Regulatory B cells (Bregs) are a subset of B cells with immunomodulatory effects. The study of Bregs began with a variety of animal models of immune diseases. Studies in patients with autoimmune diseases have further clarified that Bregs are a group of immune cells that secrete inhibitory cytokines such as interleukin-10. Abnormal functions and numbers of Bregs have been found in a variety of autoimmune diseases. The study of the negative immune regulatory network involving Bregs is expected to provide new therapeutic ideas for diseases such as immune diseases, cancer, infection and inflammation. Starting from the discovery and immune regulation mechanism of Bregs, this paper focuses on its regulatory mechanism and clinical research value in the occurrence and development of autoimmune diseases, tumors, infectious diseases and inflammation.
The application of gene therapy in ocular diseases is gradually expanding from mono-gene inherited diseases to multigene, multifactorial, common and chronic diseases. This emerging therapeutic approach is still in the early exploratory stage of treating diseases, and the expected benefits and risks remain highly uncertain. In the delivery process of gene therapy drugs, viral vector is currently one of the most mature and widely used vectors. The occurrence of vector-associated immunity will affect the short-term and long-term effects of gene therapy, and even cause permanent and serious damage to visual function. Therefore, gene therapy vector-associated immunity is the focus and challenge for the safety and long-term efficacy of gene therapy. During the perioperative and follow-up of gene therapy, attention should be paid to the monitoring of vector-associated immune inflammation, and appropriate measures should be taken to deal with the corresponding immune response, so as to achieve the best visual benefits for patients.
Objective To investigate the relevance and changes of mucosal immunity in asthma rats’lung, nose and intestine. Methods Twenty Wistar rats were randomly divided into a normal group and an asthma group. Asthma rat model was established by sensitization and challenge with ovalbumin. CD4 + ,CD8 + , eotaxin protein and its mRNA in rats’lung tissues, rhinal and intestinal mucosa were measured by immunohistochemical methods and situ hybridization. The content of sIgA in bronchoalveolar lavage fluid ( BALF) , nasopharyngeal washings and intestinal mucus supernatant were detected by enzyme-linked immunosorbent assay. Results Compared with the normal group, the levels of CD4 + , CD8 + in rats’lung tissues, rhinal and intestinal mucosa, the expression of eotaxin protein and mRNA in rats’lung tissues, the content of sIgA in nasopharyngeal washing, and the expression of eotaxin protein in intestinal mucosa were significantly higher in the asthma group( P lt; 0. 05) . There were no significant differences of other indices between the two groups. In the normal group, the eotaxin protein expression had a negative correlationbetween lung tissue and rhinal mucosa( r = - 0. 572, P = 0. 008) , and a positive correlation between intestinal and rhinal mucosa( r=0. 638, P =0. 002) . The eotaxin mRNA expression had a positive correlation between lung tissue and rhinal mucosa( r= 0. 502, P = 0. 024) , and a positive correlation between intestinaland rhinal mucosa( r=0. 594, P =0. 006) . In the asthma group, such a correlation was not found except the eotaxin protein expression which had a negative correlation between lung tissue and intestinal mucosa( r =- 0. 448, P = 0. 048) . Conclusions Mucosal immunity in lung, nose and intestine remains a dynamic balance. The balance of mucosal immunity is destroyed in asthma.
Objective To investigate the expression and significance of Fork head /winged helix protein 3 (Foxp3) , retinoic acid-related orphan receptorγt (RORγt) , and interleukin-17 (IL-17) in Guinea pigs with emphysema. Methods Smoking and active immunization with elastin were separately used in guinea pigs to establish emphysema model. Then the destruction of lung tissue was assayed by measurement of the average radius of alveolar. The expressions of Foxp3 , RORγt, and IL-17 in lung tissue of the guinea pigs were detected by immunohistochemical technique. The results were compared with the normal control group by the analysis of variance or kruskal-Wallis test. Spearman rank correlation was used to analyze the correlation between the ratio of Foxp3/RORγt and IL-17, also the correlation between Foxp3/RORγt and the average radius of alveolar. Results In the smoking group and the active immunization group, the average radius of alveolar were significantly longer than the control group (Plt;0.05) . And the expression of Foxp3/RORγt was significantly unbalanced, with the number of Foxp3-positive cells decreased and RORγt-positive cells increased (Plt;0.05) . Meanwhile the level of IL-17 was significantly increased compared with the control group ( Plt;0.05) . The difference between the smoking group and the active immunization group was not significant (Pgt;0.05) . The ratio of Foxp3/RORγt was negatively correlated with the level of IL-17 and the average radius of alveolar. Conclusions Active immunization with elastin can induce emphysema in guinea pigs. The Foxp3/RORγt expression was unbalanced in lung tissue of guinea pigs with emphysema.This imbalance may be an important mechanism attributed to the disordered expression of CD4+ Treg cells and Th17 cells, which may be involved in autoimmune regulation and development of chronic obstructive pulmonary disease.
Objective To investigate the relationship between blood CD4 + CD25 + regulatory T cells ( Treg cells) and cell immunity in patients with sepsis and its prognostic value.Methods 27 patients with sepsis admitted during August 2007 and August 2008 in ICU were enrolled, while 40 healthy volunteers served as control. According to the clinical outcome after 28 days’ treatment, the sepsis patients were assigned to a death group( n=8) and a survival group ( n =19) . Blood Treg% and CD4 /CD8 were detected by flow cytometry and total AgNOR area/nucleus area per cell ( IS%) was measured by silver nitrate staining and image processing. Results The Treg% in the patients with sepsis was significant higher than that in the normal control [ ( 5. 61 ±1. 60) % vs. ( 0. 78 ±0. 23) % , P lt; 0. 01 ] , while the level of CD4 /CD8 and IS% were significant lower[ CD4 /CD8: ( 1. 09 ±0. 30) vs. ( 1. 71 ±0. 36) , IS% : ( 5. 19 ±1. 07) % vs. ( 6. 76 ±0. 92) % , both P lt; 0. 01] . Significant correlations were found between Treg% and CD4 /CD8( r= - 0. 484, P lt;0. 01) , and between Treg% and IS% ( r = - 0. 588, P lt;0. 01) . Compared with the survival group, Treg% was significant higher [ ( 7. 09 ±1. 17) % vs. ( 5. 00 ±1. 33) % , P lt; 0. 01] , and CD4 /CD8 and IS% were significant lower[ CD4 /CD8: ( 0. 87 ±0. 22) vs. ( 1. 18 ±0. 29) , IS% : ( 3. 97 ±0. 42) % vs. ( 5. 71 ±0. 81) % , both P lt; 0. 01] in the death group. Conlusion Blood Treg% level can reflect the cell immune state of patients with sepsis and is of clinical value to assess the prognosis.
Objective To investigate the effects of ulinastatin on Treg/Th17 and immune status in patients with severe sepsis.Methods A total of 80 patients with severe sepsis, who were hospitalized in ICU during October 2011 to July 2012, were randomly divided into a routine group and a ulinastatin group. The patients in the ulinastatin group were intravenously administered 30mg ulinastatin three times per day for 5 days in addition to routine bundle treatment. The expression of Treg, Th17 and HLA-DR were detected on the first day in ICU and 5 days after treatment. 20 healthy individuals served as controls. Results Compared with the control group, the severe sepsis group had overexpression of Treg and Th17 ( P lt;0. 01) , higher ratio of Treg/Th17( P lt;0. 01) , and decreased HLA-DR expression of CD14 monocyte ( P lt; 0. 01) . In the severe sepsis patients, ulinastatin injection reduced the abnormal expression of Treg and Th17 ( P lt; 0. 01) , decreased the ratio of Treg/Th17( P lt; 0. 01) , and improved the expression of HLA-DR ( P lt; 0. 01) more effectively compared with the routine treatment. Ulinastatin also lowered 28-day mortality of the patients with sepsis, but the difference between the ulinastatin group and the routine group was not significant. Conclusions In severe sepsis patients, there were abnormal overexpression of Treg and Th17, imbalance of Treg/Th17, and underexpression of HLA-DR which imply an immune suppression. Ulinastatin can decrease the expression of Treg and Th17, inverses the ratio of Treg/Th17, and improve the expression of HLA-DR, so as to improve the prognosis of severe sepsis patients.
Wireless power transfer (WPT) is a new power transmission way, which can be widely used in electric vehicles and other fields. Its electromagnetic environment must be analyzed to ensure safe application. A low-power wireless power transfer system experimental platform was built, with 25 W receiving power and 47 kHz resonant frequency, which was used to carry out animal experiments. Treatment mice were exposed to environment of wireless power transfer system for 5 h a day and 6 days as one cycle. At the end of every cycle, learning memory behavior of mice were detected in T-shaped maze. The exposure experiment lasted for 12 weeks. Finally, immune parameters, sex hormones and part of organ physiological structure were detected. The results are as follows: as exposure time increased, memory behavior of mice did not change obviously with no statistical difference in sex hormone either (P > 0.05), the concentration of immune factors including tumor necrosis factor-α (TNF-α), interleukin 6 (IL-6) and interleukin-1 beta (IL-1β) significantly increased (P < 0.05), and the structure of some organs showed some changes. The experimental results show that the environment of the wireless power transfer system has no effect on the memory behavior of mice, and has some effect on physiological properties of mice.
ObjectiveIn order to provide a data base for fund project applicants and funding priorities, we would summarize the basic situation and key points of basic research in liver transplantation by analyzing the projects funded by the Natural Science Foundation of China (NSFC) in the field of liver transplantation.MethodsThrough the big data knowledge management and service platform of NSFC, internet-based science information system, and shared service network of NSFC, we searched the funding project information in the liver transplantation relevant field from 2010 to 2019, then analyzed the effectiveness of the Young Scientists Fund of NSFC in promoting young researchers and the research focus and development direction of funding projects.ResultsIn the latest 10 years, NSFC persistently and stably funded the basic research in the field of liver transplantation, with the total number of funding projects was 387, and the funding budget was 198.215 million yuan. The main types of funding projects were the General Program and the Youth Science Fund. There were 210 General Program project (54.3%) with an amount of 113.14 million yuan (57.1%), 127 Young Scientists Fund (32.8%) with an amount of 27.9 million yuan (14.1%), and 22 Fund for Less Developed Regions (5.7%) with an amount of 9.03 million yuan (4.6%). Sun Yat-sen University and Zhejiang University were far ahead of other supporting institutions in both the total number of projects undertaken and the amount of funds granted. The youth/surface ratio reached as high as 72.2% (13/18). The conversion rate of Young Scientists Fund to higher-level projects reached about 50%, which was significantly higher than the overall level of 24.7% (21/85) in the field of liver transplantation. The funding projects were mainly distributed in application code H0318 (liver regeneration, liver protection, liver failure, and artificial liver, 58, 15.0%), H0321 (organ transplantation of digestive system, 169, 43.7%), and H1006 (organ transplantation and transplantation immunity, 50, 12.9%). The main research fields were transplantation immunity and liver injury and liver protection. At the same time, projects such as graft function and complications of liver transplantation were also funded. There were few studies on the immune status of long-term survival in patients after liver transplantation and the mechanism on prevention of immunosuppressant-related diseases.ConclusionsThe NSFC has a great leading effect on the discipline development and talent cultivation of liver transplantation. However, there are still some problems in the discipline layout, such as the lack of attention to the mechanism of long-term graft function and chronic immune rejection.
ObjectiveTo study the effect of bacillus calmette-guerin(BCG) polysaccharides nucleic acid on humoral immunity, interleukin(IL)-8 and tumor necrosis factor(TNF)-αin patients with chronic obstructive pulmonary disease (COPD), and to provide theoretical basis for evaluation of its clinical effectiveness. MethodsThirty hospitalized elderly patients with AECOPD treated from March 2012 to February 2013 and 60 patients with stable COPD treated at the same time were randomly selected as the study subjects. At the same time, 60 healthy people from our physical examination center were also enrolled and divided into two groups:the elderly healthy group (n=30) and nonelderly healthy group (n=30). IL-8, TNF-α, IgA, IgG and IgM levels were determined. The stable COPD group was randomly divided into two groups:group A (n=30) and group B (n=30). Group A received only routine therapy; group B received both routine therapy and intramuscular injection of BCG polysaccharide nucleic acid (0.35 mg/day, three times a week). IL-8, TNF-α, IgA, IgG and IgM levels in peripheral blood were investigated before treatment and one month later. ResultsThere were no statistically significant differences in IL-8 and TNF-αlevels in peripheral blood between elderly healthy group and nonelderly healthy group (P > 0.05), but the IgA, IgG and IgM levels were lower in the nonelderly healthy group than in the elderly healthy group (P < 0.05). Compared with the elderly healthy grouping, IgG and IgM levels were significantly lower in AECOPD group and stable COPD group (P < 0.05), but IL-8 and TNF-αlevels were significantly higher (P > 0.05). There were statistically significant differences in TNF-α, IgA, IgG and IgM levels between group B before and after treatment (P > 0.05). ConclusionsHuman's humoral immunity decreases with age. Elderly COPD patients are at high risks of abnormal immunologic function, particularly in the acute exacerbation period. The BCG polysaccharides nucleic acid can strength patients' humoral immunity. The levels of inflammatory cytokines can be reduced using BCG polysaccharides nucleic acid.
OBJECTIVE L-arginine is a semiessential dibasic amino acid for humans and animals. This paper aims to investigate the therapeutic effect of L-arginine supplementation on partial-thickness burned patients. METHODS A randomized controlled clinical trial was designed to evaluate the cellular immune function (T cell count, ratio of CD4/CD8, natural killer cell activity and IL-2 level) and protein metabolism (transferrin, prealbium and nitrogen balance) of patients in the experimental group which daily given 15 g arginine and the control group which daily given 25 g glycine. RESULTS The natural killer cell activity and IL-2 production in the experimental group were higher than that of the control group. The suppression of transferrin and prealbium was alleviated and the nitrogen balance was improved in the experimental group. CONCLUSION It suggests that exogenous arginine supplementation is beneficial for recovery of cellular immunity function and protein anabolism in partial-thickness burned patients.