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1.
Clin Radiol ; 79(6): e842-e853, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38582632

RESUMO

AIM: We design a feasibility study to obtain a set of metabolic-hemodynamic habitats for tackling tumor spatial metabolic patterns with hemodynamic information. MATERIALS AND METHODS: Preoperative data from 69 high-grade gliomas (HGG) patients with subsequent histologic confirmation of HGG were prospectively collected (January 2016 to March 2020) after concurrent chemoradiotherapy (CCRT). Four vascular habitats were automatically segmented by multiparametric magnetic resonance imaging (MRI). The metabolic information, either at enhancing or edema tumor regions, was obtained by two neuroradiologists. The relative habitat volumes were used for weight estimation procedures for computing the coefficients of a linear regression model using weighted least squares (WLS) for metabolite semiquantifications (i.e. the Cho/NAA ratio and the Cho/Cr ratio) at vascular habitats. Multivariate Cox proportional hazard regression analyses are used to obtain the odds ratio (OR) and develop a nomogram using weighted estimators corresponding to each covariate derived from Cox regression coefficients. RESULTS: There was a strongly correlation between perfusion indexes and the Cho/Cr ratio (rCBV, r=0.71) or Cho/NAA ratio (rCBV, r=0.66) at high-angiogenic enhancing tumor habitats (HAT) habitat. Compared isocitrate dehydrogenase (IDH) mutation to their wild type, the IDH wild type had significantly decreased Cho/Cr ratio (IDH mutation: Cho/Cr ratio = 2.44 ± 0.33, IDH wildtype: Cho/Cr ratio = 2.66 ± 0.36, p=0.02) and Cho/NAA ratio (IDH mutation: Cho/Cr ratio = 4.59 ± 0.61, IDH wildtype: Cho/Cr ratio = 4.99 ± 0.66, p=0.022) at the HAT. The C-index for the median progression-free survival (PFS) prediction was 0.769 for the Cho/NAA nomogram and 0.747 for the Cho/Cr nomogram through 1000 bootstrapping validation. CONCLUSIONS: Our findings suggest that spatial metabolism combined with hemodynamic heterogeneity is associated with individual PFS to HGG patients post-CCRT.


Assuntos
Neoplasias Encefálicas , Estudos de Viabilidade , Glioma , Hemodinâmica , Intervalo Livre de Progressão , Humanos , Glioma/diagnóstico por imagem , Glioma/patologia , Glioma/terapia , Feminino , Masculino , Neoplasias Encefálicas/diagnóstico por imagem , Neoplasias Encefálicas/terapia , Neoplasias Encefálicas/patologia , Pessoa de Meia-Idade , Hemodinâmica/fisiologia , Adulto , Estudos Prospectivos , Idoso , Imageamento por Ressonância Magnética Multiparamétrica/métodos
2.
Zhonghua Wai Ke Za Zhi ; 60(4): 343-350, 2022 Apr 01.
Artigo em Zh | MEDLINE | ID: mdl-35272425

RESUMO

Biliary tract cancer has insidious onset and high degree of malignancy, and radical resection is often impossible when it is diagnosed.Conversion therapy can achieve tumor downgrading, so that patients who were initially unresectable have a chance to achieve R0 resection.However, due to the high heterogeneity and complex immune microenvironment of biliary tract cancer, conversion therapy is still in the stage of active exploration.As a new type of conversion therapy, combination of targeted therapy and immunotherapy is of great significance to effectively improve the efficiency of conversion therapy.Further exploration of combination mechanism and improvement of immune microenvironment are expected to become the future direction of combination of targeted therapy and immunotherapy.


Assuntos
Neoplasias do Sistema Biliar , Protocolos de Quimioterapia Combinada Antineoplásica , Neoplasias do Sistema Biliar/cirurgia , Terapia Combinada , Gastrectomia , Humanos , Imunoterapia , Microambiente Tumoral
3.
Zhonghua Wai Ke Za Zhi ; 59(4): 260-264, 2021 Apr 01.
Artigo em Zh | MEDLINE | ID: mdl-33706442

RESUMO

Biliary tract cancer is found in the middle and advanced stages mostly and patients will deprive surgical indications. Conversion therapy can make the stage of some patients down and thus make radical resection feasible. Biliary tract cancer is highly heterogeneous in clinical features, cell origin, histology, molecular biology and other aspects, resulting in a lack of specific and effective conversion therapy strategies. Currently, it is the important development direction to evaluate and classify different individual conditions and select individualized conversion therapy regimens. With the deepening of the research on the pathogenesis and the improvement of treatment protocols, the future conversion therapy will undoubtedly develop towards the direction of individualization and precision.

4.
Zhonghua Yi Xue Za Zhi ; 100(4): 261-264, 2020 Feb 04.
Artigo em Zh | MEDLINE | ID: mdl-32075352

RESUMO

Objective: To analysis of the efficacy of tubular paraspinal approach and conventional semi-laminar approach in treating lumbar stenosis. Methods: Retrospective research of clinical data of 56 lumbar stenosis cases who were operated in neurosurgery department of first center of PLA general hospital from May 2015 to June 2018. Collecting the information of sex, age, operating time, intraoperative blood loss, postoperative duration in bed, as well as length of hospital stay of those patients. The 2 groups of cases, tubular paraspinal approach group (n=35)and semi-laminal approachgroup (n=21), compared by Japanese orthopedic association (JOA) score and visual analogue scale to assess the functional situation of the patients before operation, 1 week after operation, 1 month after operation, 6 months after operation, and the last follow up. Results: The operating time(83.1±7.3 vs 86.1±9.6 min), intraoperative blood loss(18.2±3.9 vs 40.5±13.3 ml), postoperative duration in bed(37.4±7.8 vs 63.7±15.8 h), as well as length of hospital stay (3.8±1.1 vs 6.5±2.0 d)were all obviously better in tubular paraspinal approach group than in traditional semi-laminar approach group(P<0.05). The postoperative 1 week, 1month, and 6 months JOA score (21.8±3.4, 23.6±2.4, 24.2±2.4 vs 19.9±3.7, 21.6±2.8, 22.4±2.1)and VAS (2.2±1.0, 2.0±1.1, 0.4±0.1 vs 3.1±1.2, 2.6±1.3, 0.5±0.1) were better in tubular paraspinal approach group than semi-laminar approach group (P<0.05). While at the last follow up, the JOA score and VAS were similar in the 2 groups (P>0.05) . Conclusions: In non-fusion techniques for treating lumbar stenosis, tubular paraspinal approach demonstrated less blood loss, shorter stay in bed as well as in hospital, and better symptom relief in early postoperative period than traditional semi-laminal approach. While at long term follow up, both approaches achieved satisfactory outcome.


Assuntos
Fusão Vertebral , Constrição Patológica , Humanos , Vértebras Lombares , Região Lombossacral , Estudos Retrospectivos , Resultado do Tratamento
5.
Zhonghua Wai Ke Za Zhi ; 58(4): 280-283, 2020 Apr 01.
Artigo em Zh | MEDLINE | ID: mdl-32241057

RESUMO

Hepatitis B is a common and multiplex disease in China. Recently, epidemiological studies have shown that hepatitis B virus(HBV) infection is a high-risk factor for the development of intrahepatic cholangiocarcinoma(ICC). Based on a retrospective analysis of relevant literature of recent years, this article concludes that HBV-associated ICC is very different from other ICC regarding clinicopathological characteristics and treatment. Distinctive features of patients with HBV-associated ICC included younger age, preponderance of male patients, frequent elevation of alpha fetoprotein, decrease of CA19-9, frequent appearance of cirrhosis, infrequent lymph node metastasis and better prognosis. Because these clinicopathological features are similar to those of HBV-associated hepatocellular carcinoma(HCC), we speculate that the cell origin of HBV-associated ICC and HBV-associated HCC are consistent. In addition, this article also discusses that HBV-associated ICC should be treated with surgery-based comprehensive treatment in order to improve prognosis.


Assuntos
Neoplasias dos Ductos Biliares/virologia , Carcinoma Hepatocelular/virologia , Colangiocarcinoma/virologia , Hepatite B/complicações , Neoplasias Hepáticas/virologia , China , Vírus da Hepatite B , Humanos , Masculino , Estudos Retrospectivos , Fatores de Risco
6.
Insect Mol Biol ; 28(4): 550-567, 2019 08.
Artigo em Inglês | MEDLINE | ID: mdl-30739379

RESUMO

The cotton mealybug Phenacoccus solenopsis Tinsley (Hemiptera: Pseudococcidae) is a polyphagous insect that attacks tens of plant and causes substantial economic loss. Insect chitinases are required to remove the old cuticle to allow for continued growth and development. Though insect chitinases have been well studied in tens of insects, their functions in mealybug are still not addressed. Here, we sequenced the transcriptomes of adult males and females, from which eight chitinase genes were identified. We then used the method of rapid amplification of cDNA ends to amplify their full length. Phylogenetic analysis indicated that these genes clustered into five subgroups. Among which, group II PsCht2 had the longest transcript and was highly expressed at second instar nymph. PsCht10, PsCht3-3 and PsIDGF were highly expressed in the adult females, whereas PsCht4 and PsCht4-1 were significantly expressed at the male pupa and adult male. Next, we knocked down all eight chitinase genes by feeding the double-stranded RNA. Knockdown of PsCht4 or PsCht4-1 led to the failure of moult and, silencing PsCht5 resulted in pupation defect, while silencing PsCht10 led to small body size, suggesting these genes have essential roles in development and can be used as a potential target for pest control.


Assuntos
Quitinases/genética , Hemípteros/genética , Proteínas de Insetos/genética , Muda/genética , Transcriptoma , Sequência de Aminoácidos , Animais , Quitinases/química , Quitinases/metabolismo , Feminino , Hemípteros/enzimologia , Hemípteros/crescimento & desenvolvimento , Hemípteros/metabolismo , Proteínas de Insetos/química , Proteínas de Insetos/metabolismo , Masculino , Ninfa/enzimologia , Ninfa/genética , Ninfa/crescimento & desenvolvimento , Ninfa/metabolismo , Filogenia , Alinhamento de Sequência , Caracteres Sexuais , Fatores Sexuais
8.
Hong Kong Med J ; 29(2): 174.e1-174.e3, 2023 04.
Artigo em Inglês | MEDLINE | ID: mdl-37088704
9.
Zhonghua Yu Fang Yi Xue Za Zhi ; 52(10): 1023-1028, 2018 Oct 06.
Artigo em Zh | MEDLINE | ID: mdl-30392321

RESUMO

Objective: This study was designed to identify the relative factors, bacteriological profile and their antibiotic susceptibility pattern of neonatal sepsis. Methods: A retrospective survey was conducted on the clinical information, pathogen identification and antibiotic sensitivity results of 425 newborns with neonatal sepsis admitted to Nanjing Maternity and Child Health Care Hospital from 2010 to 2017. Of the 425 positive blood-cultures, 148 (34.82%) were early-onset neonatal sepsis (EOS) and 277 (65.18%) were late-onset neonatal sepsis (LOS). Clinical information and pathogen identification were compared between EOS and LOS. Antibiotic sensitivity of gram negative organisms (G(-)) and gram positive organisms (G(+)) were also detected. Results: The rates of premature delivery (78.70%, n=218), low birth weights (67.15%, n=186) and cesarean delivery (59.57%, n=165) were significantly increased in LOS (P<0.05) compared with those rates in EOS, which were 41.89% (n=62), 37.84% (n=56) and 46.62% (n=69). Parturients fever (18.24%, n=27) and meconium like amniotic fluid (25.68%, n=38) were significantly increased in EOS (P<0.05) compared with those rates in LOS, which were 7.94% (n=22) and 5.42% (n=15). Among the identified pathogen, the incidence of G(-) and G(+) bacteria were 216 (50.83%) and 201 (47.29%) respectively, and the rest was Candida glabrata (1.88%, n=8). Escherichia coli 68 (16.00%) was the predominant isolate followed by Klebsiella pneumoniae (13.18%, n=56). The detection rate of Hemolytic staphylococcus (10.81%, n=16) was significantly increased in EOS (P<0.001) compared with LOS (1.44%, n=4). However, the incidence of Klebsiella pneumonia (5.88%, n=44) was higher in LOS (P=0.024) compared with EOS (8.11%, n=12). Most of the gram positive isolates exhibited high resistance to penicillin (90.32%-100.00%) and cephalosporin group antibiotics (25.00%-100.00%). Similarly, the majority of the gram negative isolates showed higher resistance to ampicillin (83.33%-100.00%), but susceptible to aminoglycosides (0-11.76%), quinolones (0-17.65%) and ß-lactams (0-5.88%). Conclusion: Among the study population, the percent of preterm, low birth weight and cesarean section were higher in LOS while parturients fever and meconium-like amniotic fluid were higher in EOS. The pathogens with the highest detection rate were Escherichia coli and Klebsiella pneumoniae. The results of antibiotic susceptibility test showed that common pathogens had high resistance to commonly used antibacterial drugs.


Assuntos
Farmacorresistência Bacteriana , Sepse Neonatal , Feminino , Humanos , Recém-Nascido , Testes de Sensibilidade Microbiana , Gravidez , Estudos Retrospectivos , Fatores de Risco
10.
Inorg Chem ; 56(9): 4990-4995, 2017 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-28406625

RESUMO

Double-ReO3-type structure compound NaSbF6 undergoes a low-temperature rhombohedral to high-temperature cubic phase between 303 and 323 K, as revealed by temperature-dependent X-ray diffractions. Although many double-ReO3-type fluorides exhibit either low thermal expansion or negative thermal expansion (NTE), NaSbF6 exhibits positive thermal expansion (PTE) with a large volumetric coefficient of thermal expansion, αv = 62 ppm/K, in its cubic phase. Raman spectroscopy reveals that the low-frequency transverse vibration of fluorine atoms is stiffened in NaSbF6, compared with the typical NTE compound CaZrF6 with the same structure. The related weak contraction associated with the polyhedral rocking would be overcome by the notable elongation of the Na-F bond length on heating, thus leading to the large volumetric PTE. Unlike ScF3 and CaZrF6 which are insulators with a wide band gap, a relative small band gap of 3.76 eV was observed in NaSbF6. The small band gap can be attributed to the hybridization between the Sb 5s and F 2p orbitals.

12.
Artigo em Zh | MEDLINE | ID: mdl-28241698

RESUMO

Objective: To explore prognostic factors of acute paraquat poisoning (APP) , analyze the correlation between base excess (BE) and plasma concentration of paraquat (C-PQ) and discuss BE level in evalua-tion of prognosis of acute paraquat poisoning patients. Methods: We retrospectively selected 84 APP patients who admitted to Emergency Intensive Care Unit (EICU) of our hospital from 2009.9.1 to 2015.8.31.Clinical data from 84 APP patients were analyzed. BE、C-PQ、time of gastric lavagesince ingestion、time of hemoperfusion since ingestion、severity index of paraquat poisoning (SIPP) 、white blood cell (WBC) 、percentage of neutrophils (N%) 、hemoglobin (HB) 、creatinine (Cr) 、alanine aminotransferase (ALT) 、aspartate aminotransferase (AST) 、partial pressure of oxygen (PaO(2)) 、partial pressure of carbon dioxide (PaCO(2)) and other laboratory parameters were measured. A total of 41 patients in non-survivors died during the 30 days after admission and 43 patients in survivors survived during the 30 days. The factors of prognosis in paraquat poisoining and the role of BE in evalu-ating prognosis was analyzed, as well as the correlation between BE and C-PQ. Results: 1.Logistic regression analyses showed BE、C-PQ、ALT、AST、Cr was of prognostic significance[odds ratio (OR) of BE: 0.511, 95%CI 0.267, 0.978; C-PQ:-=0.999, 95%CI 0.999, 1.000; both P<0.05] ; 2.The area under the receiver operating characteristic curve (ROC curve) of BE、C-PQ and prognosis were 0.775、0.927 respectively, BE≤-1.7 mmol/L was the best cut-off value, the sensitivity、specificity for predicting were 82.9%、62.8%, the evaluation value was lower to C-PQ>3 273.935 ng/ml (AUC 0.927, 78.0%、95.3%) ; 3.BE negative correlated with C-PQ[-1.100 (-4.100, -0.200) , -5.900(-8.650, -2.500) , both P<0.05]. (r=-0.4, P<0.01). Conclusion: These results suggest that BE may be useful for the prediction of prognosis in PQ poisoning and BE negative correlated with C-PQ.


Assuntos
Hemoperfusão , Paraquat/intoxicação , Intoxicação/diagnóstico , Humanos , Paraquat/sangue , Intoxicação/mortalidade , Prognóstico , Curva ROC , Estudos Retrospectivos
13.
Clin Genet ; 90(5): 451-455, 2016 11.
Artigo em Inglês | MEDLINE | ID: mdl-26948280

RESUMO

Chromosomal aberration mostly occurs in chromosomes 21, 18 and 13, with an incidence approximately 1 out of 160 live births in humans, therefore making prenatal diagnosis necessary in clinics. Current methods have drawbacks such as time consuming, high cost, complicated operations and low sensitivity. In this paper, a novel method for rapid and accurate prenatal diagnosis of aneuploidy is proposed based on pyrosequencing, which quantitatively detects the peak height ratio (PHR) of different bases of segmental duplication. A direct polymerase chain reaction (PCR) approach was undertaken, where a small volume of amniotic fluid was used as the starting material without DNA extraction. Single-stranded DNA was prepared from PCR products and subsequently analyzed using pyrosequencing. The PHR between target and reference chromosome of 2.2 for euploid and 3:2 for a trisomy fetus were used as reference. The reference intervals and z scores were calculated for discrimination of aneuploidy. A total of 132 samples were collected, within trisomy 21 (n = 11), trisomy 18 (n = 3), trisomy 13 (n = 2), and unaffected controls (n = 116). A set of six segmental duplications were chosen for analysis. This method had consistent results with karyotyping analysis, a correct diagnosis with 100% sensitivity and 99.9% specificity.


Assuntos
Transtornos Cromossômicos/diagnóstico , Síndrome de Down/diagnóstico , Diagnóstico Pré-Natal , Trissomia/diagnóstico , Aberrações Cromossômicas , Transtornos Cromossômicos/genética , Cromossomos Humanos Par 13/genética , Cromossomos Humanos Par 18/genética , Cromossomos Humanos Par 21/genética , DNA de Cadeia Simples/genética , Síndrome de Down/genética , Síndrome de Down/fisiopatologia , Feminino , Sequenciamento de Nucleotídeos em Larga Escala , Humanos , Cariotipagem , Gravidez , Duplicações Segmentares Genômicas/genética , Trissomia/genética , Trissomia/fisiopatologia , Síndrome da Trissomia do Cromossomo 13 , Síndrome da Trissomía do Cromossomo 18
14.
Br J Dermatol ; 175(3): 604-7, 2016 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-26851874

RESUMO

Chagas disease is a parasitosis endemic to South America. It is normally treated with benznidazole as first choice, which has been associated with numerous cutaneous reactions. However, very few benznidazole-associated severe cutaneous adverse reactions have been reported to date. The rise of Chagas disease in nonendemic countries represents a growing public health challenge. We report two patients who met the criteria for drug reaction with eosinophilia and systemic symptoms syndrome and Stevens-Johnson syndrome/toxic epidermal necrolysis according to the RegiSCAR scoring systems. They were thus deemed overlapping cases, with a lymphocyte transformation test positive for benznidazole. Both required intensive care unit admission and both survived. Considering the rising application of this drug for trypanosomiasis in immigrant populations, clinicians should be aware of this newly reported, potentially life-threatening risk.


Assuntos
Doença de Chagas/tratamento farmacológico , Toxidermias/etiologia , Nitroimidazóis/efeitos adversos , Síndrome de Stevens-Johnson/etiologia , Tripanossomicidas/efeitos adversos , Adulto , Dermatite Esfoliativa/induzido quimicamente , Edema/induzido quimicamente , Feminino , Humanos , Masculino , Síndrome de Stevens-Johnson/diagnóstico
15.
Phys Chem Chem Phys ; 18(31): 21710-9, 2016 Aug 21.
Artigo em Inglês | MEDLINE | ID: mdl-27430158

RESUMO

We describe a technique to measure the viscosity of stably levitated single micron-sized aerosol particles. Particle levitation allows the aerosol phase to be probed in the absence of potentially artefact-causing surfaces. To achieve this feat, we combined two laser based techniques: optical trapping for aerosol particle levitation, using a counter-propagating laser beam configuration, and fluorescent lifetime imaging microscopy (FLIM) of molecular rotors for the measurement of viscosity within the particle. Unlike other techniques used to measure aerosol particle viscosity, this allows for the non-destructive probing of viscosity of aerosol particles without interference from surfaces. The well-described viscosity of sucrose aerosol, under a range of relative humidity conditions, is used to validate the technique. Furthermore we investigate a pharmaceutically-relevant mixture of sodium chloride and salbutamol sulphate under humidities representative of in vivo drug inhalation. Finally, we provide a methodology for incorporating molecular rotors into already levitated particles, thereby making the FLIM/optical trapping technique applicable to real world aerosol systems, such as atmospheric aerosols and those generated by pharmaceutical inhalers.

16.
Genet Mol Res ; 15(4)2016 Dec 02.
Artigo em Inglês | MEDLINE | ID: mdl-27966745

RESUMO

Myostatin (MSTN) is expressed in the myotome and developing skeletal muscles, and acts to regulate the number of muscle fibers. Wuding chicken large body, developed muscle, high disease resistance, and tender, delicious meat, and are not selected for fast growth. Broiler chickens (Avian broiler) are selected for fast growth and have a large body size and high muscle mass. Here, 240 one-day-old chickens (120 Wuding chickens and 120 broilers) were examined. Twenty chickens from each breed were sacrificed at days 1, 30, 60, 90, 120, and 150. Breast and leg muscle samples were collected within 20 min of sacrifice to investigate the effects of MSTN gene expression on growth performance and carcass traits. Body weight, carcass traits, and skeletal muscle mass in Wuding chickens were significantly (P < 0.05) lower than those in broiler chickens at all time points. Breast muscle MSTN mRNA was lower in Wuding chickens than in broilers before day 30 (P < 0.05). After day 30, breast muscle MSTN expression was higher in Wuding chicken than in broilers (P < 0.05). Leg muscle MSTN mRNA expression was higher in Wuding chicken than in broilers at all ages except for day 60 (P < 0.05). Correlation analysis revealed that breast muscle MSTN expression has a greater effect in slow growing Wuding chickens than in the fast growing broilers. In contract, leg muscle MSTN mRNA level has a greater effect in broilers than in Wuding chickens. MSTN regulates growth performance and carcass traits in chickens.


Assuntos
Peso Corporal/genética , Galinhas/crescimento & desenvolvimento , Galinhas/genética , Expressão Gênica , Miostatina/genética , Animais , Proteínas Aviárias/genética , Proteínas Aviárias/metabolismo , Cruzamento , Galinhas/metabolismo , Feminino , Regulação da Expressão Gênica , Masculino , Desenvolvimento Muscular , Miostatina/metabolismo , Especificidade de Órgãos , Fenótipo , Locos de Características Quantitativas
17.
Genet Mol Res ; 15(4)2016 Oct 05.
Artigo em Inglês | MEDLINE | ID: mdl-27808377

RESUMO

Chicken skeletal muscle satellite cells are located between the basement membrane and the sarcolemma of mature muscle fibers. Avian broilers have been genetically selected based on their high growth velocity and large muscle mass. The Wuding chicken is a famous local chicken in Yunnan Province that undergoes non-selection breeding and is slow growing. In this study, we aimed to explore differences in the proliferation and differentiation properties of satellite cells isolated from the two chicken breeds. Using immunofluorescence, hematoxylin-eosin staining and real-time polymerase chain reaction analysis, we analyzed the in vitro characteristics of proliferating and differentiating satellite cells isolated from the two chicken breeds. The growth curve of satellite cells was S-shaped, and cells from Wuding chickens entered the logarithmic phase and plateau phase 1 day later than those from Avian chicken. The results also showed that the two skeletal muscle satellite cell lines were positive for Pax7, MyoD and IGF-1. The expression of Pax7 followed a downward trend, whereas that of MyoD and IGF-1 first increased and subsequently decreased in cells isolated from the two chickens. These data indicated that the skeletal muscle satellite cells of Avian chicken grow and differentiate faster than did those of Wuding chickens. We suggest that the methods of breeding selection applied to these breeds regulate the characteristics of skeletal muscle satellite cells to influence muscle growth.


Assuntos
Galinhas/metabolismo , Células Satélites de Músculo Esquelético/citologia , Animais , Diferenciação Celular , Proliferação de Células , Forma Celular , Células Cultivadas , Imunofluorescência , Desenvolvimento Muscular , Reação em Cadeia da Polimerase em Tempo Real , Células Satélites de Músculo Esquelético/metabolismo
18.
J Biol Chem ; 289(18): 12791-804, 2014 May 02.
Artigo em Inglês | MEDLINE | ID: mdl-24644284

RESUMO

The urokinase-type plasminogen activator receptor (uPAR) is a glycosylphosphatidylinositol-linked membrane protein with no cytosolic domain that localizes to lipid raft microdomains. Our laboratory and others have documented that lung fibroblasts from patients with idiopathic pulmonary fibrosis (IPF) exhibit a hypermotile phenotype. This study was undertaken to elucidate the molecular mechanism whereby uPAR ligation with its cognate ligand, urokinase, induces a motile phenotype in human lung fibroblasts. We found that uPAR ligation with the urokinase receptor binding domain (amino-terminal fragment) leads to enhanced migration of fibroblasts on fibronectin in a protease-independent, lipid raft-dependent manner. Ligation of uPAR with the amino-terminal fragment recruited α5ß1 integrin and the acylated form of the Src family kinase, Fyn, to lipid rafts. The biological consequences of this translocation were an increase in fibroblast motility and a switch of the integrin-initiated signal pathway for migration away from the lipid raft-independent focal adhesion kinase pathway and toward a lipid raft-dependent caveolin-Fyn-Shc pathway. Furthermore, an integrin homologous peptide as well as an antibody that competes with ß1 for uPAR binding have the ability to block this effect. In addition, its relative insensitivity to cholesterol depletion suggests that the interactions of α5ß1 integrin and uPAR drive the translocation of α5ß1 integrin-acylated Fyn signaling complexes into lipid rafts upon uPAR ligation through protein-protein interactions. This signal switch is a novel pathway leading to the hypermotile phenotype of IPF patient-derived fibroblasts, seen with uPAR ligation. This uPAR dependent, fibrotic matrix-selective, and profibrotic fibroblast phenotype may be amenable to targeted therapeutics designed to ameliorate IPF.


Assuntos
Movimento Celular , Fibroblastos/metabolismo , Integrina alfa5beta1/metabolismo , Microdomínios da Membrana/metabolismo , Receptores de Ativador de Plasminogênio Tipo Uroquinase/metabolismo , Animais , Western Blotting , Caveolinas/genética , Caveolinas/metabolismo , Células Cultivadas , Fibroblastos/citologia , Fibronectinas/metabolismo , Humanos , Fibrose Pulmonar Idiopática/sangue , Fibrose Pulmonar Idiopática/metabolismo , Fibrose Pulmonar Idiopática/patologia , Integrina alfa5beta1/genética , Camundongos , Microscopia de Fluorescência , Ligação Proteica , Proteínas Proto-Oncogênicas c-fyn/genética , Proteínas Proto-Oncogênicas c-fyn/metabolismo , Interferência de RNA , Receptores de Ativador de Plasminogênio Tipo Uroquinase/sangue , Receptores de Ativador de Plasminogênio Tipo Uroquinase/genética , Índice de Gravidade de Doença , Proteínas Adaptadoras da Sinalização Shc/genética , Proteínas Adaptadoras da Sinalização Shc/metabolismo , Transdução de Sinais , Ativador de Plasminogênio Tipo Uroquinase/genética , Ativador de Plasminogênio Tipo Uroquinase/metabolismo
19.
J Viral Hepat ; 22(1): 55-63, 2015 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-24548489

RESUMO

Hepatitis D virus (HDV) infection is acquired as a co- /superinfection of Hepatitis B virus (HBV) and can modulate the pathophysiology of chronic hepatitis B and related liver diseases including hepatocellular carcinoma. Among the eight distinct HDV genotypes reported, relatively few studies have attempted to investigate the prevalence of HDV mixed genotypes and RNA recombination of HDV. With a recorded prevalence of 10-20% HBV infection in Vietnam, this study investigated the HDV variability, HDV genotypes and HDV recombination among twenty-one HDV isolates in Vietnamese HBsAg-positive patients. HDV subgenomic and full-length genome sequences were obtained using newly established HDV-specific RT-PCR techniques. The nucleotide homology was observed from 74.6% to 99.4% among the investigated full-length genome of the HDV isolates. We observed HDV genotype 1 and HDV genotype 2 in the investigated Vietnamese patients. Although no HDV genotype mixtures were observed, we report here a newly identified recombinant of HDV genotypes (HDV 1 and HDV 2). The identified recombinant HDV isolate C03 revealed sequence homology to both HDV genotype 1 (nt1 to nt907) and HDV genotype 2 (nt908 to nt1675; HDAg coding region) with a breakpoint at nt908. Our findings demonstrate the prevalence of intergenotypic recombination between HDV genotypes 1 and 2 in a Vietnamese HBsAg-positive patient. Extended investigation on the distribution and prevalence of HDV, HDV mixed genotypes and recombinant HDV genotypes in a larger Vietnamese population offers vital insights into understanding of the micro-epidemiology of HDV and subsequent pathophysiology in chronic HBV- /HDV-related liver diseases.


Assuntos
Variação Genética , Antígenos de Superfície da Hepatite B/sangue , Hepatite B/complicações , Hepatite D/virologia , Vírus Delta da Hepatite/classificação , Vírus Delta da Hepatite/genética , Adulto , Idoso , Povo Asiático , Feminino , Genótipo , Vírus Delta da Hepatite/isolamento & purificação , Humanos , Masculino , Pessoa de Meia-Idade , Dados de Sequência Molecular , Filogenia , RNA Viral/genética , Recombinação Genética , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Análise de Sequência de DNA , Homologia de Sequência , Adulto Jovem
20.
Osteoporos Int ; 26(12): 2823-33, 2015 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-26089135

RESUMO

UNLABELLED: This meta-analysis aimed to investigate the associations between osteocalcin (Ocn) and fasting plasma glucose (FPG) and glycated hemoglobin A1c (HbA1c). It was revealed that both total Ocn and undercarboxylated Ocn (unOcn) were negatively related with FPG and HbA1c, and the association of unOcn with FPG was more pronounced in men. INTRODUCTION: The aim of this study was to investigate the strength of associations between Ocn and FPG and HbA1c using a meta-analysis approach. METHODS: A search was carried out using the databases of PubMed, ISI Web of Science, and the Cochrane library from 2007 to 2014 to identify related studies. A pooled effect size with 95 % confidence intervals (CI) was derived. RESULTS: The meta-analysis included 39 studies involving 23,381 participants. The overall correlation was -0.16 (95 % CI, -0.19 to -0.14) between total Ocn (tOcn) and FPG and -0.15 (95 % CI, -0.20 to -0.11) between undercarboxylated Ocn (unOcn) and FPG. In the analysis of the association between Ocn and HbA1c, the pooled correlation was -0.16 (95 % CI, -0.18 to -0.14) for tOcn and -0.16 (95 % CI, -0.23 to -0.08) for unOcn. The magnitude of the correlation between unOcn and FPG is significantly higher in men than in women (r = -0.18, 95 % CI, -0.21 to -0.14; r = -0.09, 95 % CI, -0. 13 to -0.05, respectively; P for interaction < 0.05). Similar trend was also found between unOcn and HbA1c but without significance (for men, r = -0.19, 95 % CI, -0.24 to -0.14; for women, r = -0.09, 95 % CI, -0.22 to 0.04, respectively; P for interaction > 0.05). No indication of significant publication bias was found in any method. CONCLUSIONS: This meta-analysis demonstrated that both unOcn and tOcn were similarly and negatively correlated with FPG and HbA1c in humans. The negative correlations between unOcn and glucose metabolism appear to be more pronounced in men than in women.


Assuntos
Glicemia/metabolismo , Osteocalcina/sangue , Teste de Tolerância a Glucose , Hemoglobinas Glicadas/metabolismo , Humanos , Viés de Publicação , Sensibilidade e Especificidade
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