Preparation and performance characteristics of spider venom peptide nanocapsules.

BACKGROUND: ω-hexatoxin-Hvn1b is an insecticidal toxin produced by the Tasmanian funnel-web spider (Hadronyche venenata), that can be exploited for development of novel bioinsecticides. Due to its larger size and low membrane permeability, this toxin usually has a slower mode of action compared to conventional small molecule insecticides. Nanoscale materials have unique optical, electrical, mechanical and biological properties, and show great application prospects for pesticide delivery. RESULTS: The physical and chemical properties of nanocapsules were characterized using transmission electron microscopy, laser particle size analysis, Fourier transform infrared spectroscopy, contact angle testing and with a fluorescence spectrophotometer. The results indicated that the nanocapsules were spherical, with an average particle size of 197.70 nm, the encapsulation efficiency rate was 75.82% and the Zeta potential was -32.90 mV. Penetration experiments showed that the nanocapsules could promote protein passage through the intestinal tract of Spodoptera litura and reach the body fluid. Then we expressed ω-hexatoxin-Hvn1b by prokaryotic expression. Bioassay results showed that the oral toxicity of ω-hexatoxin-Hvn1b nanocapsules to S. litura was higher than that of the ω-hexatoxin-Hvn1b. CONCLUSION: In this paper, we reported a construction method of spider venom peptide nanocapsules based on polylactic-co-glycolic acid by multiple emulsion for delivery of protein to improve the insecticidal effect and oral activity of ω-hexatoxin-Hv1a. © 2022 Society of Chemical Industry.

Efficacy and Pharmacological Mechanism of Poria cocos-Based Formulas Combined With Chemotherapy for Ovarian Cancer: A Integrated Systems Pharmacology Study.

Previous studies have shown that Poria cocos-based formulas combined with chemotherapy can improve the quality of life of ovarian cancer patients. However, the results are still controversial. We systematically searched the literature from eight databases to evaluate the efficacy and safety of Poria cocos-based formulas in combination with paclitaxel-carboplatin in treating ovarian cancer (OC). Subsequently, network pharmacology, molecular docking and cell experiments were performed to further verify the underlying molecular mechanism. Thirteen randomized controlled trials, including 922 patients with OC, were enrolled in the study. The results indicated that Poria cocos-based compounds combined with paclitaxel-carboplatin significantly improved patients' tumor response rate, traditional Chinese medicine syndrome score, Karnofsky Performance Scale, physical and social function, and reduced side effects of chemotherapy compared to the paclitaxel-carboplatin alone. According to the network pharmacological analysis, tumulosic acid were the most bioactive compounds of Poria cocos. BCL2L1 is highly expressed in OC and is associated with a worse prognosis which could become potential drug target. Functional enrichment analysis suggested that the anti-OC effect of Poria cocos may be related to PI3K-Akt signaling pathway. The molecular docking results indicated that tumulosic acid might inhibit OC by regulating BCL2L1. Vitro experiment confirmed tumulosic acid that induced cell apoptosis by modulating PI3K/AKT signaling and BCL2L1. Our study may provide a clinical basis and theoretical rationale for combining Poria cocos-based formulas with chemotherapy for OC. In addition, the integrated pharmacological strategy proposed in our study provides an excellent example for exploring the mechanism of complex formulas.

Can Elderly Patients With Pancreatic Cancer Gain Survival Advantages Through More Radical Surgeries? A SEER-Based Analysis.

BACKGROUND AND AIMS: In recent years, the best treatment method for pancreatic cancer in elderly patients has remained controversial. Surgery is the main treatment modality for pancreatic cancer. This study aimed to determine whether elderly patients with pancreatic cancer can gain survival advantages through more active and radical surgical treatment and evaluate the best treatment method and potential prognostic factors. METHODS: From the Surveillance, Epidemiology, and End Results program (SEER) database, 10,557 elderly patients (aged ≥65 years) with pancreatic cancer were included as Cohort 1, and Propensity Score Matching (PSM) evaluation was performed to generate Cohort 2 (424 pairs). Overall Survival (OS) and Cause-Specific Survival (CSS) were determined using Kaplan-Meier survival curves, and differences were assessed using the Log-rank test. Multivariate logistic regression analysis and the forest plot of hazard ratio (HR) was made to assess the association between potential prognostic factors, including surgery and different surgical methods, and survival in elderly patients. RESULTS: We identified 10,557 eligible patients with pancreatic cancer, who formed Cohort 1. The total OS and CSS in the surgery group were significantly higher than those in the non-surgery group (P < 0.001). Age, stage (AJCC 8th), grade, lymph node metastasis, radiation, chemotherapy, and surgical methods were independent factors affecting the prognosis of elderly patients. In Cohort 2, Total pancreatectomy (Total PT) had the lowest risk ratio (HR = 0.31, P < 0.001) and longest median CSS (18.000 months), while Extension Total pancreatectomy (Ex-Total PT, HR = 0.34, P < 0.001) showed the lower median CSS (17.000 months) and median OS (14.000 months). Partial pancreatectomy (Partial PT, HR = 0.46, P < 0.001) showed the lowest median CSS (13.000 months) and median OS (12.000 months), although they were still higher than the median CSS (6.000 months) and median OS (5.000 months) in the non-surgery group. CONCLUSIONS: Based on the SEER database, surgical treatment is an independent prognostic factor in elderly patients with pancreatic cancer. Compared with other surgical methods, Total PT can offer elderly patients the best survival advantages. However, Ex-Total PT, a more radical method, does not seem to be the best treatment option for the survival and benefit of elderly patients.