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1.
Eur Rev Med Pharmacol Sci ; 27(12): 5356-5369, 2023 06.
Article in English | MEDLINE | ID: mdl-37401270

ABSTRACT

OBJECTIVE: This study aims to investigate the CT-DNA (Calf thymus DNA) binding properties and HeLa cell viabilities of metal complexes derived from (E)-2-hydroxy-N'-((thiophen-2-yl)methylene)benzohydrazone (H2L1) and (E)-N'-((thiophen-2-yl)methylene)isonicotinylhydrazone (HL2). MATERIALS AND METHODS: A series of metal complexes derived from (E)-2-hydroxy-N'-((thiophen-2-yl)methylene)benzohydrazone (H2L1) and (E)-N'-((thiophen-2-yl)methylene)isonicotinylhydrazonewere (HL2) were synthesized, and their structures were characterized through FT-IR, ESI-MS, elemental analysis, molar conductivities and X-ray diffraction. DNA binding properties between CT-DNA and metal complexes were investigated by UV-Vis spectrophotometry and viscosity titration. The toxicological properties of compounds on HeLa cell were measured in vitro. RESULTS: Ligand H2L1 or HL2 exhibits a tridentate and anion ligand and uses oxygen anion, nitrogen atom and sulfur atom to coordinate with metal ions. When coordinated with metal ions, the unit O=C-NH- of each ligand has been enolized and deprotonated into -O-C=N-. The suggested chemical formulas of metal complexes are: [Co(HL1)2], [Ni(HL1)2], [Cu(HL1)2], [Co(L2)2], [Cu(L2)2], [Zn(L2)2], [ScL2(NO3)2(H2O)2], [Pr(L2)2(NO3)] and [Dy(L2)2(NO3)]. Both ligands and their metal complexes can bind strongly to CT-DNA through hydrogen bond and intercalation with Kb of 104~105 L mol-1 compared to ethidium bromide [classical DNA intercalator, Kb(EB-DNA) = 3.068 × 104 L mol-1]; however, the groove pattern cannot be excluded. The coexistence of multiple binding modes may be a common form of drug binding to DNA. HeLa cell shows lower viabilities in the presence of [Ni(HL1)2] and [Cu(HL1)2] (*p < 0.05) compared to the other compounds, with the LC50 of 2.6 µmol L-1 and 2.2 µmol L-1, respectively. CONCLUSIONS: These compounds, especially [Ni(HL1)2] and [Cu(HL1)2], will be promising for anti-tumor drugs, which should be further studied.


Subject(s)
Coordination Complexes , Humans , Coordination Complexes/pharmacology , Coordination Complexes/chemistry , Thiophenes , Cell Survival , HeLa Cells , Ligands , Spectroscopy, Fourier Transform Infrared , DNA/metabolism
2.
Pol J Vet Sci ; 24(1): 43-49, 2021 Mar.
Article in English | MEDLINE | ID: mdl-33847096

ABSTRACT

In this study, we developed a SYBR Green I real-time PCR method for the rapid and sensitive detection of novel porcine parvovirus 7 (PPV7). Specific primers were designed based on the highly conserved region within the Capsid gene of PPV7. The established method was 1,000 times more sensitive than the conventional PCR method and had a detection limit of 35.6 copies. This method was specific and had no cross-reactions with PCV2, PCV3, PRV, PEDV, PPV1, and PPV6. Experiments testing the intra and interassay precision demonstrated a high reproducibility. Testing the newly established method with 200 clinical samples revealed a detection rate up to 17.5% higher than that of the conventional PCR assay. The established method could provide technical support for clinical diagnosis and epidemiological investigation of PPV7.


Subject(s)
Benzothiazoles , Diamines , Parvoviridae Infections/veterinary , Parvovirus, Porcine/isolation & purification , Quinolines , Real-Time Polymerase Chain Reaction/methods , Swine Diseases/virology , Animals , Parvoviridae Infections/diagnosis , Parvoviridae Infections/virology , Reproducibility of Results , Sensitivity and Specificity , Swine , Swine Diseases/diagnosis
3.
Pol J Vet Sci ; 23(2): 197-202, 2020 Jun.
Article in English | MEDLINE | ID: mdl-32627977

ABSTRACT

In this study, a SYBR Green-based real-time quantitative polymerase chain reaction (qPCR) assay was developed for rapid detection of porcine parvovirus (PPV) 6. Primer pairs targeting the conserved regions of PPV6 Capsid gene were designed. Sensitivity analyses revealed the lowest detection limit of the SYBR Green-based real-time PCR assay to be 47.8 copies/µL, which indicated it was 1000 times higher than that found in the conventional PCR investigations. This assay was specific and showed no cross-species amplification with other six porcine viruses. The assay demonstrated high repeatability and reproducibility; the intra- and inter-assay coefficients of variation were 0.79% and 0.42%, respectively. The positive detection rates of 180 clinical samples with SYBR Green-based real-time PCR and conventional PCR were 12.22% (22/180) and 4.44% (8/180), respectively. Our method is sensitive, specific, and reproducible. The use of SYBR Green-based real-time PCR may be suitable for the clinical detection and epidemiological investigation of PPV6.


Subject(s)
Benzothiazoles , Diamines , Parvoviridae Infections/veterinary , Parvovirus, Porcine/isolation & purification , Quinolines , Real-Time Polymerase Chain Reaction/veterinary , Swine Diseases/virology , Animals , Parvoviridae Infections/diagnosis , Parvoviridae Infections/virology , Parvovirus, Porcine/classification , Real-Time Polymerase Chain Reaction/methods , Reproducibility of Results , Sensitivity and Specificity , Swine , Swine Diseases/diagnosis
4.
Zhonghua Jie He He Hu Xi Za Zhi ; 42(11): 838-844, 2019 Nov 12.
Article in Chinese | MEDLINE | ID: mdl-31694094

ABSTRACT

Objective: To compare the efficacy and safety profiles of tiotropium/olodaterol with the mono-components in Chinese and total study population from TONADO trial. Methods: In the replicate, double-blind, parallel-group, active-controlled, randomized, 52-week, Phase Ⅲ TONADO studies (TONADO 1+2), patients received tiotropium/olodaterol, tiotropium, or olodaterol via the Respimat(®) Inhaler (Boehringer Ingelheim, Germany). Primary end points were forced expiratory volume in 1 second (FEV(1)) area under the curve from 0 to 3 hours (AUC(0-3h)) response and trough FEV(1) response, and St George's respiratory questionnaire (SGRQ) total score at 24 weeks. Adverse events were also collected. This subgroup analysis only focused on the efficacy and safety of the drug at the approved dose in China. Results: 548 Chinese patients were randomized, aged 41 to 82 years [mean age, (63±8) years] and most were male (526, 96%), 111 received tiotropium/olodaterol 5/5 µg, and 127 received tiotropium 5 µg and 95 received olodaterol 5 µg. The baseline characteristics of these groups were similar. After 24 weeks, treatment with tiotropium/olodaterol 5/5 µg, tiotropium 5 µg and olodaterol 5 µg resulted in an adjusted mean FEV(1) AUC(0-3h) response of 0.240, 0.157 and 0.079 L, and trough FEV(1) response of 0.117, 0.068 and-0.001 L, respectively. Tiotropium/olodaterol 5/5 µg significantly improved SGRQ scores in Chinese patients compared with olodaterol 5 µg (32.729 and 37.202, respectively). Generally, the safety profile of tiotropium/olodaterol was comparable with mono-components in 52 weeks. Conclusion: Compared with tiotropium or olodaterol, tiotropium/olodaterol in Chinese patients provided significant improvement in lung function and quality of life, and the safety profiles were similar.


Subject(s)
Benzoxazines/administration & dosage , Bronchodilator Agents/administration & dosage , Pulmonary Disease, Chronic Obstructive/drug therapy , Quality of Life , Tiotropium Bromide/administration & dosage , Administration, Inhalation , Adrenergic beta-2 Receptor Agonists , Adult , Aged , Aged, 80 and over , Benzoxazines/therapeutic use , Bronchodilator Agents/therapeutic use , China/epidemiology , Double-Blind Method , Forced Expiratory Volume , Humans , Male , Middle Aged , Pulmonary Disease, Chronic Obstructive/ethnology , Pulmonary Disease, Chronic Obstructive/psychology , Tiotropium Bromide/therapeutic use , Treatment Outcome
5.
Eur Rev Med Pharmacol Sci ; 23(15): 6394-6403, 2019 Aug.
Article in English | MEDLINE | ID: mdl-31378877

ABSTRACT

OBJECTIVE: We aimed to explore the role of microRNA-449b-5p in osteogenic differentiation of bone marrow mesenchymal stem cells (BMSCs) and its mechanism of action. MATERIALS AND METHODS: Quantitative Real Time-Polymerase Chain Reaction (qRT-PCR) assay was used to detect the expression levels of microRNA-449b-5p and osteogenic markers including RUNX2, OCN during BMSCs differentiation. The microRNA-449b-5p mimic and microRNA-449b-5p inhibitors were transfected into BMSCs to achieve microRNA-449b-5p overexpression and knockdown, then the expressions of osteogenic markers were detected by qRT-PCR. The ALP activity staining and the alizarin red staining were used to detect the activity of ALP and the mineralization ability of cells after overexpression and knockdown of microRNA-449b-5p. Binding sites for microRNA-449b-5p and Satb2 were predicted by TargetScan, the PicTar and microRNAanda programs, and confirmed by dual-luciferase reporter gene assay. The relationship between microRNA-449b-5p and Satb2 was analyzed by QRT-PCR and Western blot. The microRNA-449b-5p inhibitor and shSATB2 lentivirus were simultaneously transfected in BMSCs, and the expression levels of RUNX2, OCN and ALP were detected by qRT-PCR and ALP activity assays. RESULTS: microRNA-449b-5p expression gradually decreased during osteogenic differentiation. Overexpression of microRNA-449b-5p inhibited BMSCs differentiation by down-regulating ALP activity, RUNX2, and OCN expression, while the opposite result was observed after knockdown of microRNA-449b-5p. MicroRNA-449b-5p can bind to the 3'UTR end of Satb2, which was involved in the osteogenic differentiation of microRNA-449b-5p-regulated BMSCs, and silencing of Satb2 can abolish the positive effect of the microRNA-449b-5p inhibitor on osteoblasts differentiation. CONCLUSIONS: microRNA-449b-5p could aggravate osteoporosis by inhibiting osteogenic differentiation of BMSCs through targeting Satb2.


Subject(s)
Cell Differentiation/physiology , Matrix Attachment Region Binding Proteins/metabolism , Mesenchymal Stem Cells/metabolism , MicroRNAs/metabolism , Osteogenesis/physiology , Osteoporosis/metabolism , Transcription Factors/metabolism , Animals , Cells, Cultured , Disease Progression , Protein Binding/physiology , Rats
6.
Zhonghua Jie He He Hu Xi Za Zhi ; 42(8): 596-601, 2019 Aug 12.
Article in Chinese | MEDLINE | ID: mdl-31378021

ABSTRACT

Objective: To evaluate the feasibility of cell-free tumor DNA in pleural effusion supernatant for assessing the tumor mutational burden (TMB) of advanced lung cancers. Methods: From December 2016 to August 2018, 34 lung cancer patients (19 males and 15 females) with pleural effusion were enrolled at Zhongshan Hospital, Fudan University. The median age of the patients was 65 (range, 34-85) years. Before systemic or local antitumor therapy, tumor specific mutations in tumor tissue, pleural effusion supernatant, pleural effusion sediment, and plasma samples from these patients were examined using targeted next-generation sequencing, and TMB levels were calculated respectively. Subgroup analysis was based on smoking history and driver mutation status. Statistical differences were determined using SPSS 16.0 software, and individual groups were compared using the one-way analysis of variance (ANOVA) and LSD-t test. Results: The median TMB level of pleural effusion supernatant was 6.23 mutations/Mb, similar to that of tumor tissue (6.23 vs 6.86 mutations/Mb, t=1.174, P=0.245), but significantly higher than that of pleural effusion sediment (2.49 mutations/Mb, t=3.044, P=0.003) and plasma (2.49 mutations/Mb, t=2.464, P=0.016). Compared with tumor tissue in TMB assessment, pleural effusion supernatant had a positive percentage agreement of 52% (9/17), and a negative percentage agreement of 65% (11/17). Subgroup analysis showed that the TMB level was higher in smokers (n=11) than that in non-smokers (n=23, 14.4 vs 5.4 mutations/Mb, t=3.238, P=0.003). Conclusion: For advanced lung cancer patients with pleural effusion, pleural effusion supernatant is a promising substitute to tumor tissue for TMB assessment, which is a potential biomarker for immunotherapy.


Subject(s)
Carcinoma, Non-Small-Cell Lung/therapy , Circulating Tumor DNA , Immunotherapy/methods , Lung Neoplasms/pathology , Lung Neoplasms/therapy , Pleural Effusion , Adult , Aged , Aged, 80 and over , Carcinoma, Non-Small-Cell Lung/genetics , Female , Humans , Lung Neoplasms/genetics , Male , Middle Aged , Mutation/genetics , Treatment Outcome
7.
Zhonghua Jie He He Hu Xi Za Zhi ; 41(10): 778-782, 2018 Oct 12.
Article in Chinese | MEDLINE | ID: mdl-30347549

ABSTRACT

Objective: To investigate if concomitant gene alterations impact the therapeutic efficacy of epidermal growth factor receptor-tyrosine kinase inhibitors (EGFR-TKI) in advanced non-small cell lung cancer (NSCLC) patients with epidermal growth factor receptor (EGFR) sensitive mutation. Methods: From November 2016 to December 2017, 51 patients (19 males and 32 females, age 37-85 years) with histology or cytology diagnosed,locally advanced or metastatic NSCLC from Zhongshan Hospital Fudan University were prospectively recruited in the study. All patients harboring EGFR sensitive mutation detected by a 123 lung cancer specific gene panel of next-generation sequencing(NGS) analysis were under treatment of EGFR-TKIs. Multi-factors analysis of the correlation between EGFR-TKIs efficacy and concomitant gene alterations were analyzed by multivariate Cox regression model. Results: 82% of the NSCLC patients with EGFR mutation presented concomitant gene alterations with an average number of 2.1. Patients not harboring concomitant gene alterations had a longer median progression free survival (mPFS: not reached vs 8.8 m, P=0.008). Those who had less than 2 concomitant genes had a higher objective response rate[ORR: 52% (17/33) vs 33% (6/18) , P=0.251]and better mPFS (13.8 vs 8.0 m, P=0.003). The top 3 concomitant gene alterations were TP53 gene mutation(55%, 28/51), EGFR gene amplification (26%, 13/51) and RB1 gene mutation (18%,9/51) respectively. The mPFS of EGFR-TKI treatment in patients with either one of these 3 concomitant genes was 8.0, 8.0, and 6.0 months respectively, significantly shorter than those without one of the 3 gene alterations (13.8, 13.1, and 10.8 months respectively). Multivariate Cox regression revealed that concomitant gene abnormalities (P=0.036) and accompanied by RB1 gene mutation (P=0.025) were independent risk factors for the survival benefit of EGFR-TKI in the treatment of advanced NSCLC with EGFR-sensitive mutation. Conclusions: The efficacy of EGFR-TKI decreased significantly in advanced NSCLC with EGFR-sensitive mutation who had concomitant gene abnormalities, especially accompanied by more than 2 of the 3 gene alterations (TP53 gene mutation, EGFR gene amplification or RB1 gene mutation). This study suggested that the concomitant gene alterations should be an important issue for consideration when applying a personalized combination therapy for advanced NSCLC harboring EGFR sensitive mutation.


Subject(s)
Carcinoma, Non-Small-Cell Lung/drug therapy , Carcinoma, Non-Small-Cell Lung/therapy , ErbB Receptors/antagonists & inhibitors , Lung Neoplasms/drug therapy , Lung Neoplasms/therapy , Mutation , Protein Kinase Inhibitors/therapeutic use , Carcinoma, Non-Small-Cell Lung/genetics , Female , Humans , Lung Neoplasms/genetics , Lung Neoplasms/pathology , Male , Treatment Outcome
8.
Clin Transl Oncol ; 16(5): 463-8, 2014 May.
Article in English | MEDLINE | ID: mdl-24002945

ABSTRACT

BACKGROUND: Bevacizumab is a monoclonal antibody with high antitumor activity against malignant diseases. Previous studies have demonstrated the efficacy of first-line bevacizumab combination therapy in advanced, non-squamous non-small cell lung cancer (NS-NSCLC). SAiL (MO19390), an open-label, multicenter, single-arm study, evaluated the safety and efficacy of first-line bevacizumab-based treatment in clinical practice. This report presents the results of a subgroup analysis of Chinese patients enrolled in SAiL. METHODS: Chemo-naive Chinese patients with locally advanced, metastatic or recurrent NSCLC were randomized to receive Bev 15 mg/kg every 3 weeks plus carboplatin + paclitaxel for maximum of six cycles, followed by single-agent bevacizumab until disease progression. The primary endpoint was safety. Secondary endpoints included time to progression and overall survival. RESULTS: The Chinese intent-to-treat (ITT) population consists of 198 Chinese patients, among whom 107 (54 %) were non-smokers and 90 (45.5 %) were female. The median cycle of bevacizumab administration was 10 and median duration of bevacizumab treatment was 29.5 weeks. Only eight cases of severe adverse events were observed in the study, which were deemed to be related to bevacizumab. The incidence of AEs over grade 3 in Chinese ITT patients was generally low (<9 %). No new safety signals were reported. Objective response rate in 195 evaluable Chinese patients was 68.8 %, including four complete responses (2.1 %). Time to disease progression (TTP) and overall survival were 8.8 and 18.5 months, respectively. CONCLUSIONS: The safety and efficacy of first-line bevacizumab-based treatment in Chinese population with advanced NS-NSCLC are consistent with those in previous studies as well as in Asian subgroup population from SAiL study. No new safety signals were reported.


Subject(s)
Angiogenesis Inhibitors/administration & dosage , Antibodies, Monoclonal, Humanized/administration & dosage , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Carcinoma, Non-Small-Cell Lung/drug therapy , Lung Neoplasms/drug therapy , Adult , Aged , Antineoplastic Agents/administration & dosage , Asian People , Bevacizumab , Carboplatin/administration & dosage , Female , Humans , Male , Middle Aged , Paclitaxel/administration & dosage , Treatment Outcome
9.
Lung Cancer ; 80(3): 333-8, 2013 Jun.
Article in English | MEDLINE | ID: mdl-23510626

ABSTRACT

BACKGROUND: The X-box binding protein 1 (XBP1) is a critical transcription factor in the endoplasmic reticulum stress response, which is essential for the maintenance of cellular homeostasis. Here, we investigated whether the regulatory variant rs2269577 of the XBP1 gene influences clinical outcome in advanced non-small cell lung cancer (NSCLC) patients undergoing platinum-based chemotherapy. PATIENTS AND METHODS: We recruited 663 Chinese patients with advanced NSCLC treated with platinum-based regimens and assessed the association between rs2269577 and clinical outcome. Subsequent functional analyses, including real-time quantitative PCR and dual-luciferase assays, were performed to explore possible molecular mechanisms. RESULTS: The G/G genotype of rs2269577 was significantly associated with severe gastrointestinal toxicity compared with the homozygous C/C genotype (P=0.012, odds ratio=2.755), particularly in the female, performance status 0-1, and adenocarcinoma subgroups. No significant relevance was found between rs2269577 and treatment efficacy. In gastric epithelial cells, in vitro molecular analyses demonstrated that XBP1 mRNA expression levels decreased after treatment with cisplatin and the G allele of rs2269577 weakened the transcriptional activity of the XBP1 promoter. CONCLUSION: This is the first study to evaluate the effect of XBP1 polymorphism on severe chemotherapy-related adverse outcomes in platinum-treated advanced NSCLC patients using both pharmacogenomics and functional molecular analyses.


Subject(s)
Carcinoma, Non-Small-Cell Lung/drug therapy , DNA-Binding Proteins/genetics , Gastrointestinal Tract/pathology , Lung Neoplasms/drug therapy , Platinum/administration & dosage , Transcription Factors/genetics , Adult , Aged , Aged, 80 and over , Biomarkers, Tumor/genetics , Carcinoma, Non-Small-Cell Lung/pathology , China , Drug-Related Side Effects and Adverse Reactions , Female , Gastrointestinal Tract/drug effects , Genotype , Humans , Lung Neoplasms/pathology , Male , Middle Aged , Neoplasm Staging , Polymorphism, Genetic , Promoter Regions, Genetic , Regulatory Factor X Transcription Factors , X-Box Binding Protein 1
10.
Tumour Biol ; 34(2): 953-61, 2013 Apr.
Article in English | MEDLINE | ID: mdl-23412975

ABSTRACT

Valosin-containing protein (VCP), or p97, is a member of the ATP-binding protein family, and is involved in numerous cellular events, such as, protein degradation, membrane fusion, and chaperone activity. VCP has been demonstrated playing a critical role in non-small-cell lung cancer (NSCLC) pathogenesis and progression recently. We investigated the association between VCP polymorphisms and clinical outcome in advanced NSCLC patients undergoing platinum-based chemotherapy. We recruited 663 Chinese advanced NSCLC patients who were treated with platinum-based regimens, and using their clinical data, we assessed the efficacy and side effects of their treatment. Three tag-single nucleotide polymorphisms (SNPs) of VCP were genotyped. SNP rs2074549 showed a significant association with severe neutropenia. Its G/G genotype increased the risk of grade 3 or 4 neutropenia compared with wild-type homozygotes A/A (P = .001, odds ratio = 2.975). Haplotype association analysis revealed that CGA was associated with the increased incidence of severe neutropenia (P = .041, odds ratio = 1.439). However, no significant relationship was found between the presence of VCP polymorphisms and treatment efficacy when objective response, progression-free survival, and overall survival (OS) were evaluated. Our study is the first to provide evidence that VCP polymorphisms are associated with a severe chemotherapy-related adverse outcome in platinum-treated advanced NSCLC patients.


Subject(s)
Adenosine Triphosphatases/genetics , Antineoplastic Combined Chemotherapy Protocols/adverse effects , Carcinoma, Non-Small-Cell Lung/mortality , Cell Cycle Proteins/genetics , Lung Neoplasms/mortality , Organoplatinum Compounds/adverse effects , Polymorphism, Single Nucleotide/genetics , Adenocarcinoma/drug therapy , Adenocarcinoma/genetics , Adenocarcinoma/mortality , Adult , Aged , Aged, 80 and over , Biomarkers, Tumor/genetics , Carcinoma, Non-Small-Cell Lung/drug therapy , Carcinoma, Non-Small-Cell Lung/genetics , Carcinoma, Squamous Cell/drug therapy , Carcinoma, Squamous Cell/genetics , Carcinoma, Squamous Cell/mortality , DNA/blood , DNA/genetics , Female , Follow-Up Studies , Haplotypes/genetics , Humans , Lung Neoplasms/drug therapy , Lung Neoplasms/genetics , Lymphatic Metastasis , Male , Middle Aged , Neoplasm Staging , Neutropenia/chemically induced , Polymerase Chain Reaction , Prognosis , Survival Rate , Valosin Containing Protein
11.
J Int Med Res ; 40(5): 1735-44, 2012.
Article in English | MEDLINE | ID: mdl-23206455

ABSTRACT

OBJECTIVES: To investigate the presence of aquaporin (AQP) 1 and AQP2 in kidneys of cirrhotic rats with ascites, and to determine the effect of terlipressin on AQP1 and AQP2 levels and its therapeutic efficacy in ascites treatment. METHODS: Eighteen rats were randomly divided into normal noncirrhotic rats treated with saline, cirrhotic rats treated with saline and cirrhotic rats treated with terlipressin (n = 6 per group). In all rats, 24-h net fluid-excretion volume, presence or absence of ascites and portal vein pressure were measured; AQP1 and AQP2 mRNA and protein levels in renal tissue were evaluated. RESULTS: Terlipressin resolved ascites in all animals in the terlipressin-treated group, and significantly increased the 24-h net fluid-excretion volume and decreased portal vein pressure compared with saline treatment. AQP1 and AQP2 were significantly upregulated in cirrhotic rat kidneys compared with normal control rat kidneys. Terlipressin administration significantly down regulated AQP2 in rat kidneys but did not affect AQP1. CONCLUSIONS: AQP1 and AQP2 are important factors in ascites induction. Terlipressin appears to be an effective drug for the treatment of ascites due to liver cirrhosis in a rat model, possibly due to AQP2 reduction in kidneys.


Subject(s)
Aquaporin 2/genetics , Ascites/drug therapy , Down-Regulation , Liver Cirrhosis/drug therapy , Lypressin/analogs & derivatives , Vasoconstrictor Agents/pharmacology , Alanine Transaminase/blood , Animals , Aquaporin 1/genetics , Aquaporin 1/metabolism , Aquaporin 2/metabolism , Arginine Vasopressin/blood , Ascites/blood , Ascites/physiopathology , Bilirubin/blood , Blood Pressure/drug effects , Blood Urea Nitrogen , Kidney/metabolism , Liver Cirrhosis/blood , Liver Cirrhosis/physiopathology , Lypressin/pharmacology , Lypressin/therapeutic use , Male , Rats , Rats, Sprague-Dawley , Serum Albumin/metabolism , Terlipressin , Vasoconstrictor Agents/therapeutic use
13.
J Investig Allergol Clin Immunol ; 21(3): 185-92, 2011.
Article in English | MEDLINE | ID: mdl-21548446

ABSTRACT

BACKGROUND: Proliferation of activated CD4+ T lymphocytes is inhibited by indoleamine 2,3-dioxygenase (IDO). OBJECTIVE: We undertook the present study to test the hypothesis that IDO-expressing immature DCs (imDCs) can restore immune tolerance in mice suffering from allergic airway inflammation. METHODS: imDCs were generated from murine bone marrow cells using granulocyte-macrophage colony-stimulating factor.The imDCs were subsequently transfected with an IDO expression vector (pEGFP-N1-IDO). Surface marker expression, including CD11c, MHCII, CD80, and CD86, was analyzed using flow cytometry. IDO-expressing imDCs were injected into the trachea of ovalbumin (OVA)-sensitized mice, and lung histopathology and cytokine expression in bronchoalveolar lavage fluid were assessed. The splenic CD4+ T cells of OVA-sensitized mice were isolated and co-cultured with pEGFP-N1-IDO-expressing imDCs, and apoptosis of CD4+ T cells was detected using the terminal deoxynucleotidyl transferase dUTP nick end labeling assay. RESULTS: Expression of IDO in imDCs did not alter cell surface molecule expression. We observed marked lung inflammation, elevated total cell and eosinophil count, and altered cytokine levels in OVA-sensitized mice. These parameters improved upon inoculation with IDO-expressing imDCs. Co-culture with IDO-expressing imDCs also induced apoptosis, inhibited IL-4 and IL-5 expression, and upregulated IFN-gamma expression in CD4+ T cells. CONCLUSIONS: IDO-expressing imDCs induced T(H)2 cell apoptosis and reduced T(H)2 cell activation and allergic airway inflammation in OVA-sensitized mice. Thus, upregulation of IDO expression may provide a novel immunointervention strategy for asthma treatment.


Subject(s)
Bronchial Hyperreactivity/immunology , Dendritic Cells/immunology , Indoleamine-Pyrrole 2,3,-Dioxygenase/immunology , Ovalbumin/immunology , Animals , Apoptosis/physiology , Asthma/genetics , Asthma/immunology , Asthma/metabolism , Bone Marrow Cells/metabolism , Bronchial Hyperreactivity/metabolism , Bronchial Hyperreactivity/pathology , Bronchoalveolar Lavage Fluid/immunology , CD4-Positive T-Lymphocytes/immunology , Cytokines/biosynthesis , Cytokines/genetics , Cytokines/immunology , Dendritic Cells/enzymology , Dendritic Cells/metabolism , Eosinophils/immunology , Eosinophils/metabolism , Female , Flow Cytometry/methods , Genes, MHC Class II , Granulocyte-Macrophage Colony-Stimulating Factor/metabolism , Immune Tolerance/immunology , Indoleamine-Pyrrole 2,3,-Dioxygenase/biosynthesis , Indoleamine-Pyrrole 2,3,-Dioxygenase/genetics , Indoleamine-Pyrrole 2,3,-Dioxygenase/pharmacology , Interferon-gamma/genetics , Interferon-gamma/metabolism , Male , Mice , Mice, Inbred BALB C , Ovalbumin/pharmacology , Th2 Cells/immunology , Th2 Cells/metabolism , Up-Regulation
14.
Clin Exp Immunol ; 153(3): 410-9, 2008 Sep.
Article in English | MEDLINE | ID: mdl-18647319

ABSTRACT

Aquaporin 5 (AQP5) is one of the water channel proteins which participate in a wide array of physiological processes and are primary determinants of membrane osmotic water permeability. The AQP5 gene is located in human chromosome 12q, the same region as the location of the major asthma susceptibility loci. In this study we try to determine whether the AQP5 knock-out has some effect on allergen-induced asthma. With a mouse asthma model induced by ovalbumin (OVA), we found that deletion of AQP5 reduced some major characteristic features of asthma, such as less inflammation cell infiltration in lung tissues, lower cytokine expression and fewer inflammation cells in bronchoalveolar lavage fluids compared with those from wild-type (WT) mice. Because it was found that mice injected intratracheally with OVA-pulsed dendritic cells (DCs), the AQP5 gene knock-out (AQP5(-/-)) ones presented fewer inflammation cells. Because DCs are major antigen-presenting cells that play an important role in antigen-induced asthma, we also probed into the possible effect of gene knock-out on DCs. Surprisingly, reverse transcription-polymerase chain reaction and fluorescence activated cell sorter analysis showed high levels of AQP5 on the surface of DCs from in vivo or bone marrow monocyte-derived DCs (mDC) in vitro. Immature mDC from AQP5 knock-out mice (AQP5(-/-)) showed decreased expression of CD80 and CD86 and endocytosis ability compared with that from WT, but the difference disappeared after mDCs matured with lipopolysaccharide. AQP5-mediated water transmembrane may play some role in the function of DCs. However, the mechanism of the effect of AQP5 on the DCs' function needs to be investigated further.


Subject(s)
Aquaporin 5/metabolism , Asthma/immunology , Dendritic Cells/immunology , Animals , Antigen Presentation , B7-1 Antigen/metabolism , B7-2 Antigen/metabolism , Bone Marrow Cells/immunology , Bronchoalveolar Lavage Fluid/immunology , Case-Control Studies , Cell Membrane Permeability , Cytokines/metabolism , Disease Models, Animal , Flow Cytometry , Fluorescence , Gene Knockout Techniques , Mice , Mice, Inbred BALB C , Mice, Inbred C57BL , Mice, Knockout , Ovalbumin/pharmacology , Reverse Transcriptase Polymerase Chain Reaction
15.
Eur J Neurol ; 14(5): 510-6, 2007 May.
Article in English | MEDLINE | ID: mdl-17437609

ABSTRACT

The matrix metalloproteinases (MMPs) have come to be highlighted by their close relation to the cell invasion of gliomas. The inhibitors of MMPs have undergone extensive development because of its effectiveness against tumor invasion and angiogenesis. Therefore, a suitable animal model is necessary for searching new MMPs inhibitors against gliomas. In this study, we established an experimental model by implanting 9L glioma cells stereotactically into Fisher344 (F344) rat's brain, and the expression and enzymatic activity of MMP-2 and MMP-9 in 9L glioma cells and in tumor tissue was determined by means of reverse transcription polymerase chain reaction (RT-PCR), sodium dodecyl sulfate polyacrylamide gel electrophoresis (SDS-PAGE) zymography, in situ film zymography and immunostaining. The results of RT-PCR showed that the mRNA level of MMP-2 in 9L glioma cells was higher than that of MMP-9, and the mRNA expression of MMP-9 was increased along with the growth of malignant gliomas. SDS-PAGE zymography revealed that the expression of MMP-2 and MMP-9 were significantly increased in tumor tissues, and the MMP-9 wasn't detected in normal tissue. The positive stain of MMP-2 and MMP-9 was enhanced with the growth of malignant gliomas, especially for MMP-9. The expression of active gelatinase was found in tumor tissue. In conclusion, the expression of active MMP-2 and MMP-9 was increased in 9L/F344 rat brain during the growth of malignant gliomas at different time intervals, which indicate that 9L/F344 animal model may be a prospective animal model to test new MMPs inhibitors.


Subject(s)
Biomarkers, Tumor/metabolism , Brain Neoplasms/enzymology , Glioma/enzymology , Matrix Metalloproteinase 2/metabolism , Matrix Metalloproteinase 9/metabolism , Neoplasm Invasiveness/physiopathology , Animals , Antineoplastic Agents/pharmacology , Antineoplastic Agents/therapeutic use , Biomarkers, Tumor/analysis , Brain Neoplasms/physiopathology , Cell Line, Tumor , Disease Models, Animal , Enzyme Activation/physiology , Enzyme Inhibitors/pharmacology , Enzyme Inhibitors/therapeutic use , Extracellular Matrix/enzymology , Glioma/physiopathology , Male , Matrix Metalloproteinase 2/genetics , Matrix Metalloproteinase 9/genetics , Matrix Metalloproteinase Inhibitors , Neoplasm Transplantation , Predictive Value of Tests , RNA, Messenger/metabolism , Rats , Rats, Inbred F344 , Up-Regulation/physiology
16.
Sheng Li Xue Bao ; 52(2): 143-6, 2000 Apr.
Article in Chinese | MEDLINE | ID: mdl-11961584

ABSTRACT

To elucidate the effects of hypoxia on the proliferation and differentiation of CD34(+) hematopoietic stem/progenitor cells and their response to cytokines, the cells were isolated from umbilical cord blood by using a high-gradient magnetic cell sorting system (MACS). Mononuclear cells (MNC) and CD34(+) cells were incubated in severe hypoxia (1% oxygen) culture system, and the colony forming cells and antigen expression were studied by colony forming assays and FACS analysis. The results showed that incubation in severe hypoxia increased the number of erythroid bursts (BFU-E) (324.8+/-41.4/10(4) cells) generated from CD34(+) cells (191.2+/-34.5/10(4) cells in the control group, P<0.01). Severe hypoxia also enhanced the maintenance and cloning efficiency of BFU-E in a liquid culture system without growth factors, the number of BFU-E (152.4+/-22.6/10(4)cells) was much bigger than that in the control group (74.2+/-9.3/10(4) cells, P<0.01). In cultures incubated in hypoxia, the percentage of CD34(+) cells was significantly higher (2.5+/-1.2-fold, P<0.05) than in those incubated in air. BFU-E cloning efficiency of MNC was not significantly affected by hypoxia. The above results show that hypoxia enhances the maintenance of erythroid progenitor cells generated from CD34(+) hematopoietic stem/progenitor cells, no matter growth factors are present or not. These positive effects of hypoxia did not occur for the other progenitors.


Subject(s)
Fetal Blood/cytology , Hematopoietic Stem Cells/cytology , Leukocytes, Mononuclear/cytology , Antigens, CD34/biosynthesis , Cell Division , Cell Hypoxia , Cells, Cultured , Granulocyte-Macrophage Colony-Stimulating Factor/pharmacology , Humans , Interleukin-3/pharmacology
17.
Zhonghua Yan Ke Za Zhi ; 30(5): 382-5, 1994 Sep.
Article in Chinese | MEDLINE | ID: mdl-7805546

ABSTRACT

Sclero-circular compression operation was performed on 20 unilateral rabbit eyes to make a model of intraocular hypertension which persisted for 3 days, 1, 3 and 4 weeks respectively in 4 groups of rabbits and another 4 rabbits were used as normal controls. The trabecular meshwork and aqueous plexus of the experimental rabbits' eyes were examined under transmission electron microscope on various post-operative days: 3 days, 1, 3 and 4 weeks. It was discovered that the corneo-scleral and uveal trabecular meshworks were obviously distended and their core collagenous and elastoid fibers were hyperplastic, the phenomenon being more marked with the prolongation of the duration of the intraocular hypertension. Many endothelial cells were detached from the trabecular cords and freely located in the intertrabecular spaces. Persistent hyperplasia of collagenous fibers and accumulation of extracellular plague materials occurred in the endothelial meshwork, leading to its compactness. The giant vacuoles in the endothelial cells lining the inner wall of the canal of aqueous plexus were gradually decreased in number and the cytoplasm of the cells became attenuated and some fenestrations appeared. The results show that the main site of the resistance of the aqueous outflow occurring during intraocular hypertension is at endothelial meshwork and the above experimental morphological changes are quite similar to those of glaucoma patients.


Subject(s)
Anterior Chamber/ultrastructure , Ocular Hypertension/pathology , Animals , Microscopy, Electron , Rabbits , Trabecular Meshwork/ultrastructure
18.
Zhonghua Jie He He Hu Xi Za Zhi ; 16(6): 335-7, 373, 1993 Dec.
Article in Chinese | MEDLINE | ID: mdl-8033229

ABSTRACT

The change of blood gases, hemodynamics and oxygen delivery after weaning and the treatment of sodium nitroprusside were respectively studied in seven and twelve patients with cor pulmonale. Weaning resulted in decrement of pulmonary vascular resistance (from 48.4 +/- 16.6 to 37.6 +/- 18.5 kPa.s-1.L-1, P < 0.01) and increment of oxygen pressure of mixed venous blood (from 5.35 +/- 0.71 to 6.00 +/- 0.89 kPa.s-1.L-1, P < 0.01). Although artery pressure of oxygen (from 12.20 +/- 4.24 to 10.07 +/- 2.83 kPa, P < 0.01) was decreased after the treatment of sodium nitroprusside, cardiac index (from 44.5 +/- 10.3 to 53.0 +/- 13.7 ml.s-1.m-2, P < 0.05) and oxygen delivery index (from 7.9 +/- 1.6 to 9.3 +/- 2.2 ml.s-1.m-2, P < 0.05) were improved. It indicates that adequate weaning and application of vasodilator is useful to mechanically ventilated patients.


Subject(s)
Hemodynamics , Nitroprusside/therapeutic use , Pulmonary Heart Disease/therapy , Ventilator Weaning , Aged , Blood Gas Analysis , Female , Humans , Male , Middle Aged , Oxygen/metabolism , Pulmonary Heart Disease/physiopathology , Respiratory Insufficiency/physiopathology , Respiratory Insufficiency/therapy
19.
Zhonghua Nei Ke Za Zhi ; 32(6): 388-91, 1993 Jun.
Article in Chinese | MEDLINE | ID: mdl-8269771

ABSTRACT

The effects of sodium nitroprusside and almitrine bismesylate on blood gases, hemodynamics and oxygen delivery were respectively studied in twenty-one and eighteen patients with cor pulmonale. The treatment of sodium nitroprusside resulted in significant decrease in pulmonary artery pressure. Although physiological shunt was increased (from 12.6 +/- 10.5 to 20.1 +/- 10.9%, P < 0.01) and arterial oxygen tension was decreased (from 12.6 +/- 4.0 to 9.9 +/- 2.5 kPa, P < 0.01) in patients undergoing mechanical ventilation, cardiac index (from 44.8 +/- 10.5 to 53.3 +/- 12.8 ml.s-1/m-2, P < 0.05) and oxygen delivery index (from 7.8 +/- 1.7 to 9.2 +/- 2.3 ml.s-1/m-2, P < 0.05) were improved. After treatment with almitrine bismesylate, improvement of arterial oxygen tension was observed in patients with spontaneous breathing (from 6.7 +/- 0.6 to 7.8 +/- 0.6 kPa, P < 0.05) and undergoing mechanical ventilation (from 10.9 +/- 1.9 to 13.4 +/- 2.5 kPa, P < 0.01), but increment of mean pulmonary artery pressure (from 3.8 to 0.5 and 3.1 +/- 0.8 to 6.3 +/- 0.7 and 3.6 +/- 0.9 kPa, respectively, P < 0.01) was noted.


Subject(s)
Almitrine/therapeutic use , Hemodynamics/drug effects , Nitroprusside/therapeutic use , Pulmonary Heart Disease/drug therapy , Aged , Almitrine/pharmacology , Blood Gas Analysis , Female , Humans , Male , Middle Aged , Nitroprusside/pharmacology , Oxygen Consumption/drug effects , Pulmonary Heart Disease/metabolism , Pulmonary Heart Disease/physiopathology
20.
Zhonghua Jie He He Hu Xi Za Zhi ; 15(4): 220-1, 255, 1992 Aug.
Article in Chinese | MEDLINE | ID: mdl-1307516

ABSTRACT

Effects of control ventilation (CV) and synchronized intermittent mandatory ventilation (SIMV) were comparatively studied in 9 patients with chronic obstructive pulmonary disease. Cardiac index (from 2.99 +/- 0.65 to 3.60 +/- 0.651.min-1.m-2, P < 0.05) and oxygen delivery index (from 537 +/- 89 to 645 +/- 101 ml.min-1.m-2, P < 0.05) were significantly increased during SIMV comparing with CV. Mixed venous oxygen tension (from 5.63 +/- 0.66 to 6.06 +/- 0.59 kPa, P < 0.01) was improved by SIMV. The results showed that SIMV could improve cardiac output, oxygen delivery and oxygen supply of tissue.


Subject(s)
Lung Diseases, Obstructive/therapy , Respiration, Artificial/methods , Aged , Carbon Dioxide/blood , Female , Hemodynamics , Humans , Intermittent Positive-Pressure Ventilation , Lung Diseases, Obstructive/blood , Lung Diseases, Obstructive/physiopathology , Male , Middle Aged , Oxygen/blood
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