• Preventive Nutrition and Food Science
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• v.22 no.1
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• pp.1-8
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• 2017

About 20 chemical elements are nutritionally essential for humans with defined molecular functions. Several essential and nonessential biometals are either functional nutrients with antidiabetic actions or can be diabetogenic. A key question remains whether changes in the metabolism of biometals and biominerals are a consequence of diabetes or are involved in its etiology. Exploration of the roles of zinc (Zn) in this regard is most revealing because 80 years of scientific discoveries link zinc and diabetes. In pancreatic ${\beta}$- and ${\alpha}$-cells, zinc has specific functions in the biochemistry of insulin and glucagon. When zinc ions are secreted during vesicular exocytosis, they have autocrine, paracrine, and endocrine roles. The membrane protein ZnT8 transports zinc ions into the insulin and glucagon granules. ZnT8 has a risk allele that predisposes the majority of humans to developing diabetes. In target tissues, increased availability of zinc enhances the insulin response by inhibiting protein tyrosine phosphatase 1B, which controls the phosphorylation state of the insulin receptor and hence downstream signalling. Inherited diseases of zinc metabolism, environmental exposures that interfere with the control of cellular zinc homeostasis, and nutritional or conditioned zinc deficiency influence the pathobiochemistry of diabetes. Accepting the view that zinc is one of the many factors in multiple gene-environment interactions that cause the functional demise of ${\beta}$-cells generates an immense potential for treating and perhaps preventing diabetes. Personalized nutrition, bioactive food, and pharmaceuticals targeting the control of cellular zinc in precision medicine are among the possible interventions.

• Journal of the korean academy of Pediatric Dentistry
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• v.25 no.3
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• pp.635-648
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• 1998

The clinical use of fluoride with a well known osteogenic action in osteoporotic patients is rational, because this condition is characterized by impaired bone formation. However, its anabolic effect has not been demonstrated well in vitro. The purpose of this study was to investigate the effects of sodium fluoride on the physiological role of osteoblastic cell. Osteoblastic cells were isolated from fetal rat calvaria. The results were as follows : 1. Mineralized nodules were shown in osteoblastic cell cultures, which had been maintained in the presence of ascorbic acid and ${\beta}-glycerophosphate$ up to 21 days. When cultures were treated with pulses of 48 hr duration before apparent mineralization was occurring, 2-fold increased in their number was detected. 2. Alkaline phosphatase activity of osteoblastic cells was inhibited by sodium fluoride in dose dependent manner. 3. The effect of sodium fluoride on the osteoblastic cell proliferation was measured by the incorporation of $[^3H]$-thymidine into DNA. As a result, sodium fluoride at $1{\sim}100{\mu}M$ increased the $[^3H]$-thymidine incorporation into DNA in a dose dependent manner. 4. The signaling mechanism activated by sodium fluoride dose-dependently enhanced the tyrosine phosphorylation of the adaptor molecule $Shc^{p66}$ and their association with Grb2, one of earlier events in a MAP kinase activation pathway cascade used by a significant subset of G protein-coupled receptors. 5. The phosphorylation of CREB(cAMP response element binding protein)was inhibited by the sodium fluoride in MC3T3E1 cells. In conclusion, the results of this study suggested that the mitogenic effect of the sodium fluoride in MC3T3E1 cell was stimulated in a dose-dependent manner and suggested "an important role for the interaction between She and Grb2" in controlling the proliferation of osteoblasts.

• Korean Journal of Pharmacognosy
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• v.52 no.2
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• pp.77-83
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• 2021

The number of people suffering from diabetes have been increased around the world. In this study, we investigated the antidiabetic and antioxidant effects of Anthriscus sylvestris(L.) Hoffm and its main compounds. It was divided into root(R) and aerial part(AP) for comparative analysis. Total polyphenol, total flavonoid content was higher in AP extract, but nodakenin content was higher in R(1169.13 ± 6.00 mg/g) extract. Antioxidant activity was also higher in AP extract. To compare antidiabetic efficacy, we analyzed the effects of R and AP extracts on ɑ-glucosidase inhibition(AGI), dipeptidyl peptidase-4(DPP-4) and protein tyrosine phosphatase(PTP)1B activity. R and AP extracts showed similar effects on AGI and DPP-4 activity in a concentration dependent manner, and there was no effect on PTP1B activation. Glucose uptake(139.51 ± 3.19%) in 3T3-L1 cells was more effective in the AP extract-treated group than the positive control, rosiglitazone, group. Both R and AP extracts were effective in protecting against pancreatic beta cell damage caused by hyperglycemia. These results suggest that Anthriscus sylvestris(L.) Hoffm. could be used as a candidate for diabetes treatment.

• Asian-Australasian Journal of Animal Sciences
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• v.32 no.5
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• pp.614-628
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• 2019

Objective: The inhibitory leukocyte immunoglobulin-like receptors (LILRBs) play an important role in innate immunity. The present study represents the first description of the cloning and structural and functional analysis of LILRB1 and LILRB3 isolated from two genetically disparate chicken lines. Methods: Chicken LILRB1-3 genes were identified by bioinformatics approach. Expression studies were performed by transfection, quantitative polymerase chain reaction. Signal transduction was analyzed by western blots, immunoprecipitation and flow cytometric. Cytokine levels were determined by enzyme-linked immunosorbent assay. Results: Amino acid homology and phylogenetic analyses showed that the homologies of LILRB1 and LILRB3 in the chicken line 6.3 to those proteins in the chicken line 7.2 ranged between 97%-99%, while homologies between chicken and mammal proteins ranged between 13%-19%, and 13%-69%, respectively. Our findings indicate that LILRB1 and LILRB3 subdivided into two groups based on the immunoreceptor tyrosine-based inhibitory motifs (ITIM) present in the transmembrane domain. Chicken line 6.3 has two ITIM motifs of the sequence LxYxxL and SxYxxV while line 7.2 has two ITIM motifs of the sequences LxYxxL and LxYxxV. These motifs bind to SHP-2 (protein tyrosine phosphatase, non-receptor type 11) that plays a regulatory role in immune functions. Moreover, our data indicate that LILRB1 and LILRB3 associated with and activated major histocompatibility complex (MHC) class I and ${\beta}2-microglobulin$ and induced the expression of transporters associated with antigen processing, which are essential for MHC class I antigen presentation. This suggests that LILRB1 and LILRB3 are transcriptional regulators, modulating the expression of components in the MHC class I pathway and thereby regulating immune responses. Furthermore, LILRB1 and LILRB3 activated Janus kinase2/tyrosine kinase 2 (JAK2/TYK2); signal transducer and activator of transcription1/3 (STAT1/3), and suppressor of cytokine signaling 1 genes expressed in Macrophage (HD11) cells, which induced Th1, Th2, and Th17 cytokines. Conclusion: These data indicate that LILRB1 and LILRB3 are innate immune receptors associated with SHP-2, MHC class I, ${\beta}2-microglobulin$, and they activate the Janus kinase/signal transducer and activator of transcription signaling pathway. Thus, our study provides novel insights into the regulation of immunity and immunopathology.

• Korean Journal of Pharmacognosy
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• v.40 no.3
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• pp.196-204
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• 2009

This study was carried out to investigate the in vivo and in vitro inhibitory effect of a traditional herbal complex (HC) extract prepared from a mixture of four oriental herbs (Dioscorea Rhizoma, Glycine soja Sieb. et Zucc, Bombycis corpus, Fermented Glycine soja) that have been widely used for the treatment and prevention of diabetes mellitus on hyperglycemia. The water extract of HC showed potent inhibitory effect on $\alpha$-glucosidase with $IC_{50}$ value of 1.24 mg/mL. Additionally, the ethanol extract of HC was also found to exhibit significant inhibitory effect against protein tyrosine phosphatase $1{\beta}$ ($PTP1{\beta}$), which is known as a major regulator of both insulin and leptin signaling. In the $PTP1{\beta}$ inhibitory assay, the most active n-hexane fraction obtained from the ethanol extract of HC, was identified as a mixture of fatty acid derivatives by gas chromatography-mass spectrometry (GC-MS). In high-fat diet-low dose streptozotocin (STZ)-induced diabetic rat, the water extract of HC improved the oral glucose intolerance as compared with rosiglitazone. HC also caused a marked decrease of body weight and fasting blood glucose and a significant improvement on glucose tolerance in metabolic syndrome mice model. These findings support that this traditional HC may be useful in the control of blood glucose in diabetes mellitus and metabolic syndrome.

• Journal of Acupuncture Research
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• v.19 no.6
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• pp.111-124
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• 2002

A line of study reported that electroacupuncture(EA) modulate natural killer cell(NK Cell) activities. One report suggested that EA enhanced splenic interferon-gamma($IFN-{\gamma}$), interleukin-2(IL-2), and NK cell activity in Sprague-Dawley rats. Another study suggested that $IFN-{\gamma}$ mediates the up-regulation of NK cell activity, and endogenous ${\beta}$-endorphin secretion also play a role in the up-regulation of NK cell activity induced by EA stimulation. In order to better understand the molecular regulation underlying the activation of NK cell induced by EA, we have utilized cDNA microarray to elucidate how EA alters program of gene expression of spleen in rats. First, we divided three groups, group I was EA group treated with EA in restriction holder, group II was sham group with only holder stress, and last group III was control group with no treatment. We measured NK cell activity after EA stimulation three times for 2 days using $^{51}Cr$ release assay. Second, Biotin-labeled cDNA probes synthesized from EA group and sham group, were competitively hybridized to the microarray that contained variable genes. Such high-throughput screening has identified a number of EA-responsive gene candidates. Of these, we found that EA induced a subset of genes of genes that functionally could modulatory effects on NK cell activity. Genes(vascular cell adhesion molecule-1, protein-tyrosine kinase, CD94 mRNA) related to boost NK cell activity, were increased by EA And, genes(protein-tyrosine-phospatase mRNA, protein-tyrosine phosphatase(SHP-1) mRNA) related to inhibit NK cell activity, were decreased by EA. These EA-responsive genes may provide key insights from which to understand mechanisms of activation of NK cell induced by EA.

• Asian Pacific Journal of Cancer Prevention
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• v.16 no.3
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• pp.1011-1018
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• 2015

This study was conducted to investigate the plasma phosphoproteome and differential plasma phosphoproteins in cases of of Opisthorchis viverrini (OV)-related cholangiocarcinoma (CCA). Plasma phosphoproteomes from CCA patients (10) and non-CCA subjects (5 each for healthy subjects and OV infection) were investigated using gel-based and solution-based LC-MS/MS. Phosphoproteins in plasma samples were enriched and analyzed by LC-MS/MS. STRAP, PANTHER, iPath, and MeV programs were applied for the identification of their functions, signaling and metabolic pathways; and for the discrimination of potential biomarkers in CCA patients and non-CCA subjects, respectively. A total of 90 and 60 plasma phosphoproteins were identified by gel-based and solution-based LC-MS/MS, respectively. Most of the phosphoproteins were cytosol proteins which play roles in several cellular processes, signaling pathways, and metabolic pathways (STRAP, PANTHER, and iPath analysis). The absence of serine/arginine repetitive matrix protein 3 (A6NNA2), tubulin tyrosine ligase-like family, member 6, and biorientation of chromosomes in cell division protein 1-like (Q8NFC6) in plasma phosphoprotein were identified as potential biomarkers for the differentiation of healthy subjects from patients with CCA and OV infection. To differentiate CCA from OV infection, the absence of both serine/threonine-protein phosphatase 2A 56 kDa regulatory subunit beta isoform and coiled-coil domain-containing protein 126 precursor (Q96EE4) were then applied. A combination of 5 phosphoproteins may new alternative choices for CCA diagnosis.

• Molecules and Cells
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• v.41 no.3
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• pp.244-255
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• 2018

Low-grade pro-inflammatory state and leptin resistance are important underlying mechanisms that contribute to obesity-associated hypertension. We tested the hypothesis that Astragaloside IV (As IV), known to counteract obesity and hypertension, could prevent obesity-associated hypertension by inhibiting pro-inflammatory reaction and leptin resistance. High-fat diet (HFD) induced obese rats were randomly assigned to three groups: the HFD control group (HF con group), As IV group, and the As IV + ${\alpha}$-bungaratoxin (${\alpha}-BGT$) group (As IV+${\alpha}-BGT$ group). As IV ($20mg{\cdot}Kg^{-1}{\cdot}d^{-1}$) was administrated to rats for 6 weeks via daily oral gavage. Body weight and blood pressure were continuously measured, and NE levels in the plasma and renal cortex was evaluated to reflect the sympathetic activity. The expressions of leptin receptor (LepRb) mRNA, phosphorylated signal transducer and activator of transcription-3 (p-STAT3), phosphorylated phosphatidylinositol 3-kinase (p-PI3K), suppressor of cytokine signaling 3 (SOCS3) mRNA, and protein-tyrosine phosphatase 1B (PTP1B) mRNA, pro-opiomelanocortin (POMC) mRNA and neuropeptide Y (NPY) mRNA were measured by Western blot or qRT-PCR to evaluate the hypothalamic leptin sensitivity. Additionally, we measured the protein or mRNA levels of ${\alpha}7nAChR$, inhibitor of nuclear factor ${\kappa}B$ kinase subunit ${\beta}/nuclear$ factor ${\kappa}B$ ($IKK{\beta}/NF-KB$) and pro-inflammatory cytokines ($IL-1{\beta}$ and $TNF-{\alpha}$) in hypothalamus and adipose tissue to reflect the anti-inflammatory effects of As IV through upregulating expression of ${\alpha}7nAChR$. We found that As IV prevented body weight gain and adipose accumulation, and also improved metabolic disorders in HFD rats. Furthermore, As IV decreased BP and HR, as well as NE levels in blood and renal tissue. In the hypothalamus, As IV alleviated leptin resistance as evidenced by the increased p-STAT3, LepRb mRNA and POMC mRNA, and decreased p-PI3K, SOCS3 mRNA, and PTP1B mRNA. The effects of As IV on leptin sensitivity were related in part to the up-regulated ${\alpha}7nAchR$ and suppressed $IKK{\beta}/NF-KB$ signaling and pro-inflammatory cytokines in the hypothalamus and adipose tissue, since co-administration of ${\alpha}7nAChR$ selective antagonist ${\alpha}-BGT$ could weaken the improved effect of As IV on central leptin resistance. Our study suggested that As IV could efficiently prevent obesityassociated hypertension through inhibiting inflammatory reaction and improving leptin resistance; furthermore, these effects of As IV was partly related to the increased ${\alpha}7nAchR$ expression.

• Journal of Physiology & Pathology in Korean Medicine
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• v.20 no.4
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• pp.853-860
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• 2006

This study was performed to investigate genes which are differently expressed in human blood by administrating of OLT-2. OLT-2 was medical precipitation composed of three medicinal herbs, Ginseng Radix, Astragali Radix, Glycyrrhizae Radix, and anti-leukemia effect of it was evaluated from Byung Hun Jeon of Wonkwang University this study was approved by Institutional Review Board of Korea Institute of Oriental Medicine (Taejeon, Korea) and four male subjects participated in this study. Gene expressions were evaluated by cDNA chip, in which 24,000 genes were spotted. Hierarchical cluster and biological process against the genes, which expression changes were more than 1.6 fold, were constructed by cluster 3.0 providing Stanford University and EASE(http://apps1 .maid.nih.gov/DAVID). Five groups were clustered according to their expression patterns. Group A contained gene decreased by OLT-2 and increased genes by OLT-2 were involved in Group B, C, D. In biological process, expression of genes involved in cytokine or cell calcium signaling, such as interleukin 18 and G-protein beta 4 were increased, but protein tyrosine phosphatase receptor type c, which function is cell adhesion between antigen-presenting cell and T or B-cell, was decreased by OLT-2. This study provides the most comprehensive available survey of gene expression changes in response to anti-leukemia effect of OLT-2 in human blood.

• The Korean Journal of Physiology and Pharmacology
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• v.2 no.3
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• pp.377-384
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• 1998

Gold compounds depress phagocytic cell responses, including chemotaxis, and respiratory burst. However, the effects of gold compounds on the function of phagocytic cells are variable according to the preparation of medicine. In this study, effect of tetrachloroauric acid on activated neutrophil responses, including respiratory burst, lysosomal enzyme release and change of intracellular $Ca^{2+}$ level and on the synthesis of interleukin-8 and granulocyte-macrophage colony stimulating factor by macrophages was studied. This study further examines how gold compounds affect the activation processes. The respiratory burst stimulated by complement C5a, degraded IgG and PMA in neutrophils was inhibited by tetrachloroauric acid. In contrast to C5a and degraded IgG, PMA-stimulated superoxide production was weakly inhibited by tetrachloroauric acid. Staurosporine, genistein, EGTA and verapamil inhibited superoxide and $H_2O_2$ production caused by C5a and degraded IgG. PMA-stimulated superoxide production was inhibited by staurosporine but was not affected by genistein. Tetrachloroauric acid, genistein, EGTA and verapamil inhibited the release of acid phosphatase and myeloperoxidase, while the effect of staurosporine was not detected. The synthesis of interleukin-8 and granulocyte-macrophage colony stimulating factor by $interleukin-1{\beta}$ in macrophages was inhibited by tetrachloroauric acid. Preincubation with tetrachloroauric acid, genistein, EGTA and verapamil, the elevation of [$Ca^{2+}_i$] evoked by C5a was inhibited. Store-regulated $Ca^{2+}$ entry in thapsigargin-pretreated neutrophils was decreased by the addition of tetrachloroauric acid and genistein. The effect of staurosporine on intracellular $Ca^{2+}$ mobilization was not observed. In conclusion, tetrachloroauric acid may suppress neutrophil responses through its inhibitory action on elevation of intracellular $Ca^{2+}$ level and protein kinase C. It might exhibit an inhibitory effect on the action of protein tyrosine kinase. Tetrachloroauric acid depresses cytokine production by macrophages.