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2.
Clin Radiol ; 77(3): e241-e249, 2022 03.
Artigo em Inglês | MEDLINE | ID: mdl-35042612

RESUMO

AIM: To assess the predictive value of major adverse cardiac events (MACEs) in patients with acute myocardial infarction (AMI) by T2-mapping texture analysis (TA) of the myocardial remote zone. MATERIALS AND METHODS: Data from 155 patients, who were diagnosed with AMI and were treated with primary percutaneous coronary intervention (PPCI), and 32 healthy controls who underwent cardiac magnetic resonance imaging (CMRI) were analysed retrospectively. T2-mapping TA of the myocardial remote zone was conducted accordingly. The patients were divided into two subgroups according to the occurrence of MACEs. The primary outcome was a composite of MACEs. RESULTS: Among 155 patients, 32 (20.6%) patients suffered MACEs, and the most common event was non-sustained ventricular tachycardia (84.3%). Five independent texture features on T2-mapping were selected: Perc.50%, S(4,-4)AngScMom, S(1,1)InvDfMom, S(0,2)DifEntrp, and Horzl_LngREmph. Among them, the mean value of Horzl_LngREmph in the myocardial remote zone among all patients, MACEsnegative, and MACEs-positive was 21.64, 19.12, and 34.52, respectively. Horzl_LngREmph provided the highest area under the receiver operating characteristic (ROC) curve (AUC) value, which enabled two subgroups to be distinguished (AUC = 0.914, p<0.05). According to the results of the univariate analysis, combined with late gadolinium enhancement (LGE) extent and the presence of left ventricular hypertrophy, Horzl_LngREmph, was strongly associated with the occurrence of MACEs (p<0.05, hazard ratio: 1.64, 95% confidence interval: 1.10-4.51). CONCLUSION: Together with LGE extent, Horzl_LngREmph, a texture feature obtained from T2-mapping TA of the myocardial remote zone, could predict the occurrence of MACEs in AMI patients.


Assuntos
Coração/diagnóstico por imagem , Imageamento por Ressonância Magnética/métodos , Infarto do Miocárdio/diagnóstico por imagem , Idoso , Estudos de Casos e Controles , Feminino , Insuficiência Cardíaca/etiologia , Humanos , Masculino , Pessoa de Meia-Idade , Infarto do Miocárdio/complicações , Infarto do Miocárdio/patologia , Infarto do Miocárdio/cirurgia , Miocárdio/patologia , Intervenção Coronária Percutânea , Valor Preditivo dos Testes , Estudos Retrospectivos , Acidente Vascular Cerebral/etiologia , Taquicardia Ventricular/etiologia
3.
Clin Radiol ; 76(3): 236.e9-236.e19, 2021 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-33272531

RESUMO

AIM: To assess the potential of texture analysis (TA) applied in T1 maps and extracellular volume (ECV) obtained using cardiac magnetic resonance (CMR) in the diagnosis of hypertrophic cardiomyopathy (HCM) and hypertensive heart disease (HHD) compared with normal controls (NC). Strain parameters were analysed to compare with final TA models. MATERIALS AND METHODS: This retrospective study included 66 HCM patients, 39 HHD patients, and 41 NC. Step-wise dimension reduction and feature selection were performed by reproducibility, machine learning, collinearity, and multivariable regression analysis to select the texture features that enable diagnosis of and differentiation between HCM and HHD. Strain parameters were calculated by short-axis and three long-axis cine sequences. RESULTS: Independent features in T1 maps and ECV analysis allowed for the differentiation between patients (HCM and HHD) and NC. Of the best-calculated model, the areas under the receiver operating curve (AUCs) were as follows: 0.969 for T1 map and 0.964 for ECV. To distinguish HCM from HHD, two independent features were screened out for both T1 and ECV maps. The AUCs were as follows: 0.793 for T1 map and 0.894 for ECV. Radial, circumferential, and longitudinal strain parameters could differentiate patients from NC, but only longitudinal strain parameters was significantly different between HCM and HHD. CONCLUSIONS: Texture analysis of T1 maps and ECV shows high accuracy in differentiating hypertrophic myocardium from NC, and HCM from HHD. Strain parameters are able to demonstrate the difference between patients and NC, but were less impressive in differentiating HCM and HHD.


Assuntos
Cardiomiopatia Hipertrófica/diagnóstico por imagem , Hipertensão/diagnóstico , Imageamento por Ressonância Magnética/métodos , Adulto , Cardiomiopatia Hipertrófica/patologia , Feminino , Coração/diagnóstico por imagem , Humanos , Hipertensão/patologia , Masculino , Pessoa de Meia-Idade , Miocárdio/patologia , Reprodutibilidade dos Testes , Estudos Retrospectivos
4.
Clin Biomech (Bristol, Avon) ; 80: 105108, 2020 12.
Artigo em Inglês | MEDLINE | ID: mdl-32736277

RESUMO

BACKGROUND: Cranial pia mater, the innermost layer of the meninges, protects the central nervous system by tightly wrapping the brain and damping the external impact force to the brain. Accurate experimental data of the mechanical property of the cranial pia mater can enhance the theoretical prediction of traumatic brain injury or the scientific surgery design for brain disease. The aim of this study is to characterize the mechanical behavior of the cranial pia mater. METHODS: In vitro tensile and stress-relaxation experiments of ovine cranial pia mater specimens were conducted at eight strain rates to characterize the rate-dependent viscoelastic property. The tensile and stress-relaxation experimental data were fitted by an Ogden hyper-viscoelastic model with a strain rate function to describe the mechanical behavior of the cranial pia mater. FINDINGS: The elastic modulus and the ultimate stress are significantly increased from 5.545 MPa and 0.535 MPa at 0.00167 s-1 to 18.345 MPa and 2.547 MPa at 0.83 s-1 (p < .0001), respectively. The initial stress and the long-term stress (300 s) are also increased significantly with the increasing strain rates (p < .0001). A good fit of the experimental data with the Ogden hyper-viscoelastic model incorporated with a strain rate function was achieved (R2 > 0.93). INTERPRETATION: The cranial pia mater exhibits as a rate-dependent hyper-viscoelastic material in the tensile and stress-relaxation experiments. Compared with the brain, the stiffer nature of the cranial pia mater indicates its essential role in brain protection. The rate-dependent constitutive model provides a proper description of the hyper-viscoelastic characteristics of the cranial pia mater in tension and may provide a basic constitutive relationship for numerical simulations of traumatic brain injury.


Assuntos
Módulo de Elasticidade , Pia-Máter/fisiologia , Estresse Mecânico , Animais , Fenômenos Biomecânicos , Humanos , Ovinos , Viscosidade
5.
Curr Oncol ; 27(3): e259-e264, 2020 06.
Artigo em Inglês | MEDLINE | ID: mdl-32669931

RESUMO

Background: Gastric stump ("remnant") cancer is the development of a malignancy related to previous gastric surgery. Prognosis in gastric stump cancer, compared with that in primary gastric cancer, is still controversial. Methods: From January 1988 to December 2012 at a single medical centre in Taiwan, 105 patients with gastric stump cancer, including 85 with previous peptic ulcer disease and 20 with previous gastric cancer, were analyzed for clinicopathologic characteristics and overall survival (os). Results: The 5-year os rates for patients with gastric stump cancer and with primary gastric cancer were 51.2% and 54.5% respectively (p = 0.035). Analysis of clinicopathologic characteristics indicated that, compared with patients having primary gastric cancer, those with gastric stump cancer had more lymph node metastasis (p < 0.001) and had been diagnosed at a more advanced stage (p = 0.047). Multivariate analysis with os as an endpoint showed that age [p = 0.015; hazard ratio (hr): 2.300; 95% confidence interval (ci): 1.173 to 4.509], tumour size (p = 0.037; hr: 1.700; 95% ci: 1.031 to 2.801), stromal reaction (p = 0.021; hr: 1.802; 95% ci: 1.094 to 2.969), and pathologic N category (p = 0.001; hr: 1.449; 95% ci: 1.161 to 1.807) were independent predictors in gastric stump cancer. The os rates for patients with gastric stump cancer who previously had gastric cancer or peptic ulcer disease were 72.9% and 50.0% respectively (p = 0.019). The Borrmann classification was more superficial (p = 0.005), lymph node metastases were fewer (p = 0.004), and staging was less advanced (p = 0.025) in patients with gastric stump cancer who previously had gastric cancer than in their counterparts who previously had peptic ulcer disease. Conclusions: Survival is poorer in patients with gastric stump cancer who previously had peptic ulcer disease than in those who previously had primary gastric cancer. Patients with gastric stump cancer who previously had gastric cancer and could receive curative gastrectomy tended to have a better prognosis because of a more superficial Borrmann classification. Regular follow-up in patients who have undergone gastric surgery is recommended for the early detection of gastric stump cancer.


Assuntos
Coto Gástrico/fisiopatologia , Neoplasias Gástricas/complicações , Neoplasias Gástricas/cirurgia , Idoso , Feminino , Humanos , Masculino , Prognóstico , Estudos Retrospectivos , Neoplasias Gástricas/mortalidade , Análise de Sobrevida
6.
Folia Biol (Praha) ; 64(3): 103-111, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30394268

RESUMO

Autophagy and poly(ADP-ribose) polymerase 1 (PARP-1) are activated and involved in a series of cell processes under oxidative stress, which is associated with pathogenesis of atherosclerosis. Research on their relationship under oxidative stress has been limited. In this study, we aimed to investigate the activation, relationship, and role of autophagy and PARP-1 in vascular smooth muscle cell (VSMC) death under oxidative stress. This study explored the signal molecule PARP-1 and autophagy in VSMCs using gene silencing and the hydrogen peroxide (H2O2)-stimulated oxidative stress model. We observed that H2O2 could induce autophagy in VSMCs, and the inhibition of autophagy could protect VSMCs against oxidative stress-mediated cell death. Meanwhile, PARP-1 could also be activated by H2O2. Additionally, we analysed the regulatory role of PARP-1 in oxidative stress-mediated autophagy and found that PARP-1 was a novel factor involved in the H2O2-induced autophagy via the AMPK-mTOR pathway. Finally, PARP-1 inhibition protected VSMCs against caspase-dependent apoptosis. These data suggested that PARP-1 played a critical role in H2O2-mediated autophagy and both of them were involved in apoptosis of VSMCs.


Assuntos
Apoptose , Autofagia , Músculo Liso Vascular/patologia , Miócitos de Músculo Liso/metabolismo , Miócitos de Músculo Liso/patologia , Estresse Oxidativo , Poli(ADP-Ribose) Polimerases/metabolismo , Animais , Apoptose/efeitos dos fármacos , Autofagia/efeitos dos fármacos , Caspases/metabolismo , Peróxido de Hidrogênio/toxicidade , Camundongos Endogâmicos C57BL , Miócitos de Músculo Liso/efeitos dos fármacos , Estresse Oxidativo/efeitos dos fármacos
7.
Gene ; 677: 332-339, 2018 Nov 30.
Artigo em Inglês | MEDLINE | ID: mdl-30103007

RESUMO

MicroRNA (miRNA) are endogenous small noncoding RNA gene products, on average 22 nt long, that play important regulatory roles in mediating gene expression by binding to and targeting mRNAs for degradation or translational repression. In this paper we identify both novel and conserved miRNA sequences present in the genome of the gray mouse lemur, Microcebus marinus. In total, 122 conserved and 44 novel miRNA were identified with high confidence from the lemur genome (Mmur_2.0) and were used for expression analysis. All conserved and novel miRNA were subjected to relative quantification by RT-qPCR in liver samples from control and torpid lemurs. A total of 26 miRNA (16 conserved and 10 novel) showed increased levels during primate torpor, whereas 31 (30 conserved and 1 novel) decreased. Additional in silico mapping of the predicted mRNA targets of torpor-responsive mature miRNA suggested that miRNA that increased during torpor were collectively involved in cell development and survival pathways, while miRNA that decreased were enriched in targeting immune function. Overall, the study suggests new regulatory mechanisms of primate torpor via miRNA action.


Assuntos
Cheirogaleidae/genética , Sequência Conservada/genética , Lemur/genética , MicroRNAs/genética , Torpor/genética , Animais , Fígado/metabolismo , Biossíntese de Proteínas/genética , RNA Mensageiro/genética
8.
Clin Otolaryngol ; 43(4): 1065-1072, 2018 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-29575557

RESUMO

OBJECTIVES: Ultrasound-guided aspiration cytology (US-FNAC) was previously used to diagnose lymph node metastasis of papillary thyroid carcinoma (PTC). Combined US-FNAC with nodal thyroglobulin (LN-FNA-Tg) significantly improved the diagnostic rate. However, diagnostic accuracy depends on proper node selection. Therefore, it is crucial to choose the nodes with reliable sonographic features to guide clinician for confirmation. DESIGN AND SETTING: Retrospective cohort study was carried out in one medical centre from 2011 to 2014. PARTICIPANTS: A total of 148 patients with PTC, being treated by total thyroidectomy and radioiodine, were assessed for potential nodal metastases by ultrasound. MAIN OUTCOME MEASURES: Lymph nodes with cystic content, peripheral hypervascularity, calcification, hyperechoic content, the absence of hilum and Solbiati index < 2 indicated risk of malignancy. US-FNAC and LN-FNA-Tg were both performed. Positive nodal metastasis was further confirmed by dissection. Risk impact of these sonographic features on LN-FNA-Tg to diagnose nodal metastasis was tested by logistic regression analysis based on the significance in both univariate and multivariate models. RESULTS: Overall, 49 lymph nodes were documented as recurrent nodal metastasis. LN-FNA-Tg greater than serum thyroglobulin and higher than 1 ng/mL achieved 100% of diagnostic rate for recurrent nodal metastasis. The malignant sonographic features that significantly cohered with positive LN-FNA-Tg were cystic and hyperechoic content and lack hilum, in sequence. CONCLUSIONS: LN-FNA-Tg is an excellent tool to quantitatively diagnose nodal metastasis. To achieve ideal diagnosis, the most reliable sonographic features were cystic content, hyperechoic content and the absence of hilum in lymph nodes, but not calcification or Solbiati index < 2.

9.
J Appl Microbiol ; 123(3): 594-601, 2017 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-28688204

RESUMO

AIMS: The purpose of this study was to produce a recombinant pseudorabies virus (PRV) glycoprotein E (gE) protein with the correct antigenicity for use as a low-cost diagnostic antigen. METHODS AND RESULTS: The gene fragment encoding the amino-terminal immunodominant region of PRV gE (codons 31-270) (gEN31-270) was codon optimized and expressed constitutively and secreted using a Pichia pastoris expression system. Yeast-expressed gEN31-270 (ygEN31-270) was harvested from the culture supernatant, and ygEN31-270 was shown to exhibit N-linked glycosylation. An indirect sandwich enzyme-linked immunosorbent assay (ELISA) was developed using ygEN31-270 as a coating antigen, and the results showed that the assay had high sensitivity and specificity, as well as almost perfect concordance with a commercial gE ELISA kit. CONCLUSIONS: The immunodominant region (amino acids 31-270) of gE was expressed successfully in P. pastoris using a codon optimization strategy. ygEN31-270 was secreted and N-glycosylated. The ygEN31-270-based indirect sandwich ELISA showed high sensitivity and specificity to detect gE-specific antibodies in swine serum samples. SIGNIFICANCE AND IMPACT OF THE STUDY: The ygEN31-270-based indirect sandwich ELISA may provide an alternative method for developing a diagnostic kit with easy manipulation and low cost.


Assuntos
Ensaio de Imunoadsorção Enzimática/métodos , Herpesvirus Suídeo 1/isolamento & purificação , Pichia/genética , Pseudorraiva/diagnóstico , Proteínas do Envelope Viral/análise , Animais , Anticorpos Antivirais/análise , Anticorpos Antivirais/sangue , Glicosilação , Herpesvirus Suídeo 1/genética , Herpesvirus Suídeo 1/imunologia , Pichia/metabolismo , Pseudorraiva/sangue , Pseudorraiva/virologia , Proteínas Recombinantes/análise , Proteínas Recombinantes/genética , Proteínas Recombinantes/imunologia , Sensibilidade e Especificidade , Suínos , Proteínas do Envelope Viral/classificação , Proteínas do Envelope Viral/genética , Proteínas do Envelope Viral/imunologia
10.
Oncogene ; 36(21): 2946-2956, 2017 05 25.
Artigo em Inglês | MEDLINE | ID: mdl-28092674

RESUMO

Aberrant epidermal growth factor (EGF) receptor (EGFR) signaling contributes to neoplastic initiation and progression in lung. Mutated EGFR has become as an important therapeutic target in lung cancer, whereas targeted treatment is not available for wild-type EGFR or its ligands. In this study, we found that heparin-binding (HB)-EGF, a member of the EGF family, was highly expressed in a subset of lung cancer, proliferation of which was dependent on HB-EGF signaling. Silencing of HB-EGF with RNA interference inhibited cell cycle progression in lung cancer cells. We observed that, upon HB-EGF induction, CITED4 was induced through a signal transducer and activator of transcription 3 (STAT3)-dependent pathway, regulating cell proliferation. CITED4 interacted with MYC and potentiated MYC-mediated transactivation of the CCND1 promoter, leading to cell cycle progression. Correlation analysis revealed that HB-EGF and CITED4 were significantly positively associated in primary lung tumors, and expression of HB-EGF predicted a poor survival outcome in patients. In vitro and in vivo experiments revealed that pharmacological inhibition of HB-EGF with CRM197 significantly attenuated tumor cell growth. Thus, CITED4 functions as a molecular switch in HB-EGF-induced growth control, and HB-EGF provides a novel therapeutic target for lung cancer intervention.


Assuntos
Carcinogênese/genética , Carcinoma Pulmonar de Células não Pequenas/genética , Fator de Crescimento Semelhante a EGF de Ligação à Heparina/fisiologia , Neoplasias Pulmonares/genética , Fatores de Transcrição/fisiologia , Células A549 , Animais , Antineoplásicos/farmacologia , Antineoplásicos/uso terapêutico , Carcinogênese/efeitos dos fármacos , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Carcinoma Pulmonar de Células não Pequenas/patologia , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Proliferação de Células/genética , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Células HEK293 , Fator de Crescimento Semelhante a EGF de Ligação à Heparina/genética , Humanos , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/patologia , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Nus , Terapia de Alvo Molecular , Transdução de Sinais/efeitos dos fármacos , Transdução de Sinais/genética , Fatores de Transcrição/antagonistas & inibidores , Fatores de Transcrição/genética , Ensaios Antitumorais Modelo de Xenoenxerto
11.
J Nanosci Nanotechnol ; 16(4): 4141-6, 2016 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-27451778

RESUMO

Prussian blue (PB) nanoparticles, one of many cyano-bridged coordination polymers, are successfully incorporated into chitosan (CS) polymer to prepare PB/CS mixed matrix membranes (MMMs). The PB nanoparticles are uniformly distributed in the MMMs without the collapse of the original PB structure. As-prepared PB/CS MMMs are used for ethanol dehydration at 25 °C in the pervaporation process. The effect of loading PB in CS matrix on pervaporation performance is carefully investigated. The PB/CS membrane with 30 wt% PB loading shows the best performance with a permeate flux of 614 g. m-2 . h-1 and a separation factor of 1472. The pervaporation using our PB/CS membranes exhibits outstanding performance in comparison with the previously reported CS-based membranes and MMMs. Furthermore, the addition of PB allows PB/CS MMMs to be tolerant of acidic environment. The present work demonstrates good pervaporation performance of PB/CS MMMs for the separation of an ethanol/water (90:10 in wt%) solution. Our new system provides an opportunity for dehydration of bioethanol in the future.


Assuntos
Quitosana/química , Etanol/isolamento & purificação , Ferrocianetos/química , Membranas Artificiais , Nanopartículas/química , Água/química , Dessecação/métodos , Etanol/química , Teste de Materiais , Polímeros/química
12.
Opt Express ; 23(24): 30641-50, 2015 Nov 30.
Artigo em Inglês | MEDLINE | ID: mdl-26698696

RESUMO

We report on the realization of adiabatic light transfer in lithium niobate (LiNbO3) waveguides. This peculiar adiabatic tunneling scheme was implemented in a three-waveguide coupling configuration with the intermediate waveguide being inclined with respect to the outer waveguides to facilitate the adiabatic passage process. We have investigated and determined the adiabatic conditions of the LiNbO3 device in terms of the structure configuration of the waveguide system and found optimal structure parameters by both simulation and experimental approaches. Broadband adiabatic couplings of bandwidth ~456 and 185 nm and peak coupling efficiencies of >0.96 have been obtained with a 2-cm long device for TE- and TM-polarized fundamental modes, respectively. Longer (5 cm) devices were also studied and found to be useful in increasing the adiabaticity of the device, especially for the TM-polarized mode.

13.
Compr Psychiatry ; 62: 80-5, 2015 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-26343470

RESUMO

OBJECTIVES: Psychotic symptoms are commonly observed among heroin users. Low serum brain-derived neurotrophic factor (BDNF) levels have been reported in schizophrenia and psychosis; however, studies assessing the relationship between serum BDNF levels and psychotic symptoms in heroin dependence are lacking. METHOD: A total of 31 heroin-dependent patients who had never experienced psychotic symptoms during heroin consumption and 21 patients with a history of psychotic symptoms were consecutively recruited. We measured by enzyme-linked immunosorbent assay (ELISA) serum BDNF levels during early abstinence. A gender- and age-matched sample of healthy controls was also recruited and underwent measurement of BDNF. RESULTS: BDNF levels were significantly lower in patients with psychotic symptoms than in those without psychotic symptoms (P<0.001). BDNF levels were not found to be correlated with sex, age, age of onset, duration of heroin use, average daily dose of heroin use, frequency of heroin use, SDS scores, BAI scores and BDI scores in the psychotic subsamples (all P>0.05). CONCLUSIONS: Our findings suggest that heroin-dependent patients with psychotic symptoms share some of the neurotrophic insult that characterizes schizophrenia and psychosis.


Assuntos
Fator Neurotrófico Derivado do Encéfalo/sangue , Dependência de Heroína/sangue , Dependência de Heroína/psicologia , Transtornos Psicóticos/sangue , Transtornos Psicóticos/complicações , Adulto , Estudos de Casos e Controles , Feminino , Dependência de Heroína/complicações , Humanos , Masculino , Pessoa de Meia-Idade , Transtornos Psicóticos/psicologia
14.
Oncogene ; 34(29): 3791-803, 2015 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-25263444

RESUMO

Epidermal growth factor receptor (EGFR) regulates multiple signaling cascades essential for cell proliferation, growth and differentiation. Using a genetic approach, we found that Drosophila FERM and PDZ domain-containing protein tyrosine phosphatase, dPtpmeg, negatively regulates border cell migration and inhibits the EGFR/Ras/mitogen-activated protein kinase signaling pathway during wing morphogenesis. We further identified EGFR pathway substrate 15 (Eps15) as a target of dPtpmeg and its human homolog PTPN3. Eps15 is a scaffolding adaptor protein known to be involved in EGFR endocytosis and trafficking. Interestingly, PTPN3-mediated tyrosine dephosphorylation of Eps15 promotes EGFR for lipid raft-mediated endocytosis and lysosomal degradation. PTPN3 and the Eps15 tyrosine phosphorylation-deficient mutant suppress non-small-cell lung cancer cell growth and migration in vitro and reduce lung tumor xenograft growth in vivo. Moreover, depletion of PTPN3 impairs the degradation of EGFR and enhances proliferation and tumorigenicity of lung cancer cells. Taken together, these results indicate that PTPN3 may act as a tumor suppressor in lung cancer through its modulation of EGFR signaling.


Assuntos
Carcinoma Pulmonar de Células não Pequenas/metabolismo , Movimento Celular , Proliferação de Células , Receptores ErbB/metabolismo , Neoplasias Pulmonares/metabolismo , Proteína Tirosina Fosfatase não Receptora Tipo 3/metabolismo , Proteínas Adaptadoras de Transdução de Sinal/genética , Proteínas Adaptadoras de Transdução de Sinal/metabolismo , Animais , Animais Geneticamente Modificados , Carcinoma Pulmonar de Células não Pequenas/genética , Carcinoma Pulmonar de Células não Pequenas/patologia , Linhagem Celular , Linhagem Celular Tumoral , Endocitose , Feminino , Células HEK293 , Humanos , Immunoblotting , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/patologia , Masculino , Microdomínios da Membrana/metabolismo , Camundongos Endogâmicos BALB C , Camundongos Nus , Microscopia Confocal , Mutação , Fosforilação , Proteína Tirosina Fosfatase não Receptora Tipo 3/genética , Interferência de RNA , Transplante Heterólogo
15.
J Clin Pharm Ther ; 40(2): 240-4, 2015 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-25487647

RESUMO

WHAT IS KNOWN AND OBJECTIVE: Dosage adjustment of 500 mg ertapenem daily is recommended for patients with advanced kidney disease. 30% of ertapenem is cleared by a session of haemodialysis (HD). However, because most published carbapenems studies have excluded patients on dialysis, little is known about the dosing of ertapenem to avoid central nervous system (CNS) toxicity in regular HD patients. We report of four patients who developed CNS toxicity in such patients. CASE SUMMARY: The 4 HD patients developed unexplained CNS toxicity manifested as seizures, hallucination and cognitive dysfunction after receiving 3-7 consecutive recommended doses of ertapenem. Their symptoms of CNS toxicity were completely resolved within 8 days after discontinuation of ertapenem. In one of our presented cases, we demonstrated the very high level of plasma ertapenem accumulating with several consecutive doses. Cognitive function gradually recovered in line with a corresponding decline in blood level of ertapenem. WHAT IS NEW AND CONCLUSIONS: This is the first report of ertapenem-associated CNS toxicity in patients on regular HD and utilizing the plasma ertapenem concentration to demonstrate the causal relationship. The recommended dosage of 500 mg ertapenem daily may be still too high in regular HD patients, especially in Asians, owing to their relatively small body size. An increased awareness of ertapenem-associated CNS toxicity would avoid unnecessary examinations, hospitalization, and potentially catastrophic complications.


Assuntos
Antibacterianos/efeitos adversos , Antibacterianos/farmacocinética , Doenças do Sistema Nervoso Central/induzido quimicamente , Diálise Renal , beta-Lactamas/efeitos adversos , beta-Lactamas/farmacocinética , Idoso , Povo Asiático , Relação Dose-Resposta a Droga , Ertapenem , Feminino , Humanos , Masculino , Insuficiência Renal
16.
Br J Cancer ; 111(9): 1765-71, 2014 Oct 28.
Artigo em Inglês | MEDLINE | ID: mdl-25233396

RESUMO

BACKGROUND: The detection of microRNA (miRNA) dysregulation in stool is a novel approach for the diagnosis of colorectal carcinoma (CRC). The aim of this study is to investigate the use of miR-221 and miR-18a in stool samples as non-invasive biomarkers for CRC diagnosis. METHODS: A miRNA expression array containing 667 miRNAs was performed to identify miRNA dysregulation in CRC tissues. We focused on miR-221 and miR-18a, two significantly upregulated miRNAs which were subsequently verified in 40 pairs of CRC tissues and 595 stool samples (198 CRCs, 199 polyps and 198 normal controls). RESULTS: miR-221 and miR-18a were upregulated in the miRNA expression array. miR-221 and miR-18a levels were also significantly higher in 40 CRC tumours compared with their respective adjacent normal tissues. In stool samples, miR-221 and miR-18a showed a significant increasing trend from normal controls to late stages of CRC (P<0.0001). The levels of stool miR-221 and miR-18a were both significantly higher in subjects with stages I+II (miR-221: P<0.0001, miR-18a: P<0.0001) and stages III+IV of CRC (miR-221: P=0.0004, miR-18a: P<0.0001) compared with normal controls. The AUC of stool miR-221 and miR-18a were 0.73 and 0.67 for CRC patients as compared with normal controls, respectively. No significant differences in stool miR-221 and miR-18a levels were found between patients with proximal and distal CRCs. The use of antibiotics did not influence stool miRNA-221 and miRNA-18a levels. CONCLUSIONS: Stool-based miR-221 can be used as a non-invasive biomarker for the detection of CRC.


Assuntos
Biomarcadores Tumorais/genética , Neoplasias Colorretais/diagnóstico , Neoplasias Colorretais/genética , Fezes/química , MicroRNAs/genética , Idoso , Estudos de Casos e Controles , Feminino , Seguimentos , Perfilação da Expressão Gênica , Regulação Neoplásica da Expressão Gênica , Humanos , Masculino , Pessoa de Meia-Idade , Análise de Sequência com Séries de Oligonucleotídeos , Prognóstico , Curva ROC
17.
J Virol ; 88(18): 10662-72, 2014 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-24991008

RESUMO

UNLABELLED: Undifferentiated nasopharyngeal carcinoma (NPC) has a 100% association with Epstein-Barr virus (EBV). However, only three EBV genomes isolated from NPC patients have been sequenced to date, and the role of EBV genomic variations in the pathogenesis of NPC is unclear. We sought to obtain the sequences of EBV genomes in multiple NPC biopsy specimens in the same geographic location in order to reveal their sequence diversity. Three published EBV (B95-8, C666-1, and HKNPC1) genomes were first resequenced using the sequencing workflow of target enrichment of EBV DNA by hybridization, followed by next-generation sequencing, de novo assembly, and joining of contigs by Sanger sequencing. The sequences of eight NPC biopsy specimen-derived EBV (NPC-EBV) genomes, designated HKNPC2 to HKNPC9, were then determined. They harbored 1,736 variations in total, including 1,601 substitutions, 64 insertions, and 71 deletions, compared to the reference EBV. Furthermore, genes encoding latent, early lytic, and tegument proteins and glycoproteins were found to contain nonsynonymous mutations of potential biological significance. Phylogenetic analysis showed that the HKNPC6 and -7 genomes, which were isolated from tumor biopsy specimens of advanced metastatic NPC cases, were distinct from the other six NPC-EBV genomes, suggesting the presence of at least two parental lineages of EBV among the NPC-EBV genomes. In conclusion, much greater sequence diversity among EBV isolates derived from NPC biopsy specimens is demonstrated on a whole-genome level through a complete sequencing workflow. Large-scale sequencing and comparison of EBV genomes isolated from NPC and normal subjects should be performed to assess whether EBV genomic variations contribute to NPC pathogenesis. IMPORTANCE: This study established a sequencing workflow from EBV DNA capture and sequencing to de novo assembly and contig joining. We reported eight newly sequenced EBV genomes isolated from primary NPC biopsy specimens and revealed the sequence diversity on a whole-genome level among these EBV isolates. At least two lineages of EBV strains are observed, and recombination among these lineages is inferred. Our study has demonstrated the value of, and provided a platform for, genome sequencing of EBV.


Assuntos
Variação Genética , Herpesvirus Humano 4/genética , Herpesvirus Humano 4/isolamento & purificação , Neoplasias Nasofaríngeas/virologia , Adulto , Sequência de Bases , Biópsia , Carcinoma , Feminino , Genoma Viral , Herpesvirus Humano 4/classificação , Humanos , Masculino , Pessoa de Meia-Idade , Dados de Sequência Molecular , Mutagênese Insercional , Carcinoma Nasofaríngeo , Filogenia , Deleção de Sequência , Adulto Jovem
18.
Mitochondrial DNA ; 25(5): 351-2, 2014 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-23815319

RESUMO

In this study, we cloned and sequenced the complete mitochondrial genome of Abramis brama orientalis Berg. The genome was 16,610 bp (LR) in length and consisted of 13 protein-coding genes, 22 tRNA genes, 2 ribosomal RNA genes and 2 main non-coding regions [the control region (CR) and the origin of the light strand replication], the gene composition and order of which was similar to those reported from other fish mitochondrial genomes. The overall base composition of the heavy strand was T 26.7%, C 26.5 %, A 30.0% and G 16.8%, with a slight A+T bias of 56.7%. This mitogenome sequence data would play an important role in population genetics and phylogenetic analysis of the Leuciscinae.


Assuntos
Cipriniformes/genética , Genoma Mitocondrial , Análise de Sequência de DNA/métodos , Animais , Composição de Bases , Clonagem Molecular , Genes , Genética Populacional , Dados de Sequência Molecular , Filogenia
19.
Genet Mol Res ; 12(3): 3755-65, 2013 Sep 19.
Artigo em Inglês | MEDLINE | ID: mdl-24085437

RESUMO

Octopus in the family Octopodidae (Mollusca: Cephalopoda) has been generally recognized as a "catch-all" genus. The monophyly of octopus species in China's coastal waters has not yet been studied. In this paper, we inferred the phylogeny of 11 octopus species (family Octopodidae) in China's coastal waters using nucleotide sequences of two mitochondrial DNA genes: cytochrome c oxidase subunit I (COI) and 16S rRNA. Sequence analysis of both genes revealed that the 11 species of Octopodidae fell into four distinct groups, which were genetically distant from one another and exhibited identical phylogenetic resolution. The phylogenies indicated strongly that the genus Octopus in China's coastal waters is also not monophyletic, and it is therefore clear that the Octopodidae systematics in this area requires major revision. It is demonstrated that partial sequence information of both the mitochondrial genes 16S rRNA and COI could be used as diagnostic molecular markers in the identification and resolution of the taxonomic ambiguity of Octopodidae species.


Assuntos
DNA Mitocondrial/genética , Octopodiformes/classificação , Octopodiformes/genética , Filogenia , Animais , Sequência de Bases , China , Complexo IV da Cadeia de Transporte de Elétrons/genética , Dados de Sequência Molecular , RNA Ribossômico 16S/genética , Alinhamento de Sequência , Análise de Sequência de DNA
20.
Genet Mol Res ; 12(3): 2670-3, 2013 Jul 30.
Artigo em Inglês | MEDLINE | ID: mdl-23979892

RESUMO

Twelve new polymorphic microsatellite loci were developed for the hard-shelled mussel, Mytilus coruscus. In 32 individuals from a wild population of coastal Zhoushan, Zhejiang Province, China, the number of alleles at these loci varied from 3 to 15, with a mean of 5.667. The mean observed and expected heterozygosities were 0.6927 and 0.6591, respectively. Among these polymorphic microsatellite loci, three (MC42, MC129, and MC180) significantly deviated from Hardy-Weinberg equilibrium after sequential Bonferroni's correction. All other microsatellite loci were in linkage equilibrium. These microsatellite loci will be useful for detecting genetic differences and for planning aquaculture management of M. coruscus.


Assuntos
Repetições de Microssatélites , Mytilus/genética , Alelos , Animais , Variações do Número de Cópias de DNA , Loci Gênicos , Marcadores Genéticos , Desequilíbrio de Ligação
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