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Bavachin is a dihydroflavonoid compound isolated from Psoralea corylifolia, and exhibits anti-bacterial, anti-inflammatory, anti-tumor and lipid-lowering activities. Recent attention has gradually drawn on bavachin-induced apoptosis in many human cancer cell lines. However, the anti-cancer effects and related mechanisms in colorectal cancer remain unknown. Here, we investigated the effects of bavachin on colorectal cancer in vivo and in vitro. The results showed that bavachin inhibited the proliferation of human colorectal cancer cells and induce apoptosis. These changes were mediated by activating the MAPK signaling pathway, which significantly up-regulated the expression of Gadd45a. Furthermore, Gadd45a silencing obviously attenuated bavachin-mediated cell apoptosis. Inhibition of the MAPK signaling pathway by JNK/ERK/p38 inhibitors also weakened the up-regulation of Gadd45a by bavachin. The anticancer effect of bavachin was also validated using a mouse xenograft model of human colorectal cancer. In conclusion, these findings suggest that bavachin induces the apoptosis of colorectal cancer cells through activating the MAPK signaling pathway.
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Humanos , Transdução de Sinais , Flavonoides/farmacologia , Proteínas/farmacologia , Sistema de Sinalização das MAP Quinases , Neoplasias Colorretais/metabolismo , Apoptose , Linhagem Celular Tumoral , Proliferação de Células , Proteínas de Ciclo Celular/farmacologiaRESUMO
Objective:The experimental animal model was established to unravel the mechanism of radiation-induced myocardial fibrosis and validate the role of recombinant human endostatin in aggravating the process of radiation-induced myocardial fibrosis via the TGF-β 1, Smad 2 and Smad 3 signaling pathways. Methods:Sixty male adult Sprague-Dawley rats were randomly divided into the following groups: radiotherapy (RT)25 Gy, recombinant human endostatin (RE) 6 mg/kg, RE 12 mg/kg, RT 25 Gy+ RE 6 mg/kg, RT 25 Gy+ RE 12 mg/kg and blank control groups. Five rats were sacrificed in each group at 1 and 3 months after interventions. The myocardial tissues were collected. The pathological changes were observed by Hematoxylin and eosin staining. The degree of fibrosis was assessed by Masson trichrome staining. The expression levels of TGF-β 1, Smad 2, Smad 3 and Collagen-I mRNA and protein were quantitatively measured by real-time PCR and Western blotting. Results:At 3 months after intervention, Masson trichrome staining revealed that the collagen deposition in the RT 25Gy and RT 25Gy+ RE (6 and 12 mg/kg) groups was more significant than that in the control group. In addition, The expression levels of TGF-β 1, Smad 2, Smad 3 and Collagen-I mRNA and protein in these groups were significantly up-regulated compared with those in the control group. Conclusions:Radiation with a total physical dose of 25 Gy can induce myocardial fibrosis in the SD rat models. TGF-β 1 and Smad 2 signaling pathways are the common signaling pathways of myocardial fibrosis induced by radiation combined with recombinant human endostatin.
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Objective:To assess the effects of recombinant human endostatin (rh-ES) on radiation-induced myocardial fibrosis.Methods:Totally 40 SD rats were randomly divided into 4 groups, including A group as normal control, B group receiving rh-ES with a dosage of 6 mg·kg -1·d -1, in traperitoneal injection, for 14 consecutive days, C group with local heart irradiation delivered to the precordial region of rats in five fractions with a dose of 25 Gy, D group receiving rh-ES as the same as B group and local heart irradiation as C group. At 1 and 3 months after irradiation, five rats were killed under anesthesia. Mason staining was used to observe myocardial injury and fibrosis. Western blotting was used to detect the expression of TGF-β1, CTGF and COL-I in myocardium. Results:Masson staining showed that no obvious myocardial fibrosis was found in group B at 1 month and 3 months after irradiation, while collagen fibers were distributed in myocardium in groups C and D. One month after irradiation, the result of semi-quantitative analysis showed that the CVF in group A was (5.20 ±0.75)%, which was significantly lower than that in group C (10.12 ±2.17)% ( t=4.74、4.93, P<0.01) and the CVF in group D (10.32 ±1.36), and the CVF of group C was similar to that of group D ( P<0.01). Three months after irradiation, CVF in group C (13.17±2.67)% was still higher than that in group A (5.23 ±1.32)% ( t=4.49, P<0.01), but lower than that in group D (16.92 ±3.58)% ( t=3.19, P<0.05). One month after irradiation, the expression of TGF-β1 in group A was 0.441 ±0.063, lower than that in group C (0.817 ±0.079, t=5.81, P<0.01). Three months after irradiation, the expression of TGF-β1 in group A was 0.501 ±0.110, lower than that in group C (0.832 ±0.150, t=4.19, P<0.01), and the expression of TGF-β1 in group D was 1.403 ±0.133, which was significantly higher than that in group C ( t=7.24, P<0.01). Conclusions:Radiation can cause the formation of myocardial fibrosis, and recombinant human endostatin may aggravate the formation of late radiation fibrosis.
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Objective@#To analyze the genetic characteristics of the hemagglutinin(HA) and neuraminidase(NA) genes of the influenza A/H1N1(09pdm) viruses isolated in the city of Yancheng in 2014-2017.@*Methods@#The throat swab specimens of patients with influenza-like illness (ILI) from sentinel surveillance hospitals and outbreak sites were detected using the method of real time RT-PCR. The influenza A/H1N1(09pdm) viruses were isolated using MDCK cell culture method in 2014-2017. The strains in 2014-2017 were selected randomly and their sequences of the HA1 and NA genes were amplified through one step RT -PCR method and the PCR products were sequenced. The mutations of genes and acid locus were analyzed and the evolutional trees were generated using bioinformatics software.@*Results@#The clustering relationships of the respective branches of HA1 and NA genes of seventeen A/H1N1(09pdm) strains isolated in Yancheng area were basically the same and the phylogenetic trees of HA1 and NA genes were respectively clustered into four evolutionary branches. Compared with the vaccine strain A/California/07/2009(H1N1pdm)in the Northern Hemisphere, a total of three antigen epitopes (Ca, Sa, Sb) in HA1 genes of strains in Yancheng area were involved in six antigenic sites (K154R, S162N, K163Q, S185T, L191I, S203T); there were three mutations (D222G/N, G223R, E224K) in the 220 ring and one locus (L191I) in the 190 helix of the receptor binding sites; the two strains (A/Jiangsu-YC/SWL1540/2017, A/Jiangsu-YC/SWL1545/2017) isolated in 2017 increased the 162NQS glycosylation site. Because the strains of the antigen epitopes, receptor binding sites and glycosylation sites in the HA1 genes had a certain degree of variations in Yancheng area in 2014-2017, the protective effects of vaccine strain A/California/07/2009 (H1N1pdm) was limited at the gene level. The two strains (A/Jiangsu-YC/SWL1540/2017 and A/Jiangsu-YC/SWL1545/2017) isolated in 2017 were clustered with vaccine strain A/Michigan/45/2015(H1N1pdm) and had better protective effects. Seventeen A/H1N1(09pdm) strains had no mutations in catalytic residues and drug resistant sites of NA genes, but a part of strains had a certain degree of variations in glycosylation sites of NA genes.@*Conclusions@#These results indicated the HA1 and NA genes of influenza A/H1N1(09pdm) viruses circulated in Yancheng area in 2014-2017 changed gradually. The accumulation of these mutations would result in antigenic drift of influenza A/H1N1(09pdm) viruses.
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Objective@#To analyze the genotypes and the genetic evolution of the hemagglutinin genes of measles viruses in the city of Yancheng in 2016.@*Methods@#Using a set of primers and probes for screening positive for measles viruses, specimens of throat swab were detected using the method of real time RT-PCR. The sequences of the nucleoprotein and hemagglutinin genes of measles viruses were amplified through one step RT-PCR method and the PCR products were sequenced. The sequences of nucleotide and amino acid of the nucleoprotein and hemagglutinin genes of measles viruses were analyzed and the evolutional trees were generated using bioinformatics software.@*Results@#The genotypes of measles viruses in the Yancheng area in 2016 included subgenotype H1a and genotype D8. Phylogenetic trees analysis showed that the five representative strains of subgenotype H1a in Yancheng area and Jiangxi representative strain (KJ136545) clustered into independent evolutionary branches, belonged to the clade of H1a -1 evolutionary genes. The seven representative strains of genotype D8 in Yancheng area were clustered with the American representative strain in 2009 (JN635404), belonged to the D8-3-2 small clade genes. Compared with vaccine strain of Shanghai S191, the amino acid site in 240thof the five representative strains of subgenotype H1a in Yancheng area mutated from serine to asparagine, leading to a loss of the N-glycosylation site NLS238-240. The seven representative strains of genotype D8 in Yancheng area had no change in N-glycosylation.@*Conclusions@#In 2016, the prevalent strains of measles viruses in Yancheng area were mainly Chinese H1a dominant subgenotype and D8 imported genotype. In addition to a loss of the N-glycosylation site NLS238-240in 240thof the five representative strains of subgenotype H1a, most of the major neutralizing antigen sites of hemagglutinin gene of measles viruses in Yancheng area did not mutate. The Chinese vaccine of Shanghai S191 can effectively prevent infection caused by subgenotype H1a and subgenotype D8 strains.
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Objective To investigate the effect of down-regulation of lysine specific demethylase 1 (LSD1) by shRNA on the apoptosis and cell cycle of human acute myelogenous leukemia cells.Methods The lentiviral vector-mediated LSD1-shRNA was transfected into human acute promyelocytic leukemia HL-60 cells and acute monocytic leukemia SHI-1 cells.The expressions of LSD1 mRNA and protein were examined by real time quantitative PCR and Western blot,respectively.The flow cytometry was applied to detect the apoptosis and cell cycle distribution after AnnexinV-PE/7-AAD and PI dying,respectively.Results The expressions of LSD1 mRNA and protein in HL-60 and SHI-1 LSD1-shRNA group were significantly decreased compared with the blank control group and the negative shRNA group (P ＜ 0.01,respectively).The apoptosis levels of HL-60 and SHI-1 cells were significantly increased after knockdown of LSD1 (P ＜ 0.01).Moreover,the cell cycle distribution in the G0/G1 phases was also significantly increased(P ＜ 0.01).Conclusion LSDI-shRNA promotes cell apoptosis and increases the percentage of cells in the G0/G1 phases of human acute myelogenous leukemia cells.
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Objective To investigate the changes of red blood cells (RBC) and blood lipid in Han high altitude immigration dur‐ing the process of altitude acclimatization and their correlation .Methods Forty male Han nationality teachers entering Xizang Ali area and working for 1 year were selected .The blood samples were collected before entering plateau and within 3 d after returning to plain .The blood routine and the blood lipid level were detected .Results In the early return to plain ,the RBC ,TG ,CHO and LDL‐C levels in the research subjects were increased ,in which RBC and TG were significantly increased (P< 0 .01) ,HDL‐C was significantly decreased .After returning to plain ,RBC was positively correlated with TG and CHO (r=0 .46 ,P<0 .01 and r=0 .36 , P<0 .05) .Conclusion High altitude hypoxia environment is the primary cause leading to the change of RBC and blood lipid inde‐xes in the plain population after entering the plateau environment .
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Objective To evaluate the effectiveness and side effect of MT regimen (mitoxantrone plus teniposide) in inductive chemotherapy and explore the relationship between the effectiveness and karyotype. Methods 33 patients with acute monocytic leukemia were divided into two groups according to the treatment history or risk status according to cytogenetics MRC criteria. Group A (n=23) and B (n=10) were primary treatment and no remission following one course of DA (daunorubicin plus cytarabine) or HDA (Harringtonine,daunorubicin plus cytarabine) regimen,respectively. According to MRC criteria,group C (n=29) and D (n=4) were intermediate and adverse group. All the cases received two courses MT regimen chemotherapies to induce remission. The results and side effects were analysed. Results The complete remission rate and effective rate in group A and B were 83 % (19/23) and 60 % (6/10),91 % (21/23) and 70 % (7/10) respectively. The complete remission rate and effective rate in group C and D was 83 % (24/29) and 25 % (1/4),88 % (26/29) and 50 % (2/4) respectively. In complex cytogenetic group and 11q23 abnormal without complex cytogenetic group,CR rate was 0 (0/3) and 100 % (4/4). The time point,count of WBC nadir and the duration of WBC were less than 1×109/L is (7±3) day after chemotherapy,(0.4±0.2)×l09/L,(8±5) day. Chemotherapy related mortality was 0. Conclusion MT regimen was highly effective and safe in inducing remission in acute monocytic leukemia,including the cases which achieved no remission following one course of DA or HDA regimen. The effectiveness of MT regimen relates to the cytogenetics. MT regimen may be highly effective in cases with 11q23 abnormal and poor effective in cases with complex cytogenetic.
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Objective To evaluate the clinical effects and immune function of shenqi 11 flavor capsule as an adjuvant treatment in advanced NSCLC patients during chemotherapy.Methods 58 cases of advanced NSCLC were divided into two groups by mean of digital random table method,with 29 patients in each group.GP scheme chemotherapy was applied to patients in group B,using gemcitabine (1000 mg/m2) on the 1st and 8th day intravenously (procedure should be finished within 30 minutes) and cisplatin (75 mg/m2) on the 1st day intravenously.Each cycle was 3 weeks,two cycles in total.Same scheme was applied to patients in group A and with an addition of shenqi 11 flavor capsule(1.65 g/time,3 times/d) throughout the whole procedure of chemothrapy.Recent curative effect,life quality,toxic reactions and changes in immune indexes of both groups were observed.Results Short-term response rate in group A was 48.27％ and 41.38％ in the group B (x2=0.279,P＞0.05),which showed no significant differences between the two groups.Toxic reactions such as leukopenia,hematochrome decrease and gastrointestinal reactions in the group B were significantly severe compared to group A after chemotherapy(x2 were 4.678,4.549 and 4.687 respectively,P＜0.05).As for immune indexes after chemotherapy,CD3+ (55.21 ± 3.28) ％,CD4+ (38.84±5.13) ％,CD8+ (29.86±4.83) ％,CD4+/CD8+( 1.29± 0.17) and NK cells (20.12± 2.11 ) ％in the group B indicated significant differences compared to those in group A[(62.96±4.12)％、(45.21±3.43)％、(25.23±2.79)％、(1.82±0.21)、(25.78±3.36)％],(P＜0.05).The life quality was 58.62％ in group A and 31.03％ in the group B,which showed significant difference (x2=4.462,P＜0.05).Conclusion Shenqi 11 flavor capsule as an adjuvant treatment in advanced NSCLC patients during chemotherapy can not only improve life quality of patients,alleviate the symptoms,but also enhance their immune function.
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Objective To evaluate the effectiveness and side effects in sibling and unrelated HLA identical allogeneic hematopoietic stem cell transplantation for multiple myeloma patients under 45-year-old at early stage. Methods Three patients with multiple myeloma ranged from 38 to 44-year-old received two courses of chemotherapies and achieved partial remission. Sibling HLA identical allogeneic hematopoietic stem cell transplantations were underwent in case 1 and 2, and unrelated were in case 3. The conditioning regimens for case 1 and 2 included fludarabine, busulfan plus cyclophosphamide, and of case 3 included modified busulfan, cyclophosphamide plus antithymocyte globulin. Cycloporine A combined with methotrexate were used to prevent GVHD in the case 1 and 2, and methotrexate, mycophenolate and cycloporine A were used in case 3. Results All patients achieved full donor chimerism without graft failure. Grade Ⅱ acute GVHD and extensive chronic GVHD were found in case 1, but not in case 2 and 3. The period of follow-up of case 1, 2 and 3 were 48, 27 and 6 months, respectively, and all of them were alive with no signs of relapse. Conclusion The multiple myeloma patients under 45-year-old underwent sibling and unrelated HLA identical allogeneic hematopoietic stem cell transplantation at early stage after chemotherapy remission have the low treatment-related mortality, high complete remission rate and may prolong long-term survival.
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Objective To compare the therapeutic and adverse effects of MT regimen (mitoxantrone plus teniposide) and DA regimen (daunorubicin plus cytarabine) on initial treatment to acute monocytic leukemia. Methods 40 patients with initial treatment to acute monocytic leukemia were randomly divided into MT group(n=23) and DA group(n=17). All patients were treated with MT or DA regimen. The result and adverse effects of the two regimens were compared. Results Complete remission(CR) rate in the first course chemotherapy in MT and DA regimen was 65 % and 18 %, respectively. The total CR rate in MT and DA regimen was 83 % and 47 % respectively. The total effective rate was 92 % and 59 %, respectively. Significant differences were found. Severe myelosuppression occurred in both groups. The counts of wbc nadir and the durations of wbc less than 1×10~9/L were not significantly different in two group. The time points of wbc nadir, the start and end time points of wbc less than 1×10~9/L were significantly later in MT group than in DA group. Conclusion MT regimen is significant better than DA regimen in inducing remission in initial treatment acute monocytic leukemia, and it is a good choice for inducing remission strategy. The degrees of myelosuppression in two groups are similar. But the occurrent time of myelosuppression is later in MT group than in DA group. The great attention should be paid to anti-infection and support therapy at time properly.
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Eight patients with severe aplastic anemia received unrelated cord blood transplantation at the Guangzhou First People’s Hospital from June 1998 to December 2007. The patients were conditioned with decreased dosage of immunosuppressive agents of cyclophosphamide and antilymphocytic globulin. The median infused donor total nucleated cell were 5.69?10 7/kg of recipient weight, and the CD34+ cell was 4.10?105/kg of recipient weight. Methotrexate and corticoid methylprednisolone were used for prophylaxis of graft versus host disease (GVHD). The time to reach an absolute neutrophil count of 0.5?109/L ranged from 7 to 25 days (median: 17 days) and the time to reach a platelet count of 20?109/L ranged from 13 to 102 days (median: 35 days) after transplantation. DNA finger print map of 7 patients showed donor and recipient chimera. Two patients developed grade I to II acute GVHD, which was controlled. One patients developed grade II chronic GVHD, which was controlled by using methylprednisolone. Five patients had lived for 10-108 months, with no diseases. Taken together, unrelated umbilical cord blood transplantation is effective for adult patients. Partial conditioning regiment could ensure engraft of unrelated umbilical cord blood transplantation.
