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Protective Effect of Astragalus polysaccharides on Liver Injury Induced by Several Different Chemotherapeutics in Mice

  • Liu, Wen;Gao, Fang-Fang;Li, Qun;Lv, Jia-Wei;Wang, Ying;Hu, Peng-Chao;Xiang, Qing-Ming;Wei, Lei
    • Asian Pacific Journal of Cancer Prevention
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    • v.15 no.23
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    • pp.10413-10420
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    • 2015
  • Side effects are an unavoidable consequence of chemotherapy drugs, during which liver injury often takes place. The current study was designed to investigate the protective effect of Astragalus polysaccharides (APS) against the hepatotoxicity induced by frequently-used chemical therapy agents, cyclophosphamide (CTX), docetaxel (DTX) and epirubicin (EPI)) in mice. Mice were divided into five groups, controls, low or high dose groups ($DTX_L$, $CTX_L$, $EPI_L$ or $DTX_H$, $CTX_H$, $EPI_H$), and low or high dose chemotherapeutics+APS groups ($DTX_L$+APS, $CTX_L$+APS, $EPI_L$+APS or $DTX_H$+APS, $CTX_H$+APS, $EPI_H$+APS). Controls were treated with equivalent normal saline for 28 days every other day; low or high dose group were intraperitoneal (i.p) injected with low or high doses of CTX, DTX and EPI for 28 days every other day; low or high dose chemotherapeutics+APS group were separately intraperitoneal (i.p) injected with chemotherapeutics for 28 days every other day and i.p with APS (100 mg/kg) for 7 days continually from the 22th to the 28th days. The body weight, serum levels of alanine aminotransferase (ALT) and aspartate aminotransferase (AST), histopathological features, and ultrastructure morphological change of liver tissues, protein expression level of caspase-3 were estimated at different time points. With high dose treatment of DTX, CTX and EPI, weight gain was inhibited and serum levels of ALT and AST were significantly increased. Sections of liver tissue showed massive hepatotoxicity in $CTX_H$ group compared to the control group, including hepatic lobule disorder, granular and vacuolar degeneration and necrosis in hepatic cells. These changes were confirmed at ultrastructural level, including obvious pyknosis, heterochromatin aggregation, nuclear membrane resolution, and chondrosome crystal decrease. Western blotting revealed that the protein levels of caspase-3 increased in $CTX_H$ group. The low dose groups exhibited trivial hepatotoxicity. More interestingly, after 100 mg/kg APS, liver injury was redecued not only regarding serum transaminase activities (low or high dose chemotherapeutics+APS group), but also from pathological and ultrastructural changes and the protein levels of caspase-3 ($CTX_H$+APS group). In conclusion, DTX, CTX and EPI induce liver damage in a dose dependent manner, whereas APS exerted protective effects.

A novel herbal formulation consisting of red ginseng extract and Epimedium koreanum Nakai-attenuated dextran sulfate sodium-induced colitis in mice

  • Saba, Evelyn;Lee, Yuan Yee;Kim, Minki;Hyun, Sun-Hee;Park, Chae-Kyu;Son, Eunjung;Kim, Dong-Seon;Kim, Sung-Dae;Rhee, Man Hee
    • Journal of Ginseng Research
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    • v.44 no.6
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    • pp.833-842
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    • 2020
  • Background: Ulcerative colitis (UC) is a commonly encountered large intestine disease in the contemporary world that terminates into colorectal cancer; therefore, the timely treatment of UC is of major concern. Panax ginseng Meyer is an extensively consumed herbal commodity in South East Asian countries, especially Korea. It exhibits a wide range of biologically beneficial qualities for almost head-to-toe ailments in the body. Epimedium koreanum Nakai (EKN) is also a widely used traditional Korean herbal medicine used for treating infertility, rheumatism, and cardiovascular diseases. Materials and methods: Separately the anti-inflammatory activities of both red ginseng extracts (RGEs) and EKNs had been demonstrated in the past in various inflammatory models; however, we sought to unravel the anti-inflammatory activities of the combination of these two extracts in dextran sulfate sodium (DSS)-induced ulcerative colitis in mice model because the allopathic remedies for UC involve more side effects than benefits. Results: Our results have shown that the combination of RGE + EKN synergistically alleviated the macroscopic lesions in DSS-induced colitic mice such as colon shortening, hematochezia, and weight loss. Moreover, it restored the histopathological lesions in mice and decreased the levels of proinflammatory mediators and cytokines through the repression of nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) and nucleotide-binding domain (NOD)-like receptor protein 3 (NLRP-3) expression. In vitro, this combination also reduced the magnitude of nitric acid (NO), proinflammatory mediators and cytokine through NF-κB and mitogen-activated protein kinase (MAPK) pathways in RAW 264.7 mouse macrophage cells. Conclusion: In the light of these findings, we can endorse this combination extract as a functional food for the prophylactic as well as therapeutic treatment of UC in humans together with allopathic remedies.

Usefulness of RPS4Y Gene on Sex Determination in Human Teeth (사람치아에서 성별감정시 RPS4Y 유전자의 유용성)

  • Yoon, Wang-Ro;Ahn, Jong-Mo;Yoon, Chang-Lyuk
    • Journal of Oral Medicine and Pain
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    • v.33 no.1
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    • pp.59-66
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    • 2008
  • Ribosomal Protein S4Y(RPS4Y) gene is the human sex-linked gene on the Y chromosome. There are a number of reports on the sex determination using RPS4Y gene analysis for prevention and diagnosis in sex-linked disease. Thus RPS4Y gene is a reliable genetic marker for sex determination in forensic medicine. In general, the sex determination of an unidentified body can be achieved based on anatomical characteristics, but sometimes sex determination was considered to be difficult such as pre-adolescent bodies or decomposed, mutilated bodies. In this case, Sex determination using PCR method in human teeth produces good results. Because human teeth have a great structural durability, the DNA well preserved in the teeth. So author isolated nuclear DNA from the 20 human teeth(10 males, 10 females), performed to detect RPS4Y gene by PCR method. Samples were divided four group(10 pulp and 10 dentinal tissue in male, 10 pulp and 10 dentinal tissue in female). It was found that detection of RPS4Y gene for sex determination was possible in all the male pulp tissues and 6 out of 10 male dentinal tissues. But there was not detected in female pulp and dentinal tissues. In the view of this results demonstrates the possibility that detection of RPS4Y gene with other sex chromosome genes from the human teeth is useful to sex determination in forensic medicine.

In Vitro and In Vivo Effects of Piceatannol and Resveratrol on Glucose Control and TLR4-NF-κB Pathway (피세아테놀과 레스베라트롤의 혈당조절 및 TLR4-NF-κB 경로 조절 작용)

  • Lee, Hee Jae;Lee, Hae-Jeung;Yang, Soo Jin
    • Journal of the Korean Society of Food Science and Nutrition
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    • v.46 no.2
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    • pp.267-272
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    • 2017
  • Piceatannol (PIC) is a natural hydroxylated analog of resveratrol (RSV), which is a polyphenol known to extend lifespan by stimulating sirtuins. The aim of this study was to investigate the effects of PIC and RSV on the toll-like receptor 4 (TLR4)-nuclear factor kappa B ($NF-{\kappa}B$) pathway in mouse hepatocytes and an obese/diabetic KK/HlJ mouse model. AML12 mouse hepatocytes in the absence or presence of palmitic acids (PA) were treated with PIC ($50{\mu}M$) or RSV ($50{\mu}M$). Male KK/HlJ mice at 20 weeks of age were divided into three subgroups as follows: 1) obese and diabetic control (KK), 2) KK_PIC, and 3) KK_RSV. PIC and RSV were administered orally at a dose of 10 mg/kg/d for 4 weeks. Four weeks of PIC and RSV treatment did not affect body weight or food intake in KK mice. Serum fasting blood glucose was significantly reduced in KK_PIC, and 2 h oral glucose tolerance test area under the curve was significantly reduced by PIC and RSV treatment in KK mice. PIC tended to improve homeostasis model assessment of the insulin resistance index (HOMA-IR) and HOMA beta-cells in diabetic KK mice. TLR4 and $NF-{\kappa}B$ were down-regulated by PIC and RSV treatments in hepatocytes in the absence or presence of PA. Insulin receptor, AMP-activated protein kinase, peroxisome proliferator-activated receptor gamma, nucleotide oligomerization domain-like receptor family pyrin domain-containing 3, interleukin-1, and $NF-{\kappa}B$ were altered in PIC-treated livers. Collectively, PIC and RSV inhibited the $TLR4-NF-{\kappa}B$ pathway, and PIC seems to be more effective than RSV in the regulation of analyzed targets, which are involved in insulin signaling and inflammation in vivo.

Determination of Iodine Contents in Ten kinds of Frequently used Oriental Herb Medicinal Products for Cancer Patient (암환자에게 다빈도로 활용되는 한약제제 10종에 대한 요오드의 함량 분석)

  • Lee, Chang-Hee;Choi, Jung-Eun;Kim, Sun-Ha;Chung, Yong-Sam;Moon, Jong-Hwa;Yoo, Hwa-Seung
    • Journal of Korean Traditional Oncology
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    • v.16 no.1
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    • pp.41-53
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    • 2011
  • Background and Objectives: Iodine is an essential constituent of the thyroid hormones associated with the growth and development of humans and animals as an inorganic nutrition. This element may be accumulated in human blood, tissues and body through the intake of foodstuffs, a beverage, a nutritional supplement and a medicine, among others. The aim of the research is to find out a better medicinal stuff for the thyroid cancer patient who required a low level of iodine diet. Methods: Neutron activation analysis (NAA) used for the iodine analysis is one of nuclear analytical techniques using radiation and radioisotopes and very useful as sensitive analytical technique for performing both qualitative and quantitative multi-elemental non-destructive analysis of major, minor and trace components in variety of environmental and biological materials. In this study, iodine contents in ten kinds of oriental herb medicinal products, which is frequently used to cancer patients are determined by using instrumental neutron activation analysis (INAA) at the HANARO research reactor. The samples prescribed are manufactured as powdered form for taking medicine easily. The analytical quality control is performed to assure an uncertainty of the measurement and to compensate the measured data using a biological certified reference material, NIST SRM 1572, Citrus Leaves. The measured value is $1.89{\pm}0.35mg/kg$, and the relative error is 2.88%, and relative standard deviation is 19 % due to high counting error by small counts of gamma ray spectrum. The standard deviations for other elements such as Cl, K, Mn and Na were in the range of 2 to 8%. Result: The level of iodine contents of Biki-huan, Chungryong-huan and Chungcho-huan, samples detected is less than 6 mg/kg except Hangam Plus sample (more than 210 mg/kg) and six samples were not detected. Iodine in the samples of Shoxiho-tang, Shopunghualhyl-tang, Shocungryong-tang, Banhasaxim-tang, Insampaedox-san and Myunyuk Plus were not measured, but possible level of content can be estimated from the detection limits. In addition, the concentrations of some major elements like Cl, K, Mn, Na, in the samples were determined with the detection limits. Conclusions: Most of samples showed low iodine contents of less than 6 mg/kg but it turned out that most of testing samples can be used to classify the level of iodine diet samples considering the recommended low level of iodine diet 50 ${\mu}g$/day, and a better medicinal stuff for the thyroid cancer patient can be found.

Effect of lactoferrin hydrolysates on inflammatory cytokine modulation in HEK-293, RBL-2H3, and HMC-1 cells

  • Son, Ji Yoon;Bae, Hyung Churl;Renchinkhand, Gereltuya;Nam, Myoung Soo;Kim, Woan-sub
    • Korean Journal of Agricultural Science
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    • v.47 no.1
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    • pp.83-93
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    • 2020
  • Lactoferrin (LF) is an iron-binding glycoprotein that is present in colostrum, milk, and other body secretions. The objective of this study was to investigate the effects of lactoferrin hydrolysates (LHs) on the production of immunomodulatory factors, including inflammatory related cytokines. The nuclear factor (NF)-κB reporter assay using human embryonic kidney 293 cells (HEK-293) revealed that NF-κB activity was significantly decreased by 1, 50, and 100 ㎍/mL of LH and the fractions above and below the 10 kDa LH. The mRNA expression of interferon (IFN)-γ in rat basophilic leukemia mast cells (RBL-2H3) treated with the fraction above the 10 kDa LH decreased in a dose-dependent manner, but the cells treated with LH and the fraction below the 10 kDa LH showed an increased expression of IFN-γ in a dose-dependent manner. The level of cyclooxygenase (COX)-2 expression decreased dose-dependently in RBL-2H3 cells treated with LH and the fraction above the 10 kDa LH, but the cells treated with the fraction below the 10 kDa LH showed an increased COX-2 expression in a dose-dependent manner. The mRNA expression of interleukin (IL)-4) was dose-dependently decreased by the fraction below the 10 kDa LH in human mast cells (HMC-1). The mRNA expressions of tumor necrosis factor (TNF)-α and IL-6 were significantly dose-dependently decreased by the fractions above and below the 10 kDa LH, but was dose-dependently increased by LH. The production of IL-4 was a little increased by the fraction above the 10 kDa LH compared to the positive control, but was decreased with LH and the fraction below the 10 kDa LH in HMC-1 cells. It was concluded that LF hydrolysates had an immunomodulating effect on anti-, pro-inflammatory and anti-allergic reactions.

Manufacture of Immobilization Device (Vac-lok) and the Usefulness of Evaluation for Reproducibility of Patients in the Radiotherapy (환자의 재현성을 위한 고정장치(Vac-lok) 제작과 방사선치료에서 유용성 평가)

  • Lee, Jae-Seung;Kim, Gyoung-Hee;Jeong, Kyu-Hwan;Kweon, Dae-Cheol;Goo, Eun-Hoe;Park, Cheol-Woo;Im, In-Chul;Dong, Kyung-Rae;Chung, Woon-Kwan
    • Journal of Radiation Protection and Research
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    • v.36 no.1
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    • pp.8-16
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    • 2011
  • We manufactured the Vac-lok that can be applied to patient of special body shape and need to special set-up position and evaluated the usefulness in the radiation therapy. The manufacture Vac-lok, It was used EVA resin and biobeadform of a diameter 1.5 mm. carried out the test of functionality, structural and analyzed the relative reproducibility of phantoms and patients. During the total period of radiation therapy, Vacuum pressure bring variety to a very small amount in the test of functionality of the manufacture Vac-lok. But It was a negligible quantity. The manufacture Vac-lok improved the relative reproducibility of phantoms than the existing Vac-lok and tolerance has a confidence less than 4% error. Also, relative reproducibility of patient increased error than phantom in the antero-posterior and lateral plan. However, the maximum set-up error was less than ${\pm}\;2.3$ mm. In conclusion, If tolerance set-up error of radiotherapy is less than ${\pm}\;3$ mm, the manufacture Vac-lok was enough possible to use and improvement of reproducibility, considering supply with the Vac-lok made to measure of special patient that produced at a low price and without delay.

Anticancer Activity of Methyl Gallate in RC-58T/h/SA#4 Primary Human Prostate Cancer Cells (인체 전립선 암세포에서 Methyl Gallate의 항암효과)

  • Kwon, Soon Jae;Lee, Ju Hye;Kim, Jae Yong;Moon, Kwang Deog;Yee, Sung Tae;Seo, Kwon Il
    • Journal of the Korean Society of Food Science and Nutrition
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    • v.43 no.3
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    • pp.367-373
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    • 2014
  • In this study, we investigated the anticancer activity of methyl gallate (MG), which is the major biologically active component of Galla Rhois, in RC-58T/h/SA#4 human prostate cancer cells. MG inhibited cell proliferation in a dose-dependent manner. Cell death induced by MG increased the population of cells in sub-G1 phase, formation of apoptotic bodies, nuclear condensation, and DNA fragmentation. Apoptosis induced by MG was associated with activation of initiator caspases-8 and -9 as well as effector caspase-3. Endocrine disruptors such as dioxin and bisphenol A increased growth of RC-58T/h/SA#4 cells in charcoal-treated FBS (cFBS) medium. Cell proliferation was highest upon treatment with 1 nM and $0.1{\mu}M$ dioxin and bisphenol A, respectively. MG also dose-dependently inhibited cell proliferation in RC-58T/h/SA#4 cells treated with endocrine disruptors. These results indicate that MG exerts anticancer effects on RC-58T/h/SA#4 primary human prostate cancer cells.

Factors Predicting Early Release of Thyroid Cancer Patients from the Isolation Room after Radioiodine-131 Treatment

  • Fatima, Nosheen;Zaman, Maseeh uz;Zaman, Areeba;Zaman, Unaiza;Tahseen, Rabia;Shahid, Wajiha
    • Asian Pacific Journal of Cancer Prevention
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    • v.17 no.1
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    • pp.125-129
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    • 2016
  • Background: Patients with differentiated thyroid cancers (DTC) who receive radioactive iodine-131 (RAI) are released from isolation when their dose rate is below the regulatory requirements. The purpose of this study was establish predicting factors for early release from the isolation facility after RAI administration in patients with DTC. Materials and Methods: This was a prospective study which included 96 (58 females and 38 males) patients with DTC who had received RAI from April 2013 till August 2015. The study was duly approved by the ethical committee of the institute. Patients who had complete information of primary tumor size (PTS), serum TSH, stimulated thyroglobulin level [sTg] with antibodies (IU/ml) at the time of RAI treatment were included. All had a normal serum creatinine level. To attain lower effective half-life good hydration and administration of soft laxative were ensured. Dose rate was measured (immediately, 24 h and 36 h) at 1 meter distance from anterior mid trunk and a dose rate <$50{\mu}Sv/h$ was considered as the releasing criterion. At 24 h 50 patients were released while the remaining 46 patients were released at 36 h. A post-ablative whole body scan (PA-WBIS) was performed 5-8 days after RAI ablation in all patients. Results: Patients released after 24 h were significantly younger, had smaller lesions with higher proportion of papillary cancer, lower sTg, lower sTg/TSH ratio and had received a lower dose of RAI as comapred to those who were discharged after 36 h. Serum TSH and gender were not found to have any significant correlation between two cohorts. ROC and multivariate analysis have shown age ${\leq}37years$, PTS ${\leq}3.8cm$, $RAI{\leq}150mCi$, $sTg{\leq}145ng/ml$ and $sTg/TSH{\leq}1.085$ as strong indepedent predictors for early release. Conclusions: We conclude that younger age (${\leq}37years$), smaller tumor size (${\leq}3.8cm$), lower RAI dose (${\leq}150mCi$), lower sTg (${\leq}145ng/ml$) and a lower sTg/TSH ratio (${\leq}1.085$) are significant independent predictors for release at 24 h after RAI treatment in DTC patients. Effective utilization of these factors could help the treating physicians to use limited number of internment facilities with higher throughput, lower cost and lower psychological stress to patients.

Maternal Low-protein Diet Alters Ovarian Expression of Folliculogenic and Steroidogenic Genes and Their Regulatory MicroRNAs in Neonatal Piglets

  • Sui, Shiyan;Jia, Yimin;He, Bin;Li, Runsheng;Li, Xian;Cai, Demin;Song, Haogang;Zhang, Rongkui;Zhao, Ruqian
    • Asian-Australasian Journal of Animal Sciences
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    • v.27 no.12
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    • pp.1695-1704
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    • 2014
  • Maternal malnutrition during pregnancy may give rise to female offspring with disrupted ovary functions in adult age. Neonatal ovary development predisposes adult ovary function, yet the effect of maternal nutrition on the neonatal ovary has not been described. Therefore, here we show the impact of maternal protein restriction on the expression of folliculogenic and steroidogenic genes, their regulatory microRNAs and promoter DNA methylation in the ovary of neonatal piglets. Sows were fed either standard-protein (SP, 15% crude protein) or low-protein (LP, 7.5% crude protein) diets throughout gestation. Female piglets born to LP sows showed significantly decreased ovary weight relative to body weight (p<0.05) at birth, which was accompanied with an increased serum estradiol level (p<0.05). The LP piglets demonstrated higher ratio of bcl-2 associated X protein/B cell lymphoma/leukemia-2 mRNA (p<0.01), which was associated with up-regulated mRNA expression of bone morphogenic protein 4 (BMP4) (p<0.05) and proliferating cell nuclear antigen (PCNA) (p<0.05). The steroidogenic gene, cytochrome P450 aromatase (CYP19A1) was significantly down-regulated (p<0.05) in LP piglets. The alterations in ovarian gene expression were associated with a significant down-regulation of follicle-stimulating hormone receptor mRNA expression (p<0.05) in LP piglets. Moreover, three microRNAs, including miR-423-5p targeting both CYP19A1 and PCNA, miR-378 targeting CYP19A1 and miR-210 targeting BMP4, were significantly down-regulated (p<0.05) in the ovary of LP piglets. These results suggest that microRNAs are involved in mediating the effect of maternal protein restriction on ovarian function through regulating the expression of folliculogenic and steroidogenic genes in newborn piglets.