ObjectiveTo understand the role of complement system in the immune mechanism of hepatocellular carcinoma (HCC) and its potential therapy value. MethodThe national and international literature relavant researches of complement system in the HCC was reviewed. ResultsBased on HCC as an immunogenic cancer and the complement system as a part of the innate immune system, it had potential application value in immunotherapy. Eight complement components (complement intrinsic components C1q, C3, and mannose binding lectin, soluble regulatory proteins complement factor H and C4b, and membrane regulatory proteins CD46 and CD59, as well as complement receptor C5aR1) were closely associated with HCC. The activation of the complement system could participate in the occurrence and development of HCC through various mechanisms. The complement inhibitor, it could regulate the activity of complement related activation pathways, enhance anti-tumor ability, and provide a potential new strategy for immunotherapy of HCC. ConclusionsAt present, only a few complement components have been found in HCC research. Although it has been found that multiple complement components play a role in regulating the immune mechanism of HCC, there is still no definite or recognized theoretical basis. In the future, further exploration of the protective or pathogenic mechanisms of complement components in HCC immunity is needed to objectively evaluate the risks and benefits of complement related inhibitor therapy and in combination with other anti-tumor immune therapies.
【摘要】 目的 探讨同种异基因骨髓间充质干细胞（bone mesenchamal stem cells，BMSC）静脉输注对大鼠到小鼠胰岛移植物的功能保护和小鼠糖尿病状态改善。 方法 全骨髓培养法获得C57BL/6小鼠BMSC。不连续梯度离心法分离纯化Sprague-Dawley（SD）大鼠胰岛，将300胰岛当量的胰岛单独或与BMSC联合移植入链脲菌素诱导的糖尿病BALB/c小鼠肾包膜下，并通过尾静脉在移植后0、3和5 d注射CM-DiI标记的BMSC 5×105/只，对照组给于磷酸盐缓冲溶液。移植后监测血糖，第9天处死小鼠，取肝、脾、胸腺、淋巴结和移植胰岛的肾脏，冰冻切片，荧光显微镜观察CM-DiI标记细胞的组织分布；免疫荧光法观察移植物中胰岛素和胰高血糖素表达，评价胰岛的功能。 结果 BMSC静脉输注后主要分布于胸腺，其次是脾脏和淋巴结，肾和肝组织中未观察到BMSC；BMSC联合胰岛移植组血糖控制水平优于其他组，且在第7天的口服糖耐量实验优于单纯胰岛移植组。 结论 与胰岛联合移植的BMSC对受者免疫器官和组织有明显的趋向性，且对胰岛细胞的体内存活有一定保护作用。【Abstract】 Objective To research on the protection function by the allogeneic rat bone mesenchymal stem cells (BMSC) on rat to mouse islet transplantation and the improvement of diabetic state in mouse. Methods BMSC were prepared from C57BL/6 mouse bone marrow cells and identified by flow cytometry (FCM). Islets were isolated from Sprague-Dawley (SD) rats with Ficoll discontinuous centrifugation. CM-DiI labeled BMSC at 5×105 for one mouse were intravenously infused into STZ induced diabetic BALB/c mice after rat to mouse islet transplantation at day 0, 3 and 5. Mice with PBS intravenously infused after islet transplantation were set as the negative controls. Blood glucose was monitored every day at the first 3 days after transplantation, and then monitored every two days. At day 9 after transplantation, spleen, thymus, lymph nods, liver and islets recipient kidney were harvested. Ice slices were prepared and CM-DiI labeled cells were investigated with fluorescence microscope. Results CM-DiI-labeled BMSC were mainly distributed in thymus followed by spleen and lymph nodes. In liver and kidney, there was no red fluorescence observed. The blood sugar control for combined BMSC infusion group was superior to other groups, and the control level of islet combined BMSC infusion group were better than single islet transplantation group in OGTT at day 7. Conclusion Allogeneic BMSC can sustain the insulin secretion of islets in vivo and tend to distribute in immune organs or adenoid tissues after infusion.
ObjectiveTo observe the immunological regulation effects of human umbilical cord mesenchymal stem cells (hUCMSC) on glucose-damaged rhesus retinal vascular endothelial cells (RF/6A). MethodshUCMSC and RF/6A were co-culture according to 1:1 ratio in the co-culture system (Transwell plates), hUCMSC cells were added to upper chamber, while the lower chamber containing 25mmol/L glucose and RF/6A. There were three groups including RF/6A blank control group, high glucose treated RF/6A group, and high glucose treated RF/6A with hUCMSC co-culture group. MTT was used to measure the RF/6A cell viability. Western blot was used to to detect protein level of Foxp3. Enzyme-linked immunosorbent assay (ELISA) was used to detect the concentration of interleukin (IL)-17. ResultsMTT assay revealed that at the first day, the survival rate of the three groups had no significant difference (F=0.030, P > 0.05). On day 3 and day 7, the cell viability of the high glucose group was significantly lower than that of the control group (t=36.072, 27.890; P < 0.05), the cell viability of the high glucose treated RF/6A with hUCMSC co-culture group was higher than that of high glucose group (t=36.072, 19.650; P < 0.05).Western blot analysis showed that Foxp3 in high glucose RF/6A group was significantly lower than that in the control group at day 7 after culture (t=7.826, P < 0.05) and high glucose RF/6A with hUCMSC group (t=19.936, P < 0.05). ELISA showed that IL-17 in the high glucose group, high glucose with hUCMSC co-culture group was significantly higher than that of the control group (F=1 267.503, P < 0.05), while IL-17 in the hUCMSC co-culture group was significantly lower than that in high glucose group (t=17.386, P < 0.05). ConclusionhUCMSC can regulate the expression of Foxp3 and IL-17 to increase the proliferative ability of RF/6A, which was suppressed by high glucose.
Using the techniques of monoclonal antibody and radioactive isotope,we found that the total glueosides of paeony (TGP) could almost regain peripheral blood T cell subsets increased or decreased ,supressed cellular immune function and disordered humor immune function of the patients with endogenous uveitis(ElJ) to normal level ,but could not regain those evidently of the patients in control group. The result suggested that TGP might possess double immunomodulatory effect on the patients with EU. （Chin J Ocul Fundus Dis,1994,10:146-148）
ObjectiveThrough the analysis of quantitative and functional changes in peripheral blood CD4+ CD25+FOXP3+ regulatory T cells (Treg) of early HCC patients before and after operation, to discuss the operation effect on the immune function from the aspect of immune suppression. MethodsExtracted the lymphocytes of peripheral blood in HCC patients before and after operation (case group, n=15) and normal people (control group, n=5 cases), and analyze the number and function of Treg by flow cytometer after extracellular (CD4, CD25) and intracellular (FOXP3) staining. ResultsCD4+CD25+ T cells and CD25+FOXP3+ T cells in preoperative peripheral blood in case group were significantly higher than those in control group (12.43±2.57)% vs. (5.56±1.02)%, (5.14±1.4)% vs. (2.18±0.83)%, Plt;0.05). These two cells decreased at 1 week after operation. 〔(10.56±2.13)%, (4.28±1.08)%〕, but there was not statistically significant (Pgt;0.05), they decreased significantly at 2 weeks after operation 〔(7.30±0.89)%, (3.43±0.83)%， Plt;0.05〕. CD8+ T cells and CD4+CD25- T cells in preoperative peripheral blood in case group were significantly lower than those in control group 〔（23.42±1.80）% vs. （29.22±2.26）%， （36.14±1.12）% vs. （43.69±2.78）%， Plt;0.05〕， These two cells decreased significantly at 2 weeks after operation 〔（27.15±1.71）%， （40.30±2.00）%〕. The analysis on the Treg and AFP correlation found that they have low correlation (r=048, Plt;0.05 ). ConclusionsThe hepatectomy can improve the immune response of HCC patient. Treg may have a certain auxiliary significance in the diagnosis, treatment and prognosis of patients with hepatocellular carcinoma.
Objective To explore the role of high endothelial venule (HEV) in chronic obstructive pulmonary disease (COPD) at the single cell level. Methods A total of 219257 cells from the lung tissues of 18 COPD patients and 28 healthy controls in the GEO public database (GSE136831) were used to analyze the relationship between HEV with T lymphocytes, B lymphocytes, and dendritic cells. Results Endothelial cells were extracted using single cell analysis technique, and sorting out venous endothelium, CCL14, IGFBP7, POSTN were used as marker genes for HEV endothelial cells. The ratio of HEV endothelial cells was also identified as up-regulated expression in COPD. The function of the differential genes of HEV endothelial cells was analyzed, suggesting the presence of immune regulation. By trajectory analysis, it was suggested that the differential genes of HEV endothelial cells were enriched for extracellular matrix deposition in late development. Finally, by receptor-ligand pairing, it was suggested that HEV endothelial cells was recruited through a series of ligands with T lymphocytes, B lymphocytes, and dendritic cells. Conclusions HEV endothelial cells are elevated in COPD and have an immunomodulatory role by secreting a series of ligands after recruiting T lymphocytes, B lymphocytes as well as dendritic cells for immune action. HEV may be a potential target for the study of COPD therapy.
Acute pancreatitis (AP) is a gastroenterological emergency with an acute onset and a high mortality rate. The main pathogenesis of AP is pancreatic damage and excessive activation of inflammatory cells induced by multiple factors. Due to anatomical features, the liver is the first extrapancreatic organ to be attacked by high concentrations of trypsin and inflammatory mediators during AP. Hepatic macrophages have been shown to be a major source of AP-related inflammatory factors. Interventions targeting hepatic macrophages may be critical to block liver injury/failure during AP, promote tissue repair, and reduce systemic symptoms. This review summarizes the pathological role of hepatic macrophages in AP and targeted interventions to provide new ideas and approaches to resolve the pathogenesis of AP and alleviate concurrent liver injury.
Since the emergence of novel coronavirus pneumonia in late 2019, it has quickly spread to many countries and regions around the world, causing a significant impact on human beings and society, posing a great threat to the global public health system. Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) was highly infectious, and some complications emerged rapidly in some patients, including acute respiratory distress syndrome, and multiple organ failure. The virus could trigger a series of immune responses, which might lead to excessive immune activation, thereby bringing about the immune system imbalance of the body. Up to now, there was no specific antiviral drug, and we conjectured that immunomodulatory therapy might play an essential part in the treatment of coronavirus disease 2019 (COVID-19) as adjuvant therapy. Therefore, we analyzed the possible mechanism of immune imbalance caused by the new coronavirus, and summarized the immunotherapeutic means of COVID-19 based on the mechanisms, to provide some reference for follow-up research and clinical prevention and treatment of COVID-19.
Objective To review the research progress in the construction strategy and application of bone/cartilage immunomodulating hydrogels. Methods The literature related to bone/cartilage immunomodulating hydrogels at home and abroad in recent years was reviewed and summarized from the immune response mechanism of different immune cells, the construction strategy of immunomodulating hydrogels, and their practical applications. Results According to the immune response mechanism of different immune cells, the biological materials with immunoregulatory effect is designed, which can regulate the immune response of the body and thus promote the regeneration of bone/cartilage tissue. Immunomodulating hydrogels have good biocompatibility, adjustability, and multifunctionality. By regulating the physical and chemical properties of hydrogel and loading factors or cells, the immune system of the body can be purposively regulated, thus forming an immune microenvironment conducive to osteochondral regeneration. ConclusionImmunomodulating hydrogels can promote osteochondral repair by affecting the immunomodulation process of host organs or cells. It has shown a wide application prospect in the repair of osteochondral defects. However, more data support from basic and clinical experiments is needed for this material to further advance its clinical translation process.