Objective To explore the role of macrophage-stimulating protein ( MSP) and receptor tyrosine kinase RON in the airway inflammation of chronic obstructive pulmonary disease( COPD) , and investigate its possible mechanism. Methods The rat COPDmodel was established by exposing the rats to cigarette smoke daily for three months. Rat alveolar macrophages ( AMs) were isolated in vivo and cultured,and then challenged with different concentrations of MSP for 24 hours. The concentrations of MSP in broncho-alveolar lavage fluid ( BALF) and serum, and the levels of IL-1β, TNF-α, IL-8, and IL-10 in the supernatants were measured by ELISA. The expression of RONmRNA in lung tissue was assessed by reverse transcription-polymerase chain reaction. The levels of RON protein in the lung tissue and AMs cultured in vitro were observed by immunohistochemistry. The activity of superoxide dismutase ( SOD) and malondialdehyde ( MDA) content in the culture solution were measured with chromatometry method. Results Compared with the control group, the concentrations of MSP in serum and BALF of the COPD rats were significantly higher ( P lt;0. 01) . The levels of RONmRNA and RON protein in the COPD rats were also upregulated significantly ( P lt; 0. 01) . MSP evoked the AMs isolated from the normal and COPD rats to generate more content of MDA and caused a reduction in activity of SOD. In addition, MSP stimulated TNF-α, IL-8, IL-1βand IL-10 release fromAMs of the normal and COPD rats dose-dependently. The levels of TNF-α, IL-8, and IL-1βwere higher, while the level of IL-10 and the SOD activity were lower in AMs of the COPD group than those of the control group in the same dose of MSP ( P lt;0. 01) . The more significant increase in the levels of TNF-α, IL-8, IL-1β, and the more notable decrease in the activity of SOD was found in the COPD group compared with the control group. But the degree of increasing MDA and IL-10 in the AMs of the COPD group was lower than that in the control group. Linear correlation analysis showed that the MSP concentration and the RON protein level in the COPD rats were positively associated with the total cellcounts and AM counts in BALF, and were related to the indexes for pulmonary emphysema. Conclusions There is a close correlation between the MSP and receptor tyrosine kinase RON with the airway inflammation of COPD. The mechanism might be that MSP promote the macrophages release inflammatory factors and increase the production of oxygen free radicals.
ObjectiveThis study applied Mendelian randomization to explore the potential causal relationship between inflammatory factors and diabetic nephropathy. MethodsSummary-level data from genome-wide association studies of inflammatory factors and diabetic nephropathy were used, and inverse variance weighted analysis was used as the primary analytical method, complemented by results from weighted median, MR-Egger regression, simple model, and median model approaches. Sensitivity analysis was used to test the reliability of the MR analysis results. ResultsIn the inverse variance weighted method, stem cell factor (OR=1.28, 95%CI 1.04 to 1.58, P=0.020) and interferon-γ (OR=1.36, 95%CI 1.10 to 1.70, P=0.005) were positively correlated with diabetic nephropathy, and diabetic nephropathy was positively correlated with interferon-inducible protein 10 (OR=0.90, 95%CI 0.83 to 0.98, P=0.012) were negatively correlated with diabetic nephropathy. Sensitivity analysis showed that MR analysis was reliable. ConclusionStem cell factors and interferon-γ are associated with an increased risk of developing diabetic nephropathy, and diabetic nephropathy decreases the expression of interferon-inducible protein 10 in vivo. Our results demonstrate a potential causal relationship between inflammatory factors and the development of diabetic nephropathy. This finding is of clinical significance for the pre-diagnosis and treatment of diabetic nephropathy.
ObjectiveTo explore the levels of serum leptin,TNF-α,IL-8 and hypersensitivity C-reactive protein (hs-CRP) in stable COPD patients with different body mass index (BMI). Methods30 healthy controls with BMI 18.5 to 23.9 kg/m2 and 105 patients with stable COPD were recruited in the study. The serum levels of leptin,TNF-α,and IL-8 were determined by radioimmunoassay and hs-CRP level was determined by versatile biochemical automatic analyzer. The COPD patients were divided into a low BMI group (BMI<18.5 kg/m2,n=32),a normal BMI group (BMI 18.5-23.9 kg/m2,n=48),and a high BMI group (BMI≥23.9 kg/m2,n=25). ResultsSerum leptin level in the COPD patients was significantly reduced compared with the control subjects (P<0.05). Serum leptin levels were reduced in the low BMI and the high BMI groups compare with the normal BMI group [(7.89±3.16)ng/L and (10.52±5.98)ng/L vs. (13.04±5.73) ng/L,P<0.01 or P<0.05]. Leptin level in the low BMI group was lower than that in the high BMI group (P<0.05). Serum TNF-α levels were significantly increased in the low BMI group compared with the normal BMI and high BMI groups [(229.39±89.57)μg/L vs. (180.06±74.24) μg/L and (189.46±82.41) μg/L,P<0.01]. Serum TNF-α level in the COPD patients was significantly increased compared with the control subjects [(192.37±83.65) μg/L vs. (178.59±60.38) μg/L,P<0.05]. The IL-8 levels were not significant different among three BMI groups with COPD. The hs-CRP level in the high BMI group was higher than that in the low BMI and normal BMI groups (P<0.05). ConclusionLeptin and TNF-α may be involved in weight-loss of COPD malnutritional patients.
This study aims to investigate the protective effect of resveratrol against liver injury in hindlimb unloading rats. Thirty 2-month-old male SD rats were randomly divided into normal group (Control), hindlimb unloading model group (Model), and hindlimb unloading+resveratrol administration group (Model+Res). The Model + Res group was injected intraperitoneally with 30 mg/kg of resveratrol, and the Control and Model groups were injected intraperitoneally with an equal volume of 0.9% NaCl. Liver tissues were collected after 28 days and analyzed for oxidative stress, inflammatory factors, energy metabolism indices, Na+-K+-ATPase and Ca2+-Mg2+-ATPase activity, and morphological changes were observed by hematoxylin-eosin staining. The protein expression levels of Bax, Bcl-2, p-PI3K, PI3K, p-AKT, and AKT were detected by Western blotting. Compared with the Control group, hepatocytes in the Model group showed swelling, abnormal morphology, nuclear consolidation, and cell membrane disruption. Oxidative stress, inflammatory factor levels, hepatic glycogen accumulation, and energy metabolism were increased in the liver tissues of the Model group, while resveratrol treatment significantly reversed these changes. The results of Western blotting showed that resveratrol significantly reduced the expression of Bax and increased the expression levels of Bcl-2, and the proteins of p-PI3K/PI3K and p-AKT/AKT expression levels. It is suggested that 28 days of hindlimb unloading treatment could lead to liver tissue injury in rats, which is manifested as oxidative stress, inflammatory response, energy metabolism disorder and increased apoptosis level, and resveratrol has a certain mitigating effect on this.
Obstructive sleep apnea hypopnea syndrome (OSAHS) is a disease in which apnea and hypopnea occur during sleep, and the main symptoms are sleep snoring. OSAHS is not only closely related to the occurrence of various eye diseases, but also the severity of OSAHS can affect the progression of related eye diseases. At present, continuous positive airway pressure (CPAP) is an effective means to treat OSAHS, and the progression of related eye diseases has been improved correspondingly after CPAP treatment. In the future, it is necessary to further study the pathogenesis of OSAHS and enrich the research evidence of the association between OSAHS and eye diseases, so as to provide more comprehensive theoretical evidence for the prevention and treatment of OSAHS-related eye diseases.
Abstract： Objective To explore the feasibility of using protamine-agarose gel to achieve heparin-free cardiopulmonary bypass （CPB）. Methods A total of 12 healthy adult dogs were chosen, the dogs were between 2-3 years old,either male or female, with their mean body weight of 23.3±3.7 kg （ranging from 20 to 28 kg）. All the dogs were randomly divided into two groups with 6 dogs in each group. In the heparinized group, conventional CPB technique was used; in the non-heparinized group, protamine-agarose gel column was used to absorb plasma clotting factors in CPB without use of heparin. At the beginning of CPB and 1 h, 2 h, 3 h after CPB, arterial blood samples were collected from dogs in both groups. The expression levels of tumor necrosis factor-α （TNF-α）, interleukin-6 （IL-6） and interleukin-8 （IL-8） were measured by enzyme-linked immunosorbent assay（ELISA）and compared. Results There was no thrombus formation in the membrane oxygenators during CPB by naked eye observation in both groups. Activated coagulation time （ACT） was always greater than 480 s during CPB. The vital signs of the dogs were all stable during CPB. At the beginning of CPB, there was no statistical difference in plasma concentrations of TNF-α, IL-6, IL-8 between the two groups. At 1 h, 2 h and 3 h after CPB, the expression levels of TNF-α and IL-8 of the non-heparinized group were significantly higher than those of the heparinized group （CPB 3 h TNF-α：156.48±16.65 ng/L vs. 115.87±15.63 ng/L, t=4.356, P=0.001；CPB 3 h IL-8：365.38±46.18 ng/L vs. 299.29±34.50 ng/L, t=2.808, P=0.019）. There was no statistical difference in the expression level of IL-6 between the two groups （P＞0.05）. Conclusion Using protamine-agarose gel to absorb plasma clotting factors is an effective technique to establish heparin-free CPB. But this method can induce significant systemic inflammatory response.
ObjectiveTo investigate whether the miR-33s negatively regulates LPS-induced production of inflammatory cytokines by targeting p38 MAPK. MethodsHuman monocytes THP-1 cells were cultured in vitro and transfected with miR-33s mimic (25 nmol/L) or miR-33s inhibitor (25 nmol/L)by TransIT-X2® Dynamic Delivery System for 24 h. Then the transfected THP-1 cells were stimulated by LPS of 10.0 ng/mL for 24 h. The expression of miR-33s and p38 MAPK protein were measured by semi-quantitative RT-PCR. The concentrations of TNF-α,IL-6 and IL-1β in the cultured supernatant were assessed by ELISA. ResultsThe transfection of miR-33s mimic significantly increased the release of TNF-α,IL-6 and IL-1β(P<0.05). The expression of p38 MAPK protein was also significantly reduced(P<0.05). However,the pre-treatment of miR-33s inhibitor reversed the LPS-induced release of TNF-α,IL-6,and IL-1β,and the expression of p38 MAPK protein of THP-1 cells. ConclusionmiR-33s may play an important role in the regulation in inflammatory factors released from THP-1 cells by targeting p38 MAPK.
ObjectiveTo systematically review the influence of dexmedetomidine on early postoperative cognitive dysfunction (POCD) and serum inflammatory factors in elderly patients.MethodsWe searched PubMed, EMbase, The Cochrane Library, CBM, CNKI, WanFang Data and VIP databases from inception to April 2017, to collect randomized controlled trials (RCTs) about dexmedetomidine for early POCD in elderly patients. Two reviewers independently screened literature, extracted data, and assessed the risk of bias of included studies. Then, meta-analysis was performed by RevMan 5.3 software.ResultsA total of 23 RCTs, including 2 026 patients were enrolled. The results of meta-analysis showed that, the incidence of POCD in the dexmedetomidine group was lower than that in the control group (the first day: RR=0.40, 95%CI 0.30 to 0.53, P<0.000 01; the third day: RR=0.33, 95%CI 0.23 to 0.48,P<0.000 01; the seventh day: RR=0.42, 95%CI 0.22 to 0.78,P=0.006). Meanwhile, compared with the control group, the dexmedetomidine group significantly decreased the serum levels of TNF-α (immediately after operation: MD=–5.43, 95%CI –7.44 to –3.42, P<0.000 01; 1 h after operation: MD=–4.64, 95%CI –6.92 to –2.36,P<0.000 1; 24 h after operation: MD=–3.27, 95%CI –4.92 to –1.63,P<0.000 1) and IL-6 (immediately after operation: MD=–30.69, 95%CI –41.39 to –20.00,P<0.000 01; 1h after operation: MD=–20.84, 95%CI –28.87 to –12.80,P<0.000 01; 24 h after operation: MD=–13.42, 95%CI –19.90 to –6.94,P<0.000 1).ConclusionCurrent evidence indicates that dexmedetomidine could relief early POCD in elderly patients, in which the reduction of serum inflammatory factors alleviate inflammation response may play a vital role. Due to the limited quality and quantity of included studies, more high quality RCTs are required to verify the above conclusion.
ObjectiveTo bioinformatically analyze the gene chip data of chondrocytes from osteoarthritis patients from the Gene Expression Omnibus (GEO) database, and explore the molecular mechanisms of osteoarthritis.MethodsWe searched the GEO database (up to April 23rd, 2021) for data of chondrocytes and gene expression profiling in human knee osteoarthritis via the key words of “osteoarthritis OR cartilage OR chondrocyte*”. Then, we selected the samples by our inclusion criteria. The data were normalized before analysis. After differentially expressed genes were identified, Gene Ontology, Kyoto Encyclopedia of Genes and Genomes, Search Tool for the Retrival of Interacting Genes/Proteinsm, R language, Perl language, Cytoscape software, and DAVID database were used to perform differentially expressed gene analysis, functional annotation, and enrichment analysis.ResultsThe differentially expressed genes were mostly enriched in cell components and some extracellular regions, which participated in cell division, mitosis, cell proliferation and inflammatory response mainly via the regulation of protein kinase activity. The differentially expressed genes were mainly involved in the cell proliferation signaling pathway, mitogen-activated protein kinase signaling pathway, oocyte meiosis, cell cycle and so on.ConclusionsMultiple signaling pathways are involved in the changes of chondrocytes in human knee osteoarthritis, mainly about cell cycle and protein metabolism genes/pathways. Inflammatory factors and cytokines may be the most important links in the pathogenesis of osteoarthritis.
ObjectiveTo systematically review the data of peripheral inflammatory markers in patients with Alzheimer’s disease (AD) and vascular dementia (VaD) to further indicate pathogenesis and antidiastole.MethodsPubMed, EMbase, The Cochrane Library, CNKI, WanFang Data and VIP databases were electronically searched to collect studies on peripheral inflammatory markers in patients with AD and VaD from inception to July 2020. Two reviewers independently screened literature, extracted data, and assessed risk of bias of included studies, and meta-analysis was performed by using Stata 15.1SE software.ResultsA total of 30 studies involving 2 377 patients were included. The results of meta-analysis showed that the IL-6 level was higher in VaD group than that in AD group (SMD=−0.477, 95%CI −0.944 to −0.009, P=0.046). However, there were no statistical difference in peripheral IL-1β (SMD=−0.034, 95%CI −0.325 to 0.257, P=0.818), TNF-α (SMD=0.409, 95%CI −0.152 to 0.970, P=0.153) or CRP (SMD=0.277, 95%CI −0.228 to 0.782, P=0.282) levels.ConclusionsThese findings suggest that IL-6 may be sensitive markers to distinguish AD from VaD. Due to limited quality and quantity of the included studies, more high-quality studies are required to verify the conclusions.