Breast cancer metastasis is the main cause of cancer death in women, so far, no effective treatment has inhibited breast cancer metastasis. Sulforaphane (SFN), a natural compound derived from broccoli, has shown potential health benefits in many cancers. However, research on breast cancer metastasis is still insufficient. Here, we showed that SFN, including its two isomers of R-SFN and S-SFN, significantly inhibited TGF-β1-induced migration and invasion in breast cancer cells. Proteomic and phosphoproteomic analysis showed that SFN affected the formation of the cytoskeleton. Subsequent experiments confirmed that SFN significantly inhibited TGF-β1-induced actin stress fiber formation and the expression of actin stress fiber formation-associated proteins, including paxillin, IQGAP1, FAK, PAK2, and ROCK. Additionally, SFN is directly bound to RAF family proteins (including ARAF, BRAF, and CRAF) and inhibited MEK and ERK phosphorylation. These in vitro results indicate that SFN targets the RAF/MEK/ERK signaling pathway to inhibit the formation of actin stress fibers, thereby inhibiting breast cancer cell metastasis.

This study aimed to validate the chronic obstructive pulmonary disease (COPD) Population Screener (COPD-PS) questionnaire as a screening tool in a cohort of Chinese subjects who underwent a health examination, and to summarise its overall performance through a meta-analysis. We enrolled 997 subjects aged ≥40 years who underwent a health examination, both lung function and COPD-PS data were collected. The screening performance of COPD-PS was evaluated with a receiver operating characteristic (ROC) curve analysis, using the area under the curve (AUC) to assess the screening accuracy. A standard diagnostic meta-analysis was used to summarise the screening performance of COPD-PS for COPD. Of the 997 subjects, 157 were identified as having COPD. The COPD-PS score was significantly higher in COPD patients than controls (5.03 ± 5.11 vs. 2.72 ± 1.80, p < .001). At a cut-off of 4, the sensitivity and specificity of COPD-PS for identifying COPD were 74.52 and 70.24%, respectively, with an AUC of 0.79. Eight studies (including this study) were included in this meta-analysis. The pooled estimates for COPD-PS were as follows: sensitivity of 0.66 (95% CI: 0.47–0.63), specificity of 0.86 (95% CI: 0.84–0.89), positive likelihood ratio of 3.00 (95% CI: 1.65–5.47), negative likelihood ratio of 0.43 (95% CI: 0.35–0.52) and diagnostic odds ratio of 7.24 (95% CI: 3.91–13.40). The AUC of the summary ROC curve was 0.78. COPD-PS appears to be a useful tool for screening individuals with a high risk of COPD and guiding the selection of individuals for subsequent spirometry examination.

Cardiovascular diseases are the leading cause of mortality and disability worldwide. We have previously found that sphingosylphosphorylcholine (SPC) is the key molecule leading to vasospasm. We have also identified the SPC/Src family protein tyrosine kinase Fyn/Rho-kinase (ROK) pathway as a novel signaling pathway for Ca²⁺ sensitization of vascular smooth muscle (VSM) contraction. This study aimed to investigate whether hesperetin can inhibit the SPC-induced contraction with little effect on 40 mM K⁺-induced Ca²⁺-dependent contraction and to elucidate the underlying mechanisms. Hesperetin significantly inhibited the SPC-induced contraction of porcine coronary artery smooth muscle strips with little effect on 40 mM K⁺-induced contraction. Hesperetin blocked the SPC-induced translocation of Fyn and ROK from the cytosol to the membrane in human coronary artery smooth muscle cells (HCASMCs). SPC decreased the phosphorylation level of Fyn at Y531 in both VSMs and HCASMCs and increased the phosphorylation levels of Fyn at Y420, myosin phosphatase target subunit 1 at T853, and myosin light chain (MLC) at S19 in both VSMs and HCASMCs, which were significantly suppressed by hesperetin. Our results indicate that hesperetin inhibits the SPC-induced contraction at least in part by suppressing the Fyn/ROK pathway, suggesting that hesperetin can be a novel drug to prevent and treat vasospasm.

The cleavage of osteopontin (OPN) by thrombin results in an N-terminal fragment (OPN-N), which exposes a cryptic integrin-binding motif that promotes the adherence of cells, and plays a proinflammatory role. However, the effect of OPN-N on abdominal aortic aneurysm (AAA) remains unknown. The aim of this study was to investigate the expression of OPN-N in aortic tissue samples obtained from patients, who underwent acute aortic dissection (AD), and normal aorta, effect of OPN-N on angiotensin (Ang) II-induced AAA in mice, and relationship between OPN-N and pyroptosis-related inflammatory factorsin vitro. Hematoxylin and eosin staining was conducted to detect histological changes. Next, we detected the expression of the OPN-N protein. Additionally, ApoE−/− mice were divided into four groups: control, control + M5Ab (to block the OPN-N function in mice), Ang II, and Ang II + M5Ab. All mice were euthanized after a 28-day infusion and whole aortas, including thoracic and abdominal aortas, were collected for morphological and histological analysis of the AAA. The OPN-N protein expression was higher in patients with AD than in normal individuals, while histological changes in the aortas of Ang II mice were suppressed in Ang II + M5Ab mice. The expression of OPN-N, NOD-, LRR-, and pyrin domain-containing protein 3, pro-Caspase-1, ASC, Gasdermin-d, interleukin (IL)-18, IL-1β, matrix metalloproteinase (MMP) 2, and MMP9 was lower in the Ang II + M5Ab group than in the Ang II group. The gene expression of monocyte chemoattractant protein-1, IL-6, and tumor necrosis factor-α was suppressed in the aortic tissues of the Ang II + M5Ab group compared with the Ang II group. Moreover, the expression of α-smooth muscle actin was lower in the Ang II group than in the Ang II + M5Ab group.In vitroresults showed that the increase in the expression of pyroptosis-related inflammatory factors induced by OPN was mediated through the nuclear factor (NF)-κB pathway. In conclusion, OPN-N promotes AAA by increasing the expression of pyroptosis-related inflammatory factors through the NF-κB pathway, inflammation, and extracellular matrix degradation. These results highlight the potential of OPN-N as a new therapeutic target to prevent AAA expansion.