Astragaloside IV-PESV inhibits prostate cancer tumor growth by restoring gut microbiota and microbial metabolic homeostasis via the AGE-RAGE pathway.

BACKGROUND: Prostate cancer (PCa) is becoming the most common malignancy in men worldwide. We investigated the effect of astragaloside IV combined with PESV on the gut microbiota and metabolite of PCa mice and the process of treating PCa. METHODS: Nude mice were genetically modified to develop tumors characteristic of PCa. The treatment of PCa mice involved the administration of a combination of astragaloside IV and peptides derived from scorpion venom (PESV). Feces were collected for both 16 S rDNA and metabolic analysis. Fecal supernatant was extracted and used for fecal transplantation in PCa mice. Tumor development was observed in both PCa mice and nude mice. Tumor histopathology was examined, and the expression of inflammatory factors and the AGE-RAGE axis in PCa tissues were analyzed. RESULTS: PCa mice treated with Astragaloside IV in combination with PESV showed a significant reduction in tumor volume and weight, and stabilization of gut microbiota and metabolites. At the Genus level, significant differences were observed in Porphyromonas, Corynebacterium, Arthromitus and Blautia, and the differential metabolites were PA16_016_0, Astragaloside+, Vitamin A acid, Nardosinone, a-Nortestoster, D-Pantethine, Hypoxanthine, Pregnenolone, cinnamic acid, Pyridoxa, Cirtruline and Xanthurenate. There was a correlation between gut microbiota and metabolites. After the fecal transplantation, tumor growth was effectively suppressed in the PCa mice. Notably, both the mRNA and protein levels of the receptor for advanced glycation end products (RAGE) were significantly decreased. Furthermore, the expression of inflammatory factors, namely NF-κB, TNF-α, and IL-6, in the tumor tissues was significantly attenuated. Conversely, upregulation of RAGE led to increased inflammation and reversed tumor growth in the mice. CONCLUSION: Astragaloside IV combined with PESV could treat PCa by intervening in gut microbiota composition and metabolite by targeting RAGE.

Four cases report: Treatment of knee joint cartilage defects using autologous chondrocyte patch implantation.

Introduction: Autologous chondrocyte implantation (ACI) is a crucial method for the treatment of defects in articular cartilage. However, the extant methods for the preparation of autologous chondrocyte patch are relatively complicated and money-consuming. Therefore, an efficient, reliable, easy-to-follow, and cost-effective technique is needed to overcome constraints. This case report aims to introduce an autologous chondrocyte patch fabrication technique to repair knee joint cartilage defects and report our typical cases with a 2-year follow-up. Case presentation: We described four cases in which patients complained of knee joint pain. According to radiological examination, the patients were diagnosed as knee joint cartilage defect. Arthroscopy and autologous chondrocyte patch implantation were performed as well as a 2-year follow up of patients. The autologous chondrocyte patch for knee joint cartilage repair was fabricated using a "sandwich" technique. The preoperative and postoperative knee function was evaluated by four subjective evaluation systems. MRI was performed for all patients to achieve more intuitionistic observation of the postoperative radiological changes of defect sites. The quality of repaired tissue was evaluated by Magnetic Resonance Observation of Cartilage Repair Tissue (MOCART). Postoperative follow-up showed improvement in clinical and MOCART scores for all patients. However, one patient complained of knee joint pain after walking for a long time or recreational activities from 12- to 18-month postoperatively. The location of pain for this patient was not in accordance with the location of cartilage defect. Conclusion: The patients undergoing autologous chondrocyte patch implantation demonstrated clinical improvement and good quality of repaired tissue postoperatively. The procedure is an efficient and cost-effective treatment for knee joint cartilage defect in this report. In addition, patients with osteoarthritis carry the risk of a poor outcome after the procedure, and whether to have a procedure should be considered carefully.

Diagnostic and Therapeutic Role of Extracellular Vesicles in Articular Cartilage Lesions and Degenerative Joint Diseases.

Two leading contributors to the global disability are cartilage lesions and degenerative joint diseases, which are characterized by the progressive cartilage destruction. Current clinical treatments often fail due to variable outcomes and an unsatisfactory long-term repair. Cell-based therapies were once considered as an effective solution because of their anti-inflammatory and immunosuppression characteristics as well as their differentiation capacity to regenerate the damaged tissue. However, stem cell-based therapies have inherent limitations, such as a high tumorigenicity risk, a low retention, and an engraftment rate, as well as strict regulatory requirements, which result in an underwhelming therapeutic effect. Therefore, the non-stem cell-based therapy has gained its popularity in recent years. Extracellular vesicles (EVs), in particular, like the paracrine factors secreted by stem cells, have been proven to play a role in mediating the biological functions of target cells, and can achieve the therapeutic effect similar to stem cells in cartilage tissue engineering. Therefore, a comprehensive review of the therapeutic role of EVs in cartilage lesions and degenerative joint diseases can be discussed both in terms of time and favorability. In this review, we summarized the physiological environment of a joint and its pathological alteration after trauma and consequent changes in EVs, which are lacking in the current literature studies. In addition, we covered the potential working mechanism of EVs in the repair of the cartilage and the joint and also discussed the potential therapeutic applications of EVs in future clinical use.