The DD98M alloy was prepared by electron beam smelting, and the effect of electron beam smelting parameters on the inclusion removal behavior was studied. The inclusion removal thermodynamics and kinetic mechanisms were analyzed. The results show that the O and N in the DD98M alloy can be reduced by 92.5% and 88.4% when smelted for 30 min with power of 12 kW, and no obvious inclusions are found in the microstructures. Increasing the smelting power or prolonging the smelting time will promote the removal of inclusion effectively. The inclusions are concentrated in the central area of the electron beam under the combined action of buoyancy and Marangoni effect. The inclusions in the near-surface area of the melt can be removed by dissolution, and the inclusion particles floating above the melt level can be decomposed under the action of electron beam bombardment.
In this paper, the high temperature oxidation behavior of superalloys prepared by the electron beam smelting (EBS) and vacuum induction melting (VIM) at 900°C and 1000°C is investigated. Experimental results indicate that EBS alloys show better oxidation resistance and oxide layer integrity. The relationship between the growth rates of Al2O3 and Ta2O5 and the oxygen partial pressure at the oxide/substrate interface is explained by the growth model of n-type semiconductor oxides. Lower oxygen partial pressure at the oxide/substrate interface due to the higher purity of the EBS alloys. This effectively slows down the growth rate of the n-type semiconductor oxides such as Al2O3 and Ta2O5 and thickening rates of the other n-type oxides, which ultimately leads to better oxidation resistance.
Abstract Although accumulating evidence has linked mesenchymal stem cells (MSCs) with tumor growth, the underlying mechanisms are poorly understood. Here, we demonstrated for the first time that human umbilical cord MSCs (hUCMSCs) dramatically increased the growth of lung adenocarcinoma (LUAD) cancer cells in a xenograft tumor model. Then, we observed that hUCMSC-derived extracellular vesicles (hUCMSC-EVs) contribute to the hUCMSC-promoted LUAD cell growth through a direct effect on LUAD cells. Furthermore, we showed that hUCMSC-EV-mediated LUAD growth is associated with increased proliferation and decreased apoptosis in LUAD cells, concomitant with reduced PTEN expression mediated by the hUCMSC-EV-transmitted miR-410. Our findings provide novel insights into the intercellular communications between cancer cells and MSCs through MSC-EV-miRNA and suggest that modification of hUCMSC-EVs might be an attractive therapeutic option for the clinical application of hUCMSC-EVs that would reduce unwanted side effects.
Objective To investigate the effect of portal vein embolization (PVE) on the growth rate of colorectal liver metastases.Methods There were 22 patients who had undergone preoperative PVE and 20 matched controls.Tumnour growth rate was calculated by the change in tumour volume (CT/MRI volumetric assessment) from diagnosis to resection.Resected histological specimens were examined by two histopathologists independently for cell differentiation,percentage of tumour cell necrosis and mitotic rate.Immunochemical staining with proliferation cell nuclear antigen (Ki-67) was carried out using the Ki-67 antibody (MIB-1) monoclonal antibody and quantified using a Glasgow cell-counting graticule.The groups were comparable in demographics,stage of primary disease,volume of liver metastases at presentation and chemotherapy given.Results The tumour growth rate calculated from imaging was more rapid in the PVE group than in controls [control:(0.05 ± 0.25) ml/day,PVE:(0.36 ± 0.68) ml/day,P ＞ O.05].Histologically,no difference in the degree of differentiation,extent of necrosis or apoptosis between the two groups.However,mitotic rate was higher in PVE group than in control group (P ＜ 0.05).Conclusion This study has confirmed that tumour growth rate was increased following PVE,and PVE is related to the differentiation of tumour cells.
Key words:
Portal vein embolisation; Colorectal carcinoma; Liver metastases; Liver resection
Abstract Introduction Rheumatoid arthritis (RA) is a chronic inflammatory disease involving a variety of immune cells, including adaptive T and B cells and innate lymphoid cells (ILCs). Understanding the pathogenic role of these immune cells in RA provides new insights into the intervention and treatment of RA. Methods A total of 86 patients with RA (RA group) and 50 healthy controls (HC) were included in the study. The immune cells of CD4 + , CD19 + B, NK, Th17, Treg, ILCs, and their subsets (i.e., ILC1s, ILC2s, and ILC3s) were characterized in peripheral blood mononuclear cells by flow cytometry. Cytokines (i.e., IFN-γ, IL-4, IL-10, IL-17A, IL-22, and IL-33) in sera were detected using ELISA. The above immune cells and cytokines were analyzed in patients with different disease activity status and positive ( +) or negative ( −) rheumatoid factor (RF)/anti-citrullinated protein antibodies (ACPA). Results Patients with RA had higher percentages of CD4 + T, CD19 + B, Th17, ILC2s, and ILC3s and lower percentages of Treg and ILC1s than HC. Patients with RA had elevated levels of IFN-γ, IL-4, IL-17A, and IL-22 and decreased level of IL-10. Compared with HC, patients with high disease activity had higher percentages of Th17, ILC2s, and ILC3s; lower percentages of ILC1s; and lower level of IL-10. The percentage of Treg cells in remission, low, moderate, and high disease activities decreased, whereas the level of IL-17A increased compared with HC. Furthermore, RF + or ACPA + patients exhibited elevated percentages of CD19 + B, ILC2s, and ILC3s and had decreased percentage of ILC1s and Treg cells than HC. The percentage of Th17 cells increased in RF − /ACPA − and RF + /ACPA + patients. However, the above immune cells between RF or ACPA positive and negative patients were not significantly different. Conclusion Th17, Treg, and ILC subset dysregulations are present in patients with RA but may not be associated with conventionally defined seropositive RF and ACPA. Key Points • Th17, Treg, and ILC subset dysregulations are present in patients with RA but may reflect inflammation rather than specific diseases and stages. • No difference for the distribution of Th17, Treg, and ILC subsets between RF + and RF − patients and between ACPA + and ACPA − patients. The screening spectrum of RF and ACPA serology should be expanded to elucidate the role of immune cells in RA pathogenesis.
Asthma is a prevalent respiratory disease, and its management remains largely unsatisfactory. Mesenchymal stem cells (MSCs) have been demonstrated to be efficacious in reducing airway inflammation in experimental allergic diseases, representing a potential alternative treatment for asthma. Migrasomes are recently identified extracellular vesicles (EVs) generated in migrating cells and facilitate intercellular communication. The objective of this study was to investigate the therapeutic effects of migrasomes obtained from MSC in a model of asthma. Migrasomes produced by human umbilical cord MSCs (hUCMSCs) were isolated by sequential centrifugation. Characterization of hUCMSC-derived migrasomes were carried out by transmission electron microscopy and western blot analysis. The therapeutic effects of migrasomes on airway inflammation in ovalbumin (OVA)-induced asthmatic mice were evaluated by hematoxylin-eosin (HE) and periodic-acid schiff (PAS) staining, and their mechanism were further testified by immunofluorescent staining, real-time PCR and flow cytometry. Here, we showed that inhibition of migrasomes' production dramatically impaired the anti-inflammatory effects of hUCMSCs in OVA animals, as evidenced by a notable increase in both the infiltration of inflammatory cells and the number of epithelial goblet cells. We successfully isolated hUCMSC-migrasomes, which were morphologically intact and positive for the specific migrasomes markers. The administration of hUCMSC-migrasomes was observed to significantly ameliorate the symptoms of airway inflammation and mucus production in asthmatic mice. Additionally, the expression of Th2 cytokines (IL-4, IL-5 and IL-13) were found to be reduced, while the activation of dendritic cells (DCs) was inhibited. HUCMSC-migrasomes could possibly be delivered to lung region after injection, and were able to be taken in by DCs both in vivo and in vitro. Notably, in vitro, migraosmes decreased the capacity of BMDCs to stimulate OVA-specific Th2-cell responses. More importantly, we found that adoptive transfer of hUCMSC-migrasomes-treated BMDCs was sufficient to protect mice from allergic airway inflammation. In addition, we found that hUCMSC-migrasomes inhibited the receptor for advanced glycation end-products (RAGE) signal in OVA-treated BMDCs in vitro and in asthma mice lung in vivo. Our results provided the first evidence that hUCMSC-migrasomes possess anti-inflammatory properties in OVA-induced allergic mice, which may provide a novel "MSC-cell free" therapeutic agent for the management of asthma.
Recent evidence has shown that long noncoding RNAs (lncRNAs) play major roles in tumorigenesis and cancer progression. The cancer genome atlas program (TCGA) database was used to screen colon adenocarcinoma (COAD)-related differentially expressed lncRNAs, which revealed that lncRNA ELFN1-AS1 was highly expressed in COAD. This study aimed to explore the regulatory role of ELFN1-AS1 in COAD and construct a gene delivery system based on extracellular vesicles (EVs). We found that ELFN1-AS1 levels were obviously increased in COAD patients and COAD tumor cells. Knockdown of ELFN1-AS1 expression by siRNA inhibited COAD cell proliferation and migration. Moreover, silencing ELFN1-AS1 significantly reduced the activation of extracellular signal-regulated protein kinase (Erk), up-regulated the protein expression of E-cadherin and down-regulated vimentin. In addition, we treated human umbilical cord mesenchymal stem cells (hUCMSCs) with siRNA-ELFN1-AS1 and found that EVs from siRNA-ELFN1-AS1-treated hUCMSCs could inhibit COAD cell proliferation and migration in vitro. These findings suggested that ELFN1-AS1 could promote the progression of COAD and that hUCMSC-EVs might be an attractive vehicle for the clinical administration of lncRNA-specific siRNAs in patients with COAD.
To assess the influence of glycolytic pathway on the proportion and numbers of regulatory T cells during Schistosoma japonicum infection.A S. japonicum -infected mouse model was established, and C57/BL6 male mice infected with S. japonicum were subjected to intraperitoneal injections of with the glycolytic inhibitor 2-Deoxy-D-glucose (2DG) or PBS for 6 times, and then the cells from spleen or mesenteric lymph nodes (LNs) were isolated and analyzed by flow cytometry (FCM) to detect the percentage of Glut1+CD4+ T cells and Treg cells.The proportions of Glut1+CD4+ T cells in the spleen (43.58%±2.50% vs. 21.15%±0.96%; t = 8.834, P < 0.01) and mesenteric LNs (38.97%±1.97% vs. 28.40%±2.11%; t = 3.662, P < 0.05) were higher in the normal mice than those in the infected mice, and the percentages of Treg cells in the spleen (6.83%±0.21% vs. 13.30%±0.35%; t = 15.65, P < 0.01) and LNs (8.26%±0.15% vs. 14.37%±0.44%; t = 13.14, P < 0.01) were lower in the normal mice than those in the infected mice. In addition, the proportions of Treg cells in the spleen (15.50%±0.76% vs. 13.07%±0.15%; t = 3.130, P < 0.05) and LNs (17.00% ±0.41% vs. 13.83%±0.18%; t = 6.947, P < 0.01) were higher in the infected mice injected intraperitoneally with 2DG than those in the infected mice injected intraperitoneally with PBS.Glycolytic pathway inhibits Treg differentiation in the spleen and mesenteric LNs of S. japonicum-infected mice.[摘要] 目的 探索日本血吸虫感染过程中糖酵解途径对小鼠调节性T (Treg) 细胞数量和功能的影响。方法 建立日 本血吸虫感染小鼠模型, 用糖酵解抑制剂2-Deoxy-D-glucose (2DG) 或PBS对日本血吸虫感染小鼠进行6次腹腔注射后, 分离脾脏细胞和肠系膜淋巴结, 采用流式细胞术 (FCM) 检测分离得到的细胞中Glut1+CD4+ T细胞以及Treg细胞比例。结 果 未感染组小鼠脾脏 (43.58%±2.50% vs. 21.15%±0.96%; t = 8.834, P < 0.01) 和肠系膜淋巴结中Glut1+CD4+ T细胞比例 (38.97%±1.97% vs. 28.40%±2.11%; t = 3.662, P < 0.05) 均显著高于感染日本血吸虫8 周小鼠, 但未感染组小鼠脾脏 (6.83%±0.21% vs. 13.30%±0.35%; t = 15.65, P < 0.01) 和肠系膜淋巴结中Treg细胞比例 (8.26%±0.15% vs. 14.37%±0.44%; t = 13.14, P < 0.01) 均显著低于感染组小鼠。感染小鼠给与2DG腹腔注射后, 脾脏 (15.50%±0.76% vs. 13.07%±0.15%; t = 3.130, P < 0.05) 和肠系膜淋巴结中Treg细胞比例 (17.00%±0.41% vs. 13.83%±0.18%; t = 6.947, P < 0.01) 显著高于给与 PBS注射小鼠。结论 糖酵解途径抑制了日本血吸虫感染小鼠Treg细胞分化。.
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