ObjectiveTo summarize the anti-inflammatory effects of irisin in inflammatory diseases.MethodThe relevant literatures at home and abroad in recent years were systematically searched and read to review the anti-inflammatory effects of irisin in the inflammatory diseases.ResultsThe irisin was widely distributed in the body and played a physiological role in inducing the browning of white adipocytes, improving energy metabolism and glucose utilization. A grow body of evidences demonstrated that the irisin exerted the anti-inflammatory effects by inhibiting increased pro-inflammatory cytokines and tumor necrosis factor-α, antagonizing apoptosis and activation of nuclear factor-κB, and improving tissue damage in many inflammatory diseases, such as acute lung injury, inflammatory bowel disease, septic cardiomyopathy, acute pancreatitis, nonalcoholic fatty liver disease, and malignant tumors.ConclusionsIrisin plays an important anti-inflammatory role in pathogenesis of inflammatory diseases. Irisin is considered as a promising candidate biomarker for diagnosis and prognosis of inflammatory diseases, and a novel target for treatment of inflammatory diseases.
Objective This study aims to investigate the changes of inflammatory markers of oropharynx and its correlation with prognosis in the stable phase of chronic obstructive pulmonary disease (COPD). Methods Sixty-two patients with COPD in stable stage were divided into smoking and non-smoking groups, and 31 healthy persons were selected as controls. The pharyngeal swabs were collected to determine tumor necrosis factor-α (TNF-α), interleukin-8 (IL-8), collagen type Ⅳ (COL-4), and fibronectin (FN) by an enzyme-linked immunosorbent assay. Meanwhile, eosinophil count and C-reactive protein (CRP) in peripheral blood were measured. The correlations between the above metrics and COPD and the prognosis of the patients were analyzed. Results TNF-α, IL-8, COL-4, FN and CRP levels in patients with COPD were significantly higher compared with control groups (P<0.05), and there were significant differences between smoking and non-smoking groups in inflammatory markers such as TNF-α, IL-8, FN, CRP (P<0.05). The forced expiratory volume in one second (FEV1) and FEV1%pred of patients with COPD were significantly lower than the control group (P<0.05). The smoking index of patients with COPD in smoking group was significantly higher than that in smoking control group (P<0.05). TNF- α and IL-8 were positively associated with blood CRP in patients with COPD. Conclusion The inflammatory markers of oropharynx in patients with COPD are different from those in healthy persons and smoking may promote the increase of inflammatory markers of oropharynx in patients with COPD; the non-invasive detection of paired pharyngeal inflammatory markers may be helpful in determining acute onset and prognosis.
ObjectiveTo analyze the correlations between the immune function and inflammatory factors levels of patients with hepatocellular carcinoma (HCC) and the results of in vitro high-throughput drug sensitivity, and to provide a reference for personalized drug selection for patients with HCC. MethodsThe patients with HCC who met the inclusion criteria from December 2019 to June 2021 in the First Affiliated Hospital of Chongqing Medical University were included. The HCC cells were used to perform in vitro high-throughput drug sensitivity screening, the result was classified into sensitive and insensitive. The correlations between drug sensitivity results and immune function and inflammatory factors levels of corresponding patients were analyzed, and the relation between these indexes (P<0.05) and drug sensitivity of HCC cells to drugs or combination regimen of drugs was further analyzed by univariate logistic regression. ResultsA total of 74 patients with HCC were included in this study. The results showed that the level of interleukin-6 was negatively correlated with sorafenib, caffezomib, gemcitabine, oxaliplatin + epirubicin + irinotecan + 5-fluorouracil, oxaliplatin + irinotecan + epirubicin, and oxaliplatin + epirubicin regimens on the inhibition rates of HCC in vitro (P<0.05), and positively correlated with bortezomib (P<0.05). However, the level of interleukin-6 was not related to the sensitivity of HCC cells to these single drugs or combined regimens (P>0.05). Meanwhile it was found that tumor necrosis factor (TNF)-α was negatively correlated with cabotinib, apatinib, caffezomib, and epirubicin on the inhibition rates of HCC in vitro (P<0.05), and positively correlated with epirubicin (P<0.05). But only it was found that tumor necrosis factor-α level was related to the sensitivity of HCC cells to epirubicin (P<0.05). ConclusionsTumor necrosis factor-α level in peripheral blood of patients with HCC has a certain relation with epirubicin on inhibition rate of HCC in vitro and it might have a certain value in predicting sensitivity of HCC cells to epirubicin. Meanwhile, although it is found that level of IL-6 is related to sorafenib, caffezomib, gemcitabine, or including combination regiems including oxaliplatin and epirubicin on inhibition rates of HCC in vitro, their value is not found in predicting sensitivity of HCC cells to these single drugs or combined regimens.
Objective To investigate the protective effect of annexin A1 (ANXA1) derived from human umbilical cord mesenchymal stem cells (HucMSCs) on lipopolysaccharide (LPS) -induced acute lung injury (ALI). Methods Six-week-old male C57BL/6 mice were randomly divided into a sham group, a LPS group, a LPS+HucMSC-cm (LPS+cm) group, a LPS+nc-cm group, and a LPS+si-cm group, with 6 mice in each group. LPS (5 mg/kg) was intratracheally injected to induce ALI model. Then, normal saline, HucMSC-cm (HucMSC conditioned medium), HucMSC-nc-cm (normal ANXA1 expression) and HucMSC-si-cm (knockout of ANXA1) were injected intratracheally with 50 μL each after LPS treatment for 4 hours. After 72 hours of LPS administration, the mice were killed, and the blood and lung tissues were retained. After corresponding treatment, the blood and lung tissues were preserved. The expression of IL-6 in peripheral blood of mice was detected by enzyme-linked immunosorbnent assay, the pathological changes of lung tissues were observed by hematoxylin-eosin staining, and the expressions of interleukin-6 (IL-6) and vascular cell adhesion molecule-1 (VCAM-1) in lung tissues of each group were detected by Western blot and immunohistochemistry. Results Compared with the sham group, the lung histopathology of mice in the LPS group showed significantly increased inflammatory factor infiltration, alveolar collapse, and lung tissue structure destruction as well as lung tissue injury score and wet/dry weight ratio (W/D) increased (all P<0.05). Accordingly, IL-6 and VCAM-1 protein levels in lung tissue and IL-6 expression in peripheral blood were increased (all P<0.05). Compared with the LPS group, the pathological injury of lung tissue in the LPS+cm group was improved, the lung tissue injury score and the W/D ratio decreased while IL-6, VCAM-1 protein levels in lung tissue and IL-6 expression in peripheral blood were decreased (all P<0.05). But there were no significant differences between the LPS+cm group and the LPS+ nc-cm group (all P>0.05). Compared with the LPS+nc-cm group, lung tissue pathological injury was aggravated again, lung tissue injury score and W/D were also increased in the LPS+si-cm group (all P<0.05). IL-6 and VCAM-1 protein levels in lung tissue and IL-6 expression in peripheral blood were increased again (all P<0.05). Conclusion ANXA1 derived from HucMSCs has certain protective effect in LPS-induced ALI model.
ObjectiveTo investigate the effects of melatonin (MT) on bone mass and serum inflammatory factors in rats received ovariectomy (OVX) and to investigate the effects of MT on the levels of inflammatory factors in culture medium and osteogenic ability of bone marrow mesenchymal stem cells (BMSCs) stimulated by lipopolysaccharide. Methods Fifteen 12-week-old Sprague Dawley (SD) rats were randomly divided into 3 groups. The rats in Sham group only received bilateral lateral abdominal incision and suture, the rats in OVX group received bilateral OVX, and the rats in OVX+MT group received 100 mg/(kg·d) MT oral intervention after bilateral OVX. After 8 weeks, the levels of serum inflammatory factors [interleukin-1β (IL-1β), IL-6, and tumor necrosis factor α (TNF-α)] were detected using ELISA assay. Besides, the distal femurs were detected by Micro-CT to observe changes in bone mass and microstructure, and quantitatively measured bone volume fraction, trabecular thickness, and trabecular number. The BMSCs were extracted from the femurs of three 3-week-old SD rats using whole bone marrow culture method and passaged. The 3rd-5th passage BMSCs were cultured with different concentrations of MT (0, 1, 10, 100, 1 000 μmol/L), and the cell viability was then detected using cell counting kit 8 (CCK-8) to select the optimal concentration of MT for subsequent experiments. Cells were devided into osteogenic induction group (group A) and osteogenic induction+1/5/10 μg/mL lipopolysaccharide group (group B-D). The levels of inflammatory factors (IL-1β, IL-6 and TNF-α) in cell culture medium were detected using ELISA assay after corresponding intervention. According to the results of CCK-8 method and ELISA detection, the cells were intervened with the most significant concentration of lipopolysaccharide for stimulating inflammation and the optimal concentration of MT with osteogenic induction, defining as group E, and the cell culture medium was collected to detect the levels of inflammatory factors by ELISA assay. After that, alkaline phosphatase (ALP) staining and alizarin red staining were performed respectively in groups A, D, and E, and the expression levels of osteogenic related genes [collagen type Ⅰ alpha 1 chain (Col1a1) and RUNX family transcription factor 2 (Runx2)] were also detected by real time fluorescence quantitative PCR (RT-qPCR). ResultsELISA and Micro-CT assays showed that compared with Sham group, the bone mass of the rats in the OVX group significantly decreased, and the expression levels of serum inflammatory factors (IL-1β, IL-6, and TNF-α) in OVX group significantly increased (P<0.05). Significantly, the above indicators in OVX+MT group were all improved (P<0.05). Rat BMSCs were successfully extracted, and CCK-8 assay showed that 100 μmol/L was the maximum concentration of MT that did not cause a decrease in cell viability, and it was used in subsequent experiments. ELISA assays showed that compared with group A, the expression levels of inflammatory factors (IL-1β, IL-6, and TNF-α) in the cell culture medium of groups B-D were significantly increased after lipopolysaccharide stimulation (P<0.05), and in a concentration-dependent manner. Moreover, the expression levels of inflammatory factors in group D were significantly higher than those in groups B and C (P<0.05). After MT intervention, the expression levels of inflammatory factors in group E were significantly lower than those in group D (P<0.05). ALP staining, alizarin red staining, and RT-qPCR assays showed that compared with group A, the percentage of positive area of ALP and alizarin red and the relative mRNA expressions of Col1a1 and Runx2 in group D significantly decreased, while the above indicators in group E significantly improved after MT intervention (P<0.05). ConclusionMT may affect the bone mass of postmenopausal osteoporosis by reducing inflammation in rats; MT can reduce the inflammation of BMSCs stimulated by lipopolysaccharide and weaken its inhibition of osteogenic differentiation of BMSCs.
Systemic inflammatory response (SIR) evoked by cardiopulmonary bypass (CPB) is still one of the major causes of postoperative multiple organs injuries. Since the concentrations of circulating inflammatory factors are positively associated with postoperative adverse events, removal or inhibition of inflammatory factors are considered as effective treatments to improve outcomes. After more than 20 years of research, however, the results are disappointed as neither neutralization nor removal of circulating inflammatory factors could reduce adverse events. Therefore, the role of circulating inflammatory factors in CPB-related organs injuries should be reconsidered in order to find effective therapies. Here we reviewed the association between circulating inflammatory factors and the outcomes, as well as the current therapies, including antibody and hemadsorption. Most importantly, the role of circulating inflammatory factors in SIR was reviewed, which may be helpful to develop new measures to prevent and treat CPB-related organs injuries.
Objective To investigate the regulatory effects of SHP2 inhibition on the secretion of macrophage-associated inflammatory factors in KRAS-mutant lung cancer cells and to elucidate the underlying mechanisms by which this inhibition remodels the tumor immune microenvironment. Methods Three KRAS-mutant lung cancer cell lines were treated with the SHP2 inhibitor SHP099. The levels of phosphorylated SHP2 and ERK were assessed by Western blot. The expression levels of related inflammatory factors were analyzed using Luminex assay and qRT-PCR assay. Transcriptome sequencing was performed to identify differentially expressed genes and conduct KEGG pathway enrichment analysis. The expression of CXCL8 was validated by flow cytometry and Western blot. Survival analysis and gene set correlation analysis were conducted based on the TCGA database. Results SHP099 significantly inhibited the expression of p-SHP2 and p-ERK proteins, and reduced the secretion of multiple macrophage-related inflammatory factors. qRT-PCR confirmed a decrease in CXCL8 mRNA levels. Transcriptome analysis revealed significant enrichment of the rheumatoid arthritis pathway. Flow cytometry and Western blot validated a significant reduction in CXCL8 protein expression. Survival analysis showed that patients with KRAS-mutant lung adenocarcinoma and high CXCL8 expression had a shorter overall survival, and CXCL8 was positively correlated with M2 macrophage marker genes. Conclusion Targeted inhibition of SHP2 can suppress the expression of some macrophage-related inflammatory factors in KRAS-mutant lung cancer cells, with the most significant inhibition of CXCL8 expression. The mechanism may involve SHP2 regulating the transcription factor AP-1.
Objective To investigate the relationship of cluster of differentiation 40L (CD40L) between inflammatory response mediated by vascular endothelial injury and Stanford A type aortic dissection (STAAD). Methods In this study from August 2016 to February 2017, a total of 215 blood samples from 95 STAAD patients (67 males and 28 females aged 48.33±12.19 years) and 120 healthy volunteers (94 males and 26 females aged 48.64±10.13 years) were collected. The patients with aortic dissection were taken blood 1 hour before the operation and the healthy volunteers were taken blood from the elbow vein. All STAAD patients were diagnozed by computed tomography angiography (CTA) and patients with Marfan syndrome were excluded. Blood samples were tested by enzyme-linked immunosorbent assay (ELISA) for CD40L, vascular cell adhesion molecule (VCAM-1), E-selectin, interleukin-1 (IL-1) beta, IL-6, tumor necrosis factor-alpha (TNF-α) and so on. ResultsCompared with the healthy population, the level of SCD40L(26.87±5.50 ng/ml vs. 13.39±4.03 ng/ml, P<0.001) in the STAAD patients was significantly higher. E-Selectin (116.62±25.24 ng/ml vs. 77.05±14.30 ng/ml, P<0.001), VCAM-1 (P<0.001), TNF-α (55.35±9.12 ng/ml vs. 37.33±5.61 pg/ml, P<0.001), IL-1β (62.12±13.37 ng/ml vs. 48.68±9.86 pg/ml, P<0.001), IL-6 (499.54±90.45 ng/ml vs. 422.44±34.00 pg/ml, P<0.001) significantly increased. Conclusion The increased expression of SCD40L in STAAD patients and the inflammatory reaction induced by endothelial injury in aortic dissection patients are obvious.
A new independent subtype CD4+ T cell which massively secreted interleukin-17 (IL-17) was found at the beginning of the 21st century, and thus it was named as T helper cell 17 (Th17 cell). With the progress of the research in recent years, Th17 cells were found to be widely involved in a variety of the human diseases such as autoimmune diseases, infections and tumors through secretion of IL-17. The relationship between Th17 cells, IL-17 and the occurrence, development and prognosis of lung cancer was reviewed.
Objective To observe the effect of “Luo’s Roujin Technique” on the inflammatory response and joint capsule fibrosis in white rabbits with scapulohumeral periarthritis model. Methods Thirty healthy male New Zealand white rabbits were randomly divided into a control group, a model group, and a treatment group, with 10 rabbits in each group. Scapulohumeral periarthritis models were established in the model group and the treatment group, while the control group received identical restraint procedures at the same timepoints. Six rabbits in the model group and seven in the treatment group were successfully modeled. The subsequent experiment included all six successfully modeled rabbits from the model group, along with six rabbits randomly selected from each of the control and treatment groups. On the second day after successful modeling, blood samples were collected from the auricular marginal vein in all three groups. After blood collection, the treatment group began massage therapy for 21 consecutive days, while the other two groups underwent the same restraint procedure simultaneously. On Day 22, all the three groups were euthanized after blood collection from the auricular marginal vein, and the synovial tissue of the affected shoulder joint was completely collected. Hematoxylin-eosin staining was used to examine the histopathological features of the synovial tissue. Enzyme-linked immunosorbent assay was employed to measure the concentrations of interleukin (IL)-1β, IL-6, IL-17, and tumor necrosis factor-α (TNF-α). Western blot and reverse transcription polymerase chain reaction were used to assess the protein and mRNA expression levels of vascular endothelial growth factor (VEGF), connective tissue growth factor (CTGF), transforming growth factor-β1 (TGF-β1), and Smad3. Results After treatment, the control group showed no significant inflammatory cell infiltration or fibrous tissue proliferation in the synovial tissue. The model group exhibited synovial cell hyperplasia in the lining layer and inflammatory cell infiltration in the sublining layer. The treatment group displayed mild inflammatory cell infiltration in the sublining layer. Compared with the control group, the model group showed significantly increased concentrations of IL-1β, IL-6, IL-17, and TNF-α in both serum and synovial homogenate, as well as elevated protein and mRNA expression of VEGF, CTGF, TGF-β1, and Smad3 in synovial tissue (P<0.05). Compared with the model group, the treatment group exhibited significantly lower serum levels of IL-1β, IL-6, and TNF-α, as well as reduced synovial homogenate levels of IL-1β, IL-6, IL-17, and TNF-α (P<0.05); furthermore, protein expression of VEGF, CTGF, TGF-β1, and Smad3 and mRNA expression of VEGF and CTGF in synovial tissue were significantly decreased in the treatment group (P<0.05). Conclusions “Luo’s Roujin Technique” can significantly alleviate local inflammatory infiltration in the synovial tissue of rabbits with scapulohumeral periarthritis, and reduce the levels of IL-1β, IL-6, IL-17, and TNF-α in both serum and synovial tissue. The underlying mechanism may involve suppression of VEGF, CTGF, TGF-β1, and Smad3 expression, leading to attenuated inflammatory responses and inhibition of fibroblast-to-myofibroblast transition. Thereby, it mitigates fibrotic changes in the shoulder joint capsule, exerting anti-inflammatory and analgesic effects and improving joint mobility.
