Your browser doesn't support javascript.
loading
Show: 20 | 50 | 100
Results 1 - 10 de 10
Filter
Add more filters










Publication year range
1.
Can Respir J ; 2020: 1350872, 2020.
Article in English | MEDLINE | ID: mdl-32104517

ABSTRACT

Introduction. Some studies have found that cilia were shorter in COPD smokers than in nonsmokers or healthy smokers. However, the structural abnormalities of cilia and the cause of such abnormalities in COPD patients still remain unknown. Tumor necrosis factor alpha receptor 3 interacting protein 1 (MIP-T3) may play an important role in the progress of ciliary protein transporting. Objectives: This study aimed at exploring the dominated structural abnormalities of cilia and the involvement of MIP-T3 in the pathogenesis of cilia of COPD patients. Methods: Patients who accepted pulmonary lobectomy were divided into 3 groups: the chronic obstructive pulmonary disease (COPD) smoker group, the healthy smoker group, and the nonsmoker group, according to smoking history and pulmonary function. The ultrastructure of cilia and the percentage of abnormal cilia were analyzed using a transmission electron microscope. Real-time PCR, immunohistochemical staining, and western blotting in bronchial epithelium were used to determine MIP-T3 mRNA and protein expression. The relationship between the percentage of abnormal cilia and lung function and MIP-T3 protein expression was analyzed. Results: Patients in the COPD smoker group had increased percentage of abnormal cilia comparing to both the healthy smoker group and the nonsmoker group (both P values <0.05). MIP-T3 expression was significantly declined in the COPD smoker group (P values <0.05). MIP-T3 expression was significantly declined in the COPD smoker group (P values <0.05). MIP-T3 expression was significantly declined in the COPD smoker group (P values <0.05). MIP-T3 expression was significantly declined in the COPD smoker group (. Conclusions: Our results suggested that the abnormal ciliary ultrastructure, which was common in COPD patients, might be due to MIP-T3 downregulation.


Subject(s)
Cilia , Microtubule-Associated Proteins/genetics , Pulmonary Disease, Chronic Obstructive , Respiratory Mucosa/metabolism , Smoking , Cilia/physiology , Cilia/ultrastructure , Down-Regulation , Female , Gene Expression Profiling , Humans , Immunohistochemistry , Male , Microscopy, Electron, Transmission/methods , Middle Aged , Pulmonary Disease, Chronic Obstructive/metabolism , Pulmonary Disease, Chronic Obstructive/physiopathology , Respiratory Function Tests/methods , Smoking/metabolism , Smoking/physiopathology
3.
Chin Med J (Engl) ; 122(8): 960-6, 2009 Apr 20.
Article in English | MEDLINE | ID: mdl-19493423

ABSTRACT

BACKGROUND: Cigarette-smoke induced DNA damage can cause airway cell apoptosis and death, which may be associated with the development of chronic obstructive pulmonary disease (COPD). However, only 20% - 30% of smokers develop COPD, suggesting that different degrees of DNA repair produce different outcomes in smokers, i.e., part of them develop COPD. We investigated the association between polymorphisms in DNA repair genes hOGG1 (Ser326Cys) and XRCC1 (Arg399Gln), alone or in combination, and susceptibility of COPD. METHODS: Altogether 201 COPD patients and 309 controls were recruited and frequency-matched on age and sex. hOGG1 and XRCC1 genotypes were determined by PCR-restriction fragment length polymorphism analysis. RESULTS: The risk of COPD was not significantly different among individuals with Ser/Cys and Cys/Cys genotypes compared with those with hOGG1 Ser/Ser genotype. The risk of COPD was not significantly different among individuals with Gln/Gln genotype compared with those with XRCC1 Arg/Arg genotype, but it was significantly elevated among individuals with Arg/Gln genotype (adjusted odds ratios (OR) = 1.55, 95% confidence intervals (CI) 1.05 - 2.29, P = 0.029). Assessment of smoking status in current smokers compared with those with hOGG1 Ser/Ser genotype revealed that the risk of COPD was significantly elevated among individuals with Cys/Cys genotype (adjusted OR = 5.07, 95% CI 1.84 - 13.95, P = 0.002). Compared with those with XRCC1 Arg/Arg genotype, the risk of COPD was significantly elevated among individuals with Arg/Gln genotype (adjusted OR = 2.77, 95% CI 1.52 - 5.07, P = 0.001). Assessment of smoking exposure in light smokers compared with those with hOGG1 Ser/Ser genotype showed that the risk of COPD was significantly elevated among individuals with Cys/Cys genotype (adjusted OR = 4.02, 95% CI 1.05 - 16.80, P = 0.042). Compared with those with XRCC1 Arg/Arg genotype, the risk of COPD was significantly elevated among individuals with Gln/Gln genotype (adjusted OR = 4.48, 95% CI 1.35 - 14.90, P = 0.014). In heavy smokers compared with those with XRCC1 Arg/Arg genotype, the risk of COPD was significantly elevated among individuals with Arg/Gln genotype (adjusted OR = 2.55, 95% CI 1.42 - 4.58, P = 0.002). When hOGG1 Ser326Cys and XRCC1 Arg399Gln polymorphisms were evaluated together, compared with those with 0 - 1 of hOGG1 326Cys and XRCC1 399Gln alleles, the risk of COPD was significantly elevated among individuals with 3 - 4 of hOGG1 326Cys and XRCC1 399Gln alleles (adjusted OR = 3.18, 95% CI 1.86 - 5.43, P = 0.000). Assessment of smoking status and smoking exposure in current/light/heavy smokers showed that the risk of COPD was significantly elevated among individuals with 3 - 4 of hOGG1 326Cys and XRCC1 399Gln alleles (adjusted OR = 8.32, 95% CI 3.59 - 19.27, P = 0.000; OR = 5.46, 95% CI 2.06 - 14.42, P = 0.001; OR = 2.93, 95% CI 1.43 - 6.02, P = 0.003; respectively). CONCLUSIONS: hOGG1 Ser326Cys and XRCC1 Arg399Gln polymorphisms are associated with the susceptibility to COPD. The risk of COPD is significantly elevated among current/light smokers with hOGG1 326Cys and XRCC1 399Gln.


Subject(s)
DNA Glycosylases/genetics , DNA-Binding Proteins/genetics , Genetic Predisposition to Disease , Polymorphism, Genetic , Pulmonary Disease, Chronic Obstructive/genetics , Aged , Aged, 80 and over , Female , Genetic Predisposition to Disease/genetics , Genotype , Humans , Male , Middle Aged , Polymerase Chain Reaction , Polymorphism, Restriction Fragment Length , X-ray Repair Cross Complementing Protein 1
4.
Zhongguo Shi Yan Xue Ye Xue Za Zhi ; 16(5): 1055-9, 2008 Oct.
Article in Chinese | MEDLINE | ID: mdl-18928594

ABSTRACT

This study was aimed to investigate the effect of recombinant mutant human TNF-related apoptosis-inducing ligand (rmhTRAIL) combined with As(2)O(3) on inducing apoptosis of adriamycin-resistant leukemia cell line K562/A02 (mdr-1(+)). The morphologic changes of cells treated with rmhTRAIL were observed by inverted microscope, taking adriamycin-sensitive cell line K562 (mdr-1(-)) as control; the inhibitory rate of cell proliferation after being treated with rmhTRAIL, As(2)O(3) alone or combined was assayed by MTT method; the apoptosis peaks of K562/AO2 and K562 were quantitatively detected by flow cytometry with PI staining after being treated with rmhTRAIL, As(2)O(3) alone or in combination. The results indicated that the inhibition effect of rmhTRAIL and As(2)O(3) in combination on K562/AO2 and K562 cells was higher than that of riTRAIL and As(2)O(3) alone (p < 0.01), rmhTRAIL combined with As(2)O(3) had synergistic effect in killing K562/AO2 and K562 cells by king's formula. The apoptosis rates of K562/AO2 and K562 cells were 34.93 +/- 0.10% and 10.53 +/- 0.16% (p < 0.01), as well as 5.95 +/- 0.07%, and 3.50 +/- 0.01% (p < 0.05), 50.95 +/- 0.91% and 20.75 +/- 0.95% (p < 0.05) respectively when their cells were treated by rmhTRAIL and As(2)O(3) alone. The apoptosis rate in K562/AO2 group was higher than that in K562 group. It is concluded that rmhTRAIL can induce K562/A02 and K562 cell apoptosis; rmhTRAIL combined As(2)O(3) had synergistic effects; the efficacy of on rmhTRAIL or As(2)O(3) inducing K562/AO2 cell apoptosis is higher than that on their parental cell line K562.


Subject(s)
Apoptosis/drug effects , Arsenicals/pharmacology , Oxides/pharmacology , TNF-Related Apoptosis-Inducing Ligand/pharmacology , Arsenic Trioxide , Doxorubicin/pharmacology , Drug Resistance, Multiple/drug effects , Drug Resistance, Neoplasm/drug effects , Drug Synergism , Humans , K562 Cells , Recombinant Proteins/pharmacology
5.
Zhonghua Zhong Liu Za Zhi ; 30(11): 808-12, 2008 Nov.
Article in Chinese | MEDLINE | ID: mdl-19173823

ABSTRACT

OBJECTIVE: To evaluate the inhibitory effects of recombinant mutant tumor necrosis factor-related apoptosis-inducing ligand (rmhTRAIL) combined with chemotherapeutic agent gemcitabine (GEM) on human lung cancer cell line NCI-H460 cells in vitro and in vivo. METHODS: MTT was used to evaluate the cytotoxic effects of rmhTRAIL and GEM either used alone or in combination treatment on NCI-H460 cells. BAL B/c nude mice were transplanted with NCI-H460 tumor. The tumor-bearing nude mice were randomly divided into 6 groups (n = 6): negative control group (to be injected intraperitoneally with normal saline); rmhTRAIL group; GEM group; rmhTRAIL plus GEM group; GEM plus DDP group; rmhTRAIL plus GEM andDDP group. The tumor size was measured every 3 - 4 days. Twenty one days after the administration of different drugs the mice were killed and the tumors were taken out and weighed. RESULTS: The growth inhibition of NCI-H460 cells was dose-dependent after exposure to rmhTRAIL, GEM alone or together. The combination of rmhTRAIL and GEM showed a synergistic inhibitory effect at different concentrations. The relative tumor volume of rmhTRAIL group, rmhTRAIL plus GEM group, GEM plus DDP group and rmhTRAIL plus GEM and DDP group were 4.75 +/- 3.04, 2.53 +/- 1.25, 4.52 +/- 2.87, and 1.69 +/- 0.97, respectively, all significantly smaller than that of the negative control group (8.82 +/- 5.62, P < 0.05 or P < 0.01). The tumor weight of these four groups were (2.23 +/- 0.29) g, (1.12 +/- 0.77) g, (2.51 +/- 0.87) g, and 0.60 +/- 0.18 g, respectively, all significantly less then that of the negative control group (4.71 g +/- 0.97 g, all P < 0.01). Both the relative tumor volume and tumor weight of rmhTRAIL plus GEM group were significantly smaller than those of either rmhTRAIL group or GEM group (P < 0.05 and P < 0.01, respectively). Both the relative tumor volume and tumor weight of rmhTRAIL plus GEM and DDP group were significantly smaller than those of either rmhTRAIL group or GEM plus DDP group (P < 0.05 and P < 0.01, respectively). CONCLUSION: The combination of rmhTRAIL and GEM has a synergistic inhibitory effect on human NSCLC cell line NCI-H460 cells either in vitro and in vivo.


Subject(s)
Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Carcinoma, Non-Small-Cell Lung/drug therapy , Deoxycytidine/analogs & derivatives , Lung Neoplasms/drug therapy , TNF-Related Apoptosis-Inducing Ligand/administration & dosage , Animals , Carcinoma, Non-Small-Cell Lung/pathology , Cell Line, Tumor , Cell Proliferation/drug effects , Cisplatin/administration & dosage , Deoxycytidine/administration & dosage , Drug Synergism , Female , Humans , Lung Neoplasms/pathology , Mice , Mice, Inbred BALB C , Mice, Nude , Neoplasm Transplantation , Recombinant Proteins/administration & dosage , Tumor Burden/drug effects , Gemcitabine
6.
Zhongguo Shi Yan Xue Ye Xue Za Zhi ; 14(6): 1123-8, 2006 Dec.
Article in Chinese | MEDLINE | ID: mdl-17204177

ABSTRACT

The aim of study was to investigate the combined effect of recombinant mutant human TRAIL (rmhTRAIL) with daunorubicin (DNR) or alone on K562 and U937 leukemia cell lines and its mechanism. The fibroblasts (MRC-5) of normal-human embryonic lung were used as control cells. After being treated with rmhTRAIL and DNR or only with rmTRAIL, the cytotoxic effect and the apoptosis rate in K562, U937 cells were measured by MTT assay. The expression levels of TRAIL death receptor and TRAIL decoy receptor mRNA in these three cell lines were assayed by semiquantitive RT-PCR before and after treatment with DNR. The results indicated that K562 and U937 were sensitive to rmhTRIAL. DNR had synergistic inhibitory effect with rmhTRAIL on the growth of K562 and U937 cell lines (P < 0.05). The expression level of DR4 and DR5 mRNA was significantly higher in K562 and U937 with combined treatment of rmhTRAIL and DNR than that in those alone, while the expressions of DcR1 and DcR2 mRNA were not influenced. It is concluded that in vitro, rmhTRAIL alone or in combination with DNR can obviously inhibit the growth of leukemia cell lines and induce cell apoptosis, DNR and rmhTRAIL have a synergistic inhibitory effect on growth of K562 and U937. The mechanism may correlate with the up-regulation of DR4 and DR5 of K562 and U937.


Subject(s)
Apoptosis/drug effects , Daunorubicin/pharmacology , TNF-Related Apoptosis-Inducing Ligand/pharmacology , Antibiotics, Antineoplastic/pharmacology , Drug Synergism , Humans , K562 Cells , Mutation , Receptors, TNF-Related Apoptosis-Inducing Ligand/biosynthesis , Receptors, TNF-Related Apoptosis-Inducing Ligand/genetics , Recombinant Proteins/pharmacology , U937 Cells , Up-Regulation
7.
Article in Chinese | MEDLINE | ID: mdl-21162237

ABSTRACT

AIM: To study the effects and the mechanisms of cholecystokinin octapeptide(CCK-8) on hippocampal injury during endotoxic shock (ES). METHODS: Rabbits were injected intravenously with lipopolysaccharide (LPS, 8 mg/kg) to establish ES model. Thirty-two Rabbits were divided into 4 groups at random (n = 8): control (saline, iv), LPS, CCK-8 + LPS (CCK-8 pre-administrated 30 min before LPS, iv), proglumide (Pro, nonspecific antagonist of CCK receptors) + LPS (Pro pre-administrated 30 min before LPS, iv) group. The changes of mean arterial pressure (MAP) were measured. The morphologic changes in the hippocampus were observed through light microscope (LM) and transmission electron microscope (TEM). The alterations of activities of nitric oxide synthase (NOS) and superoxide dismutase (SOD), contents of nitric oxide (NO) and malondialdehyde (MDA) in the hippocampus were assayed. Twelve Sprague-Dawley rats, grouped as that of the rabbits, were used to detect the expression of inducible NOS (iNOS) and neuronal NOS (nNOS) protein by immunohistochemistry staining. RESULTS: LPS administration resulted insignificant reduction in MAP (P < 0.01 vs control group) and hydropic degeneration of neurons in the hippocampus. Compared with those of control group, the NOS activity, NO level and MDA content were increased significantly (P < 0.05, P < 0.01 and P < 0.05), while SOD activity was reduced (P < 0.01) in the hippocampus of ES rabbits. LPS administration induced the expression of iNOS protein in the cytoplasm of hippocampus neurons, and lead to stronger positive signals of nNOS than that of control group. CCK-8 pre-administration could alleviate the changes induced by LPS, while Pro pre-administration aggravated those alterations. CONCLUSION: CCK-8 could protect hippocampus neurons against the injury induced by LPS during ES, which might be associated with its effects of suppressing the over production of NO and free radicals.


Subject(s)
Hippocampus/metabolism , Shock, Septic/metabolism , Sincalide/analogs & derivatives , Animals , Disease Models, Animal , Male , Nitric Oxide/metabolism , Rabbits , Rats , Rats, Sprague-Dawley , Signal Transduction , Sincalide/pharmacology
8.
Zhonghua Yi Xue Za Zhi ; 85(29): 2021-5, 2005 Aug 03.
Article in Chinese | MEDLINE | ID: mdl-16313792

ABSTRACT

OBJECTIVE: To evaluate the therapeutic effects of recombinant mutant human tumor necrosis factor-related apoptosis-inducing ligand (rmhTRAIL) on non-small cell cancer (NSCLC). METHODS: NSCLC cells of the line NCI-H460 were cultured and underwent agarose gel electrophoresis. rmhTRAIL of different concentrations was added into the culture fluid to observe the influence of rmhTRAIL. Nude BALB/c rats were transplanted with rat NCI-H460 tumor. Then the rats carrying xenografts were randomly divided into 5 groups of 8 rats: negative control group to be injected intraperitoneally with normal saline; positive control group to be injected with vancristine; low-dose rmhTRAIL group, to be injected with 1.7 mg/kg rmhTRAIL, middle-dose rmhTRAIL group to be injected with rmhTRAIL 5.0 mg/kg, and high-dose rmhTRAIL group to be injected with 15.0 mg/kg rmhTRAIL. The size of tumor was measured every 3 approximately 4 days. Ten days after the administration of different drugs the rats were killed and the tumors were taken out to undergo TUNEL staining for microscopy. RESULTS: The relative tumor volume of the low-dose rmhTRAIL group and high-dose rmhTRAIL group were 3.19 +/- 2.05 and 1.47 +/- 0.77 respectively, both significantly smaller than that of the negative group (8.48 +/- 5.87, P < 0.05 and P < 0.01). The relative tumor growth rate of the low-dose rmhTRAIL group and high-dose rmhTRAIL group were 37.6% and 17.3% respectively. The tumor weight of low-dose rmhTRAIL group and high-dose rmhTRAIL group were 1.09 g +/- 0.55 g and 0.31 g +/- 0.09 g respectively, both significantly lighter than that of the negative control group (2.78 +/- 0.77, both P < 0.01). Large amount of apoptotic cells were seen in the tumor tissues of the rmhTRAIL -treated rats and tumors cells cultured with rmhTRAIL. Agarose gel electrophoresis showed apoptosis-characteristic ladder in the DNA extracted from the rmhTRAIL -treated tumors cells. CONCLUSION: rmhTRAIL dose-dependently inhibit the growth of NSCLC cells, primarily by inducing apoptosis of tumor cells.


Subject(s)
Apoptosis/drug effects , Carcinoma, Non-Small-Cell Lung/therapy , Lung Neoplasms/therapy , TNF-Related Apoptosis-Inducing Ligand/therapeutic use , Animals , Female , Mice , Mice, Inbred BALB C , Mice, Nude , Neoplasm Transplantation , Rats , Recombinant Proteins/therapeutic use
9.
Acta Pharmacol Sin ; 26(11): 1373-81, 2005 Nov.
Article in English | MEDLINE | ID: mdl-16225761

ABSTRACT

AIM: To investigate the antitumor activity and safety of a novel recombinant mutant human tumor necrosis factor-related apoptosis-inducing ligand (rmh TRAIL). METHODS: Antitumor activity of rmh TRAIL was evaluated by using several tumor cell lines by MTT assay in vitro, and by using a mouse xenograft model in vivo. rmh TRAIL-induced apoptosis in tumor cells was detected by cell death enzyme-linked immunosorbent assay (ELISA), TdT-mediated dUTP nick-end labeling (TUNEL) assay and flow cytometry. The safety of rmh TRAIL was also evaluated in several normal human cell lines. RESULTS: At the concentration of 0.32-1 000 ng/mL, rmh TRAIL remarkably inhibited the proliferation of 5 tumor cell lines from lung, colon, and breast cancer compared with wild type (wt TRAIL) in vitro, whereas at the concentration of 1 ng/mL-10 microg/mL, rmh TRAIL showed no or mild cytotoxicity in the normal cell lines. rmh TRAIL (3, 15 mg/kg, ip, once daily for 10 d) exerted a significant inhibition on the growth of xenograft tumor NCI-H460 in nude mice compared with the saline group (P<0.01), and was more potent than wt TRAIL, a positive control. The apoptosis of NCI-H460 cells was markedly induced in a concentration-dependent and time-dependent manner after rmh TRAIL treatment. The percentage of apoptotic cells induced by rmh TRAIL in NCI-H460 cells was significantly higher than that by wt TRAIL. CONCLUSION: rmh TRAIL provided potent antitumor activity in vivo and in vitro, whereas most normal human cells were resistant to rmh TRAIL. The results suggested that rmh TRAIL might be a useful anticancer agent in future.


Subject(s)
Antineoplastic Agents/pharmacology , Apoptosis/drug effects , Carcinoma, Non-Small-Cell Lung/pathology , Lung Neoplasms/pathology , TNF-Related Apoptosis-Inducing Ligand/pharmacology , Animals , Cell Line, Tumor , Cell Proliferation/drug effects , Dose-Response Relationship, Drug , Humans , Mice , Mice, Inbred BALB C , Mice, Nude , Mutation , Neoplasm Transplantation , TNF-Related Apoptosis-Inducing Ligand/administration & dosage , TNF-Related Apoptosis-Inducing Ligand/genetics
10.
Sheng Li Xue Bao ; 55(2): 201-5, 2003 Apr 25.
Article in Chinese | MEDLINE | ID: mdl-12715112

ABSTRACT

For investigation of the regulatory mechanism of cholecystokinin-octapeptide (CCK-8) on pulmonary circulation in rabbits with endotoxic shock (ES) induced by lipopolysaccharides (LPS), mean arterial pressure (MAP) and pulmonary arterial pressure (PAP) were evaluated for 5 h in five groups of rabbits: group of LPS (8 mg/kg, i.v.)-induced ES, group of CCK-8 pretreatment (15 microg/kg, i.v.) 15 min before LPS administration (8 mg/kg, i.v.), group of proglumide pretreatment (1 mg/kg, i.v.) 15 min before LPS administration (8 mg/kg, i.v.), group of CCK (15 microg/kg, i.v.) only, and normal saline (control) group. The pulmonary arterial tension was measured with isolated vascular ring technique. The results showed that LPS-induced pulmonary arterial hypertension was abolished by CCK-8. In contrast, proglumide, a nonspecific antagonist of CCK-8 receptor, potentiated the deleterious effect of LPS. The contractile response of isolated pulmonary artery to alpha-adrenoceptor agonist phenylephrine (PE) was enhanced and the relaxation response to acetylcholine (ACh) was depressed significantly after LPS was injected, but the effect could be reversed by CCK-8. These results suggest that pulmonary circulation is improved by CCK-8 in ES, and the regulatory effects of CCK-8 may be brought about by modulating the pulmonary arterial tension.


Subject(s)
Hypertension, Pulmonary/physiopathology , Pulmonary Artery/physiology , Shock, Septic/physiopathology , Sincalide/pharmacology , Animals , Hypertension, Pulmonary/etiology , Male , Pulmonary Artery/drug effects , Rabbits , Shock, Septic/complications , Vasodilation/drug effects
SELECTION OF CITATIONS
SEARCH DETAIL
...