ABSTRACT
Background Due to the limited availability of established research models, very few studies addressed the health effects and underlying mechanisms following exposure to diesel exhaust during the initiation of pulmonary respiration. It is highly demanded to elucidate such health effects and underlying mechanisms, so as to exert protective measures during the early stages of life. Objective To evaluate the health effects of diesel exhaust very-early-in-life inhalation in hatchling chicken with a novel chicken embryo air cell inhalation exposure model, and to explore the potential roles of aryl hydrocarbon receptor signaling pathways in the observed effects with a specific aryl hydrocarbon receptor inhibitor. Methods Fertilized chicken eggs were assigned into five groups randomly (15 eggs per group): control group, air control group, aryl hydrocarbon receptor inhibitor (PDM2) group, diesel exhaust group, and diesel exhaust + aryl hydrocarbon receptor inhibitor (PDM2) group. Fertilized eggs were incubated with standard procedure. At embryonic day 17 (ED17), aryl hydrocarbon receptor inhibitor was administered to the corresponding animals. During embryonic day 18-19 (ED18-19), chicken embryos were exposed to diesel exhaust via air cell inhalation, then placed back to incubator until hatch. The air control group received clean air infusion during ED18-19, while the control group did not receive any treatment. Within 24 h post-hatch, 26 hatchling chickens were anesthetized with sodium pentobarbital, subjected to electrocardiography, and sacrificed to harvest tissue samples of heart and lung. Cardiopulmonary toxicities were evaluated by histopathology, and potential changes in the protein expression levels of aryl hydrocarbon receptor pathway molecule cytochrome P450, family 1, subfamily A, polypeptide 1 (CYP1A1) and fibrosis-related pathway molecule phosphorylated SMAD family member 2 (pSMAD2) were assessed by Western blotting. The remaining 29 hatchling chickens were reared until two weeks old, and then subjected to identical treatments. Results The inhalation exposure to diesel exhaust at initiation of pulmonary respiration resulted in thickened right ventricular wall (by 220.3% relative to the control group, same hereafter) and elevated heart rate (17.4%) in one-day-old hatchling chickens. Although no remarkable fibrotic lesions were observed at this point, the expression levels of CYP1A1 and phosphorylation levels of SMAD2 in the lung tissues significantly increased (by 81.3% and 71.6%, respectively). Such changes were effectively abolished by the aryl hydrocarbon receptor inhibitor PDM2 pretreatment. In the two-week-old animals, the thickened right ventricular wall (by 339.3%) and elevated heart rate (by 18.9%) persisted, and significant fibrotic lesions were observed in the lung tissue samples under Masson staining. Again, the aryl hydrocarbon receptor inhibitor PDM2 pretreatment effectively abolished such changes. In addition, no statistically significant changes in CYP1A1 expression levels were observed in the two-week-old chicken lung samples, and a remarkable down-regulation of SMAD2 phosphorylation was observed. The aryl hydrocarbon receptor inhibitor PDM2 pretreatment independently decreased the phosphorylation levels of SMAD2 in the two-week-old chicken lung samples. Conclusion Inhalation exposure to diesel exhaust at initiation of pulmonary respiration could result in persistent cardiopulmonary injury in hatchling chickens, and the underlying mechanism might be associated with the regulation of pSMAD2 by the aryl hydrocarbon receptor signaling pathway.
ABSTRACT
Objective:To investigate the dynamic change of Notch1 expression level on the surface of myeloma cells in patients with multiple myeloma (MM) and its clinical significance.Methods:A total of 38 patients with MM in the Fifth Affiliated Hospital of Sun Yat-Sen University from April 2013 to July 2019 were selected. At the same time, 18 patients with mild iron deficiency anemia were selected as controls. Flow cytometry was used to detect Notch1 expression levels on the surface of myeloma cells for MM patients at the first diagnosis (before the treatment), in remission stage (the time of best effect during the treatment) and in the advanced stage (disease progression), and on the surface of normal plasma cells of the control group. The therapeutic efficacy was analyzed, and the expression levels of Notch 1 were compared among the different stages of MM patients and the control group.Results:Among 38 MM patients, 6 cases (15.8%) had strict complete remission (sCR), 14 cases (36.8%) had complete remission (CR), 10 cases (26.3%) had very good partial remission (VGPR), 6 cases (15.8%) had partial remission (PR), 2 cases (5.3%) died after the first course of treatment. Notch 1 detection was performed in 36 patients. The expression rate of Notch1 on the surface of myeloma cells at the first diagnosis, in remission stage, and in the advanced stage of MM patients and on the surface of normal plasma cells of the control group was (13.1±3.9)%, (2.7±1.2)%, (5.4±1.7)% and (2.1±0.3)%; the difference was statistically significant ( F = 151.4, P < 0.01). The expression rate of Notch1 in MM patients at the first diagnosis and in advanced stage was higher than that in remission stage (all P < 0.01), while the expression rate of Notch1 on the surface of myeloma cells in remission stage was higher than that on the surface of normal plasma cells in the control group ( t = 2.219, P = 0.038). Conclusion:The Notch1 signaling pathway may play an important role in the occurrence and development of MM, and Notch1 detection has a certain guiding significance for the monitoring, treatment and prognosis assessment of MM.
ABSTRACT
Objective To explore the relationship between the expression of transcription factor ⅡB-related factor 1 (Brf1) and the prognosis of non-small cell lung cancer (NSCLC).Methods Collected 96 cases of NSCLC Surgical specimens and clinical data of patients from January 2013 to August 2015 in our hospital.First of all,we compared the expression of Brf1 in NSCLC tissues and adjacent lung tissues by Western blot and RT-qPCR.Then,Immunohistochemistry was used to detect the expression of Brf1 in NSCLC tissues,and analysis of the relationship between Brf1 expression level and clinical case characteristics.Survival curves were plotted using the Kaplan-Meier method and Log-rank test and multivariate Coxv regression analysis were performed.Results Western blot and RT-qPCR results showed that the expression of Brf1 in NSCLC tissues was significantly higher than that in adjacent lung tissues (P ＜0.01).The positive expression rate of Brf1 in 96 cases of NSCLC was 72.9％.The Brf1 expression level was higher in the poorly differentiated group than in the moderately-highly differentiated group(Mean Rank 62.33 ＞ 43.89,Z =-2.914,P =0.004),and the lymph node metastasis group was higher than the non-metastasis group(Mean Rank 60.34 ＞ 42.58,Z =-3.055,P =0.002),which was independent of patient gender,age,smoking status,tumor size,TNM stage,and pathological type (P ＞0.05).Single-factor survival analysis by Log-rank test showed that the survival rate of Brf1 positive expression group was lower than that of the negative group (x2 =7.560,P ＜0.01).Multivariate analysis of Cox regression model found that Brf1 positive expression (HR =2.043,95％ CI:1.082-3.860) was an independent observational index that affects the prognosis of patients with NSCLC.Conclusion Brf1 is overexpressed in NSCLC tissues,and Brf1 negative expression has a good clinical prognosis,suggesting that Brf1 may be one of the indicators of malignant degree and prognosis of NSCLC.
ABSTRACT
BACKGROUND:As the high proliferation and low apoptosis of the bone marrow in polycythemia vera patients, hematopoietic stem cels transplanted into NOD/SCID mice can differentiate into erythroid cels, but whether hematopoietic stem cels transplantation could improve the hematopoietic function of aplastic anemia mice is not yet reported. OBJECTIVE:To investigate whether transplantation of bone marrow mononuclear cels with JAK2V617F mutation from polycythemia vera patients can influence hematopoietic reconstruction in aplastic anemia mice. METHODS:Severe aplastic anemia mouse models were established by using recombinant human interferon-γplus busulfan, and then, these mouse models were randomly divided into experimental group (n=10) and control group (n=10). Bone marrow mononuclear cels isolated from polycythemia vera patients with positive JAK2V617F mutation were transplanted into the mice in the experimental group via tail vein at 5 days after drug withdrawal.The same volume of normal saline was administered to the control group. Routine peripheral blood test, morphology of bone marrow cels, bone marrow biopsy, and percentage of CD45+ cels in the peripheral blood and marrow were determined at 14 days after transplantation. RESULTS AND CONCLUSION: At 14 days after transplantation, pancytopenia occurred in the experimental group, bone marrow smears showed scattered lymphocytes and hematopoietic progenitors, and bone marrow biopsy presented that hematopoietic tissues were reduced and a smal amount of granulocyte cels and erythroblasts could be seen, but megakaryocytes were rare. In contrast to the control group, there was no improvement in the hematopoietic function of mice in the experimental group. CD45+ cels were detectable in the peripheral blood and bone marrow in the experimental group, but not in the control group; and a higher percentage of CD45+ cels was measured in the bone marrow than in the peripheral blood of experimental group mice. Experimental findings indicate that bone marrow mononuclear cels from polycythemia vera patients with positive JAK2V617F mutation can be engrafted into aplastic anemia mice, but cannot improve the hematopoietic function of mice.
ABSTRACT
Objective To evaluate the significance of platelet activation and the expression of inter-leukin (IL)-1β in patients with RA. Methods The activation of platelets and the expression of IL-1β in pla-telets in 50 RA patients(22 high-active, 28 mediate/low active ) and 30 normal controls were determined us-ing flow cytometry. Meanwhile, inflammatory indicators such as erythrocyte sedimentation(ESR), C-reactive protein (CRP) and DAS28 were also recorded. T test and correlation analysis were performed. Results The platelet activation in RA group(19.2±4.8) was higher than the control group(9.0±2.9)(t=10.5, P=0.001). The expression of IL-1β in platelets in RA group(41±11) was higher than control group(21±8)(t=9.01, P =0.000) .The platelet activation in high-active RA group(22 ±4) was higher than mediate/low active RA group(17 ±4)(t =3.96,P =0.001). The expression of IL-1β in platelets in high-active RA group(45 ±10) was higher than mediate/low active RA group (38 ±10)(t =2.329,P =0.024). The expression of IL-1β in platelets in RA group was positively correlated with the level of ESR、CRP and DAS28 (r value and P value were 0.576, 0.578, 0.618 and 0.000, 0.000, 0.000 respectively). Conclusion The platelets of patients with RA are activated and may suggest that IL-1β, which may associate with disease activity. Our research suggest that platelet may play a role in the inflammatory process of RA by secreting IL-1β.
ABSTRACT
BACKGROUND:It is important to establish an ideal mouse model of severe aplastic anemia for investigating the mechanism and finding new therapies for aplastic anemia. OBJECTIVE:To establish a severe aplastic anemia mouse model by using recombinant human interferon-γand busulfan. METHODS:Sixty healthy Kunming female mice were randomly divided into two groups:model group (n=50) and control group (n=10). The model group was given recombinant human interferon-γat a dose of 1×104 U/d by intraperitoneal injection and busulfan at a dose of 18 mg/(kg·d) through stomach feeding for 7 days. The same volume of physiological saline was given to control group. Multi-parameters, including general condition, body weight, blood cellcount, morphology and biopsy of bone marrow were analyzed in two groups. RESULTS AND CONCLUSION:At day 7 after treatment, the weight, white blood cellcount, hemoglobin, blood platelet, reticulocyte count in model group were significantly lower than control group (P<0.05). Bone marrow smears and biopsy of model group showed marked reduction of bone marrow proliferation and increases of percentages of non-hematopoietic cellclusters and adipose tissue. The oil drop and fat vacuole were apparently seen in the model group. Severe aplastic anemia mouse model can be established by using recombinant human interferon-γand busulfan successful y, which is economic, stable and easy to operate.
ABSTRACT
Objective To compare the clinical efficacy and safety of two different conditioning regimens in nonmyeloablative autologous peripheral blood stem cell transplantation (NAST) for the treatment of systemic lupus erythematosus (SLE).Methods Different conditioning regimens were used in two groups:cytarabin combined cyclophosphamide in group 1 and ATG combined cyclophosphamide in group 2.Different recovery time of leucocytes,neutrophils and platelets in the two groups were compared.Statistical analysis were carried out by paired t-test.Results The mean time for peripheral leucocytes reaching 1.0×109/L,neutrophils getting up to 0.5×109/L,platelet raising to 100×l09/L and hemoglobin rising to 120 g/L in group 1 were [(7.2±1.3),(8.0±1.5),(10.5±1.4),(22.1±2.3)days] and [(10.4±2.1),(12.0±1.9),(19.3±2.1),(28.1± 2.4)] days in group 2.The difference was statistically significant (P＜0.01).CD4+ cell count and the ratio of CD4+/CD8+ of pre- and pro-NAST was changed.No significant differences were observed in the two groups.Conclusion For the sake of safety and hematopoietic reconstitution,we recommend cytarabin combined cyclophosphamide as the preferred conditioning regimen.
ABSTRACT
Objective To investigate the long-term efficacy of nonmyeloablative autologous peripheral blood stem cell transplantation(NAST) to cure refractory autoimmune disease(AD).MethodLong-term follow up of four cases of AD patients with NAST were summarized.The pretreatment regimen was intravenous injection of cytarabin (200 mg· kg-1· d-1 ) and cyclophosphamide (40 mg· kg-1· d-1).The therapeutic effect was evaluated by the change of symptoms and signs and long term complications.Changes of immune function were detected by flow-cytometry.ResultsFive cases of patients had been successfully engrafted.The average time for peripheral leucocytes count to reach 4.0×109/L was 12 days.It needed 10 days for platelets to return to 100×109/L and 22 days for hemoglobin to 120 g/L.Apparent remission of symptoms and signs was observed after transplantation.Lymphocyte subtypes analysis pre- and post- NAST showed that count of CD4+ and the ratio of CD4 +/CD8 + was returned to normal.One patient gave birth to a healthy baby four years after transplantation.Three female patients returned tonormal life. Conclusions Compared with classical myeloablative stem cell transplantation,NAST has a rapid hematopoietic recovery and good long-term therapeutic effect in AD.The quality of life in AD patients treated with NAST is higher than those treated with myeloablative hematopoietic stem cell transplantation.
ABSTRACT
Objective To study the effctiveness and safety of arsenic trioxide(As2O3)combined with Homoharringtoninum in the chronic myelocytic leukmia-chonic phase(CML-CP).Methods Seven patients were treated with As2O3 10mg per day for 2~3 week and with Homoharringtoninum 3~4mg per day for 1~2.Results All patients were clinic remission,of which there were 4 complete remission who were all initial therapy,and 3 partial remission,2 of who were initial therapy and 1 was resume threapy.4 patients of CR were treated with second strengthen therapy and continued hematologic CR.The main side effects were grade 3 hematologic toxicity and light liver damage,and no significant nausea,emesis,diarrhea or mucositis.Conclusion As2O3 combined with Homoharringtonium in the CML-CP is a safe and effctive regimen.