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OBJECTIVE:To optimize the formulation of Curcumin (CUR)transethosomes(CUR-TEs). METHODS :The contents of CUR in CUR-TEs were determined by HPLC. CUR-TEs were prepared by injection method. Using comprehensive score of encapsulation efficiency and drug loading as index ,based on signal factor test ,Box-Behnken design-response surface method was used to optimize and validate the formulation. The property of CUR-TEs prepared by the optimal formulation was investigated. RESULTS:The optimal formulation of CUR-TEs was as follows as lecithin of 4%,CUR of 0.13%,1,2-propylene glycol of 25%,tween-80 of 1%. Results of validation test of optimal formulation showed that comprehensive score of encapsulation efficiency and drug loading of CUR-TEs was 93.04±2.16,relative error of which to predicted value (91.19)was 2.03%. The encapsulation efficiency of CUR-TEs prepared by optimal formulation was (91.17±1.35)%,and its drug loading was (0.94± 0.02)%. The particle size was (190.64±15.97)nm with polydispersity index of 0.086±0.007,and Zeta potential was (-12.74± 1.60)mV. CONCLUSIONS :The optimized formulation of CUR-TEs is stable ,feasible and repeatable ,with good stability.
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BackgroundCoronavirus infectious disease 2019 (COVID-19) has developed into a global pandemic. It is essential to investigate the clinical characteristics of COVID-19 and uncover potential risk factors for severe disease to reduce the overall mortality rate of COVID-19. MethodsSixty-one critical COVID-19 patients admitted to the intensive care unit (ICU) and 93 severe non-ICU patients at Huoshenshan Hospital (Wuhan, China) were included in this study. Medical records, including demographic, platelet counts, heparin-involved treatments, heparin-induced thrombocytopenia-(HIT) related laboratory tests, and fatal outcomes of COVID-19 patients were analyzed and compared between survivors and nonsurvivors. FindingsSixty-one critical COVID-19 patients treated in ICU included 15 survivors and 46 nonsurvivors. Forty-one percent of them (25/61) had severe thrombocytopenia, with a platelet count (PLT) less than 50x109/L, of whom 76% (19/25) had a platelet decrease of >50% compared to baseline; 96% of these patients (24/25) had a fatal outcome. Among the 46 nonsurvivors, 52{middle dot}2% (24/46) had severe thrombocytopenia, compared to 6{middle dot}7% (1/15) among survivors. Moreover, continuous renal replacement therapy (CRRT) could induce a significant decrease in PLT in 81{middle dot}3% of critical CRRT patients (13/16), resulting in a fatal outcome. In addition, a high level of anti-heparin-PF4 antibodies, a marker of HIT, was observed in most ICU patients. Surprisingly, HIT occurred not only in patients with heparin exposure, such as CRRT, but also in heparin-naive patients, suggesting that spontaneous HIT may occur in COVID-19. InterpretationAnti-heparin-PF4 antibodies are induced in critical COVID-19 patients, resulting in a progressive platelet decrease. Exposure to a high dose of heparin may trigger further severe thrombocytopenia with a fatal outcome. An alternative anticoagulant other than heparin should be used to treat COVID-19 patients in critical condition. FundingThis investigation was supported by grants 2016CB02400 and 2017YFC1201103 from the National Major Research and Development Program of China.
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An excessive immune response contributes to SARS-CoV, MERS-CoV and SARS-CoV-2 pathogenesis and lethality, but the mechanism remains unclear. In this study, the N proteins of SARS-CoV, MERS-CoV and SARS-CoV-2 were found to bind to MASP-2, the key serine protease in the lectin pathway of complement activation, resulting in aberrant complement activation and aggravated inflammatory lung injury. Either blocking the N protein:MASP-2 interaction or suppressing complement activation can significantly alleviate N protein-induced complement hyper-activation and lung injury in vitro and in vivo. Complement hyper-activation was also observed in COVID-19 patients, and a promising suppressive effect was observed when the deteriorating patients were treated with anti-C5a monoclonal antibody. Complement suppression may represent a common therapeutic approach for pneumonia induced by these highly pathogenic coronaviruses. One Sentence SummaryThe lectin pathway of complement activation is a promising target for the treatment of highly pathogenic coronavirus induced pneumonia.
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An HPLC method for simultaneous determination of chlorogenic acid and mangiferin in original medicinal materials and decoction pieces of Pyrrosiae Folium was developed. The assay was performed on a Diamonsil C18 (4.6 mm x 250 mm, 5 microm) column eluted with a mobile phase consisted of acetonitrile and 0.5% phosphoric acid solution in gradient elution at a flow rate of 1.0 mL x min(-1). The column temperature was set at 25 degrees C. The detection wavelength was 320 nm. The results showed that The linear ranges of chlorogenic acid and mangiferin were 5.2-130 mg x L(-1) (r = 0.9999) and 1.2-18 microg x mL(-1) (r = 0.9999), and the average recoveries (n=6) were 97.9% (RSD 1.9%) and 99.6% (RSD 2.9%), respectively. The method was simple, reproducible and valid. It can be used for quality evaluation and control of original medicinal materials and decoction pieces of Pyrrosiae Folium.
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Ácido Clorogénico , Cromatografía Líquida de Alta Presión , Plantas Medicinales , Química , Reproducibilidad de los Resultados , XantonasRESUMEN
Objective To establish a HPLC method to determine the content of acteoside in Conghuang Bushen Capsule. Methods The HPLC method was employed with a column of Hypersil ODS2(4.6 mm? 250 mm,5 ? m) and a mobile phase of acetonitrile-methanol-1 % HOAc(13 ∶ 9 ∶ 78),the detection wavelength being at 334 nm,flow rate being 1.0 mL/min and the column temperature being at 40 ℃ . Results The linear range was 0.108 5 ? g ~ 0.650 7 ? g,r=0.999; 1.The average recovery of acteoside and RSD were 98.42 % and 1.89 %,respectively. Conclusion The present method is simple,rapid and reproducible. It can be used for quality control of Conghuang Bushen Capsule.