Background Breast cancer (BC) has a high incidence and mortality rate in females. Its conventional clinical characteristics are far from accurate for the prediction of individual outcomes. Therefore, we aimed to develop a novel signature to predict the survival of patients with BC. Methods We analyzed the data of a training cohort from the Cancer Genome Atlas (TCGA) database and a validation cohort from the Gene Expression Omnibus (GEO) database. After the applications of Gene Set Enrichment Analysis (GSEA) and Cox regression analyses, a glycolysis-related signature for predicting the survival of patients with BC was developed; the signature contained AK3, CACNA1H, IL13RA1, NUP43, PGK1, and SDC1. Furthermore, on the basis of expression levels of the six-gene signature, we constructed a risk score formula to classify the patients into high- and low-risk groups. The receiver operating characteristic (ROC) curve and the Kaplan-Meier curve were used to assess the predicted capacity of the model. Later, a nomogram was developed to predict the outcomes of patients with risk score and clinical features over a period of 1, 3, and 5 years. We further used Human Protein Atlas (HPA) database to validate the expressions of the six biomarkers in tumor and sample tissues, which were taken as control. Results We constructed a six-gene signature to predict the outcomes of patients with BC. The patients in the high-risk group showed poor prognosis than those in the low-risk group. The area under the curve (AUC) values were 0.719 and 0.702, showing that the prediction performance of the signature is acceptable. Additionally, Cox regression analysis revealed that these biomarkers could independently predict the prognosis of BC patients with BC without being affected by clinical factors. The expression levels of all six biomarkers in BC tissues were higher than that in normal tissues; however, AK3 was an exception. Conclusion We developed a six-gene signature to predict the prognosis of patients with BC. Our signature has been proved to have the ability to make an accurate prediction and might be useful in expanding the hypothesis in clinical research.
Acute gouty arthritis is a self-limiting inflammatory disease resulting from the deposition of monosodium urate (MSU) crystals. It has been shown that Gentiopicroside (GPS) possesses anti-inflammatory and analgesic functions. The aim of this study was to parse out whether GPS has an effect on acute gouty arthritis. We established an acute gouty arthritis model by the injection of MSU into the paw, and found that GPS relieves MSU-induced mechanical, thermal hyperalgesia, and paw swelling. Furthermore, GPS down-regulated the release of pro-inflammatory cytokines in paw tissues, including IL-1β, IL-6, IL-18, and TNF-α. The results of H&E staining and MPO activity measurement showed that GPS inhibits neutrophil infiltration. And the over-expressions of NOD-like receptor protein 3 (NLRP3), apoptosis-associated speck-like protein containing a caspase recruitment domain (ASC), and Caspase-1 induced by MSU were inhibited by treatment with GPS. These results revealed that GPS can treat acute gouty arthritis based on anti-inflammatory and analgesic properties in vivo, which might be ascribed to the inhibition on NLRP3 inflammasome. Furthermore, we performed in vitro study to confirm the results of in vivo study. Consistently, the results proved that GPS could inhibit the activation of NLRP3 inflammasome in RAW264.7 macrophages stimulated by LPS-MSU. In conclusion, this study provides an experimental basis for the application of GPS and expands the potential value of GPS in the therapy of acute gouty arthritis.
Background: Neuropathic pain (NP) is a syndrome that arises from central or peripheral nerve injury, which manifests primarily as hyperalgesia, spontaneous pain, and allodynia. The recent trend has exhibited a shift towards the development of therapies for managing NP. Activation of autophagy is involved in the function of the glial cells, which may be implicated further to attenuate pain.Methods: In this study, the analgesic effects of electroacupuncture (EA) were evaluated among NP rats developed using spared nerve injury (SNI). Acupuncture treatment or EA was carried out after 7 days of SNI at two acupoints, i.e., the Zusanli (ST36) and Huantiao (GB30).Results: The application of EA was found to attenuate mechanical hyperalgesia. The marker protein for microglial cells (CD11b) alone, without either the astrocyte marker or neuronal marker, was co-expressed with the autophagy indicator p62, as illustrated with immunofluorescence staining. Western blotting demonstrated that the expression levels of p62, Beclin-1, and LC3-II/LC3-I were elevated in the spinal cords of rats in the SNI group compared to the control levels. EA treatment resulted in reduced expression of p62, while the expressions of Beclin-1 and LC3-II/LC3-I were increased. The electron microscopy results indicated that EA could induce autophagy progression in the microglia of the spinal dorsal horn in SNI rats. Furthermore, we explored the causal relationship between EA-induced inhibition of NP and increased autophagic levels in microglia using the AMPK inhibitor compound C, and found that the mechanism of EA-induced analgesia may contribute to the promotion of AMPK/mTOR-mediated autophagy in spinal microglia.Conclusions: Our work showed that the analgesic impact of EA is partly related to AMPK/mTOR pathway activation and autophagy induction in microglial cells, providing a potential therapeutic target for NP.
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