Structured triglyceride attenuates lung injury and inflammation in lipopolysaccharide­induced acute lung injury by enhancing GPR120 expression.

Acute lung injury (ALI) is a serious clinical problem. The present study was performed to investigate the effect of structured triglyceride (STG) on the development of lipopolysaccharide (LPS)­induced ALI and its underlying mechanism of action. To establish an LPS­induced ALI mouse model, mice were intranasally administered 50 µl LPS. The pathological changes in the lung were observed via haematoxylin­eosin staining. The lung injury score, lung wet/dry weight (W/D) ratio, and myeloperoxidase (MPO) activity were used to evaluate the degree of lung injury. The expression levels of interleukin (IL)­1ß, IL­6 and tumour necrosis factor­α in lung tissues were measured through reverse transcription­quantitative polymerase chain reaction. The enzyme­linked immunosorbent assay was used to measure the levels of pro­inflammatory cytokines in bronchoalveolar lavage fluid. Furthermore, western blotting was performed to detect the activity of the transforming growth factor­α­activated kinase 1 (TAK1)/NF­κB pathway. LPS­induced ALI mice were treated with AH7614 [a G­protein coupled receptor 120 (GPR120) inhibitor] to confirm the effect of STG on GPR120. STG treatment decreased the lung pathological changes, lung injury score, lung W/D ratio, and proinflammatory cytokine expression levels and inhibited TAK1/NF­κB pathway activity in the LPS­induced ALI mouse model. Additionally, AH7614 reversed the inhibitory effects of STG on lung injury, inflammation, and TAK1/NF­κB pathway activity in ALI. Moreover, AH7614 weakened the inhibitory effects of STG on inflammation and TAK1/NF­κB pathway activity in LPS­induced RAW264.7 cells. Collectively, STG may suppress the TAK1/NF­κB pathway activity by enhancing GPR120 expression to alleviate the lung injury and inflammation in ALI. These results suggest the therapeutic potential of STG in the treatment of ALI.

High-Dose Aluminum Exposure Further Alerts Immune Phenotype in Aplastic Anemia Patients.

This study explored the relationship between immunological status and clinical characteristics of aplastic anemia (AA) patients to plasma aluminum levels, which were increased after constant exposure to high levels of this metal. Sixty-two AA patients (33 cases with high and 29 cases with low or no exposure to aluminum) and 30 healthy controls were selected for this study. Aluminum in human albumin solution was measured by inductivity coupled plasma mass spectrometry. IL-10, IL-12, IL-17, and INF-γ levels were measured by enzyme-linked immunosorbent assay. The distribution of lymphocyte subsets were determined by flow cytometry. The expression levels of immunoglobulins and complement C3 and C4 were also measured. Exposure to high aluminum raised the levels of serum aluminum in AA patients (P < 0.01). The levels of hemoglobin and complement C4 were lower in AA patients with high aluminum exposure (P < 0.05 and < 0.01, respectively). The percentage of CD4+ T cells and the ratio of CD4+/ CD8+T cells in peripheral blood in AA patients with high aluminum exposure were higher compared with control AA patients (P < 0.05 in both cases), while the percentage of CD8+ T cells was significantly lower than that in non-aluminum-exposed AA patients (P < 0.05). Compared with non-aluminum-exposed AA patients, the level of IL-10 in the high aluminum-exposed AA group was significantly higher (P < 0.05 in both cases). The immunological and clinical characteristics of AA patients from regions of high aluminum exposure are different to those in from non-aluminum areas. These results suggest that high aluminum exposure alters the immune system in patients suffering from AA.

Hypertension Among Hemorrhagic Stroke Patients in Northeast China: A Population-Based Study 2017-2019.

BACKGROUND We aimed to profile the current epidemiology of hypertension among the survivors of hemorrhagic stroke in northeast China. MATERIAL AND METHODS Our cross-sectional study included 18 796 adults aged 40 years or older and residing in northeast China. Hemorrhagic stroke was identified according to the CT and/or MRI results. Hypertension was defined based on the Chinese hypertension guidelines. RESULTS We identified 208 patients with previous hemorrhagic stroke in this population-based study. The overall prevalence of hypertension in the studied population was 88%. Out of all the survivors of hemorrhagic stroke, 80.9% were aware of their hypertensive condition, 70.5% of the patients were in antihypertensive medications treatment, and only 12% of the patients had their blood pressure under control. Furthermore, only 17.10% of the patients who took hypertensive medications achieved appropriate blood pressure. Calcium channel blockers were more commonly used than other medications. Patients with controlled hypertension had significantly higher percentages of comorbidities when compared to those with uncontrolled hypertension. In our patient sample, the rates of stage 2 and stage 3 hypertension in the hemorrhagic stroke population were 28.8% and 15.9%, respectively, and women had a significantly higher prevalence of stage 3 hypertension when compared with men (21.3% vs. 10.0%, P=0.026). CONCLUSIONS The high prevalence of uncontrolled hypertension and high rates of blood pressure at stages 2 and 3 in patients with prior hemorrhagic stroke indicated a considerable stroke burden in northeast China. Therefore, effective and long-time management of hypertension in stroke survivors should be a priority.

CARF, As An Oncogene, Promotes Colorectal Cancer Stemness By Activating ERBB Signaling Pathway.

INTRODUCTION: The role of CARF, a calcium-responsive transcription factor, in colorectal cancer initiation and development is still unknown. Here, we report that CARF promotes colorectal cancer stemness through ERBB signaling pathway. MATERIALS AND METHODS: Both colorectal cancer cell lines and primary cells were used in this study. The levels of target mRNA and protein in the cells were examined by qRT-PCR and Western blot. Gene manipulation was achieved by the lentivirus delivery system. Luciferase reporter gene assay was employed to analyze the transcriptional activity of the promoter. ChIP assay was performed for the examination of the binding between CARF and the promoters of MAPK8 and JUN. Kaplan-Meier survival curve was generated by the R2 program. Correlation analysis was performed using Spearman correlation analysis. RESULTS: Aberrant upregulation of CARF has been found in tumor tissues of colorectal cancer patients and associated with poor prognosis. Ectopic expression of CARF promoted the sphere-formation activities, as well as the expression of stem cell markers in colorectal cancer cells and knockdown of CARF, inhibited these activities. The mechanistic analysis showed that CARF directly binds to the promoter of MAPK8 and JUN, promotes the expression of MAPK8 and JUN, activates the ERBB signaling pathway, and thereby promotes the maintenance of the stemness in colorectal cancer cells. CONCLUSION: CARF, as an oncogene, promotes colorectal cancer stemness by activating ERBB signaling pathway. The ERBB signaling pathway that serves as the main downstream effector of CARF could be an efficient drug target for colorectal cancer caused by aberrant expression of CARF.