Icarisid II rescues cognitive dysfunction via activation of Wnt/ß-catenin signaling pathway promoting hippocampal neurogenesis in APP/PS1 transgenic mice.

Restoring the compromised neurogenesis has been served as a potential strategy to rescue cognitive dysfunction of Alzheimer's disease (AD). In this study, we explored whether icarisid II (ICS II), a natural product possessing powerful neuroprotection, could recover the neurogenesis dysfunction of APP/PS1 mice, and investigated its underlying mechanisms. Our results showed that oral administration of ICS II could alleviate cognitive injuries of APP/PS1 mice, promote hippocampal neurogenesis, as well as stimulate Wnt/ß-catenin signal pathway confirmed by upregulated Wnt-3a, phosphorylated glycogen synthase kinase-3ß (p-GSK-3ß), and ß-catenin. ICS II also depressed mitochondrial fission evidenced by upregulated Mitofusin 1 (Mfn 1) and Mitofusin 2 (Mfn 2), and downregulated mitochondrial fission 1 protein (Fis 1), mitochondrial fission factor (Mff), and phosphorylated dynamin-related protein 1 (p-Drp 1). However, these effects of ICS II were blunted by XAV-939, an inhibitor of Wnt/ß-catenin signaling pathway. In summary, our findings revealed that ICS II could improve neurogenesis and inhibit mitochondrial fission via activation of the Wnt/ß-catenin signaling pathway, which contributed to cognitive function restoration of APP/PS1 mice. This study discovered a novel mechanism involving neurogenesis regulation underlying the therapeutic effects of ICS II against AD.

CT-Guided Percutaneous Cryoablation for Lung Metastasis of Colorectal Cancer: A Case Series.

PURPOSE: This study aimed to evaluate the efficacy of computed tomography (CT) guided percutaneous cryoablation (CA) for the management of lung metastases in patients with metastatic colorectal cancer (mCRC). METHODS: Retrospective analysis was performed on 38 mCRC patients with lung metastases, who underwent CT-guided percutaneous CA at our center from May 1, 2020 to November 1, 2021. The technical success rate, 1-year local control (LC) rate, recurrence-free survival (RFS) and treatment-related complications were analyzed. RESULTS: The CA procedure was successfully performed in all patients, with a technical success rate of 100%. The 1-year LC rate was 94.7% (36/38), while 16 patients experienced new distant lung metastases during the follow-up period. The median RFS was 20 months (95% CI: 13.0-27.0). The median RFS of patients with and without extrapulmonary metastasis was 15 and 23 months, respectively. Complications were reported in 18 (47.4%) patients following the CA procedure. Pneumothorax was discovered in 15 (39.5%) patients, and five of these patients (13.2%) required chest tube intubation. Two patients (5.3%) presented with hemoptysis during the CA procedure. One patient developed subcutaneous emphysema as detected in the post-procedure follow-up imaging. All patients tolerated the peri-procedural pain well under local anesthesia, and the mean visual analog scale (VAS) score was 2.8. CONCLUSION: Lung CA is a safe and well-tolerated treatment with a satisfactory local control rate for patients with lung metastases derived from mCRC.

Jujuboside A inhibits oxidative stress damage and enhances immunomodulatory capacity of human umbilical cord mesenchymal stem cells through up-regulating IDO expression.

Impaired immunomodulatory capacity and oxidative stress are the key factors limiting the effectiveness of mesenchymal stem cell transplantation therapy. The present study was aimed to investigate the effects of jujuboside A (JuA) on the protective effect and immunomodulatory capacity of human umbilical cord mesenchymal stem cells (hUC-MSCs). Hydrogen peroxide was used to establish an oxidative damage model of hUC-MSCs, while PBMCs isolated from rats were used to evaluate the effect of JuA pre-treatment on the immunomodulatory capacity of hUC-MSCs. Furthermore, Hoechst 33258 staining, lactate dehydrogenase test, measurement of malondialdehyde, Western blot, high-performance liquid chromatography; and flow cytometry were performed. Our results indicated that JuA (25 µmol·L-1) promoted the proliferation of hUC-MSCs, but did not affect the differentiating capability of these cells. JuA pre-treatment inhibited apoptosis, prevented oxidative damage, and up-regulated the protein expression of nuclear factor-erythroid factor 2-related factor 2 and heme oxygenase 1 in hUC-MSCs in which oxidative stress was induced with H2O2. In addition, JuA pre-treatment enhanced the inhibitory effect of hUC-MSCs against abnormally activated PBMCs, which was related to stimulation of the expression and activity of indoleamine 2,3-dioxygenase. In conclusion, our results demonstrate that JuA pre-treatment can enhance the survival and immunomodulatory ability through pathways related to oxidative stress, providing a new option for the improvement of hUC-MSCs in the clinical setting.

Jujuboside a promotes proliferation and neuronal differentiation of APPswe-overexpressing neural stem cells by activating Wnt/ß-catenin signaling pathway.

Mobilization of hippocampal neurogenesis has been considered as a potential strategy for the treatment of neurodegenerative diseases, including Alzheimer's disease (AD). In present study, we evaluated both the neuroprotective effects and the effects on the proliferation and differentiation of APP-overexpressing neural stem cells (APP-NSCs) by Jujuboside A (JuA) in vitro. Our results demonstrated that JuA (50 µM) decreased apoptosis and suppressed oxidative stress damage of APP-NSCs. JuA (50 µM) upregulated the secretion of brain-derived neurotrophic factor and promoted the proliferation and neuronal differentiation of APP-NSCs. Moreover, JuA (50 µM) upregulated Wnt-3a and ß-catenin protein expression, and enhanced the expression of downstream genes Ccnd1, Neurod1 and Prox1. However, XAV-939, an inhibitor of the Wnt/ß-catenin signaling pathway, inhibited these positive effects of JuA. Taken together, these findings suggest that JuA promote proliferation and neuronal differentiation of APP-NSCs partly by activating the Wnt/ß-catenin signaling pathway. We hope that this study will provide a viable strategy for the treatment of AD.