Significance: Breast cancer (BrCa) is the most common cancer worldwide, and high-performance metabolic analysis is emerging in diagnosis and prognosis of BrCa. Here, we used nanoparticle-enhanced laser desorption/ionization mass spectrometry to record serum metabolic fingerprints of BrCa in seconds, achieving high reproducibility and low consumption of direct serum detection. Our analytical method, combined with the aid of machine learning algorithms, was demonstrated to provide high diagnostic efficiency with accuracy of 88.8% and desirable prognostic prediction ( P < 0.005). Furthermore, seven metabolic biomarkers differentially enriched in BrCa serum and their related pathways were identified. Together, our findings provide a tool to characterize BrCa and highlight certain metabolic signatures as potential diagnostic and prognostic factors of diseases including but not limited to BrCa.

Overexpression of the proinflammatory cytokine IL-1β is associated with diverse diseases, including cancer. Alteration of microRNAs has been observed in cancer cells exposed to proinflammatory cytokines, yet their function in inflammation stress remains elusive. Here, we show that IL-1β induces the upregulation of miR-425, which negatively regulates phosphatase and tensin homolog expression by targeting its 3’ UTR. An increase in miR-425 depends on IL-1β-induced NF-kappaB activation, which enhances miR-425 gene transcription upon IL-1β induction. Consequently, repression of phosphatase and tensin homolog by miR-425 promotes gastric cancer cell proliferation, which is required to protect cells from cisplatin-induced apoptosis. Taken together, our data support a critical role for NF-kappaB-dependent upregulation of miR-425, which represents a new pathway for the repression of phosphatase and tensin homolog activation and the promotion of cell survival upon IL-1β induction.

Although the chemopreventive effects of aspirin have been extensively investigated, the roles of many cell components, such as long non-coding RNAs, in these effects are still not completely understood. We identify an aspirin-induced upregulated lncRNA, OLA1P2, in human colorectal cancer. Aspirin induces demethylation of the FOXD3 promoter and promotes expression of the FOXD3 gene. Subsequently, upregulated FOXD3 protein transcriptionally activates lncRNA OLA1P2 expression. OLA1P2 upregulation markedly affects STAT3 signaling pathway activity by inhibiting the nuclear import of phosphorylated STAT3. The phosphorylation of tyrosine-705 of STAT3 is the first step in OLA1P2 binding, and the formation of phosphorylated STAT3 homodimers is subsequently blocked. OLA1P2 interacts directly with STAT3 due to OLA1P2 sharing the same conservative STAT3 transcription response element as STAT3 targets. Regular use of aspirin dramatically decreases the number of metastatic nodules of cancer cells in immunodeficient mouse lungs, and OLA1P2 silencing markedly weakens the anti-metastatic activity of aspirin in the lungs. Additionally, low OLA1P2 levels are associated with malignant transformation and lower overall survival in cancers. The present study finds that the aspirin-FOXD3-OLA1P2-STAT3 axis exhibits exciting anticancer effects and provides new insights into the chemopreventive mechanisms underlying aspirin use.

Chronic low-grade inflammation plays a central role in the pathophysiology of gestational diabetes mellitus (GDM). To investigate the ability of different inflammatory blood cell parameters in predicting the development of GDM and pregnancy outcomes, 258 women with GDM and 1,154 women without were included in this retrospective study. First-trimester neutrophil count outperformed white blood cell count and the neutrophil-to-lymphocyte ratio in the predictability for GDM. Subjects were grouped based on tertiles of neutrophil count during their first-trimester pregnancy. The results showed that as the neutrophil count increased, there was a stepwise increase in GDM incidence as well as in glucose and glycosylated hemoglobin levels, HOMA for insulin resistance (HOMA-IR), macrosomia incidence, and newborn weight. Neutrophil count was positively associated with prepregnancy BMI, HOMA-IR, and newborn weight. Additionally, neutrophil count was an independent risk factor for the development of GDM, regardless of the history of GDM. Spline regression showed that there was a significant linear association between GDM incidence and the continuous neutrophil count when it was >5.0 × 10⁹/L. This work suggested that the first-trimester neutrophil count is closely associated with the development of GDM and adverse pregnancy outcomes.

Background: This study aims to investigate the potential association of peripheral inflammatory blood cell parameters with the incidence and progression of chronic kidney disease (CKD) in patients with diabetes.Methods: The cross‐sectional study included 1192 subjects with diabetes derived from one center. The cohort study included 2060 subjects with diabetes derived from another two centers followed up for 4 years. Logistic regression and Cox proportional hazards models were used to evaluate the association of peripheral inflammatory blood cell with CKD.Results: In the cross‐sectional study, neutrophil count performed best as an independent risk factor for CKD (odds ratio 2.556 [95% confidence interval 1.111, 5.879]) even after 1:1 case–control matching for age, gender, history of high blood pressure and duration of diabetes. Spline regression revealed a significant linear association of CKD incidence with continuous neutrophil count in excess of 3.6 × 10⁹/L. In the cohort study, subjects were grouped based on tertile of neutrophil count and neutrophil‐to‐lymphocyte ratio. Cox regression analysis results showed that only neutrophil count was independently associated with CKD progression (the highest group vs. the lowest group, hazard ratio 2.293 [95% confidence interval 1.260, 4.171]) after fully adjusting for potential confounders. The cumulative incidence of CKD progression in patients with diabetes gradually increased with increasing neutrophil count (53 (7.7%) subjects in the lowest group vs. 60 (8.2%) in the middle group vs. 78 (12.2%) in the highest group).Conclusions: This study suggested that neutrophil count is an independent risk factor for progression of CKD in patients with diabetes.