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1.
Cell ; 152(5): 1037-50, 2013 Feb 28.
Artigo em Inglês | MEDLINE | ID: mdl-23452852

RESUMO

Although somatic cell reprogramming to generate inducible pluripotent stem cells (iPSCs) is associated with profound epigenetic changes, the roles and mechanisms of epigenetic factors in this process remain poorly understood. Here, we identify Jmjd3 as a potent negative regulator of reprogramming. Jmjd3-deficient MEFs produced significantly more iPSC colonies than did wild-type cells, whereas ectopic expression of Jmjd3 markedly inhibited reprogramming. We show that the inhibitory effects of Jmjd3 are produced through both histone demethylase-dependent and -independent pathways. The latter pathway involves Jmjd3 targeting of PHF20 for ubiquitination and degradation via recruitment of an E3 ligase, Trim26. Importantly, PHF20-deficient MEFs could not be converted to fully reprogrammed iPSCs, even with knockdown of Jmjd3, Ink4a, or p21, indicating that PHF20 is required for reprogramming. Our findings demonstrate, to the best of our knowledge, a previously unrecognized role of Jmjd3 in cellular reprogramming and provide molecular insight into the mechanisms by which the Jmjd3-PHF20 axis controls this process.


Assuntos
Reprogramação Celular , Proteínas de Homeodomínio/metabolismo , Células-Tronco Pluripotentes Induzidas/metabolismo , Histona Desmetilases com o Domínio Jumonji/metabolismo , Animais , Inibidor p16 de Quinase Dependente de Ciclina/genética , Proteínas de Ligação a DNA , Embrião de Mamíferos/citologia , Fibroblastos/metabolismo , Cinética , Camundongos , Complexo de Endopeptidases do Proteassoma/metabolismo , Proteólise , Fatores de Transcrição , Proteínas com Motivo Tripartido , Ubiquitina-Proteína Ligases/metabolismo , Ubiquitinação , Regulação para Cima
2.
J Transl Med ; 21(1): 250, 2023 04 10.
Artigo em Inglês | MEDLINE | ID: mdl-37038181

RESUMO

BACKGROUND: Lung adenocarcinoma (LUAD) is the most prevalent subtype of lung cancer with high morbidity and mortality rates. Due to the heterogeneity of LUAD, its characteristics remain poorly understood. Exploring the clinical and molecular characteristics of LUAD is challenging but vital for early diagnosis. METHODS: This observational and validation study enrolled 80 patients and 13 healthy controls. Nuclear and mtDNA-captured sequencings were performed. RESULTS: This study identified a spectrum of nuclear and mitochondrial genome mutations in early-stage lung adenocarcinoma and explored their association with diagnosis. The correlation coefficient for somatic mutations in cfDNA and patient-matched tumor tissues was high in nuclear and mitochondrial genomes. The mutation number of highly mutated genes was evaluated, and the Least Absolute Shrinkage and Selection Operator (LASSO) established a diagnostic model. Receiver operating characteristic (ROC) curve analysis explored the diagnostic ability of the two panels. All models were verified in the testing cohort, and the mtDNA panel demonstrated excellent performance. This study identified somatic mutations in the nuclear and mitochondrial genomes, and detecting mutations in cfDNA displayed good diagnostic performance for early-stage LUAD. Moreover, detecting somatic mutations in the mitochondria may be a better tool for diagnosing early-stage LUAD. CONCLUSIONS: This study identified specific and sensitive diagnostic biomarkers for early-stage LUAD by focusing on nuclear and mitochondrial genome mutations. This also further developed an early-stage LUAD-specific mutation gene panel for clinical utility. This study established a foundation for further investigation of LUAD molecular pathogenesis.


Assuntos
Adenocarcinoma de Pulmão , Ácidos Nucleicos Livres , Genoma Mitocondrial , Neoplasias Pulmonares , Humanos , Genoma Mitocondrial/genética , Detecção Precoce de Câncer , Adenocarcinoma de Pulmão/diagnóstico , Adenocarcinoma de Pulmão/genética , Neoplasias Pulmonares/diagnóstico , Neoplasias Pulmonares/genética , DNA Mitocondrial/genética
3.
Sensors (Basel) ; 24(1)2023 Dec 25.
Artigo em Inglês | MEDLINE | ID: mdl-38202979

RESUMO

In order to solve low-quality problems such as data anomalies and missing data in the condition monitoring data of hydropower units, this paper proposes a monitoring data quality enhancement method based on HDBSCAN-WSGAIN-GP, which improves the quality and usability of the condition monitoring data of hydropower units by combining the advantages of density clustering and a generative adversarial network. First, the monitoring data are grouped according to the density level by the HDBSCAN clustering method in combination with the working conditions, and the anomalies in this dataset are detected, recognized adaptively and cleaned. Further combining the superiority of the WSGAIN-GP model in data filling, the missing values in the cleaned data are automatically generated by the unsupervised learning of the features and the distribution of real monitoring data. The validation analysis is carried out by the online monitoring dataset of the actual operating units, and the comparison experiments show that the clustering contour coefficient (SCI) of the HDBSCAN-based anomaly detection model reaches 0.4935, which is higher than that of the other comparative models, indicating that the proposed model has superiority in distinguishing between the valid samples and anomalous samples. The probability density distribution of the data filling model based on WSGAIN-GP is similar to that of the measured data, and the KL dispersion, JS dispersion and Hellinger's distance of the distribution between the filled data and the original data are close to 0. Compared with the filling methods such as SGAIN, GAIN, KNN, etc., the effect of data filling with different missing rates is verified, and the RMSE error of data filling with WSGAIN-GP is lower than that of other comparative models. The WSGAIN-GP method has the lowest RMSE error under different missing rates, which proves that the proposed filling model has good accuracy and generalization, and the research results in this paper provide a high-quality data basis for the subsequent trend prediction and state warning.

4.
J Transl Med ; 20(1): 387, 2022 09 04.
Artigo em Inglês | MEDLINE | ID: mdl-36059002

RESUMO

BACKGROUND: The association between oral dysbiosis and chronic kidney disease (CKD) has gained increasing attention in recent years. Diabetes and hypertension are the most common conditions in CKD. However, a case-control study with matched confounding variables on the salivary microbiome in CKD and the influence of diabetes and hypertension on the microbiome has never been reported. METHODS: In our study, we compared the salivary microbiome profile between patients with CKD and healthy controls (HC) using 16S ribosomal DNA sequencing and examine its association with diabetes, hypertension, and immunity. RESULTS: We observed that the bacterial community was skewed in the saliva of CKD, with increased Lautropia and Pseudomonas, and decreased Actinomyces, Prevotella, Prevotella 7, and Trichococcus. No difference in the bacterial community between the CKD patients complicated with and without diabetes, and between those with and without hypertension. Prevotella 7 declined in CKD patients with/without hypertension with respect to HC, while Pseudomonas increased in CKD patients with/without hypertension. Pseudomonas was negatively associated with immunoglobin G in CKD patients. Both CKD patients with positive and negative antistreptolysin O had declined Prevotella 7 and Trichococcus compared to HC, whereas increased Pseudomonas. CONCLUSIONS: Our study identifies a distinct bacterial saliva microbiome in CKD patients characterized by alteration in composition. We unravel here that the co-occurrence diseases of diabetes and hypertension are not associated with specific bacterial alterations, suggesting that bacterial dysbiosis in saliva plays a role in renal damage regardless of the occurrence of diabetes and hypertension.


Assuntos
Diabetes Mellitus , Hipertensão , Microbiota , Insuficiência Renal Crônica , Bactérias , Estudos de Casos e Controles , Disbiose/complicações , Disbiose/microbiologia , Humanos , Hipertensão/complicações , RNA Ribossômico 16S/genética , Insuficiência Renal Crônica/complicações , Saliva
5.
J Cell Mol Med ; 25(14): 6948-6962, 2021 07.
Artigo em Inglês | MEDLINE | ID: mdl-34117724

RESUMO

Adriamycin (ADM) is currently one of the most effective chemotherapeutic agents in breast cancer treatment. However, growing resistance to ADM could lead to treatment failure and poor outcome. PLAC8 was reported as a novel highly conserved protein and functioned as an oncogene or tumour suppressor in various tumours. Here, we found higher PLAC8 expression was correlated with worse outcome and aggressive phenotype in breast cancer. Breast cancer patients with higher PLAC8 expression showed potential ADM resistance. In vitro experiments further confirmed that PLAC8 inhibited by siRNA or enforced overexpression by infecting pcDNA3.1(C)-PLAC8 plasmid correspondingly decreased or increased ADM resistance. Subsequently, we demonstrated that ectopic PLAC8 expression in MCF-7/ADMR cell blocked the accumulation of the autophagy-associated protein LC3 and resulted in cellular accumulation of p62. Rapamycin-triggered autophagy significantly increased cell response to ADM, while the autophagy inhibitor 3-MA enhanced ADM resistance. 3-MA and PLAC8 could synergistically cause ADM resistance via blocking the autophagy process. Additionally, the down-regulation of p62 by siRNA attenuated the activation of autophagy and PLAC8 expression in breast cancer cells. Thus, our findings suggest that PLAC8, through the participation of p62, inhibits autophagy and consequently results in ADM resistance in breast cancer. PLAC8/p62 pathway may act as novel therapeutic targets in breast cancer treatment and has potential clinical application in overcoming ADM resistance.


Assuntos
Autofagia , Resistencia a Medicamentos Antineoplásicos , Neoplasias Mamárias Experimentais/metabolismo , Proteínas/metabolismo , Animais , Antibióticos Antineoplásicos/uso terapêutico , Antibióticos Antineoplásicos/toxicidade , Doxorrubicina/uso terapêutico , Doxorrubicina/toxicidade , Feminino , Humanos , Células MCF-7 , Neoplasias Mamárias Experimentais/tratamento farmacológico , Neoplasias Mamárias Experimentais/genética , Camundongos , Camundongos Nus , Proteínas/genética
6.
Zhonghua Nan Ke Xue ; 27(5): 421-425, 2021 May.
Artigo em Zh | MEDLINE | ID: mdl-34914317

RESUMO

OBJECTIVE: To investigate the detection rate and complications of magnetic resonance imaging / transrectal ultrasonography (MRI/TRUS) cognitive fusion combined with 12-core systematic transperineal prostate biopsy (TPPB) in the diagnosis of clinically significant PCa (CS-PCa). METHODS: This retrospective study included 208 patients undergoing first-time MRI/TRUS cognitive fusion combined with 12-core systematic TPPB from June 2015 to May 2019. The patients, aged 54-85 (67.6 ± 7.8) years, all received digital rectal examination, PSA detection, TRUS and prostate multiparametric MRI (mpMRI) before biopsy. We analyzed the mpMRI images, identified and marked the suspected signal areas, repeated TRUS for further observation of the prostate, conducted cognitive fusion based on the mpMRI images and determined the target before 12-core systematic TPPB and subjecting the samples obtained to pathological examination. RESULTS: Of the 208 patients, 112 were diagnosed with CS-PCa (no case with tPSA < 4 µg/L, 21 cases with 4 µg/L ≤ tPSA < 10 µg/L, 47 cases with 10 µg/L ≤ tPSA < 20 µg/L, 40 cases with 20 µg/L ≤ tPSA < 100 µg/L, and 4 cases with tPSA ≥ 100 µg/L), 85 with BPH, 8 with chronic prostatitis, 2 with atypical prostatic hyperplasia, and 1 with prostatic intraepithelial neoplasia. Systemic inflammatory response syndrome occurred in 3 and gross hematuria and/or bloody stool in 12 cases after biopsy, which were all cured by anti-infection and hemostasis treatment. CONCLUSIONS: MRI/TRUS cognitive fusion combined with 12-core systematic transperineal prostate biopsy can improve the detection rate of the initial diagnosis of clinically significant PCa with a low incidence of controllable complications.


Assuntos
Próstata , Neoplasias da Próstata , Biópsia , Cognição , Exame Retal Digital , Humanos , Imageamento por Ressonância Magnética , Masculino , Próstata/diagnóstico por imagem , Neoplasias da Próstata/diagnóstico por imagem , Estudos Retrospectivos , Ultrassonografia
7.
AJR Am J Roentgenol ; 214(2): 446-454, 2020 02.
Artigo em Inglês | MEDLINE | ID: mdl-31799866

RESUMO

OBJECTIVE. The purpose of this study is to evaluate the diagnostic performance of whole-body (WB) DWI with background body suppression (DWIBS) combined with calculation of the apparent diffusion coefficient (ADC) value at 3 T compared with the diagnostic performance of 18F-FDG PET/CT for detecting bone metastases in patients with malignant tumors. SUBJECTS AND METHODS. Thirty-nine consecutive patients with suspected bone metastases underwent both WB DWIBS and FDG PET/CT. Imaging findings were independently interpreted using qualitative and quantitative analyses. Pathologic findings or clinical or radiologic follow-up data were used as the diagnostic reference standard. The sensitivity, specificity, overall accuracy, positive predictive value, and negative predictive value of both modalities were calculated. The ADCs of benign lesions and metastases were compared. RESULTS. A total of 213 metastatic bone segments were confirmed among 39 patients. The sensitivity, specificity, overall accuracy, positive predictive value, and negative predictive value were 93.0%, 87.8%, 89.6%, 79.8%, and 96.0%, respectively, for WB DWIBS and 92.5%, 92.0%, 92.1%, 85.7% and 95.9%, respectively, for FDG PET/CT. The specificity of WB DWIBS in detecting bone metastases was significantly lower than that of FDG PET/CT (p < 0.05), whereas the sensitivity, overall accuracy, positive predictive value, and negative predictive value in detecting bone metastases were not significantly different between WB DWIBS and FDG PET/CT (p > 0.05). The ADCs for benign lesions were significantly higher than those for metastases (p < 0.001). In ROC curve analysis, the AUC value was 0.901. A cutoff ADC value of 920.5 × 10-6 mm2s-1 distinguished benign lesions from bone metastases with a sensitivity of 92.9% and a specificity of 73.4%. CONCLUSION. WB DWIBS coupled with ADC analysis at 3 T is effective for detecting bone metastases.


Assuntos
Neoplasias Ósseas/diagnóstico por imagem , Neoplasias Ósseas/secundário , Imagem de Difusão por Ressonância Magnética/métodos , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada/métodos , Imagem Corporal Total/métodos , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Fluordesoxiglucose F18 , Humanos , Masculino , Pessoa de Meia-Idade , Valor Preditivo dos Testes , Compostos Radiofarmacêuticos , Sensibilidade e Especificidade
8.
Fish Physiol Biochem ; 46(3): 971-979, 2020 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-31989392

RESUMO

Methyltransferase-like 8 (mettl8) is a protein-coding gene that may demonstrate nucleic acid or protein methyltransferase activity. Although several members of the METTL protein family have been reported, the expression and function of this family are still poorly understood, especially in fish. Medaka (Oryzias latipes) is an important model organism with relatively complete genome information, and more and more genetic toolkits are available for this fish. The popularity of medaka among developmental biologists has led to important insights into vertebrate development. Here, we report the DNA sequence and expression of mettl8 in medaka. The full-length cDNA of medaka mettl8 is 1266 bp, and its predicted open reading frame codes for a protein with 393 amino acids. The predicted molecular mass was 45.8 kDa, and the theoretical isoelectric point was 8.61. It had a conserved methyltransferase domain in METTL8 proteins. Homology analysis revealed that medaka METTL8 clustered in close proximity with the METTL8 of Austrofundulus limnaeus and Nothobranchius furzeri within the Cyprinodontiformes branch, and the protein structure of METTL8 was highly conserved. During embryogenesis, the mettl8 transcript was highly expressed in early stages, while it persisted at a detectable level until the larvae stage. In adult fish, the RT-PCR result indicated that mettl8 mRNA was expressed in the brain, eye, skin, liver, intestine, ovary, and testis. Slice in situ hybridization analysis showed that mettl8 was highly expressed in the eye, intestine, ovary, and testis. The expression and distribution of mettl8 during embryogenesis were also demonstrated by whole mount in situ hybridization. The results indicated that the mettl8 is expressed significantly in the eye, somite, and otic vesicles. Immunofluorescence and Western blot analyses showed that METTL8 protein was present in both the nuclei and cytoplasm. This study lays a foundation for further research on the function of fish mettl8.


Assuntos
Proteínas de Peixes/genética , Metiltransferases/genética , Oryzias/genética , Animais , Sequência de Bases , Encéfalo/metabolismo , DNA Complementar/genética , Olho/metabolismo , Feminino , Regulação da Expressão Gênica no Desenvolvimento , Mucosa Intestinal/metabolismo , Fígado/metabolismo , Masculino , Ovário/metabolismo , Filogenia , RNA Mensageiro/metabolismo , Pele/metabolismo , Testículo/metabolismo
9.
J Xray Sci Technol ; 28(6): 1207-1218, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32925162

RESUMO

OBJECTIVE: To investigate the value of texture analysis in magnetic resonance images for the evaluation of Gleason scores (GS) of prostate cancer. METHODS: Sixty-six prostate cancer patients are retrospective enrolled, which are divided into five groups namely, GS = 6, 3 + 4, 4 + 3, 8 and 9-10 according to postoperative pathological results. Extraction and analysis of texture features in T2-weighted MR imaging defined tumor region based on pathological specimen after operation are performed by texture software OmniKinetics. The values of texture are analyzed by single factor analysis of variance (ANOVA), and Spearman correlation analysis is used to study the correlation between the value of texture and Gleason classification. Receiver operating characteristic (ROC) curve is then used to assess the ability of applying texture parameters to predict Gleason score of prostate cancer. RESULTS: Entropy value increases and energy value decreases as the elevation of Gleason score, both with statistical difference among five groups (F = 10.826, F = 2.796, P < 0.05). Energy value of group GS = 6 is significantly higher than that of groups GS = 8 and 9-10 (P < 0.005), which is similar between three groups (GS = 3 + 4, 8 and 9-10). The entropy and energy values correlate with GS (r = 0.767, r = -0.692, P < 0.05). Areas under ROC curves (AUC) of combination of entropy and energy are greater than that of using energy alone between groups GS = 6 and ≥7. Analogously, AUC of combination of entropy and energy are significantly higher than that of using entropy alone between groups GS≤3 + 4 and ≥4 + 3, as well as between groups GS≤4 + 3 and ≥8. CONCLUSION: Texture analysis on T2-weighted images of prostate cancer can evaluate Gleason score, especially using the combination of entropy and energy rendering better diagnostic efficiency.


Assuntos
Interpretação de Imagem Assistida por Computador/métodos , Imageamento por Ressonância Magnética/métodos , Neoplasias da Próstata/diagnóstico por imagem , Idoso , Humanos , Masculino , Pessoa de Meia-Idade , Gradação de Tumores , Próstata/diagnóstico por imagem , Curva ROC
11.
J Immunol ; 197(1): 151-67, 2016 07 01.
Artigo em Inglês | MEDLINE | ID: mdl-27206770

RESUMO

Single Ig IL-1R-related molecule (SIGIRR, also called IL-1R8 or Toll/IL-1R [TIR]8), a negative regulator for Toll/IL-1R signaling, plays critical roles in innate immunity and various diseases in mammals. However, the occurrence of this molecule in ancient vertebrates and its function in liver homeostasis and disorders remain poorly understood. In this study, we identified a SIGIRR homology from zebrafish (Danio rerio [DrSIGIRR]) by using a number of conserved structural and functional hallmarks to its mammalian counterparts. DrSIGIRR was highly expressed in the liver. Ablation of DrSIGIRR by lentivirus-delivered small interfering RNA in the liver significantly enhanced hepatic inflammation in response to polyinosinic-polycytidylic acid [poly(I:C)] stimulation, as shown by the upregulation of inflammatory cytokines and increased histological disorders. In contrast, depletion of TIR domain-containing adaptor inducing IFN-ß (TRIF) or administration of TRIF signaling inhibitor extremely abrogated the poly(I:C)-induced hepatic inflammation. Aided by the zebrafish embryo model, overexpression of DrSIGIRR in vivo significantly inhibited the poly(I:C)- and TRIF-induced NF-κB activations; however, knockdown of DrSIGIRR promoted such activations. Furthermore, pull-down and Duolink in situ proximity ligation assay assays showed that DrSIGIRR can interact with the TRIF protein. Results suggest that DrSIGIRR plays an inhibitory role in TRIF-mediated inflammatory reactions by competitive recruitment of the TRIF adaptor protein from its TLR3/TLR22 receptor. To our knowledge, this study is the first to report a functional SIGIRR homolog that existed in a lower vertebrate. This molecule is essential to establish liver homeostasis under inflammatory stimuli. Overall, the results will enrich the current knowledge about SIGIRR-mediated immunity and disorders in the liver.


Assuntos
Proteínas Adaptadoras de Transporte Vesicular/metabolismo , Proteínas de Peixes/metabolismo , Inflamação/imunologia , Fígado/imunologia , Receptores de Interleucina-1/metabolismo , Proteínas de Peixe-Zebra/metabolismo , Peixe-Zebra/imunologia , Proteínas Adaptadoras de Transporte Vesicular/genética , Animais , Células Cultivadas , Citocinas/metabolismo , Proteínas de Peixes/genética , Imunidade Inata , Mediadores da Inflamação/metabolismo , Fígado/patologia , Mamíferos , NF-kappa B/metabolismo , Poli I-C/imunologia , RNA Interferente Pequeno/genética , Receptores de Interleucina-1/genética , Transdução de Sinais/genética , Receptor 3 Toll-Like/metabolismo , Proteínas de Peixe-Zebra/genética
12.
Eur Radiol ; 27(8): 3436-3442, 2017 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-27975147

RESUMO

OBJECTIVE: To retrospectively assess the safety and efficacy of percutaneous vertebroplasty (PVP) for painful osteolytic spinal metastases when treating more than three vertebrae per session. METHODS: A total of 153 patients with painful osteolytic spinal metastases underwent PVP. Group A patients (n = 93) underwent PVP at up to three vertebral levels per session. Group B patients (n = 60) underwent PVP at more than three levels in one session. Pain, quality of life (QoL), and mobility were assessed before and after PVP. Minor and major complications were systematically assessed. RESULTS: Both groups experienced significant pain relief and QoL improvement after the intervention (p < 0.001). Mobility improvement was observed in both groups, despite worse mobility status before PVP in group B compared with group A. There was no significant difference between the two groups throughout the follow-up period in overall pain relief and improvement in QoL and mobility. There was also no significant difference between groups in minor and major complications. CONCLUSIONS: Multilevel vertebroplasty is safe and effective for the treatment of multiple osteolytic spinal metastases. Multilevel PVP relieves pain and improves QoL and mobility. KEY POINTS: • Percutaneous vertebroplasty is safe and effective for painful osteolytic spinal metastases. • Multilevel vertebroplasty does not cause more complications than single-level vertebroplasty. • Multiple spinal metastases patients may regain functional independence after multilevel vertebroplasty.


Assuntos
Osteólise/cirurgia , Neoplasias da Coluna Vertebral/secundário , Neoplasias da Coluna Vertebral/cirurgia , Vertebroplastia/efeitos adversos , Adulto , Idoso , Dor nas Costas/diagnóstico por imagem , Dor nas Costas/etiologia , Dor nas Costas/cirurgia , Feminino , Humanos , Avaliação de Estado de Karnofsky , Masculino , Pessoa de Meia-Idade , Osteólise/diagnóstico por imagem , Osteólise/etiologia , Manejo da Dor/métodos , Medição da Dor/métodos , Qualidade de Vida , Estudos Retrospectivos , Fraturas da Coluna Vertebral/etiologia , Fraturas da Coluna Vertebral/cirurgia , Neoplasias da Coluna Vertebral/complicações , Neoplasias da Coluna Vertebral/diagnóstico por imagem , Tomografia Computadorizada por Raios X , Vertebroplastia/métodos
13.
Proc Natl Acad Sci U S A ; 111(46): 16538-43, 2014 Nov 18.
Artigo em Inglês | MEDLINE | ID: mdl-25359211

RESUMO

Why different species are predisposed to different tumor spectra is not well understood. In particular, whether the physical location of tumor suppressor genes relative to one another influences tumor predisposition is unknown. Renal cancer presents a unique opportunity to explore this question. Renal cell carcinoma (RCC) of clear-cell type (ccRCC), the most common type, begins with an intragenic mutation in the von Hippel-Lindau (VHL) gene and loss of 3p (where VHL is located). Chromosome 3p harbors several additional tumor suppressor genes, including BRCA1-associated protein-1 (BAP1). In the mouse, Vhl is on a different chromosome than Bap1. Thus, whereas loss of 3p in humans simultaneously deletes one copy of BAP1, loss of heterozygosity in the corresponding Vhl region in the mouse would not affect Bap1. To test the role of BAP1 in ccRCC development, we generated mice deficient for either Vhl or Vhl together with one allele of Bap1 in nephron progenitor cells. Six2-Cre;Vhl(F/F);Bap1(F/+) mice developed ccRCC, but Six2-Cre;Vhl(F/F) mice did not. Kidneys from Six2-Cre;Vhl(F/F);Bap1(F/+) mice resembled kidneys from humans with VHL syndrome, containing multiple lesions spanning from benign cysts to cystic and solid RCC. Although the tumors were small, they showed nuclear atypia and exhibited features of human ccRCC. These results provide an explanation for why VHL heterozygous humans, but not mice, develop ccRCC. They also explain why a mouse model of ccRCC has been lacking. More broadly, our data suggest that differences in tumor predisposition across species may be explained, at least in part, by differences in the location of two-hit tumor suppressor genes across the genome.


Assuntos
Carcinoma de Células Renais/genética , Modelos Animais de Doenças , Genes Supressores de Tumor , Falência Renal Crônica/genética , Neoplasias Renais/genética , Proteínas Supressoras de Tumor/fisiologia , Ubiquitina Tiolesterase/fisiologia , Proteína Supressora de Tumor Von Hippel-Lindau/fisiologia , Idade de Início , Alelos , Animais , Linhagem da Célula , Mapeamento Cromossômico , Feminino , Genes Reporter , Genes Sintéticos , Predisposição Genética para Doença , Humanos , Doenças Renais Císticas/genética , Doenças Renais Císticas/patologia , Falência Renal Crônica/sangue , Falência Renal Crônica/patologia , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Camundongos Transgênicos , Modelos Genéticos , Células-Tronco Multipotentes/metabolismo , Células-Tronco Multipotentes/patologia , Mutação , Fenótipo , Lesões Pré-Cancerosas/genética , Lesões Pré-Cancerosas/patologia , Especificidade da Espécie , Proteínas Supressoras de Tumor/antagonistas & inibidores , Proteínas Supressoras de Tumor/genética , Ubiquitina Tiolesterase/antagonistas & inibidores , Ubiquitina Tiolesterase/genética , Proteína Supressora de Tumor Von Hippel-Lindau/antagonistas & inibidores , Proteína Supressora de Tumor Von Hippel-Lindau/genética
14.
Fish Shellfish Immunol ; 43(2): 491-501, 2015 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-25652289

RESUMO

Superoxide dismutases (SODs) belong to a significant and ubiquitous family of metalloenzymes for eliminating excess reactive oxygen species (ROS). In this paper, the complete open reading frames (ORFs) of intracellular Cu/Zn-SOD (icCu/Zn-SOD), Mn-SOD and extracellular Cu/Zn-SOD (ecCu/Zn-SOD) were identified from the large yellow croaker (Pseudosciaena crocea, designated as LycSOD1, LycSOD2 and LycSOD3). The sequences were 465 bp, 678 bp and 645 bp (GenBank accession no. KJ908287, KJ908285 and KJ908286), encoding 154, 225 and 215 amino acid (aa) residues respectively. The deduced aa sequences of LycSOD1, LycSOD2 and LycSOD3 shared high identity to the known icCu/Zn-SODs, Mn-SODs and ecCu/Zn-SODs with BLASTp and Phylogenetic analysis. Two conserved Cu-/Zn-binding sites (H-44, H-47, H-64, H-121 for Cu binding and H-64, H-72, H-81, D-84 for Zn binding in LycSOD1, H-98, H-100, H-115, H-164 for Cu binding and H-115, H-163, H-166, D-169 for Zn binding in LycSOD3) and one conserved manganese coordinating sites (H-57, H-101, D-186, H-190 in LycSOD2) were identified. The total length of DNA sequences of LycSOD1, LycSOD2 and LycSOD3 were 3447 bp, 3387 bp and 3886 bp respectively, and there were 4 introns and 5 exons in Cu/Zn-SODs (LycSOD1 and LycSOD3), but only 3 exons and 2 introns in LycSOD3. Spatial expression analysis indicated the highest mRNA expression of three SODs all appeared in liver among eight detected tissues, the highest expression level was LycSOD1, then LycSOD2 and the lowest was LycSOD3 for almost each tissue. The expression of LycSOD1, LycSOD2 and LycSOD3 mRNA were all up-regulated in liver after Vibrio alginolyticus stimulation. The temporal expression peak of LycSOD1 and LycSOD2 were around 9-fold and 8-fold compared to control respectively, whereas, LycSOD3 got the highest level at 48 h post-injection (about 4.2-fold). All the results gave several new and useful evidences for further understanding the regulatory mechanism of superoxide dismutases in the innate immune system of sciaenidae fish.


Assuntos
Doenças dos Peixes/imunologia , Proteínas de Peixes/genética , Perciformes , Superóxido Dismutase/genética , Vibrioses/veterinária , Sequência de Aminoácidos , Animais , Sequência de Bases , Doenças dos Peixes/genética , Doenças dos Peixes/microbiologia , Proteínas de Peixes/metabolismo , Perfilação da Expressão Gênica/veterinária , Dados de Sequência Molecular , Família Multigênica , Fases de Leitura Aberta , Especificidade de Órgãos , Filogenia , Alinhamento de Sequência/veterinária , Superóxido Dismutase/química , Superóxido Dismutase/metabolismo , Superóxido Dismutase-1 , Vibrioses/genética , Vibrioses/imunologia , Vibrioses/microbiologia , Vibrio alginolyticus/fisiologia
15.
J Vasc Interv Radiol ; 25(7): 1112-7, 2014 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-24801501

RESUMO

PURPOSE: To evaluate the feasibility of percutaneous cementoplasty and interventional internal fixation for stabilization of impending pathologic fracture of the proximal femur. MATERIALS AND METHODS: From May 2012 to August 2013, six consecutive patients (three men and three women; median age, 58.33 y ± 21.45; age range, 18-78 y) who underwent percutaneous cementoplasty plus interventional internal fixation for the treatment of metastases to the proximal femur were retrospectively analyzed. The Karnofsky performance status (KPS) and visual analog scale (VAS) score for pain were assessed before and 1 week after the procedure; moreover, the procedure duration, length of hospital stay, risk of fracture at the procedural site, and complications were assessed. RESULTS: The KPS increased from 66.67 ± 12.11 (range, 60-90) before the procedure to 76.67 ± 13.66 (range, 60-100) 1 week after the procedure. For symptomatic patients (n = 5), the VAS score decreased from 6.80 ± 2.39 (range, 3-9) before the procedure to 1.80 ± 0.84 (range, 1-3) at 1 week after the procedure. The mean procedure duration was 90.00 minutes ± 10.56 (range, 72-102 min). The average length of hospital stay was 7 days ± 2 (range, 4-10 d). The only complication noted consisted of thrombophlebitis in one patient, on the operative side, at 15 days after the procedure. No cases of procedural site fracture during follow-up were noted (median, 192 d; range, 30-365 d). CONCLUSIONS: Percutaneous cementoplasty plus interventional internal fixation is a feasible technique for stabilization of impending pathologic fracture of the femur.


Assuntos
Cementoplastia , Fraturas do Fêmur/prevenção & controle , Neoplasias Femorais/terapia , Fixação Interna de Fraturas , Fraturas Espontâneas/prevenção & controle , Radiografia Intervencionista , Adolescente , Idoso , Cementoplastia/efeitos adversos , Terapia Combinada , Estudos de Viabilidade , Feminino , Fraturas do Fêmur/diagnóstico por imagem , Fraturas do Fêmur/etiologia , Neoplasias Femorais/complicações , Neoplasias Femorais/diagnóstico por imagem , Neoplasias Femorais/secundário , Fluoroscopia , Fixação Interna de Fraturas/efeitos adversos , Fraturas Espontâneas/diagnóstico por imagem , Fraturas Espontâneas/etiologia , Humanos , Avaliação de Estado de Karnofsky , Tempo de Internação , Masculino , Pessoa de Meia-Idade , Medição da Dor , Radiografia Intervencionista/métodos , Estudos Retrospectivos , Fatores de Tempo , Tomografia Computadorizada por Raios X , Resultado do Tratamento
16.
J Vasc Interv Radiol ; 25(7): 1094-100, 2014 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-24801500

RESUMO

PURPOSE: To evaluate combined radiofrequency (RF) ablation and percutaneous osteoplasty (POP) in patients with painful extraspinal bone metastases. MATERIALS AND METHODS: In a retrospective study, 38 patients with 54 extraspinal bone metastases (ilium, n = 24; acetabulum, n = 21; femur, n = 7; ischium, n = 1; tibia, n = 1) were treated with RF ablation and POP. All patients had pain refractory to analgesic medication with intensity > 3 on a visual analog scale (VAS). Changes in quality of life were evaluated based on pain relief (VAS score), function on a Karnofsky performance scale, and analgesic dose before and immediately after the procedure and during follow-up. VAS score was the primary outcome, and the others were secondary outcomes. RESULTS: Technical success was achieved in 37 patients (97.4%). Mean VAS score declined significantly from 7.1 ± 1.5 before treatment to 2.2 ± 2.0 at 24 hours after treatment (P < .05), 1.6 ± 1.8 at 3 months after treatment (P < .05), and 1.3 ± 1.8 at 6 months after treatment (P < .05). Pain relief immediately after the procedure was reported by 35 patients (92.1%); pain regressed completely in 7 (18.4%) patients. After 6 months, narcotic analgesia had been suspended in 32 of 33 patients (97.0%). Pain was controlled by nonsteroidal antiinflammatory drugs in 8 patients (24.2%), and no analgesia was necessary in 24 patients (72.7%). Mean Karnofsky performance scale score after treatment was higher than before treatment (P < .05). The major complication rate was 2.6% (1 of 38 patients), with one case of vasovagal shock. The minor complication rate was 23.7% (9 of 38 patients). CONCLUSIONS: RF ablation with POP is effective for pain relief and functional recovery in patients with painful extraspinal bone metastases and can significantly improve quality of life.


Assuntos
Neoplasias Ósseas/secundário , Neoplasias Ósseas/terapia , Ablação por Cateter , Cementoplastia , Manejo da Dor/métodos , Dor/prevenção & controle , Cuidados Paliativos , Adulto , Idoso , Analgésicos/uso terapêutico , Neoplasias Ósseas/complicações , Ablação por Cateter/efeitos adversos , Cementoplastia/efeitos adversos , China , Terapia Combinada , Feminino , Humanos , Avaliação de Estado de Karnofsky , Imageamento por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Dor/diagnóstico , Dor/etiologia , Manejo da Dor/efeitos adversos , Medição da Dor , Qualidade de Vida , Estudos Retrospectivos , Fatores de Tempo , Resultado do Tratamento , Adulto Jovem
17.
AJR Am J Roentgenol ; 202(3): W298-305, 2014 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-24555629

RESUMO

OBJECTIVE: The purpose of this study was to determine the safety and efficacy of percutaneous vertebroplasty and interventional tumor removal in the management of metastatic spinal tumors and malignant vertebral compression fractures. SUBJECTS AND METHODS: Thirty-one patients with metastatic spinal tumors and malignant vertebral compression fractures were treated with percutaneous vertebroplasty and interventional tumor removal. Insertion of a 14-gauge needle and guidewire into the vertebral body was followed by sequential dilation of the track with working cannulae until the last cannula reached the anterior portions of the pedicle. Interventional tumor removal was performed with marrow nucleus rongeurs, and 5-10 mL of cement was injected into the treated vertebra. Outcome data (visual analog scale score, Oswestry disability index score, and Karnofsky performance scale score) were collected preoperatively; 1 week and 1, 3, and 6 months after the procedure; and every 6 months thereafter until death. RESULTS: The overall clinical assessment at the last follow-up evaluation showed that pain was completely resolved in 23 patients, decreased in six patients, and unimproved in two patients, yielding a pain relief rate of 94%. The average preoperative visual analog scale score was 7.2, which decreased to 2.4 at 1 month, 1.9 at 6 months, and 1.6 at 1 year and was maintained at 1.3 at the follow-up evaluations performed after more than 1 year. Statistically significant improvement in Oswestry disability index and Karnofsky performance scale scores was also seen between the preoperative evaluation and every follow-up assessment postoperatively (p<0.001). CONCLUSION: Percutaneous vertebroplasty and interventional tumor removal are safe, effective, and minimally invasive palliative therapies for reducing pain and improving function in patients with metastatic spinal tumors and malignant vertebral compression fractures.


Assuntos
Extravasamento de Materiais Terapêuticos e Diagnósticos/etiologia , Fraturas por Compressão/terapia , Laminectomia/métodos , Fraturas da Coluna Vertebral/terapia , Neoplasias da Coluna Vertebral/secundário , Neoplasias da Coluna Vertebral/terapia , Vertebroplastia/efeitos adversos , Adulto , Idoso , Terapia Combinada , Extravasamento de Materiais Terapêuticos e Diagnósticos/diagnóstico , Extravasamento de Materiais Terapêuticos e Diagnósticos/prevenção & controle , Feminino , Fraturas por Compressão/etiologia , Humanos , Laminectomia/efeitos adversos , Masculino , Pessoa de Meia-Idade , Fraturas da Coluna Vertebral/etiologia , Neoplasias da Coluna Vertebral/complicações , Resultado do Tratamento , Vertebroplastia/métodos
18.
Gen Comp Endocrinol ; 204: 181-4, 2014 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-24861804

RESUMO

MicroRNAs (miRNAs) play an important role in gonadal development and differentiation in fish. However, understanding of the mechanism of this process is hindered by our poor knowledge of miRNA expression patterns in fish gonads. In this study, miRNA libraries derived from adult gonads of Paralichthys olivaceus were generated by using next-generation sequencing (NGS) technology. Bioinformatics analysis was performed to distinguish mature miRNA sequences from two classes of small RNAs represented in the sequencing data. A total of 141 mature miRNAs were identified, in which 21 miRNAs were found in P. olivaceus for the first time. Variance and preference of miRNAs expression were concluded from the deep sequencing reads. Some miRNAs, such as pol-miR-143, pol-miR-26a and pol-let-7a were found with quite high expression levels in both gonads, while some exhibited a clear sex-biased expression in different gonad. Approximate 20.0% and 13.1% of the isolated miRNAs were preferentially expressed in the testis (FC<0.5) or ovary (FC>2), respectively. The identification and the preliminary analysis of the sex-biased expression of miRNAs in P. olivaceus gonads in our work by using NGS will provide us a basic catalog of miRNAs to facilitate future improvement and exploitation of sexual regulatory mechanisms in P. olivaceus.


Assuntos
Linguado/genética , Gônadas/metabolismo , Sequenciamento de Nucleotídeos em Larga Escala/métodos , MicroRNAs/genética , Ovário/metabolismo , Testículo/metabolismo , Animais , Biologia Computacional , Feminino , Linguado/crescimento & desenvolvimento , Gônadas/crescimento & desenvolvimento , Masculino , Reação em Cadeia da Polimerase em Tempo Real , Reação em Cadeia da Polimerase Via Transcriptase Reversa
19.
Acta Radiol ; 55(8): 976-84, 2014 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-24132769

RESUMO

BACKGROUND: Percutaneous vertebroplasty (PVP) is associated with incomplete pain relief and vertebral instability due to cement leakages. PURPOSE: To evaluate the feasibility of a new method of PVP, radiofrequency ablation (RFA) and interventional tumor removal (ITR) for malignant spinal tumor and malignant vertebral compression fractures without epidural involvement. MATERIAL AND METHODS: Twelve patients were treated with PVP, RFA, and ITR. A 14 G needle and a guidewire were inserted into the vertebral body, followed by sequential dilatation of the tract with the working cannula until the last working cannula reached the anterior portions of the pedicle. Thereafter, tumors were ablated with a radiofrequency probe, and ITR was performed with a marrow nucleus rongeurs. Then, cement was injected into the extirpated vertebral body. The data were collected and follow-up was performed after 1, 3, and 6 months, and thereafter every 6 months postoperatively. RESULTS: PVP, RFA, and ITR were technically successful in all patients. The average preoperative pain visual analog scale (VAS) score was 7.0 ± 1.0, which decreased to 2.1 ± 1.2 at 1 month, to 1.6 ± 1.4 at 6 months, to 1.8 ± 1.7 at 1 year, and was maintained at 1.3 ± 1.1 at >1-year follow-up. A total of 92% patients (11/12) obtained excellent and good pain relief with improvement of quality of life. Seven patients continued with follow-up healthcare, and five patients died of the underlying disease. CONCLUSION: PVP, RFA, and ITR may be a feasible approach for malignant spinal tumor and malignant vertebral compression fractures without epidural involvement.


Assuntos
Ablação por Cateter/métodos , Fraturas por Compressão/cirurgia , Fraturas da Coluna Vertebral/cirurgia , Neoplasias da Coluna Vertebral/cirurgia , Vertebroplastia/métodos , Idoso , Estudos de Viabilidade , Feminino , Seguimentos , Fraturas por Compressão/complicações , Humanos , Masculino , Pessoa de Meia-Idade , Dor/complicações , Dor/prevenção & controle , Complicações Pós-Operatórias/prevenção & controle , Qualidade de Vida , Fraturas da Coluna Vertebral/complicações , Neoplasias da Coluna Vertebral/complicações , Resultado do Tratamento
20.
Curr Med Imaging ; 2024 Mar 15.
Artigo em Inglês | MEDLINE | ID: mdl-38494937

RESUMO

BACKGROUND: Residual breast tumors may remain after vacuum-assisted excisional biopsy (VAEB). OBJECTIVE: To determine the incidence of residual breast tumors in patients after VAEB and the efficacy of magnetic resonance imaging (MRI) in detecting these tumors. METHODS: This retrospective analysis examined patients who received VAEB before a diagnosis of breast cancer (BC) at our hospital from 2015 to 2019. The incidence of residual tumors after VAEB was determined by MRI and pathological examination. The diagnostic value of MRI in detecting residual tumors was determined for all patients and different subgroups. Logistic regression analysis was used to identify factors associated with residual tumors. RESULTS: We examined 147 patients and obtained pathological samples from 146 patients, including 103 (70.5%) with residual tumors and 43 (29.5%) without residual tumors. The MRI examinations demonstrated the complete tumor resection rate was 48.9%. Compared to the pathological results, MRI had a positive predictive value of 77.8%, negative predictive value of 48.8%, specificity of 65.6%, and sensitivity of 60.7%. Further analysis indicated that MRI had moderate accuracies for patients with stage pT-1 (71.9%), stage pTNM-IA (73.1%), and luminal B subtype (78.3%). Binary logistic regression analysis showed that the risk of tumor residue correlated with the pathological stage. CONCLUSION: Tumor residue is common after VAEB, and MRI has limited accuracy in detecting these residual tumors. However, for small breast tumors and luminal B subtype BC, MRI had higher accuracy in the detection of residual tumors. The risk of tumor residue is closely associated with the pathological stage.

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