虫草素生理功效的研究进展

综述了虫草素生理功效的研究进展。虫草素的分子结构为3′-脱氧腺苷,它具有抗菌、抗病毒、抗肿瘤、调节免疫等作用,在医药、食品等领域具有广阔的应用前景。     

Overexpression and Immunological Characterization of the Serine Protease AgSp24D from the Malaria Mosquito, Anopheles gambiae

ABSTRACT Serine proteases are a class of proteolytic enzymes that play regulatory roles in protein processing and degradation. Previous molecular characterization of a mosquito serine protease, AgSp24D , indicated that it is a nondigestive chymotrypsin-like enzyme that is developmentally regulated, and is strongly expressed during the adult stage. Since the biological role of AgSp24D is unknown, we were interested in further characterizing the gene product. Thus, a polyclonal antibody against an AgSp24D fusion protein was produced. The antiserum recognizes two polypeptides of 50 kDa and 60 kDa in immunoblots of whole body homogenates from adult mosquitoes. Western blot analysis showed the strongest signal in a homogenate of thoraces. The signal was also detected in the head, midgut, cuticle plus fat body, ovary, and Malpighian tubules. No signal was detected in the hemolymph. A comparison of Anopheles gambiae, Aedes aegypti, Armigeres subalbatus, Drosophila melanogaster, Acheta domesticus, Manduca sexta , and bovine cardiac muscle and skeletal muscle showed that the polyclonal antibody cross-reacted to similarly sized polypeptides in all samples.     

Neurotrophins improve synaptic transmission in the adult rodent diaphragm

Neurotrophins are usually viewed as secreted proteins that control long-term survival and differentiation of neurons. However, recent studies have established that among the most important functions of neurotrophins is their capacity to regulate synaptic functions and plasticity. When altering synaptic function, neurotrophins are able to produce two types of outcomes, an immediate effect on synaptic transmission and long-term control of synaptic structure and function. The first effect occurs within seconds or minutes after the neurotrophic factor has been applied and usually involves acute modification of synaptic transmission. The second effect takes hours and days, as protein synthesis is required to complete the structural changes. Neurotrophins and their receptors are expressed within the neuromuscular system, making these agents ideal candidates for the short-and long-term regulation of skeletal muscle function. For instance, neurotrophins can alter neuromuscular function acutely, by modulating the amount of neurotransmitter released with each nerve impulse, or chronically, by changing postsynaptic properties or the content and size of synaptic vesicles. It is obvious that the effects of neurotrophins depend on the specific neurotrophin involved (four neurotrophins have been found in mammals; these are nerve growth factor, brain-derived neurotrophic factor, and neurotrophins-3 and-4) and on the specific synapse being studied. Growing evidence highlights the role of neurotrophins in the development and function of neuromuscular synapses. This review will examine the role of neurotrophins in the regulation of neuromuscular transmission. Neirofiziologiya/Neurophysiology, Vol. 39, Nos. 4/5, pp. 327–337, July–October, 2007.     

Mathematical Model of BCG Immunotherapy in Superficial Bladder Cancer

Immunotherapy with Bacillus Calmette–Guérin (BCG)—an attenuated strain of Mycobacterium bovis (M. bovis) used for anti tuberculosis immunization—is a clinically established procedure for the treatment of superficial bladder cancer. However, the mode of action has not yet been fully elucidated, despite much extensive biological experience. The purpose of this paper is to develop a first mathematical model that describes tumor-immune interactions in the bladder as a result of BCG therapy. A mathematical analysis of the ODE model identifies multiple equilibrium points, their stability properties, and bifurcation points. Intriguing regimes of bistability are identified in which treatment has potential to result in a tumor-free equilibrium or a full-blown tumor depending only on initial conditions. Attention is given to estimating parameters and validating the model using published data taken from in vitro, mouse and human studies. The model makes clear that intensity of immunotherapy must be kept in limited bounds. While small treatment levels may fail to clear the tumor, a treatment that is too large can lead to an over-stimulated immune system having dangerous side effects for the patient.     

An entomopathogenic bacterium, Xenorhabdus nematophila, inhibits hemocyte phagocytosis of Spodoptera exigua by inhibiting phospholipase A(2)

Phagocytosis is a hemocytic behavior against bacterial infection. An entomopathogenic bacterium, Xenorhabdus nematophila, inhibits immune responses of target insects and causes hemolymph septicemia. This study analyzed how X. nematophila could inhibit phagocytosis to increase its pathogenicity. Granular cells and plasmatocytes were the main phagocytic hemocytes of Spodoptera exigua determined by observing fluorescence-labeled bacteria in the cytosol. X. nematophila significantly inhibited phagocytosis of both hemocytes, while heat-killed X. nematophila lost its inhibitory potency. However, co-injection of X. nematophila with arachidonic acid did not show any significant inhibition of hemocyte phagocytosis. In fact, hemocytes of S. exigua infected with X. nematophila showed significant reduction in phospholipase A(2) (PLA(2)) activity. Dexamethasone, a specific PLA(2) inhibitor, significantly inhibited phagocytosis of both cell types. However, the inhibitory effect of dexamethasone was recovered by addition of arachidonic acid. Incubation of hemocytes with benzylideneacetone, a metabolite of X. nematophila, inhibited phagocytosis in a dose-dependent manner. These results suggest that X. nematophila produces and secretes PLA(2) inhibitor(s), which in turn inhibit the phagocytic response of hemocytes.     

A chronic viral infection model with immune impairment

In this paper, a chronic viral infection model with cell-mediated immunity and immune impairment is proposed and studied, under the assumption that the presence of the antigen can both stimulate and impair immunity. It is shown that the virus persists in the host if the basic reproductive ratio of the virus is greater than 1. The immune cells persist when there is only one positive equilibrium. The system can exhibit two positive equilibria if the basic reproductive ratio of the virus is above a threshold. This allows a bistable behavior, and the immune cells persist or die out, i.e., infection will result in disease or immune control outcome, depending on the initial conditions. By theoretical analysis and numerical simulations, we show that therapy could shift the patient from a disease progression to an immune control outcome, despite that the therapy is not necessarily lifelong. This would allow the immune response to control the virus in the long term even in the absence of continued therapy.     

Simple scaling laws for influenza A rise time, duration, and severity

Simple scaling laws are developed for the severity and characteristic time scales of influenza A infection in man. The scaling laws are based on a model of the infection described by six coupled ordinary differential equations that describe the time courses of the numbers of infectious viral particles, activated cytotoxic T-lymphocytes, interferon molecules, infected cells, uninfected cells, and the subset of uninfected cells that are protected by interferon from viral infection. Computer simulations show that the disease can be regarded approximately as a two-stage process. In the first stage, the growth in the number of infected cells is determined primarily by the interferon-enhanced limitation in the available number of target cells. In the second stage, the bulk of the duration of the infection is determined mainly by the destruction of the infected cells by the cytotoxic T-lymphocytes. The severity and characteristic times of the infection are found to depend simply on the logarithm of the initial number of viruses.     

Modeling regulation mechanisms in the immune system

We develop a mathematical framework for modeling regulatory mechanisms in the immune system. The model describes dynamics of key components of the immune network within two compartments: lymph node and tissue. We demonstrate using numerical simulations that our system can eliminate virus-infected cells, which are characterized by a tendency to increase without control (in absence of an immune response), while tolerating normal cells, which are characterized by a tendency to approach a stable equilibrium population. We experiment with different combinations of T cell reactivities that lead to effective systems and conclude that slightly self-reactive T cells can exist within the immune system and are controlled by regulatory cells. We observe that CD8+ T cell dynamics has two phases. In the first phase, CD8+ cells remain sequestered within the lymph node during a period of proliferation. In the second phase, the CD8+ population emigrates to the tissue and destroys its target population. We also conclude that a self-tolerant system must have a mechanism of central tolerance to ensure that self-reactive T cells are not too self-reactive. Furthermore, the effectiveness of a system depends on a balance between the reactivities of the effector and regulatory T cell populations, where the effectors are slightly more reactive than the regulatory cells.     

Modeling the mechanisms of acute hepatitis B virus infection

Mathematical models have been used to understand the factors that govern infectious disease progression in viral infections. Here we focus on hepatitis B virus (HBV) dynamics during the acute stages of the infection and analyze the immune mechanisms responsible for viral clearance. We start by presenting the basic model used to interpret HBV therapy studies conducted in chronically infected patients. We then introduce additional models to study acute infection where immune responses presumably play an important role in determining whether the infection will be cleared or become chronic. We add complexity incrementally and explain each step of the modeling process. Finally, we validate the model against experimental data to determine how well it represents the biological system and, consequently, how useful are its predictions. In particular, we find that a cell-mediated immune response plays an important role in controlling the virus after the peak in viral load.     

Neutrophil effector functions triggered by Fc-gamma and/or complement receptors are dependent on B-ring hydroxylation pattern and physicochemical properties of flavonols

Tissue damage in autoimmune diseases involves excessive production of reactive oxygen species (ROS) triggered by immune complexes (IC) and neutrophil (PMN) interactions via receptors for the Fc portion of IgG (FcgammaR) and complement receptors (CR). Modulation of both the effector potential of these receptors and ROS generation may be relevant to the maintenance of body homeostasis. In the present study, the modulatory effect of four flavonols (myricetin, quercetin, kaempferol, galangin) on rabbit PMN oxidative metabolism, specifically stimulated via FcgammaR, CR or both classes of receptors, was evaluated by luminol- and lucigenin-dependent chemiluminescence assays. Results showed that flavonol inhibitory effect was not dependent on the cell membrane receptor class stimulated but related to the lipophilicity of the compounds (their apparent partition coefficient values were obtained by high-performance liquid chromatography), and was also inversely related to the number of hydroxyl groups in the flavonol B ring and the ROS-scavenger activity (assessed by the luminol--H2O2--horseradish peroxidase reaction). Under the experimental conditions the flavonols tested were not toxic to PMNs (evaluated by lactate dehydrogenase release and trypan blue exclusion) and did not interfere with IC-induced phagocytosis (evaluated by transmission electron microscopy). Our results suggested that inhibition of IC-stimulated PMNs effector functions by the flavonols tested herein was the result of cooperation of different cellular mechanisms.