Phloridzin reduces synovial hyperplasia and inflammation in rheumatoid arthritis rat by modulating mTOR pathway.

Rheumatoid arthritis (RA) is an inflammatory autoimmune disease and management of it still a challenge. Given report evaluates protective effect of phlorizin on RA and also postulates the molecular mechanism of its action. Bovine type II collagen (CIA) and Freund's incomplete adjuvant (1:1 and 1 mg/ml) was administered on 1st and 8th day of protocol to induce RA in rats and treatment with phlorizin 60 and 120 mg/kg was started after 4th week of protocol. Level of inflammatory cytokines and expression of proteins were estimated in phlorizin treated RA rats. Moreover in-vitro study was performed on Fibroblast-like synoviocytes (FLSs) and effect of phlorizin was estimated on proliferation, apoptosis and expression of mTOR pathway protein after stimulating these cell lines with Tumour Necrosis Factor alpha (TNF-α). Data of study suggest that phlorizin reduces inflammation and improves weight in CIA induced RA rats. Level of inflammatory cytokines in the serum and expression of Akt/PI3K/mTOR proteins in the join tissue was reduced in phlorizin treated RA rats. Phlorizin also reported to reverse the histopathological changes in the joint tissue of RA rats. In-vitro study supports that phlorizin reduces proliferation and no apoptotic effect on TNF-α stimulated FLSs. Expression of Akt/PI3K/mTOR proteins also downregulated in phlorizin treated TNF-α stimulated FLSs. In conclusion, phlorizin protects inflammation and reduces injury to the synovial tissues in RA, as it reduces autophagy by regulating Akt/PI3K/mTOR pathway.

Phlorizin Regulates Synovial Hyperplasia and Inflammation in Rats With Rheumatoid Arthritis by Regulating the mTOR Pathway.

BACKGROUND/AIM: Rheumatoid arthritis (RA) is an inflammatory autoimmune disease, and management of it is still a challenge. The present investigation assessed the potential preventive effect of phlorizin on rats with RA. MATERIALS AND METHODS: A total of 40 healthy Wistar rats were used for this study. Bovine type II collagen and Freund's incomplete adjuvant (1:1 and 1 mg/ml) were administered on days 1 and 8 of the protocol to induce RA in rats; treatment with phlorizin at 60 or 120 mg/kg was started after the 4th week of the protocol, and its effect on inflammation, level of inflammatory cytokines, and expression of proteins were estimated in RA rats. Moreover, an in vitro study was performed on fibroblast-like synoviocytes (FLSs), and the effects of phlorizin on proliferation, apoptosis, and expression of the mechanistic target of rapamycin kinase pathway protein after stimulating these cells with tumor necrosis factor α (TNF-α) were estimated. RESULTS: The data obtained from the study indicate that phlorizin has the potential to mitigate inflammation and enhance weight management in rats with RA induced by bovine type II collagen (CII). The level of inflammatory cytokines in the serum and the expression of protein kinase B (AKT), phosphatidylinositol-4,5-bisphosphate 3-kinase (PI3K), and mechanistic target of rapamycin kinase (mTOR) proteins in the joint tissue were reduced in phlorizin-treated rats with RA. In this investigation, phlorizin was shown to reverse the histological abnormalities in the joint tissue of rats with RA. The in-vitro study showed that phlorizin reduced proliferation and had no apoptotic effect on TNF-α-stimulated FLSs. Expression of AKT, PI3K, and mTOR proteins was also down-regulated in phlorizin-treated TNF-α-stimulated FLSs. CONCLUSION: Phlorizin protects against inflammation and reduces injury to synovial tissues in RA by modulating the AKT/PI3K/mTOR pathway.

Expression and clinical significance of zinc-α2-glycoprotein 1 in osteosarcoma tissues / 中国肿瘤生物治疗杂志

@#[Abstract] Objective: To investigate the expression of zinc-α2-glycoprotein 1 (AZGP1) in osteosarcoma tissue and its relationship with clinicopathological features and prognosis of patients. Methods: A total of 62 pairs of cancer tissue and adjacent normal tissue samples from patients with osteosarcoma treated in the Department of Orthopedics, Second People's Hospital of Nanyang City were collected from August 2012 to August 2014. The expressions of AZGP1 in osteosarcoma tissues and adjacent tissues were detected by using immunohistochemical staining. All patients were followed up on the second day after the operation. The deadline was August 31, 2019. All patients were followed up for 5 years, with death as the end event. The number of end events within 5 years and overall survival (OS) time of the patients were recorded. Kaplan-Meier method was used for survival analysis, and Cox proportional hazard model was used for multivariate analysis of factors affecting patients’ survival. Results: The positive expression rate of AZGP1 in the osteosarcoma tissues was significantly higher than that in the adjacent tissues (77.42% vs 32.26%, P<0.01). There were significant differences in the positive expression rates of AZGP1 in patients with different Eneeking stages, soft tissue infiltration or not and lung metastasis conditions (all P<0.05). Kaplan-Meier survival analysis showed that the average OS time and 5-year OS rate of patients in the AZGP1 positive expression group were significantly lower than those in the negative expression group [(24.19±2.68) months vs (43.07±3.70) months, P<0.01; 18.75% vs 64.29%, P<0.01]. The lung metastasis and positive expression of AZGP1 were risk factors affecting the prognosis of patients with osteosarcoma (HR=3.407, 3.647, all P<0.05). Conclusion: AZGP1 is highly expressed in osteosarcoma tissues, and it is related to the malignant indicators and prognosis of patients. It may be a potential marker for evaluating the prognosis of osteosarcoma patients.