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.
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.
Objective To investigate the difference of anticoagulant efficacy of heparin and citric acid during continuous renal replacement therapy (CRRT) in patients with severe acute pancreatitis, and analyze their effects of on filter life span, length of hospital stay and mortality. Methods Patients with severe acute pancreatitis in Intensive Care Unit of the First Affiliated Hospital of Hebei North University between January 2018 and July 2022 were retrospectively enrolled, and they were divided into heparin group (control group) and citric acid group (research group) according to anticoagulation methods. The differences of anticoagulant catheter blockage during CRRT, filter life span, length of hospital stay, and 90-day mortality between the two groups were analyzed. Results A total of 108 patients were enrolled, including 56 in the research group and 52 in the control group. In pre-CRRT treatment, the balance value of fluid intake and outflow in the research group was significantly lower than that in the control group (P<0.05). The 108 patients received 217 times of CRRT treatment totally, with a median length of treatment of 63 h (range 44-87 h). The severity of catheter blockage in the research group was lower than that in the control group (P=0.003). The filter life span was longer in the research group than that in the control group [42.5 vs. 29.0 h; hazard ratio=1.83, 95% confidence interval (1.23, 2.73), P<0.001]; in the comparison of 90-day mortality, there was no significant difference between the two groups (P>0.05). The mean use of filters in the research group was less than that in the control group (1.93±0.09 vs. 2.17±0.14, P<0.001). The downtime of CRRT due to filter life in the research group was obviously shorter than that in the control group [120 (0, 720) vs. 300 (0, 890) min, P=0.029], while the duration of CRRT in the research group was remarkably better than that in the control group [10.6 (4.9, 27.7) vs. 8.1 (3.6, 25.0) d, P=0.024], and the risk of filter replacement due to special conditons in the research group was lower than that in the control group (46.4% vs. 65.4%, P=0.048). There was no statistically significant difference in the length of intensive care unit hospitalization or total hospitalization between the two groups (P>0.05). Conclusion Both heparin and citric acid could assist the treatment of CRRT, while citric acid might be apt to improve local coagulation and systemic inflammatory response.
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.
ObjectiveTo explore the application value of transoral snare traction in endoscopic submucosal dissection (ESD) for patients with early gastric cancer (EGC). MethodsA total of 90 EGC patients admitted to Xinxiang Central Hospital from January 2020 to April 2023 were selected and randomly divided into a study group and a conventional group using a random number table method. The conventional group was received ESD, while the study group was received transoral snare traction in combination with ESD. Baseline data, treatment efficacy, as well as the serum inflammatory-stress factors (tumor necrosis factor alpha, interleukin-6, adrenocorticotropic hormone, and cortisol) and gastrointestinal hormones (motilin and gastrin), surgical indicators, gastrointestinal function recovery indicators before surgery and on day 1 and 3 after surgery, postoperative complications, improvement in quality of life, and 2-year recurrence rate were compared between the two groups. The test level was set at α=0.05. ResultsThere were no statistically significant differences in age, gender, body mass index, disease duration, longest tumor diameter, lesion location, and tumor differentiation degree between the study group and the conventional group (P>0.05). The total effective rate in the study group was higher than that in the conventional group [95.6% (43/45) vs. 80.0% (36/45), χ2=5.075, P=0.024]. The results of repeated-measures ANOVA showed statistically significant between-group, time, and between-group-time interaction effects of serum inflammatory-stress factor and gastrointestinal hormone levels in the study and conventional groups (P<0.05), the effect of the time factor on inflammatory-stress factors and gastrointestinal hormones varied with intervention (P<0.001), postoperative inflammatory-stress factors levels in the study group exhibited aninitial increase followed by a decline, ultimately falling below those of the conventional group, the levels of serum motilin and gastrin in the study group continued to decrease than those before surgery and the reduction was smaller in the study group than in the control group. The operation duration, recovery of bowel sounds, the first exhaust, the first defecation, and the first meal time in the study group were shorter than those in the conventional group (P<0.05), and the intraoperative blood loss was less than that in the conventional group (P<0.05), the overall complication rate was lower than that in the conventional group [4.4% (2/45) vs. 17.8% (8/45), χ2=4.050, P=0.044], and the improvement rate in quality of life was higher than that in the conventional group [77.8% (35/45) vs. 57.8% (26/45), χ2=4.121, P=0.042]. There was no significant difference in the recurrence rate between the two groups after a 2-year follow-up [7.0% (3/43) vs. 17.1%(7/41), χ2=1.191, P=0.275]. ConclusionThe results of this study suggest that the treatment of early gastric cancer with transoral snare traction combined with ESD has significant efficacy, which can optimize surgical procedures, reduce inflammatory-stress reaction, improve gastrointestinal hormone levels, promote disease recovery, reduce the occurrence of complications, and achieve good short- and medium-term outcomes.
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.
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.
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.