• Title/Summary/Keyword: exposure pathways

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Increased Innate Lymphoid Cell 3 and IL-17 Production in Mouse Lamina Propria Stimulated with Giardia lamblia

  • Lee, Hye-Yeon;Park, Eun-Ah;Lee, Kyung-Jo;Lee, Kyu-Ho;Park, Soon-Jung
    • Parasites, Hosts and Diseases
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    • v.57 no.3
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    • pp.225-232
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    • 2019
  • Innate lymphoid cells (ILCs) are key players during an immune response at the mucosal surfaces, such as lung, skin, and gastrointestinal tract. Giardia lamblia is an extracellular protozoan pathogen that inhabits the human small intestine. In this study, ILCs prepared from the lamina propria of mouse small intestine were incubated with G. lamblia trophozoites. Transcriptional changes in G. lamblia-exposed ILCs resulted in identification of activation of several immune pathways. Secretion of interleukin (IL)-17A, IL-17F, $IL-1{\beta}$, and interferon-${\gamma}$ was increased, whereas levels of IL-13, IL-5, and IL-22, was maintained or reduced upon exposure to G. lamblia. Goup 3 ILC (ILC3) was found to be dominant amongst the ILCs, and increased significantly upon co-cultivation with G. lamblia trophozoites. Oral inoculation of G. lamblia trophozoites into mice resulted in their presence in the small intestine, of which, the highest number of parasites was detected at the 5 days-post infection. Increased ILC3 was observed amongst the ILC population at the 5 days-post infection. These findings indicate that ILC3 from the lamina propria secretes IL-17 in response to G. lamblia, leading to the intestinal pathology observed in giardiasis.

Bioconversion of Gentiana scabra Bunge increases the anti-inflammatory effect in RAW 264.7 cells via MAP kinases and NF-κB pathway

  • Kim, Min-A;Lee, Han-Saem;Chon, So-Hyun;Park, Jeong-Eun;Lim, Yu-Mi;Kim, Eun-Jeong;Son, Eun-Kyung;Kim, Sang-Jun;So, Jai-Hyun
    • Journal of Applied Biological Chemistry
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    • v.62 no.1
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    • pp.39-50
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    • 2019
  • Mitogen-activated protein (MAP) kinases play an important role in cell growth and differentiation, as well as the modulation of proinflammatory cytokines. The objective of this study was to examine the increase in the anti-inflammatory effect of Gentiana scabra Bunge (GSB), due to bioconversion with the Aspergillus kawachii crude enzyme, via inhibition of the $NF-{\kappa}B$ signaling and MAP kinase pathways in RAW 264.7 cells. The expression of inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 in RAW 264.7 cells treated with the GSB ethyl acetate fraction bioconverted with A. kawachii crude enzyme (GE-BA), was dramatically suppressed as compared to GSB ethyl acetate fraction non-bioconverted with the A. kawachii crude enzyme (GE-UA). The phosphorylation of p38, extracellular signal-regulated kinases, and inhibitory ${\kappa}B$ in RAW 264.7 cells treated with GE-BA was further suppressed, as compared to exposure to GE-UA. Moreover, the mRNA expression of interleukin 6, interleukin 1-beta, and tumor necrosis $factor-{\alpha}$ was further suppressed by GE-BA, compared to GE-UA. Similarly, anti-oxidant activities, such as 2,2-diphenyl-1-picrylhydrazyl hydrate and 2,2'-azino-bis(3-ethylbenzothiazoline-6-sulphonic acid) radical scavenging activity, of GE-BA were further increased compared to GE-UA. These observations demonstrate that the anti-oxidant and anti-inflammatory activities of GSB ethyl acetate fraction increases as a result from bioconversion with the A. kawachii crude enzyme.

Phloroglucinol Attenuates Ultraviolet B-Induced 8-Oxoguanine Formation in Human HaCaT Keratinocytes through Akt and Erk-Mediated Nrf2/Ogg1 Signaling Pathways

  • Piao, Mei Jing;Kim, Ki Cheon;Kang, Kyoung Ah;Fernando, Pincha Devage Sameera Madushan;Herath, Herath Mudiyanselage Udari Lakmini;Hyun, Jin Won
    • Biomolecules & Therapeutics
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    • v.29 no.1
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    • pp.90-97
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    • 2021
  • Ultraviolet B (UVB) radiation causes DNA base modifications. One of these changes leads to the generation of 8-oxoguanine (8-oxoG) due to oxidative stress. In human skin, this modification may induce sunburn, inflammation, and aging and may ultimately result in cancer. We investigated whether phloroglucinol (1,3,5-trihydroxybenzene), by enhancing the expression and activity of 8-oxoG DNA glycosylase 1 (Ogg1), had an effect on the capacity of UVB-exposed human HaCaT keratinocytes to repair oxidative DNA damage. Here, the effects of phloroglucinol were investigated using a luciferase activity assay, reverse transcription-polymerase chain reactions, western blot analysis, and a chromatin immunoprecipitation assay. Phloroglucinol restored Ogg1 activity and decreased the formation of 8-oxoG in UVB-exposed cells. Moreover, phloroglucinol increased Ogg1 transcription and protein expression, counteracting the UVB-induced reduction in Ogg1 levels. Phloroglucinol also enhanced the nuclear translocation of nuclear factor erythroid 2-related factor 2 (Nrf2) as well as Nrf2 binding to an antioxidant response element located in the Ogg1 gene promoter. UVB exposure inhibited the phosphorylation of protein kinase B (PKB or Akt) and extracellular signal-regulated kinase (Erk), two major enzymes involved in cell protection against oxidative stress, regulating the activity of Nrf2. Akt and Erk phosphorylation was restored by phloroglucinol in the UVB-exposed keratinocytes. These results indicated that phloroglucinol attenuated UVB-induced 8-oxoG formation in keratinocytes via an Akt/Erk-dependent, Nrf2/Ogg1-mediated signaling pathway.

Green tea polyphenol (-)-epigallocatechin-3-gallate prevents ultraviolet-induced apoptosis in PC12 cells

  • Woo, Su-Mi;Kim, Yoon-Jung;Cai, Bangrong;Park, Sam-Young;Kim, Young;Kim, Ok Joon;Kang, In-Chol;Kim, Won-Jae;Jung, Ji-Yeon
    • International Journal of Oral Biology
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    • v.45 no.4
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    • pp.179-189
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    • 2020
  • Green tea polyphenol (-)-epigallocatechin-3-gallate (EGCG) is a potent antioxidant with protective effects against neurotoxicity. However, it is currently unclear whether EGCG protects neuronal cells against radiation-induced damage. Therefore, the objective of this study was to investigate the effects of EGCG on ultraviolet (UV)-induced oxidative stress and apoptosis in PC12 cells. The effects of UV irradiation included apoptotic cell death, which was associated with DNA fragmentation, reactive oxygen species (ROS) production, enhanced caspase-3 and caspase-9 activity, and poly (ADP-ribose) polymerase cleavage. UV irradiation also increased the Bax/Bcl-2 ratio and mitochondrial pathway-associated cytochrome c expression. However, pretreatment with EGCG before UV exposure markedly decreased UV-induced DNA fragmentation and ROS production. Furthermore, the UV irradiation-induced increase in Bax/Bcl-2 ratio, cytochrome c upregulation, and caspase-3 and caspase-9 activation were each ameliorated by EGCG pretreatment. Additionally, EGCG suppressed UV-induced phosphorylation of p38 and rescued UV-downregulated phosphorylation of ERK. Taken together, these results suggest that EGCG prevents UV irradiation-induced apoptosis in PC12 cells by scavenging ROS and inhibiting the mitochondrial pathways known to play a crucial role in apoptosis. In addition, EGCG inhibits UV-induced apoptosis via JNK inactivation and ERK activation in PC12 cells. Thus, EGCG represents a potential neuroprotective agent that could be applied to prevent neuronal cell death induced by UV irradiation.

Antioxidant and Antimelanogenic Activities of Kimchi-Derived Limosilactobacillus fermentum JNU532 in B16F10 Melanoma Cells

  • Meng, Ziyao;Oh, Sejong
    • Journal of Microbiology and Biotechnology
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    • v.31 no.7
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    • pp.990-998
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    • 2021
  • Melanin is a natural skin pigment produced by specialized cells called melanocytes via a multistage biochemical pathway known as melanogenesis, involving the oxidation and polymerization of tyrosine. Melanogenesis is initiated upon exposure to ultraviolet (UV) radiation, causing the skin to darken, which protects skin cells from UVB radiation damage. However, the abnormal accumulation of melanin may lead to the development of certain skin diseases, including skin cancer. In this study, the antioxidant and antimelanogenic activities of the cell-free supernatant (CFS) of twenty strains were evaluated. Based on the results of 60% 2,2-diphenyl-1-picrylhydrazyl scavenging activity, 21% 2,2'-azino-bis (3-ethylbenzthiazoline-6-sulfonic acid) scavenging capacity, and a 50% ascorbic acid equivalent ferric reducing antioxidant power value, Limosilactobacillus fermentum JNU532 was selected as the strain with the highest antioxidant potential. No cytotoxicity was observed in cells treated with the CFS of L. fermentum JNU532. Tyrosinase activity was reduced by 16.7% in CFS-treated B16F10 cells (but not in the cell-free system), with >23.2% reduction in melanin content upon treatment with the L. fermentum JNU532-derived CFS. The inhibitory effect of the L. fermentum JNU532-derived CFS on B16F10 cell melanogenesis pathways was investigated using quantitative reverse transcription polymerase chain reaction and western blotting. The inhibitory effects of the L. fermentum JNU532-derived CFS were mediated by inhibiting the transcription of TYR, TRP-1, TRP-2, and MITF and the protein expression of TYR, TRP-1, TRP-2, and MITF. Therefore, L. fermentum JNU532 may be considered a potentially useful, natural depigmentation agent.

The presence of carcinogenic radon in the Padma River water, adjacent to the Rooppur Nuclear Power Plant

  • M.M. Mahfuz Siraz;M.S. Alam;Jubair A.M.;S.C. Das;J. Ferdous;Z. Hossain;S. Das;Mayeen Uddin Khandaker;D.A. Bradley;Shinji Tokonami;S. Yeasmin
    • Nuclear Engineering and Technology
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    • v.55 no.8
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    • pp.3046-3053
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    • 2023
  • Radon is a naturally occurring carcinogenic agent, poses a serious health hazard when inhaled or ingested in significant amounts. The water of the Padma river will be used as a tertiary coolant for the soon-to-be-commissioned 'Rooppur Nuclear Power Plant'. Hence, it is important to assess the radiological status of the river prior to the commission of this power plant. Therefore, for the first time, 25 samples of water were collected from various locations of the Padma River and analyzed for radon concentration using the RAD H2O (DURRIDGE) radon monitoring device. The radon concentrations were found in the range from 0.077 ± 0.036 to 0.494 ± 0.211 Bq/L with a mean of 0.250 ± 0.093 Bq/L. All the concentrations were found to be below the recommended limits of WHO (100 Bq/L) and USEPA (11.1 Bq/L). The mean annual effective dose due to the radon exposure via inhalation and ingestion pathways were 0.638 µSv/y and 0.629 µSv/y, respectively, which were all well below the annual effective dose recommended by WHO (0.1 mSv/y). Since Bangladesh lacks a national safety limit of radon in water, this pioneering study provides baseline data on radon levels for the environment around Rooppur Nuclear Power Plant.

Korean Red Ginseng suppresses emphysematous lesions induced by cigarette smoke condensate through inhibition of macrophage-driven apoptosis pathways

  • Jeong-Won Kim;Jin-Hwa Kim;Chang-Yeop Kim;Ji-Soo Jeong;Je-Won Ko;Tae-Won Kim
    • Journal of Ginseng Research
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    • v.48 no.2
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    • pp.181-189
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    • 2024
  • Background: Cigarette smoke is generally accepted as a major contributor to chronic obstructive pulmonary disease (COPD), which is characterized by emphysematous lesions. In this study, we investigated the protective effects of Korean Red Ginseng (KRG) against cigarette smoke condensate (CSC)-induced emphysema. Methods: Mice were instilled with 50 mg/kg of CSC intranasally once a week for 4 weeks, KRG was administered to the mice once daily for 4 weeks at doses of 100 or 300 mg/kg, and dexamethasone (DEX, positive control) was administered to the mice once daily for 2 weeks at 3 mg/kg. Results: KRG markedly decreased the macrophage population in bronchoalveolar lavage fluid and reduced emphysematous lesions in the lung tissues. KRG suppressed CSC-induced apoptosis as revealed by terminal deoxynucleotidyl transferase deoxyuridine triphosphate nick-end labeling staining and Caspase 3 immunohistochemistry. Additionally, KRG effectively inhibited CSC-mediated activation of Bcl-2-associated X protein/Caspase 3 signaling, followed by the induction of cell survival signaling, including vascular endothelial growth factor/phosphoinositide 3-kinase/protein kinase B in vivo and in vitro. The DEX group also showed similar improved results in vivo and in vitro. Conclusion: Taken together, KRG effectively inhibits macrophage-mediated emphysema induced by CSC exposure, possibly via the suppression of pro-apoptotic signaling, which results in cell survival pathway activation. These findings suggest that KRG has therapeutic potential for the prevention of emphysema in COPD patients.

Thermal impacts on transcriptome of Pectoralis major muscle collected from commercial broilers, Thai native chickens and its crossbreeds

  • Yuwares Malila;Tanaporn Uengwetwanit;Pornnicha Sanpinit;Wipakarn Songyou;Yanee Srimarut;Sajee Kunhareang
    • Animal Bioscience
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    • v.37 no.1
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    • pp.61-73
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    • 2024
  • Objective: The main objective of this study was to define molecular mechanisms associated with thermal stress responses of chickens from commercial broilers (BR, Ross 308), Thai native chickens (NT) and crossbreeds between BR×NT (H75). Methods: Twenty days before reaching specific market age, chickens from each breed were divided into control and thermal-stressed groups. The stressed groups were exposed to a cyclic thermal challenge (35℃±1℃ for 6 h, followed by 26℃±1℃ for 18 h) for 20 days. Control group was raised under a constant temperature of 26℃±1℃. Pectoralis major (n = 4) from each group was collected for transcriptome analysis using HiSeq Illumina and analysis of glycogen and lactate. Gene expression patterns between control and thermal-stressed groups were compared within the same breeds. Results: Differentially expressed transcripts of 65, 59, and 246 transcripts for BR, NT, and H75, respectively, were revealed by RNA-Seq and recognized by Kyoto encyclopedia of genes and genomes database. Pathway analysis underlined altered glucose homeostasis and protein metabolisms in all breeds. The signals centered around phosphatidylinositol 3-kinase (PI3K)/Akt signaling, focal adhesion, and MAPK signaling in all breeds with slight differences in molecular signal transduction patterns among the breeds. An extensive apoptosis was underlined for BR. Roles of AMPK, MAPK signaling and regulation of actin cytoskeleton in adaptive response were suggested for H75 and NT chickens. Lower glycogen content was observed in the breast muscles of BR and NT (p<0.01) compared to their control counterparts. Only BR muscle exhibited increased lactate (p<0.01) upon exposure to the stress. Conclusion: The results provided a better comprehension regarding the associated biological pathways in response to the cyclic thermal stress in each breed and in chickens with different growth rates.

Mechanisms Regulating the Expression of Cytochrome P450 (CYP) Enzymes Involved in Xenobiotic Metabolism (외인성 화학물질의 대사에 관여하는 Cytochrome P450 (CYP) 효소의 발현조절 기전)

  • Gyesik Min
    • Journal of Life Science
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    • v.34 no.3
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    • pp.199-207
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    • 2024
  • Cytochrome P450s (CYP) enzymes play a central role in the metabolism of both endogenous and xenobiotic chemical compounds. In particular, therapeutic drugs, natural products and environmental toxicants regulate expression of the tissue-specific CYP enzymes, This can cause CYP-mediated interactions among the chemical compounds such as the ingested drugs and toxicants, resulting in changes in their metabolism. This can lead to the modifications of their therapeutic and toxic effects. Intense investigations in this field throughout the last several decades have resulted in considerable progress in understanding the molecular mechanisms mediating the regulation of CYP gene expression. Now, it is well established that xenobiotic chemicals regulate the expression of specific CYP genes, and the corresponding xenobiotic-sensing receptors that mediate the expression control of specific CYP genes and their signal transduction pathways are involved in this process. This review summarizes the molecular mechanisms by which the well-known major xenobiotic-sensing receptors and other regulators affect the induction of CYP gene expression in response to exposure to various chemicals.

Radiological Dose Analysis to the Public Resulting from the Operation of Daedeok Nuclear Facilities (대덕부지 원자력관련시설 운영에 따른 주민피폭선량 현황분석)

  • Jeong, Hae Sun;Kim, Eun Han;Jeong, Hyo Joon;Han, Moon Hee;Park, Mi Sun;Hwang, Won Tae
    • Journal of Radiation Protection and Research
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    • v.39 no.1
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    • pp.38-45
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    • 2014
  • This paper describes the results of assessment of radiological dose resulting from operation of the Daedeok nuclear facilities including the HANARO research reactor, which has been performed to assure whether or not to comply with the regulation standards of the radioactive effluents releases. Based on the meteorological data and the radiation source term, the maximum individual doses were evaluated from 2010 to 2012. The atmospheric dispersion and the deposition factors of gaseous effluents were calculated using the XOQDOQ computer code. ENDOS-G and ENDOS-L code systems were also used for maximum individual dose calculation from gaseous and liquid effluents, respectively. The results were compared with the regulation standards for the radioactive effluents presented by the Nuclear Safety and Security Commission (NSSC). The effective doses and the thyroid doses of the maximum individual were calculated at the maximum exposed point in the Daedeok site, and contributions of exposure pathways to the radiological doses resulting from gaseous and liquid radioactive effluents were evaluated at each facility of the Daedeok site. As a result, the maximum exposed age was analysed to be the child group, and the operation of HANARO research reactor had a major effect more than 90% on the individual doses. The main exposure pathways for gaseous radioactive effluent were from ingestion and inhalation. The effective doses and the thyroid doses were considerably influenced by tritium and iodine, respectively. The gaseous radioactive effluents contributed more than 90% on the total doses, whereas the contributions of the liquid radioactive effluents were relatively low. Consequently, the maximum individual dose due to radioactive effluents from the nuclear facilities within the Daedeok site were less than 3% of the regulation standard over 3 years; therefore, it can be concluded that radioactive effluents from the nuclear facilities were well managed, with the radiation-induced health detriment for residents around the site being negligible.