Objective To investigate the role of alveolar macrophages ( AMs ) in airway inflammation of smoke-induced COPD rat model and its possible regulating mechanism. Methods Twelve Wistar rats were randomly divided into a COPD group and a control group. The rat model of COPD was established with smoke exposure and LPS intrathacheal instillation. Bronchoalveolar lavage fluid ( BALF)was collected for measurement of total and differential cell counts. Then AMs were isolated and identified byimmunofluorescence. Western blot was employed to analyze the cytoplasmic and nuclear NF-κB p65 expression of AMs. The concentrations of TNF-α,macrophage inflammatory protein 2 ( MIP-2) and IL-10 in cell culture supernatantwere assayed by ELISA.Results The scores of bronchitis and mean liner intercepts in the COPD group were significantly higher than those in the control group [ 4. 33 ±1. 16 vs. 1. 33 ±0. 58,P =0. 016; ( 168. 77 ±11. 35) μm vs. ( 93. 61 ±4. 16) μm, P = 0. 000) ] . The total cell count in BALF of the COPD group was significantly higher than that in the control group ( P lt; 0. 05) , and the AMs and neutrophils were predominant [ ( 72. 00 ±2. 22) % and ( 18. 29 ±8. 34) % ] . The cytoplasmic NF-κB p65 expression of AMs in the COPD group was significantly lower , while the nuclear NF-κB p65 expression was significantly higher ( P lt; 0. 05) compared with the control group. The ELISA results showed that the concentrations of TNF-αand MIP-2 in culture supernatant of AMs in the COPD group were significantly higher than those in the control group ( P lt;0. 05) , while the concentration of IL-10 was not significantly different between the two groups ( P gt;0. 05) . Conclusions COPD rat model was established successfully with smoke exposure and LPS intratracheal instillation with a profile of macrophage-based chronic inflammation and increased secretion of TNF-αand MIP-2. The mechanismis closely related to activation of NF-κB.
The hallmark lesions of age-related macular degeneration (AMD) are drusen and basal linear deposit which are lipid substances deposited in Bruch membrane or the compartment on the Bruch membrane. There is a prevailing hypothesis that lipid and its oxidized derivant deposited in retina may have important roles in the pathogenesis of AMD. Lipid oxidation products are toxic, may affect the adjacent cells, induce inflammation, and trigger neovascularization.7-ketocholestoral (7KCh), a naturally occurring oxidized form of cholesterol, had been found to be toxic to retinal cells and able to induce chronic inflammation, which may play a critical role in the development of AMD. However the precise mechanism remains to be elucidated. Thus we will make a brief review of 7KCh and its association with AMD.
ObjectiveTo explore the relationship of the level of inflammation and nutritional status with the occurrence and prognosis of refractory diabetic foot.MethodsA total of 70 patients with refractory diabetic foot between August 2015 and August 2017 were randomly selected as the observation group. Another 70 patients with diabetes mellitus (without foot ulcer) who visited the hospital in the same period were set as the control group. The observation group was subgrouped into the non-amputation group and the amputation group according to the follow-up endpoint events, and into the grade Ⅲ, Ⅳ, and Ⅴ groups according to Wagner classification method. The blood levels of inflammatory markers and nutritional markers between groups were compared.ResultsIn the observation group, vascular cell adhesion molecule-1 (VCAM-1), fibroblast growth factor 2 (FGF2), fibrinogen (FIB), tumor necrosis factor-α (TNF-α), interleukin (IL)-6, IL-18, lipoprotein phospholipase A2 (LP-PLA2), C-reactive protein (CRP) levels were significantly higher than those in the control group, and albumin (ALB), prealbumin (PA), and transferrin (TRF) levels were significantly lower than those in the control group, with statistically significant differences (P<0.01). The blood levels of FGF2, FIB, IL-6, IL-18, LP-PLA2, and CRP in the amputation group were significantly higher than those in the non-amputation group, and the levels of TRF, ALB, and PA were significantly lower than those in the non-amputation group (P<0.01). There were statistically significant differences in the levels of FGF2, FIB, IL-6, IL-18, LP-PLA2, CRP, TRF, ALB, and PA in patients with diabetic foot with different Wagner grades (P<0.05). The result of multiple logistic regression analysis showed that IL-6 [odds ratio (OR)=1.487, 95% confidence interval (CI) (1.023, 2.120), P<0.001], IL-18 [OR=1.274, 95%CI (1.052, 1.665), P<0.001], LP-PLA2 [OR=1.478, 95%CI (1.126, 1.789), P<0.001], and CRP [OR=2.085, 95%CI (1.574, 2.782), P<0.001] were independent risk factors for the occurrence of refractory diabetic foot, and TRF [OR=0.645, 95%CI (0.002, 0.898), P<0.001], ALB [OR=0.838, 95%CI (0.429, 0.923), P<0.001], and PA [OR=0.478, 95%CI (0.201, 0.984), P<0.001] were independent protective factors for the occurrence of refractory diabetic foot.ConclusionIn the clinical treatment of diabetic foot, we should pay attention to the monitoring of the level of inflammatory factors and nutritional status, and it is necessary to timely carry out anti-inflammatory treatment and appropriate nutritional support treatment.
ObjectiveTo summarize the advance of triggering receptor expressed on myeloid cells-1 (TREM-1). MethodsLiteratures about the recent studies on the TREM-1 were reviewed. ResultsTREM1 was a mediator of inflammation. It could amplify the inflammation and lead to overexpression of inflammation in final. ConclusionTREM-1 is very important in development of many diseases and provide a new molecule target to cure.
In recent years, with the development of neuroimaging and the improvement of people’s awareness, the incidence of cerebral venous sinus thrombosis (CVST) has been increasing year by year. CVST with venous infarction or haemorrhage is severe, accounting for about 60% of CVST, and its clinical manifestations are serious. The current therapies including anticoagulation and intravascular treatment have not significantly improved the prognosis of severe CVST patients. The incidence of long-term poor prognosis (modified Rankin scale score≥2) is up to 56.1%. Recent research indicates that inflammation may be an important factor leading to severe CVST and is significantly associated with poor prognosis. Anti-inflammatory treatment with glucocorticoids may provide a novel method for severe CVST, but further clinical studies are needed to verify it. This paper introduces the relationship between inflammation and severe CVST in order to explore the feasibility of glucocorticoid for severe CVST.
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.
ObjectiveTo study the effects of the new small molecular oxygen free radical scavenger Tempol on the survival and vasculogenesis of the long random pattern skin flap (LRPSF) and its mechanism. MethodsEighty-four male Sprague Dawley rats were randomly divided into control and Tempol groups (42 rats in each group). LRPSF of 9 cm×3 cm in size were prepared on the backs of rats in two groups based on the Mcfarlane flap. Rats were administered with Tempol (100 mg/kg) in the Tempol group and with normal saline in the control group by intraperitoneal injection at 15 minutes before operation and at 1-7 day after operation. The rat and the skin flap survival conditions were observed after operation; the survival rate of skin flap was measured, and the vascular structure, vascular volume, and total length of blood vessels were analyzed with Micro-CT three-dimensional imaging after 7 days; HE staining was used to observe the structure of the skin flaps and inflammation, immumohistochemical staining to observe vascular endothelial growth factor (VEGF) expression; water-soluble tetrazolium-1 method was used to measure the content of superoxide dismutase (SOD) and malondialdehyde (MDA), and ELISA to detect the expressions of tumor necrosis factor α (TNF-α) and interleukin 6 (IL-6) after 1, 3, and 7 days. ResultsAll of rats survived after operation, without hemorrhage, edema, and infection. With the extension of time, necrosis occurred in the distal part of the skin flaps in 2 groups, but the necrosis degree of the Tempol group was lower than that of control group; meanwhile, the blood vessel distribution and continuity were better than those of control group. The skin flaps survival rate, vascular volume, and total length of blood vessels of Tempol group were significantly higher than those of control group after 7 days (P<0.05). The clearer skin flaps structure, lighter inflammation reaction and inflammation cell infiltration, and higher VEGF staining intensity were observed in the Tempol group than the control group after 7 days. There was no significant difference in SOD, MDA, and TNF-α, and IL-6 contents between the 2 groups at immediate after operation. SOD significantly increased, but MDA, TNF-α, and IL-6 contents significantly decreased in the Tempol group when compared with control group after 1, 3, and 7 days (P<0.05). ConclusionTempol can significantly promote the LRPSF survival rates, its mechanism is closely related to the promotion of vasculogenesis and reduction of oxidative stress and inflammation.
ObjectiveTo observe the effects of RasGRP4 gene deletion on the structure and function of the retina in diabetic mice, and to explore the mechanism of RasGRP4 in diabetic retinopathy (DR) by transcriptome sequencing in conjunction with bioinformatics analysis. MethodsA total of 12 male C57BL/6J mice were divided into normal group, diabetic group (DM group), with 6 mice in each group. Six male RasGRP4 knockout mice were uesd as RasGRP4 knockout diabetic group (DM-KO group). Mice in the DM group and DM-KO group were fed with high-fat diet combined with intraperitoneal injection of streptozotocin to establish diabetic model and body weight and blood glucose were monitored regularly. Three months after modeling, optical coherence tomography was used to detect the retinal thickness and ganglion cell layer thickness. Electroretinography was used to detect the function of the retina in mice under dark-adapted conditions. Total RNA was extracted from the retinas of mice in DM group and DM-KO group, and transcriptomic sequencing was performed to screen differentially expressed genes (DEG). Core genes were screened using MCODE and Cytohubba plug-ins of Cytoscape v3.8.2 software. At the same time, the functional enrichment analysis of gene samples (GO) of the selected DEG was performed. The mRNA relative expression levels of interleukin-8, transforming growth factor-β (TGF-β), interferon-γ (IFN-γ), NOd-like receptor thermal protein domain protein 3 (NLRP3), Caspase-1 and IL-1β in each group were detected by real-time quantitative polymerase chain reaction. t test was used to compare the two groups. One-way analysis of variance was used to compare the three groups.ResultsCompared with the DM group, there was no significant difference in blood glucose and body weight in the DM-KO group with the extension of high-fat diet (t=0.12, 2.02, 0.22, 0.10, 0.59, 0.41, 1.35, 0.31, 1.12, 1.58, 1.47, 1.20, 1.24, 0.39, 0.66, 0.14; P＞0.05). The retinal thickness and ganglion cell layer thickness of mice in the three groups were significantly reduced in the DM group compared with the normal group, while DM-KO was significantly increased compared with the DM group, and the differences were statistically significant (F=30.43, 7.81; P＜0.000 1, 0.01). Comparison of a-wave and b-wave amplitudes among the three groups showed that the DM group was significantly lower than the normal group, while the DM-KO was significantly higher than the DM group, and the differences were statistically significant (F=16.46, 35.58; P＜0.001, 0.000 1). Compared with the DM group, 184 differential genes (DEG) were screened in the DM-KO group, among which 39 up-regulated and 145 down-regulated genes were detected, respectively. The results of the MCODE plug-in analysis showed that Col1a2, Fbln1, Fbn1, Col6a3, Fmod, Ogn, Tgfb, Mfap4, Vcan, Nid2, and Col18a1 were core genes in the DEG. Cytohubba plug-in analysis showed that Col1a2, Mrc1, Cd47, Fbn1, Cybb, Cd163, Fbln1, Fmod, Adgre1, and Col6a3 were the core genes in DEG. The results of the GO functional enrichment analysis showed that DEG was mainly involved in hemoglobin complexes, MHC class Ⅱ protein complex, apical plasma membrane, inflammasome complex, immunological synapse, response to bacterium, inflammatory response, immune system processe, response to hypoxia, and cell adhesion were significantly enriched. Comparison of mRNA relative expression levels of IL-8, TGF-β, IFN-γ, NLRP3, Caspase-1 and IL-1β in the three groups showed that the DM group was significantly higher than the normal group, while the DM-KO was significantly lower than the DM group, with statistical significance (F=12.43, 15.41, 70.09, 29.04, 11.79, 41.28; P＜0.01). Conclusion RasGRP4 deficiency plays a therapeutic role in the development of DR through inhibition of inflammatory factor secretion and NLRP 3 inflammasome pathway activation.
ObjectiveTo review the research progress of microenvironment for the treatment of peripheral nervous injuries. MethodsThe recent literature concerning the treatment mechanism of peripheral nervous injuries was extensively consulted, and the microenvironment response involved in the treatment of peripheral nervous injuries was reviewed. ResultsThe complex microenvironment for treatment of peripheral nervous injuries is dependent on nerve regeneration chamber, the formation of neurotrophic factors, inflammation response, regulation of hormones, signaling pathways, and related enzymes in regulation. In-depth study will help us have a clearer understanding on the distal and proximal neurons axons at the cellular and molecular levels after peripheral nervous injuries. ConclusionIn recent years, the researches of microenvironment for the treatment of peripheral nervous injuries have achieved obvious progress. With the current nanotechnology, materials science, genetic engineering, and stem cell transplantation technology, it will provide new ideas and corresponding basis for clinical treatment.
ObjectiveTo investigate the expression of histone deacetylase 2 (HDAC2) in animal model of benign tracheal stenosis, and explore the mechanism of HDAC2 in development of tracheal stenosis.MethodsEighteen rabbits were randomly divided into a blank control group, a model group, and an erythromycin group, with 6 rats in each group. The model group and the erythromycin group underwent tracheostomy, the inner wall of trachea was brushed back and forth with a nylon brush for more than 20 times to induce benign tracheal stenosis. From 7 days before surgery to 9 days after surgery, the model group received gavage with saline, the erythromycin group received gavage with low-dose erythromycin in dose of 15 mg·kg–1·d–1, and the control group did not receive any treatment. On the 10th day after operation, all the rabbits were sacrificed and the trachea was cut to measure the tracheal stenosis. RNA and protein were extracted from the granulation tissue in the stenosis and the relative mRNA expressions of HDAC2, interleukin (IL)-6 and IL-8 in the granulation tissue were detected by real-time fluorescence quantitative PCR. The relative expression of HDAC2 protein was detected by Western blot.ResultsCompared with the blank control group, the tracheal stenosis in the model group was more obvious [(84.60±1.14)% vs.(27.00±6.44)%], the mRNA and protein expressions of HDAC2 were decreased (0.29±0.07 vs. 1.00±0.00, 0.20±0.02 vs. 0.49±0.04), the mRNA expressions of IL-6 and IL-8 were up-regulated (4.22±0.67 vs. 1.00±0.00, 162.72±23.23 vs.1.00±0.00). Compared with the model group, tracheal stenosis in the erythromycin group was relieved [(64.00±12.25)% vs. (84.60±1.14)%], the mRNA and protein expressions of HDAC2 were increased (0.42±0.14 vs. 0.29±0.07, 0.43±0.01 vs. 0.20±0.02), the mRNA expressions of IL-6 and IL-8 were decreased (0.72±0.24 vs. 4.22±0.67, 130.22±7.93 vs. 162.72±23.23). All the differences were statistically significant (all P<0.05). The Pearson correlation coefficient between tracheal stenosis and HDAC2 mRNA relative expression was –0.96 (P<0.05).ConclusionsThe down-regulation of HDAC2 expression in model of benign tracheal stenosis is related to the occurrence and development of tracheal stenosis. The low dose of erythromycin may be used to treat benign tracheal stenosis by up-regulating expression of HDAC2 and thus inhibiting the inflammatory disorder during tracheal injury repair.