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.
Dysregulation and activation of immune processes are important in age-related macular degeneration (AMD) pathogenesis. The single nucleotide polymorphism of complement factor H is widely recognized as a risk factor to AMD. Over-activation of nod-like receptor3 and polymorphism of Toll-Like Receptor 3 also associated with AMD. Except for innate immune processes, adaptive immunity also play a critical role in AMD, a growing body of evidence supports that auto-antibodies and T cells are related with AMD. Additionally A2E and lipid oxidation byproducts might also have a role in AMD pathogenesis.
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）
Age-related macular degeneration (AMD) is an age-related degenerative disease with complex pathogenesis, whose initial lesion is accompanied with immune inflammatory response. Amyloid beta (Aβ), a small-molecule protein generated by the hydrolysis of amyloid precursor protein, as the main component, is involved in the formation of drusen, which serves as the early characteristic of AMD. In the local inflammatory response of AMD, Aβ is an important pathological deposit, promoting the proliferation and differentiation of macrophages as well as changing their morphology to accelerate the progression of AMD. In addition, Aβ can also regulate immune molecules and the complement system by activating inflammatory pathways, thus mediating chronic retinal inflammation and promoting the course of AMD. However, since AMD is not caused by inflammation alone, only the immunosuppression may not be effective in inhibiting the course of AMD, and thus the future development is to rebalance the disordered immune system in AMD patients eyes.
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.
Sepsis-associated organ dysfunction arises from uncontrolled inflammation and immune dysregulation, causing microcirculatory impairment and multi-organ failure. Stellate ganglion block (SGB) may confer organ protection by regulating the sympathetic nervous system and hypothalamic-pituitary-adrenal axis to suppress excessive inflammation and oxidative stress. Available evidence, mainly from experimental and small clinical studies, suggests potential benefits of SGB in sepsis-induced acute lung injury, ventricular arrhythmias, and limb ischemia, which require confirmation in multicenter randomized controlled trials. This review outlines the mechanisms and clinical advances of SGB in sepsis-related organ dysfunction, providing a theoretical basis for its application in critical care.
ObjectiveTo investigate the effects of three-dimensional (3D) printed Ti6Al4V-4Cu alloy on inflammation and osteogenic gene expression in mouse bone marrow mesenchymal stem cells (BMSCs) and mouse mononuclear macrophage line RAW264.7.MethodsTi6Al4V and Ti6Al4V-4Cu alloys were prepared by selective laser melting, and the extracts of the two materials were prepared according to the biological evaluation standard of medical devices. The effects of two kinds of extracts on the proliferation of mouse BMSCs and mouse RAW264.7 cells were detected by cell counting kit 8 method. After co-cultured with mouse BMSCs for 3 days, the expression of osteogenesis- related genes [collagen type Ⅰ (Col-Ⅰ), alkaline phosphatase (ALP), Runx family transcription factor 2 (Runx-2), osteoprotegerin (OPG), and osteopontin (OPN)] were detected by real-time fluorescence quantitative PCR. After co-cultured with mouse RAW264.7 cells for 1 day, the expressions of inflammation-related genes [interleukin 4 (IL-4) and nitric oxide synthase 2 (iNOS)] were detected by real-time fluorescence quantitative PCR, and the supernatants of the two groups were collected to detect the secretion of vascular endothelial growth factor a (VEGF-a) and bone morphogenetic protein 2 (BMP-2) by ELISA. The osteogenic conditioned medium were prepared with the supernatants of the two groups and co-cultured with BMSCs for 3 days. The expressions of osteogenesis-related genes (Col-Ⅰ, ALP, Runx-2, OPG, and OPN) were detected by real-time fluorescence quantitative PCR.ResultsCompared with Ti6Al4V alloy extract, Ti6Al4V-4Cu alloy extract had no obvious effect on the proliferation of BMSCs and RAW264.7 cells, but it could promote the expression of OPG mRNA in BMSCs, reduce the expression of iNOS mRNA in RAW264.7 cells, and promote the expression of IL-4 mRNA. It could also promote the secretions of VEGF-a and BMP-2 in RAW264.7 cells. Ti6Al4V-4Cu osteogenic conditioned medium could promote the expressions of Col-Ⅰ, ALP, Runx-2, OPG, and OPN mRNAs in BMSCs. The differences were all significant (P<0.05).Conclusion3D printed Ti6Al4V-4Cu alloy can promote RAW264.7 cells to secret VEGF-a and BMP-2 by releasing copper ions, thus promoting osteogenesis through bone immune regulation, which lays a theoretical foundation for the application of metal prosthesis.
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.
Sepsis is a worldwide problem. Although there are many related researchs and animal experiments about sepsis, the mortality of sepsis is still high. In the early stage of sepsis, after the pathogenic bacteria invade the body, the immune response produced by the body promotes the synthesis and secretion of a series of cytokines. Among them, there are proinflammatory cytokines that promote inflammatory response and anti-inflammatory cytokines that inhibit inflammatory response. These cytokines interact with each other and maintain a dynamic balance in complex cell grid. This is to restore the steady state of the body after resisting and eliminating the invaders.Anti-inflammatory cytokines play an important role in it. They act on specific immune cells or immune regulatory receptors. Anti-inflammatory cytokines limit persistent or excessive inflammatory responses after killing invaders, and reduce or block pro-inflammatory cytokine activities. These anti-inflammatory cytokines also can heal body to restore the normal immune physiological level of the organism. This article will review the related research of anti-inflammatory cytokines in sepsis.
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.