Correlation between the Expression of VEGF and Ki67 and Lymph Node Metastasis in Non-small-Cell Lung Cancer: A Systematic Review and Meta-Analysis.

Background: Lymph node metastasis is the most common and important way of metastasis in NSCLC and is also the most important factor affecting lung cancer stage and prognosis. It is very important to analyze the relationship between the expression of vascular endothelial growth factor (VEGF) and Ki67 and lymph node metastasis (LNM) in non-small-cell lung cancer (NSCLC). Methods: We searched the PubMed, EMBASE, and Cochrane Library and conducted meta-analyses using the R meta-package. Relative risk (RR) with a 95% confidence interval (95% CI) was the main indicator. Results: Totally, 18 studies were considered eligible, with 4521 patients, including 1518 LNM-positive patients and 3033 LNM-negative patients. The incidence of LNM in Ki67-negative patients was lower than that in Ki67-positive patients (RR = 0.66, 95% CI: 0.44, 0.98). The incidence of LNM in VEGF-A-negative patients was lower than that in VEGF-A-positive patients (RR = 0.64, 95% CI: 0.49, 0.83). The incidence of LNM in VEGF-C negative patients was lower than that in VEGF-C positive patients (RR = 0.68, 95% CI: 0.53, 0.88). The incidence of LNM in VEGF-D negative and positive patients were of no significant differences (RR = 0.84, 95% CI: 0.61, 1.14). Conclusion: The high expression of Ki67, VEGF-A, and VEGF-C significantly increases the risk of lymph node metastasis in NSCLC, while the VEGF-D expression has no correlation with lymph node metastasis. The expression levels of Ki67, VEGF-A, and VEGF-C show a good potential for lymph node metastasis prediction.

Chaiqin Qingning Capsule Inhibits Influenza Virus Infection and Inflammation In Vitro and In Vivo.

BACKGROUND: Chaiqin Qingning Capsule (CQ-C) is a traditional Chinese medicine (TCM) formula commonly used to treat respiratory infectious diseases in China. The aim of this study was to detect the effect and mechanism of CQ-C treated with influenza virus in vitro and vivo. METHODS: The cytotoxicity and antiviral activity of CQ-C in vitro was determined by methyl thiazolyl tetrazolium (MTT) assay. The regulation of CQ-C on cytokine/chemokine expression was evaluated using RT-qPCR. In addition, the effect of CQ-C on the pathway protein, NF-κB, and its phosphorylation level was verified by western blotting. After virus inoculation, BALB/c mice were administered with CQ-C of different concentrations for 7 days. Body weight, viral titer, lung pathology, and mortality of the mice were measured, and the level of inflammatory cytokines was also examined using real-time RT-qPCR. RESULTS: CQ-C inhibited the proliferation of influenza virus of various strains in vitro, with the 50% inhibitory concentration (IC50) ranging from 49 to 59 µg/mL. CQ-C downregulated virus-induced gene expression of IL-6, TNF-α, CXCL8, CXCL10, CCL5, and COX-2 in a dose-dependent manner in A549 cells. Also, CQ-C inhibited the expression of NF-κB protein of the signaling pathway. Moreover, a decrease of the lung index and mortality of mice was observed in the CQ-C (1 g/kg/d) group. The related cytokine/chemokine expression was also decreased in the early stages of infection in the mRNA level. CONCLUSION: As a clinically applied Chinese prescription, our study shows that CQ-C has a wide range of effects on several influenza viruses. Moreover, CQ-C could play an important role in anti-influenza activity and anti-inflammation in vitro and in vivo. Thus, CQ-C may be a promising treatment option for influenza.

Erucic acid from Isatis indigotica Fort. suppresses influenza A virus replication and inflammation in vitro and in vivo through modulation of NF-κB and p38 MAPK pathway.

Isatis indigotica Fort. (Ban-Lan-Gen) is an herbal medicine prescribed for influenza treatment. However, its active components and mode of action remain mostly unknown. In the present study, erucic acid was isolated from Isatis indigotica Fort., and subsequently its underlying mechanism against influenza A virus (IAV) infection was investigated in vitro and in vivo. Our results demonstrated that erucic acid exhibited broad-spectrum antiviral activity against IAV resulting from reduction of viral polymerase transcription activity. Erucic acid was found to exert inhibitory effects on IAV or viral (v) RNA-induced pro-inflammatory mediators as well as interferons (IFNs). The molecular mechanism by which erucic acid with antiviral and anti-inflammatory properties was attributed to inactivation of NF-κB and p38 MAPK signaling. Furthermore, the NF-κB and p38 MAPK inhibitory effect of erucic acid led to diminishing the transcriptional activity of interferon-stimulated gene factor 3 (ISGF-3), and thereby reducing IAV-triggered pro-inflammatory response amplification in IFN-ß-sensitized cells. Additionally, IAV- or vRNA-triggered apoptosis of alveolar epithelial A549 cells was prevented by erucic acid. In vivo, erucic acid administration consistently displayed decreased lung viral load and viral antigens expression. Meanwhile, erucic acid markedly reduced CD8+ cytotoxic T lymphocyte (CTL) recruitment, pro-apoptotic signaling, hyperactivity of multiple signaling pathways, and exacerbated immune inflammation in the lung, which resulted in decreased lung injury and mortality in mice with a mouse-adapted A/FM/1/47-MA(H1N1) strain infection. Our findings provided a mechanistic basis for the action of erucic acid against IAV-mediated inflammation and injury, suggesting that erucic acid may have a therapeutic potential in the treatment of influenza.