医学纳米颗粒对类细胞膜作用的仿真研究进展

细胞膜是包围细胞质、维持细胞内部组分动态平衡的一个半透膜,参与细胞黏附、离子传导、信号传导等分子生物学过程.类细胞膜提供了有效的模型研究这些生物学过程,故而分子层面上研究医学纳米颗粒对类细胞膜的作用有助于评估纳米颗粒的生物安全性以及促进纳米颗粒的生物医学应用.本文初步探讨了医学纳米颗粒对类细胞膜作用的仿真研究进展,并在此基础上结合膜生物物理学的研究热点对后续的研究进行了展望.

三氧化二砷对心肌细胞蛋白激酶C及胞内游离钙的影响

目的 探讨三氧化二砷 (As2 O3)治疗白血病时的心脏不良反应机制。方法 Fluo 3/AM荧光探针标记豚鼠心室肌细胞 ,激光共聚焦显微镜实时测定不同浓度As2 O3干预后的心室肌胞浆 [Ca2 +]i,磷基转移法测定心室肌胞膜和胞浆内蛋白激酶C(PKC)的活性。结果 0 .5 μmol·L- 1As2 O3对台氏液中豚鼠心室肌细胞 [Ca2 +]i 无明显影响。 2 μmol·L- 1As2 O3持续作用 6min时 ,细胞 [Ca2 +]i 开始升高 ,持续约 9min后恢复到给药前水平。 10 μmol·L- 1As2 O3作用不到 3min时 ,心室肌细胞 [Ca2 +]i 持续升高至扫描结束共 2 7min ,一直没有恢复。As2 O3引起的 [Ca2 +]i 升高可被钙通道阻滞剂维拉帕米和硝苯地平不完全阻断。 2～ 10 μmol·L- 1AS2 O3作用3h可使细胞膜及胞浆相的PKC活性升高 ,10 μmol·L- 1组 ,细胞膜相的PKC升高更明显。结论 一定浓度的As2 O3可使心肌细胞内游离钙升高、PKC活化 ,细胞膜可能是As2 O3最初作用靶点。

基于定长操作数的算术膜计算系统

将膜系统看作8位处理器,利用十进制位置编码的原码、反码及补码的概念和计算方法,设计了算术膜计算(P)系统,实现了加(减)、乘、除4种运算.由于系统中操作对象数量减少,该算术P系统更容易实现大数的运算.而且,设计的算术P系统充分利用膜系统并行运算的特征,具有多项式时间复杂度.

Effects of Membrane Lipids on the Electron Transfer Activity of Cytochrome b_6f Complex from Spinach

A lipid_depleted cytochrome b 6f (Cyt b 6f) preparation was obtained from spinach (Spinacia oleracea L.) chloroplasts. Upon reconstitution of this preparation with the membrane lipids purified from spinach thylakoid, the effects of different membrane lipids on the electron transfer activity were studied. The results show that the electron transfer activity of Cyt b 6f is obviously stimulated to different extents, respectively, by monogalactosyldiacylglycerol (MGDG), digalactosyldiacylglycerol (DGDG), phosphatidylcholine (PC), phosphatidylglycerol (PG) and sulfoquinovosyldiacylglycerol (SQDG), and that the extents of stimulation may be closely related to the charge of the membrane lipids. The stimulation of non_charged lipids (MGDG, DGDG) and neutrally_charged lipid (PC) was high with a maximum enhancement of 89%, 75% and 77%, respectively; but the stimulation of two kinds of negatively_charged lipid (PG and SQDG) was relatively low with a maximum enhancement of 43% and 26%, respectively.

Responses of antioxidant defense system of epilithic mosses to drought stress in karst rock desertified areas

Barbula fallax Hedw., Erythrodontium julaceum(Schwaegr.) Par., and Bryum argenteum Hedw. are typical rock mosses growing on rocks in different terrestrial habitats. In this study, B. fallax and E. julaceum, which are epilithic mosses growing in rock desertification in Guizhou, China, were used as ecophysiological mosses in a combination of field investigations and laboratory experiments. We also investigated the reference moss B. argenteum, which is a widely distributed moss in habitats with soil as substrate. Our research focused on the response of the antioxidant defense system of epilithic mosses to drought stress. Most antioxidant defense indicators increased initially, then declined at later stages of drought stress. In contrast, the carotenoid content increased constantly. In addition, there was an initial increase(albeit variable) in relative membrane permeability, with this parameter showing a parabolic trend in all of the epilithic mosses. Among the three species, E. julaceum demonstrated the strongest resistance followed by B. fallax and then by B. argenteum. The epilithic mosses displayed stronger resistance compared to the native mosses; the increase in O_2 content and other reactive oxygen species(ROS) at the early stage of drought stress induced the enzymatic and non-enzymatic scavenging systems tosequester ROS. Moreover, the radical scavenging ability and strong drought tolerance was maintained. The longterm growth of bryophyte under drought conditions in a karst environment can help eliminate the intense response of mosses to drought stress as they adapt.

Lipid-associated membrane proteins of Mycoplasma penetrans induce production of proinflammatory cytokines in human monocytic cells

The aim of this study is to explore potential pathogenicity of Mycoplasma penetrans, and to investigate whether M. penetrans lipid-associated membrane proteins （LAMPs） could induce human monocytic cell line （THP- 1 ） to produce some proinflammatory cytokines in vitro, including interleukin- 1β （ IL- 1β）, tumor necrosis factor alpha （TNF-α）, and IL-8. THP-1 was stimulated with different concentrations of M.penetrans LAMPs and at different time to analyze the production of human IL-1β, TNF-α and IL-8. The protein levels of human IL-1β, TNF-α and IL-8 were measured by enzyme-linked immunoadsorbent assay （ELISA） and the mRNA levels of these proinflammatory cytokines were detected by reverse transcriptase-PCR （RT-PCR）. It was demonstrated in the present study that the production of IL-1β, TNF-α and IL-8 increased in dose- and time-dependent manner after stimulation with M. penetrans LAMPs in THP-1 cells. M. penetrans LAMPs also induced the expression of IL-1β, TNF-α and IL-8 mRNA. The production of IL-1β, TNF-α and IL-8 and the expression of mRNA were down-regulated by pyrrolidine dithiocarbamate （PDTC）. This study demonstrated that M. penetrans LAMPs can induce the production of proinflammatory cytokines in human monocytic cells in vitro, thus suggesting that it may be an important etiological factor.

Effect of ConA-receptor interaction on the structure of cell membrane

Recently, the effect of ligand receptor interaction on the membrane structure of liposomes has been studied extensively. However, little is known about how it exists on biological membranes. In this paper, the effect of Con-canavalin A (ConA) receptor interaction on the structure of cell membranes was studied by Circular Dichroism (CD) and 3lP Nuclear Magnetic Resonance (NMR).CD results of both the purified macrophage membranes and human erythrocyte ghosts (EG) showed that the conformation of membrane proteins changed after ConA bind ing.For further research, 31P-NMR was used to detect the organization of phospholipid molecules on macrophage mem branes. After ConA binding, the tendency to form non bi-layer structure increased with the amount of ConA. The changes of 31P-NMR spectra of living macrophages might be partly due to the above stated reason too.In addition, ConA-receptor interaction also induced similar results of 31P-NMR spectra in EG. In contrast, wheat germ agglutinin (WGA ), another kind of lectin, rarely showed the same influence.

Ion Channels as Antivirus Targets

Ion channels are membrane proteins that are found in a number of viruses and which are of crucial physiological importance in the viral life cycle. They have one common feature in that their action mode involves a change of electrochemical or proton gradient across the bilayer lipid membrane which modulates viral or cellular activity. We will discuss a group of viral channel proteins that belong to the viroproin family, and which participate in a number of viral functions including promoting the release of viral particles from cells. Blocking these channel-forming proteins may be ＂lethal＂, which can be a suitable and potential therapeutic strategy. In this review we discuss seven ion channels of viruses which can lead serious infections in human beings： M2 of influenza A, NB and BM2 of influenza B, CM2 of influenza C, Vpu of HIV-1, p7 of HCV and 2B of picomaviruses.

Diabetic retinopathy: recent advances towards understanding neurodegeneration and vision loss

Diabetic retinopathy （DR） is one of the most common retinal diseases world-wide. It has a complex pathology that involves the vasculature of the inner retina and breakdown of the blood-retinal barrier. Extensive research has determined that DR is not only a vascular disease but also has a neurodegenerative component and that essentially all types of ceils in the retina are affected, leading to chronic loss of visual function. A great deal of work using animal models of DR has established the loss of neurons and pathology of other cell types, including supporting glial cells. There has also been an increased emphasis on measuring retinal function in the models, as well as further validation and extension of the animal studies by clinical and translational research. This article will attempt to summarize the more recent developments in research towards understanding the complexities of retinal neurodegeneration and functional vision loss in DR.

The dehydration dynamics of a model cell membrane induced by cholesterol analogue 6-ketocholestanol investigated using sum frequency generation vibrational spectroscopy

Dehydration of a surface is the first step for the interaction between biomolecules and the surface. In this study, we systemati- cally investigated the influence of cholesterol analog 6-ketocholestanol （6-KC） on the dehydration of model cell membrane, using sum frequency generation vibrational spectroscopy. In pure DI water environment, two separate dehydration dynamic components were observed in neutrally charged and isotopically labeled 1,2-dimyristoyl-sn-glycero-3-phosphocholine （DMPC） and positively charged 1,2-dimyristoyl-sn-glycero-3-ethylphosphocholine（chloride salt） （DMEPC） bilayer： a large-amplitude fast component and a small-amplitude slow component, which originated from the water molecules with a weak and a strong water-membrane bound strengths, respectively. Dehydration of a negatively charged mixed DMPC/DMPG bilayer lead to the membrane-bound water being reorganized to ordered structures quickly. It is evident that the water-membrane bound strengths depend largely on the charge status of the lipid and has an order of neutrally charged membrane〈〈positively charged mem- brane〈〈negatively charged membrane. In an ionic environment, KC1 solution can not only dehydrate DMPC bilayer, but also prevent the 6-KC fiom further dehydrating this model cell membrane. We observed that the dehydration dynamics behavior of DMPC bilayer in the presence of the chaotropic anions is similar to that of the negatively charged DMPG bilayer because of the penetration of chaotropic anions into the DMPC bilayer. The degree of dehydration difficulty in kosmotropic anions fol- lows a Hofmeister series and linearly correlates with the hydration Gibbs free energy of the anions. Our results provide a molecular basis for the interpretation of the Hofmeister effect of kosmotropic anions on ion transport proteins.

KLF4 is a tumor suppressor in anaplastic meningioma stem-like cells and human rneningiomas

Meningiomas are the most common primary tumors in central nervous system. While recent studies have revealed genetic clues to lower grade human meningiomas, the molecular determinants driving the progression and recurrence of anaplastic meningi- oma, the most malignant subtype with a low prevalence but high morbidity, are still poorly understood. It has been proposed that high recurrence rates of malignant meningiomas are linked to cancer stem cells. Indeed, tumor stem-Uke cells have been iso- lated from various meningioma subtypes, but never been obtained from anaplastic meningioma, in this study, we successfully isolated stem-Uke cells from human anaplastic meningioma. These cells are capable of forming spheres and initiating xenograft tumors that recapitulate anaplastic meningioma phenotypes, and thus could serve as an in vitro model for malignant meningi- omas. KLF4, a transcription factor known for its role in sternness maintenance, was identified as one of the most frequently mutated genes in the benign secretory meningioma. Interestingly, we found that KLF4 is downregulated in anaplastic meningi- oma compared with low-grade meningioma subtypes. By manipulating KLF4 expression in anaplastic meningioma stem-like cells, we demonstrated that KLF4 acts as a tumor suppressor during malignant progression in meningioma, affecting apoptosis, prolif- eration, invasion, and cell cycle. These results suggest a potential therapeutic value of KLF4 for clinical intervention of anaplastic meningioma.

Life after the birth of the mitochondrial Na^+/Ca^(2+) exchanger,NCLX

Powered by the mitochondrial membrane potential,Ca2+ permeates the mitochondria via a Ca2+ channel termed Ca2+ uniporter and is pumped out by a Na+/Ca2+ exchanger,both of which are located on the inner mitochondrial membrane.Mitochondrial Ca2+ transients are critical for metabolic activity and regulating global Ca2+ responses.On the other hand,failure to control mitochondrial Ca2+ is a hallmark of ischemic and neurodegenerative diseases.Despite their importance,identifying the uniporter and exchanger remains elusive and their inhibitors are non-specific.This review will focus on the mitochondrial exchanger,initially describing how it was molecularly identified and linked to a novel member of the Na+/Ca2+ exchanger superfamily termed NCLX.Molecular control of NCLX expression provides a selective tool to determine its physiological role in a variety of cell types.In lymphocytes,NCLX is essential for refilling the endoplasmic reticulum Ca2+ stores required for antigen-dependent signaling.Communication of NCLX with the store-operated channel in astroglia controls Ca2+ influx and thereby neuro-transmitter release and cell proliferation.The refilling of the Ca2+ stores in the sarcoplasmic reticulum,which is controlled by NCLX,determines the frequency of action potential and Ca2+ transients in cardiomyocytes.NCLX is emerging as a hub for integrating glucose-dependent Na+ and Ca2+ signaling in pancreatic β cells,and the specific molecular control of NCLX expression resolved the controversy regarding its role in neurons and β cells.Future studies on an NCLX knockdown mouse model and identification of human NCLX mutations are expected to determine the role of mitochondrial Ca2+ efflux in organ activity and whether NCLX inactivation is linked to ischemic and/or neurodegenerative syndromes.Structure-function analysis and protein analysis will identify the NCLX mode of regulation and its partners in the inner membrane of the mitochondria.