Nano-Drug Delivery Systems Based on Natural Products.

Natural products have proven to have significant curative effects and are increasingly considered as potential candidates for clinical prevention, diagnosis, and treatment. Compared with synthetic drugs, natural products not only have diverse structures but also exhibit a range of biological activities against different disease states and molecular targets, making them attractive for development in the field of medicine. Despite advancements in the use of natural products for clinical purposes, there remain obstacles that hinder their full potential. These challenges include issues such as limited solubility and stability when administered orally, as well as short durations of effectiveness. To address these concerns, nano-drug delivery systems have emerged as a promising solution to overcome the barriers faced in the clinical application of natural products. These systems offer notable advantages, such as a large specific surface area, enhanced targeting capabilities, and the ability to achieve sustained and controlled release. Extensive in vitro and in vivo studies have provided further evidence supporting the efficacy and safety of nanoparticle-based systems in delivering natural products in preclinical disease models. This review describes the limitations of natural product applications and the current status of natural products combined with nanotechnology. The latest advances in nano-drug delivery systems for delivery of natural products are considered from three aspects: connecting targeting warheads, self-assembly, and co-delivery. Finally, the challenges faced in the clinical translation of nano-drugs are discussed.

Underwater Noise Level Recordings from a Water Intake Pontoon and Possible Impacts on Yangtze Finless Porpoises in a Natural Reserve.

Underwater noise pollution caused by human activities may affect freshwater cetaceans to different degrees. To analyze the impacts of water intake pontoons on Yangtze finless porpoises (Neophocaena asiaeorientalis), this study collected underwater noise data from such a pontoon in a nature reserve, plotted the power spectral density of acoustic signals, and calculated the root mean square sound pressure levels and the magnitude of sound source levels. The 1/3-octave sound pressure level root mean square values at the transient holding pens were <18.0 kHz, 39.5−60.0 kHz, which were slightly higher than the Yangtze finless porpoise hearing threshold curve values and therefore could be perceived. However, the results indicated that the porpoises would not develop a temporary hearing threshold shift. Meanwhile, pontoon noise did not interfere with the porpoises' high-frequency acoustic signal nor did it affect their echolocation; it significantly interfered with their low-frequency acoustic signal, however, and the mother−child communication of the finless porpoises was affected, but this effect was quickly compensated due to the limited space range of the holding pens. Through this study of Yangtze finless porpoises, this paper provides a reference for assessing whether human facilities have impacts on freshwater cetaceans.

Establishment of a new protein C detection system based on chromogenic substrate assay and its clinical diagnostic value for deep vein thrombosis.

BACKGROUND: Deficiency of protein C (PC) affects the balance between blood coagulation and fibrinolysis in the human body. Chromogenic-based assay is recommended as the preferred screening method for detecting PC deficiency. We established a PC detection system based on the chromogenic substrate assay. METHODS: First, a kit for the determination of PC activity in plasma was elaborately developed and its reaction parameters on XL-3200c were explored. Then, we evaluated its performance and collected specimens to compare the test results obtained with those of the Siemens detection system. Finally, the clinical diagnostic efficacy of this detection system for deep vein thrombosis (DVT) was assessed. RESULTS: Optimum conditions for PC detection were 0.25-0.1 U/ml protein C activator Protac® and 2.5-1 mM Pefachrome® PCa5297. The composition and concentration ranges of buffer substances and stabilizers in the kit were also explored. Satisfactory results were observed in performance evaluation. The test results of the newly built detection system were highly correlated with those of the Siemens detection system (R2  = 0.9771 in the control group and R2  = 0.9776 in the DVT group), and Bland-Altman plots also showed high consistency between the two detection systems. In addition, the area under the curve (AUC) of the newly built PC detection system for DVT was 0.888, indicating this system could effectively improve the diagnostic sensitivity and specificity for DVT. CONCLUSION: In this study, a sensitive, wide linear range and reliable PC activity detection system were established.

Comparison of immunoregulatory effects of polysaccharides from three natural herbs and cellular uptake in dendritic cells.

Polysaccharides from different types of natural herbs have not been compared with each other to determine their differential potencies on innate immune response, such as maturation of dendritic cells (DC). In addition, the role of endocytosis of polysaccharides in DC maturation has not been explored previously. Polysaccharides isolated from Astragalus membranaceus (APS), Ganoderma lucidum (GLP) and Radix ophiopogonis (OGP) were characterized and applied in bone marrow derived DC. Compared to immature DC, three polysaccharides with immunoactivities showed elongated dendrites, decreased phagocytic abilities, phenotypic changes (CD40/MHCII/CD80/CD86) and increased level of nitric oxide (NO) in a dose dependent manner. Interestingly, blockage of NO by iNOS inhibitor slightly decreased CD40 and MHCII but not CD80/CD86 expression induced by polysaccharides, indicating that NO was partially involved in DC maturation. In addition, GLP can enter cells in a dose and time dependent manner, shown as punctate distribution in the cytoplasm. Endocytic inhibitors sodium azide and brefeldinA that were demonstrated to inhibit cellular uptake of GLP can block phenotypic maturation of DC. Taken together, these results suggested that polysaccharides from natural herbs are effective immunostimulators with variable potencies ranking as GLP>APS>OGP, and the increase of NO level as well as the increase in polysaccharide endocytosis could be the novel strategies for improved innate response and immunotherapy.