RESUMO
Objective: To investigate the clinicopathological features, immunophenotypes and molecular genetics of EWSR1-SMAD3 positive fibroblastic tumor (ESFT) with an emphasis on differential diagnosis. Methods: The clinicopathological data, immunohistochemical profiles and molecular profiles of 3 ESFT cases diagnosed at the Department of Pathology, Fudan University Shanghai Cancer Center from 2018 to 2021were analyzed. The related literature was also reviewed. Results: There were two males and one female. The patients were 24, 12 and 36 years old, respectively. All three tumors occurred in the subcutis of the foot with the disease duration of 6 months to 2 years. The tumors were presented with a slowly growing mass or nodule, accompanied with pain in 1 patient. The tumors ranged in size from 0.1 to 1.6 cm (mean, 1.0 cm). Microscopically, the tumors were located in the subcutaneous tissue with a nodular or plexiform growth pattern. They were composed of cellular fascicles of bland spindle cells with elongated nuclei and fine chromatin. One of the tumors infiltrated into adjacent adipose tissue. There was no nuclear atypia or mitotic activities. All three tumors showed prominent stromal hyalinization with zonal pattern present in one case. Focal punctate calcification was noted in two cases. The immunohistochemical studies showed that tumor cells were diffusely positive for ERG and negative for CD31 and CD34, with Ki-67 index less than 2%. Fluorescence in situ hybridization on the two tested cases identified EWSR1 gene rearrangement. The next generation sequencing analysis demonstrated EWSR1-SMAD3 fusion in all three cases. During the follow up, one patient developed local recurrence 24 months after the surgery. Conclusions: ESFT is a benign fibroblastic neoplasm and has a predilection for the foot, characterized by ERG immunoreactivity and EWSR1-SMAD3 fusion. Local recurrence might occur when incompletely excised. Familiarity with its clinicopathological features is helpful in distinguishing it from other spindle cell neoplasms that tend to occur at acral sites.
Assuntos
Neoplasias de Tecido Fibroso , Neoplasias de Tecidos Moles , Adulto , Criança , Feminino , Humanos , Masculino , Biomarcadores Tumorais/análise , China , Hibridização in Situ Fluorescente , Neoplasias de Tecido Fibroso/patologia , Proteína EWS de Ligação a RNA/genética , Proteína Smad3/genética , Neoplasias de Tecidos Moles/genética , Neoplasias de Tecidos Moles/cirurgiaRESUMO
Objective: To investigate the effect of nuclear factor erythroid 2-related factor 2 (Nrf2) in the alteration of tight junction protein expression in choroid plexus epithelial cells created by lanthanum-activated matrix metalloproteinase 9 (MMP9) . Methods: In October 2020, immortalized rat choroid plexus epithelial cell line (Z310) cells were used as the blood-cerebrospinal fluid barrier in vitro, and were divided into control group and 0.125, 0.25, 0.5 mmol/L lanthanum chloride (LaCl(3)) treatment group. After treating Z310 cells with different concentrations of LaCl(3) for 24 hours, the morphological changes of Z310 cells were observed under inverted microscope, the protein expression levels of MMP9, occludin and zonula occludens-1 (ZO-1) were observed by cellular immunofluorescence method, and the protein expression levels of MMP9, tissue inhibitors of metalloproteinase1 (TIMP1) , occludin, ZO-1 and Nrf2 were detected by Western blotting. The level of reactive oxygen species (ROS) in cells was detected by flow cytometry. Results: Compared with the control group, Z310 cells in the LaCl(3) treatment group were smaller in size, with fewer intercellular junctions, and more dead cells and cell fragments. The expression level of MMP9 protein in cells treated with 0.25 and 0.5 mmol/L LaCl(3) was significantly higher than that in the control group (P<0.05) , and the expression level of TIMP1 and tight junction proteins occudin and ZO-1 was significantly lower than that in the control group (P<0.05) . Compared with the control group, the ROS production level in the 0.25, 0.5 mmol/L LaCl(3) treatment group was significantly increased (P<0.05) , and the Nrf2 protein expression level in the 0.125, 0.25, 0.5 mmol/L LaCl(3) treatment group was significantly decreased (P<0.05) . Conclusion: Lanthanum may increase the level of ROS in cells by down regulating the expression of Nrf2, thus activating MMP9 to reduce the expression level of intercellular tight junction proteins occludin and ZO-1.
Assuntos
Metaloproteinase 9 da Matriz , Fator 2 Relacionado a NF-E2 , Ratos , Animais , Metaloproteinase 9 da Matriz/metabolismo , Fator 2 Relacionado a NF-E2/metabolismo , Proteínas de Junções Íntimas/metabolismo , Ocludina/metabolismo , Ocludina/farmacologia , Plexo Corióideo/metabolismo , Espécies Reativas de Oxigênio/metabolismo , Lantânio/farmacologia , Células Epiteliais , Proteína da Zônula de Oclusão-1/metabolismo , Fosfoproteínas/metabolismo , Fosfoproteínas/farmacologiaRESUMO
Objective: To investigate the clinicopathological features, immunophenotype and differential diagnoses of SMARCA4-deificient undifferentiated carcinoma (SMARCA4-DUC) of the gastrointestinal tract. Methods: The clinicopathological data and immunohistochemical profiles of nine cases of SMARCA4-DUC of the gastrointestinal tract diagnosed in Fudan University Shanghai Cancer Center, from 2018 to 2021, were analyzed retrospectively. The relevant literature was reviewed. Results: There were seven males and two females with age at presentation ranging from 39 to 74 years (mean 58 years, median 64 years). The tumor occurred in the stomach (6 cases), right hemicolon (2 cases) and duodenum (1 case). The main symptoms included dysphagia, abdominal pain, diarrhea and melena. Five cases were resected, and the tumor sizes ranged from 5.0 to 8.7 cm (mean 6.7 cm). Microscopically, the tumor was composed of sheets of undifferentiated round to epithelioid cells with large vesicular nuclei harboring prominent nucleoli and displaying brisk mitotic activity. Foci of dyscohesive rhabdoid cells were also noted. The tumor cells were generally uniform; however, prominent pleomorphism and spindle cell component was present in one case each. Five cases contained areas of coagulative necrosis, and one case showed myxoid change of the stroma. By immunohistochemistry, eight cases showed complete loss of BRG1 (SMARCA4) and BRM (SMARCA2) expression. Whereas the expression of these two markers was lost in the epithelioid component of one case, it remained in the spindle cell component (mosaic pattern). Apart from one case with partial expression of pan-cytokeratin, all other eight cases showed either limited (<5%, n=5) or totally negative (n=3) staining of pan-cytokeratin. In addition, four cases also expressed CD34, SOX2 and SALL4. Six patients had follow-up data: four died of disease within 1 year. Conclusions: SMARCA4-DUC of the gastrointestinal tract represents a highly aggressive malignancy with poor outcome. Due to lack of cell-specific differentiation, it is not uncommonly misdiagnosed as a wide variety of poorly-differentiated or undifferentiated tumors. Increased recognition of this rare but distinctive entity not only facilitates the diagnosis and differential diagnosis, but also provides important therapeutic and prognostic information for the clinicians.
Assuntos
Biomarcadores Tumorais , Carcinoma , Biomarcadores Tumorais/genética , Carcinoma/patologia , China , DNA Helicases , Feminino , Trato Gastrointestinal/patologia , Humanos , Queratinas , Masculino , Proteínas Nucleares , Estudos Retrospectivos , Fatores de TranscriçãoRESUMO
INTRODUCTION: Although computed tomography (CT) is a useful tool for exploring occult infection in patients with sepsis in the emergency department, the potential nephrotoxicity of contrast media is a major concern. Our study aimed to investigate the association between use of contrast-enhanced CT and the risks of acute kidney injury and other adverse outcomes in patients with sepsis. METHODS: In total, 587 patients with sepsis who underwent CT scan (enhanced CT group: 105, non-enhanced CT group: 482) from January 2012 to December 2016 at a tertiary referral centre were enrolled in this retrospective analysis, and propensity score matching was performed to minimise the selection bias. The length of stay, incidences of acute kidney injury and emergent dialysis, and short-term mortality were compared between the two groups. RESULTS: Compared with patients in the non-enhanced CT group, patients in the contrast-enhanced CT group did not have increased risks of acute kidney injury (odds ratio [OR]=1.38, 95% confidence interval [CI]=0.55-3.43; P=0.489), emergent dialysis (OR=1.31, 95% CI=0.47-3.68; P=0.602), or short-term mortality (OR=0.90, 95% CI=0.48-1.69; P=0.751). In addition, there was no significant difference in the median length of hospital stay between survivors in the two groups (20 vs 19 days, P=0.742). CONCLUSIONS: Intravenous contrast administration during CT scanning was not associated with prolonged length of hospital stay in patients with sepsis in an emergency setting. Moreover, the use of contrast-enhanced CT was not associated with increased risks of acute kidney injury, emergent dialysis, or short-term mortality.
Assuntos
Injúria Renal Aguda/epidemiologia , Meios de Contraste/efeitos adversos , Sepse/diagnóstico por imagem , Injúria Renal Aguda/induzido quimicamente , Administração Intravenosa , Idoso , Estudos de Coortes , Meios de Contraste/administração & dosagem , Serviço Hospitalar de Emergência , Feminino , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , Pontuação de Propensão , Estudos Retrospectivos , Fatores de Risco , Taiwan/epidemiologia , Tomografia Computadorizada por Raios XRESUMO
Objective: To study the constitutional features of diseases spectrum of inpatients with liver disease in infectious diseases department of three comprehensive hospitals to provide resource allocation proposition for the construction of Department of Infectious Diseases. Methods: Inpatients data were extracted from the department of infectious diseases of three comprehensive hospitals (Kunming General Hospital of the People's Liberation Army, Yuxi People's Hospital and Dali People's Hospital) between January 2010 to December 2015, and were retrospectively analyzed. The distribution of patients with viral hepatitis (A, B, C, E) and severe liver disease (Severe hepatitis, cirrhosis, liver cancer) was further analyzed in hospitalized patients. Data were analyzed by one-way analysis of variance. A chi-squared test was used for comparison between groups. The change trends of disease constituent ratio in different years were checked by 2 test. Results: Liver disease, tuberculosis and AIDS were the three common diseases of three comprehensive hospitals in Yunnan, accounting for 58.61% of all admissions. However, an inpatients with liver diseases (17.25%, 3555/20606, 95% CI 16.73%-17.77%) were significantly lower than tuberculosis inpatients (33.98%, 7002/20606, 95% CI 33.34%-34.62%). An observations from different hospitals and at different time points showed that the proportion of patients with liver disease was lower than that of tuberculosis patients. The proportion of inpatients with HBV infection showed a downward trend (P < 0.001), whereas the proportions of inpatients with HCV and severe liver diseases showed an increased trend over time (P < 0.001). Conclusion: The proportion of inpatients with liver diseases was lower than tuberculosis inpatients in the Department of Infectious Diseases of three comprehensive hospitals. Hence, the paucity of the disease spectrum should be considered for resource allocation in the construction of infectious disease department.
Assuntos
Pacientes Internados/estatística & dados numéricos , Cirrose Hepática/epidemiologia , Adulto , China , Humanos , Prevalência , Estudos RetrospectivosRESUMO
OBJECTIVES: To investigate the clinical predictors and the aetiologies for surgery in patients with Naja atra (Taiwan or Chinese cobra) envenomation. METHODS: This case series was conducted in the only tertiary care centre in eastern Taiwan. Patients who presented to the emergency department with Naja atra bite between January 2008 and September 2014 were included. Clinical information was collected and compared between surgical and non-surgical patients. RESULTS: A total of 28 patients with Naja atra envenomation presented to the emergency department during the study period. Of these, 60.7% (n=17) required surgery. Necrotising fasciitis (76.5%) was the main finding in surgery. Comparisons between surgical and non-surgical patients showed skin ecchymosis (odds ratio=34.36; 95% confidence interval, 2.20-536.08; P=0.012) and a high total dose of antivenin (≥6 vials; odds ratio=14.59; 95% confidence interval, 1.10-192.72; P=0.042) to be the most significant predictors of surgery. The rate of bacterial isolation from the surgical wound was 88.2%. Morganella morganii (76.5%), Enterococcus faecalis (58.8%), and Bacteroides fragilis (29.4%) were the most common pathogens involved. Bacterial susceptibility testing indicated that combined broad-spectrum antibiotics were needed to cover mixed aerobic and anaerobic bacterial infection. CONCLUSIONS: Patients with Naja atra envenomation who present with skin ecchymosis or the need for a high dose of antivenin may require early surgical assessment. Combined broad-spectrum antibiotics are mandatory.
Assuntos
Antivenenos/administração & dosagem , Venenos Elapídicos/toxicidade , Fasciite Necrosante/cirurgia , Mordeduras de Serpentes/cirurgia , Animais , Antibacterianos/administração & dosagem , Infecções Bacterianas/epidemiologia , Infecções Bacterianas/microbiologia , Equimose/epidemiologia , Equimose/etiologia , Equimose/cirurgia , Serviço Hospitalar de Emergência , Fasciite Necrosante/epidemiologia , Fasciite Necrosante/etiologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Naja naja , Estudos Retrospectivos , Mordeduras de Serpentes/complicações , Mordeduras de Serpentes/terapia , TaiwanRESUMO
Isolated traumatic gallbladder rupture subsequent to blunt abdominal injury is rare. Most literatures on the subjects consist of case reports. We reported a rare case of isolated gallbladder rupture and discussed the possible predisposing factors to gallbladder rupture.
Assuntos
Traumatismos Abdominais/complicações , Vesícula Biliar/lesões , Ferimentos não Penetrantes/complicações , Traumatismos Abdominais/diagnóstico por imagem , Adulto , Colecistectomia , Vesícula Biliar/diagnóstico por imagem , Vesícula Biliar/cirurgia , Humanos , Masculino , Ruptura/etiologia , Ruptura/cirurgia , Tomografia Computadorizada por Raios X , Resultado do TratamentoAssuntos
Angiomiolipoma/diagnóstico por imagem , Dor no Flanco/etiologia , Hematoma/diagnóstico por imagem , Nefropatias/diagnóstico por imagem , Diagnóstico Diferencial , Humanos , Masculino , Pessoa de Meia-Idade , Sistemas Automatizados de Assistência Junto ao Leito , Ruptura Espontânea/diagnóstico por imagem , Síndrome , Tomografia Computadorizada por Raios X , UltrassonografiaAssuntos
Carcinoma/diagnóstico por imagem , Leucocitose/complicações , Síndromes Paraneoplásicas/complicações , Neoplasias da Bexiga Urinária/diagnóstico por imagem , Idoso de 80 Anos ou mais , Carcinoma/complicações , Diagnóstico Diferencial , Humanos , Masculino , Invasividade Neoplásica , Metástase Neoplásica , Síndromes Paraneoplásicas/etiologia , Abscesso do Psoas , Tomografia Computadorizada por Raios X , Neoplasias da Bexiga Urinária/complicaçõesRESUMO
Sinopodophyllum hexandrum is an alpine medicinal plant that produces the anticancer compound podophyllotoxin (PPT). Although a positive relationship between PPT content and altitude has been proved and low temperature enhances plant growth and PPT accumulation has also been revealed, the role of UV radiation in regulating growth and PPT accumulation is still unclear In this study, morphophysiological traits, metabolites content and related genes expression were investigated by exposing S. hexandrum seedlings to treatment with UV-B radiation. The results showed that the contents of soluble sugars and flavonoids, and the expression levels of genes involved in glycometabolism (XET and ß-1,3-glucanase) and flavonoid biosynthesis (PAL,C4H,4CL,CHS1 and DTX41) were enhanced in response to UV-B compared to CK. Moreover, genes involved in stress tolerance (MYB, WRKY,APX3 and EX2) were also upregulated in response to UV-B radiation. Although the whole plant biomass exhibited slightly increased values that depended largely on root development, the contents of chlorophyll and PPT and the expression levels of genes involved in photosynthesis (matK, ndhF,rbcL and ycf5) and PPT biosynthesis (C3H,CCoAMT,CCR,CAD, DPO, PLR,SDH, CPY719A23,OMT3,CYP71CU1,OMT1and 2-ODD) were significantly decreased in response to UV-B compared to CK. It can be concluded that UV-B radiation promotes soluble sugars and flavonoids accumulation, but inhibits PPT biosynthesis in S. hexandrum.
Assuntos
Flavonoides , Podofilotoxina , Expressão Gênica , Regulação da Expressão Gênica de Plantas , Raios UltravioletaRESUMO
OBJECTIVE: To study the expression of micro ribonucleic acid (miR)-320a in synovial tissues of patients with rheumatoid arthritis (RA) and explore the influences of miR-320a on the proliferation and apoptosis of fibroblast-like synoviocytes (FLSs) in RA and its mechanism. PATIENTS AND METHODS: The expression level of miR-320a in synovial tissues of 40 healthy people and 32 RA patients was detected via reverse transcription-polymerase chain reaction (RT-PCR). The FLSs were isolated from RA patients, cultured in vitro and divided into Control group and miR-320a mimic group. The proliferation and apoptosis of FLSs in each group were observed. Finally, the expression level of mitogen-activated protein kinase (MAPK)-extracellular signal-regulated kinase (ERK) 1/2 in each group was detected via Western blotting. RESULTS: The expression level of miR-320a in synovial tissues of RA patients was significantly lower than that in healthy people (p < 0.05). After miR-320a mimic was transfected into FLSs cultured in vitro, EdU staining and flow cytometry analysis were performed. The results revealed that the proportion of EdU-positive cells significantly declined in miR-320a mimic group, the proportion of cells in G0/G1 phase was increased, while the cells in G2/M and S phases were significantly decreased (p < 0.05). Above data indicated that the cell proliferation ability was significantly inhibited. In addition, the results of flow cytometry also showed that the apoptosis rate of FLSs in miR-320a mimic group was significantly higher than that in Control group (p < 0.05). The results of Western blotting manifested that the Bcl-2 associated X protein (Bax)/Bcl-2 ratio in miR-320a mimic group was also obviously increased (p < 0.05). According to further studies, the phosphorylation level of ERK1/2 in miR-320a mimic group was remarkably inhibited (p < 0.05). CONCLUSIONS: The expression level of miR-320a significantly declined in synovial tissues of RA patients. MiR-320a attenuated proliferation and promoted apoptosis of FLSs through inhibiting the activation of the MAPK-ERK1/2 signaling pathway.
Assuntos
Apoptose/genética , Artrite Reumatoide/metabolismo , Proliferação de Células/genética , Sistema de Sinalização das MAP Quinases/genética , MicroRNAs/genética , Sinoviócitos/metabolismo , Artrite Reumatoide/genética , Artrite Reumatoide/patologia , Estudos de Casos e Controles , Células Cultivadas , Expressão Gênica , Humanos , Cultura Primária de Células , Sinoviócitos/patologiaRESUMO
Mediastinitis is a life-threatening complication among patients undergoing cardiac transplantation. There are conservative and aggressive surgical treatments. From October 1987 to October 2007, we reviewed the clinical records of 315 heart transplantations for those four cases with severe mediastinis needing surgical treatment for demographic data, clinical presentation, treatment, and outcome. Conservative therapy, such as sternal debridement without muscle flap closure and closed local irrigation with drainage, was performed in two cases. The other two patients needed aggressive surgical treatment with muscle flap or omental flap performed. Only one transplant recipient with severe mediastinis had undergone previous sternotomy before cardiac transplantation. The organisms were methicillin-resistant Staphylococcus aureus in three and Aspergillus fumigatus in one case. The one subject who received conservative therapy without a flap died. The other two with muscle flap and omental flap survived. Cardiac recipients survived if there was aggressive surgical treatment for severe mediastinitis. Meanwhile, we recommend prolonged aggressive antibiotic therapy and reduced immunotherapy.
Assuntos
Transplante de Coração/efeitos adversos , Mediastinite/cirurgia , Complicações Pós-Operatórias/cirurgia , Adulto , Aspergilose/cirurgia , Aspergillus fumigatus , Feminino , Transplante de Coração/imunologia , Humanos , Imunossupressores/uso terapêutico , Masculino , Mediastinite/microbiologia , Resistência a Meticilina , Pessoa de Meia-Idade , Estudos Retrospectivos , Infecções Estafilocócicas/cirurgiaRESUMO
The incidence of tuberculosis is slightly higher among heart transplantation cases than in the general population in Taiwan. Tuberculosis shows a high mortality rate ranging from 22% to 31% in transplant recipients. From October 1987 to October 2007, we performed 315 heart transplantations. Clinical records were reviewed for demographic data, clinical presentation, treatment, and outcome. Tuberculosis was diagnosed by cultures of any body sample in association with compatible symptoms and signs. Mortality was related to tuberculosis if there was evidence of active tuberculosis at the time of death and no other etiology accounted for death. Ten patients who had received heart transplants were diagnosed as tuberculosis. There were seven pulmonary lesions and seven extrapulmonary lesions. Treatment consisted of isoniazid, rifampin, ethambutol, pyrazinamide, streptomycin, ciprofloxacin, and levofloxacin. Seven patients completed the antituberculosis treatment: the median treatment duration was 1 year. Three patients developed hepatitis. There was no tuberculosis-related mortality. Ten out of a total of 315 patients (3.17%) represented a tuberculosis rate higher than that reported for the general Taiwan population (67/100,000). This high mortality of infection may be completely treated by a combination of at least three drugs except pyrzinamide because of side effects and tolerance.
Assuntos
Transplante de Coração/efeitos adversos , Complicações Pós-Operatórias/microbiologia , Tuberculose Pulmonar/epidemiologia , Adulto , Idoso , Antituberculosos/uso terapêutico , Quimioterapia Combinada , Feminino , Rejeição de Enxerto/tratamento farmacológico , Rejeição de Enxerto/prevenção & controle , Humanos , Imunossupressores/uso terapêutico , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , TaiwanRESUMO
OBJECTIVE: miRNAs have been confirmed to be related to cell proliferation and apoptosis. In this study, we detected the potential effect of miR-448 on glioma cell proliferation and apoptosis. MATERIALS AND METHODS: miR-448 and CTTN expression levels were detected in glioma cell lines with quantitative reverse transcriptase-polymerase chain reaction (qRT-PCR). Cells were transfected with miR-448 mimics and inhibitor by using lipofectamine 2000 respectively. The proliferative ability of transfected cells was detected via methyl thiazolyl tetrazolium (MTT) and cell counting kit-8 (CCK8) assays. Cell apoptosis and cell-cycle were tested using flow cytometry. The regulatory correlation between miR-448 and CTTN was explored by bioinformatics analysis and luciferase reporter assay. RESULTS: Lower expression of miR-448 and higher level of CTTN were detected in glioma cells. MiR-448 could regulate cell proliferation, cell apoptosis, and cell cycle. CTTN was negatively regulated by miR-448. CONCLUSIONS: miR-448 downregulates CTTN to inhibit cell proliferation and promote apoptosis in glioma, which indicates a potential therapeutic target of glioma.
Assuntos
Apoptose , Proliferação de Células , Cortactina/metabolismo , MicroRNAs/metabolismo , Regiões 3' não Traduzidas , Antagomirs/metabolismo , Linhagem Celular Tumoral , Cortactina/química , Cortactina/genética , Regulação para Baixo , Pontos de Checagem da Fase G1 do Ciclo Celular , Glioma/metabolismo , Glioma/patologia , Humanos , MicroRNAs/antagonistas & inibidores , MicroRNAs/genéticaRESUMO
Coccidiosis of chickens caused by protozoan parasites of the genus Eimeria (Coccidia: Eimeriidae) is an enteric disease that results in great economic losses throughout the world, including Taiwan. Using polymerase chain reaction (PCR) with primers specific for the second internal transcribed spacer (ITS-2) of ribosomal DNA (rDNA), three species of Eimeria, E. tenella, E. maxima, and E. acervulina have been successfully characterised from chickens in Taiwan. The sizes of PCR products from various isolates representing these three species were between 370 and 580 base pairs (bp). After cloning and sequencing of the PCR products, high nucleotide sequence identity (96.8-100%) was observed within a species. In addition, ITS-2 nucleotide sequences for E. tenella had higher homology (98.5-99.3%) than E. maxima (81.6-96.5%) when compared with appropriate sequences deposited in GenBank. To our knowledge, this is the first report of a 412-bp ITS-2 sequence for E. acervulina from chickens.
Assuntos
Galinhas/parasitologia , Coccidiose/parasitologia , DNA Espaçador Ribossômico/genética , Eimeria/genética , Doenças das Aves Domésticas/parasitologia , Animais , Sequência de Bases , Clonagem Molecular , Dados de Sequência Molecular , Filogenia , Doenças das Aves Domésticas/epidemiologia , Taiwan/epidemiologiaRESUMO
The transcription factor NKX6.1 (NK6 homeobox 1) is important in the development of pancreatic ß-cells and neurons. Although recent publications show that NKX6.1 is hypermethylated and downregulated during tumorigenesis, the function of NKX6.1 in carcinogenesis remains elusive. Here, we address the metastasis suppressor function of human NKX6.1 using cell, animal and clinical analyses. Our data show that NKX6.1 represses tumor formation and metastatic ability both in vitro and in vivo. Mechanistically, NKX6.1 suppresses cell invasion by inhibiting the epithelial-to-mesenchymal transition (EMT). NKX6.1 directly enhances the mRNA level of E-cadherin by recruiting BAF155 coactivator and represses that of vimentin and N-cadherin by recruiting RBBP7 (retinoblastoma binding protein 7) corepressor. Clinical cancer tumors with metastasis show low NKX6.1 protein expression coinciding with low E-cadherin and high vimentin expression. Our results demonstrate that NKX6.1 functions as an EMT suppressor by interacting with different epigenetic modifiers, making it a potential novel therapeutic option.
Assuntos
Caderinas/genética , Transição Epitelial-Mesenquimal/genética , Proteínas de Homeodomínio/genética , Proteína 7 de Ligação ao Retinoblastoma/genética , Fatores de Transcrição/genética , Animais , Caderinas/biossíntese , Linhagem Celular Tumoral , Metilação de DNA/genética , Epigênese Genética , Transição Epitelial-Mesenquimal/efeitos dos fármacos , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Genes Supressores de Tumor , Proteínas de Homeodomínio/metabolismo , Humanos , Camundongos , Invasividade Neoplásica/genética , RNA Mensageiro/genética , Vimentina/administração & dosagemRESUMO
Myoblasts from skeletal muscle of chicken or Japanese quail embryos were infected with avian sarcoma virus 17 (ASV-17), a retrovirus carrying the jun oncogene. At high multiplicities of infection ASV-17-induced morphologic transformation inhibited fusion of myoblasts into myotubes and stimulated extended replication. The expression of the muscle-specific proteins desmin, myosin and creatine phosphokinase was inhibited in ASV-17-infected cultures. Immunofluorescent staining detected strong expression of the ASV-17 Gag-Jun fusion protein in the nuclei of infected mononuclear myoblasts, but Gag-Jun was not detectable in multinucleated myotubes that occurred in clonal populations of ASV-17-infected quail myoblasts. This result suggests that the nuclear expression of viral jun and myogenic differentiation are mutually exclusive events. A mutant of ASV-17, ts jun-1, is partly temperature-sensitive in its ability to transform chicken embryo fibroblasts. At the non-permissive temperature of 41.5 degrees C, multinucleated myotubes readily formed in ts jun-1-infected myoblast cultures and expressed muscle-specific proteins detectable by immunofluorescent staining. These myotubes also showed strong immunofluorescent staining for Gag-Jun in the cell nuclei. The nuclear expression of a Jun protein that is defective in its transforming function appears therefore to be compatible with myogenesis. Several retroviral constructs carrying various viral and cellular jun inserts, as well as jun deletion mutants and recombinants between c-jun and v-jun, were tested for their effect on myogenic differentiation. There was an approximate correlation between the ability of a construct to transform chicken embryo fibroblasts and its effectiveness in interfering with myogenic differentiation. We conclude that the expression of an oncogenic jun gene in myoblasts strongly inhibits myogenic differentiation, and that a highly transforming Jun protein cannot be expressed in the nuclei of differentiating myotubes, while the presence of transformation-defective variants of Jun is compatible with differentiation.
Assuntos
Transformação Celular Viral/genética , Genes jun/fisiologia , Músculos/citologia , Animais , Vírus do Sarcoma Aviário/genética , Diferenciação Celular/genética , Células Cultivadas , Embrião de Galinha , Coturnix , Músculos/ultraestrutura , Mutação/genética , Miofibrilas/ultraestrutura , TemperaturaRESUMO
BACKGROUND/OBJECTIVES: The prevalence of metabolic syndrome (MetS) and obesity has increased worldwide, as well as in Taiwan, particularly in women aged>40 years. The purpose of this study was to elucidate the effects of a calorie-restriction diet (CR) supplemented with protein and n-3 polyunsaturated fatty acids (PUFAs) on women with MetS. SUBJECTS/METHODS: A total of 143 eligible female participants were recruited and assigned to four dietary interventions such as 1500-kcal CR, calorie-restriction meal-replacement diet (CRMR), calorie-restriction diet with fish oil supplementation (CRF) and calorie-restriction meal-replacement diet with fish oil supplementation (CRMRF). The changes in anthropometric measures, metabolic profiles, inflammatory response and the Z-score of severity of MetS were evaluated. RESULTS: Among 143 female MetS patients enrolled, 136 patients completed the 12-week study. After the 12-week dietary interventions, we observed reductions in body weight (BW), body mass index (BMI) and waist circumference (WC) in all groups. BMI and triglyceride (TG) levels decreased significantly in the CRMR, CRF and CRMRF groups, but not in the CR group. The homeostasis model assessment of insulin resistance (HOMA-IR) had significantly improved in all four groups, and the levels of interleukin-6 (IL-6) and C-reactive protein (CRP) had significantly decreased in the CRF and CRMRF groups. Following the interventions, the changes in waist circumference (WC), mean arterial pressure (MAP), fasting blood glucose (FBG), TGs, HOMA-IR, CRP and IL-6 significantly correlated with the reductions in Z-score of MetS severity. CONCLUSIONS: Our study results indicate that a calorie-restriction dietary intervention combined with various macronutrients can reduce the severity of MetS in women and increase recovery from MetS by almost twofold in comparison with a CR alone.
Assuntos
Restrição Calórica , Proteínas Alimentares/uso terapêutico , Suplementos Nutricionais , Óleos de Peixe/uso terapêutico , Síndrome Metabólica/dietoterapia , Obesidade/complicações , Adulto , Índice de Massa Corporal , Proteína C-Reativa/metabolismo , Proteínas Alimentares/administração & dosagem , Proteínas Alimentares/farmacologia , Feminino , Óleos de Peixe/farmacologia , Humanos , Resistência à Insulina , Interleucina-6/sangue , Síndrome Metabólica/sangue , Índice de Gravidade de Doença , Circunferência da CinturaRESUMO
The Arabidopsis vacuolar H(+)-pyrophosphatase (AVP1) has been well studied and subsequently employed to improve salt and/or drought resistance in herbaceous plants. However, the exact function of H(+)-pyrophosphatase in woody plants still remains unknown. In this work, we cloned a homolog of type I H(+)-pyrophosphatase gene, designated as PtVP1.1, from Populus trichocarpa, and investigated its function in both Arabidopsis and poplar. The deduced translation product PtVP1.1 shares 89.74% identity with AVP1. Semi-quantitative reverse transcription polymerase chain reaction (RT-PCR) and quantitative real-time PCR analyses revealed a ubiquitous expression pattern of PtVP1.1 in various tissues, including roots, stems, leaves and shoot tips. Heterologous expression of PtVP1.1 rescued the retarded-root-growth phenotype of avp1, an Arabidopsis knock out mutant of AVP1, on low carbohydrate medium. Overexpression of PtVP1.1 in poplar (P. davidianaâ ×â P. bolleana) led to more vigorous growth of transgenic plants in the presence of 150â mM NaCl. Microsomal membrane vesicles derived from PtVP1.1 transgenic plants exhibited higher H(+)-pyrophosphatase hydrolytic activity than those from wild type (WT). Further studies indicated that the improved salt tolerance was associated with a decreased Na(+) and increased K(+) accumulation in the leaves of transgenic plants. Na(+) efflux and H(+) influx in the roots of transgenic plants were also significantly higher than those in the WT plants. All these results suggest that PtVP1.1 is a functional counterpart of AVP1 and can be genetically engineered for salt tolerance improvement in trees.