ABSTRACT
OBJECTIVE@#To investigate the effect of vitamin D3 on polarization of monocyte macrophages induced by serum from patients with ankylosing spondylitis (AS).@*METHODS@#Twenty AS naïve patients and 20 healthy controls from Wenzhou People's Hospital during January 2016 and December 2017 were enrolled. The macrophages were differentiated from THP1 cells induced by phorbol 12-myristate 13-acetate (PMA), and then co-cultured with the serum from healthy subjects (control group) or AS patients. Vitamin D3 was added in the medium mixed with serum from AS patients. Flow cytometry was used to analyze the ratio of CD68 and CD206 positive cells, and RT-PCR was performed to detect the mRNA expression of inducible nitric oxide synthase(iNOS) and arginase-1(Arg-1).@*RESULTS@#THP1 cells could be polarized into mononuclear-macrophages with the induction of PMA. The proportion of CD206 positive cells in AS-serum group was lower than that in the control group (=9.434, <0.05), while the proportion of CD68 positive cells was higher than that in the control group (=43.920, <0.05). The proportion of CD206 positive cells in vitamin D3 group was higher than that in AS-serum group (=8.895, <0.05), while the proportion of CD68 positive cells was lower than that in AS-serum group (=9.089, <0.05). mRNA expression of Arg-1 in AS-serum group was lower than that in the control group (=8.899, <0.05), while mRNA expression of iNOS was higher than that in the control group (=3.656, <0.05). mRNA expression of Arg-1 in vitamin D3 group was higher than that in AS-serum group (=6.219, <0.05), while mRNA expression of iNOS was lower than that in AS-serum group (=5.876, <0.05).@*CONCLUSIONS@#Vitamin D3 can regulate the polarization of mononuclear macrophages for immunoregulation in patients with AS.
Subject(s)
Humans , Adjuvants, Immunologic , Pharmacology , Cell Differentiation , Cholecalciferol , Pharmacology , Monocytes , Spondylitis, Ankylosing , BloodABSTRACT
Objective@#The aim of this study is to investigate the effect of G9a inhibitor BIX-01294 on attenuating cell proliferation in human lung adenocarcinoma A549 cell line and the underlying molecular mechanism.@*Methods@#Treated with BIX-01294, the growth and proliferation of A549 cells were detected by MTT assay and colony formation assay, and its impact on cell apoptosis was analyzed using flow cytometry. By Western blot, we explored the alterations in the expression of apoptosis-related proteins and the G9a catalysate, H3K9me and H3K9me2. In addition, in the pretreatment with caspase inhibitor Z-VAD-FMK, we detected the apoptotic dependence of BIX-01294 attenuating impact on A549 cell proliferation.@*Results@#Compared with the control group, the histone methyltransferase G9a inhibitor BIX-01294 attenuated cell proliferation in A549 cells in a dose- and time-dependent manner. There were 42.5±8.7 colonies after BIX-01294 (10 μmol/L) treatment for 7 days, while 172.7±23.0 colonies in the control group, with a statistical significance (P<0.05). After treatment with BIX-01294 (10 μmol/L) for 24 hours, the cell apoptotic rate was(47.6±8.4)%, with a significant difference in comparison with the control group [(7.2±3.6)%, P<0.05]. The expression of G9a catalysate, H3K9me and H3K9me2 was downregulated, the same with anti-apoptotic protein Bcl-2, while the proteins in mitochondrial apoptosis pathway, Bax, Bak and cleaved caspase-9, were upregulated, so was the expression of cleaved caspase-3 and cleaved PARP, and there was no alteration in the expression of cleaved caspase-8, which is a protein related with death receptor apoptosis pathway. Furthermore, after Z-VAD-FMK pretreatment, the cell apoptotic rate was decreased significantly, and the expression of apoptosis-related proteins were downregulated.@*Conclusions@#Our results indicate that BIX-01294 can attenuate cell proliferation in lung adenocarcinoma, and it can be considered as one of the underlying mechanisms, the apoptosis may be induced by activating mitochondrial pathway.
ABSTRACT
Objective To imitate the pathological process of bronchiolitis obliterans(BO) post lung transplantation and in-vestigate the phenomenon of epithelial-mesenchymal transition ( EMT ) in small airway epithelial cells and its relation to BO . Methods We established the rat model of allogeneic orthotropic left lung transplantation with grafts from F 344 rats transplanted to Lewis rats by the Tri-cuff anastomosis.Then rats were daily injected intraperitoneally with cyclosporine (5 mg· kg-1 · d-1 ) for 10 days, intratracheally applied with lipopolysaccharide(0.5 mg/kg) at the 28th day and killed at the 90th day post-surger-y.We observed the histological structure of the lung grafts by HE and Masson staining , detected E-cadherin and Vimentin ex-pression in lung grafts and normal ones of F344 rats by immunohistochemistry, then analyzed the relation between small airway remodeling and the alterations in EMT markers expression .Enumeration data was analyzed with Fisher exact test and Spearman rank correlation was applied in correlation analysis .Results We found inflammatory cell infiltration , fibroplasia of bronchiole walls and significant lumen stenosis in lung graft mesenchyma.In lung grafts, the positive expression of E-cadherin was 5(total 13), which was significantly lower than that in normal lungs(7/8, P<0.05), and conversely the positive expression of Vim-entin was higher than normal ones(10/13 vs 2/8, P <0.05).The Spearman rank correlation analysis demonstrated that E-cadherin expression bear a negative correlation with Vimentin expression(r=-0.750, P<0.01).Conclusion Our study established a disease model imitating the pathological process of BO .And EMT was observed in small airway epithelial cells of the BO-exhibited lung grafts, indicating that EMT was involved in the process of BO airway remodeling .Thus it may reveal no-vel therapeutic targets for BO post lung transplantation by further investigation into the mechanism and pathological significance of EMT in small airway epithelial cells.
ABSTRACT
Objective To discuss the clinical efficacy of internal fixation assisted by thoracoscope in treatment of rib fractures.Methods The study enrolled 180 patients with rib fractures associated with thoracic deformity hospitalized from July 2010 to June 2013.Ninety out of the patients were operated on by thoracoscope-assisted internal fixation (operation group),and the remaining 90 fractures were treated non-operatively (non-operation group).Clinical markers recorded were duration of pain,time of ventilator use,hospital length of stay and complications.Patient mental health was measured with self esteem scale (SES).Patient mobility was evaluated at follow-up.Results Between operation and non-operation groups differences were observed in duration of pain [(3.1 ± 1.0)d vs (8.9 ± 1.2) d],time of ventilator use [(3.0 ± 1.0) d vs (4.8 ± 1.0) d] and hospital length of stay [(10.0 ± 1.1) d vs (15.8 ± 1.0) d] (P ＜ 0.01).SES in operation group was (28.3 ± 2.1) versus (24.4 ± 3.3) points in non-operation group (P ＜ 0.01).No major complications occurred in operation group,but there were 20 pleural effusion,15 severe thoracic collapse or deformity,14 lung infection,10 refractory chest pain and 2 upper limb dysfunction in non-operation group (P ＜0.01).Two patients presented mobility limitation in operation group,but 12 had evident loss of mobility in non-operation group (P ＜0.01).Conclusions Thoracoscope-assisted internal fixation is effective to accelerate the pace of recovery,relieve pains,reduce complications and thus can be a priority method for treatment of rib fractures.
ABSTRACT
Objective To observe the therapeutic effect of Qili Qiangxin capsule combined with glucocorticoid for treatment of patients with dilated cardiomyopathy accompanied by refractory heart failure. Methods A prospective study was conducted. Forty-eight patients with dilated cardiomyopathy and refractory heart failure in Hebei Cangzhou Central Hospital were enrolled,and they were randomly divided into three groups:control group,treatmentⅠand treatmentⅡgroups(each,16 cases). All groups were treated with conventional anti-heart failure western treatment, meanwhile additionally prednisone was given to treatment groupⅠand groupⅡ,firstly 40 mg/d,then the dosage of 5 mg was decreased in every 5 days until reaching 5 mg per day;in treatment groupⅡ,besides the same treatment of group I,the traditional Chinese medicine therapy Qili Qiangxin capsule 4 granules(one capsule 0.3 g)each time and 3 times a day was added,2 months being the therapeutic course in all the patients. The clinical efficacy and cardiac functional indexes,such as the left ventricular end-diastolic volume(LVEDV),the left ventricular end-systolic volume(LVESV),the left ventricular ejection fraction(LVEF)and the plasma B type brain natriuretic peptide (BNP),etc. were observed in 1 week and 2 months after treatment. Meanwhile the electrocardiogram(ECG),aspartate transaminase(AST),alanine aminotransferase(ALT),urea nitrogen(BUN),serum creatinine(SCr),blood routine, urine routine examination and the adverse effects were investigated. Results The total effective rates in treatment groupⅠand treatment groupⅡwere significantly higher than those in the control group〔after treatment for 1 week:81.2%(13/16),81.2%(13/16)vs. 43.8%(7/16);after 2 months:87.5%(14/16),93.7%(15/16)vs. 50.0%(8/16), all P<0.05〕. After treatment,the LVEDV,LVESV and BNP were lowered and the LVEF was increased in the three groups,and the above indexes in treatment groupⅡwere improved more significantly than those in groupⅠ〔LVEDV (mL):142.4±33.0 vs. 174.8±52.5,LVESV(mL):111.6±23.7 vs. 132.4±29.0,LVEF:0.421±0.037 vs. 0.390±0.045,BNP(μg/L):1.944±0.751 vs. 3.038±1.905,all P<0.05〕. Conclusion Qili Qiangxin capsule combined with glucocorticoid may effectively improve the cardiac function and clinical symptoms in near and forward future in patients with dilated cardiomyopathy accompanied by refractory heart failure,thus it may elevate the patients' life quality.
ABSTRACT
Objective AMI is a prevalent global health condition.This study assessed the effects of PLGF and VEGF in a rat model of post-AMI.Methods Wistar rats underwent LAD ligation and injection of VEGF,PLGF,VEGF + PLGF,antiVEGFR1,anti-VEGFR2,anti-VEGFR1 + anti-VEGFR2,IgG2α,or saline,into the infarct border zone.We also set up a pseudo-operation group.Two weeks later,heart function was detected by hemodynamic and geometry,then the hearts were dis sected and HE stained.We assessed vW factor and α-SMA by immunohistochemistry and cardiomyocyte apoptosis rate by TUNEL.Results Rats in the VEGF + PLGF group performed significantly well in cardiac function,had weaker LV remodeling and less cardiomyocyte apoptosis.There were no obvious changes in VEGF group.The use of VEGFR1/VEGFR2 antibody didnt deteriorate the rat's cardiac function.More new-born arteries were seen in PLGF and VEGF + PLGF rats,and change wasnt found in other groups.Lastly,the most angiogenesis,the least left ventricular remodeling and the best heart function were observed in VEGF + PLGF group.Conclusion Earlier intervention with PLGF or VEGF + PLGF can improve heart function in rats with AMI; VEGF alone didnt improve heart function.VEGFR1/VEGFR2 antibody didnt aggravate the rat's heart function.This indicates that left ventricular and coronary remodeling may involve other factors.