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2.
Neurotox Res ; 37(1): 171-182, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31493120

RESUMO

Depression is a worldwide problem with a great social and economic burden in many countries. In our previous research, we found that the expression of proBDNF/p75NTR/sortilin is upregulated in patients with major depressive disorder. In addition, the treatment of proBDNF antibodies reversed both the depressive behaviors and the reduced BDNF mRNA detected in our rodent chronic stress models. Antidepressant drugs are usually only effective in a subpopulation of patients with major depression with a delayed time window of 2-4 weeks to exert their efficacy. The mechanism underlying such delayed response is not known. In this study, we hypothesize that antidepressant drugs exert their therapeutic effect by modulating proBDNF/p75NTR and mature BDNF/TrkB signaling pathways. To test the hypothesis, C57 mice were randomly divided into normal control, chronic unpredictable mild stress (CUMS), vehicle (VEH), fluoxetine (FLU), and clozapine (CLO) groups. Behavioral tests (sucrose preference, open field, and tail suspension tests) were performed before and after 4 weeks of CUMS. The gene and protein expression of proBDNF, the neurotrophin receptor (p75NTR), sortilin, and TrkB in the cortex and hippocampus were examined. At the protein level, CUMS induced a significant increase in proBDNF, p75NTR, and sortilin production while the TrkB protein level was found to be lower in the cortex and hippocampus compared with the control group. Consistently, at the mRNA level, p75NTR expression increased with reduced BDNF/TrkB mRNA in both cortex and hippocampus, while sortilin increased only in the hippocampus after CUMS. FLU and CLO treatments of CUMS mice reversed all protein and mRNA expression of the biomarkers in both cortex and hippocampus, except for sortilin mRNA in the cortex and proBDNF in the hippocampus, respectively. This study further confirms that the imbalance between proBDNF/p75NTR/sortilin and mBDNF/TrkB production is important in the pathogenesis of depression. It is likely that antidepressant FLU and antipsychotic CLO exert their antidepressant-like effect correcting the imbalance between proBDNF/p75NTR/sortilin and mBDNF/TrkB.

4.
Beijing Da Xue Xue Bao Yi Xue Ban ; 51(5): 797-804, 2019 Oct 18.
Artigo em Chinês | MEDLINE | ID: mdl-31624380

RESUMO

OBJECTIVE: To investigate inhibitory activities of a homogenous anti-human epidermal growth factor receptor 2 (HER2)-antibody drug conjugate (ADC) on the proliferation of nine tumor cell lines with different levels of HER2 expressions, and its activities on the tumor growth of five xenograft mouse models. METHODS: The HER2 expression levels of BT-474, Calu-3, MCF-7, MDA-MB-231, MDA-MB-468, SK-BR-3, SK-OV-3, HCC1954, NCI-N87 tumor cell lines were measured using QIFI KIT. For the in vitro anti-proliferation assay, serial diluted anti-HER2-ADC, ado-trastuzumab emtansine, AS269, pAF-AS269 and paclitaxel were added to the seeded cells, and after 72 or 96 hours of incubation, the cell proliferation was analyzed. For the in vivo activity, 5-6 weeks old mice were inoculated with four HER2 positive tumor cell lines HCC1954, BT-474, SK-OV-3, NCI-N87 or one HER2 negative tumor cell line MDA-MB-468. Different amounts of anti-HER2-ADC, ado-trastuzumab emtansine, trastuzumab, paclitaxel and phosphate buffered saline control were injected after the tumor volume reached a certain size, then the tumor growth inhibition was analyzed. RESULTS: The expression levels of the six high HER2-expression cell lines SK-OV-3, NCI-N87, SK-BR-3, Calu-3, HCC1954, BT-474 were between 430 000 to 800 000 receptors per cell, which were 50 times higher than those of the other three low HER2 expression tumor cell lines MDA-MB-231, MCF-7, MDA-MB-468. Anti-HER2-ADC had inhibition effects on cell lines with high level of HER2 expression in the in vitro anti-proliferation assay. The half maximal inhibitory concentrations of anti-HER2-ADC on SK-OV-3, NCI-N87, SK-BR-3, Calu-3, HCC1954, BT-474 tumor cell lines were 46 pmol/L, 17 pmol/L, 17 pmol/L, 161 pmol/L, 125 pmol/L, 50 pmol/L, respectively. Anti-HER2-ADC had a dose dependent antitumor activity in vivo in all the HER2 positive xenograft mouse models. In NCI-N87 xenograft tumor model, the same dose of anti-HER2-ADC showed better anti-tumor activity compared with trastuzumab and ado-trastuzumab emtansine, and its relative tumor proliferation rates were about 1/30 to 1/20 of the two. In HCC1954 xenograft tumor model, the complete regression of the tumor was observed. As expected, anti-HER2-ADC had no tumor inhibitory effects on MDA-MB-468 xenograft models with low HER2 expression. The antitumor activities of anti-HER2-ADC in HER2 positive xenograft tumor models were the same as or better than the activities of ado-trastuzumab emtansine. CONCLUSION: The homogenous site-specific anti-HER2-ADC obtained using unnatural amino acid technology can inhibit the growth of high HER2-expression tumor cells with high potency both in vivo and in vitro.


Assuntos
Imunoconjugados , Receptor ErbB-2 , Aminoácidos , Animais , Neoplasias da Mama , Linhagem Celular Tumoral , Humanos , Camundongos , Trastuzumab , Ensaios Antitumorais Modelo de Xenoenxerto
5.
AJNR Am J Neuroradiol ; 40(10): 1665-1671, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31537520

RESUMO

BACKGROUND AND PURPOSE: Choroidal collateral anastomosis is associated with hemorrhage recurrence in patients with Moyamoya disease. However, the relationship between recurrent ipsilateral hemorrhage and choroidal collateral anastomosis subtypes (anterior choroidal artery anastomosis, lateral posterior choroidal artery anastomosis, and medial posterior choroidal artery anastomosis) is unclear. This study aimed to assess this potential association in adult patients with Moyamoya disease. MATERIALS AND METHODS: Patients angiographically diagnosed with Moyamoya disease who underwent conservative treatment between January 2008 and December 2018 were included in this retrospective study. Two readers assessed the angiographic images to identify choroidal collateral anastomosis subtypes, and Cox proportional hazard regression models were used to estimate the risk of recurrent hemorrhage associated with each subtype. RESULTS: Thirty-nine patients (mean age = 45.2 years) were included in this study. During 52.4 ± 37.0 months of follow-up, recurrent ipsilateral hemorrhage occurred in 48.7% (19/39) of patients. Patients with recurrent hemorrhage had a higher prevalence of choroidal collateral (94.8% versus 60.0%; P = .02) and lateral posterior choroidal artery (78.9% versus 25.0%; P < .01) anastomoses than those without recurrent hemorrhage. Lateral posterior choroidal artery anastomosis was associated with recurrent hemorrhage before (hazard ratio = 6.66; 95% CI, 2.18-20.39; P < .01) and after (hazard ratio = 5.78; 95% CI, 1.58-21.13; P < .01) adjustments were made for age, sex, and other confounding factors. CONCLUSIONS: Choroidal collateral anastomosis is responsible for most cases of recurrent hemorrhage in adult patients with Moyamoya disease; lateral posterior choroidal artery anastomosis is a significant risk factor for these recurrent events.

6.
Zhonghua Yi Xue Za Zhi ; 99(34): 2681-2686, 2019 Sep 10.
Artigo em Chinês | MEDLINE | ID: mdl-31505719

RESUMO

Objective: To investigate the phenomenon of small airway epithelial-mesenchymal transition (EMT) in patients with normal pulmonary function and chronic obstructive pulmonary disease (COPD) who received surgical treatment for lung tumors. Methods: In this study, 52 patients undergoing surgical treatment for lung tumors admitted to the General Hospital of Ningxia Medical University were included from January 2018 to January 2019. According to the preoperative pulmonary function and smoking history, patients were divided into group A (non-smoking with normal pulmonary function group, 15 patients), group B (smoking with normal pulmonary function group, 21 patients), group C (COPD stable phase group, 16 patients). HE staining was performed to observe the pathological changes in small airway and lung tissue. Immunohistochemistry was used to detect the localization and expression of E-cadherin, α-smooth muscle actin (α-SMA) and Vimentin in small airway. Western blot was used to detect the levels of E-cadherin, α-SMA and Vimentin. Results: (1) There were no significant differences in age, gender, and the ratio of disease composition among the three groups (P>0.05), but forced expiratory volume in one second (FEV(1)) as percentage of predicted value (FEV(1)%pred) and FEV(1)/forced vital capacity (FEV(1)/FVC) in group C were lower than those in groups A and B (all P<0.01), while there was no significant difference between group A and group B (P>0.05); (2) the bronchial wall thickness in group B and group C were higher than that of group A [(32.4±2.4) and (54.6±4.9) vs (22.4±2.2) µm], and group C was significantly higher than group B (P=0.003); (3) the expression levels of E-cadherin in the epithelial cells of small airway in group B and group C were lower than those in group A (0.021±0.008 and 0.018±0.007 vs 0.062±0.010) (all P<0.05), while the levels of mesenchymal cell markers such as α-SMA and Vimentin in group B and group C were higher than group A, and group C was higher than group B (α-SMA: 0.641±0.113, 0.780±0.133 vs 0.404±0.123; Vimentin: 0.064±0.033, 0.083±0.022 vs 0.030±0.021) (P=0.002 and P=0.003). Conclusion: In patients undergoing surgical treatment of lung tumors, there is EMT in the small airways of patients with COPD, and EMT has occurred in the small airways of smokers with normal pulmonary function.


Assuntos
Neoplasias Pulmonares , Doença Pulmonar Obstrutiva Crônica , Transição Epitelial-Mesenquimal , Humanos , Pulmão , Neoplasias Pulmonares/complicações , Neoplasias Pulmonares/cirurgia , Doença Pulmonar Obstrutiva Crônica/complicações , Doença Pulmonar Obstrutiva Crônica/cirurgia , Testes de Função Respiratória
7.
Zhonghua Wai Ke Za Zhi ; 57(10): 14-18, 2019 Oct 01.
Artigo em Chinês | MEDLINE | ID: mdl-31510727

RESUMO

Objective: To investigate the changes of surgical invitations on necrotizing pancreatitis in recent 14 years by reviewing single center data. Methods: One thousand and eighty patients with necrotizing pancreatitis who received surgical invitation were involved in the study.All the patients were treated at Department of Pancreatic Surgery,Union Hospital,Tongji Medical College,Huazhong University of Science and Technology from January 2005 to December 2018. Six hundred and seventy-eight were males and 402 were females. The median (range) age of the study patients was 45 (20-76) years.The etiology of the disease was related to cholelithiasis in 335 cases(31.02%), hyperlipemia in 302 cases(27.96%), alcohol in 226 cases(20.93%), endoscopic retrograde cholangiopancreatography in 28 cases(2.59%), pregnancy in 50 cases(4.63%), idiopathic factors in 72 cases(6.67%) and other causes in 67 cases(6.20%). The patients were divided into two groups according to the time of admission. Group 1 included 1 475 patients that admitted from January 2005 to December 2010, and group 2 included 1 539 patients that admitted from January 2011 to December 2018. The surgical interventions, morbidity and mortality of the two group were compared, and χ(2) test was used for the statistical test. Results: Two hundred and sixty-six among the 1 080 cases were treated with drainage procedures because of the pseudocyst.One hundred and seventy-five drainage procedures were performed between January 2005 and December 2018, which account for 11.87%(175 /1 475) of all patients of necrotizing pancreatitis; 91 drainage procedures were performed between January 2011 and December 2018,which account for 5.91%(91/1 539) of all patients of necrotizing pancreatitis. Eight hundred and fourteen cases received surgical intervention for infection of necrotizing tissues. Of these cases, 410 cases received percutaneous catheter drainage(PCD) of retroperitoneal fluid or residual infection. Debridement of necrotic tissues was performed on 756 cases. Of these cases, 32 cases received minimal invasive retroperitoneal debridement with/without denotes video assistant,4 cases received transluminal endoscopic debridement, 21 cases received laparoscopic debridement, and 709 cases received open laparotic debridement.Three hundred and sixty-five cases were admitted to our institute during January 2005 to December 2010, and the other 391 cases were admitted to our institute from January 2011 to December 2018. Of the first period, all debridement were performed with open laparotic procedures. Of the second period,debridement were performed with open laparotic procedures and minimal invasive procedures. The average times of surgical invasion, morbidity of principal local complications and mortality of the two periods were 1.27 and 1.34,28.22%(103/365) and 29.92%(117/346),and 6.03%(23/365) and 6.91%(27/346), respectively. Conclusions: Minimal invasive procedures can be considered for debridement in patients with necrotizing pancreatitis in some selected conditions.The involvements of minimal invasive procedures in treatment of necrotizing pancreatitis don't decrease the morbidity of principal local complications and mortality in recent years. Rational surgical procedures and appropriate surgical timing are the keys to improve the efficacy of necrotizing pancreatitis.


Assuntos
Pancreatite Necrosante Aguda/cirurgia , Espaço Retroperitoneal/cirurgia , Adulto , Idoso , Desbridamento/métodos , Drenagem/métodos , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Pseudocisto Pancreático/etiologia , Pseudocisto Pancreático/cirurgia , Pancreatite Necrosante Aguda/complicações , Pancreatite Necrosante Aguda/mortalidade , Estudos Retrospectivos , Resultado do Tratamento , Adulto Jovem
8.
Zhonghua Yi Xue Za Zhi ; 99(29): 2270-2275, 2019 Aug 06.
Artigo em Chinês | MEDLINE | ID: mdl-31434401

RESUMO

Objective: To investigate the surgical treatment of severe congenital cervical kyphosis. Methods: The clinical data of patients with severe congenital cervical kyphosis (Cobb>40°) treated in Peking University Third Hospital from March 2004 to March 2018 were retrospectively summarized. In this series, 8 cases were enrolled, included 4 males and 4 females; the patients were 5-45 years old. According to the etiology, 4 patients were diagnosed with vertebral body underdevelopment, 2 with vertebral insufficiency, 1 with cervical spine congenital fusion and 1 with C(2) spinous process mecism. Five cases were treated with traction before final surgical correction. The surgical strategy was anterior correction or posterior correction or combined procedure in regards to different situation. The curvature of cervical angle was measured by two-line Cobb method, and the cervical kyphosis angle was measured on lateral radiographs in the neutral and extended position at the pre-operation and post-operation in each patient. The correction rate and evaluated Japanese Orthopedic Association (JOA) scoring for the function of spinal cord were also measured. The data before and after the operation were compared with t test. Results: In this series, the average kyphotic Cobb angle was 67°±18° and 8°±8° before and after surgical correction, respectively (t=8.471,P<0.05).The final correction rate was 87%±13%.The JOA score improved from 11.1±2.7 to 14.0±1.5 (t=-2.656, P<0.05) at the end of follow up. Conclusions: The pre-correction by cervical spine traction and final surgical correction by anterior, posterior or combined approaches of internal fixation and fusion can achieve good results and reduce risk and difficulty in operation for severe congenital cervical spine kyphosis with vertebral body underdevelopment without vertebral insufficiency and cervical spine congenital fusion. The final surgical correction by one-stage anterior, posterior or combined approaches of internal fixation and fusion can achieve good results for severe congenital cervical spine kyphosis with vertebral insufficiency and/or cervical spine congenital fusion.


Assuntos
Cifose , Fusão Vertebral , Adolescente , Adulto , Criança , Pré-Escolar , Feminino , Humanos , Cifose/cirurgia , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Vértebras Torácicas , Resultado do Tratamento , Adulto Jovem
9.
Zhonghua Zhong Liu Za Zhi ; 41(8): 599-603, 2019 Aug 23.
Artigo em Chinês | MEDLINE | ID: mdl-31434451

RESUMO

Objective: To investigate the relationship between systemic inflammatory markers such as neutrophil/lymphocyte ratio (NLR) and C-reactive protein/albumin ratio (CAR), and lymph node metastasis in patients with cN0 gastric cancer. To establish a nomogram model to predict the risk of lymph node metastasis in patients with cN0 gastric cancer. Methods: The preoperative systemic inflammatory markers and clinical data of 134 patients with cN0 gastric cancer were retrospectively analyzed, and these markers of patients with negative (pN0) or positive (pN+ ) lymph node metastasis in postoperative pathological diagnosis were compared. The receiver operating characteristic (ROC) curve was used to evaluate the predictive effect of preoperative systemic inflammatory markers on lymph node metastasis. The influencing factors for lymph node metastasis were assessed by univariate analysis and multivariate logistic regression analysis. A nomogram subsequently established by R software was validated by Bootstrap resampling as internal validation. Results: Compared with pN0 group, NE (P=0.022), CRP (P<0.001), NLR (P<0.001), PLR (P=0.003) and CAR (P<0.001) were higher, LY (P=0.003) and Alb (P=0.042) were lower in pN+ group. ROC curve analysis showed that the area under the curve (AUC) of postoperative pathological lymph node metastasis in patients with cN0 gastric cancer diagnosed by NLR, PLR and CAR were 0.687, 0.651 and 0.694, respectively, and the best cutoff values were 2.12, 113.59 and 0.02, respectively. The corresponding sensitivity and specificity were 62.9% and 72.2%, 77.4% and 48.6%, 74.2% and 58.3%, respectively. Univariate analysis showed that tumor size, depth of invasion, NLR, PLR and CAR were associated with lymph node metastasis in cN0 gastric cancer patients (all P<0.05). Multivariate analysis showed that depth of invasion, NLR and CAR were independent influencing factors of lymph node metastasis in patients with cN0 gastric cancer. OR were 8.084, 3.540 and 3.092, respectively (all P<0.05). The C-index of the nomogram model was 0.847 (95% CI: 0.782-0.915). The predicting calibration curve was properly fit with the ideal curve in calibration chart. Conclusion: Combination of NLR and CAR to establish a nomogram model has a good consistency and can accurately predict the risk of lymph node metastasis in patients with cN0 gastric cancer.


Assuntos
Metástase Linfática , Nomogramas , Neoplasias Gástricas/patologia , Proteína C-Reativa/análise , Humanos , Valor Preditivo dos Testes , Período Pré-Operatório , Estudos Retrospectivos , Albumina Sérica Humana/análise
10.
Zhonghua Nei Ke Za Zhi ; 58(8): 599-601, 2019 Aug 01.
Artigo em Chinês | MEDLINE | ID: mdl-31365983

RESUMO

Carotid web is a rare risk factor of ischemic stroke. A total of 32 (0.54%) patients with carotid web were finally diagnosed in 5 943 patients who underwent carotid computerized tomography angiography (CTA) in two hospitals. Only one patient received carotid endarterectomy that pathological findings were fibrous tissue hyperplasia of vascular wall with mucinous degeneration. Stent implantation was administrated in two cases. Among 13 asymptomatic patients, the observational follow-up period was (20.9±12.4) months without strokes. Carotid web is a rare aberration. Asymptomatic patients with carotid web are usually silent. Large sized cohort and long-term follow-up are further needed.


Assuntos
Artéria Carótida Interna/diagnóstico por imagem , Estenose das Carótidas/diagnóstico por imagem , Angiografia por Tomografia Computadorizada , Stents/efeitos adversos , Artéria Carótida Interna/cirurgia , Estenose das Carótidas/complicações , Estenose das Carótidas/diagnóstico , Estenose das Carótidas/cirurgia , Estudos de Coortes , Endarterectomia das Carótidas/métodos , Displasia Fibromuscular/complicações , Seguimentos , Humanos , Fatores de Risco , Acidente Vascular Cerebral/etiologia , Acidente Vascular Cerebral/fisiopatologia
12.
Sci Rep ; 9(1): 9026, 2019 Jun 21.
Artigo em Inglês | MEDLINE | ID: mdl-31227745

RESUMO

Characterization of porous media is essential in a wide range of biomedical and industrial applications. Microstructural features can be probed non-invasively by diffusion magnetic resonance imaging (dMRI). However, diffusion encoding in conventional dMRI may yield similar signatures for very different microstructures, which represents a significant limitation for disentangling individual microstructural features in heterogeneous materials. To solve this problem, we propose an augmented multidimensional diffusion encoding (MDE) framework, which unlocks a novel encoding dimension to assess time-dependent diffusion specific to structures with different microscopic anisotropies. Our approach relies on spectral analysis of complex but experimentally efficient MDE waveforms. Two independent contrasts to differentiate features such as cell shape and size can be generated directly by signal subtraction from only three types of measurements. Analytical calculations and simulations support our experimental observations. Proof-of-concept experiments were applied on samples with known and distinctly different microstructures. We further demonstrate substantially different contrasts in different tissue types of a post mortem brain. Our simultaneous assessment of restriction size and shape may be instrumental in studies of a wide range of porous materials, enable new insights into the microstructure of biological tissues or be of great value in diagnostics.

13.
Clin Microbiol Infect ; 25(11): 1415-1421, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31229593

RESUMO

OBJECTIVES: The primary objective was to evaluate whether a molecular point-of-care test (POCT) for viral and atypical pathogens added to routine real-time PCR could reduce duration of intravenous antibiotics in hospitalized patients with lower respiratory tract infection (LRTI) compared with routine real-time PCR. METHODS: In this single-centre, open-label, randomized controlled study, we enrolled hospitalized adults diagnosed with LRTI. Patients were randomized to an intervention group (POCT FilmArray Panel for 20 viruses, atypical pathogens and bacteria plus routine real-time PCR) or a control group (routine real-time PCR for ten pathogens). The primary outcome was duration of intravenous antibiotics during hospitalization. The secondary outcomes included length of stay, cost of hospitalization and de-escalation within 72 hours and between 72 hours and 7 days. Intention-to-treat analysis was used. RESULTS: Between October 2017 and July 2018, we enrolled 800 eligible patients (398 in the intervention group and 402 in the control group). Duration of intravenous antibiotics in the intervention group was shorter than in the control (7.0 days (interquartile range (IQR) 5.0-9.0) versus 8.0 days (IQR 6.0-11.0); p <0.001). Length of hospital stay in the intervention group was significantly shorter (8.0 days (IQR 7.0-11.0) versus 9.0 days (IQR 7.0-12.0; p <0.001) and the cost of hospitalization in the intervention group was significantly lower ($1804.7 (IQR 1298.4-2633.8) versus $2042.5 (IQR 1427.4-2926.2); p 0.002) than control group. More patients in the intervention group achieved de-escalation within 72 hours (7.9%, 29/367 versus 3.2%, 12/377; p 0.005) and between 72 hours and 7 days (29.7%, 109/367 versus 22.0%, 83/377; p 0.024). CONCLUSIONS: Use of molecular POCT testing for respiratory viruses and atypical pathogens might help to reduce intravenous antibiotic use in hospitalized LRTI patients. CLINICAL TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT03391076.


Assuntos
Antibacterianos/uso terapêutico , Testes Diagnósticos de Rotina/métodos , Técnicas de Diagnóstico Molecular/métodos , Testes Imediatos , Infecções Respiratórias/diagnóstico , Viroses/diagnóstico , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Uso de Medicamentos/estatística & dados numéricos , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Tempo , Adulto Jovem
14.
Eur Rev Med Pharmacol Sci ; 23(11): 4917-4923, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-31210325

RESUMO

OBJECTIVE: To investigate the effect of miRNA-182 on cardiomyocyte apoptosis of heart failure (HF). MATERIALS AND METHODS: HF model in rats was established by rapid ventricular pacing. AAV-miRNA-182 (adeno-associated virus) vector was constructed to upregulate miRNA-182 level and its negative control AAV-NC was prepared. Rats undergoing rapid pacing (pacing group) and sham operation (sham group) were injected with AAV-miRNA-182 or AAV-NC, respectively. Quantitative Real Time-Polymerase Chain Reaction (qRT-PCR) was conducted to determine the miRNA-182 level in rats. Cardiac function test was carried out after the HF model establishment. Western blot was performed to examine the protein levels of human programmed cell death4 (PDCD4) and phosphoacidic cluster sorting protein (PACS2) in rats. Finally, terminal deoxynucleotidyl transferase (TdT)-mediated dUTP Nick End Labeling (TUNEL) assay was performed to evaluate the apoptotic rate of cardiomyocytes. RESULTS: HF model in rats was successfully established by rapid pacing. Injection of AAV-miRNA-182 markedly upregulated miRNA-182 level in rats. Compared with rats in the sham group, left ventricle ejection fraction (LVEF; 81.8% ± 2.4% vs. 64.3% ± 2.2%, p<0.05) and left ventricular fractional shortening (LVFS; 44.7% ± 2.4% vs. 29.1% ± 0.9%, p<0.05) markedly decreased in the pacing + NC group, whereas heart rate (HR) and left ventricular end-diastolic pressure (LVEDP) increased. Compared with rats in the pacing + NC group, HR [(441.6 ± 22) /min vs. (368.4 ± 27)/min, p<0.05] and LVEDP [(34.8 ± 11.4) mmHg vs. (19.4 ± 10.3) mmHg, p<0.05] were reduced in the pacing + miRNA-182 group. The protein levels of PDCD4 and PACS2 were downregulated in the pacing + miRNA-182 group relative to the pacing + NC group. Rapid pacing stimulation induced cardiac structural remodeling and cardiomyocyte apoptosis, which were alleviated by injection of AAV-miRNA-182. CONCLUSIONS: MiRNA-182 inhibits cardiomyocyte apoptosis induced by non-ischemic HF via downregulating PDCD4 and PACS2.

15.
Eur Rev Med Pharmacol Sci ; 23(10): 4432-4438, 2019 May.
Artigo em Inglês | MEDLINE | ID: mdl-31173319

RESUMO

OBJECTIVE: To investigate the effect of micro ribonucleic acid (miR)-101a on myocardial cell apoptosis in the rat model of acute myocardial infarction (AMI) and its regulatory mechanism. MATERIALS AND METHODS: A total of 30 Sprague-Dawley (SD) rats were randomly divided into the Sham group, Model group, and miR-101a mimic group, with 10 rats in each group. The rat model of AMI was established by the ligation of the anterior descending coronary artery. The rat left ventricular end-diastolic volume (LVEDV) and left ventricular end-systolic volume (LVESV) were detected using a color Doppler ultrasonic apparatus. Subsequently, the miRNA online database (TargetScan) was adopted to predict miRNAs that could be able to regulate TGF-ß1. Hematoxylin and eosin (H&E) staining was conducted to reveal the histopathological morphology changes in the rat heart. The serum levels of cysteinyl aspartate specific proteinase-3 (Caspase-3) and Bcl-2-associated X protein (Bax) in rats were detected via enzyme-linked immunosorbent assay (ELISA). Moreover, the expression levels of the transforming growth factor-beta l (TGF-ß1) and c-Jun N-terminal kinase (JNK) in rat heart were measured via Western blotting. RESULTS: Through searching miRNA database, miR-101a and TGF-ß1 messenger RNAs (mRNAs) had binding sites in the 3' untranslated region (3'UTR). Compared with those in Sham group, the rat LVEDV and LVESV were notably elevated, the histopathological morphology of the heart was seriously damaged, the apoptotic rate of myocardial cells and the levels of TGF-ß1 and JNK proteins significantly increased in the Model group. Additionally, compared with those in the Model group, the LVEDV and LVESV of rats in miR-101a mimic group were significantly reduced, the histopathological morphology of the heart was markedly improved, and the apoptotic rate and the levels of TGF-ß1 and JNK in rat heart were remarkably decreased. CONCLUSIONS: The myocardial cell apoptosis in AMI rats can be suppressed by overexpression of miR-101a by inhibiting the TGF-ß1/JNK signaling pathway.

16.
Neoplasma ; 66(5): 839-846, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31167533

RESUMO

Overexpression of Sonic hedgehog (Shh) is associated with progression of several cancers. The expression of Shh in non-small cell lung cancer (NSCLC) has been reported with inconsistent results. Lung adenocarcinoma (LAC) and lung squamous cell carcinoma (LSCC) are two major subtypes of NSCLC, which have different genetic genotypes and clinical therapeutic options. The expression of Shh in specimen of patients with NSCLC has yet to be comprehensively determined according to histological subtypes. Shh expression level was determined in 167 NSCLC patients (56 LAC patients and 111 LSCC patients) by immunohistochemical assay (IHC) and disease-free survival and overall survival of patients were analyzed using the Kaplan-Meier method. Shh protein level in pleural effusion from patients with pneumonia or pleural empyema, tuberculosis, LAC and LSCC was measured with enzyme-linked immunoassay (ELISA). We found that Shh expression is increased in tumor tissues from both LAC and LSCC patients compared with the paired adjacent tissues, while Shh level is negatively correlated with tumor differentiation only in LSCC, LSCC patients containing higher-Shh expression have a poorer prognosis. Furthermore, Shh level is elevated in pleural effusion from LSCC patients compared with that of parapneumonic and LAC pleural effusion. Shh expression in tumor tissues or pleural effusion may represent a potential diagnostic and prognostic marker of LSCC patients, pleural effusion Shh may assist to distinguish between LAC and LSCC.


Assuntos
Adenocarcinoma de Pulmão/metabolismo , Carcinoma Pulmonar de Células não Pequenas/metabolismo , Carcinoma de Células Escamosas/metabolismo , Proteínas Hedgehog/metabolismo , Neoplasias Pulmonares/metabolismo , Biomarcadores Tumorais/metabolismo , Humanos , Prognóstico
17.
Eur Rev Med Pharmacol Sci ; 23(9): 3742-3748, 2019 May.
Artigo em Inglês | MEDLINE | ID: mdl-31115000

RESUMO

OBJECTIVE: Recent researches have proved that long noncoding RNAs (lncRNAs) play essential roles in tumorigenesis. The aim of this study was to investigate the exact role of lncRNA DLX6-AS1 in the development of colorectal cancer (CRC), and to explore the possible mechanism. PATIENTS AND METHODS: DLX6-AS1 expression in CRC tissues was detected by Real Time-quantitative Polymerase Chain Reaction (RT-qPCR). Function assays were conducted to detect the effect of DLX6-AS1 on the proliferation and metastasis of CRC in vitro. Furthermore, luciferase reporter gene assay and RNA immunoprecipitation assay (RIP) were used to explore the underlying mechanism of DLX6-AS1. RESULTS: DLX6-AS1 expression in CRC samples was significantly higher than that of adjacent tissues. Loss of DLX6-AS1 markedly inhibited the proliferation, migration, and invasion of CRC cells. Furthermore, luciferase reporter gene assay and RIP assay showed that DLX6-AS1 acted as a competing endogenous RNA via sponging miR-577 in CRC. CONCLUSIONS: DLX6-AS1 could promote the proliferation, migration, and invasion of CRC by sponging miR-577, which might offer a potential therapeutic target for CRC.

18.
Zhonghua Jie He He Hu Xi Za Zhi ; 42(5): 367-371, 2019 May 12.
Artigo em Chinês | MEDLINE | ID: mdl-31137113

RESUMO

Objective: To compare chronic obstructive pulmonary disease (COPD) mouse models established by two different methods-cigarette smoke (CS) exposure alone and CS exposure combined with airway instillation of bacterial LPS. Methods: Male C57 mice were randomly divided into control group(CTL group), CS exposure group (CS group) and intra-tracheal LPS instillation combined with CS exposure group (LPS+CS group) according to the random number table, with 8 rats in each group. After the models were established, we measured the lung function and collected the bronchoalveolar lavage fluid (BALF) to detect the number of inflammatory cells and the expression of mucin and inflammatory mediators. HE and PAS staining were performed to observe the pathological changes in airway and lung tissue and to detect the goblet cells in airway, respectively. Results: Total lung capacity (TLC), functional residual capacity (FRC) and airway resistance (RI) of the CS and LPS+CS groups were higher than those of the CTL group, while the FEV(50)/FVC of these 2 groups was lower (P<0.05). Moreover, both RI and FEV(50)/FVC in the LPS+CS group were higher compared with the CS group (P<0.05). HE staining of lung tissue showed that the average alveolar intercept and thickness of small airway wall in the CS and LPS+CS groups were higher compared to the CTL group. In addition, the average alveolar intercept in the LPS+CS group was lower than that in the CS group [(47.86±2.82) µm and (61.94±7.68) µm respectively, P<0.05], but the area of bronchial inflammation of LPS+CS group was higher. The number of total white blood cells, neutrophils, lymphocytes, macrophages and the level of interleukin-6 (IL-6) in BALF of CS and LPS+CS groups were higher than those of CTL group (all P<0.05). Furthermore, the number of neutrophils and IL-6 level in BALF of LPS+CS group were higher in comparison with CS group, while the number of macrophages in BALF of LPS+CS group was lower (P<0.05). PAS staining of lung tissue indicated that the number of goblet cells in large airways of CS and LPS+CS groups increased more significantly compared to the CTL group, and the number of goblet cells in the LPS+CS group was higher than that in the CS group [(0.16±0.02) and (0.09±0.02) respectively, P<0.05]. The expression levels of Muc5ac and Muc5b in BALF of LPS+CS and CS groups were also higher than those of CTL group (P<0.05), and the level of Muc5ac in BALF of LPS+CS group was higher compared with CS group[(2.69±0.72) and (2.19±0.29) respectively, P<0.05]. Conclusions: Combined exposure of LPS and CS for establishing a COPD mouse model could better simulate the pathological characteristics of human COPD during the acute exacerbation period. The COPD mouse model established by CS exposure alone was able to better imitate the basic features of human COPD in the stable period. Researchers could choose a more appropriate modeling method according to different purposes.


Assuntos
Brônquios/metabolismo , Lipopolissacarídeos/efeitos adversos , Pulmão/fisiologia , Doença Pulmonar Obstrutiva Crônica/metabolismo , Poluição por Fumaça de Tabaco/efeitos adversos , Animais , Líquido da Lavagem Broncoalveolar , Masculino , Camundongos , Doença Pulmonar Obstrutiva Crônica/etiologia , Distribuição Aleatória , Ratos , Ratos Sprague-Dawley
20.
Zhonghua Xue Ye Xue Za Zhi ; 40(3): 187-190, 2019 Mar 14.
Artigo em Chinês | MEDLINE | ID: mdl-30929383

RESUMO

Objective: To explore the relative risk factors, clinical intervention and prognosis of hemorrhagic cystitis (HC) in patients with allogeneic hematopoietic stem cell transplantation (allo-HSCT) . Methods: From January 1 2010 to May 31 2017, 425 patients with allo-HSCT received a retrospective analysis. Results: ①Among the 425 patients, 262 were male and 163 were female. The median age was 26 (2-56) years old. There were 138 cases of acute myeloid leukemia (AML) , 96 cases of acute lymphoblastic leukemia (ALL) , 29 cases of myelodysplastic syndrome (MDS) , 98 cases of severe aplastic anemia (SAA) and 64 cases of chronic myeloid leukemia (CML) . 221 cases of sibling match transplantation, 89 cases of unrelated donor transplantation and 115 cases of haplotype transplantation. ②108 patients (25.41%) developed HC, with the median time of onset of 32 (3-243) days and the median duration of 20 (3-93) days; 33 cases (30.56%) were grade Ⅰ, 49 cases of grade Ⅱ (45.36%) , 21 cases (19.44%) of grade Ⅲ, and 5 cases (4.63%) of grade Ⅳ. ③103 cases of HC were cured, 5 patients were ineffective, 12 patients died and died of transplantation related complications (infection, recurrence, severe acute GVHD, secondary implant failure) . ④Univariate analysis showed that age < 30, type of transplantation, CMV and acute GVHD were associated with the occurrence of HC after allo-HSCT. Multivariate analysis showed that acute GVHD was an independent risk factor for HC after allo-HSCT. Conclusion: Prognosis of HC after allo-HSCT was better after timely treatment.


Assuntos
Cistite , Doença Enxerto-Hospedeiro , Transplante de Células-Tronco Hematopoéticas , Adolescente , Adulto , Criança , Pré-Escolar , Cistite/etiologia , Feminino , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Fatores de Risco , Adulto Jovem
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