1.Role of extracellular vesicles in lung diseases.
Li ZHOU ; Hong LUO ; Jae Woo LEE
Chinese Medical Journal 2022;135(15):1765-1780
Extracellular vesicles (EVs) are anuclear particles composed of lipid bilayers that contain nucleic acids, proteins, lipids, and organelles. EVs act as an important mediator of cell-to-cell communication by transmitting biological signals or components, including lipids, proteins, messenger RNAs, DNA, microRNAs, organelles, etc, to nearby or distant target cells to activate and regulate the function and phenotype of target cells. Under physiological conditions, EVs play an essential role in maintaining the homeostasis of the pulmonary milieu but they can also be involved in promoting the pathogenesis and progression of various respiratory diseases including chronic obstructive pulmonary disease, asthma, acute lung injury/acute respiratory distress syndrome, idiopathic pulmonary fibrosis (IPF), and pulmonary artery hypertension. In addition, in multiple preclinical studies, EVs derived from mesenchymal stem cells (EVs) have shown promising therapeutic effects on reducing and repairing lung injuries. Furthermore, in recent years, researchers have explored different methods for modifying EVs or enhancing EVs-mediated drug delivery to produce more targeted and beneficial effects. This article will review the characteristics and biogenesis of EVs and their role in lung homeostasis and various acute and chronic lung diseases and the potential therapeutic application of EVs in the field of clinical medicine.
DNA/metabolism*
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Extracellular Vesicles/metabolism*
;
Humans
;
Lipid Bilayers/metabolism*
;
Lung Diseases/therapy*
;
Lung Injury/metabolism*
;
MicroRNAs/metabolism*
;
Proteins/metabolism*
;
Respiratory Distress Syndrome
2.Research Progress of Transmembrane Protein Abnormality in Non-Hodgkin's Lymphoma --Review.
Journal of Experimental Hematology 2022;30(5):1617-1621
Transmembrane protein, also known as integral membrane protein, can be distributed in the lipid bilayer or across the entire membrane, and it plays an important role in cell signal transduction. It has been discovered that multiple transmembrane proteins are involved in the regulation of tumor signals. Recent studies have revealed that the abnormal expression of some transmembrane protein is closely related to the occurrence, development and prognosis of non-Hodgkin's lymphoma (NHL), including programmed cell death protein 1 (PD-1), TMEM30A, NOTCH1, TOLL-like receptor (TLR), sphingosine-1-phosphate receptor, TRAIL, etc. The study on these transmembrane proteins and related genes has important clinical significance for the treatment and prognosis of NHL, and it may become a new therapeutic target. At present, there have been some research results in this field at home and abroad. This article reviewed the research progress of transmembrane protein that has inhibitory effects on NHL in recent years.
Humans
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Lipid Bilayers
;
Lymphoma, Non-Hodgkin/therapy*
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Prognosis
;
Programmed Cell Death 1 Receptor
;
Sphingosine-1-Phosphate Receptors
3.Reconstitution of large conductance calcium-activated potassium channels into artificial planar lipid bilayers.
Jun CHENG ; Xiao-Rong ZENG ; Xiao-Qiu TAN ; Peng-Yun LI ; Jing WEN ; Liang MAO ; Yan YANG
Acta Physiologica Sinica 2017;69(3):305-310
This study was aimed to establish a method to create a stable planar lipid bilayer membranes (PLBMs), in which large conductance calcium-activated potassium channels (BK) were reconstituted. Using spreading method, PLBMs were prepared by decane lipid fluid consisting of N-weathered mixture of phosphatidylcholine and cholesterol at 3:1 ratio. After successful incorporation of BKchannel into PLBMs, single channel characteristics of BKwere studied by patch clamp method. The results showed that i) the single channel conductance of BKwas (206.8 ± 16.9) pS; ii) the activities of BKchannel were voltage dependent; iii) in the bath solution without Ca, there was almost no BKchannel activities regardless of under hyperpolarization or repolarization conditions; iv) under the condition of +40 mV membrane potential, BKchannels were activated in a Caconcentration dependent manner; v) when [Ca] was increased from 1 μmol/L to 100 μmol/L, both the channel open probability and the average open time were increased, and the average close time was decreased from (32.2 ± 2.8) ms to (2.1 ± 1.8) ms; vi) the reverse potential of the reconstituted BKwas -30 mV when [K] was at 40/140 mmol/L (Cis/Trans). These results suggest that the spreading method could serve as a new method for preparing PLBMs and the reconstituted BKinto PLBMs showed similar electrophysiological characteristics to natural BKchannels, so the PLBMs with incorporated BKcan be used in the studies of pharmacology and dynamics of BKchannel.
Animals
;
Calcium
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chemistry
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Electrophysiological Phenomena
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Large-Conductance Calcium-Activated Potassium Channels
;
chemistry
;
Lipid Bilayers
;
chemistry
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Membrane Potentials
;
Patch-Clamp Techniques
4.Lipid bilayer modification alters the gating properties and pharmacological sensitivity of voltage-gated sodium channel.
Yan ZHU ; Bin WU ; Yi-Jun FENG ; Jie TAO ; Yong-Hua JI
Acta Physiologica Sinica 2015;67(3):271-282
Voltage-gated sodium channels (VGSCs) are widely distributed in most cells and tissues, performing many physiological functions. As one kind of membrane proteins in the lipid bilayer, whether lipid composition plays a role in the gating and pharmacological sensitivity of VGSCs still remains unknown. Through the application of sphingomyelinase D (SMaseD), the gating and pharmacological sensitivity of the endogenous VGSCs in neuroblastoma ND7-23 cell line to BmK I and BmK AS, two sodium channel-specific modulators from the venom of Buthus martensi Karsch (BmK), were assessed before and after lipid modification. The results showed that, in ND7-23 cells, SMaseD did not change the gating properties of VGSCs. However, SMaseD application altered the slope factor of activation with the treatment of 30 nmol/L BmK I, but caused no significant effects at 100 and 500 nmol/L BmK I. With low concentration of BmK I (30 and 100 nmol/L) treatment, the application of SMaseD exerted hyperpolarizing effects on both slow-inactivation and steady-state inactivation, and increased the recovery time constant, whereas total inactivation and recovery remained unaltered at 500 nmol/L BmK I. Meanwhile, SMaseD modulation hyperpolarized the voltage dependence of slow-inactivation at 0.1 nmol/L BmK AS and altered the slope factor of slow-inactivation at 10 nmol/L BmK AS, whereas other parameters remained unchanged. These results indicated a possibility that the lipid bilayer would disturb the pharmacological sensitivity of VGSCs for the first time, which might open a new way of developing new drugs for treating sodium channelopathies.
Cell Line, Tumor
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Humans
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Lipid Bilayers
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chemistry
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Neuroblastoma
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Scorpion Venoms
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chemistry
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Sodium Channel Blockers
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chemistry
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Voltage-Gated Sodium Channels
;
physiology
5.Sulfogalactosylglycerolipid in spermatogenesis and fertilization.
Xiao SHI ; Ting WANG ; Song QUAN
National Journal of Andrology 2015;21(2):175-178
Sulfogalactosylglycerolipid (SGG) is the main glycolipid in male mammalian germ cells, which is selectively and highly expressed in mammalian testes and helps form the lipid bilayer of cell membrane. In the process of spermatogenesis, SGG is involved in the meiosis of spermiocytes. Either deficiency or accumulation of SGG will lead to male infertility. SGG homeostasis in the testis is the premise of normal spermatogenesis. In the process of sperm-zona binding, SGG becomes a component of lipid raft and provides a platform for signal transduction. The SGG binding protein plays a role in sperm-egg recognition and membrane fusion. SGG has a great research value and application prospect in male reproduction.
Animals
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Cell Membrane
;
Galactolipids
;
physiology
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Humans
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Infertility, Male
;
etiology
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Lipid Bilayers
;
metabolism
;
Male
;
Signal Transduction
;
Sperm-Ovum Interactions
;
physiology
;
Spermatogenesis
;
physiology
;
Spermatozoa
;
metabolism
;
Testis
;
physiology
6.Nano-size uni-lamellar lipodisq improved in situ auto-phosphorylation analysis of E. coli tyrosine kinase using (19)F nuclear magnetic resonance.
Dong LI ; Juan LI ; Yonglong ZHUANG ; Longhua ZHANG ; Ying XIONG ; Pan SHI ; Changlin TIAN
Protein & Cell 2015;6(3):229-233
Escherichia coli
;
enzymology
;
Fluorine Radioisotopes
;
analysis
;
Lipid Bilayers
;
chemistry
;
Magnetic Resonance Spectroscopy
;
Maleates
;
chemistry
;
Nanoparticles
;
chemistry
;
Phosphorylation
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Polystyrenes
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chemistry
;
Protein Conformation
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Protein-Tyrosine Kinases
;
chemistry
;
metabolism
;
Tyrosine
;
metabolism
7.Antitumor efficacy of irinotecan-loaded galactosyl modified lipid bilayer-coated mesoporous silica nanoparticles against hepatocellular carcinoma cells.
Xi CHEN ; Xin-Xin ZHANG ; Fei-Fei LI ; Ya-Nan ZHAO ; Zheng JIA ; Yong GAN ; Juan LI
Acta Pharmaceutica Sinica 2014;49(5):718-725
The purpose of this study is to prepare galactosyl modified lipid bilayer-coated mesoporous silica nanoparticles (GPEM) to enhance the antitumor efficacy against hepatocellular carcinoma cells. The irinotecan (CPT-11) loaded mesoporous silica nanoparticles (MSNs) was coated with the Gal-P123 modified functional lipid bilayer by thin-film dispersion method. Nanoparticles were characterized with particle size, zeta potential, morphology and drug release in vitro. Afterwards, the cell uptake, intracellular concentration of CPT-11, cell apoptosis rate and cytotoxicity were evaluated on human hepatocellular carcinoma cell line Huh-7. The results showed that MSNs were coated with intact lipid bilayers and the nanoparticles had clear core-shell structure. GPEM is stable with the mean particle size of (78.01 +/- 2.04) nm. The low leakage rate in normal physiological conditions in vitro is contributed to the protection of stable lipid bilayer, and the fast drug release in acid environment due to the destruction of the lipid bilayer. On the cell level, the vector could improve the intracellular CPT-11 concentration by 4 times because of the functional lipid bilayer. The high CPT-11 concentration led to the increasement of apoptosis rate by 48.6%, and the reduction of half maximal inhibitory concentration (IC50) values of CPT-11 by 2 times, indicating stronger cell cytotoxicity.
Antineoplastic Agents
;
chemistry
;
pharmacokinetics
;
Apoptosis
;
Camptothecin
;
analogs & derivatives
;
chemistry
;
pharmacokinetics
;
Carcinoma, Hepatocellular
;
drug therapy
;
pathology
;
Drug Carriers
;
chemistry
;
Drug Delivery Systems
;
methods
;
Humans
;
Lipid Bilayers
;
chemistry
;
Liver Neoplasms
;
drug therapy
;
pathology
;
Nanoparticles
;
chemistry
;
Particle Size
;
Silicon Dioxide
;
chemistry
8.Development and Application of Cell-penetrating Peptides.
Journal of Bacteriology and Virology 2013;43(3):177-185
Intracellular transduction of hydrophilic macromolecules has been problematic owing to the biochemical restriction imposed by lipid bilayer of the cytoplasmic membrane. Several technologies have been developed to improve the intracellular delivery of the large molecules for therapeutic purpose, including cell penetrating peptide. Cell penetrating peptides or cell permeable peptides (CPPs) were initially discovered based on the potency of certain full-length proteins or proteins to translocate across the plasma membrane. Currently, CPPs are broadly applied for intracellular delivery of biologically functional molecules in vivo and vitro, varying from small molecules, peptides, proteins, liposomes and nucleic acids. With introducing the history and characteristics of CPPs, this review will focus on the intracellular transduction mechanism and application of CPPs.
Cell Membrane
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Cell-Penetrating Peptides
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Endocytosis
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Lipid Bilayers
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Liposomes
;
Nucleic Acids
;
Peptides
;
Proteins
9.Preliminary study on pH-sensitive lipid bilayer-coated mesoporous silica nanoparticles as a novel drug carrier for antitumor drug.
Fei-Fei LI ; Xin-Xin ZHANG ; Shi-Yan GUO ; Yong GAN ; Juan LI
Acta Pharmaceutica Sinica 2013;48(2):291-297
This study plans to prepare lipid bilayer-coated mesoporous silica nanoparticles (LMSNs) which are pH sensitive with core-shell structure to improve the tumor cell lethality of antitumor drug. The lipid coated mesoporous silica nanoparticles loaded with irinotecan (CPT-11) (CPT-11-LMSNs) were prepared by hot water-film hydration method, and the characterized its morphology, particle size and release in vitro. Meanwhile, the intracellular uptake and cell toxicity of CPT-11-LMSNs and intracellular accumulation of CPT-11 were evaluated on human breast carcinoma cell line (MCF-7). The results indicated that the mean diameter of the spherical LMSNs was (120.27 +/- 5.91) nm. The slow release in simulated normal physiological conditions and a rapid release under simulated intracellular condition demonstrated the pH sensitivity of CPT-11-MSNs in vitro. Moreover, the CPT-11-LMSN could improve the intracellular CPT-11 cumulant 2.1 times and reduce half maximal inhibitory concentration (IC50) values of CPT-11 1.4 times compared with CPT-11-MSNs, demonstrating a stronger cell lethality.
Antineoplastic Agents, Phytogenic
;
administration & dosage
;
pharmacology
;
Camptothecin
;
administration & dosage
;
analogs & derivatives
;
pharmacology
;
Cell Proliferation
;
drug effects
;
Drug Carriers
;
Humans
;
Hydrogen-Ion Concentration
;
Lipid Bilayers
;
administration & dosage
;
chemistry
;
MCF-7 Cells
;
Nanoparticles
;
Particle Size
;
Porosity
;
Silicon Dioxide
;
administration & dosage
;
chemistry
10.Mutation of the critical pH-gating residues histidine 231 to glutamate increase open probability of outer membrane protein G in planar lipid bilayer.
Mu YU ; Peibei SUN ; Yao HE ; Liang XIAO ; Demeng SUN ; Longhua ZHANG ; Changlin TIAN
Protein & Cell 2013;4(11):803-806
Bacterial Outer Membrane Proteins
;
chemistry
;
genetics
;
metabolism
;
Escherichia coli Proteins
;
chemistry
;
genetics
;
metabolism
;
Glutamic Acid
;
genetics
;
metabolism
;
Histidine
;
genetics
;
Hydrogen-Ion Concentration
;
Ion Channel Gating
;
genetics
;
Lipid Bilayers
;
metabolism
;
Mutant Proteins
;
chemistry
;
genetics
;
metabolism
;
Mutation
;
Porins
;
chemistry
;
genetics
;
metabolism

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