Timosaponin A III promotes cisplatin sensitivity in A549/DDP cells via JAK-2/STAT3/PD-L1 signaling pathway / 中国药理学通报

Aim To explore the mechanism of timosaponin A III increasing cisplatin sensitization of non-small cell lung cancer cisplatin-resistant A549/DDP cells. Methods The cell proliferation was detected by CCK8,the cell apoptosis was detected by Annexin V/ PI,and the cell cycle distribution was measured by PI. The effect of the combined drug on cell proliferation was detected by cell clone formation. The mRNA expression levels of C-myc, cysteinyl aspartate-specific protease-3 (caspase-3) were detected by reverse transcription polymerase chain reaction (RT-PCR). Western blot and Flow Cytometry were performed for the mechanism study. Results The results of CCK8 and clone formation showed that the timosaponin AM group significantly increased the sensitivity of cisplatin to A549/DDP cells. Compared with the cisplatin group a-lone,the combination of timosaponin AM and cisplatin significantly elevated the apoptosis rate of A549/DDP cells (P < 0.05) , induced cell cycle arrest in G

Effect of Astragalus injection on cardiomyocyte apoptosis, endoplasmic reticulum stress and expression of connexin in cardiomyopathy rats induced by adriamycin / 中国应用生理学杂志

OBJECTIVES@#To investigate the effect of Astragalus injection on cardiomyocyte apoptosis, endoplasmic reticulum stress and connexin protein in cardiomyopathy rats induced by adriamycin.@*METHODS@#Thirty-six male Wister rats were randomly divided into control group (=12), adriamycin(ADR) group (=12) and Astragalus group (=12). The normal saline (10 ml/kg body weight) was injected intraperitoneally in control group rats, ADR (2 mg/kg body weight) was injected intraperitoneally in ADR group rats, ADR (10 ml/kg body weight) and Astragalus injection (10 ml/kg body weight) were injected intraperitoneally in rats of astragalus group, one time a week, totle 3 times. By the end of the 7 week, the left ventricular end-diastolic diameter(LVEDD), left ventricular end-systolic diameter (LVESD) and left ventricular ejection fraction (LVEF) were measured by echocardiography. Then the rats in the three groups were sacrificed and the left ventricle section was stained by HE, Masson, uranyl acetate/lead citrate respectively, the cardiomyopathy and ultrastructural changes were observed under light microscope and transmission electron microscope. The apoptosis of rat cardiomyocyte were analyzed by TUNEL. The expression of connexin Cx43 and p-Cx43 was detected by immunohistochemistry. The expression of glucose-regulated protein 78 (Grp78),activating transcription factor 4 (ATF-4) and C/EBP homologous protein (CHOP) were detected by real time PCR.@*RESULTS@#Compared with control group, LVEDD, LVESD increased and LVEF decreased, myocardial fibers were disordered and edematous, infiltrated by lymphocytes, the mitochondria were destroyed and vacuolized, and the number of cardiomyocyte apoptosis was increased(<0.01) in ADR group. The expression of Grp78, ATF-4, CHOP and p-Cx43 were increased, and the expression of Cx43 was decreased in ADR group. However, compared with ADR group, LVEDD, LVESD decreased and LVEF increased, the cardiomyopathy and ultrastructural changes were significantly improved, the number of cardiomyocyte apoptosis was significantly decreased (<0. 01); the expression of Grp78, ATF-4, CHOP and p-Cx43 decreased (<0.01); the expression of Cx43 increased in Astragalus group (<0.01).@*CONCLUSIONS@#Astragalus injection may effectively improve the myocardial damage induced by adriamycin, its mechanism may be related to the inhibition of endoplasmic reticulum stress (ERS) and the decrease of phosphorylation of CX43 in cardiomyopathy rats induced by adriamycin.

Effect of BU and CY versus TBI and CY as conditioning regimens on the efficacy of haploidentical stem cell transplantation in patients with hematologic malignancy / 中华血液学杂志

<p><b>OBJECTIVE</b>To investigate the therapeutic effects of the conditioning regimen with busulfan plus cyclophosphamide (BU+CY) or total body irradiation plus cyclophosphamide (TBI+CY) on haploidentical stem cell transplantation (HSCT) in hematologic malignancy.</p><p><b>METHODS</b>The clinical outcomes of 77 HSCT recipients with hematologic malignancy from January 2001 to December 2010, including 21 AML, 33 ALL, 19 CML and 4 MDS were retrospectively evaluated. Among them, 65 patients obtained complete remission (CR) and 12 non-remission (NR) before transplantation; 39 patients received conditioning regimen with BU+CY, and 38 with TBI+CY.</p><p><b>RESULTS</b>There were no statistically significant differences in hematopoietic reconstitution, disease free survival (DFS), and transplant- related mortality (TRM) between two groups. The estimated 3- years overall survival (OS) was 56.4% for BU+CY and 31.6% for TBI + CY (P=0.0283). The overall relapse rate was similar between two groups (15.4% vs 34.2%; P=0.1538). However, the accumulative probability of relapse at 1-year was significantly lower in BU+CY than that in TBI+CY group (2.56% vs 26.67%; P=0.0116). The incidence of grade II-IV graft-versus-host disease (GVHD) was similar between two regimens (20.5% in BU+CY group and 18.4% in TBI+CY group; P=0.8168). The incidence of chronic GVHD (cGVHD) was higher in the TBI+CY group than that of BU+CY group (84.6% vs 41.1%; P=0.0007). The extensive GVHD obtained the similar outcome (30.8% vs 10.5%; P=0.0416).</p><p><b>CONCLUSION</b>Patients using BU+CY as conditioning regimen before transplant could obtain a better 3 year OS and lower short-term relapse rate. The TBI+CY conditioning regimen could significantly increase the incidence of cGVHD without increasing the acute GVHD. BU+CY conditioning regimen could be used for HSCT, but the attention should be paid to prevent the related hemorrhagic cystitis.</p>

Allogeneic hematopoietic stem cell transplantation for chronic myelomonocytic leukemia and juvenile myelomonocytic leukemia / 中国实验血液学杂志

This study was purposed to explore the therapeutic efficacy and influencing factors of allogeneic hematopoietic stem cell transplantation (allo-HSCT) in patients with chronic myelomonocytic leukemia (CMML) and in patients with juvenile myelomonocytic leukemia (JMML). The clinical data of 3 cases of CMML and 2 cases of JMML underwent allo-HSCT were analysed in term of multiparameter. The results showed that the hematopoietic stem cells in 5 patients grafted successfully. One case of JMML died of pulmonary disease, other 4 cases survive without disease. The analysis found that the disease burden before transplant, chromosome karyotype, acute GVHD II-IV and poor risk cytogenetics all associated with the relapse rate and disease-free survival rate of CMML. The low intensity conditioning regimen was better than myeloablative conditioning regimen. Type of donor and source of stem cells did not statistically and significantly affect OS and RFS. The splenectomy before allo-HSCT as well as spleen size at time of the alloHSCT did not influence on posttransplantation outcome of JMML. However, cord blood HSCT for JMML patients delayed hematologic recovery as compared to that of bone marrow or peripheral blood HSCT. The age, GVHD, HbF level played an important role in leukemia replace. It is concluded that the allogeneic hematopoietic stem cell transplantation is a curative regimen for CMML and JMML, but there also is a serial problems to be resolved.

IL-10 gene modification on immature dendritic cells induces antigen-specific tolerance in experimental autoimmune myocarditis / 中华心血管病杂志

<p><b>OBJECTIVE</b>To investigate whether IL-10 gene modification on immature dendritic cells (iDC) could induce autoimmune tolerance in rat experimental autoimmune myocarditis (EAM).</p><p><b>METHODS</b>EAM was induced by cardiac myosin immunization on day 0 and day 7 in rats. A total of 2 x 10(6) mature DC (mDC), iDC, pcDNA3 transfected iDC, pcDNA3-IL-10 transfected iDC or PBS were injected intravenously at 5th immunization day. Three weeks later, echocardiography and HE staining were performed to observe the cardiac function and myocardial inflammation. Th1/Th2 cytokines were detected by ELISA and MHC-II molecules, costimulatory molecules were identified by flow cytometry. In vitro T lymphocyte proliferation assay and adoptive transfer of DCs were performed to determine the antigen specific tolerance induced by IL-10 gene modification on iDCs.</p><p><b>RESULTS</b>EAM rats treated with pcDNA3-IL-10 transfected iDC showed improved cardiac function and reduced inflammatory cells infiltration into myocardium. Moreover, lower Th1 and higher Th2-type response was induced, MHC-II and costimulatory molecules down-regulated and antigen specific immunological responses towards cardiac myosin inhibited in pcDNA3-IL-10-iDC treated EAM rats.</p><p><b>CONCLUSION</b>Treatment with IL-10 gene modified iDCs could ameliorates EAM by inducing Th2 polarization and down-regulation of MHC-II molecules and costimulatory molecule expressions.</p>

Analysis of Signal Peptide Fragment of Canine Distemper Virus Wild-type Strain Fusion Protein / 微生物学通报

A pairs of primers were designed according to the fusion protein(F)gene sequences of canine distemper virus(CDV)in GenBank.A 369 bp fragment aimed signal peptide fragment of F gene was amplified.The PCR products from viscera samples,blood,urine of fur animals including foxes,minks and raccoon dogs,which collected in the years 2005-2007,were cloned to pMD18-T Vector and sequenced.We obtained 13 positive signal peptide fragments from wild-type strains.The results indicated there was obviously genetic diversity between the wild-type strains and CDV3 and other vaccine strains.The homology with CDV3 is 80.7%-83.2%in nucleotide,and 64.8%-71.3%in amino acid.The analysis for the hydrophobic regions indicated the function of signal peptide fragment may be changed.This study can offer aca- demic data to research of CDV genetic variation and epidemiology.

Relationship of CTLA-4 polymorphisms with susceptibility for idiopathic dilated cardiomyopathy / 中国免疫学杂志

Objective:Autoimmune mechanisms, including cellular and humoral immune, are likely to participate in the pathogenesis of at least a subgroup of idiopathic dilated cardiomyopathy(IDC), in which cellular immune-mediated one plays a more important role. Cytotoxic T lymphocyte associated antigen-4(CTLA-4) is the major negative regulatory factor of cellular immunity. This study was conducted to investigate the association of CTLA-4 gene promoter -318C/T polymorphism, exon 1 A/G polymorphism and 3′ untranslated region microsatellite polymorphism with susceptibility to IDC in Han Chinese.Methods:Polymerase chain reaction-restriction fragment length polymorphisms(PCR-RFLP) techniques were used to analyze the polymorphisms of CTLA-4 promoter -318, exon 1 A/G and 3′ untranslated region in the unrelated Han ethnic population in Heilongjiang Province(including 72 IDC patients and 100 normal controls). Serum sCTLA-4 was tested by ELISA. The relationship of CTLA-4 genotype and alleles frequencies with sCTLA-4 was evaluated by linear regression analysis.Results:Compared with controls, the frequencies of GG genotype(0.604 2 and 0.739 6, P=0.012) and the G allele(0.360 0 and 0.560 0, P=0.008) were significantly increased in patients with IDC. Increased serum sCTLA-4 was found in the IDC group compared with the controls[(1.87?1.06)?g/L vs (0.54?0.19)?g/L, P