低功率光照疗法对机体免疫应答的影响（英文）

最近几年,采用红至红外波长(600~1100 nm)的低功率光照(low-dose light,LDL)疗法对组织代谢系统、神经系统、血液循环系统和免疫系统等方面的调节效应已经引起了广泛关注.同时,生物能学和光生物学基础研究的发展推动了低功率光照在疾病治疗领域的革新.有报道指出,巨噬细胞、肥大细胞、中性粒细胞和淋巴细胞等免疫细胞能响应低功率光照,产生细胞因子和保护性的蛋白质分子来缓解一些疾病的进程.因此,本文将从分子、细胞和组织水平对低功率光照改善的一些疾病的免疫学现象及机制进行归纳总结.     

低功率He-Ne激光照射下细胞内活性氧自由基的产生和游离Ca^2＋浓度的研究

在临床应用中,低功率He-Ne激光(632.8 nm)能促进骨骼肌修复,加速创伤愈合,降低牙齿的超敏感性,减缓疼痛等.大量研究表明:低功率He-Ne激光能调节细胞的众多行为,如细胞增殖、分泌、迁移、粘附、蛋白质合成和基因表达等.但低功率He-Ne激光调节细胞行为的分子机制并未阐明,考察低功率He-Ne激光照射后细胞内活性氧自由基的产生水平和游离ca2 浓度是否会发生变化,通过激光扫描共聚焦显微镜,分别利用H:DCFDA和Fluo-3/AM这两种荧光探针,检测到经He-Ne激光照射后,肺腺癌细胞内活性氧自由基的水平上调以及游离Ca2 浓度增加.该研究为低功率He-Ne激光的生物光刺激效应提供了可能的分子机理.     

光照强度和肥力变化对垂穗披碱草生长的影响

在野外条件下,采用析因设计,对光照和肥力变化影响下垂穗披碱草的生长参数进行测定,评估垂穗披碱草对异质环境的适应特性。光照分为高光照(100%光照强度)、中度光照(43.5%光照强度)与低光照(6.74%光照强度);肥力分为施肥与不施肥。结果表明,垂穗披碱草在光照强度由高光照(100%)向中度光照(43.5%)变化情况下,地上生物量、分蘖数无变化,株高增大,光照强度减小到6.74%时,地上生物量、分蘖数、株高均减小。比叶面积(SLA)随光照强度的减弱而增加,相对生长率(RGR)随光照强度的减弱而减小,施肥对SLA和RGR无影响。根冠比在中度光照和低光照下各处理之间差异均不显著,高光照(100%)下增加肥力,根冠比增大。施肥时,叶分配随光照强度的减弱而增加,繁殖分配减小,不施肥时,叶分配与繁殖分配在高光照(100%)和中度光照(43.5%)下无差异,低光照(6.74%)下,叶分配增大,繁殖分配减小。施肥时茎分配在中度光照强度(43.5%)下最大,高光照强度(100%)下次之,低光照强度(6.74%)下最小,不施肥时,茎分配在高光照(100%)和中度光照(43.5%)下无差异,低光照(6.74%)下减小。研究表明:垂穗披碱草是一个光照耐受型物种,光照强度减小到全光照一半时仍可正常生长。在低光环境中,垂穗披碱草通过增加株高和大而薄的叶片,来适应环境,资源主要在叶分配、茎分配、繁殖分配之间进行了权衡。     

脂肪因子visfatin的调节与功能多样性

内脏脂肪素(visfatin)是一种由内脏脂肪细胞分泌的分子质量为52 ku的蛋白质细胞因子．基因序列分析显示其cDNA编码序列与前B细胞集落增强因子(PBEF)同源且在进化中高度保守．Visfatin被发现具有多种迥然不同的生物活性：通过与胰岛素受体相互作用,在不同的情况下visfatin可表现出类胰岛素或抗胰岛素样作用;在细胞质中,visfatin具有烟酰胺磷酸核糖转移酶(Nampt)活性,能够催化烟酰胺腺嘌呤二核苷酸(NAD)的生物合成;作为分泌型的细胞因子,visfatin还可以诱导多种炎性因子的表达,如TNFα、IL-1β和IL-6．Visfatin与一些代谢疾病和急、慢性炎性疾病的关系日益受到重视,如糖尿病、肥胖、急性肺损伤、类风湿性关节炎、败血症、心肌梗塞和炎性肠病等．最近,对visfatin的启动子区及其单核苷酸多态性(SNP)的研究,进一步深化了人们对其在疾病发病机制中作用的认识．重点讨论visfatin的结构、功能多态性以及它与多种疾病的关系．     

褐潮——一种新型生态系统破坏性藻华

Aureococcus anophagefferens和Aureoumbra lagunensis隶属于棕鞭藻门(Ochrophyta)、海金藻纲(Pelagophyceae),在美国及南非的一些河口形成生态系统破坏性褐潮(brown tide)已经有20多年了,近年来在中国河北沿海发生的大规模褐潮也使中国成为世界上第3个受褐潮影响的国家。褐潮藻能够利用多种有机营养,在低光照及低营养条件下达到高生长速率,对贝类养殖产业、经济以及娱乐产业等造成严重的负面影响。本文总结了20多年来褐潮在全球的发生及其所造成的严重危害,对褐潮藻的形态结构、生理特征及分子遗传学,特别是促进褐潮形成及持续的关键蛋白的编码基因等研究作了简要介绍,并概括了国内褐潮的研究现状。在此基础上,展望今后褐潮的研究方向,以期为褐潮的研究、预警预报和生态学防治及其防灾减灾提供借鉴。     

薇甘菊和飞机草抗氧化物和膜脂过氧化物对光照和土壤水分的响应

田间温室控制条件下研究入侵杂草薇甘菊(Mikania micrantha)和飞机草(Chromolaena odoratum)在不同光照(高、中、低光照)和土壤水分(高、中、低水分含量)交互作用下, 叶片超氧化物歧化酶(SOD)和过氧化氢酶(CAT)活性, 脯氨酸(Pro)、谷胱甘肽(GSH)以及膜脂过氧化物丙二醛(MDA)含量的变化, 探讨两种杂草对不同光照和土壤水分交互作用的生理适应性。结果表明: 高光下低水处理的两种杂草MDA含量均显著高于全水处理, 表现出明显的胁迫。此胁迫条件下薇甘菊通过迅速提高SOD和CAT活性, 提高Pro和GSH含量来清除活性氧, 维持代谢平衡, 但不能在干旱条件下维持较长时间; 飞机草的SOD活性、Pro和GSH含量也迅速提高, 在高光缺水的适应性响应中起了重要作用, CAT则未能发挥保护作用。相对于其他光照, 低光显著降低了薇甘菊的SOD、CAT活性和MDA含量, 而对飞机草上述指标的影响较小, 说明低光降低了两种杂草尤其是薇甘菊的抗氧化物代谢水平。     

资源异质性环境中三种匍匐茎草本植物克隆内资源共享和分株功能特化(英文)

研究了 3种来自中国北方林下、草地和碱化草甸匍匐茎型克隆草本植物绢毛匍匐委陵菜 (PotentillareptansL .var.sericophyllaFranch .)、鹅绒委陵菜 (P .anserinaL .)和金戴戴 (Halerpestesruthenica (Jacq .)Qvcz .)对由高光照低养分斑块和低光照高养分斑块组成的资源交互斑块性生境的适应性对策。当生长于高光照低养分条件下分株(HL分株 )与生长于低光照高养分条件下分株 (LH分株 )之间的匍匐茎连接时 ,3种克隆植物HL分株、LH分株以及整个分株对系统 (HL分株 LH分株 )的生物量均得到显著提高。同时 ,LH分株根冠比显著增加 ,而HL分株根冠比显著下降。这表明 ,当互连分株置于由低光照高养分斑块和高光照低养分斑块组成的异质性环境中时 ,3种植物克隆分株均发生了环境诱导的功能特化。克隆内资源共享以及克隆内不同分株的功能特化有利于整个分株系统对局部丰富资源的获取 ,从而能够缓解资源交互斑块性生境对克隆植物的不利影响     

新型蛋白质配体-亲和体研究进展

亲和体(affibody)是一种衍生于葡萄球菌A蛋白B结构域的人工蛋白质分子．B结构域含58个氨基酸,形成3个α螺旋结构,分子质量约为6.5 ku．其中第一及第二螺旋中的13个特定位点的氨基酸对其结构无明显影响,这些位点可被随机突变形成理论上可与任何靶分子结合的亲和体文库．筛选该文库可获得能与某一靶分子特异结合的亲和体．亲和体与靶分子的结合特性与抗体相似,但与抗体相比具有一些独特的优势,如：通过体外筛选即可获得,以化学合成方法或原核表达即可大量制备,分子质量小、在生物体内组织穿透性强、血浆清除率高,理化稳定性好,可以通过交联或融合表达与标记分子(如荧光蛋白、生物素等)结合而不影响其与靶分子的结合能力．亲和体可作为抗体的替代品,用于蛋白质识别、分离及纯化、实验诊断、分子显像及靶向治疗．     

混合表型急性白血病的细胞及分子遗传学研究进展

混合表型急性白血病(mixed-phenotype acute leukemia, MPAL)是一类同时表达不止一个谱系特异性抗原的恶性克隆性疾病,发生率低,仅占急性白血病的2%~5%。多数MPAL患者可检测出克隆性染色体异常及分子遗传学改变,其中一些特异性异常如t(9;22)(q34;q11)及KMT2A重排在MPAL的诊断分型、靶向治疗及预后判断中具有重要的指导意义。近年来,随着全基因组测序、全外显子测序、靶向测序及单核苷酸多态性-微阵列比较基因组杂交等分子生物学技术的广泛应用,人们发现一些新的分子遗传学异常如ZNF384重排及WT1基因突变等也与疾病的发生发展及预后密切相关。这些发现进一步丰富了对MPAL发病机制的认识。现将有关MPAL细胞及分子遗传学的研究进展进行综述。     

资源异质性环境中三种匍匐茎草本植物克隆内资源共享和分株功能特化

研究了3种来自中国北方林下、草地和碱化草甸匍匐茎型克隆草本植物绢毛匍匐委陵菜 (Potentilla reptans L. var. sericophylla Franch.)、鹅绒委陵菜 (P. anserina L.) 和金戴戴 (Halerpestes ruthenica (Jacq.) Qvcz.) 对由高光照低养分斑块和低光照高养分斑块组成的资源交互斑块性生境的适应性对策.当生长于高光照低养分条件下分株 (HL分株) 与生长于低光照高养分条件下分株 (LH分株) 之间的匍匐茎连接时, 3种克隆植物HL分株、LH分株以及整个分株对系统 (HL分株 + LH分株) 的生物量均得到显著提高.同时, LH分株根冠比显著增加, 而HL分株根冠比显著下降.这表明, 当互连分株置于由低光照高养分斑块和高光照低养分斑块组成的异质性环境中时, 3种植物克隆分株均发生了环境诱导的功能特化.克隆内资源共享以及克隆内不同分株的功能特化有利于整个分株系统对局部丰富资源的获取, 从而能够缓解资源交互斑块性生境对克隆植物的不利影响.     

Uptake and degradation of low density lipoproteins in atherosclerotic rabbit aorta: role of local LDL modification

The uptake of native and modified low density lipoprotein (LDL) in foam cells in atherosclerotic tissue was studied in an in vitro perfusion system for rabbit aorta. Experimental atherosclerosis was induced in rabbits by a combination of cholesterol feeding and mechanical injury. The aorta was perfused in an incubation chamber. A trace-label, radioiodinated tyramine-cellobiose, was used to study cellular uptake of lipoproteins. After perfusion, the tissue was digested and cells were isolated by centrifugation in a density gradient. About 40 times more LDL per cell was accumulated in the foam cell fraction than in the smooth muscle cell fraction. When the cellular uptake of LDL and acetylated LDL (AcLDL) was compared, about 4 times more AcLDL than LDL was taken up by the foam cells, suggesting that the scavenger receptor is expressed in these cells. In a competition experiment, the uptake of LDL into foam cells was reduced by 70% when a tenfold excess of AcLDL was added. This experiment suggests that native LDL is taken up by the same mechanism as AcLDL. The accumulation of radiolabeled LDL in plaques and in foam cells was reduced by 30-55% by adding vitamin E (0.1 mg/ml) to the system. These studies show an uptake of LDL by foam cells in the atherosclerotic tissue. Furthermore, these cells seem to express the scavenger receptor. The competition experiment would suggest that native LDL is taken up by the scavenger receptor. The observation that an antioxidant, vitamin E, may decrease this uptake suggests that oxidative modification of LDL is of importance for this process.     

Hypochlorite-modified low-density lipoprotein induces the apoptotic machinery in Jurkat T-cell lines

Myeloperoxidase is abundantly present in inflammatory diseases where activation of monocytes/macrophages and T-cell-mediated immune response occurs. The potent oxidant hypochlorous acid (HOCl), generated by the myeloperoxidase–H₂O₂–chloride system of activated phagocytes, converts low-density lipoprotein (LDL) into a proinflammatory lipoprotein particle. Here, we investigated the apoptotic effect of HOCl–LDL, an in vivo occurring LDL modification, on human T-cell lymphoblast-like Jurkat cells. Experiments revealed that HOCl–LDL, depending on the oxidant:lipoprotein molar ratio, induces apoptosis via activation of caspase-3, PARP cleavage and accumulation of reactive oxygen species. The absence of Fas-associated protein with death domain or caspase-8 in mutant cells did not prevent HOCl–LDL induced apoptosis. In contrast, overexpression of the anti-apoptotic Bcl-2 protein protects Jurkat cells against HOCl–LDL-induced apoptosis and prevents accumulation of reactive oxygen species. We conclude that HOCl–LDL-mediated apoptosis in Jurkat cells follows predominantly the intrinsic, mitochondrial pathway. Insitu experiments revealed that an antibody raised against HOCl–LDL recognized epitopes that colocalize both with myeloperoxidase and CD3-positive T-cells in human decidual tissue where local stimulation of the immune system occurs. We provide convincing evidence that formation of HOCl-modified (lipo)proteins generated by the myeloperoxidase–H₂O₂–chloride system contributes to apoptosis in T-cells.     

Adenosine signaling and adenosine deaminase regulation of immune responses: impact on the immunopathogenesis of HIV infection

Infection by human immunodeficiency virus (HIV) causes the acquired immune deficiency syndrome (AIDS), which has devastating effects on the host immune system. HIV entry into host cells and subsequent viral replication induce a proinflammatory response, hyperactivating immune cells and leading them to death, disfunction, and exhaustion. Adenosine is an immunomodulatory molecule that suppresses immune cell function to protect tissue integrity. The anti-inflammatory properties of adenosine modulate the chronic inflammation and immune activation caused by HIV. Lack of adenosine contributes to pathogenic events in HIV infection. However, immunosuppression by adenosine has its shortcomings, such as impairing the immune response, hindering the elimination of the virus and control of viral replication. By attempting to control inflammation, adenosine feeds a pathogenic cycle affecting immune cells. Deamination of adenosine by ADA (adenosine deaminase) counteracts the negative effects of adenosine in immune cells, boosting the immune response. This review comprises the connection between adenosinergic system and HIV immunopathogenesis, exploring defects in immune cell function and the role of ADA in protecting these cells against damage.     

Oxidized low-density lipoprotein promotes mature dendritic cell transition from differentiating monocyte

Proinflammatory oxidized phospholipids are generated during oxidative modification of low-density lipoproteins (LDL). The production of these proinflammatory oxidized phospholipids is controlled by secreted enzymes that circulate as proteins complexed with LDL and high-density lipoprotein. During the acute phase response to tissue injury, profound changes occur in lipoprotein enzymatic composition that alter their anti-inflammatory function. Monocytes may encounter oxidized phospholipids in vivo during their differentiation to macrophages or dendritic cells (DC). In this study we show that the presence of oxidized LDL (oxLDL) at the first day of monocyte differentiation to DC in vitro yielded phenotypically atypical cells with some functional characteristics of mature DC. Addition of oxLDL during the late stage of monocyte differentiation gave rise directly to phenotypically mature DC with reduced uptake capacity, secreting IL-12 but not IL-10, and supporting both syngeneic and allogeneic T cell stimulation. In contrast to known mediators of DC activation, oxLDL did not trigger maturation of immature DC. An intriguing possibility is that a burst of oxidized phospholipids is an endogenous activation signal for the immune system, which is tightly controlled by lipoproteins during the acute phase response.     

Dynamic imaging of the immune system: progress, pitfalls and promise

Both innate and adaptive immunity are dependent on the migratory capacity of myeloid and lymphoid cells. Effector cells of the innate immune system rapidly enter infected tissues, whereas sentinel dendritic cells in these sites mobilize and transit to lymph nodes. In these and other secondary lymphoid tissues, interactions among various cell types promote adaptive humoral and cell-mediated immune responses. Recent advances in light microscopy have allowed direct visualization of these events in living animals and tissue explants, which allows a new appreciation of the dynamics of immune-cell behaviour. In this article, we review the basic techniques and the tools used for in situ imaging, as well as the limitations and potential artefacts of these methods.     

Ecoimmunity: immune tolerance by symmetric co-evolution

It is widely accepted that immune tolerance toward "self" is established by central and peripheral adaptations of the immune system. Mechanisms that have been demonstrated to play a role in the induction and maintenance of tolerance include thymic deletion of self-reactive T cells, peripheral T cell anergy and apoptosis, as well as thymic and peripheral induction of regulatory T cells. However, a large body of experimental findings cannot be rationalized solely based on adaptations of the immune system to its environment. Here we propose a new model termed Ecoimmunity, where the immune system and the tissue are viewed as two sides of a continuously active and co-evolving predator-prey system. Ecoimmunity views self-tolerance, not as an equilibrium in which autoimmunity is chronically suppressed, but as a symmetrical balanced conflict between the ability of immune cells to destroy tissue cells by numerous mechanisms, and the capacity of adapted tissue cells to avoid predation. This balance evolves during ontogeny, in parallel to immune adaptations, embryonic tissue cells adapt their phenotype to the corresponding immune activity by developing the ability to escape or modulate damaging local immune responses. This phenotypic plasticity of tissue cells is directed by epigenetic selection of gene expression pattern and cellular phenotype amidst an ongoing immune pressure. Thus, whereas some immune cells prey predominantly on pathogens and infected cells, self-reactive cells continuously prey on incompetent tissue cells that fail to express the adapted phenotype and resist predation. This model uses ecological generalization to reconcile current contradictory observations as well as classical enigmas related to both autoimmunity and to tolerance toward foreign tissues. Finally, it provides empirical predictions and alternative strategies toward clinical challenges.     

LOX‐1: Its cytotopographical variance and disease stress

Lectin‐like oxidized low‐density lipoprotein receptor‐1 (LOX‐1) is a canonical receptor for oxidized LDL (oxLDL) among the known modified LDL particles. Topographical variance on LOX‐1 expression in different cell types and its influence on the atherogenic potential of the particular cell type is the main focus of this review. Characteristic features of LOX‐1 on the atherogenic potential of aortic endothelial cells, macrophages, platelets, and vascular smooth muscle cells have been discussed. Nonspecificity of ligands, besides oxLDL, is also the highlight of this review to show the chameleon characteristics in the functional activity of the receptor protein. Induction of LOX‐1 has been reported in diseases like atherosclerosis, diabetes, and hypertension, as well as in the inflammatory response of immune reactions. The expression of LOX‐1 is upregulated by the vicious cycle of stimulatory response from proatherogenic molecules.     

Photodynamic therapy: illuminating the road from cell death towards anti-tumour immunity

Photodynamic therapy (PDT) utilizes the destructive power of reactive oxygen species generated via visible light irradiation of a photosensitive dye accumulated in the cancerous tissue/cells, to bring about their obliteration. PDT activates multiple signalling pathways in cancer cells, which could give rise to all three cell death modalities (at least in vitro). Simultaneously, PDT is capable of eliciting various effects in the tumour microenvironment thereby affecting the tumour-associated/-infiltrating immune cells and by extension, leading to infiltration of various immune cells (e.g. neutrophils) into the treated site. PDT is also associated to the activation of different immune phenomena, e.g. acute-phase response, complement cascade and production of cytokines/chemokines. It has also come to light that, PDT is capable of activating ‘anti-tumour adaptive immunity’ in both pre-clinical as well as clinical settings. Although the ability of PDT to induce ‘anti-cancer vaccine effect’ is still debatable, yet it has been shown to be capable of inducing exposure/release of certain damage-associated molecular patterns (DAMPs) like HSP70. Therefore, it seems that PDT is unique among other approved therapeutic procedures in generating a microenvironment suitable for development of systemic anti-tumour immunity. Apart from this, recent times have seen the emergence of certain promising modalities based on PDT like-photoimmunotherapy and PDT-based cancer vaccines. This review mainly discusses the effects exerted by PDT on cancer cells, immune cells as well as tumour microenvironment in terms of anti-tumour immunity. The ability of PDT to expose/release DAMPs and the future perspectives of this paradigm have also been discussed.     

The adaptive immune system as a fundamental regulator of adipose tissue inflammation and insulin resistance

Over the past decade, chronic inflammation in visceral adipose tissue (VAT) has gained acceptance as a lead promoter of insulin resistance in obesity. A great deal of evidence has pointed to the role of adipokines and innate immune cells, in particular, adipose tissue macrophages, in the regulation of fat inflammation and glucose homeostasis. However, more recently, cells of the adaptive immune system, specifically B and T lymphocytes, have emerged as unexpected promoters and controllers of insulin resistance. These adaptive immune cells infiltrate obesity expanded VAT and through cytokine secretion and macrophage modulation dictate the extent of the local inflammatory response, thereby directly impacting insulin resistance. The remarkable ability of our adaptive immune system to regulate insulin sensitivity and metabolism has unmasked a novel physiological function of this system, and promises new diagnostic and therapeutic strategies to manage the disease. This review highlights critical roles of adipose tissue lymphocytes in governing glucose homeostasis.     

Initiating and guiding migration: lessons from border cells

Cell migration occurs in many different contexts. Amoebae and other isolated cells migrate in culture. In animals, 'professional' migratory cells of the immune system constantly survey the body for intruders, whereas other cell types perform specific developmentally regulated migrations. One simple model for the latter type of event is migration of border cells during Drosophila oogenesis. Recent findings have shed light on how border cell fate is induced and on how the migration is guided. This article discusses the implications of these studies and compares (invasive) migration through a tissue with what is known about cells crawling on a flat substratum.