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1.
Lipid nanoparticles (LNPs) are becoming popular as a means of delivering therapeutics, including those based on nucleic acids and mRNA. The mRNA-based coronavirus disease 2019 vaccines are perfect examples to highlight the role played by drug delivery systems in advancing human health. The fundamentals of LNPs for the delivery of nucleic acid- and mRNA-based therapeutics, are well established. Thus, future research on LNPs will focus on addressing the following: expanding the scope of drug delivery to different constituents of the human body, expanding the number of diseases that can be targeted, and studying the change in the pharmacokinetics of LNPs under physiological and pathological conditions. This review article provides an overview of recent advances aimed at expanding the application of LNPs, focusing on the pharmacokinetics and advantages of LNPs. In addition, analytical techniques, library construction and screening, rational design, active targeting, and applicability to gene editing therapy have also been discussed. 相似文献
2.
ObjectiveThe beneficial effects of carnitine supplementation on nonalcoholic fatty liver disease are unclear. We conducted a systematic review and meta-analysis to evaluate the effects of carnitine supplementation on liver function, lipid profile, body mass index, body weight, and homeostasis model assessment of insulin resistance in patients with nonalcoholic fatty liver disease.MethodsA comprehensive search of PubMed, Web of Science, Scopus, Cochrane Library, and Google Scholar databases were performed. Only randomized placebo-controlled human studies that examined the effects of carnitine supplementation on liver function, lipid profile, body mass index, body weight, and homeostasis model assessment of insulin resistance up to September 2019 were included. Fixed effects or random-effects models were applied to compute the pooled effect size. Heterogeneity assessments were performed using Cochran’s Q test and I-squared statistics. The quality of the studies was assessed using the Jaded scale.ResultsA total of 5 articles were selected, including 334 individuals (167 in control and 167 in intervention groups). The results demonstrated that carnitine supplementation significantly reduced homeostasis model assessment of insulin resistance (HOMA-IR) (WMD: −0.91; 95 % CI: −1.11, −0.72; p < 0.001, I2 = 0.0 %) and the levels of aspartate aminotransferase (AST) (WMD: −16.62; 95 % CI: −28.11, −5.14; IU/l; p = 0.005, I2 = 93.5 %), alanine aminotransferase (ALT) (WMD: -33.39; 95 % CI: −45.13, −21.66; IU/l; p < 0.001, I2 = 93.4 %), and triglycerides (TG) (WMD: −22.13; 95 % CI: −38.91, −5.34; mg/dl; p = 0.01; I2 = 0.0 %). However, the results of the pooled effect size did not show any significant effect of carnitine supplementation on body mass index (BMI) (WMD: 0.07; 95 % CI: −0.15, 0.29; p = 0.55; I2 = 0.0 %), body weight (WMD: −0.28; 95 % CI: −2.23, 1.68; p = 0.78; I2 = 45.7 %), the levels of gamma-glutamyl transferase (γGT) (WMD: −11.31; 95 % CI: −24.35, 1.73; IU/l; p = 0.09, I2 = 61.1 %), cholesterol (WMD: −13.58; 95 % CI: −46.77, 19.60; mg/dl; p = 0.42; I2 = 94.9 %), high-density lipoprotein-cholesterol (HDL-C) (WMD: 1.36; 95 % CI: −0.96, 3.68; mg/dl; p = 0.25; I2 = 64.7 %), and low density lipoprotein-cholesterol (LDL-C) (WMD: −14.85; 95 % CI: −45.43, 15.73; mg/dl; p = 0.34; I2 = 96.4 %).ConclusionsThis analysis shows that carnitine supplementation for patients with nonalcoholic fatty liver disease demonstrates a reduction in AST, ALT, TG levels and HOMA-IR. However, no significant effect of carnitine supplementation was observed on BMI, body weight, the levels of γGT, TC, HDL-cholesterol and LDL-cholesterol. 相似文献
3.
目的:探究金水宝片联合依诺肝素对维持性血液透析患者血脂代谢的影响。方法:选取2018年12月至2019年3月马鞍山十七冶医院血液净化中心进行透析的患者154例作为研究对象,根据用药不同分为对照组和观察组,每组77例。对照组常规应用依诺肝素抗凝,观察组在对照组抗凝基础上加用金水宝片,各组均干预3个月,比较2组患者血脂变化及持续血液透析并发症发生情况。结果:治疗后,观察组患者三酰甘油、总胆固醇及低密度脂蛋白胆固醇水平下降,高密度脂蛋白胆固醇升高,与治疗前比较差异均有统计学意义(P<0.05),与对照组治疗后比较,差异有统计学意义(P<0.05);观察组总并发症发生率明显低于对照组,2组比较差异有统计学意义(P<0.05);2组患者维持性血液透析不良反应发生率均较低,组间比较差异无统计学意义(P>0.05)。结论:金水宝片联合依诺肝素有助于改善维持性血液透析患者血脂代谢水平,降低维持性血液透析相关并发症,值得临床推广应用。 相似文献
4.
鸡抗内毒素卵黄抗体IgY的制备 总被引:2,自引:1,他引:1
目的:研究分别应用内毒素(LPS)、类脂A(LipidA)和大肠杆菌突变株15免疫鸡后其蛋黄中抗内毒素抗体IgY的产量、纯度、效价并筛选最佳免疫抗原。方法:分别应用内毒素(LPS)、类脂A(LipidA)和大肠杆菌J5突变株作为抗原免疫25周龄Leghom鸡,水溶法(WD)提取蛋黄中抗体IgY,双紫外光测定抗体含量,SDS-PSGE电泳检测抗体纯度,细胞酶联染色和ELISA检测抗体特异性、效价及筛选最佳免疫抗原。结果:3种抗内毒素IgY含量和效价分别为14.4mg/ml和1:12 800(J5)、10.61mg/ml和1:12 800(LPS)、9.26mg/ml和1:3200(LipidA),抗体纯度均为95%左右。结论:大肠杆菌突变株J5和内毒素(LPS)为最佳免疫抗原,免疫鸡后其蛋黄中抗内毒素抗体IgY的产量和效价最高。 相似文献
5.
Ernst R. Kuse Joerg Kotzerke Silke Müller Björn Nashan Rainer Lück Karsten Jaeger 《Transplant international》2002,15(6):272-277
It has been demonstrated that total parenteral nutrition (TPN) modulates the function of the hepatic reticuloendothelial system (RES). The objective of this study was to evaluate the impact of two different TPN lipid emulsions on the recovery of allograft RES function after orthotopic liver transplantation (OLTx). In a prospective, double-blind study, OLTx patients were randomly assigned to two treatment groups. Group I ( n=13) received a TPN regimen that included long-chain triglycerides (LCT). Group II ( n=9) received a TPN regimen that included a fat emulsion consisting of both medium-chain triglycerides (MCT) and LCT. At baseline, i.e., on days 2 or 3 after OLTx ( t1), before lipids for TPN were started, hepatic RES function was determined using the human serum albumin millimicrosphere technique (K-value, 1/min). A second measurement ( t2) was obtained after 7 days of TPN, including one of the study's two fat emulsions. The mean (+/- SD) K-value (1/min) was 0.48+/-0.16 in the LCT group and 0.55+/-0.28 in the MCT/LCT group at t1, and it improved to 0.62+/-0.21 in the LCT group and to 0.86+/-0.32 in the MCT/LCT group at t2. RES function recovery was significantly better in the MCT/LCT group ( P< or = 0.05). MCT/LCT emulsion appears to be the TPN fat emulsion of choice after OLTx as it seems to have less impact on hepatic RES recovery. 相似文献
6.
Robbert-Jan Roozeman Lasse Murtomäki Kyösti Kontturi 《Journal of electroanalytical chemistry (Lausanne, Switzerland)》2005,575(1):9-17
A recently introduced setup to measure the dynamic interfacial tension of expanding drops was used to compare the adsorption behaviour of a series of lipids at the electrified water∣dichloroethane interface. Phospholipids with saturated carbon chains of different length (DMPC, DPPC, DSPC, DAPC, DBPC), an unsaturated phospholipid (DOPC) and an ethanolamine (DSPE) were compared. It was found that the adsorption decreases with increasing chain length. Also, the increase of the flow rate reduces the degree of adsorption effectively. On the timescale of the experiments, the DSPE, DAPC and DBPC adsorption showed no potential dependence, whereas the adsorption of DOPC was stronger than that of the saturated lipids. Adsorption was modelled using the Langmuir adsorption isotherm; the potential dependence of adsorption is discussed. 相似文献
7.
Claus Jacob Alexander Y. Safronov Sonia Wilson H.Allen O. Hill Tim F. Booth 《Journal of electroanalytical chemistry (Lausanne, Switzerland)》1997,431(1):7-10
A novel chiral redox-active ferrocene compound (FcVI) with amphiphilic properties has been synthesized. Cryogenic Transmission Electron Microscopy (cryo-TEM) has been used to estimate the shape and size of the FcVI aggregates in solution. Uni- and multi-lamellar vesicles (between 40 and 300 nm in diameter) were observed in water. Large particles (of more than 1 μm in diameter) with a hexagonal fine structure were found in 50 mM aqueous Na2SO4 solution. Sonication transformed the latter into ‘rosette’-like structures. Cyclic voltammetry has been employed to investigate the electrochemical properties of FcVI. The amphiphile adsorbed on graphite electrodes and a reversible electrochemical behaviour, characteristic of ferrocene, was observed with redox potentials between 330 and 350 mV. 相似文献
8.
高龄初产妊高征孕妇过氧化反应的研究 总被引:3,自引:0,他引:3
目的:探讨高龄初产妊高征孕妇体内过氧化反应。方法:测定正常初产妇、妊高征孕妇妊娠晚期母血过氧化脂质(LPO)、超氧化物歧化酶(DOD)的含量。结果:1.高龄初产妇母血LPO较非高龄初产妇明显升高,SOD明显下降,P<0.05。孕妇年龄与母血LPO呈明显正相关,与SOD呈明显负相关,P均<0.05。2.妊高征孕妇LPO较正常孕妇显著增高,SOD显著下降,P<0.05,并随病情加重LPO水平升高、SOD水平下降更为显著,P<0.05。3.高龄初产妊高征孕妇母血LPO含量较非高龄初产妊高征孕妇明显增高,P<0.05,而SOD则无显著变化,P>0.05。4.妊高征孕妇胎儿宫内生长发育迟缓(IUGR)发生率较正常孕妇显著升高,P<0.025,各组脐血清LPO、SOD含量无显著差异,P<0.05。结论:高龄初产妊高征孕妇体内过氧化作用明显增强,LPO水平的升高可能为高龄初产妇妊高征发生率及IUGR发生率增加的原因之一。 相似文献
9.
Toxic effects of Fusarium mycotoxin butenolide on rat myocardium and primary culture of cardiac myocytes. 总被引:1,自引:0,他引:1
Jing-Bo Liu Yi-Mei Wang Shuang-Qing Peng Gang Han Yan-Sheng Dong Hai-Ying Yang Chang-Hui Yan Guo-Qiang Wang 《Toxicon》2007,50(3):357-364
Mycotoxin toxicosis has been implicated in the etiopathogenesis of Keshan disease (KD), an endemic cardiomyopathy prevailing in some regions of China. Butenolide (4-acetamido-4-hydroxy-2-butenoic acid gamma-lactone, CAS No. 16275-44-8), a mycotoxin produced by several Fusarium species such as Fusarium tricinctum and Fusarium graminearum, is frequently detected from the cereals in the endemic areas of KD. The present study is undertaken to investigate whether this mycotoxin can induce myocardial damage. Exposure of primary culture of cardiac myocytes to butenolide resulted in significant cytotoxicity, manifested by changes in cell morphology and decreases in cell viability. Consistent with the in vitro findings, distinct myocardial toxicity in vivo was observed after administration of rats by gavage with butenolide (10 and 20 mg/kg/day) for 2 months, and the myocardial injuries were characterized by focal necrosis of myocardium and fragmentation of myofiber. Butenolide also induced significant oxidative damage to the myocardium in vitro evidenced by a concentration-dependent lipid peroxidation in the myocardial homogenates, whereas antioxidants superoxide dismutase (SOD), N-acetylcysteine (NAC) and glutathione (GSH) provided significant protections against this oxidative effect. Taken together, these results clearly reveal that butenolide possesses the potential to induce myocardial toxicity. The present findings may reinforce the hypothesis that toxicosis by mycotoxins is one of the etiological factors for KD. 相似文献
10.
Kimie Sai Takashi Umemura Atsuya Takagi Ryuichi Hasegawa Yuji Kurokawa 《Cancer science》1992,83(1):45-51
The roles of glutathione (GSH), cysteine, vitamin C., liposome-encapsulated superoxide dismutase (L-SOD) and vitamin E in preventing oxidative DNA damage and cytotoxicity in the rat kidney after administration of potassium bromate (KBrO3 ) to male F344 rats were investigated by measuring 8-hydroxydeoxyguanosine (8-OH-dG), an oxidative DNA product, lipid peroxidation (LPO) levels and relative kidney weight (RKW). Combined pre- and posttreatment of animals with 2 × 800 mg/kg GSH i.p. inhibited the increase of 8-OH-dG, LPO levels and RKW caused by 80 mg/kg KBrO3 i.p. administration. In contrast, pretreatment with 0.3 ml/kg diethylmaleate (DEM) i.p., a depletor of tissue GSH, was associated with elevation of 8-OH-dG, LPO levels and RKW after a 20 mg/kg KBrO3 i.p. treatment, which itself caused no change. Administration of KBrO3 itself reduced renal non-protein thiol levels, but this was inhibited by the two doses of exogenous GSH. Combined treatment with DEM and KBrO3 lowered the non-protein thiol level in the kidney more than did DEM treatment alone. Protective effects against the oxidative damage caused by KBrO3 were also observed for pre- and posttreatment with 400 mg/kg cysteine i.p., another sulfhydryl compound, and daily i.g. application of 200 mg/kg vitamin C for 5 days. However, no influence was evident after pre- and posttreatment with 18,000 U/kg L-SOD i.p. or daily i.g. 100 mg/kg of vitamin E for 5 days. The results suggest that intracellular GSH plays an essential protective role against renal oxidative DNA damage and nephrotoxicity caused by KBrO3 . 相似文献