Mesenchymal stem cells (MSC) are a kind of non-hematopoietic adult stem cells with self-renewal and multilineage differentiation potential, which have special biological characteristics, such as secreting various cytokines, promoting hematopoiesis, accelerating stem cells homing and reconstructing hematopoietic microenvironment. MSC are collected and amplified easily, and can be transfected by exogenous gene. Many reports indicated that MSC were applied in therapy for variety of tissues and organs injury, meanwhile the treatment for acute radiation sickness has made significant progress. In this review, the biological characteristics and new research advance on MSC in treatment of severe acute radiation sickness are summarized and discussed.
Acute Radiation Syndrome ; surgery ; Humans ; Mesenchymal Stem Cell Transplantation

OBJECTIVETo investigate the expression of eosinophil major basic protein (MBP) mRNA in bronchial asthma and explore its significance.

METHODSPeripheral blood eosinophil MBP mRNA levels were measured in 40 patients with asthma and 20 normal controls by semi-quantitative RT-PCR. The association of MBP mRNA levels with eosinophil count and pulmonary function was also analyzed.

RESULTSCompared with the normal control group, MBP mRNA level were significantly increased in asthma patients (0.37-/+0.11 vs 0.17-/+0.04, P<0.001), so was the eosinophil count (0.86-/+0.52 vs 0.21-/+0.10, P<0.001). MBP mRNA levels in patients with moderate persistent asthma (0.42-/+0.05) and those with severe persistent asthma (0.47-/+0.05) were significantly higher than those in patients with mild persistent asthma (0.25-/+0.06, P<0.001), and the difference in MBP mRNA levels between moderate persistent asthma patients and severe ones was also significant (P<0.05). Among the asthma patients, MBP mRNA levels showed an inverse correlation with pulmonary function (r=-0.7490, P<0.001).

CONCLUSIONIncreased MBP mRNA expression level may correlate with the severity of asthma. MBP may play an important role in the development of asthma.

Adult ; Asthma ; genetics ; pathology ; Blood Proteins ; genetics ; Eosinophil Major Basic Protein ; Female ; Humans ; Male ; Middle Aged ; Proteoglycans ; genetics ; RNA, Messenger ; genetics ; metabolism ; Reverse Transcriptase Polymerase Chain Reaction

This study was aimed to investigate the biological effects of Rhesus bone marrow mesenchymal stem cells (R-BMMSC) transfected by adenovirus bearing extracellular superoxide dismutase gene (AD-ECSOD). Using density gradient centrifugation and adherent culture way, the R-BMMSC transfected by AD-ECSOD and reporter gene EGFP were isolated, cultured and purified; the transfection efficiency was detected by fluorescence microscopy and flow cytometry; the ECSOD protein expression in cell culture supernatant were detected by ELISA; the surface antigens on R-BMMSC (CD34, CD29, CD45, CD90, HLA-DR) were detected by flow cytometry; and differentiation capability of transfected R-BMMSC were detected by oil red O and alizarin staining; the proliferation capability of R-BMMSC was assay by MTT method. The results showed that the transfection efficiency of AD-ECSOD (MOI 500, 1 000, 1 500 and 2 000) for R-BMMSC was > 95%. At 24 h after transfection, the ECSOD protein could be detected in cell culture supernatant, and its level was significantly higher than that of control group (P < 0.01). At 48 h after transfection, the expression level of ECSOD protein on MOI 1 500 and 2 000 was the highest. The proliferative capability, surface antigen expression and multi directive differentiation ability of transfected R-BMMSC were similar to non-transfected R-BMMSC. It is concluded that the AD-ECSOD can effectively transfect the R-BMMSC without influences on its biological features.
Adenoviridae ; genetics ; Adipogenesis ; Animals ; Bone Marrow Cells ; cytology ; Cell Differentiation ; Cells, Cultured ; Genetic Vectors ; Macaca mulatta ; Mesenchymal Stromal Cells ; cytology ; Osteoblasts ; cytology ; Superoxide Dismutase ; genetics ; Transfection

Objective Methylglyoxal can cause the injury of human proximal tubular epithelial cell line(HK-2 cells),but the exact mechanism is still unclear. The present study aimed to explore the influence of oxidative stress and the expression of NLRP3 inflammasome in HK-2 cells induced by methylglyoxal. Methods HK-2 cells at logarithmic phase were divided into six groups:control group and 100,200,400,800,1600 μmol/L methylglyoxal groups (cells were cultured in 100,200,400,800,1600 μmol/L methylg-lyoxal concentration for 24 h). Superoxide dismutase(SOD)levels were assayed by thibabituric acid method. Release of lactate dehydro-genase(LDH)activity was detected by assay kit.ROS production was measured by DCFH-DA staining. The expression levels of NLRP3,caspase-1,IL-1β and NF-κB were evaluated by western blot. Results Compared with control group,different methylglyoxal concen-trations could enhance ROS level and LDH activity in HK-2 cells(P<0.05)and reduce SOD level significantly(P<0.05). The results of western blot showed the protein levels of NLRP3,caspase-1,IL-1β and NF-κB were significant up-regulated after the addition of methylglyoxal(P<0.05). Conclusion Methylglyoxal may induce the injury of HK-2 cells by oxidant stress and activating of NLRP3 inflammasome signaling.

Objective To investigate the mechanism of treatment of granulocyte colony-stimulating factor(rhG-CSF),recombinant human interleukin-11(rhIL-11)and recombinant human interleukin-2 (rhIL-2)on hematopoietic injuries induced by 4.5 Gy60 Coγ-ray irradiation in beagles,and to provide experimental evidence for the clinical treatment of extremely severe myeloid acute radiation sickness (ARS).Methods Sixteen beagle dogs were given 4.5 Gy60 Co γ-ray total body irradiation(TBI),then randomly assigned into irradiation control group,supportive care group or cytokines+supportive care (abbreviated as cytokines)group.In addition to supportive care,rhG-CSF,rhlL-11 and rhIL-2 were administered subcutaneously to treat dogs in cytokines group.The percentage of CD34+cells,cell cycle and apoptosis of nucleated cells in peripheral blood were examined by Flow cytometry.Results After 4.5 Gy 60 Co γ-ray irradiation,the CD34+cells in peripheral blood declined obviously(61.3%and 52.1% of baseline for irradiation control and supportive care group separately).The cell proportion of nucleated cells in Go/G1 phase was increased notably(99.27% and 99.49% respectively).The rate of apoptosis(26.93% and 21.29% separately)and necrosis(3.27% and 4.14%,respectively)of nucleated cells were elevated significantly when compared with values before irradiation(P<0.05) 1 d post irradiation.When beagles were treated with cytokines and supportive care,the CD34+cells in peripheral blood were markedly increased(135.6% of baseline).The effect of G0/G1 phase blockage of nucleated cells became more serious(99.71%).The rate of apoptosis(5.66%)and necrosis(1.60%)of nucleated cells were significantly lower than that of irradiation control and supportive care groups 1 d after exposure.Conclusions Cytokines maybe mobilize CD34+cells in bone marrow to peripheral blood,indce cell cycle block at G0/G1 phase and reduce apoptosis,and eventually cure hematopoieticinjuries induced by irradiation.

Objectivc To observe the therapeutic effects of combined cytokines on hematopoietic injuries induced by 4.5 Gy60 Co γ-rays irradiation in beagles,and to provide experimental evidences for the clinical treatment of extremely severe myeloid acute radiation sickness(ARS).Methods 16 beagles were given 4.5 Gy60 Co γ-rays total body irradiation,and then randomly assigned into irradiation control group,supportive care group and cytokines group.In addition to supportive care,recombinant human granulocyte colony-stimulating factor (rhG-CSF),recombinant human interleukin-11(rhIL-11)and recombinant human interleukin-2(rhIL-2)were administered subcutaneouly to dogs in cytokines group.Peripheral blood hemogram was examined once every two days.Bone marrow and peripheral blood were collected to proceed colony cultivation 4 d pre-irradiation and 1 and 45 d post-irradiation.Conventional histopathological sections of sternum were prepared to observe the histomorphology changes. Results After irradiation,the population of all kinds of cells in peripheral blood declined sharply.WBC nadir Was elevated(1.04×109/L,but 0.28×109/L and 0.68×109/L for the irradiation control group and the supportive care group separately),the duration of thrombocytopenia was shortened (24 days,but 33 days for the supportive care groug) and red blood cell counts were maintained in the range of normal values after cytokincs treatment in combination.The colony forming efficiency of haemopoietic stem cells(HSCs)in bone marrow and peripheral blood decreased obviously 1 d post irradiation,but recovered to the level of that before irradiation 45 d post irradiation after supportive care and cytokines treatment.Hematopoietic cells disappeared in bone marrow of animals in irradiation control group,but hematopoietic functions were recovered after cytokines were administrated.Conclusions RhG-CSF.rhIL-11 and rhIL-2 used in combination could elevate WBC nadir,accelerate the recovery of leukocytes,platelets and red blood cells and promote the proliferation,differentiation and maturity of HSPCs left in the body after 4.5 Gy γ-rays total body irradiation,eventually restore the hematopoietic function.Hence,combination of rhG-CSF,rhIL-11 and rhIL-2 could serve as better therapeutic strategy to treat extremely severe myeloid ARS.

Objective To explore the mechanisms of cytokines on acute radiation disease in irradiated beagles.Methods The sera of beagles irradiated with 4.5 Gy γ-rays with cytokines treatment was collected at different time points post irradiation.The two-dimensional gel electrophoresis(2-DE)was used to isolate and compare the differentially expressed proteins in sera.HD-MS was used to analyze the differentially expressed proteins with significance,and the amino acid sequences should be determined. Results High resolution 2-DE gel map was obtained.There were six differentially expressed proteins in sera of irradiated beagles at different time points.Four protein spots were successfully identified by MS.A significant spot was identified as serum amyloid A(SAA)by HD-MS,with relative molecular mass of 13 077 and isoelectfie point of 6.26.Expression of SAA was not found 1 d pre-irradiation and 36 d postirradiation,but increased slightly 1 d(0.2166)and significantly 14 d post-irradiation(0.4577). Conclusions The expression of serum amyloid A was consistent with the process of acute radiation injury,which might indicate the turnover of the disease.

Objective To evaluate the effects of combined administration of recombinant human interleukin-11(rhIL-11),recombinant human G-CSF(rhG-CSF)and recombinant human interleukin-2 (rhIL-2)on acute radiation sickness(ARS)beagles.Methods Sixteen beagle were irradiated with 4.5 Gy60 Co γ-rays to establish ARS models,and were divided into irradiation control group,supportive care group and combined cytokines treatment group.After irradiation irradiation control group was given no treatment,the dogs in supportive care group received purely symptomatic treatment,while combined cytokines treatment group received rhIL-11 50μg/(kg·d)and rbG-CSF 10μg/(kg·d)subcutaneously(0-14 d)and rhIL-2 1×1 06 U/d(29-43 d)besides symptomatic treatment.Manifestation and characteristics of ARS beagles were observed,and the survival time were recorded.At last,post-mortem examination and histological examination were performed.Results All animals underwent nausea,diarrhea and fever.After irradiation,all animals in irradiation control group died in two weeks,and the mean survival time was 12.7 d,while only one died at 33 d in supportive care group.All dogs in combined cytokine group survived at 45 day after exposure,and their haematopoiesis and gastrointestinal tract were recovered.Conclusions Combination of rhIL-11 + rhG-CSF + rhIL-2 treatment could be significantly effective on ARS beagles irradiated by 4.5 Gy60 Co γ-rays,which could accelerate injured haemotopoiesis and intestinal tract recovery,increase the survival rate and improve the life quality of animals.

OBJECTIVETo investigate the histological criteria of breast cancer response to neoadjuvant therapy.

METHODSOne hundred and fifty-four cases of breast cancer receiving neoadjuvant therapy were collected from June, 2005 to June, 2007 and the clinical data were analyzed. All patients were operated on within 4 weeks after neoadjuvant therapy. All specimens were assessed by the standard method of Miller and Payne (MP) grading system. The response to neoadjuvant therapy were assessed by two pathologists independently, using MP grading system and common grading system separately.

RESULTSThe response rate using the MP grading system were grade 1 in 12 cases (7.8%), grade 2 in 33 cases (21.4%), grade 3 in 64 cases (41.6%), grade 4 in 31 cases (20.1%) and grade 5 in 14 cases (9.1%). Using the common grading system, the response were mild in 51 cases (33.1%), moderate in 71 cases (46.1%) and severe in 32 cases (20.8%). MP grading system may be related to common grading system (chi2 = 186.660, P < 0.01). Follow up information were available in 147 cases, with 14 cases showing recurrence, metastasis or death from the disease. The MP grading system may be related to the outcome (chi2 = 11.612, P = 0.020), but not the common grading system (chi2 = 0.881, P = 0.644).

CONCLUSIONMP grading system may be one of the prognostic factors in the neoadjuvant therapy of breast cancer.

Biopsy, Needle ; Breast ; pathology ; Breast Neoplasms ; drug therapy ; pathology ; surgery ; Carcinoma, Ductal, Breast ; drug therapy ; pathology ; surgery ; Female ; Follow-Up Studies ; Humans ; Mastectomy, Modified Radical ; Mastectomy, Radical ; Neoadjuvant Therapy ; Neoplasm Recurrence, Local ; Preoperative Period

OBJECTIVEto investigate the pathologic basis of the difference between clinical response and pathologic response of breast carcinoma after neoadjuvant chemotherapy.

METHODStwo hundred and nine cases of breast cancer with neoadjuvant therapy were analyzed and clinical data were collected from June, 2005 to December, 2007. All patients had core needle biopsy taken before neoadjuvant chemotherapy and were operated within 4 weeks after neoadjuvant chemotherapy. Clinical examination, X-ray of breast and/or B ultrasonography of primary breast focus were taken before and after neoadjuvant chemotherapy. Clinical responses of breast primary focus were evaluated according to RECIST (response evaluation criteria in solid tumors) version 1.1.Pathologic responses of breast primary focus were evaluated according to Miller and Payne (MP) grading system. SPSS 15.0 software was used to statistical analysis.

RESULTS(1) Clinical responses basing on clinical examination showed complete response, partial response, stable disease and progressive response, in 33, 124, 41 and 11 cases respectively. (2) Eighty-seven cases had X-ray of breast taken before and after neoadjuvant chemotherapy. Clinical response basing on X-ray, showed complete response, partial response and stable disease in 8, 42 and 37 cases respectively. (3) Pathologic responses of breast primary focus were as MP1 (14 cases), MP2 (35 cases), MP3 (106 cases), MP4 (36 cases) and MP5 (18 cases). (4) The clinical response basing on clinical examination were related to the pathologic response (χ(2) = 33.668, P = 0.001); and the clinical response basing on X-ray of breast were also related to the pathologic response (χ(2) = 22.404, P = 0.004). (5) The pathologic basis of the difference between the pathologic response and the clinical response basing on X-ray of breast were: embolism of carcinoma, mucinous carcinoma, intraductal carcinoma with ossifying-type calcification, nodular fibrosis and others.

CONCLUSIONSthe clinical response may be related to the pathologic response. The difference between the two may be caused by pathologic changes. Some benign and malignant pathologic changes may contribute to the under-estimation of clinical response over pathologic response; whereas embolism of carcinoma may contribute to the over-estimation of clinical response over pathologic response.

Adenocarcinoma, Mucinous ; diagnostic imaging ; drug therapy ; pathology ; Adult ; Aged ; Breast Neoplasms ; diagnostic imaging ; drug therapy ; pathology ; Carcinoma, Ductal, Breast ; diagnostic imaging ; drug therapy ; pathology ; Carcinoma, Intraductal, Noninfiltrating ; diagnostic imaging ; drug therapy ; pathology ; Carcinoma, Lobular ; diagnostic imaging ; drug therapy ; pathology ; Disease Progression ; Female ; Humans ; Middle Aged ; Neoadjuvant Therapy ; Radiography ; Remission Induction