Serum CEA, CYFRA-211, and NSE as Diagnostic Biomarkers for Bone Metastasis in Lung Cancer.

Objective: This study aims to assess the diagnostic efficacy of serum carcinoembryonic antigen (CEA), cytokeratin fragment 21-1 (CYFRA21-1), and neuron-specific enolase (NSE) in detecting bone metastases in patients with non-small cell lung cancer (NSCLC). Methods: A retrospective analysis was conducted on 120 NSCLC patients diagnosed between January 2023 and June 2023. Patients were categorized into bone metastasis (n=60) and non-bone metastasis (n=60) groups. Bone metastasis severity was graded using Soloway criteria, and serum biomarker levels were measured via electrochemiluminescence. Results: No significant differences in basic information were observed between the two groups (P > .05). Patients with bone metastasis exhibited higher levels of CEA, NSE, and CYFRA21-1 compared to those without bone metastasis (P < .001). The OR with 95% CI for NSE (ng/mL) was 1.966 (95%CI: 1.672 - 2.311), for CEA (ng/mL) was 6.854 (95%CI: 5.419 - 8.688), and for CYFRA21-1 (ng/mL) were 1.527 (95%CI: 1.291 - 1.805). Biomarker levels increased with bone metastasis (P < .05). The NSE (ng/mL) values for Level II vs Level I were OR = 1.155 (95%CI: 1.024 - 1.303), and for Level III vs Level I, the OR was 1.455 (95%CI: 1.291 - 1.637). The CEA (ng/mL) values for Level II vs Level I were OR = 1.111 (95%CI: 0.998 - 1.237), and for Level III vs Level I, the OR was 1.324 (95%CI: 1.184 - 1.483). The CYFRA21-1 (ng/mL) values for Level II vs. Level I were OR = 1.102 (95%CI: 0.988 - 1.230), and for Level III vs Level I, the OR was 1.332 (95%CI: 1.190 - 1.491). In addition, CEA demonstrated an AUC of 0.789, while the combined diagnosis AUC was 0.816. Conclusion: Serum CEA, CYFRA21-1, and NSE levels correlate with bone metastases severity in NSCLC and have the potential to improve diagnostic efficacy.

Exercise Reduces Morphine-Induced Hyperalgesia and Antinociceptive Tolerance.

Chronic morphine intake for treating various pain is frequently concomitant with morphine-induced hyperalgesia and tolerance. The mechanisms can be explained by the activation of p38-MAPK proteins in microglia in the spinal cord horn. Exercise has been shown to prevent the development of microglia overactivation. Thus, we designed to test whether exercise prevents the morphine-induced hyperalgesia and tolerance as well as suppression of p38 phosphorylation. A p38 inhibitor SB203580, exercise, and exercise preconditioning were used for treating morphine-induced hyperalgesia and tolerance development in the present study. The behavior tests for hyperalgesia and tolerance were performed in male Wistar rats before and after morphine administration. Western blotting and immunostaining for examining phosphorylated-p38 expression were performed after the behavior tests. Our results showed that SB203580 and exercise, but not exercise preconditioning, prevented the occurrence of morphine-induced hyperalgesia and tolerance. Meanwhile, exercise decreased morphine-induced phosphorylated-p38 overexpression. In summary, exercise prevented the development of morphine-induced hyperalgesia and tolerance. The mechanism may be related to inhibition of p38 phosphorylation.

Circ_ZFR contributes to the paclitaxel resistance and progression of non-small cell lung cancer by upregulating KPNA4 through sponging miR-195-5p.

BACKGROUND: A growing body of evidence has demonstrated the vital roles of circular RNAs (circRNAs) in cancer progression and drug resistance. We intended to explore the roles and mechanisms of circ_ZFR in the paclitaxel (PTX) resistance and progression of non-small cell lung cancer (NSCLC). METHODS: Two NSCLC cell lines A549 and H460 were used in this study. Quantitative real-time polymerase chain reaction (qRT-PCR) assay was conducted to measure the levels of circ_ZFR, ZFR, miR-195-5p and karyopherin subunit alpha 4 (KPNA4) mRNA. RNase R assay was used to analyze the characteristic of circ_ZFR. MTT assay was carried out to assess PTX resistance and cell proliferation. Flow cytometry analysis was utilized to analyze cell cycle and apoptosis. Transwell assay was used to examine cell migration and invasion. Western blot assay was conducted to measure the protein levels of Ki67, Twist1, E-cadherin and KPNA4. Dual-luciferase reporter assay was adopted to verify the combination between miR-195-5p and circ_ZFR or KPNA4. Murine xenograft model assay was used to investigate the effect of circ_ZFR on PTX resistance of NSCLC in vivo. RESULTS: Circ_ZFR level was enhanced in PTX-resistant NSCLC tissues and cells. Knockdown of circ_ZFR suppressed PTX resistance, cell cycle process, proliferation, migration and invasion and induced apoptosis in PTX-resistant NSCLC cells. For mechanism analysis, circ_ZFR knockdown markedly downregulated the expression of KPNA4 by sponging miR-195-5p, thereby promoting PTX sensitivity and suppressing cell progression in PTX-resistant NSCLC cells. In addition, circ_ZFR silencing enhanced PTX sensitivity of NSCLC in vivo. CONCLUSION: Circ_ZFR knockdown played a positive role in overcoming PTX resistance of NSCLC via regulating miR-195-5p/KPNA4 axis, which might provide a possible circRNA-targeted therapy for NSCLC.