RESUMO
The inflammatory process plays a significant role in the pathophysiology of Alzheimer's disease (AD). Anti-neuroinflammatory cascade is now considered an important measure for AD treatment. Astragaloside IV (AS-IV), a saponin of Astragali radix, has shown significant anti-inflammatory properties and protective effects against neurodegenerative diseases. However, the mechanisms of AS-IV in treating Alzheimer's disease (AD) have not been fully determined. The experiment research was carried out to comprehensively confirm the beneficial effects and underlying molecular mechanisms of AS-IV to AD. In this research, BV-2 cells were cultured in vitro and treated by AS-IV under the stimulation of LPS, qRT-PCR was adopted to analyze the mRNA expression level of inflammatory factors. Western-blot was carried out to analyze the phosphorylation level of NF-κB signaling pathway. 5xFAD mice were administrated AS-IV mixed in the diet for 3 months. Behavioral experiments were adopted to analyze learning and memory abilities. Immunohistochemical staining was adopted to observe the proliferation of microglias and the accumulation of Aß plaques. AS-IV cut down the mRNA expression of IL-1ß, COX-2, iNOS and TNF-α in LPS-stimulated BV-2 cells by suppressing the phosphorylation of IκB and p65, and inhibited the phosphorylated p65 from entering the nucleus. AS-IV increased the frequency of recognizing new objects in the novel object recognition test, shortened the escape latency, raised the number of crossing platform in the Morris water maze, inhibited the hyperplasia of microglias, and reduced the production of senile plaques in 5xFAD mice. In brief, AS-IV ameliorates learning and memory impairment by relieving the intensity of neuroinflammatory response in AD. Therefore, AS-IV is very promising to be a herbal medicine for AD treatment.
RESUMO
PURPOSE: Assessing the downstaging effects of neoadjuvant chemotherapy (NACT) in patients with locally advanced nasopharyngeal carcinoma (LANPC) and predicting response to treatment remain challenging. The present study aimed to evaluate the long-term prognosis of downstaging after NACT in patients with LANPC and to investigate the prognostic value of post-NACT tumor downstaging on treatment outcomes in the era of concurrent chemoradiotherapy (CCRT). METHODS: This retrospective study included 226 patients with stage III (n = 188) and IVA (n = 38) NPC admitted to Haikou People's Hospital between 1 October 2009 and 1 October 2012. The patients were grouped as downstaging or no after NACT. Overall survival (OS), locoregional failure-free survival (LFFS), and distant failure-free survival (DFFS) were analyzed. RESULTS: Among 226 patients, 196 (86.7%) were in the downstaging group and 30 (13.3%) were in the non-downstaging group. The longest follow-up was 76 months, and the median was 45 months. The 3-year OS rates of the downstaging group and non-downstaging group were 91.0% (95% CI 0.89-0.93) and 69.5% (95% CI 0.66-0.72) (P = 0.005). The 5-year OS rates were 81.6% (95% CI 0.78-0.86) and 53.3% (95% CI 0.49-0.61) (P = 0.001). N downstaging (3-year OS, HR 0.491, 95% CI 0.221-0.881, P = 0.022; 5-year OS, HR = 0.597, 95% CI 0.378-0.878, P = 0.021) was independently associated with OS. CONCLUSION: In the treatment of LANPC, the patients with downstaging after NACT have a better prognosis than those without downstaging. This study suggests that NACT can improve the prognosis for patients with LANPC if there is downstaging.