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There is an urgent medical need to develop effective therapies that can ameliorate damage to the radiation-exposed hematopoietic system. Nanozymes with robust antioxidant properties have a therapeutic potential for mitigating radiation-induced hematopoietic injury. However, enhancing nanozyme recruitment to injured tissues in vivo while maintaining their catalytic activity remains a great challenge. Herein, we present the design and preparation of a biomimetic nanoparticle, a mesenchymal stem cell membrane camouflaged Prussian blue nanozyme (PB@MSCM), which exhibits biocompatible surface properties and demonstrates enhanced injury site-targeting towards the irradiated murine bone marrow niche. Notably, the constructed PB@MSCM possessed redox enzyme-mimic catalytic activity and could scavenge overproduced reactive oxygen species in the irradiated bone marrow cells, both in vitro and ex vivo. More importantly, the administration of PB@MSCM significantly mitigated hematopoietic cell apoptosis and accelerated the regeneration of hematopoietic stem and progenitor cells. Our findings provide a new targeted strategy to improve nanozyme therapy in vivo and mitigate radiation-induced hematopoietic injury. [ABSTRACT FROM AUTHOR]

Objective: To examine the effects of sodium pyruvate (SP) on metabolic acidosis.Methods: For thein vivoexperiments, we evaluated effects of SP on an ammonium chloride (NH4Cl)-induced hyperchloremic acidosis rat model. SP was infused at overall doses of 2, 4, and 6 mmol·kg− 1for the SP1, SP2, and SP3groups, respectively. Treatment with sodium bicarbonate (SB) was used as a positive control (2 mmol·kg− 1), and treatment with normal saline (NS) was used as a volume control (2 mL·kg− 1). Blood was sampled from the ophthalmic venous plexus for pH, blood gases, electrolytes, glucose, creatinine (Cr), and urea analysis after injection. For thein vitroexperiment, propionate was applied to induce intracellular acidosis in human endothelial cells. Intracellular pH (pHi) was fluorimetrically measured after the addition of SP.Results: In thein vivostudy, the pH of SP1group showed no significant difference compared with that of the NS group. The SP2and SP3groups had a higher pH than the NS group (P< 0.01). The SP3group had a higher pH than the SB group (P< 0.05) and SP1group (P< 0.05). Moreover, SP treatment ameliorated the abnormality of calcium and decreased the blood potassium levels. The SP3group had higher glucose levels than SP1group (P< 0.05). No significant differences were observed between all the groups in the plasma Cr and urea levels. In thein vitrostudy, the pHi increased immediately after the addition of SP.Conclusion: The data suggest that intravascular treatment with SP represents a novel therapeutic strategy to ameliorate metabolic acidosis. [ABSTRACT FROM PUBLISHER]

The kinetic studies and drug designs of butyrylcholinesterase play an important role in the development of Alzheimer's disease therapeutics. In this research, automated docking studies were performed to provide useful insights into butyrylcholinesterase inhibition binding modes with designed 4-acyloxy-biphenyl-4′- N-butylcarbamates (compounds 1- 8). Moreover, several significant linear correlations between experimental and calculated docking results are observed. Among compounds 1- 7, compound 3, which exhibits the strongest hydrophobicity and has four carbonyl hydrogen bindings, shows the highest binding affinity ( Ki = 1.4 μmol/L) with a binding energy of −7.99 kcal/mol. The observed linear correlation of experimental and calculated inhibition constants ( Ki) indicates that the molecular docking results are reliable. Moreover, a good linear correlation is observed between calculated binding energies and experimental p Ki. The experimental Hansch hydrophobicity constants (π values) are also correlated with the docked binding energy. This study reveals important correlations between butyrylcholinesterase experimental and docking results that contribute to the kinetic based identification of antagonists for the treatment of Alzheimer's disease. Furthermore, these docked models provide important insights into a potential series of 4,4′-biphenol-based inhibitors of butyrylcholinesterase. [ABSTRACT FROM AUTHOR]

Leonurus japonicus Houtt., also known as motherwort, is a traditional Chinese medicine that was first identified in Shennong Bencao Jing , the first and essential pharmacy monograph in China. L. japonicus has been regarded as a good gynecological medicine since ancient times. It has been widely used in clinical settings for treatment of gynecological diseases and postnatal rehabilitation with good efficacy and low adverse effects. The main purpose of this study was to determine the angiogenic and wound healing effects of total alkaloid fraction from L. japonicus Houtt. (TALH) in vivo and in vitro. In addition, the main bioactive components of total alkaloids were to be identified and analyzed in this study. First, the UHPLC/Q-TOF-MS method was used to identify and quantify the major components in the TALH extract. The wound healing activity was evaluated in vivo using a rat full-thickness cutaneous wound model. Histological study of wound healing in rat model was performed via immunohistochemistry and immunofluorescence. Cell proliferation was determined by MTT assay. Wound healing and transwell assays were used for detection of cell migration. The effect on tube formation was determined by tube formation assay in HUVECs. Western blot and RT-PCR were used to detect the expressions of relative proteins and genes respectively. Knock-down of SRC by siRNA was done to verify the crucial role of SRC in promotion of angiogenesis induced by TALH. Seven characteristic peaks were recognized in the UHPLC/Q-TOF-MS spectrum, while four of the main components were quantified. The wound model in rats showed that treatment of TALH promoted wound healing by stimulating cellular proliferation and collagen deposition. In vitro experiments showed that co-treatment of TALH and VEGF increased cell proliferation, migration and tube formation in HUVECs. Mechanistic studies suggested that the co-treatment increased gene expressions of SRC, MEK1/2 and ERK1/2, as well as the phosphorylation levels of these proteins. Furthermore, the effect of co-treatment was attenuated after SRC knockdown, suggesting that SRC plays an important role in angiogenesis and wound healing induced by TALH and VEGF co-treatment. Our results showed that TALH was one of the main active components of L. japonicus that promoted angiogenesis and wound healing by regulating the SRC/MEK/ERK pathway. Our study provided scientific basis for better clinical application of L. japonicas. [Display omitted] [ABSTRACT FROM AUTHOR]

[Objective]Antioxidant activities of sugarcane wine and sugarcane vinegar, which were two new kinds of fermented products of sugarcane juice, were investigated and tested using several antioxidant systems in order to provide technical references for developing new sugarcane health products. [Method]With Vc, gallic acid and KDTA as the control, scavenging activities of sugarcane wine and sugarcane vinegar against DPPH free radical, hydroxyl radical ( ·OH), superoxide radical (O2-) and nitrite (NO2-) were measured and their chelation activity against metal ions was evaluated. [Result]The results showed that sugarcane wine and sugarcane vinegar had strong scavenging activity against DPPI 1 free radical, hydroxyl radical (·OH) .superoxide radical (O2- ) and nitrite (NO2-), and more volume meant stronger scavenging activity. The scavenging rate was higher than those of Vc and gallic acid. Sugarcane wine and sugarcane vinegar also exhibited good chelation on metal ions. Sugarcane vinegar had better antioxidant ability than sugarcane wine. [Conclusion]Due to their good antioxidant and scavenging activity, sugarcane wine and sugarcane vinegar are beneficial for human health and their large-scale production is feasible. [ABSTRACT FROM AUTHOR]