• IMMUNE NETWORK
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• 제13권2호
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• pp.75-79
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• 2013

Evidence for immunoregulatory roles of prostaglandins (PGs) is accumulating. Since our observation of PG production by human follicular dendritic cells (FDCs), we investigated the regulatory mechanism of PG production in FDC and attempted to understand the functions of released PGs in the responses of adjacent lymphocytes. Here, using FDC-like cells, HK cells, we analyzed protein expression alterations in cyclooxygenase-2 (COX-2) in the presence of IL-4 or histone deacetylase (HDAC) inhibitors. Both IL-4 and HDAC inhibitors suppressed COX-2 expression in dose-dependent manners. Their effect was specific to COX-2 and did not reach to COX-1 expression. Interestingly, HDAC inhibitors gave rise to an opposing effect on COX-2 expression in peripheral blood monocytes. Our results suggest that IL-4 may regulate COX-2 expression in FDCs by affecting chromatin remodeling and provide insight into the role of cellular interactions between T cells and FDC during the GC reaction. Given the growing interests in wide-spectrum HDAC inhibitors, the differential results on COX-2 expression in HK cells and monocytes raise cautions on their clinical use.

• Journal of Communications and Networks
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• 제13권5호
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• pp.442-448
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• 2011

It's a challenging task to design a high performance modulation for satellite and space communications due to the limited power and bandwidth resource. Constant envelope modulation is an attractive scheme to be used in such cases for their needlessness of input power back-off about 2~3 dB for avoidance of nonlinear distortion induced by high power amplifier. The envelope of Feher quadrature phase shift keying (FQPSK) has a least fluctuation of 0.18 dB (quasi constant envelope) and can be further improved. This paper improves FQPSK by defining a set of new waveform functions, which changes FQPSK to be a strictly constant envelope modulation. The performance of the FQPSK adopting new waveform is justified by analysis and simulation. The study results show that the novel FQPSK is immune to the impact of HPA and outperforms conventional FQPSK on bit error rate (BER) performance. The BER performance of this novel modulation is better than that of FQPSK by more than 0.5 dB at least and 2 dB at most.

• Journal of Dairy Science and Biotechnology
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• 제39권3호
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• pp.94-103
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• 2021

The lack of an effective treatment for Alzheimer's disease (AD) stems primarily from incomplete understanding of AD's causes. A rapidly growing number of scientific reports highlight important roles played by peripheral infections and intestinal bacterial flora in pathological and physiological functions involving the microbiome-intestine-brain axis. The microbiome controls basic aspects of the central nervous system (CNS), immunity, and behavior, in health and disease. Changes in the density and composition of the microbiome have been linked to disorders of the immune, endocrine, and nervous systems, including mood changes, depression, increased susceptibility to stressors, and autistic behaviors. There is no doubt that in patients with AD, restoration of the intestinal microbiome to a composition reminiscent of that found in healthy adult humans will significantly slow the progression of neurodegeneration, by ameliorating inflammatory reactions and/or amyloidogenesis. In the near future, better understanding of bidirectional communication between the brain and microbiota will allow the development of functional diets using specific probiotic bacteria.

• BMB Reports
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• 제51권12호
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• pp.636-641
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• 2018

DPP4 (dipeptidyl peptidase-4), a highly conserved transmembrane glycoprotein with an exo-peptidase activity, has been shown to contribute to glucose metabolism, immune regulation, signal transduction, and cell differentiation. Here, we show that DPP4 is involved in control of activin/nodal signaling in Xenopus early development. In support of this, gain of function of DPP4 augmented Smad2 phosphorylation as well as expression of target genes induced by activin or nodal signal. In addition, Dpp4 and Xnr1 showed synergistic effect on induction of ectopic dorsal body axis, when co-injected at suboptimal doses in early embryos. Conversely, saxagliptin, a DPP4 inhibitor repressed activin induction of Smad2 phosphorylation. Notably, overexpression of Dpp4 disrupted specification of dorsal body axis of embryo, leading to malformed phenotypes such as spina bifida and a shortened and dorsally bent axis. Together, these results suggest that DPP4 functions as a potentiator of activin/nodal signaling pathway.

• Molecules and Cells
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• 제42권8호
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• pp.597-603
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• 2019

Glyceraldehyde-3-phosphate dehydrogenase (GAPDH) is a core enzyme of the aerobic glycolytic pathway with versatile functions and is associated with cancer development. Recently, Kornberg et al. published the detailed correlation between GAPDH and di- or monomethyl fumarate (DMF or MMF), which are well-known GAPDH antagonists in the immune system. As an extension, herein, we report the crystal structure of MMF-bound human GAPDH at $2.29{\AA}$. The MMF molecule is covalently linked to the catalytic Cys152 of human GAPDH, and inhibits the catalytic activity of the residue and dramatically reduces the enzymatic activity of GAPDH. Structural comparisons between $NAD^+$-bound GAPDH and MMF-bound GAPDH revealed that the covalently linked MMF can block the binding of the $NAD^+$ cosubstrate due to steric hindrance of the nicotinamide portion of the $NAD^+$ molecule, illuminating the specific mechanism by which MMF inhibits GAPDH. Our data provide insights into GAPDH antagonist development for GAPDH-mediated disease treatment.

• BMB Reports
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• 제52권1호
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• pp.47-55
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• 2019

Cellular senescence (CS) is one of hallmarks of aging and accumulation of senescent cells (SCs) with age contributes to tissue or organismal aging, as well as the pathophysiologies of diverse age-related diseases (ARDs). Genetic ablation of SCs in tissues lengthened health span and reduced the risk of age-related pathologies in a mouse model, suggesting a direct link between SCs, longevity, and ARDs. Therefore, senotherapeutics, medicines targeting SCs, might be an emerging strategy for the extension of health span, and prevention or treatment of ARDs. Senotherapeutics are classified as senolytics which kills SCs selectively; senomorphics which modulate functions and morphology of SCs to those of young cells, or delays the progression of young cells to SCs in tissues; and immune-system mediators of the clearance of SCs. Some senolytics and senomorphics have been proven to markedly prevent or treat ARDs in animal models. This review will present the current status of the development of senotherapeutics, in relation to aging itself and ARDs. Finally, future directions and opportunities for senotherapeutics use will discussed. This knowledge will provide information that can be used to develop novel senotherapeutics for health span and ARDs.

• Journal of Yeungnam Medical Science
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• 제38권1호
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• pp.27-33
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• 2021

The gut is a complex organ that has played an important role in digestion, absorption, endocrine functions, and immunity. The gut mucosal barriers consist of the immunologic barrier and nonimmunologic barrier. During critical illnesses, the gut is susceptible to injury due to the induction of intestinal hyperpermeability. Gut hyperpermeability and barrier dysfunction may lead to systemic inflammatory response syndrome. Additionally, gut microbiota are altered during critical illnesses. The etiology of such microbiome alterations in critical illnesses is multifactorial. The interaction or systemic host defense modulation between distant organs and the gut microbiome is increasingly studied in disease research. No treatment modality exists to significantly enhance the gut epithelial integrity, permeability, or mucus layer in critically ill patients. However, multiple helpful approaches including clinical and preclinical strategies exist. Enteral nutrition is associated with an increased mucosal barrier in animal and human studies. The trophic effects of enteral nutrition might help to maintain the intestinal physiology, prevent atrophy of gut villi, reduce intestinal permeability, and protect against ischemia-reperfusion injury. The microbiome approach such as the use of probiotics, fecal microbial transplantation, and selective decontamination of the digestive tract has been suggested. However, its evidence does not have a high quality. To promote rapid hypertrophy of the small bowel, various factors have been reported, including the epidermal growth factor, membrane permeant inhibitor of myosin light chain kinase, mucus surrogate, pharmacologic vagus nerve agonist, immune-enhancing diet, and glucagon-like peptide-2 as preclinical strategies. However, the evidence remains unclear.

• Biomolecules & Therapeutics
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• 제29권4호
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• pp.427-433
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• 2021

Free fatty acid receptor 2 (FFA2, also known as GPR43), a G-protein-coupled receptor, has been known to recognize short-chain fatty acids and regulate inflammatory responses. FFA2 gene deficiency exacerbated disease states in several models of inflammatory conditions including asthma. However, in vivo efficacy of FFA2 agonists has not been tested in allergic asthma. Thus, we investigated effect of 4-chloro-α-(1-methylethyl)-N-2-thiazoylylbenzeneacetanilide (4-CMTB), a FFA2 agonist, on antigen-induced degranulation in RBL-2H3 cells and ovalbumin-induced allergic asthma in BALB/c mice. Treatment of 4-CMTB inhibited the antigen-induced degranulation concentration-dependently. Administration of 4-CMTB decreased the immune cell numbers in the bronchoalveolar lavage fluid and suppressed the expression of inflammatory Th2 cytokines (IL-4, IL-5, and IL-13) in the lung tissues. Histological studies revealed that 4-CMTB suppressed mucin production and inflammation in the lungs. Thus, results proved that FFA2 functions to suppress allergic asthma, suggesting 4-CMTB activation of FFA2 as a therapeutic tool for allergic asthma.

• 대한두경부종양학회지
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• 제37권2호
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• pp.1-9
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• 2021

Thyroid cancer refers to various cancers arising from thyroid gland. Differentiated thyroid cancers (DTCs) include papillary, follicular, and Hurthle cell carcinomas and represent cancers retain normal thyroid functions such as iodine uptake. Radioactive iodine (RAI) is generally used for upfront treatment of metastatic DTCs, but RAI refractory DTCs remain to be clinical challenges. Sorafenib and lenvatinib were approved for the treatment of RAI refractory DTCs and more recently, genomics-based targeted therapies have been developed for NTRK and RET gene fusion-positive DTCs. Poorly differentiated and anaplastic thyroid cancers (ATCs) are extremely challenging diseases with aggressive courses. BRAF/MEK inhibition has been proven to be highly effective in BRAF V600E mutation-positive ATCs and immune checkpoint inhibitors have shown promising activities. Medullary thyroid cancers, which arise from parafollicular cells of thyroid, represent a unique subset of thyroid cancer and mainly driven by RET mutation. In addition to vandetanib and cabozantinib, highly specific RET inhibitors such as selpercatinib and pralsetinib have demonstrated impressive activity and are in clinical use.

• Journal of Animal Science and Technology
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• 제64권4호
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• pp.640-653
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• 2022

Deoxynivalenol (DON) is the most common mycotoxin contaminant of cereal-based food and animal feed. The toxicity of DON is very low compared to that of other toxins; however, the most prominent signs of DON exposure include inappetence and body weight loss, which causes considerable economic losses in the livestock industry. This review summarizes critical studies on biological DON mycotoxin mitigation strategies and the respective in vitro and in vivo intestinal effects. Focus areas include growth performance, gut health in terms of intestinal histomorphology, epithelial barrier functions, the intestinal immune system and microflora, and short-chain fatty acid production in the intestines. In addition, DON detoxification and modulation of these parameters, through biological supplements, are discussed. Biological detoxification of DON using microorganisms can attenuate DON toxicity by modulating gut microbiota and improving gut health with or without influencing the growth performance of pigs. However, the use of microorganisms as feed additives to livestock for mycotoxins detoxification needs more research before commercial use.