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Rhodosporidium toruloides - A potential red yeast chassis for lipids and beyond.
Wen, Z, Zhang, S, Odoh, CK, Jin, M, Zhao, ZK
FEMS yeast research. 2020;(5)
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Abstract
The red yeast Rhodosporidium toruloides naturally produces microbial lipids and carotenoids. In the past decade or so, many studies demonstrated R. toruloides as a promising platform for lipid production owing to its diverse substrate appetites, robust stress resistance and other favorable features. Also, significant progresses have been made in genome sequencing, multi-omic analysis and genome-scale modeling, thus illuminating the molecular basis behind its physiology, metabolism and response to environmental stresses. At the same time, genetic parts and tools are continuously being developed to manipulate this distinctive organism. Engineered R. toruloides strains are emerging for enhanced production of conventional lipids, functional lipids as well as other interesting metabolites. This review updates those progresses and highlights future directions for advanced biotechnological applications.
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Colloidal aspects of digestion of Pickering emulsions: Experiments and theoretical models of lipid digestion kinetics.
Sarkar, A, Zhang, S, Holmes, M, Ettelaie, R
Advances in colloid and interface science. 2019;:195-211
Abstract
Lipid digestion is a bio-interfacial process that is largely governed by the binding of the lipase-colipase-biosurfactant (bile salts) complex onto the surface of emulsified lipid droplets. Therefore, engineering oil-water interfaces that prevent competitive displacement by bile salts and/or delay the transportation of lipase to the lipidoidal substrate can be an effective strategy to modulate lipolysis in human physiology. In this review, we present the mechanistic role of Pickering emulsions i.e. emulsions stabilised by micron-to-nano sized particles in modulating the important fundamental biological process of lipid digestion by virtue of their distinctive stability against coalescence and resilience to desorption by intestinal biosurfactants. We provide a systematic summary of recent experimental investigations and mathematical models that have blossomed in the last decade in this domain. A strategic examination of the behavior and mechanism of lipid digestion of droplets stabilised by particles in simulated biophysical environments (oral, gastric, intestinal regimes) was conducted. Various particle-laden interfaces were considered, where the particles were derived from synthetic or biological sources. This allowed us to categorize these particles into two classes based on their mechanistic role in modifying lipid digestion. These are 'human enzyme-unresponsive particles' (e.g. silica, cellulose, chitin, flavonoids) i.e. the ones that cannot to be digested by human enzymes, such as amylase, protease and 'human enzyme-responsive particles' (e.g. protein microgels, starch granules), which can be readily digested by humans. We focused on the role of particle shape (spherical, anisotropic) on modifying both interfacial and bulk phases during lipolysis. Also, the techniques currently used to alter the kinetics of lipid digestion using intelligent physical or chemical treatments to control interfacial particle spacing were critically reviewed. A comparison of how various mathematical models reported in literature predict free fatty acid release kinetics during lipid digestion highlighted the importance of the clear statement of the underlying assumptions. We provide details of the initial first order kinetic models to the more recent models, which account for the rate of adsorption of lipase at the droplet surface and include the crucial aspect of interfacial dynamics. We provide a unique decision tree on model selection, which is appropriate to minimize the difference between experimental data of free fatty acid generation and model predictions based on precise assumptions of droplet shrinkage, lipase-binding rate, and nature of lipase transport process to the particle-laden interface. Greater insights into the mechanisms of controlling lipolysis using particle-laden interfaces with appropriate mathematical model fitting permit better understanding of the key lipid digestion processes. Future outlook on interfacial design parameters, such as particle shape, size, polydispersity, charge, fusion, material chemistry, loading and development of new mathematical models that provide closed-loop equations from early to later stages of kinetics are proposed. Such future experiments and models hold promise for the tailoring of particle-laden interfaces for delaying lipid digestion and/or site-dependent controlled release of lipidic active molecules in composite soft matter systems, such as food, personal care, pharmaceutical, healthcare and biotechnological applications.
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A review on cationic lipids with different linkers for gene delivery.
Zhi, D, Bai, Y, Yang, J, Cui, S, Zhao, Y, Chen, H, Zhang, S
Advances in colloid and interface science. 2018;:117-140
Abstract
Cationic lipids have become known as one of the most versatile tools for the delivery of DNA, RNA and many other therapeutic molecules, and are especially attractive because they can be easily designed, synthesized and characterized. Most of cationic lipids share the common structure of cationic head groups and hydrophobic portions with linker bonds between both domains. The linker bond is an important determinant of the chemical stability and biodegradability of cationic lipid, and further governs its transfection efficiency and cytotoxicity. Based on the structures of linker bonds, they can be grouped into many types, such as ether, ester, amide, carbamate, disulfide, urea, acylhydrazone, phosphate, and other unusual types (carnitine, vinyl ether, ketal, glutamic acid, aspartic acid, malonic acid diamide and dihydroxybenzene). This review summarizes some research results concerning the nature (such as the structure and orientation of linker groups) and density (such as the spacing and the number of linker groups) of linker bond for improving the chemical stability, biodegradability, transfection efficiency and cytotoxicity of cationic lipid to overcome the critical barriers of in vitro and in vivo transfection.
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Comparison of Intensive Versus Moderate Lipid-Lowering Therapy on Fibrous Cap and Atheroma Volume of Coronary Lipid-Rich Plaque Using Serial Optical Coherence Tomography and Intravascular Ultrasound Imaging.
Hou, J, Xing, L, Jia, H, Vergallo, R, Soeda, T, Minami, Y, Hu, S, Yang, S, Zhang, S, Lee, H, et al
The American journal of cardiology. 2016;(5):800-6
Abstract
Despite marked clinical benefit, reduction in atheroma volume with statin therapy is minimal. Changes in plaque composition may explain this discrepancy. We aimed in the present study to assess the effect of statin therapy on coronary plaque composition and plaque volume using serial multimodality imaging. From an open-label, single-blinded study, patients with angiographically mild-to-moderate lesion were randomized to receive atorvastatin 60 (AT 60) mg or atorvastatin 20 (AT 20) mg for 12 months. Optical coherence tomography was used to assess fibrous cap thickness (FCT) and intravascular ultrasound to assess atheroma burden at 3 time points: baseline, at 6 months, and at 12 months. Thirty-six lipid-rich plaques in 27 patients with AT 60 mg and 30 lipid-rich plaques in 19 patients with AT 20 mg were enrolled in this study. Low-density lipoprotein cholesterol level was significantly decreased at 6 months without further reduction at 12 months. AT 60 mg induced greater reduction in low-density lipoprotein cholesterol compared with AT 20 mg. Optical coherence tomography revealed continuous increase in FCT from baseline to 6 months and to 12 months in both groups. AT 60 mg induced greater increase in FCT compared with AT 20 mg at both follow-up points. The prevalence of thin-cap fibroatheroma and the presence of macrophage at 6 months were significantly lower in AT 60 mg compared with AT 20 mg. Plaque burden did not change significantly in both groups. In conclusion, both intensive and moderate statin therapy stabilizes coronary plaques, with a greater benefit in the intensive statin group. However, no significant changes in plaque volume were observed over time regardless of the intensity of statin therapy.
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Gender specific effect of LIPC C-514T polymorphism on obesity and relationship with plasma lipid levels in Chinese children.
Wang, H, Zhang, D, Ling, J, Lu, W, Zhang, S, Zhu, Y, Lai, M
Journal of cellular and molecular medicine. 2015;(9):2296-306
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Abstract
Hepatic lipase (LIPC) is a key rate-limiting enzyme in lipoprotein catabolism pathways involved in the development of obesity. The C-514T polymorphism in the promoter region is associated with decreased LIPC activity. We performed a case-controlled study (850 obese children and 2119 controls) and evaluated the association between LIPC C-514T polymorphism, obesity and plasma lipid profile in Chinese children and adolescents. Additionally, we conducted a meta-analysis of all results from published studies as well as our own data. A significant association between the polymorphism and obesity is observed in boys (P = 0.042), but not in girls. And we observed a significant relationship of the polymorphism with total cholesterol (TC) and high density lipoprotein cholesterol (HDL-C) independent of obesity in boys. The T allele carriers have higher levels of low density lipoprotein cholesterol (LDL-C) in obese boys, and triglyceride (TG), TC and LDL-C in non-obese girls (all P < 0.05). In the meta-analysis, under dominant model the T allele increased body mass index (BMI) level in boys, while it decreased BMI in girls, and increased the levels of TC both in the overall and subgroups, TG and HDL-C in the overall and boys, and LDL-C in the overall (all P < 0.05). Our results suggest that the T allele might carry an increased risk of obesity in Chinese boys. The meta-analysis suggests that T allele acts as a risk allele for higher BMI levels in male childhood, while it is a protective allele in female childhood. And the polymorphism is associated with the levels of plasma lipids, which may be modulated by obesity and gender.
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[Research on cationic vector-mediated RNAi].
Zhang, X, Ding, H, Wang, B, Cui, S, Zhao, Y, Jin, W, Zhang, S, Jin, M
Sheng wu yi xue gong cheng xue za zhi = Journal of biomedical engineering = Shengwu yixue gongchengxue zazhi. 2012;(4):722-6
Abstract
In order to study the efficiency of small interfering RNA (siRNA) transfer mediated by cationic liposome, we used luciferase siRNA to evaluate the gene silencing activity in the Hep-2 cells, which were stably transduced with a luciferase gene. The pDNA transfection was studied, and siRNA arrearage assay was conducted to determine the capability of cationic liposome with siRNA. Different concentrations of siRNA was used to silence luciferase gene' activity, and then the result was examined by microplate reader. Cell viability was analyzed after transfection by MTT assay. The results suggested that Lipofectamine 2000 could transfer the pDNA efficiently, and have strong binding capacity with siRNA. The silencing efficiency of luciferase was obtained with low concentration of siRNA. The cell viability was influenced by RNA interference (RNAi) very slightly, but the cell survival rate decreased with the increase of siRNA concentrations. It was well concluded that by optimizing the experimental conditions, cationic liposome can transfer low concentration siRNA to silence target gene's activity efficiently.
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Cationic compounds used in lipoplexes and polyplexes for gene delivery.
Zhang, S, Xu, Y, Wang, B, Qiao, W, Liu, D, Li, Z
Journal of controlled release : official journal of the Controlled Release Society. 2004;(2):165-80
Abstract
Gene transfer represents an important advance in the treatment of both genetic and acquired diseases. Many cationic lipids and cationic polymers naturally occurred or synthesized have been used for gene transfer. They have the advantages over viral gene transfer as non-immunogenic, easy to produce and not oncogenic. These cationic compounds, however, have the major limitations of inefficient transfection and toxicity to cells. For overcoming these problems, many new cationic compounds were developed since the first cationic lipid, DOTMA, was found usage in gene therapy. This article reviews cationic lipids for gene therapy from chemistry viewpoint and we classify these compounds as monovalent cationic lipids, polyvalent cationic lipids, cationic polymers, guanidine containing compounds, cationic peptides and cholesterol containing compounds, and hope to provide suggestions on the development of this variety of cationic compounds through the discussion.