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1.
Clin Spine Surg ; 2024 May 09.
Article in English | MEDLINE | ID: mdl-38723028

ABSTRACT

STUDY DESIGN: Intraoperative neurophysiological monitoring (IONM) as a guide to bone layer estimation was examined during posterior cervical spine lamina grinding. OBJECTIVE: To explore the feasibility of IONM to estimate bone layer thickness. SUMMARY OF BACKGROUND DATA: Cervical laminoplasty is a classic operation for cervical spondylosis. To increase safety and accuracy, surgery-assistant robots are currently being studied. It combines the advantages of various program awareness methods to form a feasible security strategy. In the field of spinal surgery, robots have been successfully used to help place pedicle screws. IONM is used to monitor intraoperative nerve conditions in spinal surgery. This study was designed to explore the feasibility of adding IONM to robot safety strategies. METHODS: Chinese miniature pig model was used. Electrodes were placed on the lamina, and the minimum stimulation threshold of DNEP for each lamina was measured (Intact lamina, IL). The laminae were ground to measure the DNEP threshold after incomplete grinding (Inner cortical bone preserved, ICP) and complete grinding (Inner cortical bone grinded, ICG). Subsequently, the lateral cervical mass screw canal drilling was performed, and the t-EMG threshold of the intact and perforated screw canals was measured and compared. RESULT: The threshold was significantly lower than that of the recommended threshold of DENP via percutaneous cervical laminae measurement. The DNEP threshold decreases with the process of laminae grinding. The DNEP threshold of the IL group was significantly higher than ICP and ICG group, while there was no significant difference between the ICP group and the ICG group. There was no significant relationship between the integrity of the cervical spine lateral mass screw path and t-EMG threshold. CONCLUSIONS: It is feasible to use DENP threshold to estimate lamina thickness. Cervical lateral mass screw canals by t-EMG showed no help to evaluate the integrity.

2.
J Ethnopharmacol ; 327: 117946, 2024 Jun 12.
Article in English | MEDLINE | ID: mdl-38447615

ABSTRACT

ETHNOPHARMACOLOGICAL RELEVANCE: In China, Xanthoceras sorbifolium Bunge was first documented as "Wen Guan Hua" in the "Jiu Huang Ben Cao" in 1406 A.D. According to the "National Compilation of Chinese Herbal Medicine," X. sorbifolium leaves are sweet and flat in nature and can dispel wind and dampness, suggesting that their extract can be used to treat rheumatoid arthritis. X. sorbifolium Bunge has also been used to treat arteriosclerosis, hyperlipidemia, hypertension, chronic hepatitis, and rheumatism, complications associated with hyperuricemic nephropathy (HN), a condition characterized by kidney damage resulting from high levels of uric acid (UA) in the blood. AIM OF THE STUDY: The purpose of this study was to investigate the effects and underlying mechanisms of a 70% ethanol extract from X. sorbifolium leaves (EX) in alleviating HN. MATERIALS AND METHODS: A mouse model of hyperuricemia was established to initially evaluate the hypouricemic effects and determine the effective dose of EX. Phytochemical analyses were conducted using ultra high-performance liquid chromatography and liquid chromatography-mass spectroscopy. The potential key pathways of EX in the alleviation of HN were inferred using network pharmacology and bioinformatics. An HN rat model was then established, and experiments including biomarker detection, western blotting, reverse transcription quantitative polymerase chain reaction, immunohistochemical and Masson's trichrome staining, and transmission electron microscopy were conducted to evaluate the effect of EX on UA transporter expression in vitro. RESULTS: Network pharmacology and bioinformatics analyses revealed that the phosphoinositide 3-kinase (PI3K)/AKT signaling pathway was the key pathway for the alleviation of HN progression by EX. EX treatment reduced serum biomarkers in HN rats, downregulated the expression of p-PI3K, p-AKT, glucose transporter 9 (GLUT9), urate transporter 1 (URAT1), Collagen I, matrix metalloproteinase (MMP)-2, and MMP-9, and upregulated the expression of ATP binding cassette subfamily G member 2 (ABCG2) to improve renal interstitial fibrosis in HN rats. A high content of both quercitrin and cynaroside were identified in EX; their administration inhibited the increased expression of GLUT9 and URAT1 in damaged HK-2 cells. CONCLUSION: Our study provides evidence that EX alleviates HN. The potential mechanism underlying this effect may be the regulation of UA transporters, such as GLUT9 and URAT1, by limiting the activation of the PI3K/AKT signaling pathway to improve renal injury.


Subject(s)
Hyperuricemia , Kidney Diseases , Mice , Rats , Animals , Uric Acid , Phosphatidylinositol 3-Kinases/metabolism , Proto-Oncogene Proteins c-akt/metabolism , Phosphatidylinositol 3-Kinase/metabolism , Kidney , Kidney Diseases/metabolism , Signal Transduction , Biomarkers/metabolism
3.
Article in Chinese | MEDLINE | ID: mdl-35822367

ABSTRACT

Objective:To analyzed allergens and screen for common airborne allergens in patients with allergic rhinitis (AR) in Shenzhen, and identified the distribution pattern of allergens in this region. We aimed to provide scientific and feasible statistical and clinical basis for prevention and treatment of allergenic rhinitis. Methods:For 3351 suspected cases of allergenic rhinitis, 18 kinds of airborne allergen serum-specific IgE were determined using a detection system of BioSciTec GmbH company, and statistical analysis was carried out according to sex, age, severity and seasonal allergen. Results:A total of 3,351 cases with allergic rhinitis were positive for airborne allergens. The top five inhalation allergens were Blomia tropicalis (2231, 66.6%), Dermatophagoides pterronyssinus (2212, 66.0%), Dermatophagoides farinae (1986, 59.3%), Cockroach (967, 28.9%), and Short ragweed (844, 25.2%). For the severity of the allergen, Dermatophagoides pterronyssinus ≥ level 3 accounted for 41.3% (1385/3351 cases) and Dermatophagoides farinae ≥level 3 accounted for 40.6% (1360/3351 cases). Blomia tropicalis were classified as level 2, and other allergens were mainly classified as level 1 or 2. The detection rate among different age groups and gender is significantly different. Conclusion:The main airborne allergens in Shenzhen were Blomia tropicalis, Dermatophagoides pterronyssinus, Dermatophagoides farinae, Cockroach, as well as Short ragweed. The distribution of allergens was affected by sex, age and season.


Subject(s)
Cockroaches , Rhinitis, Allergic , Rhinitis , Allergens/analysis , Animals , Humans , Immunoglobulin E , Skin Tests
4.
Mil Med Res ; 8(1): 57, 2021 11 01.
Article in English | MEDLINE | ID: mdl-34724985

ABSTRACT

BACKGROUND: Mitochondria have been shown to play vital roles during severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and coronavirus disease 2019 (COVID-19) development. Currently, it is unclear whether mitochondrial DNA (mtDNA) variants, which define mtDNA haplogroups and determine oxidative phosphorylation performance and reactive oxygen species production, are associated with COVID-19 risk. METHODS: A population-based case-control study was conducted to compare the distribution of mtDNA variations defining mtDNA haplogroups between healthy controls (n = 615) and COVID-19 patients (n = 536). COVID-19 patients were diagnosed based on molecular diagnostics of the viral genome by qPCR and chest X-ray or computed tomography scanning. The exclusion criteria for the healthy controls were any history of disease in the month preceding the study assessment. MtDNA variants defining mtDNA haplogroups were identified by PCR-RFLPs and HVS-I sequencing and determined based on mtDNA phylogenetic analysis using Mitomap Phylogeny. Student's t-test was used for continuous variables, and Pearson's chi-squared test or Fisher's exact test was used for categorical variables. To assess the independent effect of each mtDNA variant defining mtDNA haplogroups, multivariate logistic regression analyses were performed to calculate the odds ratios (ORs) and 95% confidence intervals (CIs) with adjustments for possible confounding factors of age, sex, smoking and diseases (including cardiopulmonary diseases, diabetes, obesity and hypertension) as determined through clinical and radiographic examinations. RESULTS: Multivariate logistic regression analyses revealed that the most common investigated mtDNA variations (> 10% in the control population) at C5178a (in NADH dehydrogenase subunit 2 gene, ND2) and A249d (in the displacement loop region, D-loop)/T6392C (in cytochrome c oxidase I gene, CO1)/G10310A (in ND3) were associated with a reduced risk of severe COVID-19 (OR = 0.590, 95% CI 0.428-0.814, P = 0.001; and OR = 0.654, 95% CI 0.457-0.936, P = 0.020, respectively), while A4833G (ND2), A4715G (ND2), T3394C (ND1) and G5417A (ND2)/C16257a (D-loop)/C16261T (D-loop) were related to an increased risk of severe COVID-19 (OR = 2.336, 95% CI 1.179-4.608, P = 0.015; OR = 2.033, 95% CI 1.242-3.322, P = 0.005; OR = 3.040, 95% CI 1.522-6.061, P = 0.002; and OR = 2.890, 95% CI 1.199-6.993, P = 0.018, respectively). CONCLUSIONS: This is the first study to explore the association of mtDNA variants with individual's risk of developing severe COVID-19. Based on the case-control study, we concluded that the common mtDNA variants at C5178a and A249d/T6392C/G10310A might contribute to an individual's resistance to developing severe COVID-19, whereas A4833G, A4715G, T3394C and G5417A/C16257a/C16261T might increase an individual's risk of developing severe COVID-19.


Subject(s)
COVID-19 , DNA, Mitochondrial , COVID-19/genetics , Case-Control Studies , China , DNA, Mitochondrial/genetics , Humans , Mitochondria/genetics , Phylogeny , Risk Factors
5.
Pharmacol Res ; 157: 104821, 2020 07.
Article in English | MEDLINE | ID: mdl-32360481

ABSTRACT

AIM: Since December 2019, new COVID-19 outbreaks have occurred and spread around the world. However, the clinical characteristics of patients in other areas around Wuhan, Hubei Province are still unclear. In this study, we performed epidemiological and clinical characteristics analysis on these regional cases. METHODS: We retrospectively investigated COVID-19 patients positively confirmed by nucleic acid Q-PCR at Taihe Hospital from January 16 to February 4, 2020. Their epidemiological, clinical manifestations, and imaging characteristics were analysed. RESULTS: Among the 73 patients studied, 12.3 % developed symptoms after returning to Shiyan from Wuhan, and 71.2 % had a history of close contact with Wuhan personnel or confirmed cases. Among these patients, 9 cases were associated with family clustering. The first main symptoms presented by these patients were fever (84.9 %) and cough (21.9 %). The longest incubation period was 26 days, and the median interval from the first symptoms to admission was 5 days. Of the patients, 67.1 % were originally healthy people with no underlying diseases, others mostly had common comorbidities including hypertension (12.3 %) and diabetes (5.5 %), 10.9 % were current smokers, 30.1 % had low white blood cell counts and 45.2 % showed decreased lymphocytes at the first time of diagnosis. CT scans showed that multiple patchy ground glass shadows outside of the patient lungs were commonly observed, and a single sub-pleural sheet of ground glass shadow with enhanced vascular bundles was also found located under the pleura. Patient follow-up to February 14 presented 38.4 % severe cases and 2.7 % critical cases. After follow-up, the parameter of lymphocyte counts below 0.8 × 109/L cannot be used to predict severe and critical groups from the ordinary group, and a lower proportion of smokers and higher proportion of diabetes patients occur in the poor outcome group. Other co-morbidities are observed but did not lead to poor outcomes. CONCLUSION: The epidemiological characteristics of patients in the area around Wuhan, such as Shiyan, at first diagnosis are described as follows: Patients had histories of Wuhan residences in the early stage and family clustering in the later period. The incubation period was relatively long, and the incidence was relatively hidden, but the virulence was relatively low. The initial diagnosis of the patients was mostly ordinary, and the percentage of critical patients who evolved into the ICU during follow-up is 2.7 %, which is lower than the 26.1 % reported by Wuhan city. According to the Shiyan experience, early diagnosis with multiple swaps of the Q-PCR test and timely treatment can reduce the death rate. Diabetes could be one of the risk factors for progression to severe/critical outcomes. No evidence exists that smoking protects COVID-19 patients from developing to severe/critical cases, and the absolute number of lymphocytes at initial diagnosis could not predict the progression risk from severe to critical condition. Multivariate regression analysis should be used to further guide the allocation of clinical resources.


Subject(s)
Betacoronavirus , Coronavirus Infections/diagnosis , Coronavirus Infections/epidemiology , Cough/epidemiology , Diabetes Mellitus/epidemiology , Fever/epidemiology , Hypertension/epidemiology , Pneumonia, Viral/diagnosis , Pneumonia, Viral/epidemiology , Adult , Aged , COVID-19 , China/epidemiology , Comorbidity , Coronavirus Infections/diagnostic imaging , Female , Hospitalization , Humans , Infectious Disease Incubation Period , Male , Middle Aged , Pandemics , Pneumonia, Viral/diagnostic imaging , Retrospective Studies , SARS-CoV-2 , Time Factors , Young Adult
6.
J Cancer Res Clin Oncol ; 146(6): 1441-1450, 2020 Jun.
Article in English | MEDLINE | ID: mdl-32248302

ABSTRACT

INTRODUCTION: Poliovirus receptor (PVR) is a tumor promoter and a regulatory checkpoint that enhances immunosuppression. We investigated PVR expression by applying immunohistochemistry (IHC) staining. A positive association existed between PVR expression and cytotoxic T lymphocyte-associated antigen 4 (CTLA4) expression in patients with surgically resected non-small-cell lung cancer (NSCLC). PVR expression is a prognosis predictor of lung adenocarcinoma. PURPOSE: To investigate the prognostic significance of PVR expression and CTLA4 expression for surgically resected NSCLC. PATIENTS AND METHODS: The medical records of 108 Chinese patients with primary NSCLC who underwent surgery were retrospectively reviewed. The expression of PVR and CTLA4 were measured through IHC. Clinical characteristics, the association between PVR and CTLA4, and the prognostic significance of PVR were analyzed. RESULTS: A significant positive association was observed between PVR and CTLA4 expression in NSCLC (P = 0.016). PVR had a high positive rate among females, nonsmokers, and patients with adenocarcinoma and advanced lung cancer. The overall survival (OS) of patients with negative PVR expression was significantly longer than that of patients with positive PVR expression (P = 0.049), especially among females (P = 0.03) and nonsmokers (P = 0.025). Multivariate analysis results showed that advanced tumor stage and PVR expression were independent prognosis predictors of poor OS. CONCLUSION: PVR can potentially serve as a prognostic predictor and biomarker for NSCLC and cancer anti-CTLA4 immunotherapy response.


Subject(s)
CTLA-4 Antigen/metabolism , Carcinoma, Non-Small-Cell Lung/metabolism , Lung Neoplasms/metabolism , Receptors, Virus/metabolism , Adult , Aged , Biomarkers, Tumor/metabolism , Carcinoma, Non-Small-Cell Lung/pathology , Carcinoma, Non-Small-Cell Lung/surgery , Female , Humans , Lung Neoplasms/pathology , Lung Neoplasms/surgery , Male , Middle Aged , Prognosis , Retrospective Studies
7.
Polymers (Basel) ; 11(8)2019 Aug 02.
Article in English | MEDLINE | ID: mdl-31382385

ABSTRACT

Viscoelastic surfactant (VES) fluid and hydrolyzed polyacryamide (HPAM) solution are two of the most common fracturing fluids used in the hydraulic fracturing development of unconventional reservoirs. The filtration of fracturing fluids in porous media is mainly determined by the flow patterns in pore-throat structures. In this paper, three different microdevices analogue of porous media allow access to a large range of Deborah number (De) and concomitantly low Reynolds number (Re). Continuous pore-throat structures were applied to study the feedback effect of downstream structure on upstream flow of VES fluid and HPAM solution with Deborah (De) number from 1.11 to 146.4. In the infinite straight channel, flow patterns between VES fluids and HPAM solution were similar. However, as pore length shortened to 800 µm, flow field of VES fluid exhibited the triangle shape with double-peaks velocity patterns. The flow field of HPAM solution presented stable and centralized streamlines when Re was larger than 4.29 × 10-2. Additionally, when the pore length was further shortened to 400 µm, double-peaks velocity patterns were vanished for VES fluid and the stable convergent flow characteristic of HPAM solution was observed with all flow rates.

8.
Medicine (Baltimore) ; 98(20): e15689, 2019 May.
Article in English | MEDLINE | ID: mdl-31096508

ABSTRACT

INTRODUCTION: Pulmonary sarcomatoid carcinomas (PSCs) are rare tumors within the sarcomatoid carcinoma group. Giant cell carcinoma of the lung (GCCL) is a rare type of PSCs that consists entirely of highly pleomorphic tumor giant cells; the prognosis is poor. PATIENT CONCERNS: A patient presented with a single cyst and was diagnosed with GCCL. The patient was a 59-year-old male who was admitted to the hospital with a cough. A chest computerized tomography (CT) scan showed a single, thin-walled cyst containing air in the left upper lobe of the lung. Bronchoscopy revealed chronic bronchitis. The initial diagnosis was pulmonary infection and the patient was treated with antibiotics. The cyst wall increased in thickness, and the cyst eventually formed a cavity. DIAGNOSIS: Surgery was performed, and a diagnosis of GCCL was established. The stage was pT1bN1M0 (equal to stage IIB). INTERVENTIONS: The patient underwent video-assisted thoracoscopic surgery and 4 cycles of adjuvant chemotherapy consisting of cisplatin and docetaxel. After 9 months, the patient occurred mediastinal lymph node metastasis, and received radiotherapy (60Gy/30F). OUTCOMES: His prognosis was good without progression (complete response) based on serial CT scans over 9 months of follow-up evaluations, then the patient occurred mediastinal lymph node metastasis. The patient lived during 30 months of follow-up, after which he was lost to follow-up. CONCLUSION: A solitary pulmonary parenchymal cystic lesion usually suggests an infectious disease or congenital abnormality; however, a cystic lesion is occasionally encountered in GCCL.


Subject(s)
Carcinoma, Giant Cell/diagnosis , Carcinoma, Giant Cell/pathology , Lung Neoplasms/diagnosis , Lung Neoplasms/pathology , Bronchoscopy/methods , Carcinoma, Giant Cell/diagnostic imaging , Carcinoma, Giant Cell/therapy , Chemotherapy, Adjuvant , Cysts/diagnostic imaging , Diagnosis, Differential , Humans , Lung Neoplasms/diagnostic imaging , Lung Neoplasms/therapy , Male , Middle Aged , Tomography, X-Ray Computed
9.
Oncol Rep ; 40(1): 454-462, 2018 Jul.
Article in English | MEDLINE | ID: mdl-29750300

ABSTRACT

Lung cancer is the most frequent and deadliest cancer in the world, especially in China. However, the molecular mechanisms involved in lung cancer remain unclear. Occludin (OCLN), one of the first identified tight junction proteins, has been revealed to be a necessary integral protein for tight junction structure and function. In the present study, we investigated the role of occludin in lung tumorigenesis. We found that occludin protein expression was highly increased in human lung cancer patient samples. Western blotting results also revealed that occludin expression was different in several lung cancer cell lines, with the highest level in SPC­A1 cells. Moreover, occludin knockdown inhibited lung cancer cell proliferation in vitro and in vivo. In addition, occludin knockdown promoted the apoptosis of lung cancer cell lines and reduced the invasion ability. Mechanistically, the activity of key growth pathway AKT/PI3K was compromised after occludin knockdown. Expression of apoptosis­related proteins, BAX, caspase­3, caspase­9 and AIF, but not Bcl­2, were upregulated after silencing of occludin. Collectively, our findings for the first time identify the role of occludin as a tumor promoter and a pro­metastatic factor in lung cancer, demonstrating that occludin is a potential prognostic biomarker and therapeutic target in lung cancer.


Subject(s)
Biomarkers, Tumor/genetics , Carcinogenesis/genetics , Carcinoma, Non-Small-Cell Lung/genetics , Occludin/genetics , A549 Cells , Animals , Apoptosis/genetics , Carcinoma, Non-Small-Cell Lung/pathology , Cell Movement/genetics , Cell Proliferation/genetics , Gene Expression Regulation, Neoplastic , Humans , Mice , Neoplasm Metastasis , Neoplasm Proteins/genetics , Signal Transduction , Xenograft Model Antitumor Assays
10.
Oncol Lett ; 12(2): 1041-1045, 2016 Aug.
Article in English | MEDLINE | ID: mdl-27446391

ABSTRACT

Bronchial fibroma is uncommon, with only 18 cases reported since 1948. The current study presents a rare case of endobronchial fibroma, along with a relevant literature review. A 54-year-old male patient with pneumoconiosis and a history of tuberculosis was admitted to the Taihe Hospital Affiliated With Hubei University of Medicine, Shiyan, China, due to refractory dry cough. Computed tomography of the chest showed multiple nodular and confluent opacities in the lung and one cavitation in the right upper lobe region. Bronchoscopy revealed an endobronchial mass in the left main bronchus. A bronchoscopic resection was performed, and the pathological evaluation confirmed fibroma. The patient's dry cough resolved following the removal of the fibroma, and no recurrence was detected during 6 months of follow-up. Endobronchial fibroma is an extremely rare disease, for which a pathological analysis is typically required for an accurate diagnosis. Bronchoscopic treatments, including removal by forceps, argon plasma coagulation and laser or electrocautery snares, may be used to treat patients affected by endobronchial fibroma.

11.
Zhonghua Xue Ye Xue Za Zhi ; 36(3): 191-5, 2015 Mar.
Article in Chinese | MEDLINE | ID: mdl-25854460

ABSTRACT

OBJECTIVE: To detect JAK2 V617F mutation burden and its clinical implications in patients with myeloproliferative neoplasm (MPN). METHODS: JAK2 V617F mutation burden were detected by using MGB Taqman probes and its clinical significance were retrospectively studied in 415 MPN patients. RESULTS: JAK2 V617F was found in 56.9% of all patients [83.5% in polycythemia vera (PV), 55.9% in essential thrombocythemia (ET), 41.9% in primary myelofibrosis (PMF) and 64.7% in MPN-unclassifiable)]. The majority of patients carried heterozygous JAK2 V617F mutation and homozygote was found only in 12 cases (4 in PV, 4 in MPN-U, 2 in PMF, 1 in ET, and 1 in chronic neutrophilic leukemia). Most patients (68.8%) were lower mutation burden (mutation burden<50%), but PV had the highest burden, the moderate burden in PMF and the least in ET. The patient's age and WBC count were significantly correlated with higher mutation burden in PV. WBC count was significantly related to higher mutation burden in ET. WBC count, Hb level and the platelet count were significantly related to higher mutation burden in PMF. CONCLUSION: The mutation burden of JAK2 V617F from high to low was PV, ET and PMF. The majority of JAK2 V617F mutation was heterozygous. JAK2 V617F mutation burden was positively correlated with age, WBC, Hb and platelet counts.


Subject(s)
Mutation , Myeloproliferative Disorders , Homozygote , Humans , Janus Kinase 2 , Leukocyte Count , Platelet Count , Polycythemia Vera , Retrospective Studies , Thrombocythemia, Essential
12.
J Org Chem ; 79(22): 11084-90, 2014 Nov 21.
Article in English | MEDLINE | ID: mdl-25321858

ABSTRACT

A novel FeCl2·4H2O-mediated internal-oxidant relay cascade reaction has been developed by functionalization of O-substituted benzohydroxamic acids or N-chloro-arylamides with [60]fullerene. Depending on the nature of the N-substituted groups, fullerenooxazoles or rare hydroxyfullerenyl amides could be obtained in a straightforward and flexible manner. Such a new transformation provides a unique strategy for the synthesis of fullerenooxazoles or hydroxyfullerenyl amides.

13.
Zhonghua Jie He He Hu Xi Za Zhi ; 28(4): 263-7, 2005 Apr.
Article in Chinese | MEDLINE | ID: mdl-15854440

ABSTRACT

OBJECTIVE: To investigate the effect of human angiotensin II (AngII) type 1 receptor (AT(1)R) antisense cDNA (ahAT(1)) on migration, proliferation, and apoptosis of cultured human pulmonary artery smooth muscle cells (PASMC). METHODS: Two recombinant adenoviral vectors, AdCMVahAT(1) containing full length antisense cDNA targeting to human AT(1)R mRNA, and AdCMVLacZ containing LacZ, were constructed by orientation clone technology and homologous recombination. The PASMC was divided into 3 groups (DMEM, AdCMVLacZ, AdCMVahAT(1)) and different interventions were given to different groups. AT(1)R expression was detected by RT-PCR and immunohistochemistry method; migration of PASMC was measured by Boyden's Chamer method. Other PASMC was divided into 4 groups (DMEM, AngII, AdCMVLacZ + AngII and AdCMVahAT(1) + AngII), and only the last 2 groups were respectively transfected with AdCMVLacZ and AdCMVahAT(1) before administration of AngII. From 6 h to 96 h after stimulation by AngII (10(-7) mol/L), proliferation index (PI) and apoptosis of PASMC were determined by flow cytometry. RESULTS: At the 48 h the level of AT(1)R mRNA was significantly less in PASMC transfected AdCMVahAT(1) than that in group DMEM and in group AdCMVLacZ. The protein level showed a same difference (P < 0.01). At 24 h the migration distance of PASMC also was significantly less in group AdCMVahAT(1) than that in group DMEM and Group AdCMVLacZ (P < 0.01). Stimulated by AngII for 48 h, in group AngII the PI of PASMC markedly increased (P < 0.01 vs group DMEM). But in Group AdCMVahAT(1) + AngII PI of PASMC clearly decreased (P < 0.01 vs group AngII and group DMEM respectively). There was no statistic difference of PI between group AdCMVLacZ + AngII and group AngII. Moreover, apoptosis peak emerged only in group AdCMVahAT(1) + AngII. The rate of apoptosis in those PASMC used AdCMVahAT(1) and AngII was 24.70 +/- 4.04 (P < 0.01 vs the other 3 groups respectively). CONCLUSIONS: These results indicate that AngII stimulates proliferation via AT(1) receptors in human PASMC, and antisense cDNA targeting to human AT(1)R transfection mediated by adenoviral vector has powerful inhibitory effects on AngII-induced migration and proliferation of human PASMC by attenuating AT(1)R mRNA and protein expression. Also, it can promote apoptosis of human PASMC. That demonstrate that AT(1)R antisense cDNA is a potent inhibitors of the actions of AngII on PASMC. Antisense inhibition targeting to AT(1)R has therapeutic potential for the treatment of pulmonary vascular diseases.


Subject(s)
Muscle, Smooth, Vascular/metabolism , Myocytes, Smooth Muscle/metabolism , Pulmonary Artery/metabolism , Receptor, Angiotensin, Type 1/genetics , Adenoviridae , Apoptosis , Cell Differentiation , Cell Proliferation , Cells, Cultured , DNA, Antisense/genetics , DNA, Complementary/genetics , Genetic Vectors , Humans
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