Macrophages are essential inflammatory cells which regulate the features of immune reactions within tumors. Many studies have reported their regulatory roles in immunity through cytokines and cell signaling. However, relatively few studies have focused on their metabolic features and mechanisms. We aimed to determine the signaling pathway regulating cell metabolism and the mechanism related to the regulation of human tumor‐associated macrophages (TAMs) in gastric cancer (GC). Tumor‐infiltrated macrophages were isolated from human GC tissues using magnetic beads, gene transcription was determined by real‐time PCR, protein expression was monitored using western blots, metabolites were determined using HPLC, and transcriptional regulation was analyzed by the luciferase‐based reporter gene system. A significant decrease in microRNA (miR)‐30c and an increase in regulated in development and DNA damage responses 1 (REDD1) were detected in human GC TAMs, the transcription of miR‐30c was negatively correlated with REDD1. MicroRNA‐30c expression was suppressed by hypoxia‐inducible factor‐1α activation and related to decreased mTOR activity as well as glycolysis in human GC TAMs. Hypoxia‐regulated miR‐30c downregulated REDD‐1 expression by targeting its 3′UTR. Overexpression of miR‐30c or restored mTOR activity in macrophages with miR‐30cLow expression promoted M1 macrophage differentiation and function in TAMs. Therefore, hypoxia in the human GC microenvironment suppressed the expression of miR‐30c, and decreased mTOR activity as well as glycolysis in GC TAMs, thus inhibiting M1 differentiation and function. These results provide a novel metabolic strategy for tumor microenvironment‐based therapy.
Background: Wogonin, a natural flavonoid-like chemical compound, exhibits anti-inflammatory, antitumor, antiviral, neuroprotective, and anxiolytic effects by modulating a variety of cellular signaling pathways including PI3K-Akt, p53, nuclear factor κB (NF-κB), mitogen-activated protein kinase (MAPK) pathways. In this study, its antiviral effect against herpes simplex virus (HSV) type 1 and 2 (HSV-1 and HSV-2) replication was investigated. Results: Wogonin suppressed HSV-2-induced cytopathic effect (CPE) and reduced viral mRNA transcription, viral protein synthesis, and infectious virion particle titers in a dose-dependent manner. A time-of-drug-addition assay demonstrated that wogonin acted as a postentry viral inhibitor. Wogonin also significantly reduced HSV-induced NF-κB and MAPK pathway activation, which has previously been demonstrated to be important for viral replication. Conclusions: Our results suggest that the anti-herpes effect of wogonin may be mediated by modulation of cellular NF-κB and JNK/p38 MAPK pathways and imply that wogonin may be useful as an anti-HSV agent.
Background Dyslipidaemia plays an important role in coronary atherosclerotic disease (CAD). The relationship between the atherogenic index of plasma (AIP) and CAD in elderly individuals was explored in this study. Methods Elderly individuals (age ≥ 65 years) who underwent coronary angiography from January 2016 to October 2020 were consecutively enrolled in the study. Results A total of 1313 individuals, including 354 controls (non-CAD) and 959 CAD patients, were enrolled. In univariate analysis of all populations, the adjusted AIP (aAIP) in the CAD group was 1.13 (0.96, 1.3), which was significantly higher than that in the controls [1.07 (0.89, 1.26)]. However, in subgroup analyses, this phenomenon was only present in males. In addition, further study showed that aAIP was positively related to CAD severity. In binary logistic regression analyses, after adjusting for sex, age, smoking status, primary hypertension (PH), type 2 diabetes mellitus (T2DM), heart rate (HR), white blood cell (WBC) and platelet (PLT), AIP remained independently related to CAD in elderly individuals and was superior to traditional and other nontraditional lipid indices. Subgroup analyses showed that AIP independently influenced CAD risk in males. Ultimately, sensitivity analyses were performed excluding all coronary emergencies, and the final results were similar. Conclusions AIP was positively related to the risk and severity of CAD in elderly individuals and was superior to traditional and other nontraditional lipid profiles. However, this association only exists in elderly males.
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