[Optimization of Stabilizing Agent of Camptothecin Extraction from Nothapodytes pittosporoides Roots].

Objective: To optimize the stabilizing agent of camptothecin extraction from Nothapodytes pittosporoides roots. Methods: The single factor experiment had been conducted to study the impact on the yield of camptothecin with different kinds of stabilizer, stabilizer concentration and temperature. Results: The results showed that with 0. 5% ferrous sulfate at 80 ℃,the best concentration of camptothecin extraction from Nothapodytes pittosporoides roots was got, and the yield of camptothecin after concentration reached to 94. 58%. Conclusion: This process method is efficient and simple, which can be used to solve camptothecin reduction when the extract is concentrated, and the method is benefit for the industrialization of camptothecin extraction.

Well-defined alginate oligosaccharides ameliorate joint pain and inflammation in a mouse model of gouty arthritis.

Background: Gouty arthritis causes severe pain and inflammation. Alginate oligosaccharides (AOSs) are natural products derived from alginate and have anti-inflammatory properties. We explored the potential effects of AOSs with different degrees of polymerization (Dp) on gouty arthritis and associated mechanisms. Methods: We established a mouse model of gouty arthritis by injecting monosodium urate (MSU) into ankle joint. Nocifensive behavior, gait and ankle swelling were used to study AOS's effects. Biochemical assays, in vivo imaging, live cell Ca2+ imaging, electrophysiology, RNA-sequencing, etc. were used for mechanism exploration. Results: AOS2 (Dp=2), AOS3 (Dp=3) and AOS4 (Dp=4) all inhibited ankle swelling, whereas AOS2&3 produced the most obvious analgesia on model mice. AOS3, which was picked for further evaluation, produced dose-dependent ameliorative effects on model mice. AOS3 reversed gait impairments but did not alter locomotor activity. AOS3 inhibited NLRP3 inflammasome activation and inflammatory cytokine up-regulation in ankle joint. AOS3 ameliorated MSU-induced oxidative stress and reactive oxygen species (ROS) production both in vivo and in vitro and reversed the impaired mitochondrial bioenergetics. AOS3 activated the Nrf2 pathway and promoted Nrf2 disassociation from Keap1-bound complex and Nrf2 nuclear translocation, thus facilitating antioxidant gene expression via Nrf2-dependent mechanism. Nrf2 gene deficiency abolished AOS3's ameliorative effects on pain, inflammation and oxidative stress in ankle joints of model mice. AOS3 reduced TRPV1 functional enhancement in DRG neurons and constrained neuroactive peptide release. Conclusions: AOS3 ameliorates gouty arthritis via activating Nrf2-dependent antioxidant signaling, resulting in suppression of ROS-mediated NLRP3 inflammasome activation and TRPV1 enhancement. AOS3 may be novel therapeutics for gouty arthritis.

Development and Validation of a Nomogram for Renal Survival Prediction in Patients with Autosomal Dominant Polycystic Kidney Disease.

Introduction: Due to the wide variation in the prognosis of autosomal dominant polycystic kidney disease (ADPKD), prediction of risk of renal survival in ADPKD patients is a tough challenge. We aimed to establish a nomogram for the prediction of renal survival in ADPKD patients. Methods: We conducted a retrospective observational cohort study in 263 patients with ADPKD. The patients were randomly assigned to a training set (N = 198) and a validation set (N = 65), and demographic and statistical data at baseline were collected. The total kidney volume was measured using stereology. A clinical prediction nomogram was developed based on multivariate Cox regression results. The performance and clinical utility of the nomogram were assessed by calibration curves, the concordance index (C-index), and decision curve analysis (DCA). The nomogram was compared with the height-adjusted total kidney volume (htTKV) model by receiver operating characteristic curve analysis and DCA. Results: The five independent factors used to construct the nomogram for prognosis prediction were age, htTKV, estimated glomerular filtration rate, hypertension, and hemoglobin. The calibration curve of predicted probabilities against observed renal survival indicated excellent concordance. The model showed very good discrimination with a C-index of 0.91 (0.83-0.99) and an area under the curve of 0.94, which were significantly higher than those of the htTKV model. Similarly, DCA demonstrated that the nomogram had a better net benefit than the htTKV model. Conclusion: The risk prediction nomogram, incorporating easily assessable clinical parameters, was effective for the prediction of renal survival in ADPKD patients. It can be a useful clinical adjunct for clinicians to evaluate the prognosis of ADPKD patients and provide individualized decision-making.