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OBJECTIVE: To assess the correlation between lesion location and swallowing function characteristics in post-stroke dysphagia (PSD) patients. MATERIALS AND METHODS: We enrolled 133 PSD. The patients were divided into supratentorial and infratentorial stroke groups. We compared the measurements in the videofluoroscopic swallowing study (VFSS) with 3ml and 5 ml of diluted and thickened barium liquid data between supratentorial and brainstem stroke groups. We further compared the difference of VFSS measurements between patients with left hemispheric or right hemispheric lesions (further divided into unilateral hemispheric cortical and subcortical subgroups) and brianstem leison stroke group.To explore the lesion location's effect on different bolus volume, the VFSS measurements of 3ml and 5ml in each subgroups were compared respectively. The measurements of VFSS included the oral transit time, soft palate elevation duration, hyoid bone movement duration (HMD), UES opening duration, pharyngeal transit duration (PTD), stage of ansition duration, and laryngeal closure duration (LCD), the upper esophageal sphincter opening (UESO), hyoid bone superior horizontal displacement, and hyoid bone anterior horizontal displacement. General swallowing function was assessed using the Penetration Aspiration Scale (PAS) and Functional Oral Intake Scale (FOIS). We performed the paired t-test, Spearman's correlation, and Kruskal-Wallis test analysis to characterize the parameters among the groups. RESULTS: Fifty-eight patients were assessed in the final analysis. The HMD (p = 0.019), PTD (p = 0.048) and LCD (p = 0.013) were significantly different between the supratentorial and brainstem lesion groups in 5ml volume. The HMD was significantly different (p = 0.045) between the left cortical and brainstem lesion groups. Significant differences in the HMD (p = 0.037) and LCD (p = 0.032) between the left subcortical and brainstem lesion groups were found in 5ml volume bolus. There was no group different when taking the 3ml volume bolus. Regarding the relationship between food bolus volume and swallowing functions, only the UESO demonstrated a significant difference in the subcortical lesion of the right hemisphere (p = 0.0032) compared the 3 ml and 5 ml volume bolus. The PTD demonstrated a moderate correlation with the PAS scores (r = 0.38, p = 0.0044). The HMD (r = 0.32, p = 0.018) and LCD (r = 0.29, p = 0.039) demonstrated weak correlations with the PAS scores. We did not identify any correlation between the VFSS parameters and FOIS scores in each subgroup level. CONCLUSION: The PSD with brainstem lesion shows more sever dysfunction in the pharyngeal phases. The left hemisphere was engaged in both the oral and pharyngeal phases. Lesions in the bilateral cortical, subcortical, and brainstem regions may impair sensory input.
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Transtornos de Deglutição , Deglutição , Acidente Vascular Cerebral , Gravação em Vídeo , Humanos , Transtornos de Deglutição/fisiopatologia , Transtornos de Deglutição/etiologia , Transtornos de Deglutição/diagnóstico , Transtornos de Deglutição/diagnóstico por imagem , Masculino , Feminino , Idoso , Pessoa de Meia-Idade , Acidente Vascular Cerebral/fisiopatologia , Acidente Vascular Cerebral/complicações , Acidente Vascular Cerebral/diagnóstico , Fluoroscopia , Valor Preditivo dos Testes , Idoso de 80 Anos ou mais , Fatores de Tempo , Fatores de Risco , Estudos RetrospectivosRESUMO
Multiphase flows through reservoir rocks are a universal and complex phenomenon. Relative permeability is one of the primary determinants in reservoir performance calculations. Accurate estimation of the relative permeability is crucial for reservoir management and future production. In this paper, we propose inferring relative permeability curves from sparse saturation data with an ensemble Kalman method. We represent these curves through a series of positive increments of relative permeability at specified saturation values, which guarantees monotonicity within, and boundedness between 0 and 1. The proposed method is validated by the inference performances in two synthetic benchmarks designed by SPE and a field-scale model developed by Equinor that includes certain real field features. The results indicate that the relative permeability curves can be accurately estimated within the saturation intervals having available observations and appropriately extrapolated to the remaining saturations by virtue of the embedded constraints. The predicted well responses are comparable to the ground truths, even though they are not included as the observation. The study demonstrates the feasibility of using ensemble Kalman method to infer relative permeability curves from saturation data, which can aid in the predictions of multiphase flow and reservoir production.
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BACKGROUND: Myocardial extracellular volume fraction (ECV) assessment can be affected by various technical and subject-related factors. PURPOSE: To evaluate the role of contour-based registration in quantification of ECV and investigate normal segment-based myocardial ECV values at 3T. MATERIAL AND METHODS: Pre- and post-contrast T1 mapping images of the left ventricular basal, mid-cavity, and apical slices were obtained in 26 healthy volunteers. ECV maps were generated using motion correction with and without contour-based registration. The image quality of all ECV maps was evaluated by a 4-point scale. Slices were dichotomized according to the occurrence of misregistration in the source data. Contour-registered ECVs and standard ECVs were compared within each subgroup using analysis of variance for repeated measurements and generalized linear mixed models. RESULTS: In all three slices, higher quality of ECV maps were found using contour-registered method than using standard method. Standard ECVs were statistically different from contour-registered ECVs in global (26.8% ± 2.8% vs. 25.8% ± 2.4%; P = 0.001), mid-cavity (25.4% ± 3.1% vs. 24.3% ± 2.5%; P = 0.016), and apical slices (28.7% ± 4.1% vs. 27.2% ± 3.4%; P = 0.010). In the misregistration subgroups, contour-registered ECVs were lower with smaller SDs (basal: 25.2% ± 1.8% vs. 26.7% ± 2.6%; P = 0.038; mid-cavity: 24.4% ± 2.3% vs. 26.8% ± 3.1%; P = 0.012; apical: 27.5% ± 3.6% vs. 29.7% ± 4.5%; P = 0.016). Apical (27.2% ± 3.4%) and basal-septal ECVs (25.6% ± 2.6%) were statistically higher than mid-cavity ECV (24.3% ± 2.5%; both P < 0.001). CONCLUSION: Contour-based registration can optimize image quality and improve the precision of ECV quantification in cases demonstrating ventricular misregistration among source images.
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Meios de Contraste , Miocárdio , Humanos , Valor Preditivo dos Testes , Imageamento por Ressonância Magnética/métodos , Imagem Cinética por Ressonância Magnética/métodosRESUMO
INTRODUCTION: Integrin α6 is an attractive diagnostic biomarker for molecular imaging of hepatocellular carcinoma (HCC) as it has an extremely high positive rate (approximately 94%) in clinical early-stage HCC. In this study, based on our previously identified integrin α6-targeted peptide, we developed an optimized integrin α6-targeted magnetic resonance (MR) probe dubbed DOTA(Gd)-ANADYWR for MR imaging of HCC in mice. MATERIALS AND METHODS: The longitudinal (R1) relaxivity of DOTA(Gd)-ANADYWR was measured on a 3.0 T MR system . The specific tumor enhancement of the agent was investigated in four distinct mouse models, including subcutaneous, orthotopic, genetically engineered and chemically induced HCC mice. RESULTS: The R1 relaxivity value of DOTA(Gd)-ANADYWR is 5.11 mM-1s-1 at 3.0 T, which is similar to that of the nonspecific clinical agent Gadoteridol. DOTA(Gd)-ANADYWR generated superior enhanced MR signal in HCC lesions and provided complementary enhancement MR signals to the clinically available hepatobiliary MR contrast agent gadoxetate disodium (Gd-EOB-DTPA). Importantly, DOTA(Gd)-ANADYWR could efficiently visualize small HCC lesion (approximately 1 mm) which was hardly detected by the clinical Gd-EOB-DTPA. CONCLUSION: These findings suggest the potential application of this integrin α6-targeted MR probe for the detection of HCC, particularly for small HCC.
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Sepsis-induced diaphragm dysfunction (SIDD) which is mainly characterized by decrease in diaphragmatic contractility has been identified to cause great harms to patients. Therefore, there is an important and pressing need to find effective treatments for improving SIDD. In addition, acetylcholinesterase (AChE) activity is a vital property of the diaphragm, so we evaluated both diaphragmatic contractility and AChE activity. Though neuregulin-1ß (NRG-1ß) is known to exert organ-protective effects in some inflammatory diseases, little is known about the potential of NRG-1ß therapy in the diaphragm during sepsis. Our study was aimed at exploring the effects of NRG-1ß application on diaphragmatic contractility and AChE activity during sepsis. Proinflammatory cytokines, muscle injury biomarkers in serum, contractile force, AChE activity, proinflammatory cytokines, oxidative parameters, histological condition, terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL) staining, and expression of phosphoinositide 3-kinase (PI3K)/protein kinase B (PKB/Akt) signaling proteins in the diaphragm were measured and compared between nonseptic and septic groups with or without NRG-1ß treatment. In vitro, the effects of NRG-1ß on reactive oxygen species (ROS) production in the lipopolysaccharide- (LPS-) stimulated L6 rat muscle skeletal cells with or without the Akt inhibitor MK-2206 were detected. NRG-1ß inhibited proinflammatory cytokine release and muscle injury biomarkers soaring in serum and improved the sepsis-induced diaphragm dysfunction and AChE activity decrease significantly during sepsis. Meanwhile, the inflammatory response, oxidative stress, pathological impairment, and cell apoptosis in the diaphragm were mitigated by NRG-1ß. And NRG-1ß activated the PI3K/Akt signaling in the diaphragm of septic rats. Elevated ROS production in the LPS-stimulated L6 rat skeletal muscle cells was reduced after treatment with NRG-1ß, while MK-2206 blocked these effects of NRG-1ß. In conclusion, our findings underlined that NRG-1ß could reduce circulating levels of proinflammatory cytokines in rats with sepsis, adjust diaphragmatic proinflammatory cytokine level, mitigate diaphragmatic oxidative injury, and lessen diaphragm cell apoptosis, thereby improving diaphragmatic function, and play a role in diaphragmatic protection by activating PI3K/Akt signaling.
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Diafragma/efeitos dos fármacos , Neuregulina-1/uso terapêutico , Fosfatidilinositol 3-Quinases/metabolismo , Proteínas Proto-Oncogênicas c-akt/metabolismo , Sepse/tratamento farmacológico , Animais , Inflamação , Masculino , Neuregulina-1/farmacologia , Estresse Oxidativo , Ratos , Ratos Sprague-DawleyRESUMO
Osteoporosis is characterized by the reduction of bone mineral density and deterioration of bone quality which leads to high risk of fractures. Some microRNAs (miRNAs) have been confirmed as potential modulators of osteoblast differentiation to maintain bone mass maintenance. We aimed to clarify whether miR-122 could regulate osteoblast differentiation in ovariectomized rats with osteoporosis. miR-122 was upregulated and Purkinje cell protein 4 (PCP4) was downregulated in ovariectomized rats. PCP4 was identified as a target of miR-122 by dual-luciferase reporter gene assay. We transfected isolated osteoblasts from ovariectomized rats with miR-122 mimic or inhibitor or PCP4 overexpression vectors. Proliferation and differentiation of osteoblasts were repressed by the overexpression of miR-122 but enhanced by overexpression of PCP4. miR-122 could induce the activation of the c-Jun NH2-terminal kinase (JNK) signaling pathway, while PCP4 blocked this pathway. Rescue experiments further demonstrated that the inhibiting effects of miR-122 on osteoblast differentiation could be compensated by activation of the PCP4 or inhibition of JNK signaling pathway. Collectively, our data imply that miR-122 inhibits osteoblast proliferation and differentiation in rats with osteoporosis, highlighting a novel therapeutic target for osteoporotic patients.
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OBJECTIVE: The aim of this study was to analyze the radiologic features of adolescent idiopathic cervical kyphosis. SUMMARY OF BACKGROUND DATA: There are few previous reports about radiographic analysis of cervical sagittal alignment of adolescent idiopathic cervical kyphosis. A new method was proposed in this article to evaluate the severity of cervical kyphosis. PATIENTS AND METHODS: A total of 41 adolescent patients with cervical kyphosis were reviewed. Several angles were measured from the radiographs utilizing the 2-line Cobb method and Harrison posterior tangent method. Ishihara's Curvature Index (CI), Kyphosis Index (KI), kyphosis levels, and the apex of the kyphosis were also measured. RESULTS: The results showed that the apex of the kyphosis is located at the posterior-superior edge of C4 (70.7%) and C5 (29.3%). C2-C7 angles ranged from 4.7 to 71.3 degrees (36.2±13.6 degrees) and from 9.8 to 83.1 degrees (36.4±15.1 degrees) in the above 2 methods, respectively. Local angles of kyphotic area ranged from 21.8 to 96.3 degrees (50.5±23.7 degrees) in 2-line Cobb method and from 19.8 to 105.6 degrees (52.0±19.5 degrees) in Harrison posterior tangent method. CI and KI ranged from 8.6 to 79.8 (36.8±16.7) and 15.2 to 141.9 (50.6±23.7), respectively. Statistical analysis showed that there was significant positive correlation between KI and kyphosis angle. CONCLUSIONS: In adolescent idiopathic cervical kyphosis, the alteration of the sagittal profile only occurs on partial cervical alignment rather than the whole cervical spine. The apex of the kyphosis locates at posterior-superior edge of the vertebrae. It seems that KI can accurately depict the severity of cervical kyphosis.
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Vértebras Cervicais/diagnóstico por imagem , Doença de Scheuermann/diagnóstico por imagem , Adolescente , Vértebras Cervicais/patologia , Criança , Feminino , Humanos , Masculino , Adulto JovemRESUMO
PURPOSE: Tibial pilon fractures remain challenging for an orthopaedic surgeon to repair. External fixation (ExFix) and open reduction and internal fixation (ORIF) are two widely used methods for repairing tibial pilon fractures. However, conclusions of comparative studies regarding which method is superior are controversial. Our aim is to compare ORIF and ExFix and clarify which method is better in terms of reduction and union results and major complications. METHODS: A computerized research of MEDLINE, EMBASE, Springer, and Cochrane Library (before December 2014) for studies of any design comparing ORIF and ExFix was conducted. Weighted mean difference (WMD), risk ratio (RR) and corresponding 95% confidence intervals (CI) were used for esti- mating the effects of the two methods. Statistical analyses were done using Review Manager Version 5.2. RESULTS: Ten cohort studies and one randomized clinical trial were included in our ultimate analysis. And the analysis found no significant difference between the two methods in deep infection (p = 0.13), reduction (p = 0.11), clinical evaluation (p = 0.82), post-traumatic arthrosis (p = 0.87), and union time (p = 0.35). Besides, ExFix group was found to have a higher rate of superficial infection (p =0.001), malunion (p = 0.01) and nonunion (p = 0.02), but have a lower risk of unplanned hardware removal (p = 0.0002). CONCLUSIONS: We suggest that ORIF has a relatively lower incidence rate of superficial infection, malunion and nonunion, but a higher rate of unplanned hardware removal. No difference was found in deep infection, reduction, clinical evaluation, post-traumatic arthrosis and union time.
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Fixadores Externos , Fixação Interna de Fraturas/métodos , Fraturas da Tíbia/cirurgia , Fixadores Externos/efeitos adversos , Fixação Interna de Fraturas/efeitos adversos , HumanosRESUMO
FGF10 is a member of fibroblast growth factors (FGFs). We previously showed that FGF10 protects neuron against oxygen-glucose deprivation injury in vitro; however, the effect of FGF10 in ischemic stroke in vivo is unknown. In the present study, we showed that FGF10 was mainly expressed in neurons but not astrocytes, and detected FGF10 in mouse cerebrospinal fluid. The FGF10 levels in neurons culture medium and cell lysate were much higher than those in astrocytes. FGF10 expression in brain tissue and FGF10 level in CSF were increased in mouse middle cerebral artery occlusion (MCAO) model. Administration of FGF10 into lateral cerebroventricle not only decreased MCAO-induced brain infarct volume and neurological deficit, but also reduced the number of TUNEL-positive cells and activities of Caspases. Moreover, FGF10 treatment depressed the triggered inflammatory factors (TNF-α and IL-6) and NF-κB signaling pathway, and increased phosphorylation of PI3K/Akt signaling pathway. Blockade of PI3K/Akt signaling pathway by wortmannin and Akt1/2-kinase inhibitor, partly compromised the neuroprotection of FGF10. However, blockade of PI3K/Akt signaling pathway did not impair the anti-inflammation action of FGF10. Collectively, our results demonstrate that neuron-derived FGF10 ameliorates cerebral ischemia injury via inhibiting NF-κB-dependent neuroinflammation and activating PI3K/Akt survival signaling pathway in mice.
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Isquemia Encefálica/metabolismo , Fator 10 de Crescimento de Fibroblastos/metabolismo , NF-kappa B/metabolismo , Neurônios/metabolismo , Fosfatidilinositol 3-Quinases/metabolismo , Proteínas Proto-Oncogênicas c-akt/metabolismo , Traumatismo por Reperfusão/metabolismo , Transdução de Sinais , Animais , Apoptose/efeitos dos fármacos , Isquemia Encefálica/patologia , Modelos Animais de Doenças , Fator 10 de Crescimento de Fibroblastos/farmacologia , Inflamação/metabolismo , Inflamação/patologia , Masculino , Camundongos , Modelos Biológicos , Neurônios/efeitos dos fármacos , Fármacos Neuroprotetores/farmacologia , Traumatismo por Reperfusão/patologia , Transdução de Sinais/efeitos dos fármacosRESUMO
Identification of genetic risk factors is the hotspot of adolescent idiopathic scoliosis (AIS). Through candidate gene approach and genome-wide association studies (GWAS), some genes were preliminary identified. To review AIS related genes,and construct the gene network map of AIS gene. We searched on NCBI PubMed and Web of Science database using search terms "adolescent idiopathic scoliosis" and "gene", to classify induction genes. We then constructed gene diagram using string-db. We found 35 AIS genes relating to connective tissue, nervous system active substances, melatonin synthesis and metabolism, puberty and growth, and genes whose function is unknown. Gene diagram shows that a network relationship between gene and other genes,in which IL6, ESR1, ESR2, VDR, TGFB1, IGF1 gene may as the key gene about AIS' genetic mechanism. Two sites of 3 GWAS results outside the network, it is suggesting new pathway that need to be explored. The study about AIS susceptibility gene is still preliminary, requiring in-depth research to identify the new networks.
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Estudo de Associação Genômica Ampla , Escoliose/genética , Adolescente , Predisposição Genética para Doença , Humanos , Fator de Crescimento Insulin-Like I/genética , Proteínas Matrilinas/genética , Fator de Crescimento Transformador beta1/genéticaRESUMO
Although increases in mean temperature (MT) and extreme high temperature (EHT) can greatly affect population dynamics of insects under global warming, how concurrent changes in both MT and EHT affect invasive species is largely unknown. We used four thermal regimes to simulate the increases in summer temperature and compared their effects on the life-history traits of three geographical populations (Chongqing, Wuhan and Shanghai) of an invasive insect, Corythucha ciliata, in China. The four thermal regimes were control (i.e., natural or ambient), an increase in MT (IMT), an increase in EHT, and a combination of IMT + EHT. We found that the three warming regimes significantly increased the developmental rate but did not affect the survival, sex ratio, longevity, or fecundity of C. ciliata. Consequently, the intrinsic rate of natural increase (rm) was enhanced and the number of days required for population doubling (t) was reduced by the warming regimes. The demographic parameters did not significantly differ among the three populations. These results indicate that population size of C. ciliata may be enhanced by increases in both temperature means and extremes. The increases in summer temperature associated with climate change, therefore, would likely facilitate population outbreaks of some thermophilic invasive insects.
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Mudança Climática , Herbivoria/fisiologia , Heterópteros/crescimento & desenvolvimento , Espécies Introduzidas , Temperatura , Animais , China , Feminino , Heterópteros/fisiologia , Longevidade , Masculino , Dinâmica Populacional , Reprodução/fisiologia , Estações do Ano , Razão de MasculinidadeRESUMO
IRF-1, a kind of transcription factor, is expressed in many cell types, except in early embryonal cells. IRF-1 has played an essential role in various physiological and pathological processes, including tumor immune surveillance, viral infection, development of immunity system and pro-inflammatory injury. However, the expression and function of IRF-1 in spinal cord injury (SCI) are still unknown. In this study, we have performed an acute SCI model in adult rats and investigated the dynamic changes of IRF-1 expression in the spinal cord. Western blot have shown that IRF-1 protein levels gradually increased, reaching a peak at day 3 and then gradually declined to a normal level at day 14 after SCI. Double immunofluorescence staining showed that IRF-1 immunoreactivity was found in neurons, but not in astrocytes and microglia. Additionally, colocalization of IRF-1/active caspase-3 was detected in neurons. In vitro, IRF-1 depletion, by short interfering RNA, obviously decreases neuronal apoptosis. In conclusion, this is the first description of IRF-1 expression in spinal cord injury. Our results suggested that IRF-1 might play crucial roles in CNS pathophysiology after SCI.
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Apoptose , Fator Regulador 1 de Interferon/metabolismo , Neurônios/metabolismo , Traumatismos da Medula Espinal/metabolismo , Animais , Astrócitos/metabolismo , Células Cultivadas , Fator Regulador 1 de Interferon/genética , Masculino , Ratos , Ratos Sprague-Dawley , Regulação para CimaRESUMO
Under high temperature conditions, insects can tolerate to survive through various physiological mechanisms, which have been well documented in laboratory studies. However, it is still unclear as to whether these laboratory data can scale up to those in the field. Here we studied dynamics of heat-induced metabolites in Corythucha ciliata adults under both laboratory and field conditions to examine their significance in thermal tolerance of the species. We compared the effects of controlled thermal treatments (2h at 33-43 °C at 2 °C intervals in the laboratory) and naturally increasing thermal conditions (10:00-14:00 at 2-h intervals (33.5-37.2 °C) on a hot summer day in a field in Shanghai, China) on water content and levels of water-soluble protein, triglycerides, mannitol, and sorbitol in the adult bodies. The results showed that water content significantly decreased and all other metabolic parameters significantly increased in response to temperature stresses with similar patterns in both the laboratory and field, although the respective threshold temperatures were different under the two conditions. The close linkage observed in the two conditions suggests that a short period of heat stress induces water loss and accumulation of thermal metabolites in C. ciliata adults. This heat-resistance provides a defense mechanism counteracting thermal damage in C. ciliata.
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Resposta ao Choque Térmico , Heterópteros/fisiologia , Animais , Heterópteros/metabolismo , Manitol/metabolismo , Proteínas/metabolismo , Sorbitol/metabolismo , Triglicerídeos/metabolismo , Água/metabolismoRESUMO
Ras association (RalGDS/AF-6) domain family member RASSF5 has been implicated in a variety of key biological processes, including cell proliferation, cell cycle regulation and apoptosis. It is believed to play an important role in tumorigenesis as a tumor suppressor in a number of malignancies. Yet, little is known concerning the function and underlying mechanisms of RASSF5 in human osteosarcoma (OS). The expression of RASSF5 was examined by immunohistochemical assay using a tissue microarray in 45 cases of OS tissues. A gain-of-function approach was used to observe the effects of lentiviral vector-mediated overexpression of RASSF5 (Lv-RASSF5) on cell growth, invasion and apoptosis, respectively, as indicated by MTT, Transwell and flow cytometry assays, and the expression levels of mammalian sterile 20-like (MST1) kinase, large tumor suppressor 1 (LATS1), proliferating cell nuclear antigen (PCNA), matrix metallopeptidase-9 (MMP-9) and p53 were detected by real-time PCR and western blot assays in OS cells (MG-63 and U-2 OS). The results indicated that the expression of RASSF5 protein was significantly downregulated in OS tissues compared to that in adjacent non-cancerous tissues (ANCT) (40.0 vs. 73.3%, P=0.002), and had a negative correlation with distant metastasis of the tumor (P=0.01). Overexpression of RASSF5 markedly suppressed cell proliferation and invasion, and induced cell apoptosis in the OS cell lines with increased expression of MST1, LATS1 and p53 and decreased expression of PCNA and MMP-9. Taken together, our findings demonstrate that RASSF5 expression is negatively correlated with distant metastasis of OS, and RASSF5 may function as a tumor suppressor in OS cells through activation of the MST1/LATS1 pathway.
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Apoptose/genética , Neoplasias Ósseas/genética , Proliferação de Células/genética , Proteínas Monoméricas de Ligação ao GTP/genética , Osteossarcoma/genética , Proteínas Serina-Treonina Quinases/metabolismo , Proteínas Adaptadoras de Transdução de Sinal , Proteínas Reguladoras de Apoptose , Neoplasias Ósseas/metabolismo , Neoplasias Ósseas/patologia , Linhagem Celular Tumoral , Feminino , Humanos , Peptídeos e Proteínas de Sinalização Intracelular , Masculino , Metaloproteinase 9 da Matriz/metabolismo , Proteínas Monoméricas de Ligação ao GTP/metabolismo , Invasividade Neoplásica/genética , Osteossarcoma/metabolismo , Osteossarcoma/patologia , Antígeno Nuclear de Célula em Proliferação/metabolismo , Reação em Cadeia da Polimerase em Tempo Real , Transdução de Sinais , Proteína Supressora de Tumor p53/metabolismo , Adulto JovemRESUMO
CXC chemokine receptor 7 (CXCR7) has been implicated in tumor development and metastasis in multiple malignancies. Yet, the function and molecular mechanisms of CXCR7 in human osteosarcoma (OS) are still unclear. The aim of the present study was to investigate the role of CXCR7 in human OS. The expression of CXCR7 was assessed by immunohistochemical assay using a tissue microarray procedure in 45 cases of OS tissues. A lossof-function approach was used to observe the effects of lentiviral vector-mediated CXCR7 siRNA (Lv-siCXCR7) on biological behaviors including proliferative activities and invasive potential, as indicated by MTT and Transwell assays in OS (MG-63 and U-2 OS) cells. The results showed that the expression of CXCR7 protein in OS tissues was significantly increased compared to that in adjacent non-cancerous tissues (68.9 vs. 53.3%, P=0.033), and was correlated with the distant metastasis of the tumors (P=0.004). Knockdown of CXCR7 suppressed proliferation and invasion of OS cells through decreased expression of PI3K, AKT, ß-arrestin, proliferating cell nuclear antigen (PCNA), and matrix metalloproteinase-9 (MMP-9). In addition, the tumor volume in U-2 OS subcutaneous tumor models treated with Lv-siCXCR7 was significantly smaller than the tumor volume in the negative control group (P<0.01). Collectively, our findings indicate that upregulation of CXCR7 expression is correlated with distant metastasis of OS, while knockdown of CXCR7 blocks the development of OS cells through inhibition of the PI3K/AKT and ß-arrestin pathways, suggesting that CXCR7 may serve as a potential therapeutic target for the treatment of cancer.
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Neoplasias Ósseas/metabolismo , Neoplasias Ósseas/terapia , Osteossarcoma/metabolismo , Osteossarcoma/terapia , Receptores CXCR/metabolismo , Transdução de Sinais , Animais , Neoplasias Ósseas/genética , Neoplasias Ósseas/patologia , Linhagem Celular Tumoral , Movimento Celular , Proliferação de Células , Feminino , Regulação Neoplásica da Expressão Gênica , Técnicas de Silenciamento de Genes , Terapia Genética , Humanos , Masculino , Camundongos , Neoplasias Experimentais , Osteossarcoma/genética , Osteossarcoma/patologia , Receptores CXCR/genética , Análise Serial de TecidosRESUMO
Tumor necrosis factor-α-inducible protein-1 (TNFAIP1) plays a role in DNA synthesis, DNA repair, cell apoptosis and human diseases including cancer, and may be involved in tumor progression and metastases. However, little is known concerning the function of TNFAIP1 in human osteosarcoma (OS). The aim of the present study was to investigate the function and underlying mechanisms of TNFAIP1 in human OS. The expression of TNFAIP1 was examined by immunohistochemical assay using a tissue microarray procedure. A loss-of-function experiment was performed to explore the effects of lentiviral-mediated TNFAIP1 siRNA (siTNFAIP1) on cell proliferation, invasive potential and apoptosis by MTT and Transwell assays and flow cytometric analysis in OS (MG-63 and U-2 OS) cells. The results showed that the expression of TNFAIP1 protein was significantly increased in OS tissues compared with that in adjacent non-cancerous tissues (ANCTs) (73.3 vs. 48.9%, P=0.018), and was correlated with the distant metastasis of the patients with OS (P=0.029). Knockdown of TNFAIP1 suppressed cell proliferation and invasion, and induced cell apoptosis in the OS cells together with the downregulation of p65 nuclear factor-κB (NF-κB), proliferating cell nuclear antigen (PCNA) and matrix metalloproteinase-2 (MMP-2) and upregulation of caspase-3. Collectively, our findings indicate that high expression of TNFAIP1 is associated with distant metastasis of OS, and knockdown of TNFAIP1 inhibits the growth and invasion, and induces apoptosis in OS cells through inhibition of the NF-κB pathway, suggesting that TNFAIP1 may act as a potential therapeutic target for the treatment of cancer.
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Neoplasias Ósseas/metabolismo , Osteossarcoma/metabolismo , Proteínas/genética , Proteínas/metabolismo , RNA Interferente Pequeno/metabolismo , Fator de Transcrição RelA/metabolismo , Proteínas Adaptadoras de Transdução de Sinal , Apoptose , Neoplasias Ósseas/genética , Neoplasias Ósseas/patologia , Linhagem Celular Tumoral , Movimento Celular , Proliferação de Células , Regulação Neoplásica da Expressão Gênica , Técnicas de Silenciamento de Genes , Humanos , Masculino , Osteossarcoma/genética , Osteossarcoma/patologia , Transdução de Sinais , Análise Serial de Tecidos , Regulação para CimaRESUMO
PURPOSE: To investigate the efficacy of diffusion-weighted MRI (DWI) in differentiating recurrent tumor from chronic inflammation and fibrosis after cystectomy or transurethral resection of bladder cancer. METHODS: Eleven patients with suspected tumor recurrence underwent pelvic DWI and dynamic contrast-enhanced (DCE) MRI at 3 months to 7 years following bladder cancer resection. The diagnosis was histologically confirmed in all patients by transurethral or cystoscopic resection of 27 lesions within 2 weeks of MR examinations. RESULTS: The accuracies, sensitivities, specificities, and positive predict values of DWI (92.6%, 100%, 81.8%, and 88.9%) were higher than those of DCE MRI (59.3%, 81.3%, 27.3%, and 54.2%) for detecting recurrent tumors. Using receiver operating characteristic analysis, the accuracy of DWI was significantly higher than that of DCE MRI (P < 0.05). There was no significant difference between DWI diagnosis and histopathology (P > 0.05), whereas the difference between diagnosis of DCE MRI and histopathology was significant (P < 0.05). The normalized apparent diffusion coefficients of recurrent tumors (0.697 ± 0.219) were significantly (P < 0.05) lower than those of postoperative inflammation or fibrosis (1.019 ± 0.143). CONCLUSIONS: DWI is superior to DCE MRI for differentiating recurrent bladder tumors from postoperative inflammation or fibrosis. DWI can be included in the follow-up MRI protocol after bladder cancer surgery.
Assuntos
Imagem de Difusão por Ressonância Magnética , Recidiva Local de Neoplasia/diagnóstico , Neoplasias da Bexiga Urinária/diagnóstico , Idoso , Cistectomia , Diagnóstico Diferencial , Fibrose , Humanos , Aumento da Imagem , Inflamação/patologia , Imageamento por Ressonância Magnética/métodos , Masculino , Pessoa de Meia-Idade , Bexiga Urinária/patologia , Neoplasias da Bexiga Urinária/patologiaRESUMO
High temperature often induces oxidative stress and antioxidant response in insects. This phenomenon has been well documented under controlled laboratory conditions, but whether it happens under fluctuating field conditions is largely unknown. In this study, we used an invasive lace bug (Corythucha ciliata) as a model species to compare the effects of controlled thermal treatments (2 h at 33-43 °C with 2 °C intervals in the laboratory) and naturally fluctuating thermal conditions (08:00-14:00 at 2-h intervals (29.7-37.2 °C) on a hot summer day in a field in Shanghai, China) on lipid peroxidation (malondialdehyde (MDA) was the marker) and anaerobic respiration (lactate dehydrogenase (LDH) was the marker), as well as superoxide dismutase (SOD), catalase (CAT), glutathione (GSH), and glutathione reductase (GR). The results show that MDA concentration increased significantly in response to heat stresses with similar trend in the laboratory and field. LDH activities did not significantly vary across temperatures in the laboratory-exposed individuals, but they significantly increased by rising temperature in the field. The activities or concentrations of SOD, CAT, GSH, and GR all significantly increased with increasing temperature in the two populations. These findings indicate that high temperature induces oxidative stress, resulting in high anaerobic respiration and antioxidant defenses in C. ciliata under both the laboratory and field conditions, which likely provide a defense mechanism against oxidative damage due to the accumulation of ROS.
Assuntos
Antioxidantes/metabolismo , Hemípteros/citologia , Temperatura Alta , Estresse Oxidativo , Anaerobiose , Animais , Catalase/metabolismo , Respiração Celular , Glutationa Redutase/metabolismo , Hemípteros/enzimologia , L-Lactato Desidrogenase/metabolismo , Laboratórios , Peroxidação de Lipídeos , Malondialdeído/metabolismo , Superóxido Dismutase/metabolismoRESUMO
Biological invasions are predicted to be more frequent as climate change is increasing its positive impact on the prevalence of invasive exotic species. Success of insect invaders in different temperature zones is closely related to their tolerance to temperature extremes. In this study, we used an exotic lace bug (Corythucha ciliata) as the study organism to address the hypotheses that an insect species invading a subtropical zone from temperate regions has a high capacity to survive and adapt to high temperatures, and that its thermal tolerance plays an important role in determining its seasonal abundance and geographic distribution. To test these hypotheses, the effects of heat shock on the survival and reproduction of C. ciliata adults were assessed in the laboratory. Adults were exposed to 26 (control), 35, 37, 39, 41, 43, and 45°C for 2 h, and then were transferred to 26°C. Heat-shock temperatures ranging from 35 to 41°C did not significantly affect survival pattern, longevity, and fecundity of adults, but heat shock at 43 and 45°C significantly reduced these traits. Exposing parent females to heat-shock treatments from 35 to 41°C did not significantly affect the hatching rate of their eggs, survival of the nymphs, and the proportion of female F(1) progeny, while no progeny were produced with treatments of 43 and 45°C. The results indicate that C. ciliata can tolerate high temperatures less than 41°C, which may contribute to its expansion into the lower latitudes in China where its hosts (Platanus trees) are widely planted. Our findings have important implications for predicting seasonal abundance and understanding invasion mechanisms of this important urban invader under climate change.