• 동의생리병리학회지
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• 제28권1호
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• pp.29-34
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• 2014

Bone homeostasis is maintained by balance between bone resorbing-osteoclasts and bone forming-osteoblasts. Excessive osteoclastic bone resorption plays a critical role in bone destruction in pathological bone diseases such as osteoporosis, rheumatoid arthritis, and periodontal disease. Many compounds derived from natural products have pharmacological applications and have therapeutic value for treating or preventing several bone diseases characterized by excessive bone resorption. To discover new compounds that can act as anti-resorptive agents, we screened for natural compounds that regulate osteclast differentiation, and found that water extract of Ziziphus Jujuba Mill (WEZJ) has inhibitory effects on osteoclast differentiation. In this study, WEZJ clearly inhibits the osteoclast differentiation in the presence of receptor activator of nuclear factor kB (RANKL), macrophage colony-stimulating factor (M-CSF) without cytoxicity by blocking activation of nuclear factor of activated T cells (NFAT)c1, and c-Fos. In signaling pathway, the phosphorylation of Akt, p38, c-Jun N-terminal kinases (JNK), extracellular signal-regulated kinases (ERK) and the expression of osteoclast-associated receptor (OSCAR), tartrate-resistant acid phosphates (TRAP), Integrin av, Integrin b3, Cathepsin K are suppressed, too. These result suggest that WEZJ may have therapeutic value for treating or preventing several bone diseases characterized by excessive bone destruction.

• 대한수의학회지
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• 제36권3호
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• pp.709-718
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• 1996

This experiment was carried out to clarify the effect of lead poisoning on the lead and essential trace elements homeostasis of tissues in rats. Fifty female Wistar rats, 7 weeks old, were divided into four experimental groups(B, C, D, and E) and a control(A). The four experimental groups received diets contaminated artificially with 10 (B group), 100 (C group), 1,000 (D group) and 5,000 (E group) ${\mu}g/g$ of lead as lead acetate, respectively. The control group received normal diet. Rats were necropsied on the 4th or 8th week of experimental periods and heart, liver, spleen, kidney, muscle, lung and hair were taken. The tissues were analysed for lead, copper, zinc, iron and calcium content by atomic absorption spectrophotometry. From these experiments following results ware obtained ; In C group, lead content of the heart, liver, kidney and hair were significantly increased both on the 4th and 8th week of experiment. In D and E group, lead content of all tissues including heart, liver, spleen, kidney, muscle, hair and lung were significantly increased in accordance with the lead contamination both on the 4th and 8th week of experiment. In C group, copper content of tissues were significantly increased in the heart, liver, kidney and lung on the 4th week and all tissues on the 8th week of experimental periods. In D and E group, copper content of the liver were significantly increased both on the 4th and 8th week of experiment. But the copper content of tissues were gradually decreased compared with C group in accordance with the lead contamination. Especially the content in spleen, heart or kidney were significantly decreased compared with the control group. The zinc content of kidney, heart, or spleen were decreased in D and E groups whereas the iron and calcium content showed no significant change.

• Environmental Analysis Health and Toxicology
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• 제19권4호
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• pp.359-366
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• 2004

Iron (Fe) is an essential metal in biological processes, which maintains a homeostasis in the human body. Divalent metal transporter 1 (DMT1) has been known as an iron transporting membrane protein, which is involved in the uptake Fe at the apical portion of intestinal epithelium, and may transport Fe across the membrane of acidified endosome in peripheral tissues. In this study, we studied the tissue distribution of DMT1 in the Fe supplemented (FeS) diet fed rats, and the regulation of DMT1 expression by depleting body Fe. Sprague-Dawley rats were divided into two groups, and fed FeS (120 mg Fe/kg) diet or Fe deficient (FeD, 2∼6 mg Fe/kg) diet for 4 weeks. The evaluation of body Fe status was monitored by measuring sFe, UIBC and tissue Fe concentration. Additionally, DMT1 mRNA levels were analyzed in the peripheral tissues by using the quantitative real time RT-PCR method. In the FeS diet fed rats, the tissue Fe was maintained at a relatively high level, and DMT1 was eventually expressed in all tissues studied. DMT1 was highly expressed in the testis, kidney and spleen, while a moderate levels of DMT1 expression was detected in the brain, liver and heart. In the digestive system, the highest level of DMT1 was found in the duodenum. Feeding the FeD diet caused a reduced body weight gain and depletion of body Fe with finding of decreased sFe, increased UIBC and decreased tissue Fe concentration. The depletion of body Fe upregulated DMT1 expression in the peripheral tissue. The expression of DMT1 was very sensitive to the body Fe depletion in the small intestine, especially in the duodenum, showing dramatically higher levels in the FeD rats than those of the FeS group. In the FeD diet fed animals, the expression of DMT1 was low significantly in other tissues compared with the duodenum. The expression of DMT1, however, was 60∼120% higher in the testis, kidney and spleen, and 30∼50% higher in the lung, liver and heart, compared to the FeS diet fed rats. In summary, DMT1 expression was ubiquitous in mammalian tissue, and the level of expression was the organ-dependent. The expression of DMT1 in peripheral tissues was upregulated by depletion of body Fe. Duodenum was the most sensitive tissue among organs studied during Fe depletion, and expressed the greatest level of DMT1, while other tissues were less higher than in duodenum. This study supports that DMT1 plays a role in maintaining the body Fe level through intestinal uptake as well as homeostasis of Fe in the peripheral tissue.

• 한국산업보건학회지
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• 제29권1호
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• pp.42-49
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• 2019

Objective: Chronic obstructive pulmonary disease(COPD) is characterized by persistent airflow limitations associated with chronic inflammatory response due to noxious particles or gases in the lung. Iron deficiency is associated with chronic inflammation, such as COPD. The aim of this study was to evaluate the relationship among iron deficiency, iron homeostasis, and inflammation in retired miners with COPD. Methods: The serum levels of ferritin, soluble transferrin receptor(sTfR), and transferrin saturation(TSat) as biomarkers for iron deficiency and high-sensitivity C-reactive protein(hsCRP) as a biomarker for inflammation and hepcidin as a biomarker for iron homeostasis were measured in 93 male subjects. Iron deficiency was defined as any one or more of (1) sTfR>28.1 nmol/L, (2) TSat<16%, and (3) ferritin< $12{\mu}g/L$. Results: Iron deficiency was found 28% of the study subjects. Median levels of serum hsCRP was significantly increased related to airflow limitation of COPD(GOLD 1, $0.09{\mu}g/dL$ vs. GOLD 2, $0.17{\mu}g/dL$ vs. GOLD $3{\leq}$, $0.30{\mu}g/dL$, p=0.010), and was positively correlated with hepcidin(p=0.009). Mean level of serum hepcidin was lower in COPD subjects with iron deficiency(p=0.004) and serum levels of hepcidin was negatively correlated with %$FEV_1$ predicted(p=0.030). Conclusions: These results suggest that high serum levels of hepcidin are related to severe airflow limitation or inflammation and can decrease iron availability, regardless of iron status.

• Journal of the Optical Society of Korea
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• 제19권1호
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• pp.69-73
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• 2015

The mesothelium is an essential lining for maintaining the normal homeostasis of the closed body cavity and a central component of pathophysiologic processes. The mesothelium has been known as the end target for asbestos which induces asbestos-related lung diseases. Malignant mesothelioma (MM) is a rare and fatal neoplasm predominantly due to asbestos exposure. Adaptation of an advanced and reliable technology is necessary for early detection of MM because it is difficult to diagnose this disease in its early stages. Optical coherence tomography (OCT) provides cross-sectional images of micro-tissue structures with a resolution of $2-10{\mu}m$ that can image the mesothelium with a thickness of ${\sim}100{\mu}m$ and, therefore, enable investigation of early development of MM. The mesothelium is typically located at the pleura and tunica vaginalis of the scrotum. In this study, we developed animal window models in the above two anatomical sites to visualize mesothelial layers within the mesothelium. OCT images at the two locations were also acquired.

• BMB Reports
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• 제35권6호
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• pp.623-628
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• 2002

The Th1 vs. Th2 balance is critical for the maintenance of immune homeostasis. Therefore, the genes that are selectively-regulated by the Th1 and Th2 cytokines are likely to play an important role in the Th1 and Th2 immune responses. In order to search for and identify the novel target genes that are differentially regulated by the Th1/Th2 cytokines, the human PBMC mRNAs differentially expressed upon the stimulation with IL-4 or IL-12, were screened by employing the differential display-polymerase chain reaction. Among a number of clones selected, DC21 was identified as a novel target gene that is regulated by IL-4 and IL-12. The DC21 gene expression was up-regulated either by IL-4 or IL-12, yet counter-regulated by co-treatment with IL-4 and IL-12. DC21 is a dendritic cell protein with an unknown function. The sequence analysis and conserved-domain search revealed that it has two AU-rich motifs in the 3'UTR, which is a target site for the regulation of mRNA stability by cytokines, and that it belongs to the N-acetyltransferase family. The induction of DC21 by IL-12 peaked around 8-12 h, and lasted until 24 h. LY294002 and SB203580 significantly suppressed the IL-12-induced DC21 gene expression, which implies that PI3K and p38/JNK are involved in the IL-12 signal transduction pathway that leads to the DC21 expression. Furthermore, tissue blot data indicated that DC21 is highly expressed in tissues with specialized-resident macrophages, such as the lung, liver, kidney, and placenta. Together, these data suggest a possible role for DC21 in the differentiation and maturation of dendritic cells regulated by IL-4 and IL-12.

• 동의생리병리학회지
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• 제30권6호
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• pp.452-457
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• 2016

If human body is exposed to the continuous stress, it becomes allostasis load which is the condition of homeostasis broken. Its evolutional ecologic point of view and the relation with chiljeongsnag which is a theory in Oriental Medicine were investigated. Upon evolutional ecologic point of view by Maynard Smith, people can be divided by Hawks and Doves resulting in different types of allostasis in response of the stress. Hawks people who are active and aggressive get easily anger in the stressful situation to be vulnerable to the inflammatory hepatic diseases by enhancing Th1 immune system. On the other hand, Doves people who are passive and calm get easily depressed with sadness in the stressful situation to be vulnerable to the allergic pulmonary diseases by enhancing Th2 immune system. According to constitution theory of Oriental Medicine, Yangin and Eumin show the different features of responses to the stress generating Chiljeongsang. With excessive stress continuously, Yangin consider the feeling of anger mainly resulting in Qi reversal and liver damage, while Eumin consider the feeling of sadness mainly in consumption of Qi and lung damage. Hawks and Yangin, and Doves and Eumin show the common behaviors in response to the stress demonstrating the similar features including allostasis load and Chiljeongsang. In the clinical practices with the stressful patients, the viewpoint to consider the behaviors and feelings of the subjects to receive the stress simultaneously can be the new approaching method in Psychosomatic Medicine.

• International Journal of Oral Biology
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• 제41권1호
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• pp.45-51
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• 2016

Rutin (3,3',4',5,7-pentahydroxyflavone-3-rhamnoglucoside) is a bioactive flavonoid from the plant kingdom. Rutin has been studied as potential anticancer agent due to its wide range of pharmacological properties including antioxidative, anti-inflammatory and anticancer. Autophagy is a conserved intracellular catabolic pathway to maintain cell homeostasis by formation of autophagosome. Processing of autophagy involves various molecules including ULK1 protein kinase complex, Beclin-1-Vps34 lipid kinase complex, ATG5, ATG12, and LC3 (light chain 3). Cargo-carried autophagosomes fuse with lysosomes resulting in autophagolysosome to eliminate vesicles and degrade cargo. However, the actions of rutin on autophagy are not clearly understood. In this study, we analyzed the effect of rutin on autophagy and inflammation in cancer cell lines. Interestingly, rutin induced autophagy in leukemia (THP-1), oral (CA9-22), and lung (A549) cell lines. TNF-${\alpha}$, key modulator of inflammation, was upregulated by inhibition of rutin-induced autophagy. Taken together, these data indicated that rutin induced autophagy and consequently suppressed TNF-${\alpha}$ production.

• Journal of Medicine and Life Science
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• 제15권2호
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• pp.46-50
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• 2018

Cancer, a leading mortality disease following cardiovascular disease worldwide, has high incidence as one out of every four adults in Korea. It was known to be caused by several reasons including somatic mutation, activation of oncogene and chromosome aneuploidy. Cancer cells show a faster growth rate and have metastatic and heterogeneous cell populations compared to normal cells. Cancer stem cells, the most invested field in cancer biology, is a theory to explain heterogeneous cell populations of cancer cells among several characteristics of cancer cells, which is providing the theoretical background for incidence of cancer and treatment failure by drug resistance. Cancer stem cells initially explain heterogeneous cell populations of cancer cells based on the same markers of normal stem cells in cancer, in which only cancer stem cells showed heterogeneity of cancer cells and tumor initiating ability of leukemia. Based on these results, cancer stem cells were reported in various solid cancers such as breast cancer, liver cancer, and lung cancer. Breast cancer stem cells were first reported in solid cancer which had tumor initiating ability and further identified as anti-cancer drug resistance. There were several identification methods in breast cancer stem cells such as specific surface markers and culture methods. The discovery of cancer stem cells not only explains heterogeneity of cancer cells, but it also provides theoretical background for targeting cancer stem cells to complete elimination of cancer cells. Many institutes have been developing new anticancer drugs targeting cancer stem cells, but there have not been noticeable results yet. Many researchers also reported a necessity for improvement of current concepts and methods of research on cancer stem cells. Herein, we discuss the limitations and the perspectives of breast cancer stem cells based on the current concept and history.

• 운동영양학회지
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• 제25권2호
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• pp.1-7
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• 2021

[Purpose] Recent studies have shown that COVID-19 is often associated with altered gut microbiota composition and reflects disease severity. Furthermore, various reports suggest that the interaction between COVID-19 and host-microbiota homeostasis is mediated through the modulation of microRNAs (miRNAs). Thus, in this review, we aim to summarize the association between human microbiota and miRNAs in COVID-19 pathogenesis. [Methods] We searched for the existing literature using the keywords such "COVID-19 or microbiota," "microbiota or microRNA," and "COVID-19 or probiotics" in PubMed until March 31, 2021. Subsequently, we thoroughly reviewed the articles related to microbiota and miRNAs in COVID-19 to generate a comprehensive picture depicting the association between human microbiota and microRNAs in the pathogenesis of COVID-19. [Results] There exists strong experimental evidence suggesting that the composition and diversity of human microbiota are altered in COVID-19 patients, implicating a bidirectional association between the respiratory and gastrointestinal tracts. In addition, SARS-CoV-2 encoded miRNAs and host cellular microRNAs modulated by human microbiota can interfere with viral replication and regulate host gene expression involved in the initiation and progression of COVID-19. These findings suggest that the manipulation of human microbiota with probiotics may play a significant role against SARS-CoV-2 infection by enhancing the host immune system and lowering the inflammatory status. [Conclusion] The human microbiota-miRNA axis can be used as a therapeutic approach for COVID-19. Hence, further studies are needed to investigate the exact molecular mechanisms underlying the regulation of miRNA expression in human microbiota and how these miRNA profiles mediate viral infection through host-microbe interactions.