• Journal of Life Science
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• v.34 no.6
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• pp.365-376
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• 2024

The present study assessed the cytotoxic effects on cell growth and senescence in human cancer (A-549, AGS, HCT-116, MDA-MB-231, and U 87-MG) and normal (MRC-5 and mesenchymal stem cells) cell lines treated with efavirenz (EFA), an inhibitor of non-nucleoside reverse transcriptase (RTase). Following EFA treatment, the half-maximal inhibitory concentration (IC₅₀) values were approximately 15 µM, and the IC₅₀ value was significantly (p<0.05) lower in the cancer cell lines, compared to normal cell lines. After determining the IC₅₀ values against EFA, each cell line was treated with 15 µM EFA for up to one week. Significant (p<0.05) decreases in endogenous RTase and telomerase activity were observed in the cancer cell lines. RTase and telomerase activity were absent or detected at very low levels in both EFA-untreated and treated MRC-5 and MSC normal cells. The cell doubling time (CDT) was also significantly (p<0.05) prolonged by the decreased cell growth rate in the EFA-treated cancer cell lines compared to the untreated cell lines. Furthermore, EFA-treated cancer cells displayed a high number of cells with a high intensity of senescence-associated ß-galactosidase activity (SA-ß-gal activity), compared to the untreated cells. The present study showed that inhibition of RTase activity induces cellular senescence and arrests cell growth in human cancer cell lines; however, normal cell lines showed greater tolerance against EFA. RTase treatment could offer optional chemotherapy for cancer treatment in human cancer cell lines with high RTase activity.

• Korean Journal of Medicinal Crop Science
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• v.17 no.2
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• pp.97-101
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• 2009

The present study describes the preliminary evaluation of the anti-inflammatory activities of Phellinus linteus (PL) and Phellinus linteus Grow in Germinated Brown Rice (BRPL). In order to effectively screen for anti-inflammatory agents, we first examined the extracts' inhibitory effects on the expression of pro-inflammatory cytokines activated with lipopolysaccharide. Moreover, we examined the inhibitory effects of the PL and BRPL extracts on pro-inflammatory factors such as NO, iNOS, $TNF-{\alpha}$ and $IFN-{\gamma}$ in murine macrophage RAW 264.7 cells. NO production and iNOS expression was significantly augmented in LPS treated cell, the production of NO and iNOS was greater in the BRPL than in the PL group. In addition, protein and mRNA levels of $TNF-{\alpha}$ and $IFN-{\gamma}$ in BRPL showed relatively more potent pro-inflammatory-activity inhibition compared to that of PL. These results suggest that BRPL may have significant effects on inflammatory factors, and may be a potential anti-inflammatory therapeutic materials.

• IMMUNE NETWORK
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• v.4 no.1
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• pp.60-64
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• 2004

Background: Microglial cells, major immune effector cells in the central nervous system, become activated in neurodegenerative disorders. Activated microglial cells produce proinflammatory mediators such as nitric oxide (NO), tumor necrosis factor-$\alpha$ and interleukin-$1{\beta}$(IL-$1{\beta}$). These proinflammatory mediators have been shown to be significantly increased in the neurodegenerative disorders such as Alzhimer's disease and Pakinson's disease. It was known that one of the neurodegeneration source is stress and it is important to elucidate mechanisms of the stress response for understanding the stress-related disorders and developing improved treatments. Because one of the neuropeptide which plays a main role in regulating the stress response is corticotropin-releasing hormone (CRH), we analyzed the regulation of NO release by CRH in BV2 murine microglial cell as macrophage in the brain. Methods: First, we tested the CRH receptor expression in the mRNA levels by RT-PCR. To test the regulation of NO release by CRH, cells were treated with CRH and then NO release was measured by Griess reagent assay. Results: Our study demonstrated that CRH receptor 1 was expressed in BV2 murine microglial cells and CRH treatment enhanced NO production. Furthermore, additive effects of lipopolysaccaride (LPS) and CRH were confirmed in NO production time dependantly. Conclusion: Taken together, these data indicated that CRH is an important mediator to regulate NO release on microglial cells in the brain during stress.

• Biomolecules & Therapeutics
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• v.16 no.2
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• pp.126-131
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• 2008

Immunosuppressive therapy after organ transplantation is routinely used to prevent rejection of the organ, because this decreases the risk of adverse events, infection, and malignancies. Recently, ursodeoxycholic acid (UDCA), which is isolated from the dried bile of adult Chinese bears, has been shown to reduce the incidence and severity of acute rejection of liver allograft during early phase of liver transplantation. Therefore, in this study, we investigated the effect of UDCA on the proliferation of splenocytes exposed to PMA plus ionomycin. Our results demonstrated that UDCA decreased the splenocytes' proliferation in a dose-dependent manner. The decreased cell proliferation was accompanied with the decreased secretion of cytokines such as IL-2, IFN-${\gamma}$ and TNF-${\alpha}$. In addition, the pretreatment of UDCA on splenocytes stimulated with PMA plus ionomycin decreased the mRNA levels of cytokines (IL-2, IFN-${\gamma}$ and TNF-${\alpha}$) and costimulatory molecules (B7.2 and PD-L1). These results suggest the beneficial effect of UDCA on organ transplantation by decreasing lymphocyte proliferation.

• Journal of Physiology & Pathology in Korean Medicine
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• v.21 no.1
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• pp.190-198
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• 2007

Alzheimer's disease, a representative neurodegenerative disorder, is characterized by the presence of senile plaques and neurofibrillary tangles accompanied by neuronal damages. b-Amyloid peptide is considered to be responsible for the formation of senile plagues that accumulate in the brains of patients with Alzheimer's disease. There has been compelling evidence supporting that b-amyloid-induced cytotoxicity is mediated through generation of reactive oxygen species. In this study, we have investigated the possible protective effect of Rehmannia glutihosaagainst b-amyloid-induced oxidative ceil death in cultured human neuroblastoma SH-SY5Y cells. SH-SY5Y cells treated with b-amyloid underwent apoptotic death as determined by morphological features and positive in situterminal end-labeling (TUNEL staining). Rehmannia glutinosawater extract, wine, and vinegar pretreatments attenuated b-amyloid-induced cytotoxicity and apoptosis. Rehmannia glutinosa vinegar exhibited maximum protective effect by increasing the expression of anti-apoptotic protein, Bcl-2. in addition to oxidative stress, b-amyloid-treatment caused nitrosative stress via marked increase in the levels of nitric oxide, which was effectively blocked by Rehmannia glutinosa. To further explore the possible molecular mechanisms underlying the protective effect of Rehmannia glutinosa, we assessed the mRNA expression of cellular antioxidant enzymes. Treatment of Rehmannia glutinosa vinegar led to up-regulation of heme oxygemase-1 and catalase. These results suggest that Rehmannia glutinosa could modulate oxidative neuronal cell death caused by b-amyloid and may have preventive or therapeutic potential in the management of Alzheimer's disease. Particularly, Rehmannia glutinosa vinegar can augment cellular antioxidant capacity, there by exhibiting higher neuroprotective potential.

• Asian-Australasian Journal of Animal Sciences
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• v.26 no.8
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• pp.1189-1196
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• 2013

Adipose tissue development and function play a critical role in the regulation of energy balance, lipid metabolism, and the pathophysiology of metabolic syndromes. Although the effect of zinc ascorbate supplementation in diabetes or glycemic control is known in humans, the underlying mechanism is not well described. Here, we investigated the effect of a zinc-chelated vitamin C (ZnC) compound on the adipogenic differentiation of 3T3-L1 preadipocytes. Treatment with ZnC for 8 d significantly promoted adipogenesis, which was characterized by increased glycerol-3-phosphate dehydrogenase activity and intracellular lipid accumulation in 3T3-L1 cells. Meanwhile, ZnC induced a pronounced up-regulation of the expression of glucose transporter type 4 (GLUT4) and the adipocyte-specific gene adipocyte protein 2 (aP2). Analysis of mRNA and protein levels further showed that ZnC increased the sequential expression of peroxisome proliferator-activated receptor gamma ($PPAR{\gamma}$) and CCAAT/enhancer-binding protein alpha (C/$EBP{\alpha}$), the key transcription factors of adipogenesis. These results indicate that ZnC could promote adipogenesis through $PPAR{\gamma}$ and C/$EBP{\alpha}$, which act synergistically for the expression of aP2 and GLUT4, leading to the generation of insulin-responsive adipocytes and can thereby be useful as a novel therapeutic agent for the management of diabetes and related metabolic disorders.

• Parasites, Hosts and Diseases
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• v.54 no.2
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• pp.123-132
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• 2016

Trichomonas vaginalis causes the most prevalent sexually transmitted infection worldwide. Trichomonads have been detected in prostatic tissues from prostatitis, benign prostatic hyperplasia (BPH), and prostate cancer. Chronic prostatic inflammation is known as a risk factor for prostate enlargement, benign prostatic hyperplasia symptoms, and acute urinary retention. Our aim was to investigate whether T. vaginalis could induce inflammatory responses in cells of a benign prostatic hyperplasia epithelial cell line (BPH-1). When BPH-1 cells were infected with T. vaginalis, the protein and mRNA of inflammatory cytokines, such as CXCL8, CCL2, IL-$1{\beta}$, and IL-6, were increased. The activities of TLR4, ROS, MAPK, JAK2/STAT3, and NF-${\kappa}B$ were also increased, whereas inhibitors of ROS, MAPK, PI3K, NF-${\kappa}B$, and anti-TLR4 antibody decreased the production of the 4 cytokines although the extent of inhibition differed. However, a JAK2 inhibitor inhibited only IL-6 production. Culture supernatants of the BPH-1 cells that had been incubated with live T. vaginalis (trichomonad-conditioned medium, TCM) contained the 4 cytokines and induced the migration of human monocytes (THP-1 cells) and mast cells (HMC-1 cells). TCM conditioned by BPH-1 cells pretreated with NF-${\kappa}B$ inhibitor showed decreased levels of cytokines and induced less migration. Therefore, it is suggested that these cytokines are involved in migration of inflammatory cells. These results suggest that T. vaginalis infection of BPH patients may cause inflammation, which may induce lower urinary tract symptoms (LUTS).

• Asian-Australasian Journal of Animal Sciences
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• v.25 no.9
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• pp.1300-1308
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• 2012

The 5'-adenosine monophosphate-activated protein kinase (AMPK) is a key part of a kinase-signaling cascade that acts to maintain energy homeostasis. The objective of this experiment was to investigate the possible effects of fasting and refeeding on the gene expression of hypothalamic AMPK, some appetitive regulating peptides and lipid metabolism related enzymes. Seven-day-old male broiler (Arbor Acres) chicks were allocated into three equal treatments: fed ad libitum (control); fasted for 24 h; fasted for 24 h and then refed for 24 h. Compared with the control, the hypothalamic gene expression of $AMPK{\alpha}2$, $AMPK{\beta}1$, $AMPK{\beta}2$, $AMPK{\gamma}1$, Ste20-related adaptor protein ${\beta}$ ($STRAD{\beta}$), mouse protein $25{\alpha}$ ($MO25{\alpha}$) and agouti-related peptide (AgRP) were increased after fasting for 24 h. No significant difference among treatments was observed in mRNA levels of $AMPK{\alpha}1$, $AMPK{\gamma}2$, LKB1 and neuropeptide Y (NPY). However, the expression of $MO25{\beta}$, pro-opiomelanocortin (POMC), corticotropin-releasing hormone (CRH), ghrelin, fatty acid synthase (FAS), acetyl-CoA carboxylase ${\alpha}$ ($ACC{\alpha}$), carnitine palmitoyltransferase 1 (CPT-1) and sterol regulatory element binding protein-1 (SREBP-1) were significantly decreased. The present results indicated that 24 h fasting altered gene expression of AMPK subunits, appetite regulation peptides and lipometabolism related factors in chick's hypothalamus; the hypothalamic FAS signaling pathway might be involved in the AMPK regulated energy homeostasis and/or appetite regulation in poultry.

• Korean Journal of Plant Resources
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• v.32 no.6
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• pp.714-722
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• 2019

Oxidative DNA damage negatively affects humans and the research is currently ongoing to find ways to reduce oxidative stress. Oxidative stress has been identified as a key factor in triggering various diseases. Thus, its alleviation is important for human health. Broussonetia kazinoki (B. kazinoki) has been used in traditional Korean medicine as a dermatological therapy to treat burns, pruritus, and acne. B. kazinoki is generally segregated into peeled root (PR), root bark (RB), peeled stem (PS), and stem bark (SB). To assess these components for their antioxidant activity and protection against DNA damage, their ethyl acetate fractions were examined by 1,1-diphenyl-2-picryl hydrazyl (DPPH) and 2,2'-Azino-bis (3-ethylbenzothiazoline-6-sulfonic acid) diammonium salt (ABTS) radical scavenging assay. As a result of confirming the expression of factors involved in attenuating DNA damage, the protective effect of SB on oxidative stress suppressed the expression of p-p53 and γ-H2AX. Additionally, the levels of p53 and H2AX mRNA were significantly downregulated. In conclusion, these results indicated that the SB component of B. kazinoki had the potential to be used as an effective natural antioxidant compared to the other parts of the plant.

• Journal of Microbiology and Biotechnology
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• v.27 no.12
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• pp.2094-2103
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• 2017

Aging is associated with distinct changes in immune cells and a decline in immune function, leading to increased susceptibility to infection and reduced responses to vaccination. Certain strains of lactic acid bacteria exert beneficial effects on the immune system. Previously, we reported that Weissella cibaria JW15 isolated from kimchi possesses immune stimulatory activity in vitro. In the present study, we further investigated whether oral administration of JW15 improves immune function in aged mice. Eighteen-month-old female mice were administered JW15 daily at low (JW15-L; $1{\times}10^8CFU/mouse$) or high dosage (JW15-H; $1{\times}10^9CFU/mouse$), or with Lactobacillus rhamnosus GG (LGG) using oral gavage. Two-month-old female mice were included as healthy young mice. After 4 weeks, the mice were euthanized and immune profiles were analyzed using whole blood and spleen. In complete blood count analysis, the numbers of white and red blood cells were significantly increased in the JW15-L group compared with those in the old mouse (OM) control group. In addition, administration of either JW15 of LGG resulted in higher numbers of splenocytes in comparison with the OM group. Furthermore, proliferative potentials were higher in all probiotic groups than OM. Cytokines such as IFN-${\gamma}$ and IL-6 were secreted at higher levels in splenocytes isolated from JW15-fed mice than in OM control mice. Similarly, mRNA expression of various cytokines was altered in the JW15 groups. Collectively, these results suggest that JW15 supplementation induces immunomodulatory effects in aged mice and indicate JW15 as a potential probiotic strain to improve immune function in aged animals.