Pulmonary artery hypertension (PAH)is a common clinical syndrome.The over-proliferation of pulmonary arterial smooth muscle cells (PASMCs)is a hallmark of pulmonary vascular remodeling which is a critical and fundamental pathogenesis in the development of a variety of pulmonary artery hypertension.Here,we review the advances in studies on signaling transduction pathways mediating the proliferation of PASMCs and also introduce the existing approaches in inhibiting their proliferation and relevant research advances.

[ ABSTRACT ] AIM: To investigate the effect of catalpol on the activity of osteoblasts ( OB ) and osteoclasts ( OC) , and OB estrogen receptor ( ER) α/βmRNA expression in the OB-OC co-culture system.METHODS: OB and OC were isolated from the SD rats of 1 and 5 days old.In the OB-OC co-culture system, different concentrations of catalpol including low dosage (0.05 , 0.1, 0.5 and 1 mg/L), middle dosage (2, 5 and 10 mg/L), and high dosage (20, 50 and 100 mg/L) were added into the culture medium to detect the changes of OB proliferation by MTT assay.The catalpol at maximal dosage was added to OB section to detect the alkaline phosphatase ( ALP) activity of OB by pNPP method.The mRNA expression of ERα/βin the OB treated with catalpol in the co-culture system was detected by RT-PCR.The catalpol at maximal dosage was added to OC group to detect the activity of OC by microscopy and tartrate-resistantacid phosphatase ( TRAP) activity detection.RESULTS:In 0.05~2 mg/L catalpol groups, the proliferation of OB was significantly in-creased as compared with control group in the co-culture system, and it reached the maximum value when catalpol was at 0.05 mg/L, while in 5~100 mg/L catalpol groups, the proliferation of OB was not increased.The ALP activity of OB in 0.05 mg/L catalpol group was higher than that in control group.The catalpal at 0.05 mg/L promoted the mRNA expression of ERβin OB in the co-culture system, but did not increase the mRNA expression of ERαas compared with control group. Catalpol at 0.05 mg/L obviously inhibited the bone resorption and the TRAP activity in OC.CONCLUSION: Catalpol stimulates the proliferation and activity of OB, inhibits the bone resorption and activity of OC, and increases the mRNA ex-pression of ERβin OB in the OB-OC co-culture system, suggesting that high mRNA expression of ERβmay be the regula-tory pathway of catalpol in response to bone metabolism.

Objective To observe the clinical efficacy of cytokine-induced killer cells (CIK) combined with three dimensional conformal radiotherapy synchronization XELOX regimen in the treatment of local recurrence of rectal neoplasms.Methods A total of 81 patients with local recurrence of rectal neoplasms were divided into treatment group (41 patients) and control group (40 patients) by random digits table method.In treatment group,41 patients received simultaneous three dimensional conformal radiotherapy combined with XELOX chemotherapy,then received CIK treatment.In control group,40 patients received concurrent chemoradiotherapy.The immune function,quality of life (QOL) scores,recent efficacy,survival rate and adverse reactions were analyzed.Results In treatment group,the level of CD3+,CD4+,CD4+/CD8+ and CD16+ CD56+ increased and the level of CD8+ decreased significantly after treatment than those before treatment (0.671 ± 0.012 vs.0.625 ± 0.022,0.378 ± 0.043 vs.0.315 ± 0.035,1.59 ± 1.41 vs.1.02 ± 1.14,0.184 ±0.008 vs.0.121 +0.023,0.237 ±0.030 vs.0.308 ±0.031,P ＜0.05).Compared with those in control group after treatment,the level of CD3+,CD4+,CD4+/CD8+ and CD16+ CD56+ in treatment group increased and the level of CD8+ decreased significantly (P ＜ 0.05).QOL scores of 70.7％ (29/41) patients in treatment group was improved,significantly higher than the 32.5％ (13/40) in conctol group (P =0.001).The response rate(RR) in treatment group was 92.7％(38/41),significantly higher than that in control group [75.0％ (30/40)] (P =0.030).The 1-year survival rate in treatment group and control group were 90.2％(37/41) and 85.0％(34/40),there was no significant difference (P =0.473).The side effect in treatment group and control group showed no significant difference (P＞0.05).Conclusion CIK combined with concurrent chemoradiotherapy in the treatment of local recurrence of rectal neoplasms can improve patients 'immune function,QOL and recent efficacy.

OBJECTIVE:To study the effect of catalpol on the activity and apoptosis of osteoclasts (OC) in the osteoblasts (OB)-OC co-culture system and its mechanism. METHODS:OB and OC were isolated respectively from the SD rats of 1-3 days and 5-7 days old to establish OB-OC co-culture system. After treated with 0(blank control),0.05,0.5,5,50 and 100 mg/L catal-pol for 48,72 and 96 h,the number of bone absorption lacuna for OC was observed by inverted microscope to reflect OC activity. After treated with 0(blank control)and 0.05 mg/L catalpol for 48,72 and 96 h,the activity of tartrate resistant acid phosphatase (TRACP)in OC was detected,and the apoptosis rate of OC was calculated. After treated with 0(blank control)and 0.05 mg/L ca-talpol,mRNA expression of osteoprotegerin(OPG)in OB was detected. RESULTS:In OB-OC co-culture system,the number of bone absorption lacuna in 0.05-50 mg/L catalpol groups was significantly lower than blank control group(P<0.01),indicating ca-talpol could inhibit OC activity,especially 0.05 mg/L catapol. Compared with blank control,0.05 mg/L catapol lowered the activity of TRACP but increased the apoptosis rate of OC(P<0.05);mRNA expression of OPG was up-regulated in OB(P<0.01). CON-CLUSIONS:In OB-OC co-culture system,catalpol can inhibit the activity of OC and induce the apoptosis of OC,and its mecha-nism may be associated with the mRNA expression up-regulation of OPG in OB.

Objective To evaluate the efficacy and safety of sublingual immunotherapy (SLIT) in patients with allergic asthma in order to provide reliable evidence for clinical application of SLIT.Methods To search published articles of randomized controlled trials (RCTs) in allergic asthma from CNKI,WANFANG,Pubmed and Medline databases.The methodological quality of trials was assessed by Jadadscale.The heterogeneity was examined by using Stata 11.0 software.Fixed effect model or random effect model was used to pool the data.The articles which could not be pooled were carried out by descriptive analysis.The Egger's and Begg's test were used to evaluate the publication bias.Results There were total 6 RCTs included in this text.Compared with control group,SLIT could significantly reduce asthma symptom scores (SMD =-0.89,95％ CI-1.36--0.43,P =0.000) and asthma medication scores (SMD =-4.53,95％CI-6.97--2.08,P =0.000),but not forced expiratory volume (FEV1) of lung function (SMD =0.19,95％ CI-0.02-0.41,P =0.078),neither serum sIgE levels (SMD =0.05,95％ CI -0.58-0.69,P =0.870).There were no obvious adverse events reported after treatment of SLIT.No publication bias were indicated by Egger's and Begg's tests.Conclusion SLIT significantly reduces asthma symptom scores and medication scores,suggesting that SLIT is a safe and effective approach of immunotherapy.However,it still needs more highly qualified studies of RCTs to prove.

LTB gene fragment was amplified by PCR from plasmid pMDTLT, and a recombinant plasmid pETLTBVP1 was constructed by inserting LTB gene fragment into VP1 gene expression plasmid pETVP1 constructed previously. The recombinant plasmids were transformed into E. coli BL21(DE3) and induced to express by IPTG. The recombinant protein existed in the inclusion body and its molecular weight was about 39 kD proved by SDS-PAGE analysis. Western blotting showed that the fusion protein could be reacted with both anti-FMDV and anti-cholera toxin serum demonstrating the immunoactivity of the fusion protein. Strong immune responses can be induced in mice inoculated with the fusion protein intraperitoneally, and the serum antibody level is higher than that of commercial foot-and-mouth disease vaccines.
Animals ; Antibodies, Viral ; blood ; Bacterial Toxins ; genetics ; immunology ; metabolism ; Capsid Proteins ; genetics ; immunology ; metabolism ; Enterotoxins ; genetics ; immunology ; metabolism ; Escherichia coli ; genetics ; metabolism ; Escherichia coli Proteins ; Female ; Gene Fusion ; genetics ; Mice ; Plasmids ; genetics ; Recombinant Fusion Proteins ; genetics ; immunology ; metabolism

A total of 189 stool samples from swine with diarrhea, collected in various porcine farms in the central region of China were tested for porcine enteric caliciviruses (PEC) member porcine sapoviruses (SaV) by reverse transcription polymerase chain reaction (RT-PCR) amplification using primers designed to detect porcine SaV. Selected amplicons were sequenced to establish phylogenetic relationships with reference strains. Porcine SaV were detected in 12.70% (24/189) of the samples. Phylogenetic studies based on partial RNA polymerase gene sequences indicated that the field strains of viruses isolated in China were closely related (75.6 88.3% identity) to the porcine SaV Cowden reference strain. These results provide evidence that caliciviruses of the genus sapovirus circulate in piglets in China, but further studies are needed to clarify their importance as cause of diarrhea. This is the first report of PEC in China.

OBJECTIVETo examine whether calcineurin/NFAT signaling pathway mediates endothelin-1 (ET-1)-induced proliferation of pulmonary artery smooth muscle cells (PASMCs) by regulating phosphodiesterase-5 (PDE5) and the effect of the selective calcineurin inhibitor cyclosporine A and PDE5 inhibitor sildenafil on ET-1-induced PASMC proliferation.

METHODSPASMCs were treated with ET-1 to stimulate their proliferation with or without prior treatment of the cells with CsA or sildenafil. Calcineurin activity in the cells was measured using a calcineurin activity assay kit, PDE5 expression examined using immunoblotting, and cGMP level detected using a cGMP direct immunoassay kit. PASMC proliferation following the treatments was determined using [(3)H]thymidine incorporation assay.

RESULTSET-1 caused a 2.05-fold increase in the cellular calcineurin activity, a 1.80-fold increase in PDE5 expression, and a 3.20-fold increase in the DNA synthesis rate, and reduced the cGMP level by 67%. Pretreatment of the cells with Cyclosporine blocked the effects of ET-1, and PDE5 inhibition by sildenafil pretreatment also abolished ET-1-induced reduction of cGMP level in the cells. Both Cyclosporine and sildenafil suppressed ET-1-stimulated PASMC proliferation.

CONCLUSIONActivation of calcineurin/NFAT signaling pathway mediates ET-1-induced PASMC proliferation by stimulating PDE5 expression, which further degrades cGMP. Both Cyclosporine and sildenafil can suppress ET-1-stimulated PASMC proliferation in vitro.

Animals ; Calcineurin ; metabolism ; Cell Proliferation ; drug effects ; Cells, Cultured ; Cyclic GMP ; metabolism ; Cyclic Nucleotide Phosphodiesterases, Type 5 ; metabolism ; Cyclosporine ; DNA ; biosynthesis ; Endothelin-1 ; pharmacology ; Muscle, Smooth, Vascular ; cytology ; Myocytes, Smooth Muscle ; cytology ; enzymology ; NFATC Transcription Factors ; metabolism ; Piperazines ; Pulmonary Artery ; cytology ; Purines ; Rats ; Rats, Sprague-Dawley ; Signal Transduction ; Sildenafil Citrate ; Sulfones

Objective To explore the diagnostic and score value of ultrasound on hemophiliac arthropathy referring to MRI on the diagnosis and score of hemophiliac arthropathy Methods The ultrasound and MRI examinations were performed on 42 joints of 42 hemophilia patients 14 knees 14 ankles and 14 elbows The consistency of ultrasound and magnetic resonance imaging in the detection and score of joint diseases was compared Finally inter-and intra-observer agreement of ultrasound scoring system were tested Results The consistency of ultrasound and magnetic resonance imaging was excellent κ=0 763-0 896 P < 0 001 in the detection of early soft tissue lesions effusion or hemarthrosis synovial hypertrophy hemosiderin excellent κ=0 793 P <0 001 in the detection of cartilage loss poor κ=0 133 P = 0 132 in the detection of erosions and poor κ= 0 100 P = 0 137 in the detection of subchondral cysts The consistency of ultrasound and magnetic resonance imaging was good to excellentκ=0 684-0 833 P < 0 001 in the score of early soft tissue lesions effusion or hemarthrosis synovial hypertrophy and hemosiderin and poor to good κ=0 145 -0 635 P <0 001 in the score of advanced osteochondral lesions cartilage loss and bone erosions The inter-observer agreement was good to excellent κ=0 676-0 870 P <0 001 for early soft tissue lesions and moderate to excellent κ=0 421- 0 75 1 P < 0 001 for advanced osteochondral lesions The intra-observer agreement was good to excellent κ=0 705-0 885 P <0 001 for early soft tissue lesions and moderate to good κ=0 532 -0 732 P <0 001 for advanced osteochondral lesions Conclusions Ultrasound plays an important role in detecting early soft tissue changes effusion or hemarthrosis synovial hypertrophy hemosiderin and cartilage loss which helps follow-up and guide clinical treatment.

OBJECTIVETo identify the immunological characteristics of the recombinant major pollen allergen pTSX2 of Humulus scandens and evaluate its safety in immunotherapy of allergic asthma in mice.

METHODSWestern blotting was used to characterize the immunological properties of pTSX2, and its immunogenicity in normal mice was evaluated by detecting sIgG and sIgE levels. The mouse models of allergic asthma were immunized with pTSX2 and examined for sIgE and sIgG levels, total cells and eosinophils percentage in BALF, interleukin-4 (IL-4) and interferon-γ (IFN-γ) levels in BALF and spleen homogenate, and changes in lung pathologies.

RESULTSWestern blotting showed that pTSX2 reacted with the majority (about 70%) of sera from patients allergic to Humulus pollen. In normal mice, pTSX2 mainly induced the production of sIgG. In mouse models of allergic asthma, intervention with pTSX2 caused a significant reduction of sIgE and an increase of sIgG (P<0.05), significantly decreased the total cells and eosinophils in BALF (P<0.05), obviously lowered IL-4 but increased IFN-γ in BALF and spleen homogenate (P<0.05), and diminished inflammatory cell infiltration and percentage of eosinophils in the lung tissues.

CONCLUSIONSpTSX2 shows a definite therapeutic effect and safety in the treatment of allergic asthma in mice possibly by inhibiting sIgE and inducing sIgG production, suppressing airway allergic inflammation and regulating the balance between Thl and Th2.

Allergens ; immunology ; Animals ; Asthma ; immunology ; therapy ; Bronchoalveolar Lavage Fluid ; immunology ; Disease Models, Animal ; Female ; Humans ; Humulus ; immunology ; Immunoglobulin E ; blood ; Immunoglobulin G ; blood ; Immunotherapy ; Interferon-gamma ; analysis ; Interleukin-4 ; analysis ; Mice ; Mice, Inbred BALB C ; Pollen ; immunology ; Th1 Cells ; cytology ; immunology ; Th2 Cells ; cytology ; immunology