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.
ObjectiveTo explore the effect of preoperative glucocorticoid on systemic inflammatory indexes and pulmonary inflammation after radical esophagectomy.MethodsA total of 44 patients with esophageal cancer treated in the First Affiliated Hospital of Xiamen University from July 2019 to September 2020 were selected and randomly divided into an intervention group and an observation group by random number table. There were 22 patients in the intervention group, including 20 males and 2 females with an average age of 62.86±5.22 years and 22 patients in the observation group, including 19 males and 3 females with an average age of 63.00±6.19 years. Two groups were given thoracoscope-assisted incision via right chest, upper abdomen and left neck. The intervention group was given an intravenous infusion of methylprednisolone 500 mg before induction of anesthesia, and the observation group was given the same dose of normal saline. The second generation cephalosporins were routinely used to prevent infection in the two groups. The levels of interleukin-6 (IL-6) and C-reactive protein (CRP), lymphocyte and neutrophil count before operation and 1 day, 3 days and 5 days after operation were recorded and compared between the two groups. Utrecht Pneumonia Scoring System (UPSS) score 1 day after operation, the healing of the surgical incision and the anastomotic leakage within 2 weeks after the operation were evaluated.ResultsThe level of IL-6 in the intervention group was significantly lower than that in the observation group at 1 hour and 1 day after operation (both P<0.05). CRP showed significant difference between the two groups 2 days after operation (P=0.044). The white blood cell count in the intervention group was significantly less than that in the observation group 1 day and 3 days after operation (both P<0.05). There was no significant difference in lymphocyte or neutrophil count between the two groups 1 day after operation. There was no significant difference in the rate of non-grade A wound healing or the incidence of anastomotic leakage between the two groups within 2 weeks after operation. The pneumonia score of UPSS in the intervention group was lower than that in the observation group 1 day after operation (P=0.027).ConclusionThe use of glucocorticoid before radical esophagectomy can reduce the systemic inflammatory reaction and improve the short-term postoperative pulmonary inflammation. At the same time, no adverse effect on the healing of surgical incision and anastomotic stoma is found, which has certain safety.
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.
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.
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.
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.
Objective To introduce the inflammatory microenvironment and epithelial-mesenchymal transition process of hepatocellular carcinoma, and review the relationship between them. Methods Domestic and international literatures were collected to summary the relationship between epithelial-mesenchymal transition and the inflammatory microenvironment of hepatocellular carcinoma. Result Many inflammatory factors and viral gene encoding proteins in the inflammatory microenvironment play an important role in the process of epithelial-mesenchymal transition in hepatocellular carcinoma. Conclusions The inflammatory microenvironment of hepatocellular carcinoma is an indispensable role in the process of epithelial-mesenchymal transition. The inhibition and treatment of inflammatory microenvironment may play a more active role in the control of tumor invasion and metastasis.
Objective To investigate the clinical significance of changes in cardiopulmonary function, degree of hypoxia and inflammatory factors in obstructive sleep apnea hypopnea syndrome (OSAHS) patients combined chronic obstructive pulmonary disease (COPD). Methods A retrospective case-control study was conducted on 209 patients with OSAHS admitted from October 2015 to April 2022. The OSAHS patients were divided into an OSAHS-only group, an OSAHS combined with mild COPD group, an OSAHS combined with moderate COPD group, and an OSAHS combined with severe and very severe COPD group based on pulmonary function test. The characteristics of cardiopulmonary function [(pulmonary artery pressure, N terminal pro B type natriuretic peptide (NT-proBNP), forced expiratory volume in the first second to forced vital capacity (FEV1/FVC), percent predicted value of FEV1 (FEV1%pred)], hypoxia indexes [night lowest saturation of pulse oxygen (NL-SpO2), night medial saturation of pulse oxygen (NM-SpO2), saturation of pulse oxygen less than 85% of the time (TS85), diurnal lowest saturation of pulse oxygen (DL-SpO2)], inflammatory factor indicators [procalcitonin (PCT), interleukin-6 (IL-6), hypersensitive C-reactive protein (hs-CRP), neutrophil to lymphocyte ratio (NLR)], and other characteristics were compared separately. The partial correlation analysis and logistic regression were used to analyze the influencing factors of OSAHS with COPD. Results There were statistically significant differences in age, days of hospitalization, cardiopulmonary function indexes, hypoxia indexes and inflammatory factor indexes between the OSAHS combined with COPD group and the OSAHS-only group (all P<0.05). And pulmonary artery pressure, NT-proBNP, TS85, IL-6, and NLR were higher and DL-SpO2, NL-SpO2, and NM-SpO2 were lower in the OSAHS combined with severe and very severe COPD group compared with the OSAHS combined with mild COPD group (all P<0.05). In the partial correlation analysis, FEV1%pred was negatively correlated with pulmonary artery pressure, NT-proBNP, TS85, IL-6, hs-CRP and NLR, and positively correlated with DL-SpO2, NL-SpO2 and NM-SpO2 (all P<0.05). In regression analysis, NLR and TS85 were the main risk factors for OSAHS combined with COPD (all P<0.05). Conclusions OSAHS patients combined with COPD have longer hospital days, greater burden of hypoxia, cardiopulmonary function and inflammation compared with patients with OSAHS alone, especially more significant in patients with poorer pulmonary function, and higher incidence of pulmonary heart disease, atrial fibrillation, and lower limb edema. NLR and TS85 are the main risk factors in patients with OSAHS combined with severe and very severe COPD.
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.
Acute respiratory distress syndrome (ARDS) is the most common cause of acute respiratory failure. Extensive researches have been conducted for the pathophysiology of this disease, but the mortality rate remains high. Previous studies have found that catecholamines play an important role in acute lung injury, and newly discover prompted that upregulation of phagocyte-derived catecholamines augmented the acute inflammatory response in acute lung injury which provides a new way of thinking. In the current review, we describe the mechanism of the phagocyte-derived catecholamines augmenting the acute lung injury.