lipid particles
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2022 ◽  
Author(s):  
Thi Kim Hoang Trinh ◽  
Claudio Catalano ◽  
Youzhong Guo

Membrane proteins are a ubiquitous group of bio-macromolecules responsible for many crucial biological processes and serve as drug targets for a wide range of modern drugs. Detergent-free technologies such as styrene-maleic acid lipid particles (SMALP), diisobutylene-maleic acid lipid particles (DIBMALP), and native cell membrane nanoparticles (NCMN) systems have recently emerged as revolutionary alternatives to the traditional detergent-based approaches for membrane protein research. NCMN systems aim to create a membrane-active polymer library suitable for high-resolution structure determination. Herein, we report our design, synthesis, characterization and comparative application analyses of three novel classes of NCMN polymers, NCMNP13-x, NCMNP21-x and NCMNP21b-x. Although each NCMN polymer can solubilize various model membrane proteins and conserve native lipids into NCMN particles, only the NCMNP21b-x series reveals lipid-protein particles with good buffer compatibility and high homogeneity suitable for single-particle cryo-EM analysis. Consequently, the NCMNP21b-x polymers that bring out high-quality NCMN particles are particularly attractive for membrane protein structural biology.


2022 ◽  
Author(s):  
Xianjin Hu ◽  
Xin Zhang ◽  
Qiling Gou ◽  
Runyu Ye ◽  
Zhipeng Zhang ◽  
...  

Abstract Background: Hypoxic circumstances impair endothelial function and may contribute to carotid atherosclerosis. In high-altitude areas, there is a scarcity of data on the correlation between lipid particles and carotid atherosclerosis. Methods: A total of 587 patients who underwent carotid artery ultrasound and met the inclusion and exclusion criteria were enrolled in our cross-sectional study. All participants resided in Luhuo County, Ganzi Tibetan Autonomous Prefecture, Sichuan Province, China (mean altitude: 3,860 meters). We used questionnaires, physical examination, blood sample testing, and ultrasound in our investigation. Spearman correlation analysis and multiple linear regression analysis were performed to explore the association between lipid particles and carotid atherosclerosis. We compared the disparity between lipid particles in predicting atherosclerosis using the receiver operator characteristic curve.Results: We found a statistically significant association between lipid particles and carotid atherosclerosis. After adjustment for certain variables, including age, gender, mean arterial pressure, and fasting blood glucose, we discovered that non-high-density lipoprotein-cholesterol (non-HDL-C) was a risk factor for carotid intima-media thickness (β = 0.012, p = 0.032) but not for low-density lipoprotein cholesterol (LDL-C) (p = 0.073). In terms of lifestyle, non-HDL-C was also found to be a risk factor for atherosclerosis independent of cigarette smoking and vegetarian (β = 0.012, p = 0.049). The area under the curve (AUC) of non-HDL-C was 0.644 (CI: 0.583 – 0.706) while LDL-C was 0.599 (CI: 0.534 - 0.664) in predicting carotid atherosclerosis. The optimal cut-off value of non-HDL-C was 3.625 mmol/L in predicting carotid plaques. Conclusions: Among Tibetans living in high-altitude areas, non-HDL-C is a better biomarker than LDL-C for carotid artery atherosclerosis independent of conventional risk factors. It is crucial to resolve non-HDL-C dyslipidemia in order to mitigate carotid atherosclerosis in Tibetans living at high-altitude settings.


2021 ◽  
Author(s):  
Xianjin Hu ◽  
Xin Zhang ◽  
Qiling Gou ◽  
Runyu Ye ◽  
Zhipeng Zhang ◽  
...  

Abstract Background: Hypoxic circumstances impair endothelial function and may contribute to carotid atherosclerosis. In high-altitude areas, there is a scarcity of data on the correlation between lipid particles and carotid atherosclerosis. Methods: A total of 587 patients who underwent carotid artery ultrasound and met the inclusion and exclusion criteria were enrolled in our cross-sectional study. All participants resided in Luhuo County, Ganzi Tibetan Autonomous Prefecture, Sichuan Province, China (mean altitude: 3,860 meters). We used questionnaires, physical examination, blood sample testing, and ultrasound in our investigation. Spearman correlation analysis and multiple linear regression analysis were performed to explore the association between lipid particles and carotid atherosclerosis. We compared the disparity between lipid particles in predicting atherosclerosis using the receiver operator characteristic curve.Results: We found a statistically significant association between lipid particles and carotid atherosclerosis. After adjustment for certain variables, including age, gender, mean arterial pressure, and fasting blood glucose, we discovered that non-high-density lipoprotein-cholesterol (non-HDL-C) was a risk factor for carotid intima-media thickness (β = 0.012, p = 0.032) but not for low-density lipoprotein cholesterol (LDL-C) (p = 0.073). In terms of lifestyle, non-HDL-C was also found to be a risk factor for atherosclerosis independent of cigarette smoking and vegetarian (β = 0.012, p = 0.049). The optimal cut-off value of non-HDL-C was 3.625 mmol/L in predicting carotid plaques.Conclusions: Among Tibetans living in high-altitude areas, non-HDL-C is a better biomarker than LDL-C for carotid artery atherosclerosis independent of conventional risk factors.


Pharmaceutics ◽  
2021 ◽  
Vol 13 (12) ◽  
pp. 2162
Author(s):  
Denise Steiner ◽  
Jakob F. Emmendörffer ◽  
Heike Bunjes

To overcome the poor bioavailability observed for many newly developed active pharmaceutical ingredients (APIs), an appropriate formulation strategy is necessary. One approach is the formulation of these substances in solid lipid nanoparticles and their further processing into solid dosage forms. A promising and innovative oral delivery platform could be orodispersible films (ODFs). ODFs were already investigated more closely, e.g., for the administration of API nanoparticles, and proved their suitability for this formulation approach. The current study was aimed at investigating if the HPMC (hydroxypropyl methyl cellulose) film matrix is also suitable to serve as an appropriate delivery platform for solid lipid nanoparticles. Dependent on the type of triglyceride nanoparticles embedded in the film matrix and the formulation of the lipid particles, lipid contents of up to 54 wt.% could be realized in the film matrix without the loss of the nanoparticulate state. Good mechanical properties were confirmed for these films by determining the tensile strength as well as the elongation before breakage. Interestingly, processing of a lipid suspension into this solid dosage form led to a significantly reduced transformation of the lipid particles from the metastable α- into the stable β-polymorph. This could prove very beneficial when the lipid particles are loaded with APIs.


Author(s):  
Abdul-Hamid Abubakar Zubair ◽  
Sadeeq Muhammad Sheshe ◽  
Muhammad Ribado Bashir ◽  
Sani Muhammad Sade

Associated with the old/traditional of method of drug delivery are several limitation ranging from first-pass effect, low tolerance, minimal bioavailability, fluctuation of plasma drug concentration which result to less or no desired effect produced. This call for the demand for a more efficient drug administration technique. Lipid systems are biocompatible, inert and biodegradable, stable and deliver at the target with the desired effect. This paper attempt to describe several types of lipid particles used to deliver drug compounds and their applications as therapeutic agent in treating different clinical condition.


Author(s):  
Youzhong Guo

Membrane proteins play vital roles in living organisms, serving as targets for most currently prescribed drugs. Membrane protein structural biology aims to provide accurate structural information to understand their mechanisms of action. The advance of membrane protein structural biology has primarily relied on detergent-based methods over the past several decades. However, detergent-based approaches have significant drawbacks because detergents often damage the native protein–lipid interactions, which are often crucial for maintaining the natural structure and function of membrane proteins. Detergent-free methods recently have emerged as alternatives with a great promise, e.g. for high-resolution structure determinations of membrane proteins in their native cell membrane lipid environments. This minireview critically examines the current status of detergent-free methods by a comparative analysis of five groups of membrane protein structures determined using detergent-free and detergent-based methods. This analysis reveals that current detergent-free systems, such as the styrene-maleic acid lipid particles (SMALP), the diisobutyl maleic acid lipid particles (DIBMALP), and the cycloalkane-modified amphiphile polymer (CyclAPol) technologies are not better than detergent-based approaches in terms of maintenance of native cell membrane lipids on the transmembrane domain and high-resolution structure determination. However, another detergent-free technology, the native cell membrane nanoparticles (NCMN) system, demonstrated improved maintenance of native cell membrane lipids with the studied membrane proteins, and produced particles that were suitable for high-resolution structural analysis. The ongoing development of new membrane-active polymers and their optimization will facilitate the maturation of these new detergent-free systems.


Food Control ◽  
2021 ◽  
pp. 108262
Author(s):  
Amarilis Santos de Carvalho ◽  
Stephany Cunha de Rezende ◽  
Cristina Caleja ◽  
Eliana Pereira ◽  
Lillian Barros ◽  
...  

2021 ◽  
Vol 35 (S1) ◽  
Author(s):  
Vera Nazarenko ◽  
Alina Remeeva ◽  
Yury Ryzhykau ◽  
Philipp Orekhov ◽  
Oleg Semenov ◽  
...  

2021 ◽  
Vol 22 (5) ◽  
pp. 2548
Author(s):  
Natalia Voskoboynikova ◽  
Philipp Orekhov ◽  
Marine Bozdaganyan ◽  
Felix Kodde ◽  
Malte Rademacher ◽  
...  

Amphiphilic diisobutylene/maleic acid (DIBMA) copolymers extract lipid-encased membrane proteins from lipid bilayers in a detergent-free manner, yielding nanosized, discoidal DIBMA lipid particles (DIBMALPs). Depending on the DIBMA/lipid ratio, the size of DIBMALPs can be broadly varied which makes them suitable for the incorporation of proteins of different sizes. Here, we examine the influence of the DIBMALP sizes and the presence of protein on the dynamics of encased lipids. As shown by a set of biophysical methods, the stability of DIBMALPs remains unaffected at different DIBMA/lipid ratios. Coarse-grained molecular dynamics simulations confirm the formation of viable DIBMALPs with an overall size of up to 35 nm. Electron paramagnetic resonance spectroscopy of nitroxides located at the 5th, 12th or 16th carbon atom positions in phosphatidylcholine-based spin labels reveals that the dynamics of enclosed lipids are not altered by the DIBMALP size. The presence of the membrane protein sensory rhodopsin II from Natronomonas pharaonis (NpSRII) results in a slight increase in the lipid dynamics compared to empty DIBMALPs. The light-induced photocycle shows full functionality of DIBMALPs-embedded NpSRII and a significant effect of the protein-to-lipid ratio during preparation on the NpSRII dynamics. This study indicates a possible expansion of the applicability of the DIBMALP technology on studies of membrane protein–protein interaction and oligomerization in a constraining environment.


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