• Molecules and Cells
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• v.38 no.5
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• pp.381-389
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• 2015

Autophagy is a lysosome-dependent intracellular degradation process that allows recycling of cytoplasmic constituents into bioenergetic and biosynthetic materials for maintenance of homeostasis. Since the function of autophagy is particularly important in various stress conditions, perturbation of autophagy can lead to cellular dysfunction and diseases. Accumulation of abnormal protein aggregates, a common cause of neurodegenerative diseases, can be reduced through autophagic degradation. Recent studies have revealed defects in autophagy in most cases of neurodegenerative disorders. Moreover, deregulated excessive autophagy can also cause neurodegeneration. Thus, healthy activation of autophagy is essential for therapeutic approaches in neurodegenerative diseases and many autophagy-regulating compounds are under development for therapeutic purposes. This review describes the overall role of autophagy in neurodegeneration, focusing on various therapeutic strategies for modulating specific stages of autophagy and on the current status of drug development.

• Journal of Pharmaceutical Investigation
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• v.36 no.6
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• pp.355-361
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• 2006

Intraarticular corticosteroid injections for therapy of rheumatic arthritis are administered with the aim of optimal local anti-inflammatory effect at the injection site. Since the side effects of corticosteroidal drug, dexamethasone(DEX), administered at hish dose limited the therapeutic efficacy, there was a need to design a new drug delivery system for controlled release of dexamethasone. As a prodrug for continuous therapeutic efficacy, dexamethasone-21-palmitate(DEX-PAL) was prepared via esterification of palmitoyl chloride and dexamethasone. DEX-PAL was identified by NMR and MASS analysis. DEX-PAL or DEX was entrapped in lipid nanosphere which could be prepared by using a self emulsification-solvent evaporation method. Physicochemical characteristics such as mean particle diameter, zeta potential and drug loading efficiency of the lipid nanospheres were investigated with variation of either the kind of lipid or the lipid composition. The lipid nanospheres had a mean diameter $83{\sim}95$ nm and DEX-PAL loading efficiency of up to 95%. The drug loading efficiency increased with the increase of aliphatic chain length attached to the phospholipid. The incorporation of cationic lipid was very efficient for both reducing particle size of lipid nanospheres and enhancing drug loading efficiency. The lipid nanospheres containing DEX-PAL may be a promising novel drug carrier for the controlled release of the poorly water-soluble drugs.

• Molecules and Cells
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• v.46 no.4
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• pp.191-199
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• 2023

The Golgi apparatus modifies and transports secretory and membrane proteins. In some instances, the production of secretory and membrane proteins exceeds the capacity of the Golgi apparatus, including vesicle trafficking and the post-translational modification of macromolecules. These proteins are not modified or delivered appropriately due to the insufficiency in the Golgi function. These conditions disturb Golgi homeostasis and induce a cellular condition known as Golgi stress, causing cells to activate the 'Golgi stress response,' which is a homeostatic process to increase the capacity of the Golgi based on cellular requirements. Since the Golgi functions are diverse, several response pathways involving TFE3, HSP47, CREB3, proteoglycan, mucin, MAPK/ETS, and PERK regulate the capacity of each Golgi function separately. Understanding the Golgi stress response is crucial for revealing the mechanisms underlying Golgi dynamics and its effect on human health because many signaling molecules are related to diseases, ranging from viral infections to fatal neurodegenerative diseases. Therefore, it is valuable to summarize and investigate the mechanisms underlying Golgi stress response in disease pathogenesis, as they may contribute to developing novel therapeutic strategies. In this review, we investigate the perturbations and stress signaling of the Golgi, as well as the therapeutic potentials of new strategies for treating Golgi stress-associated diseases.

• Nuclear Medicine and Molecular Imaging
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• v.40 no.2
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• pp.58-65
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• 2006

Since the development of sophisticated molecular carriers such as octereotides for peptide receptor targeting and monoclonal antibodies against various antigens associated with specific tumor types, radionuclide therapy (RNT) employing open sources of therapeutic agents is promising modality for treatment of tumors. furthermore, the emerging of new therapeutic regimes and new approaches for tumor treatment using radionuclide are anticipated in near future. In targeted radiotherapy using peptides and other receptor based tarrier molecules, the use of radionuclide with high specific activity in formulating the radiopharmaceutical is essential in order to deliver sufficient number of radionuclides to the target site without saturating the target. In order to develop effective radiopharmaceuticals for therapeutic applications, it is crucial to carefully consider the choice of appropriate radionuclides as well as the tarrier moiety with suitable pharmacokinetic properties that could result in good in vivo localization and desired excretion. Up to date, only a limited number of radionuclides have been applied in radiopharmaceutical development due to the constraints in compliance with their physical half-life, decay characteristics, cost and availability in therapeutic applications. In this review article, we intend to provide with the improved understanding of the factors of importance of appropriate radionuclide for therapy with respect to their physical properties and therapeutic applications.

• BMB Reports
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• v.49 no.6
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• pp.331-336
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• 2016

In murine collagen-induced arthritis (CIA), self-reactive T cells can recognize peptide antigens derived from type-II collagen (CII). Activation of T cells is an important mediator of autoimmune diseases. Thus, T cells have become a focal point of study to treat autoimmune diseases. In this study, we evaluated the efficacy of recombinant MHC class II molecules in the regulation of antigen-specific T cells by using a self peptide derived from CII (CII260-274; IAGFKGEQGPKGEPG) linked to mouseI-A^q in a murine CIA model. We found that recombinant I-A^q/CII260-274 molecules could be recognized by CII-specific T cells and inhibit the same T cells in vitro. Furthermore, the development of CIA in mice was successfully prevented by in vivo injection of recombinant I-A^q/CII260-274 molecules. Thus, treatment with recombinant soluble MHC class II molecules in complex with an immunodominant self-peptide might offer a potential therapeutic for chronic inflammation in autoimmune disease such as rheumatoid arthritis.

• IMMUNE NETWORK
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• v.23 no.1
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• pp.7.1-7.27
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• 2023

The mammalian intestines harbor trillions of commensal microorganisms composed of thousands of species that are collectively called gut microbiota. Among the microbiota, bacteria are the predominant microorganism, with viruses, protozoa, and fungi (mycobiota) making up a relatively smaller population. The microbial communities play fundamental roles in the maturation and orchestration of the immune landscape in health and disease. Primarily, the gut microbiota modulates the immune system to maintain homeostasis and plays a crucial role in regulating the pathogenesis and pathophysiology of inflammatory, neuronal, and metabolic disorders. The microbiota modulates the host immune system through direct interactions with immune cells or indirect mechanisms such as producing short-chain acids and diverse metabolites. Numerous researchers have put extensive efforts into investigating the role of microbes in immune regulation, discovering novel immunomodulatory microbial species, identifying key effector molecules, and demonstrating how microbes and their key effector molecules mechanistically impact the host immune system. Consequently, recent studies suggest that several microbial species and their immunomodulatory molecules have therapeutic applicability in preclinical settings of multiple disorders. Nonetheless, it is still unclear why and how a handful of microorganisms and their key molecules affect the host immunity in diverse diseases. This review mainly discusses the role of microbes and their metabolites in T helper cell differentiation, immunomodulatory function, and their modes of action.

• IMMUNE NETWORK
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• v.13 no.5
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• pp.184-193
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• 2013

Co-signaling molecules are surface glycoproteins that positively or negatively regulate the T cell response to antigen. Co-signaling ligands and receptors crosstalk between the surfaces of antigen-presenting cells (APCs) and T cells, and modulate the ultimate magnitude and quality of T cell receptor (TCR) signaling. In the past 10 years, the field of co-signaling research has been advanced by the understanding of underlying mechanisms of the immune modulation led by newly identified co-signaling molecules and the successful preclinical and clinical trials targeting co-inhibitory molecules called immune checkpoints in the treatment of autoimmune diseases and cancers. In this review, we briefly describe the characteristics of well-known B7 co-signaling family members regarding the expression, functions and therapeutic implications and to introduce newly identified B7 members such as B7-H5, B7-H6, and B7-H7.

• BMB Reports
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• v.38 no.2
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• pp.128-150
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• 2005

Invertebrate animals, which lack adaptive immune systems, have developed other systems of biological host defense, so called innate immunity, that respond to common antigens on the cell surfaces of potential pathogens. During the past two decades, the molecular structures and functions of various defense components that participated in innate immune systems have been established in Arthropoda, such as, insects, the horseshoe crab, freshwater crayfish, and the protochordata ascidian. These defense molecules include phenoloxidases, clotting factors, complement factors, lectins, protease inhibitors, antimicrobial peptides, Toll receptors, and other humoral factors found mainly in hemolymph plasma and hemocytes. These components, which together compose the innate immune system, defend invertebrate from invading bacterial, fungal, and viral pathogens. This review describes the present status of our knowledge concerning such defensive molecules in invertebrates.

• Asian Pacific Journal of Cancer Prevention
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• v.13 no.6
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• pp.2437-2444
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• 2012

Tumor metastasis remains the principal cause of treatment failure and poor prognosis in patients with colorectal cancer. It is a multistage process which includes proteolysis, motility and migration of cells, proliferation in a new site, and neoangiogenesis. A crucial step in the process of intra- and extra-vasation is the activation of proteolytic enzymes capable of degrading the extracellular matrix (ECM). In this stage, urokinase plasminogen activator receptor (uPAR) and matrix metalloproteinases (MMPs) are necessary. Micrometastases need the presence of growth factor and vascular growth factor so that they can form macrometastasis. In addition, cell adhesion molecules (CAMs) and guanine nucleotide exchange factors (GEFs) play important roles in the progression of colorectal cancer and metastatic migration. Further elucidation of the mechanisms of how these molecules contribute will aid in the identification of diagnostic and prognostic markers as well as therapeutic targets for patients with colorectal metastasis.

• IMMUNE NETWORK
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• v.9 no.3
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• pp.84-89
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• 2009

The main stream of CD137 studies has been directed to the function of CD137 in $CD8^+$ T-cell immunity, including its anti-tumor activity, and paradoxically the immunosuppressive activity of CD137, which proves to be of a great therapeutic potential for animal models of a variety of autoimmune and inflammatory diseases. Recent studies, however, add complexes to the biology of CD137. Accumulating is evidence supporting that there exists a bidirectional signal transduction pathway for the CD137 receptor and its ligand (CD137L). CD137/CD137L interactions are involved in the network of hematopoietic and nonhematopoietic cells in addition to the well characterized antigen-presenting cell-T cell interactions. Signaling through CD137L plays a critical role in the differentiation of myeloid cells and their cellular activities, suggesting that CD137L signals trigger and sustain inflammation. The overall consequence might be that the amplified inflammation by CD137L enhances the T-cell activity together with CD137 signals by upregulating costimulatory molecules, MHC molecules, cell adhesion molecules, cytokines, and chemokines. Solving this outstanding issue is urgent and will have an important clinical implication.