• The Korean Journal of Physiology and Pharmacology
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• v.19 no.5
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• pp.389-399
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• 2015

Zinc has been considered as a vital constituent of proteins, including enzymes. Mobile reactive zinc ($Zn^{2+}$) is the key form of zinc involved in signal transductions, which are mainly driven by its binding to proteins or the release of zinc from proteins, possibly via a redox switch. There has been growing evidence of zinc's critical role in cell signaling, due to its flexible coordination geometry and rapid shifts in protein conformation to perform biological reactions. The importance and complexity of $Zn^{2+}$ activity has been presumed to parallel the degree of calcium's participation in cellular processes. Whole body and cellular $Zn^{2+}$ levels are largely regulated by metallothioneins (MTs), $Zn^{2+}$ importers (ZIPs), and $Zn^{2+}$ transporters (ZnTs). Numerous proteins involved in signaling pathways, mitochondrial metabolism, and ion channels that play a pivotal role in controlling cardiac contractility are common targets of $Zn^{2+}$. However, these regulatory actions of $Zn^{2+}$ are not limited to the function of the heart, but also extend to numerous other organ systems, such as the central nervous system, immune system, cardiovascular tissue, and secretory glands, such as the pancreas, prostate, and mammary glands. In this review, the regulation of cellular $Zn^{2+}$ levels, $Zn^{2+}$-mediated signal transduction, impacts of $Zn^{2+}$ on ion channels and mitochondrial metabolism, and finally, the implications of $Zn^{2+}$ in health and disease development were outlined to help widen the current understanding of the versatile and complex roles of $Zn^{2+}$.

• Korean Journal of Clinical Laboratory Science
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• v.47 no.4
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• pp.161-167
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• 2015

These commensal intestinal bacteria can enhance the immune system and aid in nutrient absorption but can also act as opportunistic pathogens. Among these intestinal bacteria, the anaerobic Bacteroides fragilis are divided into enterotoxigenic B. fragilis (ETBF) which secrete the B. fragilis toxin (BFT) and non-enterotoxigenic B. fragilis (NTBF) which do not secrete BFT. ETBF can cause diarrhea and colitis in both humans and livestock but can also be found in asymptomatic individuals. ETBF is predominantly found in patients with inflammatory diarrheal diseases and traveller's diarrhea. Several clinical studies have also reported an increased prevalence of ETBF in human patients with inflammatory bowel disease (IBD), colitis and colorectal cancer. In small animal models (C57BL/6 wild-type mice, germ-free mice, multiple intestinal neoplasia (Min) mice, rabbits and Mongolian gerbils), ETBF have been found to initiate and/or aggravate IBD, colitis and colorectal cancer. BFT induces E-cadherin cleavage in intestinal epithelial cells resulting in loss of epithelial cell integrity. Subsequent activation of the ${\beta}$-catenin pathway leads to increased cellular proliferation. In addition, ETBF causes acute and chronic colitis in wild-type mice as well as enhances tumorigenesis in Min mice via activation of the Stat3/Th17 pathway. Currently, ETBF can be detected using a BFT toxin bioassay and by PCR. Advances in molecular biological techniques such as real-time PCR have allowed both researchers as well as clinicians to rapidly detect ETBF in clinical samples. The emergence of more sensitive techniques will likely advance molecular insight into the role of ETBF in colitis and cancer.

• Korean Journal of Plant Resources
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• v.23 no.5
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• pp.399-405
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• 2010

Rosa rugosa has been used as a folk medicine with various pharmacological properties for a long time in Asia. Recently, it has been reported that the extract of fractions from different parts of Rosa rugosa have various pharmacological effects on diverse diseases including diabetes, inflammatory diseases and tumor. We investigated effects of fructus extracts of Rosa rugosa(RRF) and semen extracts of this herb(RRS) on macrophage to evaluate the possibilities as a biological response modifier. We showed increased effects on tumoricidal activity, phagocytic activity, TNF-$\alpha$ and NO production in RRF-treated groups without direct tumor cell cytotoxicity. RRS-treated groups increased direct tumor cell cytotoxicity at high dose without tumoricial activity except increasing of TNF-$\alpha$ release. These results provide further possibilities for the beneficial immunomodulating effects of RRF on immune system with relatively larger safety margin rather than RRS.

• Journal of Life Science
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• v.30 no.10
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• pp.835-843
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• 2020

Obesity, the world's leading metabolic disease, is a serious health problem in both industrialized and developing countries. Natural substances are of great interest in preventative medicine, especially in the field of metabolic syndromes-from insulin resistance to obesity and diabetes. In the present study, we investigated the effect of A. pullulans SM-2001 Extract (Polycan^®) on the adipocyte differentiation of 3T3-L1 preadipocytes and the anti-obesity effect of 3T3-L1 adipocytes. Although β-glucan has been found to have health benefits in the regulation of the immune system and blood cholesterol levels, its role in obesity has not been fully investigated. Polycan^® suppressed lipid accumulation and glycerol-3-phosphate dehydrogenase (GPDH) activity without affecting cell viability in 3T3-L1 preadipocytes and adipocytes. Polycan^® also inhibited cellular lipid accumulation through down-regulation of transcription factors, such as PPARγ and C/EBPα, and induced dose-dependent phosphorylation of AMP-activated protein kinase (AMPK)-a cellular energy sensor-while the total AMPK protein content remained unchanged. Taken together, this shows that the activation of AMPK by Polycan^® in adipocytes plays a critical role in Polycan^®-induced inhibition of adipocyte differentiation. Our results show that Polycan^® has an anti-obesity action in vitro, suggesting a potential novel preventative agent for obesity and other metabolic diseases.

• Journal of Life Science
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• v.17 no.8 s.88
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• pp.1141-1146
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• 2007

This study investigated the effects on the biological activities of germinated brown rice soaked in mycelial culture broth of Phellinus linteus. The level of free amino acid was higher in the GBRP extract than those of BR and GBR. The major free amino acids were alanine, valine, isoleucine and methionine in both extracts. The level of ${\gamma}$-aminobutyric acid (GABA) was also increased significantly in the GBR and GBRP. Antioxidant activities of methanol extract of BR, GBR and GBRP were measured by using DPPH radical scavenging and SOD-like activity. Antioxidant activities showed the highest level of 83% and 76% when 100 mg/ml GBR and GBRP, respectively. Stimulation of the macrophages RAW264.7 cells with lipopolysaccharide (LPS) resulted in increased production of nitric oxide (NO) in the medium. However, the methanol extract of GBR and GBRP showed marked inhibition of NO synthesis in a does-dependant manner. These results showed that GBR and GBRP were significant role for activation of immune system in the pathogenesis of inflammatory diseases.

• Journal of Plant Biotechnology
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• v.32 no.3
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• pp.209-215
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• 2005

Lactoferrin is an iron-binding glycoprotein with many biological roles, including the protection against microbial and virus infection, stimulation of the immune system. We developed the transgenic Siberian ginseng (Acanthopanax senticosus) cell cultures producing the human lactoferrin (hLf) protein following Agrobacterium tumefaciens-mediated transformation. A construct containing a targeting signal peptide from tobacco endoplasmic reticulum fused to hLf cDNA under the control of an oxidative stress-inducible SWPA2 promoter was engineered. Transgenic Siberian ginseng cultured cells to produce a recombinant hLf protein were successfully generated and confirmed by PCR and Southern blot analysis. ELISA and western blot analysis showed that full length-hLf protein was synthesized in the transgenic cells. The production of hLf increased proportionally to cell growth and reached a maximal (up to 3% of total soluble proteins) at the stationary phase. These results suggest that the transgenic Siberian ginseng cultured cells in this study will be biotechnologically useful for the commercial production of medicinal plant cell cultures to produce hLf protein.

• Journal of Life Science
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• v.16 no.5
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• pp.788-793
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• 2006

This study was carried out to investigate the biological effects from Codium fragile. Methanol extract of Codium fragile increased two times at 2500 ㎍/ml the growth of Lactobacillus plantarum that associated with probiotic properties of lactic acid bacteria of Kimchi. Ethyl acetate extract of Codium fragile inhibited the cellulase activity up to approximately 60% at $2500\;{\mu}g/ml$. Methanol extract of Codium fragile was fractionated into several subfractions and their antioxidant activities were measured by using DPPH radical scavenging and SOD-like activity. Especially the antioxidative activity of ethyl acetate fraction was shown higher than that of other fractions and its fraction showed higher contents of total phenolic compounds, indicating the positive relationship between DPPH radical scavenging effect and total polyphenol content. Stimulation of the macrophages RAW264.7 cells with lipopolysaccharide (LPS) resulted in increased production of nitric oxide (NO) in the medium. However, the methanol extract of Codium fragile showed marked inhibition of NO synthesis in a dose-dependent manner. This result suggest that Codium fragile plays significant role for activation of immune system in the pathogenesis of inflammatory diseases.

• Journal of Food Hygiene and Safety
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• v.22 no.1
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• pp.1-14
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• 2007

The term, "food safety", has traditionally been viewed as a practical science aimed at assuring the prevention acute illnesses caused by biological microorganisms, and only to a minor extent, chronic diseases cause by chronic low level exposures to natural and synthetic chemicals or pollutants. "food safety" meant to prevent microbiological agents/toxins in/on foods, due to contamination any where from "farm to Fork", from causing acute health effects, especially to the young, immune-compromised, genetically-predisposed and elderly. However, today a broader view must also include the fact that diet, perse (nutrients, vitamins/minerals, calories), as well as low level toxins and pollutant or supplemented synthetic chemicals, can alter gene expressions of stem/progenitor/terminally-differentiated cells, leading to chronic inflammation and other mal-functions that could lead to diseases such as cancer, diabetes, atherogenesis and possibly reproductive and neurological disorders. Understanding of the mechanisms by which natural or synthetic chemical toxins/toxicants, in/on food, interact with the pathogenesis of acute and chronic diseases, should lead to a "systems" approach to "food safety". Clearly, the interactions of diet/food with the genetic background, gender, and developmental state of the individual, together with (a) interactions of other endogenous/exogenous chemicals/drugs; (b) the specific biology of the cells being affected; (c) the mechanisms by which the presence or absence of toxins/toxicants and nutrients work to cause toxicities; and (d) how those mechanisms affect the pathogenesis of acute and/or chronic diseases, must be integrated into a "system" approach. Mechanisms of how toxins/toxicants cause cellular toxicities, such as mutagenesis; cytotoxicity and altered gene expression, must take into account (a) irreversible or reversal changes caused by these toxins or toxicants; (b)concepts of thresholds or no-thresholds of action; and (c) concepts of differential effects on stem cells, progenitor cells and terminally differentiated cells in different organs. This brief Commentary tries to illustrate this complex interaction between what is on/in foods with one disease, namely cancer. Since the understanding of cancer, while still incomplete, can shed light on the multiple ways that toxins/toxicants, as well as dietary modulation of nutrients/vitamins/metals/ calories, can either enhance or reduce the risk to cancer. In particular, diets that alter the embryo-fetal micro-environment might dramatically alter disease formation later in life. In effect "food safety" can not be assessed without understanding how food could be 'toxic', or how that mechanism of toxicity interacts with the pathogenesis of any disease.

• Journal of Life Science
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• v.17 no.1 s.81
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• pp.105-109
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• 2007

This study was carried out to investigate the biological effects oak wood vinegar. Antimicrobial activity was tested in five microbial species at the concentration of 5 to $50{\mu}l$ of oak wood vinegar by paper disc method. Growth of P. oleovoranse, P. vulgaris, E. coli, S. aureus and Prevotella intermedia was inhibited at a dose of as low as $50{\mu}l$ of oak wood vinegar. Antioxidant activities were measured by using DPPH radical scavenging and SOD-like activity. DPPH radical scavenging and SOD-like activities were 90% and 65% at the concentration of $25{\mu}l\;and\;50{\mu}l$ of oak wood vinegar, respectively. Stimulation of the macrophages RAW264.7 cells with lipopolysaccharide (LPS) resulted in increased production of nitric oxide (NO) in the medium. However, the oak wood vinegar showed marked inhibition of NO synthesis in a dose-dependent manner. This result suggest that oak wood vinegar plays significant role for activation of immune system in the pathogenesis of inflammatory diseases.

• Animal Bioscience
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• v.34 no.10
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• pp.1590-1599
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• 2021

Objective: This study investigates the expression patterns of toll-like receptors (TLRs) and intracellular mediators in horse muscle cells after exercise, and the relationship between TLRS expression in stressed horse muscle cells and immune cell migration toward them. Methods: The expression patterns of the TLRs (TLR2, TLR4, and TLR8) and downstream signaling pathway-related genes (myeloid differentiation primary response 88 [MYD88]; activating transcription factor 3 [ATF3]) are examined in horse tissues, and horse peripheral blood mononuclear cells (PBMCs), polymorphonuclear cells (PMNs) and muscles in response to exercise, using the quantitative reverse transcription-polymerase chain reaction (qPCR). Expressions of chemokine receptor genes, i.e., C-X-C motif chemokine receptor 2 (CXCR2) and C-C motif chemokine receptor 5 (CCR5), are studied in PBMCs and PMNs. A horse muscle cell line is developed by transfecting SV-T antigen into fetal muscle cells, followed by examination of muscle-specific genes. Horse muscle cells are treated with stressors, i.e., cortisol, hydrogen peroxide (H₂O₂), and heat, to mimic stress conditions in vitro, and the expression of TLR4 and TLR8 are examined in stressed muscle cells, in addition to migration activity of PBMCs toward stressed muscle cells. Results: The qPCR revealed that TLR4 message was expressed in cerebrum, cerebellum, thymus, lung, liver, kidney, and muscle, whereas TLR8 expressed in thymus, lung, and kidney, while TLR2 expressed in thymus, lung, and kidney. Expressions of TLRs, i.e., TLR4 and TLR8, and mediators, i.e., MYD88 and ATF3, were upregulated in muscle, PBMCs and PMNs in response to exercise. Expressions of CXCR2 and CCR5 were also upregulated in PBMCs and PMNs after exercise. In the muscle cell line, TLR4 and TLR8 expressions were upregulated when cells were treated with stressors such as cortisol, H₂O₂, and heat. Migration of PBMCs toward stressed muscle cells was increased by exercise and oxidative stresses, and combinations of these. Treatment with methylsulfonylmethane (MSM), an antioxidant on stressed muscle cells, reduced migration of PBMCs toward stressed muscle cells. Conclusion: In this study, we have successfully cultured horse skeletal muscle cells, isolated horse PBMCs, and established an in vitro system for studying stress-related gene expressions and function. Expression of TLR4, TLR8, CXCR2, and CCR5 in horse muscle cells was higher in response to stressors such as cortisol, H₂O₂, and heat, or combinations of these. In addition, migration of PBMCs toward muscle cells was increased when muscle cells were under stress, but inhibition of reactive oxygen species by MSM modulated migratory activity of PBMCs to stressed muscle cells. Further study is necessary to investigate the biological function(s) of the TLR gene family in horse muscle cells.