Granulocyte-macrophage colony-stimulating factor (GM-CSF) is an important hematopoietic growth factor and immune modulator. GM-CSF also has profound effects on the functional activities of various circulating leukoc...Granulocyte-macrophage colony-stimulating factor (GM-CSF) is an important hematopoietic growth factor and immune modulator. GM-CSF also has profound effects on the functional activities of various circulating leukocytes. It is produced by a variety of cell types including T cells, macrophages, endothelial cells and fibroblasts upon receiving immune stimuli. Although GM-CSF is produced locally, it can act in a paracrine fashion to recruit circulating neutrophils, monocytes and lymphocytes to enhance their functions in host defense. Recent intensive investigations are centered on the application of GM-CSF as an immune adjuvant for its ability to increase dendritic cell (DC) maturation and function as well as macrophage activity. It is used clinically to treat neutropenia in cancer patients undergoing chemotherapy, in AIDS patients during therapy, and in patients after bone marrow transplantation. Interestingly, the hematopoietic system of GM-CSF-deficient mice appears to be normal; the most significant changes are in some specific T cell responses. Although molecular cloning of GM-CSF was carried out using cDNA library oft cells and it is well known that the T cells produce GM-CSF after activation, there is a lack of systematic investigation of this cytokine in production by T cells and its effect on T cell function. In this article, we will focus mainly on the immunobiology of GM-CSF in T cells.展开更多
Objective: To investigate the therapeutic potency of recombinant human Granulocyte-Macrophage Colony-Stimulating Factor (GM-CSF) in a rabbit myocardial infarction model. Methods: A myocardial infarction was created by...Objective: To investigate the therapeutic potency of recombinant human Granulocyte-Macrophage Colony-Stimulating Factor (GM-CSF) in a rabbit myocardial infarction model. Methods: A myocardial infarction was created by the ligation of the major ventricular branch of the left coronary artery in rabbits. After myocardial infarction, the animals were randomly assigned to GM-CSF treatment group, untreated groups and sham-operated group. The rabbits of the treated group were injected into GM-CSF by subcutaneous administration, 10 μg/kg/day, once a day for 5 days. The untreated and sham-operated group received a equal saline in the same manner as treated group. Six weeks later echocardiography and haemodynamic assessment were undertaken to assesse cardiac function. The size of the infarct region of the heart were also studied. Results: The untreated group exhibited significant higher left ventricle end-diastolic pressure, higher central venous pressure, and with significant lower mean blood pressure, lower peak first derivative of left ventricle pressure (dP/dt) than the sham group. Also, Rabbits in untreated group display significant systolic dysfunction shown by the decreased ejection fraction, diastolic dysfunction shown by increasing in the ratio of E wave to A wave (E/A), and display left ventricle enlargement. However, GS-CSF singnificantly prevented heart dysfunction, left ventricle enlargement, and reduced infarct size in treatment group. Conclusion: Administration GM-CSF after cardiac infarction can improve heart function. These findings indicate the technique may be a novel and simple therapeutic method for ischemic myocardium.展开更多
Objective: The aim of this study was to observe the therapeutic effect of cytokine induced killer (CIK) cells in combination with dendritic cells (DCs) on advanced solid carcinoma patients. Methods: Isolated per...Objective: The aim of this study was to observe the therapeutic effect of cytokine induced killer (CIK) cells in combination with dendritic cells (DCs) on advanced solid carcinoma patients. Methods: Isolated peripheral blood mononuclear cells (PBMCs) from 110 advanced solid tumor patients. Added granulocyte-macrophage colony-stimulating factor (GM-CSF), tumor necrosis factor-a (TNF-a) and interleukin-4 (IL-4) to adherent cells to induce DCs, and sensitized DCs with antigens of autologous tumor cells or extrinsic tumor cell lines. Cultured suspending cells with interferon-y (IFN-y), interleukin-2 (IL-2) and CD3 monoclonal antibody (CD3 McAb) to prepare CIK cells, then co-cultured with DCs. After analyzing the phenotype and checking tumor markers and immune function, the autologous CIK cells and DCs were transfused into the cancer patients. Results: Forty-two patients with measurable nidus, 2 achieved complete remission (CR), 9 partial remission (PR) and 15 stable disease (SD), while 37 patients with immeasurable nidus, 25 had efficient response. The tumor markers and immune function both improved significantly compared with those before treatment. Conclusion: DCs and CIK cells combinational treatment is safe and effective on advanced solid carcinoma and provide a new and efficacious immunity therapeutic methods for the cancer patients.展开更多
Bone remodeling is performed under the joint action of osteoblasts and osteoclasts. Since the effect of osteoclasts has been gradually recognized on bone and joint diseases, targeted researches toward osteoclasts have...Bone remodeling is performed under the joint action of osteoblasts and osteoclasts. Since the effect of osteoclasts has been gradually recognized on bone and joint diseases, targeted researches toward osteoclasts have become a hot research field. This article reviews the relevant medical literature concerning the possible effects of the fluid shear stress (FSS) on the osteoclastogenesis chiefly from the aspects of RANKL-RANK-OPG system, the macrophage colony-stimulating factor (M-CSF), and calcitonin receptor (CTR). On the basis of the changes of the expression of osteoclastic activities, it is suggested that FSS is a potent, important regulator of bone metabolism.展开更多
Objective To investigate expression differences of neutrophil and mononuclear phagocyte related gene mRNAs among acute myocardial infarction (AMI), stable angina (SA) and control groups, and then discuss their exp...Objective To investigate expression differences of neutrophil and mononuclear phagocyte related gene mRNAs among acute myocardial infarction (AMI), stable angina (SA) and control groups, and then discuss their expression characteristics in the stable angina pectoris (SAP) and AMI stages of coronary artery disease (CAD). Methods Whole Human Genome Oligo Microarrays were applied to assess the differential expression characteristics of neutrophil and mononuclear phagocyte related mRNAs in patients with AMI (n = 20), SA (n = 20) and controls (n = 20). Results (1) Almost all colony-stimulating factors (CSF) and their receptors related mRNAs was up-regulated in AMI and SA groups compared with the control group, and the expression of granulocyte-macrophage colony stimulating factor receptor (GM-CSFR) and granulocyte colony stimulating factor receptor (G-CSFR) mRNAs in the AMI group was significantly up-regulated compared with the other two groups (P 〈 0.01). (2) The expression of mRNAs related to monocyte chemoattractant protein-1 (MCP-1), CCR2 (MCP-1 receptor) and CXCR2 (IL-8 receptor) was significantly up-regulated (P 〈 0.01) in AMI group compared with SA and control groups IL-8 mRNA expression in the AMI group was clearly higher than the controls (P 〈 0.05). (3) All mRNAs expression related to opsonic re- ceptors (IgG FoR and C3bR/C4bR) was significantly up-regulated in AMI group compared with SA and control group (P 〈 0.01), and the SA group showed an upward trend compared with controls. (4) Most pattern recognition receptor (PRR)-related mRNAs expression was up-regulated in AMI group compared with SA and control groups. Most toll-like receptor (TLR) mRNAs expression was significantly up-regulated (P 〈 0.01) than the SA and control groups, macrophage scavenger receptor (MSR) mRNA was significantly up-regulated in AMI group compared with the control group (P 〈 0.01), and the SA group showed an upward trend compared with the controls. Conclusions The expression of most neutrophil and mononuclear-macrophage function related genes mRNAs was significantly up-regulated by stages during the progression of CAD, suggesting that the adhesive, chemotactic and phagocytic functions of neutrophil and mononudear-macrophage were strengthened in the occurrence and development of coronary atherosclerosis and AMI. This also showed a stepped up- ward trend as the disease progressed.展开更多
The splicing of many alternative exons in the precursor messenger RNA (pre-mRNA) is regulated by extracellular factors but the underlying molecular bases remain unclear. Here we report the differential regulation of B...The splicing of many alternative exons in the precursor messenger RNA (pre-mRNA) is regulated by extracellular factors but the underlying molecular bases remain unclear. Here we report the differential regulation of Bcl-x pre-mRNA splicing by extracellular factors and their distinct requirements for pre-mRNA elements. In K562 leukemia cells, treatment with interleukin-6 (IL-6) or granulocyte-macrophage colony stimulating factor (GM-CSF) reduced the proportion of the Bcl-xL variant mRNA while treatment with 12-O-tetradecanoylphorbol 13-acetate (TPA) had no effect. In U251 glioma cells, however, TPA efficiently increased the Bcl-xL level. These regulations were also seen for a transfected splicing reporter mini-gene. Further analyses of deletion mutants indicate that nucleotides 1-176 of the downstream intron are required for the IL-6 effect, whereas additional nucleotides 177-284 are essential for the GM-CSF effect. As for the TPA effect, only nucleotides 1-76 are required in the downstream intron. Thus, IL-6, GM-CSF and TPA differentially regulate Bcl-x splicing and require specific intronic pre-mRNA sequences for their respective effects.展开更多
Objective:We studied the molecular mechanisms of Yang Wei Kang Liu Power(YWKL,traditional Chinese medicine for nourishing stomach and anticancer) on anticancer and reducing chemotherapy side-effect in combination with...Objective:We studied the molecular mechanisms of Yang Wei Kang Liu Power(YWKL,traditional Chinese medicine for nourishing stomach and anticancer) on anticancer and reducing chemotherapy side-effect in combination with chemotherapy.Methods:615 pre-cancer mouse model of YWKL for 10 days and CTX 1 time,semi-quantitative reverse transcription-polymerase chain reaction(RT-PCR) to detect bone marrow granulocyte-macrophage colony-stimulating factor(GM-CSF) gene and cancer proto-oncogene Bcl-2,c-myc expression.Results:YWKL in combination with chemotherapy could obviously promoted the expression of GM-CSF gene and inhibited the expression of Bcl-2 and c-myc oncogenes of FC 615 mice.Conclusion:The molecular mechanisms of anticancer and reducing chemotherapy side-effect of YWKL in combination with chemotherapy are to promote the expression of GM-CSF gene and inhibit the expression of Bcl-2 and c-myc oncogenes.展开更多
The aim of this study was to develop a synthetic medium for the in vitro culture of bovine embryos, using various growth factors and cytokines (GF-CYK): insulin-like growth factorl (IGF-Ⅰ), insulin-like growth f...The aim of this study was to develop a synthetic medium for the in vitro culture of bovine embryos, using various growth factors and cytokines (GF-CYK): insulin-like growth factorl (IGF-Ⅰ), insulin-like growth factorⅡ (IGF-Ⅱ), basic fibroblast growth factor (bFGF), leukemia inhibitory factor (LIF), granulocyte-macrophage colony stimulating factor (GM-CSF) and transforming growth factor beta Ⅰ (TGF-β1) + hyaluronan (HA) + recombinant albumin (RA). The embryos were cultured in synthetic oviduct fluid (SOF) supplemented with: treatment 1 (T1): bovine serum albumin (BSA) + insulin, transferrin and selenium (ITS) (control); or treatment 2 (T2): GF-CYK + HA + RA. The blastocyst rates were not significantly different between TI and T2, at seven days post fertilization (dpf) (28.9% ± 2.4% and 31.8% ±2.2%), and at 8 dpf (36.5% ±2.4% and 39.1% ±1.9%), respectively (P 〉 0.05). The total cell number (TCN) was significantly higher with T2 than that with T1 at 7 dpf(164.9 ±5.3 and 149.7 ±4.0) and 8 dpf (182.7 ±6.4 and 165.0 ±5.5) (P 〈 0.05). The blastocyst diameter obtained with T2 was significantly greater (P 〈 0.05) than with T1 at 7 dpf (173.3 μm ±4.9 μm and 157.2μm ±4.1 μm, respectively), however, no significant differences were observed at 8 dpf (190.3 μm 5.2 μm and 179.7 μm ± 5.3 μm, respectively). In conclusion, the synthetic medium (T2) shows a comparable development rate to the control medium and improves the blastocyst diameter and the TCN.展开更多
Objective To observe the clinical efficacy of opposing needling for the treatment of migraine with the symptom of hyperactivity of liver yang type and its effect on NO level in plasma of patients. Methods Atotal of 60...Objective To observe the clinical efficacy of opposing needling for the treatment of migraine with the symptom of hyperactivity of liver yang type and its effect on NO level in plasma of patients. Methods Atotal of 60 migraine patients with the symptom of hyperactivity of liver yang who met the inclusive criteria were randomly divided into a opposing needling group (group A) and a routine acupuncture group (group B) by using SPSS 15.0 software according to the registration order with 30 patients in each group. Patients in group A were treated with opposing needling. Taich6ng (太冲 LR 3), Zhongzhu (中渚 TE 3), ZOlfnqi (足临泣 GB 41) and QiOxu (丘墟 GB 40) in the uninjured side were selected. After deqi, reducing method was used. Then Taixi (太溪 KI 3) in the uninjured side was selected. After deqi, rein forcing method was used. Needles were retained for 30 rain. Patients in group B were treated with routine acupuncture. Local Ash point, Sishncong ( 四神聪EX-HN1), Yifeng (翳风 TE 17), Fengchi (风池 GB 20), Sizhukong (丝竹空 TE 23), Shuaigu (率谷GB 8), Hegu (合谷 LI 4) and LiEque (列缺 LU 7) were selected. After puncturing, reducing method was used routinely and needles were retained for 30 rain. After 2 weeks treatment, migraine specific quality of life questionnaire (MSQ), visual analogue scale (VAS) and nitric oxide (NO) level in plasma of patients in two groups were observed. Results After treatment, the MSQ, VAS and NO of two groups were significantly improved compared with those before treatment. After treatment, score of MSQ functional limitation was 73.41±10.22 in group A and 60.95 ± 10.15 in group B; the score of MSQ dysfunction was 86.11 ±8.22 in group A and 75.45±8.34 in group B; score of MSQ emotion was 80.51±10.16 in group A and 75.01± 10.20 in group B. The improvements of group A were superior to those of group B, and the differences were all statistically significant (all P〈0.05). After treatment, the VAS score was 0.93 ± 1.25 in group A and 2.17± 1.70 in group B. The improvement of group A was superior to that of group B, and the difference was statistically significant (P〈0.05). After treatment, blood plasma NO level was (42.15 ± 16.15) μmol/L in group A and (62.76±15.17) μmol/L in group B. The improvement of group A was superior to that of group B, and the difference was statistically significant (P〈0.05). Overall response rate was 86.7% (26/30) in group A and 53.3% (16/30) in group B, and the difference between two groups was statistically significant (P〈0.05). Conclusion Opposing needling is an effective method for the treatment of migraine with the symptom of hyperactivity of liver yong. Its mechanism is to regulate the generation of NO in migraine patients, and improve the relaxation and contraction of cerebral vascular smooth muscle, so as to adjust the cerebral circulation.展开更多
Objective To observe the differences in therapeutic effects on primary trigeminat neuralgia between contralateral needling technique and routine acupuncture. Methods One hundred and thirty cases were randomly divided ...Objective To observe the differences in therapeutic effects on primary trigeminat neuralgia between contralateral needling technique and routine acupuncture. Methods One hundred and thirty cases were randomly divided into contralateral needling group and routine acupuncture group, 65 cases in each one. In contralateral needling group, contralateral needling technique was adopted on the acupoints on the opposite side corresponding to the affected face in neuralgia. According to the localization of trigeminal neuralgia, the points were selected. For example, for ophthalmologic branch, Yuyao (鱼腰 EX- HN 4) and Touwei (头维 ST 8) were selected as the main point. In routine acupuncture group, the corresponding acupoints were selected on the affected side of the face. The points were same as that in contralateral needling group, Three courses of treatment were required in two groups. The clinical efficacy was evaluated 4 weeks after the end of treatment. Results The total effective rate was 95.4% (62/65) in contralateral needling group, which was superior to that in routine acupuncture group E86.2% (56/65)1 (P〈0. 001). Conclusion Contralateral needling technique achieves apparently superior effects on primary trigeminal neuralgia compared with routine acupuncture.展开更多
Objective To investigate the expression of the granulocyte-macrophage colony-stimulating factor (GM-CSF) and GM-CSF/IL-3/IL-5 receptor common beta chain (βc receptor) in an adult patient with idiopathic pulmonary al...Objective To investigate the expression of the granulocyte-macrophage colony-stimulating factor (GM-CSF) and GM-CSF/IL-3/IL-5 receptor common beta chain (βc receptor) in an adult patient with idiopathic pulmonary alveolar proteinosis (PAP), so as to demonstrate the possible association of the GM-CSF and βc receptor with the pathogenesis of human PAP.Methods The GM-CSF levels were measured with a commercial ELISA kit (sensitivity 5?pg/ml) and the βc receptor expression on the cell surface was detected by flow cytometry analysis. Reverse transcription-polymerase chain reaction (RT-PCR) analysis was employed to detect the expression of the GM-CSF mRNA and the βc receptor mRNA in peripheral blood mononuclear cells and alveolar macrophages. The entire coding regions of the GM-CSF cDNA and the βc receptor cDNA were sequenced by the Sanger dideoxy-mediated chain termination method to detect possible mutations.Results The patient with PAP failed to release the GM-CSF protein either from circulating mononuclear cells or from alveolar macrophages. The expression of the GM-CSF mRNA was normal after the stimulation of lipopolysaccharide, whereas a point mutation at position 382 of the GM-CSF cDNA from 'T' to 'C' was revealed by cDNA sequencing, which caused a change in amino acid 117 of the protein from isoleucine to threonine. The βc receptor expression on the cell surface was normal, and the βc receptor mRNA expression and the sequence of the entire coding region of the βc receptor were also normal.Conclusions The decreased GM-CSF production is associated with the pathogenesis of human PAP. A point mutation of the GM-CSF cDNA may contribute to the decreased GM-CSF production in our adult PAP patient. The mutation of the βc receptor in some of paediatric patients with PAP may not be a common problem in adult patients.展开更多
Objective To observe the efficacy of treating intrauterine infected chronic hepatitis B virus (HBV) carrier children with a combination of granulocyte macrophage colony stimulating factor (GM CSF) or hepatitis B i...Objective To observe the efficacy of treating intrauterine infected chronic hepatitis B virus (HBV) carrier children with a combination of granulocyte macrophage colony stimulating factor (GM CSF) or hepatitis B immunoglobulin (HBIG) plus recombinant hepatitis B vaccine (rHBvac) Methods A total of 27 chronic HBV infected children, who were born to HBV carrier mothers and received hepatitis B immunoprophylaxis at birth, were randomized into 2 groups: one receiving a combined therapy of 50 μg of GM CSF plus 10 μg of rHBvac injected intramuscularly at the same location (GM CSF group, 14 children) or 200 IU HBIG and 10 μg rHBvac in different muscles (HBIG group, 13 children) on a monthly four dose schedule HBV DNA quantification and other HBV serological markers were tested before and after the four dose therapy Results Twelve children in each group completed the study Of them, 3 children in the GM CSF group and 4 in the HBIG group had elevated serum alanine transaminase (ALT) before the trial, and then 2 in each group became ALT normal after the treatment Before the therapy, hepatitis B e antigen (HBeAg) positivity was found in nine children in the GM CSF group and 10 in the HBIG group One from each group had an HBeAg/anti HBe seroconversion after the treatment The quantity of HBV DNA was significantly lower after the treatment ( P =0 023) in GM CSF group, but was not significantly reduced in HBIG group No subjects were found to be negative for hepatitis B surface antigen (HBsAg) after the treatment, and no serious adverse events occurred in either group Conclusion Combined GM CSF and rHBvac therapy inhibit HBV replication in carrier children who were not protected after treatment with immunoprophylaxis展开更多
Objective: To observe the effects of Cantharides vesiculation moxibustion on hematopoietic function and granulocyte-macrophage colony-stimulating factor (GM-CSF) secreted by peritoneal macrophages in mice treated w...Objective: To observe the effects of Cantharides vesiculation moxibustion on hematopoietic function and granulocyte-macrophage colony-stimulating factor (GM-CSF) secreted by peritoneal macrophages in mice treated with chemotherapy. Methods: The mice treated with Cyclophosphamide (CTX) were randomly divided into 6 groups. Ten mice in the control group were not treated. The mice in the vesiculation I-IV groups received moxibustion at Dazhui (GV 14), Shenshu (BL 23) and Zusanli (ST 36) with different concentrations of Cantharides tincture. The mice in the grain moxibustion group were treated with moxa cone of wheat-grain size at these points. The other 10 normal mice were adopted as control. The peripheral blood leukocytes count, bone marrow nucleated cells count, spleen index and the ability of peritoneal-macrophages-induced GM-CSF were detected at different stages. Results: CTX could cause significant bone marrow suppression, significant decrease of bone marrow nucleated cell counts, peripheral blood leukocytes and spleen index, and reduction of peritoneal macrophages induced GM-CSF in the mice. Vesiculation moxibustion at Dazhui (GV 14), Shenshu (BL 23) and Zusanli (ST 36), not only reduced the bone marrow suppression, promoted bone marrow hyperplasia, increased bone marrow nucleated cell count, enhanced the number of the peripheral blood white blood cell (WBC) and shorted low sustained period of WBC chemotherapy-induced, but also enhanced the ability of macrophage induced GM-CSF. Conclusion: Cantharides vesiculation moxibustion has good resistance to the bone marrow suppression in mice treated with chemotherapy, and enhance the ability of the mouse peritoneal macrophages induced GM-CSF.展开更多
Contralateral Needling is an ancient needling method recorded in Nei Jing (Inner Canon). It said in the Guan Zhen chapter of Ling Shu (chapter of needling technique of Spiritual Pivot) that contralateral needling ...Contralateral Needling is an ancient needling method recorded in Nei Jing (Inner Canon). It said in the Guan Zhen chapter of Ling Shu (chapter of needling technique of Spiritual Pivot) that contralateral needling is to needle the points on contralateral side to the affected side of the body.展开更多
This study investigated the therapeutic effects of interleukin (IL)-2 and granulocyte-macrophage colony-stimulating factor (GM-CSF) co-administrated with antibacterial agents isoniazid (INH) and rifampin (RIF)...This study investigated the therapeutic effects of interleukin (IL)-2 and granulocyte-macrophage colony-stimulating factor (GM-CSF) co-administrated with antibacterial agents isoniazid (INH) and rifampin (RIF) to treat a mouse model of tuberculo- sis (TB) infection. A drug-susceptible TB strain, H37Rv was used to infect mice and the effectiveness of IL-2 and GM-CSF was initially evaluated based on survival rate, bacterial counts in lungs and spleens and the pathological condition of the lungs. Next, the therapeutic effect of the immunotherapy regimen was assessed in multidrug-resistant strain OB35-infected mice. In the H37Rv infection model, 1L-2 and GM-CSF monotherapies reduced bacterial numbers in the lungs by 0.82 (P〈0.01) and 0.58 (P〈0.05) lg colony-forming units (CFU), respectively, and in the spleens by 1.42 (P〈0.01) and 1.22 (P〈0.01) lg CFU, re- spectively, compared with the untreated group. Mice receiving immunotherapy developed fewer lesions in the lungs compared with mice receiving antibacterial therapy alone. In the OB35 infection model, immunotherapy with either cytokine resulted in a significant reduction of bacterial load in the lungs and spleens and less severe lesions in the lungs compared with the untreated or antibacterial therapy treated mice. Notably, mice receiving immunotherapy with both cytokines had a 30% survival rate which was higher than that in other treated groups, and had significantly less CFUs in the lungs and spleens (1.02 and 1.34 lg CFU) compared with antibacterial therapy alone (P〈0.01). This study demonstrated that immunotherapy with both IL-2 and GM-CSF may be useful to treat multidrug resistant tuberculosis (MDR-TB).展开更多
文摘Granulocyte-macrophage colony-stimulating factor (GM-CSF) is an important hematopoietic growth factor and immune modulator. GM-CSF also has profound effects on the functional activities of various circulating leukocytes. It is produced by a variety of cell types including T cells, macrophages, endothelial cells and fibroblasts upon receiving immune stimuli. Although GM-CSF is produced locally, it can act in a paracrine fashion to recruit circulating neutrophils, monocytes and lymphocytes to enhance their functions in host defense. Recent intensive investigations are centered on the application of GM-CSF as an immune adjuvant for its ability to increase dendritic cell (DC) maturation and function as well as macrophage activity. It is used clinically to treat neutropenia in cancer patients undergoing chemotherapy, in AIDS patients during therapy, and in patients after bone marrow transplantation. Interestingly, the hematopoietic system of GM-CSF-deficient mice appears to be normal; the most significant changes are in some specific T cell responses. Although molecular cloning of GM-CSF was carried out using cDNA library oft cells and it is well known that the T cells produce GM-CSF after activation, there is a lack of systematic investigation of this cytokine in production by T cells and its effect on T cell function. In this article, we will focus mainly on the immunobiology of GM-CSF in T cells.
文摘Objective: To investigate the therapeutic potency of recombinant human Granulocyte-Macrophage Colony-Stimulating Factor (GM-CSF) in a rabbit myocardial infarction model. Methods: A myocardial infarction was created by the ligation of the major ventricular branch of the left coronary artery in rabbits. After myocardial infarction, the animals were randomly assigned to GM-CSF treatment group, untreated groups and sham-operated group. The rabbits of the treated group were injected into GM-CSF by subcutaneous administration, 10 μg/kg/day, once a day for 5 days. The untreated and sham-operated group received a equal saline in the same manner as treated group. Six weeks later echocardiography and haemodynamic assessment were undertaken to assesse cardiac function. The size of the infarct region of the heart were also studied. Results: The untreated group exhibited significant higher left ventricle end-diastolic pressure, higher central venous pressure, and with significant lower mean blood pressure, lower peak first derivative of left ventricle pressure (dP/dt) than the sham group. Also, Rabbits in untreated group display significant systolic dysfunction shown by the decreased ejection fraction, diastolic dysfunction shown by increasing in the ratio of E wave to A wave (E/A), and display left ventricle enlargement. However, GS-CSF singnificantly prevented heart dysfunction, left ventricle enlargement, and reduced infarct size in treatment group. Conclusion: Administration GM-CSF after cardiac infarction can improve heart function. These findings indicate the technique may be a novel and simple therapeutic method for ischemic myocardium.
基金Supported by a grant from the Foundation of Chongqing Municipal Health Bureau (No. 2010-2-301)
文摘Objective: The aim of this study was to observe the therapeutic effect of cytokine induced killer (CIK) cells in combination with dendritic cells (DCs) on advanced solid carcinoma patients. Methods: Isolated peripheral blood mononuclear cells (PBMCs) from 110 advanced solid tumor patients. Added granulocyte-macrophage colony-stimulating factor (GM-CSF), tumor necrosis factor-a (TNF-a) and interleukin-4 (IL-4) to adherent cells to induce DCs, and sensitized DCs with antigens of autologous tumor cells or extrinsic tumor cell lines. Cultured suspending cells with interferon-y (IFN-y), interleukin-2 (IL-2) and CD3 monoclonal antibody (CD3 McAb) to prepare CIK cells, then co-cultured with DCs. After analyzing the phenotype and checking tumor markers and immune function, the autologous CIK cells and DCs were transfused into the cancer patients. Results: Forty-two patients with measurable nidus, 2 achieved complete remission (CR), 9 partial remission (PR) and 15 stable disease (SD), while 37 patients with immeasurable nidus, 25 had efficient response. The tumor markers and immune function both improved significantly compared with those before treatment. Conclusion: DCs and CIK cells combinational treatment is safe and effective on advanced solid carcinoma and provide a new and efficacious immunity therapeutic methods for the cancer patients.
文摘Bone remodeling is performed under the joint action of osteoblasts and osteoclasts. Since the effect of osteoclasts has been gradually recognized on bone and joint diseases, targeted researches toward osteoclasts have become a hot research field. This article reviews the relevant medical literature concerning the possible effects of the fluid shear stress (FSS) on the osteoclastogenesis chiefly from the aspects of RANKL-RANK-OPG system, the macrophage colony-stimulating factor (M-CSF), and calcitonin receptor (CTR). On the basis of the changes of the expression of osteoclastic activities, it is suggested that FSS is a potent, important regulator of bone metabolism.
文摘Objective To investigate expression differences of neutrophil and mononuclear phagocyte related gene mRNAs among acute myocardial infarction (AMI), stable angina (SA) and control groups, and then discuss their expression characteristics in the stable angina pectoris (SAP) and AMI stages of coronary artery disease (CAD). Methods Whole Human Genome Oligo Microarrays were applied to assess the differential expression characteristics of neutrophil and mononuclear phagocyte related mRNAs in patients with AMI (n = 20), SA (n = 20) and controls (n = 20). Results (1) Almost all colony-stimulating factors (CSF) and their receptors related mRNAs was up-regulated in AMI and SA groups compared with the control group, and the expression of granulocyte-macrophage colony stimulating factor receptor (GM-CSFR) and granulocyte colony stimulating factor receptor (G-CSFR) mRNAs in the AMI group was significantly up-regulated compared with the other two groups (P 〈 0.01). (2) The expression of mRNAs related to monocyte chemoattractant protein-1 (MCP-1), CCR2 (MCP-1 receptor) and CXCR2 (IL-8 receptor) was significantly up-regulated (P 〈 0.01) in AMI group compared with SA and control groups IL-8 mRNA expression in the AMI group was clearly higher than the controls (P 〈 0.05). (3) All mRNAs expression related to opsonic re- ceptors (IgG FoR and C3bR/C4bR) was significantly up-regulated in AMI group compared with SA and control group (P 〈 0.01), and the SA group showed an upward trend compared with controls. (4) Most pattern recognition receptor (PRR)-related mRNAs expression was up-regulated in AMI group compared with SA and control groups. Most toll-like receptor (TLR) mRNAs expression was significantly up-regulated (P 〈 0.01) than the SA and control groups, macrophage scavenger receptor (MSR) mRNA was significantly up-regulated in AMI group compared with the control group (P 〈 0.01), and the SA group showed an upward trend compared with the controls. Conclusions The expression of most neutrophil and mononuclear-macrophage function related genes mRNAs was significantly up-regulated by stages during the progression of CAD, suggesting that the adhesive, chemotactic and phagocytic functions of neutrophil and mononudear-macrophage were strengthened in the occurrence and development of coronary atherosclerosis and AMI. This also showed a stepped up- ward trend as the disease progressed.
文摘The splicing of many alternative exons in the precursor messenger RNA (pre-mRNA) is regulated by extracellular factors but the underlying molecular bases remain unclear. Here we report the differential regulation of Bcl-x pre-mRNA splicing by extracellular factors and their distinct requirements for pre-mRNA elements. In K562 leukemia cells, treatment with interleukin-6 (IL-6) or granulocyte-macrophage colony stimulating factor (GM-CSF) reduced the proportion of the Bcl-xL variant mRNA while treatment with 12-O-tetradecanoylphorbol 13-acetate (TPA) had no effect. In U251 glioma cells, however, TPA efficiently increased the Bcl-xL level. These regulations were also seen for a transfected splicing reporter mini-gene. Further analyses of deletion mutants indicate that nucleotides 1-176 of the downstream intron are required for the IL-6 effect, whereas additional nucleotides 177-284 are essential for the GM-CSF effect. As for the TPA effect, only nucleotides 1-76 are required in the downstream intron. Thus, IL-6, GM-CSF and TPA differentially regulate Bcl-x splicing and require specific intronic pre-mRNA sequences for their respective effects.
文摘Objective:We studied the molecular mechanisms of Yang Wei Kang Liu Power(YWKL,traditional Chinese medicine for nourishing stomach and anticancer) on anticancer and reducing chemotherapy side-effect in combination with chemotherapy.Methods:615 pre-cancer mouse model of YWKL for 10 days and CTX 1 time,semi-quantitative reverse transcription-polymerase chain reaction(RT-PCR) to detect bone marrow granulocyte-macrophage colony-stimulating factor(GM-CSF) gene and cancer proto-oncogene Bcl-2,c-myc expression.Results:YWKL in combination with chemotherapy could obviously promoted the expression of GM-CSF gene and inhibited the expression of Bcl-2 and c-myc oncogenes of FC 615 mice.Conclusion:The molecular mechanisms of anticancer and reducing chemotherapy side-effect of YWKL in combination with chemotherapy are to promote the expression of GM-CSF gene and inhibit the expression of Bcl-2 and c-myc oncogenes.
文摘The aim of this study was to develop a synthetic medium for the in vitro culture of bovine embryos, using various growth factors and cytokines (GF-CYK): insulin-like growth factorl (IGF-Ⅰ), insulin-like growth factorⅡ (IGF-Ⅱ), basic fibroblast growth factor (bFGF), leukemia inhibitory factor (LIF), granulocyte-macrophage colony stimulating factor (GM-CSF) and transforming growth factor beta Ⅰ (TGF-β1) + hyaluronan (HA) + recombinant albumin (RA). The embryos were cultured in synthetic oviduct fluid (SOF) supplemented with: treatment 1 (T1): bovine serum albumin (BSA) + insulin, transferrin and selenium (ITS) (control); or treatment 2 (T2): GF-CYK + HA + RA. The blastocyst rates were not significantly different between TI and T2, at seven days post fertilization (dpf) (28.9% ± 2.4% and 31.8% ±2.2%), and at 8 dpf (36.5% ±2.4% and 39.1% ±1.9%), respectively (P 〉 0.05). The total cell number (TCN) was significantly higher with T2 than that with T1 at 7 dpf(164.9 ±5.3 and 149.7 ±4.0) and 8 dpf (182.7 ±6.4 and 165.0 ±5.5) (P 〈 0.05). The blastocyst diameter obtained with T2 was significantly greater (P 〈 0.05) than with T1 at 7 dpf (173.3 μm ±4.9 μm and 157.2μm ±4.1 μm, respectively), however, no significant differences were observed at 8 dpf (190.3 μm 5.2 μm and 179.7 μm ± 5.3 μm, respectively). In conclusion, the synthetic medium (T2) shows a comparable development rate to the control medium and improves the blastocyst diameter and the TCN.
基金Supported by Traditional Chinese Medicine Bureau of Guangdong Province,project number:20141240
文摘Objective To observe the clinical efficacy of opposing needling for the treatment of migraine with the symptom of hyperactivity of liver yang type and its effect on NO level in plasma of patients. Methods Atotal of 60 migraine patients with the symptom of hyperactivity of liver yang who met the inclusive criteria were randomly divided into a opposing needling group (group A) and a routine acupuncture group (group B) by using SPSS 15.0 software according to the registration order with 30 patients in each group. Patients in group A were treated with opposing needling. Taich6ng (太冲 LR 3), Zhongzhu (中渚 TE 3), ZOlfnqi (足临泣 GB 41) and QiOxu (丘墟 GB 40) in the uninjured side were selected. After deqi, reducing method was used. Then Taixi (太溪 KI 3) in the uninjured side was selected. After deqi, rein forcing method was used. Needles were retained for 30 rain. Patients in group B were treated with routine acupuncture. Local Ash point, Sishncong ( 四神聪EX-HN1), Yifeng (翳风 TE 17), Fengchi (风池 GB 20), Sizhukong (丝竹空 TE 23), Shuaigu (率谷GB 8), Hegu (合谷 LI 4) and LiEque (列缺 LU 7) were selected. After puncturing, reducing method was used routinely and needles were retained for 30 rain. After 2 weeks treatment, migraine specific quality of life questionnaire (MSQ), visual analogue scale (VAS) and nitric oxide (NO) level in plasma of patients in two groups were observed. Results After treatment, the MSQ, VAS and NO of two groups were significantly improved compared with those before treatment. After treatment, score of MSQ functional limitation was 73.41±10.22 in group A and 60.95 ± 10.15 in group B; the score of MSQ dysfunction was 86.11 ±8.22 in group A and 75.45±8.34 in group B; score of MSQ emotion was 80.51±10.16 in group A and 75.01± 10.20 in group B. The improvements of group A were superior to those of group B, and the differences were all statistically significant (all P〈0.05). After treatment, the VAS score was 0.93 ± 1.25 in group A and 2.17± 1.70 in group B. The improvement of group A was superior to that of group B, and the difference was statistically significant (P〈0.05). After treatment, blood plasma NO level was (42.15 ± 16.15) μmol/L in group A and (62.76±15.17) μmol/L in group B. The improvement of group A was superior to that of group B, and the difference was statistically significant (P〈0.05). Overall response rate was 86.7% (26/30) in group A and 53.3% (16/30) in group B, and the difference between two groups was statistically significant (P〈0.05). Conclusion Opposing needling is an effective method for the treatment of migraine with the symptom of hyperactivity of liver yong. Its mechanism is to regulate the generation of NO in migraine patients, and improve the relaxation and contraction of cerebral vascular smooth muscle, so as to adjust the cerebral circulation.
文摘Objective To observe the differences in therapeutic effects on primary trigeminat neuralgia between contralateral needling technique and routine acupuncture. Methods One hundred and thirty cases were randomly divided into contralateral needling group and routine acupuncture group, 65 cases in each one. In contralateral needling group, contralateral needling technique was adopted on the acupoints on the opposite side corresponding to the affected face in neuralgia. According to the localization of trigeminal neuralgia, the points were selected. For example, for ophthalmologic branch, Yuyao (鱼腰 EX- HN 4) and Touwei (头维 ST 8) were selected as the main point. In routine acupuncture group, the corresponding acupoints were selected on the affected side of the face. The points were same as that in contralateral needling group, Three courses of treatment were required in two groups. The clinical efficacy was evaluated 4 weeks after the end of treatment. Results The total effective rate was 95.4% (62/65) in contralateral needling group, which was superior to that in routine acupuncture group E86.2% (56/65)1 (P〈0. 001). Conclusion Contralateral needling technique achieves apparently superior effects on primary trigeminal neuralgia compared with routine acupuncture.
文摘Objective To investigate the expression of the granulocyte-macrophage colony-stimulating factor (GM-CSF) and GM-CSF/IL-3/IL-5 receptor common beta chain (βc receptor) in an adult patient with idiopathic pulmonary alveolar proteinosis (PAP), so as to demonstrate the possible association of the GM-CSF and βc receptor with the pathogenesis of human PAP.Methods The GM-CSF levels were measured with a commercial ELISA kit (sensitivity 5?pg/ml) and the βc receptor expression on the cell surface was detected by flow cytometry analysis. Reverse transcription-polymerase chain reaction (RT-PCR) analysis was employed to detect the expression of the GM-CSF mRNA and the βc receptor mRNA in peripheral blood mononuclear cells and alveolar macrophages. The entire coding regions of the GM-CSF cDNA and the βc receptor cDNA were sequenced by the Sanger dideoxy-mediated chain termination method to detect possible mutations.Results The patient with PAP failed to release the GM-CSF protein either from circulating mononuclear cells or from alveolar macrophages. The expression of the GM-CSF mRNA was normal after the stimulation of lipopolysaccharide, whereas a point mutation at position 382 of the GM-CSF cDNA from 'T' to 'C' was revealed by cDNA sequencing, which caused a change in amino acid 117 of the protein from isoleucine to threonine. The βc receptor expression on the cell surface was normal, and the βc receptor mRNA expression and the sequence of the entire coding region of the βc receptor were also normal.Conclusions The decreased GM-CSF production is associated with the pathogenesis of human PAP. A point mutation of the GM-CSF cDNA may contribute to the decreased GM-CSF production in our adult PAP patient. The mutation of the βc receptor in some of paediatric patients with PAP may not be a common problem in adult patients.
基金ThisstudywassupportedbyagrantfromtheNationalPublicHealthMinistry (No97030223)andagrantfromtheNationalNaturalScienceFoundationofChina (No 39670 667)
文摘Objective To observe the efficacy of treating intrauterine infected chronic hepatitis B virus (HBV) carrier children with a combination of granulocyte macrophage colony stimulating factor (GM CSF) or hepatitis B immunoglobulin (HBIG) plus recombinant hepatitis B vaccine (rHBvac) Methods A total of 27 chronic HBV infected children, who were born to HBV carrier mothers and received hepatitis B immunoprophylaxis at birth, were randomized into 2 groups: one receiving a combined therapy of 50 μg of GM CSF plus 10 μg of rHBvac injected intramuscularly at the same location (GM CSF group, 14 children) or 200 IU HBIG and 10 μg rHBvac in different muscles (HBIG group, 13 children) on a monthly four dose schedule HBV DNA quantification and other HBV serological markers were tested before and after the four dose therapy Results Twelve children in each group completed the study Of them, 3 children in the GM CSF group and 4 in the HBIG group had elevated serum alanine transaminase (ALT) before the trial, and then 2 in each group became ALT normal after the treatment Before the therapy, hepatitis B e antigen (HBeAg) positivity was found in nine children in the GM CSF group and 10 in the HBIG group One from each group had an HBeAg/anti HBe seroconversion after the treatment The quantity of HBV DNA was significantly lower after the treatment ( P =0 023) in GM CSF group, but was not significantly reduced in HBIG group No subjects were found to be negative for hepatitis B surface antigen (HBsAg) after the treatment, and no serious adverse events occurred in either group Conclusion Combined GM CSF and rHBvac therapy inhibit HBV replication in carrier children who were not protected after treatment with immunoprophylaxis
基金Shanghai Leading Academic Discipline Project (S30304)
文摘Objective: To observe the effects of Cantharides vesiculation moxibustion on hematopoietic function and granulocyte-macrophage colony-stimulating factor (GM-CSF) secreted by peritoneal macrophages in mice treated with chemotherapy. Methods: The mice treated with Cyclophosphamide (CTX) were randomly divided into 6 groups. Ten mice in the control group were not treated. The mice in the vesiculation I-IV groups received moxibustion at Dazhui (GV 14), Shenshu (BL 23) and Zusanli (ST 36) with different concentrations of Cantharides tincture. The mice in the grain moxibustion group were treated with moxa cone of wheat-grain size at these points. The other 10 normal mice were adopted as control. The peripheral blood leukocytes count, bone marrow nucleated cells count, spleen index and the ability of peritoneal-macrophages-induced GM-CSF were detected at different stages. Results: CTX could cause significant bone marrow suppression, significant decrease of bone marrow nucleated cell counts, peripheral blood leukocytes and spleen index, and reduction of peritoneal macrophages induced GM-CSF in the mice. Vesiculation moxibustion at Dazhui (GV 14), Shenshu (BL 23) and Zusanli (ST 36), not only reduced the bone marrow suppression, promoted bone marrow hyperplasia, increased bone marrow nucleated cell count, enhanced the number of the peripheral blood white blood cell (WBC) and shorted low sustained period of WBC chemotherapy-induced, but also enhanced the ability of macrophage induced GM-CSF. Conclusion: Cantharides vesiculation moxibustion has good resistance to the bone marrow suppression in mice treated with chemotherapy, and enhance the ability of the mouse peritoneal macrophages induced GM-CSF.
文摘Contralateral Needling is an ancient needling method recorded in Nei Jing (Inner Canon). It said in the Guan Zhen chapter of Ling Shu (chapter of needling technique of Spiritual Pivot) that contralateral needling is to needle the points on contralateral side to the affected side of the body.
基金supported in part by the Key Technologies Research and Development Program for Infectious Diseases of China (Grant No. 2012ZX10003001)the Key Project of Science and Technology of Shanghai (Grant No.10411955000)the Shanghai Science and Technology Development Funds (Grant No. 10XD1400900)
文摘This study investigated the therapeutic effects of interleukin (IL)-2 and granulocyte-macrophage colony-stimulating factor (GM-CSF) co-administrated with antibacterial agents isoniazid (INH) and rifampin (RIF) to treat a mouse model of tuberculo- sis (TB) infection. A drug-susceptible TB strain, H37Rv was used to infect mice and the effectiveness of IL-2 and GM-CSF was initially evaluated based on survival rate, bacterial counts in lungs and spleens and the pathological condition of the lungs. Next, the therapeutic effect of the immunotherapy regimen was assessed in multidrug-resistant strain OB35-infected mice. In the H37Rv infection model, 1L-2 and GM-CSF monotherapies reduced bacterial numbers in the lungs by 0.82 (P〈0.01) and 0.58 (P〈0.05) lg colony-forming units (CFU), respectively, and in the spleens by 1.42 (P〈0.01) and 1.22 (P〈0.01) lg CFU, re- spectively, compared with the untreated group. Mice receiving immunotherapy developed fewer lesions in the lungs compared with mice receiving antibacterial therapy alone. In the OB35 infection model, immunotherapy with either cytokine resulted in a significant reduction of bacterial load in the lungs and spleens and less severe lesions in the lungs compared with the untreated or antibacterial therapy treated mice. Notably, mice receiving immunotherapy with both cytokines had a 30% survival rate which was higher than that in other treated groups, and had significantly less CFUs in the lungs and spleens (1.02 and 1.34 lg CFU) compared with antibacterial therapy alone (P〈0.01). This study demonstrated that immunotherapy with both IL-2 and GM-CSF may be useful to treat multidrug resistant tuberculosis (MDR-TB).