Abstract:Immunophotonics——the application of photonics theory and technology in immunological visualization and therapy

Abstract:Optical molecular imaging, which greatly promoted the development of immunology, is one of the best methods to investigate cell morphology, movement and function in a complex regional environment in vivo. The liver is a vital organ for maintaining body’s metabolism and detoxification, and it as an immunological organ. Understanding the basic feature and function of liver immunology is significant for prevention and treatment of liver disease and associated systemic diseases. Visualization immune response under physiological or pathological condition in vivo, providing spatial-temporal and dynamic information of multiple cells involved in key events and their interactions, can greatly enrich the knowledge of liver unique immune response. This review will focus on the current liver intravital imaging techniques and methods, and the application of optical microscopic imaging techniques in liver immunology, such as multiphoton excitation confocal microscopy and spin-disk confocal microscopy, and future development directions and challenges of in vivo liver imaging are prospected.

Abstract:Immunological synapse (IS) is a specialized and sophisticated supramolecular activation cluster structure that is formed at the interface between T cell and antigen presenting cells. It is a dynamic multistage progress, involving adhesion molecules, cytokines, signaling molecules, cell cytoskeletal proteins and other molecules. IS is not only contribute to the stability of the contact between T cells and APC, but also promotes T-cell activation and proliferation through T cells signaling pathway. Studying of the immunological synapse could explain molecular mechanisms of immune activation, immune tolerance, and the mechanism of interaction between pathogenic microbes and immune cells, which will provide new ideas for further revealing the pathogenic mechanism of disease, and seeking new target molecules for disease control and prevention. Recently, optical imaging provides a powerful help for visualization on the relationship between IS formation and T-cell activation. It provides a powerful tool for studying the immune response under physiological and pathological conditions.

Abstract:The effect of low-dose light (LDL) therapy, commonly using red and near infrared (NIR) light (600-1 100 nm), has gained attention in recent years as a relatively noninvasive technique in modulating the tissue metabolic system, nervous system, blood circulation system and immune system. The progress in the basic science fields of bioenergetics and photobiology has propelled LDL into the therapeutic revolution. The immune cells including macrophages, mast cells, neutrophils and lymphocytes as responder cells by LDL have been studied in the animals and humans with producing cytokines and protective proteins. The paper will review the mechanisms of immune action of LDL at the molecular, cellular, and tissue levels on mammalian.

Abstract:Uveitis is a recurrent inflammatory disease that can lead to immune system dysfunction and multiple organ injuries. However, whether uveitis causes liver functional damage is still unclear. Herein, by using flow cytometry and confocal, we investigated the pathological and functional changes of liver in an experimental autoimmune model of uveitis (EAU). Hepatic damage was observed at the inflammatory stage of uveitis and was associated with severity of eye damage. Moreover, the expression of CD3⁺CD4⁺ T cells, CD3^-NK1.1⁺DX5^- NK cells, and CD11b⁺F4/80^-Ly6c⁺ cells were increased in the inflamed eye and liver. Furthermore, the pathological damage of EAU and hepatic impairment were aggravated after transferring CD3⁺CD4⁺ T cells into EAU mice. Additionally, vascular dilation and infiltration of CD3⁺CD4⁺ T cells were found in the eyes and livers of EAU mice. In conclusion, our findings suggest that liver injury could occur in EAU. This liver injury may be associated with increased CD3⁺CD4⁺ T cells, which may infiltrate into liver through circulatory system.

Abstract:The tumor killing and immune stimulation effects of photothermal therapy using nano graphene oxide(NGO)were studied in vitro and in vivo. For in vitro study, NGO showed a good photothermal conversion effect, increasing temperature under laser irradiation to destroy tumor cells. In addition, NGO could effectively stimulate the production of IL-6 and TNFα by macrophages and enhance the immune response of macrophages to laser-treated tumor cells. For in vivo study, two tumors were inoculated on both sides of the back of mice, serving as the local primary tumor and surrogate distal metastatic tumor. The results showed that the treatment of NGO combined with laser could effectively ablate the treated primary tumor, and inhibit the growth of untreated distal tumor. It suggested that the treatment of NGO combined with laser therapy could stimulate the anti-tumor immune response of the body to attack distal metastases.

Abstract:Human urine-derived stem cells (hUSCs) are somatic stem cells isolated from fresh urine by the way of centrifugation combined with adherence screening, which are with strong proliferation and multi-differentiation capacity, and have all kinds of similar biological characters as mesenchymal stem cells. HUSCs have the potential of playing an important role in reconstitution of damaged organs and tissues, treatment of the diseases and drug activity and toxicity screening, and urine-induced pluripotent stem cells (u-iPSCs) have been induced by many ways from hUSCs. However, several questions need to be answered prior to developing a technology for drug screen with hUSCs and u-iPSCs, such as the cell source of hUSCs, directional differentiation and efficiency of iPSCs reprogramming. In this review, recent progress in cell source, cell isolation and cultivation, cell biological characteristics, and the application of hUSCs were studied, especially various ways of inducing hUSCs to u-iPSCs and the possible application prospect were summarize, providing a reference for further study and application of hUSCs in drug development and toxicity testing.

Abstract:Mycobacterium tuberculosis is the pathogen of tuberculosis which causes about millions people death annually. M. smegmatis, as a type of non-pathogenic strain of Mycobacterium closely related to M. tuberculosis, is the most studied model strain in laboratory. Mycobacterium encodes three types of chromatin proteins, i.e. histone-like protein HU, Lsr2 and integration host factor (IHF). To investigate the functional roles of IHF in chromosomal DNA organization, we expressed and purified IHF protein from M. smegmatis (MsIHF) in Escherichia coli, and analyzed the effects of MsIHF on DNA topology in vitro. MsIHF exists as a stable homodimer in solution. MsIHF exhibits preferred binding to negatively supercoiled DNA rather than linear or relaxed DNA. This protein is also capable of constraining negative DNA supercoils. Further analyses showed modulations of topoisomerase activities by MsIHF in vitro. MsIHF obviously inhibits the relaxation of supercoiled DNA by topoisomeraseⅠ from E. coli. By contrast, this protein slightly stimulates E. coli gyrase to introduce negative supercoils into relaxed DNA. These data suggests that MsIHF may alter the topological structure of chromosomal DNA through modulation of the activities of topoisomerases, and therefore regulates the organization of chromosome.

Abstract:Phosphorylation is the major post-translation modification to proteins, and it can be classified as kinase-specific and non-kinase-specific. This paper focuses on the prediction methods of non-kinase-specificity and using Dou’s dataset of phosphorylation sites as the template, this paper develops a position-based chi-square table feature, χ²-pos, and then integrates this feature with the pseudo position-specific scoring matrix (PsePSSM). A Support Vector Machine (SVM) classifier with balanced positive and negative samples was created, and the S, T, Y independent testing results for the Matthew correlation coefficient, the inferior surface integral of the ROC curve and the precision were (0.59, 0.87, 79.74%), (0.55, 0.85, 77.68%) and (0.50, 0.81, 75.22%), respectively, which are significantly superior to the results reported previously. The integration of the χ²-pos and the PsePSSM offers a promising method to predict phosphorylation sites more accurately in proteins.

Abstract:P450 BM3 is derived from Bacillus megaterium, and its mutant (A74G, F87V, L188Q, D168H) could hydroxylate indole to indigo in Escherichia coli whereas the bioconversion yield is low under normal culture conditions (37℃, 250 r/min). Chaperones from hyperthermophilic archaea Pyrococcus furiosus were co-expressed with P450 BM3 mutant in E. coli to investigate whether they could improve the production of indigo, and results indicated that prefoldin could significantly increase the indigo production. Our research also revealed that enzyme activity was not the restrictive factor in the indigo bioconversion process. We also demonstrated that prefoldin could increase the intracellular nicotinamide adenine dinucleotide phosphate (NADPH)/NADP⁺ ratio, and this ratio was probably related to the increase of the indigo bioconversion yield.