induced by ionizing radiation, and alleviated DNA double-strand breaks. In vivo, GSPs ameliorated the pathological damage of the testes and intestines induced by ionizing radiation, and protected the endocrine function of the testes and the barrier function of the intestines. In addition, we preliminarily proved that the radioprotective effect of GSPs is related to its antioxidant effect and inhibition of MAPK signaling pathways. Our results indicate that GSPs are expected to be a safe and effective radioprotective drug.
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Trophoblast stem cells (TSCs) are derived from blastocysts and the extra-embryonic ectoderm (ExE) of post-implantation embryos and play a significant role in fetal development, but the roles that TSCs play in the earlier status of fetal diseases need further exploration. Super enhancers (SEs) are dense clusters of stitched enhancers that control cell identity determination and disease development and may participate in TSC differentiation. We identified key cell identity genes regulated by TSC-SEs via integrated analysis of H3K27ac and H3K4me1 chromatin immunoprecipitation sequencing (ChIP-seq), RNA-sequencing (RNA-seq) and ATAC-sequencing (ATAC-seq) data. The identified key TSC identity genes regulated by SEs, such as epidermal growth factor receptor (EGFR), integrin ß5 (ITGB5) and Paxillin (Pxn), were significantly upregulated during TSC differentiation, and the transcription network mediated by TSC-SEs enriched in terms like focal adhesion and actin cytoskeleton regulation related to differentiation of TSCs. Additionally, the increased chromatin accessibility of the key cell identity genes verified by ATAC-seq further demonstrated the regulatory effect of TSC-SEs on TSC lineage commitment. Our results illustrated the significant roles of the TSC-SE-regulated network in TSC differentiation, and identified key TSC identity genes EGFR, ITGB5 and Pxn, providing novel insight into TSC differentiation and lays the foundation for future studies on embryo implantation and related diseases.
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Radiation-induced lung injury (RILI) is a common serious complication and dose-limiting factor caused by radiotherapy for lung cancer. This study was to investigate radioprotective effects of grape seed proanthocyanidins (GSP) on normal lung as well as radiosensitizing effects on lung cancer. In vitro, we demonstrated radioprotective effects of GSP on normal alveolar epithelial cells (MLE-12 and BEAS/2B) and radiosensitizing effects on lung cancer cells (LLC and A549). In vivo, we confirmed these two-way effects in tumor-bearing mice. The results showed that GSP inhibited tumor growth, and played a synergistic killing effect with radiotherapy on lung cancer. Meanwhile, GSP reduced radiation damage to normal lung tissues. The two-way effects related to the differential regulation of the MAPK signaling pathway by GSP on normal lung and lung cancer. Moreover, GSP regulated secretion of cytokines IL-6 and IFN-γ and expression of p53 and Ki67 on normal lung and lung cancer. Our findings suggest that GSP is expected to be an ideal radioprotective drug for lung cancer patients who are treated with radiotherapy.
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Objective: Radiotherapy is an indispensable approach for lung cancer, especially for non-small cell lung cancer (NSCLC) with high incidence and mortality. However, cellular resistance to ionizing radiation often results in failure in treatment. In this study, we aimed to investigate the role of Sirt3 in radiotherapy on NSCLC. Materials and Methods: Resected samples from 80 pairs of lung cancer was used to prepare tissue array and Sirt3 was stained with immunochemical method. Cell survival as well as apoptosis assay were used to determine the cellular radiosensitivity. Moreover, DNA damage was evaluated by using γ-H2AX foci. Finally, an in situ lung cancer model to test the radiosensitivity in vivo. Results: Sirtuin 3 (Sirt3) was found upregulated in NSCLC cell lines, as well as lung cancer tissues compared with normal tissues. Knockdown of Sirt3 significantly increased radiation-induced cell apoptosis, and increased cell survival efficacy. In contrast, Sirt3 overexpression promoted radioresistance in lung cancer cells. Sirt3 knockdown also aggravated the G2/M cell cycle arrest caused by irradiation. Furthermore, Sirt3 was found to be critical for the activation of ATM-Chk2 pathway upon irradiation. Finally, our in vivo model showed that targeting Sirt3 significantly sensitized lung cancer to radiotherapy. Conclusion: In conclusion, our findings identified a significant role of Sirt3 in radioresistanct of NSCLC, which provides novel mechanism as well as target for radiotherapy.
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Desmoid-type fibromatosis is a rare type of soft-tissue tumor originating from connective tissue of the fascia or aponeurosis, which exhibits aggressive growth, high likelihood of relapse and less frequent distant metastasis. The present study aimed to predict the recurrence rate and time by retrospectively analyzing the clinical data (sex, age and recurrence time), imaging findings [tumor location, maximum diameter, border, computed tomography (CT) enhancement ratio, magnetic resonance enhancement ratio and T2 signal ratio] and pathological features (Ki-67 and microscopic margin) in a total of 102 cases of pathologically confirmed desmoid-type fibromatosis. The risk ratio of each factor was calculated using the Cox proportional hazards regression model and the cumulative recurrence-free survival rate was determined using the Kaplan-Meier method and the log-rank test. The cohort comprised of 73 females and 29 males, with mean age of 32.86±12.64 years (range, 6-78 years). The 1-year and 2-year recurrence rate was 31 and 54%, respectively. The median age at recurrence was 29 years. Univariate analysis indicated that sex, maximum tumor diameter, CT enhancement ratio and Ki-67 had a significant effect on the recurrence time. Furthermore, multivariate analysis revealed that sex, maximum tumor diameter, Ki-67 and T2 signal ratio were independently associated with the time of recurrence, and the risk ratios were 0.424, 1.100, 1.084 and 1.268, respectively. Therefore, in male patients with a larger maximum tumor diameter, positivity for Ki-67 and a higher T2 signal ratio, desmoid-type fibromatosis was more likely to recur after surgery.
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RATIONALE: Primary pulmonary angiosarcoma is a rare disease. Here, we report the case of primary pulmonary angiosarcoma diagnosed computed tomographic pulmonary angiography (CTPA) and discuss its specific imaging characteristics. PATIENT CONCERNS: A 46-year-old man was admitted for cough and shortness of breath. Thoracic CTPA images demonstrated a high-attenuation lesion surrounding by a halo sign in upper lobe of right lung, and the dilated vessel was also seen in lower lobe of right lung. The sign of "hillside sign" was observed on CTPA. DIAGNOSES: It was diagnosed with primary pulmonary angiosarcoma. INTERVENTIONS: Right thoracotomy and right upper lobe lobectomy were performed. OUTCOMES: Five years later, the patient dead of complete occlusion of the pulmonary artery owing to tumor recurrence. LESSONS: Although primary pulmonary angiosarcoma is a rare disease with atypical early clinical symptoms, and it is often misdiagnosed as pulmonary embolism and pulmonary infection. Therefore, it is important to recognize the CTPA imaging characteristics of primary pulmonary angiosarcoma and Surgical resection should be performed to prolong the patients' lifetime.
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Angiografia por Tomografia Computadorizada , Hemangiossarcoma/diagnóstico por imagem , Neoplasias Pulmonares/diagnóstico por imagem , Tosse/etiologia , Diagnóstico Diferencial , Dispneia/etiologia , Evolução Fatal , Hemangiossarcoma/cirurgia , Humanos , Neoplasias Pulmonares/cirurgia , Masculino , Pessoa de Meia-Idade , Recidiva Local de NeoplasiaRESUMO
We have demonstrated that grape seed proanthocyanidins (GSPs) could effectively scavenge hydroxyl radical (â¢OH) in a dose-dependent manner. Since most of the ionizing radiation- (IR-) induced injuries were caused by â¢OH, this study was to investigate whether GSPs would mitigate IR-induced injuries in vitro and in vivo. We demonstrated that GSPs could significantly reduce IR-induced DNA strand breaks (DSBs) and apoptosis of human lymphocyte AHH-1 cells. This study also showed that GSPs could protect white blood cells (WBC) from IR-induced injuries, speed up the weight of mice back, and decrease plasma malondialdehyde (MDA), thus improving the survival rates of mice after ionizing radiation. It is suggested that GSPs have a potential as an effective and safe radioprotective agent.
Assuntos
Extrato de Sementes de Uva/farmacologia , Proantocianidinas/farmacologia , Protetores contra Radiação/farmacologia , Animais , Apoptose/efeitos dos fármacos , Peso Corporal/efeitos dos fármacos , Linhagem Celular , Sobrevivência Celular/efeitos dos fármacos , Ensaio Cometa , Humanos , Contagem de Leucócitos , Masculino , Malondialdeído/sangue , Camundongos Endogâmicos BALB C , Radiação Ionizante , Taxa de SobrevidaRESUMO
BACKGROUND: the bone marrow and the intestine are the major sites of ionizing radiation (IR)-induced injury. Our previous study demonstrated that CpG-oligodeoxynucleotide (ODN) treatment mitigated IR-induced bone marrow injury, but its effect on the intestine is not known. In this study, we sought to determine if CpG-ODN have protective effect on IR-induced intestine injury, and if so, to determine the mechanism of its effect. METHODS AND FINDINGS: Mice were treated with CpG-ODN after IR. The body weight and survival were daily monitored for 30 days consecutively after exposure. The number of surviving intestinal crypt was assessed by the microcolony survival assay. The number and the distribution of proliferating cell in crypt were evaluated by TUNEL assay and BrdU assay. The expression of Bcl-2, Bax and caspase-3 in crypt were analyzed by Immunohistochemistry assay. The findings showed that the treatment for irradiated mice with CpG-ODN diminished body weight loss, improved 30 days survival, enhanced intestinal crypts survival and maintained proliferating cell population and regeneration in crypt. The reason might involve that CpG-ODN up-regulated the expression of Bcl-2 protein and down-regulated the expression of Bax protein and caspase-3 protein. CONCLUSION: CpG-ODN was effective in protection of IR-induced intestine injury by enhancing intestinal crypts survival and maintaining proliferating cell population and regeneration in crypt. The mechanism might be that CpG-ODN inhibits proliferating cell apoptosis through regulating the expression of apoptosis-related protein, such as Bax, Bcl-2 and caspase-3.