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1.
Brain ; 2024 May 03.
Article in English | MEDLINE | ID: mdl-38701344

ABSTRACT

The implication of 5-hydroxytryptamine 2C receptor (5-HT2CR) in depression is a topic of debate, and the underlying mechanisms remain largely unclear. We now elucidate hippocampal excitation-inhibition (E/I) balance underlies the regulatory effects of 5-HT2CR in depression. Molecular biological analyses showed that chronic mild stress (CMS) reduced the expression of 5-HT2CR in hippocampus. We revealed that inhibition of 5-HT2CR induced depressive-like behaviors, reduced GABA release and shifted the E/I balance towards excitation in CA3 pyramidal neurons by using behavioral analyses, microdialysis coupled with mass spectrum, and electrophysiological recording. Moreover, 5-HT2CR modulated neuronal nitric oxide synthase (nNOS)-carboxy-terminal PDZ ligand of nNOS (CAPON) interaction through influencing intracellular Ca2+ release, as determined by fiber photometry and coimmunoprecipitation. Notably, disruption of nNOS-CAPON by specific small molecule compound ZLc-002 or AAV-CMV-CAPON-125C-GFP, abolished 5-HT2CR inhibition-induced depressive-like behaviors, as well as the impairment in soluble N-ethylmaleimide-sensitive factor attachment protein receptor (SNARE) complex assembly-mediated GABA vesicle release and a consequent E/I imbalance. Importantly, optogenetic inhibition of CA3 GABAergic neurons prevented the effects of AAV-CMV-CAPON-125C-GFP on depressive behaviors in the presence of 5-HT2CR antagonist. Conclusively, our findings disclose the regulatory role of 5-HT2CR in depressive-like behaviors and highlight the hippocampal nNOS-CAPON coupling-triggered E/I imbalance as a pivotal cellular event underpinning the behavioral consequences of 5-HT2CR inhibition.

2.
Front Mol Biosci ; 11: 1366113, 2024.
Article in English | MEDLINE | ID: mdl-38560520

ABSTRACT

Kinesin motors are a large family of molecular motors that walk along microtubules to fulfill many roles in intracellular transport, microtubule organization, and chromosome alignment. Kinesin-7 CENP-E (Centromere protein E) is a chromosome scaffold-associated protein that is located in the corona layer of centromeres, which participates in kinetochore-microtubule attachment, chromosome alignment, and spindle assembly checkpoint. Over the past 3 decades, CENP-E has attracted great interest as a promising new mitotic target for cancer therapy and drug development. In this review, we describe expression patterns of CENP-E in multiple tumors and highlight the functions of CENP-E in cancer cell proliferation. We summarize recent advances in structural domains, roles, and functions of CENP-E in cell division. Notably, we describe the dual functions of CENP-E in inhibiting and promoting tumorigenesis. We summarize the mechanisms by which CENP-E affects tumorigenesis through chromosome instability and spindle assembly checkpoints. Finally, we overview and summarize the CENP-E-specific inhibitors, mechanisms of drug resistances and their applications.

3.
Front Immunol ; 15: 1376544, 2024.
Article in English | MEDLINE | ID: mdl-38638440

ABSTRACT

Background: Sarcopenia, common in the elderly, often linked to chronic diseases, correlates with inflammation.The association between SII and mortality in sarcopenia patients is underexplored, this study investigates this relationship in a U.S. adult cohort. Methods: We analyzed 1999-2018 NHANES data, focusing on 2,974 adults with sarcopenia. Mortality outcomes were determined by linking to National Death Index (NDI) records up to December 31, 2019. Using a weighted sampling design, participants were grouped into three groups by the Systemic Immune-Inflammation Index (SII). We used Cox regression models, adjusting for demographic and clinical variables, to explore SII's association with all-cause and cause-specific mortality in sarcopenia, performing sensitivity analyses for robustness. Results: Over a median follow-up of 9.2 years, 829 deaths occurred. Kaplan-Meier analysis showed significant survival differences across SII groups. The highest SII group showed higher hazard ratios (HRs) for all-cause and cause-specific mortality in both crude and adjusted models. The highest SII group had a higher HR for all-cause(1.57, 1.25-1.98), cardiovascular(1.61, 1.00-2.58), cancer(2.13, 1.32-3.44), and respiratory disease mortality(3.21, 1.66-6.19) in fully adjusted models. Subgroup analyses revealed SII's association with all-cause mortality across various demographics, including age, gender, and presence of diabetes or cardiovascular disease. Sensitivity analyses, excluding participants with cardiovascular diseases, those who died within two years of follow-up, or those under 45 years of age, largely reflected these results, with the highest SII group consistently demonstrating higher HRs for all types of mortality in both unadjusted and adjusted models. Conclusion: Our study is the first to demonstrate a significant relationship between SII and increased mortality risks in a sarcopenia population.


Subject(s)
Cardiovascular Diseases , Sarcopenia , Adult , Aged , Humans , Cause of Death , Nutrition Surveys , Inflammation
4.
Org Lett ; 25(46): 8205-8209, 2023 Nov 24.
Article in English | MEDLINE | ID: mdl-37947432

ABSTRACT

The electrochemical synthesis of 5-aminocoumaran derivatives from easily oxidizable aminophenols and readily available olefins is described. The reaction efficiently produces 5-aminocoumarans in high yield under mild and environmentally friendly conditions without the necessity of catalysts, additives, oxidizing agents, or sacrificial reagents. Hydrogen as the sole byproduct of the reaction makes the method clean, highly atom-efficient, and step-economical.

5.
Org Lett ; 24(23): 4258-4263, 2022 Jun 17.
Article in English | MEDLINE | ID: mdl-35666163

ABSTRACT

We report here an organic dye catalyzed direct radical-radical cross-coupling reaction based on the persistent free-radical effect (PRE), which is powered by visible light and does not require any external oxidants or reductants. In this reaction, benzyl trifluoroborates are oxidized by excited-state 4Cz-IPN to generate benzyl radicals, and the resulting boron trifluoride acts as a Lewis acid to reduce the reduction potential of carbonyl compounds. The dual roles of benzyl trifluoroborates enable aldehydes, ketones, diketones, and ketone esters to react with benzyl trifluoroborates to generate various sterically hindered alcohols.

6.
J Vis Exp ; (178)2021 12 28.
Article in English | MEDLINE | ID: mdl-35037651

ABSTRACT

In eukaryotes, meiosis is essential for genome stability and genetic diversity in sexual reproduction. Experimental analyses of spermatocytes in testes are critical for the investigations of spindle assembly and chromosome segregation in male meiotic division. The mouse spermatocyte is an ideal model for mechanistic studies of meiosis, however, the effective methods for the analyses of spermatocytes are lacking. In this article, a practical and efficient method for the in vivo inhibition of kinesin-7 CENP-E in mouse spermatocytes is reported. A detailed procedure for testicular injection of a specific inhibitor GSK923295 through abdominal surgery in 3-week-old mice is presented. Furthermore, described here is a series of protocols for tissue collection and fixation, hematoxylin-eosin staining, immunofluorescence, flow cytometry and transmission electron microscopy. Here we present an in vivo inhibition model via abdominal surgery and testicular injection, that could be a powerful technique to study male meiosis. We also demonstrate that CENP-E inhibition results in chromosome misalignment and metaphase arrest in primary spermatocytes during meiosis I. Our in vivo inhibition method will facilitate mechanistic studies of meiosis, serve as a useful method for genetic modifications of male germ lines, and shed a light on future clinical applications.


Subject(s)
Kinesins , Spermatocytes , Animals , Chromosomal Proteins, Non-Histone , Flow Cytometry , Fluorescent Antibody Technique , Male , Meiosis , Mice , Staining and Labeling
7.
J Clin Periodontol ; 47(12): 1496-1510, 2020 12.
Article in English | MEDLINE | ID: mdl-33010026

ABSTRACT

AIM: This systematic review and network meta-analysis aimed to evaluate the efficacy of adjunctive locally delivered antimicrobials, compared to subgingival instrumentation alone or plus a placebo, on changes in probing pocket depth (PPD) and clinical attachment level (CAL), in patients with residual pockets during supportive periodontal care. MATERIALS AND METHODS: Literature search was performed with electronic databases and by hand until 31 May 2020. Primary outcome was the changes in PPD. The treatment effects between groups were estimated with weighted mean differences (WMD) with 95% confidence intervals (CI) and prediction intervals (PI) by using random-effects network meta-analysis. RESULTS: Twenty-two studies were included. Significantly greater PPD reduction was achieved in chlorhexidine chip group (WMD: 0.65 mm, 95% CI: 0.21-1.10) and tetracycline fibre group (WMD: 0.64 mm, 95% CI: 0.20-1.08) over 6-month follow-up. Other adjunctive antimicrobial agents achieved non-significant improvements compared to scaling and root planing alone. All differences between adjunctive therapies were statistically non-significant. Similar findings were observed for CAL gain. CONCLUSION: Adjunctive local antimicrobial agents achieved small additional PPD reduction and CAL gain in residual pockets for a follow-up of up to 6 months. Tetracycline fibre and chlorhexidine chip achieved better results than other antimicrobials.


Subject(s)
Chlorhexidine , Dental Scaling , Anti-Bacterial Agents/therapeutic use , Chlorhexidine/therapeutic use , Humans , Network Meta-Analysis , Root Planing
8.
Neurobiol Dis ; 146: 105133, 2020 12.
Article in English | MEDLINE | ID: mdl-33049318

ABSTRACT

Dendritic spines are specialized structures involved in neuronal processes on which excitatory synaptic contact occurs. The microtubule cytoskeleton is vital for maintaining spine morphology and mature synapses. Spastin is related to microtubule-severing proteases and is involved in synaptic bouton formation. However, it is not yet known if spastin can be modified by Small Ubiquitin-like Modifier (SUMO) or how this modification regulates dendritic spines. Spastin was shown to be SUMOylated at K427, and its deSUMOylation promoted microtubule stability. In addition, SUMOylation of spastin was shown to affect signalling pathways associated with long term synaptic depression. SUMOylated spastin promoted the development of dendrites and dendritic spines. Moreover, SUMOylated spastin regulated endocytosis and affected the transport of the AMPA receptor, GluA1. Our findings suggest that SUMOylation of spastin promotes GluA1 internalization and regulates dendritic spine morphology through targeting of microtubule dynamics.


Subject(s)
Dendritic Spines/metabolism , Microtubules/metabolism , Receptors, AMPA/metabolism , Spastin/metabolism , Sumoylation/physiology , Animals , Long-Term Synaptic Depression/physiology , Neurons/metabolism , Rats, Sprague-Dawley , Spastin/pharmacology , Synapses/physiology
9.
BMC Surg ; 20(1): 15, 2020 Jan 17.
Article in English | MEDLINE | ID: mdl-31952499

ABSTRACT

BACKGROUND: Nonfusion fixation is an effective way to treat lumbar degeneration. In the present study, we analyzed the clinical effects and radiographic outcomes of the Isobar TTL system used to treat two-segment lumbar degenerative disease. METHOD: Forty-one patients diagnosed with two-segment lumbar degenerative disease underwent surgical implantation of the Isobar TTL dynamic stabilization system (n = 20) or a rigid system (n = 21) from January 2013 to June 2017. The mean follow-up time was 23.6 (range 15-37) months. Clinical results were evaluated with the Oswestry Disability Index (ODI), modified Macnab criteria, and the visual analog score (VAS). Radiographic evaluations included the height of the intervertebral space and the range of motion (ROM) of the treated and adjacent segments. The intervertebral disc signal was classified using the modified Pfirrmann grading system and the University of California at Los Angeles (UCLA) system. RESULTS: The clinical results, including the ODI and VAS, showed that there was significant improvement in the two groups after implantation and that the difference between the two groups was not significant. In addition, the clinical efficacy indicated by the modified Macnab criteria for the two groups was similar. Radiological outcomes included the height of the intervertebral space, lumbar mobility, and intervertebral disc signal. The height of the intervertebral space of the upper adjacent segment L2/3 in the rigid group was significantly lower than that in the Isobar TTL group at the last follow-up. Furthermore, the number of ROMs of the fixed-segment L3/4 in the Isobar TTL group was significantly less than that before implantation, suggesting that the fixed-segment ROMs in the Isobar TTL group were limited. In addition, the ROM of the upper adjacent segment L2/3 in the last follow-up of the rigid group increased significantly, while that of the Isobar TTL group did not change after implantation. Finally, the incidence of adjacent-segment degeneration (ASD) was significantly greater in the rigid group than in the Isobar TTL group according to the UCLA system. CONCLUSION: The Isobar TTL system can be clinically effective for treating two-segment lumbar degenerative disease. Compared with rigid fixation, the Isobar TTL system yielded better radiographic outcomes and maintained the mobility of the treated segments with less impact on the proximal adjacent segment.


Subject(s)
Intervertebral Disc Degeneration/surgery , Lumbar Vertebrae/surgery , Aged , Female , Humans , Lumbosacral Region , Male , Middle Aged , Radiography , Range of Motion, Articular , Retrospective Studies , Treatment Outcome
10.
Inorg Chem ; 58(2): 1481-1491, 2019 Jan 22.
Article in English | MEDLINE | ID: mdl-30601003

ABSTRACT

Three water-stable luminescent MOFs [Zn4(bptc)2(NMP)3(DMF)(H2O)2] n (1-a), [Cd4(bptc)2(NMP)3(DMF)2(H2O)1] n (1-b), and {[Zn2(bptc)(DMA)(H2O)2]·(DMA)2·H2O} n (2), possessing similar chemical components (M2:L1:Sol3) and topology structures, were synthesized by solvents control. Their excellent sensing on iron(III) cation and nitroaromatic explosives (NACs) with great selectivity, sensitivity and a high Ksv (4.54 × 104 for 1-b on PNP) were observed by quenching effects. Furthermore, Zn-MOFs exhibit interesting stimuli-responsive luminescence enhancement after the encapsulation of a series of IIIB cations stimulated different luminescent emitting and intensity enhancement through host-guest processes of the pores in MOFs, especially for two distinct responses of Zn-MOF on a Tb3+ cation.

11.
Zhonghua Jie He He Hu Xi Za Zhi ; 33(4): 265-7, 2010 Apr.
Article in Chinese | MEDLINE | ID: mdl-20646456

ABSTRACT

OBJECTIVE: To explore the role of CD(47) and P-selectin in patients with COPD. METHODS: The blood plasma levels of CD(47) and P-selectin in 20 healthy volunteers (control group) and 35 patients with COPD in acute exacerbation and at stable stage were measured by flow cytometry. Platelet count was measured by hematology analyzer. SNK-q test and Pearson correlation analysis of the regression equation were used for statistics. RESULTS: The level of CD(47) in the COPD acute exacerbation group [(93 +/- 4)%] was significantly higher than that of the COPD stable group [(72 +/- 11)%] and that of the control group [(67 +/- 10)%], q = 11.26, 13.32, all P < 0.01, but the difference in CD(47) between the stable group and the control group was not significant (q = 1.73, P > 0.05). The level of P-selectin in the acute exacerbation group [(35 +/- 11)%] was significantly higher than those of the stable group [(12 +/- 8)%] and the control group [(10 +/- 4)%] (q = 9.93, 12.19, all P < 0.05), and the level of stable group was also higher than that of the control group (q = 1.90, P < 0.05). The difference in platelet counts among the acute exacerbation group [(188 +/- 56) x 10(9)/L], the stable group [(213 +/- 57) x 10(9)/L] and the control group [(204 +/- 51) x 10(9)/L] was not significant (F = 1.74, P > 0.05). A significant positive correlation between CD(47) and P-selectin was observed in the acute exacerbation group(r = 0.77, P < 0.01), but not in the stable group and the control group (r = -0.04, -0.15, all P > 0.05). CONCLUSIONS: The levels of CD(47) and P-selectin as markers of platelet activation increase significantly during AECOPD, which suggests that platelet activation exists in AECOPD and platelets as a type of inflammatory cells participate in the disease.


Subject(s)
CD47 Antigen/blood , P-Selectin/blood , Pulmonary Disease, Chronic Obstructive/blood , Aged , Aged, 80 and over , Case-Control Studies , Female , Humans , Male , Middle Aged , Platelet Activation , Pulmonary Disease, Chronic Obstructive/physiopathology
12.
Zhonghua Jie He He Hu Xi Za Zhi ; 31(4): 291-3, 2008 Apr.
Article in Chinese | MEDLINE | ID: mdl-18846968

ABSTRACT

OBJECTIVE: To explore the role of soluble vascular cell adhesion molecule-1 (sVCAM-1) and soluble platelet endothelial cell adhesion molecular-1 (sPECAM-1) of prethrombotic state mediators in patients with chronic obstructive pulmonary disease (COPD). METHODS: The blood plasma levels of D-dimer (D-D), sVCAM-1 and sPECAM-1 in 20 healthy volunteers (control group) and 35 patients with acute exacerbation of COPD ( AECOPD) before and after treatment were measured by ELISA. The statistical analysis used Student' s t test of significance and Pearson linear correlation analysis. RESULTS: The level of D-D in patients before treatment [(4.49 +/- 1.47) mg/L] was significantly higher than that after treatment [(1.98 +/- 0.92) mg/L] and that of the control group [(0.44 +/- 0.14) mg/L] (t = 0.91, 13.10, both P < 0.001); the level of D-D in patients after treatment was also higher than that of the control group (t = 4.96, P < 0.001). The level of sVCAM-1 in patients before treatment [(11 +/- 5) nmol/L] was significantly higher than those of patients after treatment [(8 +/- 4) nmol/L] and control group [(7 +/- 4) nmol/L] (t = 2. 24, 2.75, both P < 0.001); but the difference of sVCAM-l between the post-treatment group and the control group was not significant (t = 0.75, P > 0.05). The level of sPECAM-1 in patients after treatment [(61 +/- 13) pmol/L] was significantly higher than that before treatment [(36 +/- 8) pmol/L] and that of the control group [(43 +/- 10) pmol/L] (t = 9.23, 5.91, both P < 0.001), and the level of the control group was also higher than that of patients before treatment (t = 2.35, P < 0.05). Before treatment, there was significant positive correlation between D-D and sVCAM-1 (r = 0.759, P < 0.01) but no correlation between sPECAM-1 and D-D or sVCAM-1 (r = 0.045, 0.078, both P > 0.05). After treatment, there was significant negative correlation between D-D and sPECAM-1 (r = -0.548, P < 0.01) but no correlation between sVCAM-land D-D or sPECAM-1 (r = -0.032, 0.143, both P > 0.05). There were no correlations among D-D and sPECAM-1 and sVCAM-1 respectively in the control group (r = 0.137, -0.121, 0.035, all P > 0.05). CONCLUSIONS: The levels of D-D and sVCAM-1 increase significantly during acute exacerbation of COPD, which suggests that prethrombotic state exists in acute exacerbation of COPD. The measurement of D-D and sVCAM-1 is useful to monitor prethrombotic state during acute exacerbation of COPD and may be useful in evaluating the severity. The significant increase of sPECAM-1 in plasma of patients after treatment suggests that sPECAM-1 may be a protective factor against prethrombotic state.


Subject(s)
Platelet Endothelial Cell Adhesion Molecule-1/blood , Pulmonary Disease, Chronic Obstructive/diagnosis , Thrombosis/diagnosis , Vascular Cell Adhesion Molecule-1/blood , Aged , Aged, 80 and over , Case-Control Studies , Female , Fibrin Fibrinogen Degradation Products/metabolism , Humans , Male , Middle Aged , Pulmonary Disease, Chronic Obstructive/complications , Thrombosis/etiology
13.
Zhonghua Jie He He Hu Xi Za Zhi ; 30(2): 130-2, 2007 Feb.
Article in Chinese | MEDLINE | ID: mdl-17445477

ABSTRACT

OBJECTIVE: To study the role of CD(8)(+)CD(28)(-) regulatory T cells in tuberculosis. METHODS: The positive rates of CD(3)(+)CD(8)(+)CD(28)(-) T cells, CD(3)(+) T cells, CD(3)(+)CD(8)(+) T cells and CD(8)(+)CD(28)(+) T cells, and the content of IL-6 in CD(8)(+)CD(28)(-) T cells in leukocytes of peripheral blood from 15 patients with pulmonary tuberculosis, 15 patients with chronic bronchitis and 15 healthy controls were detected by flow cytometry. RESULTS: The positive expression rates of CD(3)(+) T cells of tuberculosis group [(41 +/- 16)%] and bronchitis controls [(40 +/- 10)%] were significantly lower than those from healthy controls [(44 +/- 6)%] respectively, but no differences were found between tuberculosis group and bronchitis controls. The CD(3)(+)CD(8)(+) T cells in CD(3)(+) T cells from the tuberculosis group [(47 +/- 16)%] and bronchitis controls [(44 +/- 10)%] were significantly higher than those from the healthy controls [(41 +/- 12)%] respectively, but no differences were found between the tuberculosis group and bronchitis controls. The CD(8)(+)CD(28)(+) T cells in CD(3)(+) T cells from tuberculosis group [(15 +/- 8)%] and bronchitis controls (20 +/- 7%) were significantly lower than those from healthy controls [(32 +/- 9)%] respectively, and those of the tuberculosis group were significantly lower than those from the bronchitis controls. CD(8)(+)CD(28)(-) T cells in CD(3)(+) T cells from tuberculosis group [(27 +/- 9)%] and bronchitis controls [(22 +/- 9)%] were significantly higher than those from healthy controls [(10 +/- 4)%] respectively, and those of the tuberculosis group were significantly higher than those of the bronchitis controls. The level of IL-6 secreted by CD(8)(+)CD(28)(-) T cells from tuberculosis group [(32.4 +/- 2.4)%] was significantly higher than bronchitis controls [(19.7 +/- 3.2)%] and healthy controls [(15.2 +/- 2.7)%] and no differences were found between bronchitis controls and healthy controls. CONCLUSIONS: The number of CD(8)(+)CD(28)(-) T cells and their production of IL-6 in the peripheral blood of tuberculosis patients are significantly increased as compared with the control groups, while the number of CD(8)(+)CD(28)(+) T cells (cytotoxic T cell) is significantly decreased. The results suggest that these cells and IL-6 may be involved in the pathogenesis of pulmonary tuberculosis.


Subject(s)
CD8-Positive T-Lymphocytes/immunology , Interleukin-6/metabolism , T-Lymphocyte Subsets/immunology , Tuberculosis, Pulmonary/immunology , Adult , Aged , CD8-Positive T-Lymphocytes/metabolism , Case-Control Studies , Female , Humans , Male , Middle Aged
14.
Zhonghua Jie He He Hu Xi Za Zhi ; 29(6): 403-6, 2006 Jun.
Article in Chinese | MEDLINE | ID: mdl-17045026

ABSTRACT

OBJECTIVE: To investigate the effect of interleukin-7 and interleukin-15 on the production of Th1 cytokines interferon-gamma (IFN-gamma), tumor necrosis factor-alpha (TNF-alpha) and Th2 cytokines interleukin-4 (IL-4), IL-10 by peripheral blood mononuclear cells (PBMC) from patients with tuberculosis. METHODS: Peripheral blood was obtained from 60 tuberculosis patients and 25 healthy controls with a positive tuberculin test. PBMCs were isolated by centrifugation on a Ficoll-hypaque density gradient. According to the different stimulators, each sample was divided into six groups: RPMI-1640 group, PPD group, PPD + IL-7 group, PPD + anti-IL-7 group, PPD + IL-15 group, and PPD + anti-IL-15 group. The samples were cultured for 72 h and the supernatants were collected. The levels of IFN-gamma, TNF-alpha, IL-4 and IL-10 in the supernatants were measured by enzyme-linked immunosorbent assay (ELISA). RESULTS: Compared with the PPD group, IL-7 increased the production of IFN-gamma and TNF-alpha in the patients [(107 +/- 42) ng/L to (157 +/- 74) ng/L, (460 +/- 128) ng/L to (887 +/- 242) ng/L, respectively], but decreased the production of IL-4 and IL-10 [(58 +/- 15) ng/L to (31 +/- 9) ng/L, (153 +/- 40) ng/L to (112 +/- 32) ng/L, respectively]; IL-7 also increased the production of IFN-gamma and TNF-alpha in the healthy controls [(211 +/- 57) ng/L to (292 +/- 92) ng/L, (1,203 +/- 390) ng/L to (1,722 +/- 503) ng/L, respectively], and decreased the production of IL-4 and IL-10 [(43 +/- 13) ng/L to (36 +/- 11) ng/L, (135 +/- 37) ng/L to (96 +/- 36) ng/L, respectively]. IL-15 increased the production of IFN-gamma and TNF-alpha in the patients [(107 +/- 42) ng/L to (231 +/- 62) ng/L, (460 +/- 128) ng/L to (843 +/- 208) ng/L, respectively], but decreased the production of IL-4 and IL-10 [(58 +/- 15) ng/L to (37 +/- 9) ng/L, (153 +/- 40) ng/L to (116 +/- 41) ng/L, respectively]; IL-15 also increased the production of IFN-gamma and TNF-alpha in the healthy controls [(211 +/- 57) ng/L to (343 +/- 108) ng/L, (1,203 +/- 390) ng/L to (1,468 +/- 235) ng/L, respectively], and decreased the production of IL-4 and IL-10 [(43 +/- 13) ng/L to (36 +/- 8) ng/L, (135 +/- 37) ng/L to (90 +/- 35) ng/L , respectively]. Anti-IL-7 and anti-IL-15 decreased the production of IFN-gamma and TNF-alpha, but increased the production of IL-4 and IL-10. The levels of IFN-gamma and TNF-alpha were lower in tuberculosis patients than those in the healthy controls (P < 0.05). The levels of IL-4 and IL-10 were not different between the two groups (P > 0.05). CONCLUSION: IL-7 and IL-15 could affect the balance between Th1 and Th2 cytokines by inducing IFN-gamma and TNF-alpha production and inhibiting IL-4 and IL-10 expression. It is suggested that IL-7 and IL-15 may enhance the defense against infection of tuberculosis, and therefore may be useful for the treatment of the disease.


Subject(s)
Interleukin-15/pharmacology , Interleukin-7/pharmacology , Leukocytes, Mononuclear/immunology , Tuberculosis, Pulmonary/immunology , Adolescent , Adult , Case-Control Studies , Female , Humans , Interferon-gamma/metabolism , Interleukin-10/metabolism , Interleukin-4/metabolism , Leukocytes, Mononuclear/metabolism , Male , Middle Aged , Tuberculosis, Pulmonary/metabolism , Tumor Necrosis Factor-alpha/metabolism , Young Adult
15.
Zhonghua Jie He He Hu Xi Za Zhi ; 29(4): 266-9, 2006 Apr.
Article in Chinese | MEDLINE | ID: mdl-16750045

ABSTRACT

OBJECTIVE: To explore the clinical significance and the possible role of soluble vascular cell adhesion molecule-1 (sVCAM-1) in the pathogenesis of pulmonary tuberculosis in terms of its relationship with tumor necrosis factor-alpha (TNF-alpha) and interferon-gamma (IFN-gamma). METHODS: Blood samples were taken from 35 patients with pulmonary tuberculosis before therapy, including military pulmonary tuberculosis (type II) in 15 cases and secondary pulmonary tuberculosis (type III) in 20 cases. After 2 month therapy, samples were taken from 20 cases with type III tuberculosis again. Twenty healthy volunteers served as controls. Serum concentrations of sVCAM-1 and IFN-gamma were detected by ELISA method and TNF-alpha by radioimmunoassay. RESULTS: The serum concentrations of sVCAM-1, TNF-alpha and IFN-gamma in patients with pulmonary tuberculosis were (822 +/- 206) microg/L, (1.5 +/- 1.1) microg/L, and (23 +/- 13) microg/L, respectively; all were significantly higher than those in healthy controls [(428 +/- 73), (0.2 +/- 0.1), and (16 +/- 10) microg/L; P < 0. 01, P < 0.01, and P < 0.05, respectively]. In the subgroup of patients with military pulmonary tuberculosis, the concentrations of sVCAM-1 and TNF-alpha were (897 +/- 144) microg/L and (2.0 +/- 1.4) microg/L, respectively, which were higher than those in patients with secondary pulmonary tuberculosis [(765 +/- 230) microg/L and (1.2 +/- 0.6) microg/L, respectively, both P < 0.05]. The difference in the concentrations of IFN-gamma between type II and type III was not significant (P = 0.222). The levels of sVCAM-1 and TNF-alpha were lower after therapy [(532 +/- 103) and (0.8 +/- 0.8) microg/L, respectively] than those before therapy (both P < 0.01), but the levels of sVCAM-1 and TNF-alpha after therapy were still higher than those in healthy controls (both P < 0.01). The level of IFN-gamma was higher after therapy than that before therapy (P < 0.05), and the difference between the level after therapy and that of the controls was significant. There were significant correlations between VCAM-1 and TNF-alpha and IFN-gamma respectively in untreated pulmonary tuberculosis (r = 0.669 and 0.560, respectively both P < 0.01). CONCLUSION: The measurement of serum sVCAM-1 is useful to evaluate the severity of disease and to monitor activity of the disease during chemotherapy.


Subject(s)
Interferon-gamma/blood , Tuberculosis, Pulmonary/blood , Tumor Necrosis Factor-alpha/blood , Vascular Cell Adhesion Molecule-1/blood , Adolescent , Adult , Aged , Case-Control Studies , Female , Humans , Male , Middle Aged , Tuberculosis, Pulmonary/immunology , Young Adult
16.
Zhong Nan Da Xue Xue Bao Yi Xue Ban ; 31(6): 848-52, 2006 Dec.
Article in Chinese | MEDLINE | ID: mdl-17213581

ABSTRACT

OBJECTIVE: To determine the diagnostic value of the expression of survivin mRNA in sputum samples and pleural effusions in lung cancer. METHODS: The sputum samples of 104 patients with lung cancer and 30 patients with chronic obstructive pulmonary disease (COPD), and the pleural effusion of 56 patients with lung cancer and 30 patients with tuberculosis pleural effusions were detected.Reverse transcription-polymerase chain reaction (RT-PCR) was performed to detect the survivin mRNA expression in the specimens. The results were compared with their cytological examinations. RESULTS: The sensitivity of the cytological examinations combined with the detection of survivin mRNA in sputum samples was higher than that of either cytological examination or survivin mRNA detection of sputum samples alone (P<0.01). The sensitivity of the diagnosis for lung cancer increased from 37.5% (sputum cytology alone) to 78.8% (sputum survivin mRNA detection combined with sputum cytology) (P<0.01), and the negative predictive value increased from 31.6% (sputum cytology alone) to 43.5% (sputum survivin mRNA detection combined with sputum cytology) (P<0.01). The sensitivity of the cytological examinations combined with the detection of survivin mRNA in pleural effusion samples was higher than that of cytological examination of pleural effusion samples alone (P<0.01). The sensitivity of the diagnosis for lung cancer increased from 42.9% (pleural effusion cytology alone) to 80.4% (pleural effusion survivin mRNA detection combined with cytology) (P<0.01), and the negative predictive value increased from 48.4% (pleural effusion cytology alone) to 77.8% (pleural effusion survivin mRNA detection combined with cytology) (P<0.01). CONCLUSION: The detection of survivin mRNA from sputum samples and pleural effusions samples is a new diagnostic method for lung cancer.


Subject(s)
Inhibitor of Apoptosis Proteins/analysis , Lung Neoplasms/diagnosis , Pleural Effusion/metabolism , Sputum/metabolism , Adolescent , Adult , Aged , Female , Humans , Lung Neoplasms/genetics , Male , Middle Aged , Predictive Value of Tests , RNA, Messenger/analysis , Sensitivity and Specificity , Survivin , Young Adult
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