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1.
Biochem Biophys Res Commun ; 674: 170-182, 2023 09 24.
Artigo em Inglês | MEDLINE | ID: mdl-37423037

RESUMO

Glioblastoma multiforme (GBM) is the most common and aggressive brain tumor with a poor prognosis. The growth of GBM cells depends on the core transcriptional apparatus, thus rendering RNA polymerase (RNA pol) complex as a candidate therapeutic target. The RNA pol II subunit B (POLR2B) gene encodes the second largest subunit of the RNA pol II (RPB2); however, its genomic status and function in GBM remain unclear. Certain GBM data sets in cBioPortal were used for investigating the genomic status and expression of POLR2B in GBM. The function of RPB2 was analyzed following knockdown of POLR2B expression by shRNA in GBM cells. The cell counting kit-8 assay and PI staining were used for cell proliferation and cell cycle analysis. A xenograft mouse model was established to analyze the function of RPB2 in vivo. RNA sequencing was performed to analyze the RPB2-regulated genes. GO and GSEA analyses were applied to investigate the RPB2-regulated gene function and associated pathways. In the present study, the genomic alteration and overexpression of the POLR2B gene was described in glioblastoma. The data indicated that knockdown of POLR2B expression suppressed tumor cell growth of glioblastoma in vitro and in vivo. The analysis further demonstrated the identification of the RPB2-regulated gene sets and highlighted the DNA damage-inducible transcript 4 gene as the downstream target of the POLR2B gene. The present study provides evidence indicating that RPB2 functions as a growth regulator in glioblastoma and could be used as a potential therapeutic target for the treatment of this disease.


Assuntos
Neoplasias Encefálicas , Glioblastoma , Humanos , Animais , Camundongos , Glioblastoma/patologia , RNA Polimerase II/genética , RNA Polimerase II/metabolismo , Proliferação de Células/genética , Neoplasias Encefálicas/patologia , RNA Interferente Pequeno/genética , Linhagem Celular Tumoral , Regulação Neoplásica da Expressão Gênica
2.
Genomics ; 113(2): 827-842, 2021 03.
Artigo em Inglês | MEDLINE | ID: mdl-33515675

RESUMO

O-GlcNAcylation is important in the development and progression of pancreatic ductal adenocarcinoma (PDAC). The glycosyltransferase EGF domain-specific O-linked GlcNAc transferase (EOGT) acts as a key participant in glycosylating NOTCH1. High-throughput sequencing of specimens from 30 advanced PDAC patients identified SHCBP1 and EOGT as factors of poor prognosis. We hypothesized that they could mediate PDAC progression by influencing NOTCH1 O-GlcNAcylation. Thus, 186 PDAC tissue specimens were immunostained for EOGT and SHCBP1. Pancreatic cancer cell lines and nude mouse models were used for in vitro and in vivo experiments. Respectively, The protein expression of EOGT and SHCBP1 was significantly elevated and correlated with worse prognosis in PDAC patients. In vitro, SHCBP1 overexpression promoted pancreatic cancer cell proliferation, migration and invasion, while knocking down SHCBP1 and EOGT inhibited these malignant processes. In vivo data showed that SHCBP1 overexpression promoted xenograft growth and lung metastasis and shortened survival in mice, whereas knocking down either EOGT or SHCBP1 expression suppressed xenograft growth and metastasis and prolonged survival. We further clarified the molecular mechanisms by which EOGT and SHCBP1 enhance the O-GlcNAcylation of NOTCH1, Subsequently promoting the nuclear localization of the Notch intracellular domain (NICD) and inhibiting the transcription of E-cadherin and P21 in pancreatic cancer cells.


Assuntos
N-Acetilglucosaminiltransferases/metabolismo , Neoplasias Pancreáticas/metabolismo , Receptor Notch1/metabolismo , Proteínas Adaptadoras da Sinalização Shc/metabolismo , Acetilação , Acetilglucosamina/metabolismo , Animais , Linhagem Celular Tumoral , Feminino , Células HEK293 , Humanos , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Nus , Pessoa de Meia-Idade , N-Acetilglucosaminiltransferases/genética , Metástase Neoplásica , Neoplasias Pancreáticas/patologia , Ligação Proteica , Proteínas Adaptadoras da Sinalização Shc/genética
3.
Ocean Coast Manag ; 229: 106338, 2022 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-36059571

RESUMO

A container shipping network connects coastal countries with each other and facilitates most of the world merchandise trade. Reliable maritime connectivity ensures the availability of commodities and economic growth. The global spread of COVID-19 has led to port failures and service cancellations, resulting in decreased connectivity level of container ports. To mitigate the impact of the pandemic, a graph theory approach is proposed to strength the container shipping network connectivity by considering topology and the possibility of opening new shipping links between ports. It is designed to maximize network connectivity with limited addable routes. The network connectivity is measured by algebraic connectivity, and the possibility of opening new shipping links is estimated by an extended gravity model. A heuristic algorithm based on Fiedler vector is introduced to obtain the optimal solutions. The performance of the proposed model and algorithm are verified by testing on a real-world container shipping network based on the Alphaliner database. Experimental results illustrate that the presented model is efficient and effective for strengthening the connectivity. Policy makers can refer to the suggested optimal shipping links to facilitate better shipping network connectivity in the context of the COVID-19 pandemic.

4.
Zhongguo Dang Dai Er Ke Za Zhi ; 24(10): 1117-1123, 2022 Oct 15.
Artigo em Zh | MEDLINE | ID: mdl-36305112

RESUMO

OBJECTIVES: To investigate the risk factors for pulmonary hemorrhage and its clinical outcome in very low birth weight infants (VLBWIs). METHODS: The medical data were collected from all live VLBWIs (gestational age <35 weeks) who were admitted to Jiangsu Women and Children Health Hospital and Children's Hospital of Nanjing Medical University between January 1, 2020 and December 31, 2021. Based on inclusion and exclusion criteria, 574 VLBWIs were included in the study, with 44 VLBWIs in the pulmonary hemorrhage group and 530 VLBWIs in the non-pulmonary hemorrhage group. The clinical data were compared between the two groups. A multivariate logistic regression analysis was used to identify the risk factors for pulmonary hemorrhage. RESULTS: There were significant differences between the two groups in maternal age, rate of positive-pressure ventilation for resuscitation, rate of tracheal intubation for resuscitation, and minimum body temperature within 1 hour after birth (P<0.05). The pulmonary hemorrhage group had a higher proportion of VLBWIs with grade Ⅲ-Ⅳ respiratory distress syndrome or early-onset sepsis than the non-pulmonary hemorrhage group (P<0.05). The pulmonary hemorrhage group also had a higher proportion of VLBWIs with a capillary refilling time of >3 seconds within 1 hour after birth and with the maximum positive end-expiratory pressure (PEEP) of <5 cmH2O within 24 hours after birth (P<0.05). The multivariate regression analysis showed that maternal age of 30-<35 years (OR=0.115, P<0.05) was a protective factor against pulmonary hemorrhage, while a lower temperature (<34°C) within 1 hour after birth, the maximum PEEP of <5 cm H2O within 24 hours after birth, and early-onset sepsis were risk factors for pulmonary hemorrhage (OR=11.609, 11.118, and 20.661, respectively; P<0.05). For all VLBWIs, the pulmonary hemorrhage group had a longer duration of invasive ventilation and a higher mortality rate than the non-pulmonary hemorrhage group (P<0.05); for the survival VLBWIs, the pulmonary hemorrhage group had a higher incidence rate of bronchopulmonary dysplasia than the non-pulmonary hemorrhage group (P<0.05). CONCLUSIONS: Maintaining the stability of temperature, giving appropriate PEEP, and identifying sepsis as early as possible can reduce the incidence rate of pulmonary hemorrhage, thereby helping to reduce the incidence of bronchopulmonary dysplasia and mortality in VLBWIs.


Assuntos
Displasia Broncopulmonar , Sepse , Recém-Nascido , Lactente , Criança , Feminino , Humanos , Adulto , Displasia Broncopulmonar/epidemiologia , Recém-Nascido de muito Baixo Peso , Idade Gestacional , Fatores de Risco , Hemorragia/etiologia , Hemorragia/terapia , Peso ao Nascer
5.
Cancer Cell Int ; 21(1): 598, 2021 Nov 07.
Artigo em Inglês | MEDLINE | ID: mdl-34743716

RESUMO

BACKGROUND: Acute myeloid leukemia (AML) is a myeloid neoplasm accounts for 7.6% of hematopoietic malignancies. AML is a complex disease, and understanding its pathophysiology is contributing to the improvement in the treatment and prognosis of AML. In this study, we assessed the expression profile and molecular functions of CCAAT enhancer binding protein gamma (CEBPG), a gene implicated in myeloid differentiation and AML progression. METHODS: shRNA mediated gene interference was used to down-regulate the expression of CEBPG in AML cell lines, and knockdown efficiency was detected by RT-qPCR and western blotting. The effect of knockdown on the growth of AML cell lines was evaluated by CCK-8. Western blotting was used to detect PARP cleavage, and flow cytometry were used to determine the effect of knockdown on apoptosis of AML cells. Genes and pathways affected by knockdown of CEBPG were identified by gene expression analysis using RNA-seq. One of the genes affected by knockdown of CEBPG was Eukaryotic translation initiation factor 4E binding protein 1 (EIF4EBP1), a known repressor of translation. Knockdown of EIF4EBP1 was used to assess its potential role in AML progression downstream of CEBPG. RESULTS: We explored the ChIP-Seq data of AML cell lines and non-AML hematopoietic cells, and found CEBPG was activated through its distal enhancer in AML cell lines. Using the public transcriptomic dataset, the Cancer Cell Line Encyclopedia (CCLE) and western blotting, we also found CEBPG was overexpressed in AML. Moreover, we observed that CEBPG promotes AML cell proliferation by activating EIF4EBP1, thus contributing to the progression of AML. These findings indicate that CEBPG could act as a potential therapeutic target for AML patients. CONCLUSION: In summary, we systematically explored the molecular characteristics of CEBPG in AML and identified CEBPG as a potential therapeutic target for AML patients. Our findings provide novel insights into the pathophysiology of AML and indicate a key role for CEBPG in promoting AML progression.

6.
J Paediatr Child Health ; 54(3): 284-288, 2018 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-28960558

RESUMO

AIM: To determine the level of cystatin C (Cys-C) values in preterm babies for the purpose of becoming a good endogenous marker of renal function. METHODS: A total of 366 very low-birthweight infants (including 70 extremely low-birthweight babies) with gestational age <37 weeks born in two centres were studied. RESULTS: In very low-birthweight infants, the mean level of Cys-C was 1.96 ± 0.44 mg/L in blood samples taken on day 1, 1.78 ± 0.49 mg/L on day 7 and 1.71 ± 0.47 mg/L on day 28. In extremely low-birthweight infants, the mean level of Cys-C was 2.00 ± 0.49 mg/L on day 1, 1.63 ± 0.38 mg/L on day 7 and 1.62 ± 0.55 mg/L on day 28, respectively. Compared to serum creatinine and blood urea nitrogen, Cys-C level was independent of birthweight and gestational age. CONCLUSION: Cys-C is regarded as an alternative for assessing renal function in very low-birthweight infants, but its advantages over serum creatinine and blood urea nitrogen has not been fully proved yet. Hence, larger sample study is still necessary.


Assuntos
Cistatina C/sangue , Recém-Nascido de muito Baixo Peso/sangue , Valores de Referência , Peso ao Nascer , Nitrogênio da Ureia Sanguínea , China , Creatinina/sangue , Feminino , Idade Gestacional , Taxa de Filtração Glomerular , Humanos , Recém-Nascido , Recém-Nascido Prematuro/sangue , Unidades de Terapia Intensiva Neonatal , Masculino
7.
J Res Med Sci ; 23: 90, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30505328

RESUMO

BACKGROUND: The objective of this study is to evaluate the value of neutrophil gelatinase-associated lipocalin (NGAL) for becoming a good endogenous marker of renal function in asphyxial preterm babies. MATERIALS AND METHODS: This is a two-center retrospective study. Between October 2016 and October 2017, 71 asphyxial preterm infants were included in asphyxia group. Seventy babies were randomly included in control group. Samples were tested at 24, 48, and 96 h after birth. Quantitative data were compared by independent sample t-test or repeated measures ANOVA. For qualitative data, Pearson's Chi-squared test was performed. Draw ROC and compare the area under the curve (AUC), 95% confidence interval for AUC, specificity (Spe), sensitivity (Sen), and Youden index (Sen+Spe-1) at 24-h, 48-h, and 96-h time points. RESULTS: (1) There are no significant differences concerning on baseline data. However, blood gas, Apgar score, and resuscitation showed a significant difference (P < 0.05). (2) In 24-h samples, only uNGAL and estimated glomerular filtration rate (eGFR) showed differences between the two groups (P < 0.05). In 48-h samples, significant differences could be found in uKIM-1, uNGAL, blood urea nitrogen, and eGFR (P < 0.05). In 96-h samples, almost all indicators have significant differences except urine output and eGFR (P < 0.05). (3) All biomarkers showed statistical difference in the three time points (P < 0.05), but only uNGAL showed a downward trend after the increase of expression. (4) uNGAL has better Sen and Spe than other indicators (24-h AUC 0.870, Youden index 0.606; 48-h AUC 0.879, Youden index 0.692; and 96-h AUC 0.806, Youden index 0.606). CONCLUSION: uNGAL has a better distinguishability in asphyxial neonates compared with other indicators. Certainly, a larger sample, prospective study is still needed.

8.
Cell Physiol Biochem ; 43(6): 2548-2561, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-29130995

RESUMO

BACKGROUND/AIMS: This study aims to identify whether Urothelial Cancer Associated 1 (UCA1) regulates mitochondrial metabolic reprogramming in bladder cancer, and to explore how UCA1 participates in mitochondrial metabolism by the UCA1/miR-195/ARL2 signaling pathway; these findings may be aid in the development of tumor diagnostic and therapeutic strategies. METHODS: Bladder tissues were obtained from patients. Stable cell lines were constructed, with ectopic expression of UCA1 in UMUC2 cells and knockdown of UCA1 in 5637 cells. The expression levels of UCA1, miR-195, and ARL2 were detected by real-time PCR, western blotting, and immunohistochemistry Cell viability was detected by Cell Counting Kit-8 (CCK8) assay; mitochondrial DNA copy numbers were tested by realtime PCR; ATP level was evaluated by ATP assay kit; mitochondrial membrane potential was analyzed by 5,5',6,6'-tetrachloro-1,1',3,3'- tetraethylbenzimidazolylcarbocyanine iodide (JC-1) fluorescent probe. miRNAs between UCA1 and ARL2 were predicted by TargetScan and RNAHybrid, and then determined by real-time PCR. Dual-luciferase activity assay and RNA immunoprecipitation (RIP) assay were used to verify the relationship between UCA1 and miR-195. The expression level of ARL2 was silenced by small interfering RNA(siRNA). For in vivo experiments, UCA1-silencing 5637 cells were subcutaneously injected into BALB/C nude mice to evaluate the effects of UCA1 on tumor progression by the regulation of miR-195 and ARL2. RESULTS: We demonstrate here that UCA1 enhances mitochondrial function in bladder cancer cells. UCA1 contributes to ARL2-induced mitochondrial activity, which plays an important role in mitochondrial function. UCA1, as a competing endogenous RNA (ceRNA), regulates mitochondrial function through upregulating ARL2. In this way, it inhibited the miR-195 signaling pathway to enhance mitochondrial function in bladder cancer. Additionally, ARL2 is a direct target of miR-195 and can be repressed by either miR-195 overexpression or UCA1 inhibition. Knockdown of ARL2 was analogous to the inhibition of UCA1 and the upregulation of miR-195. Animal experiments further indicated that UCA1 promoted bladder tumor growth by regulating miR-195 /ARL2. CONCLUSION: These data suggest that UCA1 enhanced mitochondrial function and cell viability through the UCA1/miR-195/ARL2 axis in vitro and in vivo. The elucidation of this signaling network provides a more adequate theoretical basis for understanding the molecular pathology of bladder cancer, and also UCA1 as a potential diagnosis and treatment target for bladder cancer.


Assuntos
Proteínas de Ligação ao GTP/metabolismo , MicroRNAs/metabolismo , Mitocôndrias/metabolismo , RNA Longo não Codificante/metabolismo , Neoplasias da Bexiga Urinária/patologia , Regiões 3' não Traduzidas , Trifosfato de Adenosina/metabolismo , Idoso , Animais , Antagomirs/metabolismo , Sequência de Bases , Linhagem Celular Tumoral , Sobrevivência Celular , DNA Mitocondrial/análise , DNA Mitocondrial/metabolismo , Feminino , Proteínas de Ligação ao GTP/antagonistas & inibidores , Proteínas de Ligação ao GTP/genética , Humanos , Masculino , Potencial da Membrana Mitocondrial , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Nus , MicroRNAs/antagonistas & inibidores , MicroRNAs/genética , Pessoa de Meia-Idade , Mitocôndrias/genética , Interferência de RNA , RNA Longo não Codificante/antagonistas & inibidores , RNA Longo não Codificante/genética , RNA Interferente Pequeno/metabolismo , Alinhamento de Sequência , Transdução de Sinais , Transplante Heterólogo , Bexiga Urinária/metabolismo , Bexiga Urinária/patologia , Neoplasias da Bexiga Urinária/metabolismo
9.
J Clin Lab Anal ; 31(5)2017 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-27796051

RESUMO

BACKGROUND: To explore the values of cystatin C (Cys-C) in asphyxial preterm babies as an effective endogenous marker of renal function. METHODS: After birth, preterm infants with 5-minute Apgar score <8 were included into the asphyxia group. Finally, 276 preterm infants born in two neonatal intensive care units were studied (including 78 babies in the asphyxia group and 198 babies in the control group). Blood samples were obtained from peripheral veins on day 1, day 7, and day 28 when routine blood screening tests were performed. RESULTS: In first day samples, the mean levels of Cys-C were 2.21 (1.49-2.98) mg/L with gestational age (GA) >32, 1.94 (1.37-2.76) mg/L with GA 28-32, and 1.87 (1.49-2.13) mg/L with GA <28 in the asphyxia group. In seventh day samples, the mean levels of Cys-C were 2.35 (1.57-3.26) mg/L with GA>32, 2.07 (1.42-2.90) mg/L with GA 28-32, and 1.69 (1.13-2.04) mg/L with GA <28. In twenty-eighth day samples, the mean levels of Cys-C were 1.92 (1.61-2.13) mg/L with GA>32, 1.79 (1.29-1.84) mg/L with GA 28-32, and 1.66 (1.21-2.10) mg/L GA <28. There were significant differences not only between the asphyxia and control groups, but also between the mild, moderate, and severe asphyxia groups. CONCLUSION: Cys-C has a good distinguishability in asphyxial neonates in spite of gestational age or birth weight in the Chinese population. Further studies with large numbers of cases are required to assess whether Cys-C could replace creatinine (Cr) and blood urea nitrogen (BUN) as an endogenous marker of renal function.


Assuntos
Cistatina C/sangue , Adulto , Asfixia Neonatal/sangue , Asfixia Neonatal/epidemiologia , Asfixia Neonatal/terapia , Nitrogênio da Ureia Sanguínea , Estudos de Casos e Controles , China/epidemiologia , Creatinina/sangue , Feminino , Humanos , Lactente , Recém-Nascido , Recém-Nascido Prematuro/sangue , Terapia Intensiva Neonatal , Masculino
10.
J Cell Mol Med ; 20(6): 1024-35, 2016 06.
Artigo em Inglês | MEDLINE | ID: mdl-26843477

RESUMO

As the most predominant tumour-infiltrating immune cells, tumour-associated macrophages (TAMs) are significant for fostering tumour growth, progression and metastasis. CD68-positive TAMs display dissimilarly polarized programmes comprising CD11c-positive pro-inflammatory macrophages (M1) and CD206-positive immunosuppressive macrophages (M2). The aim of this study is to determine the prognostic significance of diametrically polarized TAMs in hepatocellular carcinoma (HCC) and their application to risk stratification of patients according to their specific prognostic values. This study included 80 consecutive patients with HCC, and we evaluated diametrically polarized functional status of macrophages by immunohistochemical staining of CD68, CD11c and CD206. Prognostic values and clinicopathologic features were assessed in these patients. High versus low CD11c-positive TAM density (P = 0.005) and low versus high CD206-positive TAM density (P = 0.002) were associated with better overall survival, whereas CD68-positive TAM density had no prognostic significance (low versus high, P = 0.065). Furthermore, the presence of these positive staining macrophages did not show any prognostic significance for recurrence-free survival (all P > 0.05). Multivariate Cox regression analysis identified CD11c-positive and CD206-positive TAMs as an independent prognostic factor (P < 0.001, P = 0.031, respectively). Intratumoural infiltration of diametrically polarized TAMs, a novel identified independent prognostic factor for survival in patients with HCC, could be combined with the TNM stage and the Barcelona Clinic Liver Cancer stage to improve a risk stratification system.


Assuntos
Carcinoma Hepatocelular/patologia , Carcinoma Hepatocelular/cirurgia , Polaridade Celular , Neoplasias Hepáticas/patologia , Neoplasias Hepáticas/cirurgia , Macrófagos/metabolismo , Macrófagos/patologia , Antígenos CD/metabolismo , Intervalo Livre de Doença , Feminino , Humanos , Imuno-Histoquímica , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Prognóstico
11.
J Res Med Sci ; 21: 41, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-27904587

RESUMO

BACKGROUND: In the past several years, randomized controlled trials (RCTs) have indicated that inhaled nitric oxide (iNO) can potentially lower for both the incidence of bronchopulmonary dysplasia (BPD) and mortality in affected infants. Other research has, however, disagreed with these findings. MATERIALS AND METHODS: We performed an updated meta analysis of all relevant RCTs to assess the benefits of iNO in preterm infants by searching PubMed, EMBASE, Cochrane databases, Wanfang, VIP, and CNKI databases for English and Chinese references. RESULTS: Ultimately, 22 RCTs were incorporated. (1) Risk of BPD was significantly lower in preterm infants supplemented with iNO (relative risk [RR] = 0.88; P = 0.0007). There are no differences concerning pulmonary hemorrhage (PH) (RR = 0.94; P = 0.72). (2) Incidences of necrotizing enterocolitis (NEC), retinopathy of prematurity (ROP), and severe intracranial hemorrhage (ICH) were compared. No significant difference was discovered concerning these risks (RR = 1.21, P = 0.08; RR = 1.01, P = 0.89; and RR = 0.99, P = 0.86). (3) In addition, no significant differences were found between experimental and control groups with respect to morality. (RR = 1.00, P = 0.98). CONCLUSION: Our meta analysis has shown a beneficial effect in BPD and morality. In addition, our meta analysis suggests that iNO therapy does not increase the risk of common complications, such as NEC and ROP, and that it may also have no adverse effect on bleeding tendency diseases (severe ICH and PH).

12.
Zhongguo Dang Dai Er Ke Za Zhi ; 18(2): 105-7, 2016 Feb.
Artigo em Zh | MEDLINE | ID: mdl-26903054

RESUMO

OBJECTIVE: To study the clinical features of severe neonatal necrotizing enterocolitis (NEC), and to investigate the diagnostic value of prealbumin (PA) in neonates with severe NEC. METHODS: The clinical data and results of routine blood test and blood biochemical test of 40 neonates with NEC (29 neonates with NEC II and 11 with NEC III) were analyzed. The multivariate logistic regression analysis and receiver operating characteristic (ROC) curve were applied to investigate the value of PA in the diagnosis of severe NEC. RESULTS: The multivariate logistic regression analysis showed that PA was an important index for the diagnosis of severe NEC (≥IIB). The ROC analysis showed that in the diagnosis of severe NEC (≥IIB), PA had high sensitivity (0.870) and specificity (0.647). CONCLUSIONS: PA has a good value in the diagnosis of severe NEC.


Assuntos
Enterocolite Necrosante/diagnóstico , Doenças do Recém-Nascido/diagnóstico , Pré-Albumina/análise , Enterocolite Necrosante/sangue , Feminino , Humanos , Lactente , Recém-Nascido , Doenças do Recém-Nascido/sangue , Masculino , Curva ROC , Índice de Gravidade de Doença
13.
Tumour Biol ; 36(6): 4235-41, 2015 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-25592379

RESUMO

Kindlin-1 is a member of the Kindlin family of focal adhesion proteins and is implicated in cell adhesion, proliferation, polarity, and motility. Although expression of Kindlin-1 has recently been reported in a variety of human cancers, studies on its expression in human hepatocellular carcinoma (HCC) are currently lacking. This study aimed to determine the clinicopathological parameters and prognostic value of Kindlin-1 in HCC patients after surgical resection. The messenger RNA (mRNA) and protein levels of Kindlin-1 in 22 matched HCC specimens were assessed by quantitative real-time PCR (qRT-PCR) and Western blotting assays. The clinical and prognostic significance of Kindlin-1 in 68 cases of HCC was determined by immunohistochemistry. Kindlin-1 expression was higher in HCC tumor tissues relative to that in adjacent normal tissue at the both mRNA and protein levels (p < 0.05). Immunohistochemical results revealed that overexpression of Kindlin-1 was detected in 37 of 68 (54.4 %) tumor tissues and in seven of 68 (10.3 %) adjacent non-tumor tissues (p < 0.05). Positive Kindlin-1 expression was significantly correlated with tumor size, tumor capsula, status of metastasis, and tumor-node-metastasis (TNM) stage. Additionally, Kaplan-Meier survival analysis showed that positive Kindlin-1 expression was associated with unfavorable overall survival (OS) and disease-free survival (DFS). Multivariate analysis identified Kindlin-1 as an independent prognostic predictor for OS and DFS in HCC patients (p = 0.041 and 0.027, respectively). Taken together, our data suggest that Kindlin-1 could play an important role in HCC and might serve as a promising prognostic marker and potential target for HCC therapy.


Assuntos
Biomarcadores Tumorais/biossíntese , Carcinoma Hepatocelular/genética , Neoplasias Hepáticas/genética , Proteínas de Membrana/biossíntese , Proteínas de Neoplasias/biossíntese , Prognóstico , Adulto , Idoso , Biomarcadores Tumorais/genética , Carcinoma Hepatocelular/patologia , Carcinoma Hepatocelular/cirurgia , Intervalo Livre de Doença , Feminino , Regulação Neoplásica da Expressão Gênica , Hepatectomia , Humanos , Estimativa de Kaplan-Meier , Neoplasias Hepáticas/patologia , Neoplasias Hepáticas/cirurgia , Masculino , Proteínas de Membrana/genética , Pessoa de Meia-Idade , Proteínas de Neoplasias/genética
14.
Jpn J Clin Oncol ; 45(11): 1055-63, 2015 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-26373319

RESUMO

OBJECTIVE: Long non-coding ribonucleic acid urothelial carcinoma-associated 1 has been found to be a participant in cancer development and glucose metabolism in bladder cancer. However, the role of urothelial carcinoma-associated 1 in metabolic reprogramming in cancer remains to be clarified. In this study, we aim to elucidate the molecular mechanism underlying the regulation of glutamine metabolism by urothelial carcinoma-associated 1 in bladder cancer. METHODS: The RNA levels of urothelial carcinoma-associated 1, GLS2 and miR-16 in bladder tissues and cell lines were examined by real-time reverse transcriptase-polymerase chain reaction. The protein levels of GLS2 were detected by western blot analysis. Reactive oxygen species generation was examined by the fluorescein isothiocyanate mean value and fluorescence microscope. Glutamine consumption was analyzed using the glutamine assay kit. Additionally, we performed luciferase reporter assays to validate urothelial carcinoma-associated 1 sequence whether contains miR-16 binding site and the interaction between the 3'UTR sequence of GLS2 and mature miR-16. RESULTS: Real-time reverse transcriptase-polymerase chain reaction demonstrated that the RNA level of urothelial carcinoma-associated 1 and GLS2 was positively correlated in bladder cancer tissues and cell lines. The expression of GLS2 mRNA and protein increased in cells which overexpression of urothelial carcinoma-associated 1 and decreased in cells which knocked-down of urothelial carcinoma-associated 1 cell lines. urothelial carcinoma-associated 1 reduced ROS production, and promoted mitochondrial glutaminolysis in human bladder cancer cells. Furthermore, luciferase reporter assays indicated that there was a miR-16 binding site in urothelial carcinoma-associated 1, and it showed appreciable levels of sponge effects on miR-16 as readouts in a dose-dependent manner. Moreover, the 'seed region' of miR-16 directly bound to the 3'UTR of GLS2 mRNA and regulated GLS2 expression level. CONCLUSIONS: Together, our results revealed that urothelial carcinoma-associated 1 regulated the expression of GLS2 through interfering with miR-16, and repressed ROS formation in bladder cancer cells.


Assuntos
Carcinoma de Células de Transição/metabolismo , Glutaminase/metabolismo , Glutamina/metabolismo , MicroRNAs/metabolismo , RNA Longo não Codificante/metabolismo , Espécies Reativas de Oxigênio/antagonistas & inibidores , Neoplasias da Bexiga Urinária/metabolismo , Carcinoma de Células de Transição/genética , Humanos , Neoplasias da Bexiga Urinária/genética
15.
Neurol Sci ; 36(11): 2043-51, 2015 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-26130145

RESUMO

The aim of this study was to explore the clinical characteristics and etiology of mild encephalitis/encephalopathy with a reversible splenial lesion (MERS) in China by retrospectively analyzing five MERS cases from the Jiangsu Provincial Hospital within a total of 27 reported MERS cases from available Chinese literature. Most of the 27 cases originated near the eastern and southern parts of China. Ages for 23 MERS cases were under 30 years and the female-to-male ratio was 1:1.25. The major causes of MERS included infection, antiepileptic drug withdrawal, high-altitude cerebral edema, and cesarean section (C-section). Hyponatremia was also observed in 10 MERS cases. All patients had a complete recovery within a month. Steroids and IVIG were the most commonly used therapy for MERS, but their efficiency remained questionable.


Assuntos
Encefalopatias/etiologia , Infecções por Coronavirus/complicações , Corpo Caloso/patologia , Adolescente , Adulto , Encefalopatias/patologia , Encefalopatias/fisiopatologia , Encefalopatias/terapia , Pré-Escolar , China , Infecções por Coronavirus/patologia , Infecções por Coronavirus/fisiopatologia , Infecções por Coronavirus/terapia , Feminino , Humanos , Imageamento por Ressonância Magnética , Masculino , Índice de Gravidade de Doença , Adulto Jovem
16.
Neuro Endocrinol Lett ; 36(6): 601-28, 2015 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-26812286

RESUMO

OBJECTIVES: With the improvement of premature infant cure rate and livability, the incidence of PVL has been one of the main reasons for premature infant nervous system sequelae. miRNAs are important in the regulation of cell growth, differentiation, apoptosis and carcinogenesis. The aim of the present study was to identify differentially expressed miRNAs between PVL and normal tissues. METHODS: The target genes of significant miRNA were retrieved from the miRecords database. Furthermore, GO analysis and biological process interaction network was constructed using the BiNGO and Cytoscape software. Finally, KEGG analysis from DAVID was used to find meaningful signaling pathway. RESULTS: In conclusion, this study identified 16 differentially expressed miRNAs, which may be important in the progression of PVL and miRNA 141 demonstrated the greatest quantity of target genes. In addition, Hdac4, Lamc1, Irs1 and Zeb1 are the most frequently appeared ones among proved genes. Wnt signaling pathway and Neurotrophin signaling pathway were identified to be significantly associated with PVL. CONCLUSION: This work may bring some new hints for the pathogenesis of PVL in the future work. However, further investigation regarding the specific function is required.

17.
Sichuan Da Xue Xue Bao Yi Xue Ban ; 45(6): 908-12, 2014 Nov.
Artigo em Zh | MEDLINE | ID: mdl-25571713

RESUMO

OBJECTIVE: To investigate the effects of smokeless tobacco extract (STE) on biological properties of osteoblast, and to identify possible pathological mechanisms of osseointegration. METHODS: MC3T3-E1 Sub-clone 14 cells were cultured in the presence of STE at 0 (control group),0. 01,0. 1,1,5,10 g/L. The cell proliferation was measured by MTT assay 1 d, 3 d, 5 d, and 7 d after exposure. The F-actin cytoskeleton of MC3T3 was stained with Rhodamine and DAPI, and then examined under a confocal laser scanning microscope 24 h after exposure to STE. The mRNA expressions of interleukin-6 (IL-6) and core-binding factor αl(Cbfαl) were quantified by real- time PCR (RT-qPCR) 48 h after exposure to STE. RESULTS: The MTT assay showed that 0. 01-10 g/L STE inhibited MC3T3 proliferation (P<0. 05). Prolonged time enabled 5-10 g/L STE to inhibit MC3T3 proliferation (P<0. 05). Network structure in F-actin cytoskeleton was demonstrated in the controls. In the cells exposed to STE, F-actin cytoskeleton started to change with disruptive structures. As the concentration of STE increased, the changes became more significant. STE increased the mRNA expression of IL-6 at the concentration of 5 g/L and 10 g/L (P<0.05), decreased the mRNA expression of Cbfα1 at the concentration of 0. 1-10 g/L (PO<0. 05). CONCLUSION: Tobacco may inhibit osteoblast proliferation, destroy F-actin cytoskeleton structure, increase the mRNA expression of IL-6 and decrease the mRNA expression of Cbfα1, and inhibit cell differentiation and adhesion accordingly. Smoking is a disadvantage to osseointegration.


Assuntos
Osteoblastos/efeitos dos fármacos , Tabaco sem Fumaça/efeitos adversos , Células 3T3/efeitos dos fármacos , Citoesqueleto de Actina/metabolismo , Animais , Diferenciação Celular , Proliferação de Células , Subunidades alfa de Fatores de Ligação ao Core/metabolismo , Interleucina-6/metabolismo , Camundongos
18.
Front Oncol ; 14: 1307907, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38450180

RESUMO

Objectives: To establish a radiomics model for distinguishing between the benign and malignant mammary gland nodules via combining the features from nodule and mammary regions on DCE-MRI. Methods: In this retrospective study, a total of 103 cases with mammary gland nodules (malignant/benign = 80/23) underwent DCE-MRI, and was confirmed by biopsy pathology. Features were extracted from both nodule region and mammary region on DCE-MRI. Three SVM classifiers were built for diagnosis of benign and malignant nodules as follows: the model with the features only from nodule region (N model), with the features only from mammary region (M model) and the model combining the features from nodule region and mammary region (NM model). The performance of models was evaluated with the area under the curve of receiver operating characteristic (AUC). Results: One radiomic features is selected from nodule region and 3 radiomic features is selected from mammary region. Compared with N or M model, NM model exhibited the best performance with an AUC of 0.756. Conclusions: Compared with the model only using the features from nodule or mammary region, the radiomics-based model combining the features from nodule and mammary region outperformed in the diagnosis of benign and malignant nodules.

19.
J Inflamm Res ; 17: 5025-5037, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-39081873

RESUMO

Objective: This prospective study is to explore the role of specific circRNAs in predicting the development of bronchopulmonary dysplasia (BPD). Methods: From July 1, 2021 to December 1, 2021, peripheral blood samples were collected from 62 premature infants with gestational age (GA) ≤32 weeks on the 7th, 14th, and 28th day after birth. Then, on the 28th day, the included infants were divided into the BPD group and the non-BPD group according to the definition of BPD. Serum exosomal circRNAs from peripheral blood were identified, sequenced, and compared between the BPD and non-BPD groups at different time points. Specific differentially expressed circRNAs were further verified from another 42 enrolled premature infants (GA ≤32 weeks). The classical lung biological markers in serum were also measured simultaneously. Results: Hsa_circ_0001359 in serum exosomes showed continuous differential expression between the BPD group and the non-BPD group on the 7th, 14th, and 28th day. Compared with that, classical lung biological markers like IL-6, IL-33, KL-6, and ET-1 did not exhibit continuous differences. Moreover, the expression of hsa_circ_0001359 on day 7 had a higher predictive value in predicting BPD (area under curve:0.853, 95% CI:0.738-0.968; adjusted odds ratio:6.033, 95% CI:2.373-13.326). The calibration curve further showed the mean absolute error = 0.033, mean squared error = 0.00231, and quantile of absolute error = 0.058. Conclusion: Hsa_circ_0001359 in serum exosomes is a promising marker for predicting BPD in preterm infants with gestational age ≤32 weeks.

20.
Zhonghua Yi Xue Za Zhi ; 93(31): 2454-8, 2013 Aug 20.
Artigo em Zh | MEDLINE | ID: mdl-24300263

RESUMO

OBJECTIVE: To compare the clinical efficacy of interventional thrombectomy versus thrombolytic treatment for acute mixed-type lower extremity deep venous thrombosis (LEDVT). METHODS: The clinical data of 458 patients with acute mixed type LEDVT were analyzed retrospectively.Group A: 327 patients underwent mechanical aspiration thrombectomy; Group B: 131 patients received systematic thrombolysis and anticoagulation with urokinase and heparin. RESULTS: Complete thrombus removal (Grade I): Group A was was better than group B (65.44% vs 37.4%) (P = 0.000). The circumference differences of healthy and affected limbs of knee-joints' below and above 15 cm at discharge were (1.34 ± 0.57) and (0.93 ± 0.32) cm in group A were better than (1.72 ± 0.69) and (1.29 ± 0.43) cm in group B (both P = 0.000). Among them, 411 patients had a median follow-up period of 35 (16-70) and the follow-up rate was 89.83%. At 36 months postoperation, the circumference difference of affected limbs of knee-joints' below 15 cm for group A (0.53 ± 0.22) cm was better than that for group B (1.42 ± 0.65) cm (P = 0.000) . And the sequelae occurrence rates of edema, pigmentation and ulceration of group A (29.64%, 14.01%,0%) were lower than those of group B (55.77%, 83.65%, 9.62%) (both P = 0.000). Color Doppler flow imaging revealed that the vein patency rate of group A was 90.23% and normal valve function rate 71.34%. And both were better than group B (37.50%, 15.38%) (P = 0.000; P = 0.000). The total effective rate of group A (100%) was better than that of group B (71.15%) (P = 0.000). Excellency rate: group A (88.93%) was higher than group B (29.81%) (P = 0.000). CONCLUSION: Interventional thrombectomy is better than simple thrombolysis in the treatment of acute mixed-type lower extremity deep venous thrombosis. And the former offers better protection of normal valve function.


Assuntos
Fibrinolíticos/administração & dosagem , Trombose Venosa/tratamento farmacológico , Trombose Venosa/terapia , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Fibrinolíticos/uso terapêutico , Humanos , Extremidade Inferior/irrigação sanguínea , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Trombectomia/métodos , Terapia Trombolítica/métodos , Resultado do Tratamento
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