• IMMUNE NETWORK
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• 제11권3호
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• pp.135-154
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• 2011

The great discovery of microRNAs (miRNAs) has revolutionized current cell biology and medical science. miRNAs are small conserved non-coding RNA molecules that post-transcriptionally regulate gene expression by targeting the 3' untranslated region of specific messenger RNAs for degradation or translational repression. New members of the miRNA family are being discovered on a daily basis and emerging evidence has demonstrated that miRNAs play a major role in a wide range of developmental process including cell proliferation, cell cycle, cell differentiation, metabolism, apoptosis, developmental timing, neuronal cell fate, neuronal gene expression, brain morphogenesis, muscle differentiation and stem cell division. Moreover, a large number of studies have reported links between alterations of miRNA homeostasis and pathological conditions such as cancer, psychiatric and neurological diseases, cardiovascular disease, and autoimmune disease. Interestingly, in addition, miRNA deficiencies or excesses have been correlated with a number of clinically important diseases ranging from cancer to myocardial infarction. miRNAs can repress the gene translation of hundreds of their targets and are therefore well-positioned to target a multitude of cellular mechanisms. As a consequence of extensive participation in normal functions, it is quite logical to ask the question if abnormalities in miRNAs should have importance in human diseases. Great discoveries and rapid progress in the past few years on miRNAs provide the hope that miRNAs will in the near future have a great potential in the diagnosis and treatment of many diseases. Currently, an explosive literature has focussed on the role of miRNA in human cancer and cardiovascular disease. In this review, I briefly summarize the explosive current studies about involvement of miRNA in various human cancers and cardiovascular disease.

• Asian-Australasian Journal of Animal Sciences
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• 제29권10호
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• pp.1515-1521
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• 2016

Anethole and garlic have an immune modulatory effects on avian coccidiosis, and these effects are correlated with gene expression changes in intestinal epithelial lymphocytes (IELs). In this study, we integrated gene expression datasets from two independent experiments and investigated gene expression profile changes by anethole and garlic respectively, and identified gene expression signatures, which are common targets of these herbs as they might be used for the evaluation of the effect of plant herbs on immunity toward avian coccidiosis. We identified 4,382 and 371 genes, which were differentially expressed in IELs of chickens supplemented with garlic and anethole respectively. The gene ontology (GO) term of differentially expressed genes (DEGs) from garlic treatment resulted in the biological processes (BPs) related to proteolysis, e.g., "modification-dependent protein catabolic process", "proteolysis involved in cellular protein catabolic process", "cellular protein catabolic process", "protein catabolic process", and "ubiquitin-dependent protein catabolic process". In GO analysis, one BP term, "Proteolysis", was obtained. Among DEGs, 300 genes were differentially regulated in response to both garlic and anethole, and 234 and 59 genes were either up- or down-regulated in supplementation with both herbs. Pathway analysis resulted in enrichment of the pathways related to digestion such as "Starch and sucrose metabolism" and "Insulin signaling pathway". Taken together, the results obtained in the present study could contribute to the effective development of evaluation system of plant herbs based on molecular signatures related with their immunological functions in chicken IELs.

• 농업과학연구
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• 제44권4호
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• pp.477-486
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• 2017

This review provides an overview of dietary nucleotides as an alternative to in-feed antibiotics for weaning pigs. Dietary nucleotides are composed of DNA or RNA molecules and are normally contained in protein-rich feed ingredient, brewer's yeast, yeast extract, and milk. Weaning pigs are suffering from several stresses, such as environmental challenges (i.e. crowding, transportation, and feeding). Such stressors can damage the intestinal epithelium and cause an invasion by Escherichia coli, secondary inflammatory responses, and post weaning diarrhea. To overcome weaning disorder, people often use antibiotics which reduce symptoms and boost growth performance. However, since antibiotics were banned due to concerns of antibiotic resistant bacteria, researchers are studying alternative materials to antibiotics. Dietary nucleotides are one of the alternative materials for replacing antibiotics and can be used in abnormal conditions, such as weaning diarrhea, low digestibility, and disease condition. Nucleotides have substances that have important roles in cell division and cell growth, affecting growth performance, intestinal condition, and immunological effect at the weaning stage. However, nucleotides' composition is very different between sources and this aspect makes it difficult to utilize nucleotides at the weaning stage. Therefore, this review paper focuses on i) the characteristics and functions of dietary nucleotides and ii) the effect of dietary nucleotides on the growth performance and immune system of pigs.

• Biomolecules & Therapeutics
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• 제17권4호
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• pp.446-454
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• 2009

1-Furan-2-yl-3-pyridin-2-yl-propenone (FPP-3) has recently been synthesized and characterized to have an anti-inflammatory activity through the inhibition of the production of nitric oxide and tumor necrosis factor-$\alpha$. In the present study, adverse effects of FPP-3 on immune functions were determined in female BALB/c mice. When mice were administered orally with FPP-3 at 125, 250 or 500 mg/kg for 7 consecutive days, FPP-3 suppressed the number of antibody-forming cells and reduced thymus weight at 500 mg/kg. In addition, FPP-3 administered mice exhibited reduced splenic cellularity and numbers of splenocyte subsets, such as $CD3^+$ cells, $CD3^+CD4^+$ cells, $CD3^+CD8^+$ cells and macrophages. IL-4 mRNA expression was significantly suppressed by FPP-3 treatment. Moreover, the number of $CD4^+IL-4^+$ cells was reduced following the treatment of mice with 500 mg/kg of FPP-3. These results suggested that FPP-3 at 500 mg/kg might be immunotoxic, and that FPP-3-induced immunotoxicity might be mediated, at least in part, through the inhibition of cytokine production, such as IL-4.

• 한국작물학회지
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• 제48권
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• pp.13-23
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• 2003

The trace mineral, selenium (Se), is an essential nutrient of fundamental importance to human health. It is also very toxic and can cause Se poisoning (selenosis) in human and animals when its intake exceeds a suitable amount. Se functions within mammalian systems primarily in the form of solenoprotein. About 35 selenoproteins have been identified, though many have not yet been fully elucidated. Selenoproteins contain Se as selenocyseine (Sec) and perform variety of structural and enzymic roles; the enzymic roles are best-known as the antioxidants for hydrogen peroxides and lipid peroxides, and the catalysts for production of activity thyroid hormone. Glutathione peroxidases ($\textrm{GP}_X$) among the selenoproteins prevent the generation of free radicals and decrease the risk of oxidative damage to tissues, as does thioredoxin reductase (TR). TR also provides reducing power for several biochemical processes. Selenoproteins P and W are involved with oxidant defense in plasma and muscle, respectively, A selenoprotein is also required for sperm motility and may reduce the risk of miscarriage. Some epidemiological studies have revealed an inverse correlation between Se status and cardiovascular disease, and there is considerable evidence 1mm population com-parison data and animal studies that Se is anticarcinogenic. It is also suggested that Se should be needed for the proper functioning of the immune system, and appear to be a key nutrient in counteracting the development of virulence and inhibiting HIV progression to AIDS. As research continues, the role of selenium in the etiology of chronic diseases like appropriate medical nutrition therapy can be delivered and its effectiveness assessed. Se status in individuals is affected by diet and the availability of the Se. The Se content of plants is affected by the content and availability of the element in the soil in which they are grown, and so greatly varies from country to country, while the Se composition of meat reflects the feeding patterns of livestock. This paper provides an overview on Se as an essential trace mineral for human.

• The Korean Journal of Physiology and Pharmacology
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• 제5권4호
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• pp.333-342
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• 2001

Adriamycin is a commonly used chemotherapeutic agent for cancer, including acute leukemia, lymphoma, and a number of solid human tumors. However, recent studies have recognized severe cardiotoxicity after an acute dose, which are likely the result of generation of free radicals and lipid peroxidation. Therefore, the clinical uses of adriamycin have been limited. Melatonin, the pineal gland hormone known for its ability to modulate circardian rhythm, has recently been studied in its several functions, including cancer growth inhibition, stimulating the immune system, and acting as an antioxidant and radical scavenging effects. In the present study, we evaluated the effect of melatonin administration on adriamycin-induced cardiotoxicity in rat. Heart slices were prepared using a Stadie-Riggs microtome for the measurement of malondialdehyde (MDA) content used as an index of lipid peroxidation and lactate dehydrogenase (LDH) release as an indicator of lethal cell injury. Serious adriamycin-induced lethality was observed in rat by a single intraperitoneal injection in a dose-dependent manner. A single injection of adriamycin (25 mg/kg, i.p.) induced a lethality rate of 86%, with melatonin (10 mg/kg s.c. for 6 days) treatment reducing the adriamycin-induced lethality rate to 20%. The severe body weight loss caused by adriamycin was also significantly attenuated by melatonin treatment. Treatment of melatonin marked reduced adriamycin-induced the levels of MDA formation and LDH release. A cell damage indicated by the loss of myofibrils, swelling of the mitochondria as well as cytoplasmic vacuolization was seen in adriamycin-treated group. Melatonin attenuated the adriamycin-induced structural alterations. These data provide evidence that melatonin prevents adriamycin-induced cardiotoxicity and might serve as a combination with adriamycin to limit free radical-mediated cardiotoxicity.

• IMMUNE NETWORK
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• 제3권1호
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• pp.61-68
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• 2003

Background: Fibroblast functions both as a structural element and as a vital immunoregulatory cell. Fibroblasts regulate inflammation through governing of chemokine expression. In order to elucidate the mechanisms by which the expressions of chemokines were regulated, the co-stimulatory effects of Th1 and proinflammatory cytokines were compared using nasal mucosal fibroblasts. Methods: Human nasal mucosa was obtained from surgery for septal deviation and the growth of fibroblasts was established. Fibroblasts from 4th to 6th passage were stimulated with various combinations of cytokines. To inhibit selected signaling pathways, fibroblasts were pretreated with cyclosporin A, wortmannin, staurosporine, and dexamethasone prior to the stimulation with cytokines. The supernatants were collected and chemokines were detected with a sandwich enzyme-linked immunosorbent assay. Results: $TNF-{\alpha}/IFN-{\gamma}$-induced production of RANTES was inhibited by all inhibitors used. MCP-1 was produced constitutively and $TNF-{\alpha}$-induced or $TNF-{\alpha}/IFN-{\gamma}$-induced production of MCP-1 was not inhibited by cyclosporin A or wortmannin, but by stauroporine or dexamethasone. All inhibitors used in this experiment inhibited $TNF-{\alpha}/IFN-{\gamma}$-induced or $IL-1{\beta}/IFN-{\gamma}$-induced production of MCP-2 in nasal mucosal fibroblasts. Although staurosporine or dexamethasone showed strong inhibitory effects, cyclosporin A or wortmannin did not inhibit the production of MCP-3 by $IL-1{\beta}/IFN-{\gamma}$ treatment. Conclusion: Chemokines were strongly induced by stimulation of cytokines in combination and showed different pattern of inhibition by the inhibitors. Therefore, it was assumed that cytokines acted on multiple pathways or on unknown pathways which converged to gene-specific transcription factors.

• IMMUNE NETWORK
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• 제12권1호
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• pp.27-32
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• 2012

Background: Toll-like receptors (TLRs) have been extensively studied in recent years. However, functions of these molecules in murine B cell biology are largely unknown. A TLR4 stimulant, LPS is well known as a powerful polyclonal activator for murine B cells. Methods: In this study, we explored the effect of a murine TLR9 stimulant, M6-395 (a synthetic CpG ODNs) on B cell proliferation and Ig production. Results: First, M6-395 was much more potent than LPS in augmenting B cell proliferation. As for Ig expression, M6-395 facilitated the expression of both TGF-${\beta}1$-induced germ line transcript ${\alpha}$ ($GLT{\alpha}$) and IL-4-induced $GLT{\gamma}1$ as levels as those by LPS and Pam3CSK4 (TLR1/2 agonist) : a certain Ig GLT expression is regarded as an indicative of the corresponding isotype switching recombination. However, IgA and IgG1 secretion patterns were quite different--these Ig isotype secretions by M6-395 were much less than those by LPS and Pam3CSK4. Moreover, the increase of IgA and IgG1 production by LPS and Pam3CSK4 was virtually abrogated by M6-395. The same was true for the secretion of IgG3. We found that this unexpected phenomena provoked by M6-395 is attributed, at least in part, to its excessive mitogenic nature. Conclusion: Taken together, these results suggest that M6-395 can act as a murine polyclonal activator but its strong mitogenic activity is unfavorable to Ig isotype switching.

• IMMUNE NETWORK
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• 제12권5호
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• pp.196-206
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• 2012

Besides their role as building blocks of protein, there are growing evidences that some amino acids have roles in regulating key metabolic pathways that are necessary for maintenance, growth, reproduction, and immunity. Here, we evaluated the modulatory functions of several amino acids in protective immunity against mucosal infection of herpes simplex virus type 1 (HSV-1). We found that glutamine (Gln) and leucine (Leu) showed enhanced protective immunity to HSV-1 mucosal infection when two administration of Gln and single administration of Leu per day, but not when administered in combinations. Ameliorated clinical signs of HSV-1 challenged mice by the intraperitoneal administration of Gln and Leu were closely associated with viral burden and IFN-${\gamma}$ production in the vaginal tract at 2 and 4 days post-infection. In addition, the enhanced production of vaginal IFN-${\gamma}$ appeared to be caused by NK and HSV-1 antigen-specific Th1-type CD4+ T cells recruited into vaginal tract of mice treated with Gln and Leu, which indicates that IFN-${\gamma}$, produced by NK and Th1-type CD4+ T cells, may be critical to control the outcome of diseases caused by HSV-1 mucosal infection. Collectively, our results indicate that intraperitoneal administration of Gln and Leu following HSV-1 mucosal infection could provide beneficial effects for the modulation of protective immunity, but dosage and frequency of administration should be carefully considered, because higher frequency and overdose of Gln and Leu, or their combined treatment, showed detrimental effects to protective immunity.

• 한국식품영양과학회지
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• 제35권5호
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• pp.661-670
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• 2006

Selenium (Se) obtained from dietary sources including cereals, grains and vegetables is an essential micronutrient for normal function of the body. Plants convert Se into selenomethionine and incorporate it into proteins in place of methionine, while higher animals synthesize selenoproteins containing selenocysteine. Excessive Se in the body is methylated stepwise to methylated selenium metabolites from selenide. Both inorganic and organic forms of selenium can be the nutritional sources in human, and they are transformed to selenide and then the amino acid selenocysteine attached to a specific $tRNA^{ser(sec)}$. The selenocysteine (Sec) is incorporated into selenoprotein sequences by the UGA codon. The decoding of UGA as Sec requires specific mechanisms because UGA is normally read as a stop codon: cis-acting sequences in the mRNA (the selenocysteine insertion sequence, SECIS, within the 3'untranslated region) and trans -acting factors dedicated to Sec incorporation are required for incorporation of Sec during translation of selenoprotein mRNAs. Approximately 25 selenoproteins have been identified in mammals. Several of these, including glutathione peroxidases, thioredoxin reductases and selenoprotein P, have been purified or cloned, allowing further characterization of their biological function. The antioxidant properties of selenoproteins help prevent cellular damage from free radicals which may contribute to the development of chronic disease such as cancer and heart disease. Other selenoproteins have important roles in regulation of thyroid function and play a role in the immune system. Daily selenium iatake was reported to be $42.0{\pm}16.9{\mu}g/day$ in Korean adult women. This review focuses on the metabolism and biological functions of selenium, and the nutritional status of selenium in the Korean population.