• Title/Summary/Keyword: biological pathways

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Adenine attenuates lipopolysaccharide-induced inflammatory reactions

  • Silwal, Prashanta;Lim, Kyu;Heo, Jun-Young;Park, Jong IL;Namgung, Uk;Park, Seung-Kiel
    • The Korean Journal of Physiology and Pharmacology
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    • v.22 no.4
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    • pp.379-389
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    • 2018
  • A nucleobase adenine is a fundamental component of nucleic acids and adenine nucleotides. Various biological roles of adenine have been discovered. It is not produced from degradation of adenine nucleotides in mammals but produced mainly during polyamine synthesis by dividing cells. Anti-inflammatory roles of adenine have been supported in IgE-mediated allergic reactions, immunological functions of lymphocytes and dextran sodium sulfate-induced colitis. However adenine effects on Toll-like receptor 4 (TLR4)-mediated inflammation by lipopolysaccharide (LPS), a cell wall component of Gram negative bacteria, is not examined. Here we investigated anti-inflammatory roles of adenine in LPS-stimulated immune cells, including a macrophage cell line RAW264.7 and bone marrow derived mast cells (BMMCs) and peritoneal cells in mice. In RAW264.7 cells stimulated with LPS, adenine inhibited production of pro-inflammatory cytokines $TNF-{\alpha}$ and IL-6 and inflammatory lipid mediators, prostaglandin $E_2$ and leukotriene $B_4$. Adenine impeded signaling pathways eliciting production of these inflammatory mediators. It suppressed $I{\kappa}B$ phosphorylation, nuclear translocation of nuclear factor ${\kappa}B$ ($NF-{\kappa}B$), phosphorylation of Akt and mitogen activated protein kinases (MAPKs) JNK and ERK. Although adenine raised cellular AMP which could activate AMP-dependent protein kinase (AMPK), the enzyme activity was not enhanced. In BMMCs, adenine inhibited the LPS-induced production of $TNF-{\alpha}$, IL-6 and IL-13 and also hindered phosphorylation of $NF-{\kappa}B$ and Akt. In peritoneal cavity, adenine suppressed the LPS-induced production of $TNF-{\alpha}$ and IL-6 by peritoneal cells in mice. These results show that adenine attenuates the LPS-induced inflammatory reactions.

The Effects of MeOH Extract of Hopea chinensis (Merr.) Hand.-Mazz. on the Metabolism of Amyloid Precursor Protein in Neuroblastoma Cells (Hopea chinensis (Merr.) Hand.-Mazz. 메탄올 추출물이 신경세포에서 아밀로이드 전구 단백질 대사에 미치는 영향)

  • Chandra, Shrestha Abinash;Kim, Ju Eun;Ham, Ha Neul;Jo, Youn Jeong;Bach, Tran The;Eum, Sang Mi;Leem, Jae Yoon
    • Korean Journal of Pharmacognosy
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    • v.49 no.2
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    • pp.182-187
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    • 2018
  • Many plant derived phytochemicals have been considered as the main therapeutic strategy against Alzheimer's disease (AD). AD is a progressive neurodegenerative disorder, and the most predominant cause of dementia in the elderly. Cholinergic deficit, senile plaque/${\beta}$-amyloid ($A{\beta}$) peptide deposition and oxidative stress have been identified as three main pathogenic pathways which contribute to the progression of AD. We screened many different plant species for their effective use in both modern and traditional system of medicines. In this study, we tested that MeOH extract of the stem bark of Hopea chinensis (Merr.) Hand.-Mazz. (HCM) affects on the processing of Amyloid precursor portein (APP) from the APPswe over-expressing Neuro2a cell line. We showed that HCM reduced the secretion level of $A{\beta}42$ and $A{\beta}40$ in a dose dependent manner. We found that HCM increased over 1.5 folds of the secretion level of $sAPP{\alpha}$, a metabolite of ${\alpha}$-secretase. Furthermore, we found that HCM inhibited acetylcholinesterase activity in vitro. We suggest that the stem bark of Hopea chinensis may be a useful source to develop a therapeutics for AD.

Analysis of Spatiotemporal Changes in Groundwater Recharge and Baseflow using SWAT and BFlow Models (SWAT 모형과 BFlow를 이용한 지하수 함양, 기저유출의 시공간적 변화 분석)

  • Lee, Ji Min;Park, Youn Shik;Jung, Younghun;Cho, Jaepil;Yang, Jae Eui;Lee, Gwanjae;Kim, Ki-Sung;Lim, Kyoung Jae
    • Journal of Korean Society on Water Environment
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    • v.30 no.5
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    • pp.549-558
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    • 2014
  • Occurrence frequency of flood and drought tends to increase in last a few decades, leading to social and economic damage since the abnormality of climate changes is one of the causes for hydrologic facilities by exceedance its designed tolerance. Soil and Water Assessment Tool (SWAT) model was used in the study to estimate temporal variance of groundwater recharge and baseflow. It was limited to consider recession curve coefficients in SWAT model calibration process, thus the recession curve coefficient was estimated by the Baseflow Filter Program (BFLOW) before SWAT model calibration. Precipitation data were estimated for 2014 to 2100 using three models which are GFDL-ESM2G, IPSL-CM5A-LR, and MIROC-ESM with Representative Concentration Pathways (RCP) scenario. SWAT model was calibrated for the Soyang watershed with NSE of 0.83, and $R^2$ of 0.89. The percentage to precipitation of groundwater recharge and baseflow were 27.6% and 17.1% respectively in 2009. Streamflow, groundwater recharge, and baseflow were estimated to be increased with the estimated precipitation data. GFDL-ESM2g model provided the most large precipitation data in the 2025s, and IPSL-CM5A-LR provided the most large precipitation data in the 2055s and 2085s. Overall, groundwater recharge and baseflow displayed similar trend to the estimated precipitation data.

A Study on the Application of Enhanced Phytoremediation with Plant Growth Promoting Rhizobacteria for Zn Contaminated Rice Paddy Soil (식물성장근권 미생물 적용에 의한 Zn 오염 논토양 식물상정화증진기법 적용에 관한 연구)

  • Kim, Tae-Sung;Choi, Sang-Il;Yang, Jae-Kyu;Lee, In-Sook;Bae, Bum-Han
    • Journal of Soil and Groundwater Environment
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    • v.15 no.3
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    • pp.15-26
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    • 2010
  • The contaminated soils near abandoned mine area can threaten human's health and natural ecosystems through multiple pathways. Remediation of contaminated soil using physicochemical technologies are expensive and destructive of soil environments. On the other hand, environmentally friendly approach that maximize biological remediation, that is, phytoremediation, attracts attention as a low carbon green growth technology. This research is a field demonstration study, focused on the enhanced phytoremediation by bioaugmenting PGPR(Plant Growth Promoting Rhizobacteria)that is helpful on the growth of and heavy metal removal by Echinochloa frumentacea, at a Zn contaminated paddy soil near SamBo mine at Hwasung, Kyunggi. The results showed that the zinc removal by the plant with PSM(Phosphate Solubilizing Bacteria), a kind of PGPR, was three times higher than that by the control. The results are valuable as it is a result from the field-scale technology demonstration. The results also implies that application of PGPR can enhance heavy metal removal from contaminated soil in full scale phytoremediation using Echinochloa frumentacea.

Gonadotropin-releasing Hormone and Its Receptor as a Therapeutic Concept in the Progression of Epithelial Ovarian Cancer

  • Kim, Ki-Yon;Choi, Kyung-Chul
    • Journal of Embryo Transfer
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    • v.24 no.1
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    • pp.1-14
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    • 2009
  • Ovarian cancer is a significant cause of cancer-related death in women, but the main biological causes remain open questions. Hormonal factors have been considered to be an important determinant causing ovarian cancer. Recent studies have shown that gonadotropin-releasing hormone (GnRH)-I and its analogs have clinically therapeutic value in the treatment of ovarian cancer. In addition, numerous studies have shown that the potential of GnRH-II in normal reproductive system or reproductive disorder. GnRH-I receptors have been detected in approximately 80% of ovarian cancer biopsy specimens as well as normal ovarian epithelial cells and immortalized ovarian surface epithelium cells. GnRH-II receptors have also been found to be more widely expressed than GnRH-I receptors in mammals, suggesting that GnRH receptors may have additional functions in reproductive system including ovarian cancer. The signal transduction pathway following the binding of GnRH to GnRH receptor has been extensively studied. The activation of protein kinase A/C (PKA/PKC) pathway is involved in the GnRH-I induced anti-proliferative effect in ovarian cancer cells. In addition, GnRH-I induced mitogen-activated protein kinase (MAPK) activation plays a role in anti-proliferative effect and apoptosis in ovarian cancer cells and the activation of transcriptional factors related to cellular responses. However, the role of GnRH-I and II receptors, there are discrepancies between previous reports. In this review, the role of GnRH in ovarian cancer and the mechanisms to induce anti-proliferation were evaluated.

Orthogonal Stimulus-Response as a Tool to Formulate Traditional Chinese Medicinal Herbal Combination - New Scientific-Based TCM Herbal Formulating Method -

  • Loh, Yean Chun;Tan, Chu Shan;Yam, Mun Fei;Oo, Chuan Wei;Omar, Wan Maznah Wan
    • Journal of Pharmacopuncture
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    • v.21 no.3
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    • pp.203-206
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    • 2018
  • Objectives: There is an increasing number of complex diseases that are progressively more difficult to be controlled using the conventional "single compound, single target" approach as demonstrated in our current modern drug development. TCM might be the new cornerstone of treatment alternative when the current treatment option is no longer as effective or that we have exhausted it as an option. Orthogonal stimulus-response compatibility group study is one of the most frequently employed formulas to produce optimal herbal combination for treatment of multi-syndromic diseases. This approach could solve the relatively low efficacy single drug therapy usage and chronic adverse effects caused by long terms administration of drugs that has been reported in the field of pharmacology and medicine Methods: The present review was based on the Science Direct database search for those related to the TCM and the development of antihypertensive TCM herbal combination using orthogonal stimulus-response compatibility group studies approach. Results: Recent studies have demonstrated that the orthogonal stimulus-response compatibility group study approach was most frequently used to formulate TCM herbal combination based on the TCM principles upon the selection of herbs, and the resulting formulated TCM formula exhibited desired outcomes in treating one of global concerned complex multi-syndromic diseases, the hypertension. These promising therapeutic effects were claimed to have been attributed by the holistic signaling mechanism pathways employed by the crude combination of herbs. Conclusion: The present review could serve as a guide and prove the feasibility of TCM principles to be used for future pharmacological drug research development.

Biosynthesis of Penicillins and Cephalosporins Antibiotics (페니실린과 세파로스포린계 항생제의 생합성)

  • 김경자;구양모
    • YAKHAK HOEJI
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    • v.27 no.3
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    • pp.185-205
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    • 1983
  • Penicillins and cephalosporins are biosynthesized from L-.alpha.-aminoadipic acid, L-cysteine and L-valine. A tripeptide, LLD-$\delta$-($\alpha$-aminoadipyl)cysteinylvaline(LLD-ACV) was isolated from fermentation broths of Cephalosporium acremonium as well as of Penicillium chrysogenum and it was proved that the LL-$\delta$-($\alpha$-aminoadipyl cysteine was formed first in mycelia, to which valine would be connected to give LLD-ACV. However, several points are still unsolved; first, what mechanism is involved in the configurational change from L-valine to D-valine, second, what kind of cyclization mechanism gives a $\betha$-lactam ring and a thiazolidine ring and third, what is the pathways for the ring expansion from penicillins to cephalosporins. At present, it seems clear that LLD-ACV is cyclized to give isopenicillin N, which is transformed to penicillin N and further to cepbalosporin C. Other hydrophobic penicillins, including benzyl penicillin and penicillin V, are formed from isopenicillin N by acyl-exchange reactions catalyzed by penicillin transferase, rather than by acylation reaction on 6-aminopenicillanic acid(6-APA), which was isolated from the fermentation broth of P. chrysogenum and which would be formed by hydrolysis of $\delta-(\alpha$-amincadipyl)amido moiety at the C-6 position in isopenicillin N or penicillin N by penicillin acylase. Acylation of 6-APA is catalyzed also by penicillin acylase, but the reaction is proved not to be involved in penicillin biosynthesis. Understanding the biosynthesis of penicillins and cephalsoporins would provide solutions to increase in fermentation yields of penicillins, especially of cephalosporins and a solution to biological production of 7-aminocepbalosporanic acid (7-ACA) which is of importance in pharmaceutical industry. Still regulation mechanisms in penicillin and cephalosporin biosynthesis are unveiled at all.

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Evaluation of Reservoir Drought Response Capability Considering Precipitation of Non-irrigation Period using RCP Scenario (RCP 시나리오에 따른 비관개기 누적강수량을 고려한 둑높이기 저수지의 미래 가뭄대응능력 평가)

  • Bang, JeHong;Lee, Sang-Hyun;Choi, Jin-Yong;Lee, Sung-Hack
    • Journal of The Korean Society of Agricultural Engineers
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    • v.59 no.1
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    • pp.31-43
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    • 2017
  • Recent studies about irrigation water use have focused on agricultural reservoir operation in irrigation period. At the same time, it is significant to store water resource in reservoir during non-irrigation period in order to secure sufficient water in early growing season. In this study, Representative Concentration Pathways (RCP) 4.5, 8.5 scenarios with the Global Climate Model (GCM) of The Second Generation Earth System Model (CanESM2) were downscaled with bias correlation method. Cumulative precipitation during non-irrigation season, October to March, was analyzed. Interaction between cumulative precipitation and carry-over storage was analyzed with linear regression model for ten study reservoirs. Using the regression model, reservoir drought response ability was evaluated with expression of excess and deficiency. The results showed that future droughts will be more severe than past droughts. Especially in case of non-exceedance probability of 10%, drought in southern region seemed to be serious. Nine study reservoirs showed deficiency range from 10% to 55%, which turned out to be vulnerable for future drought. Only Jang-Chan reservoir was secure for early growing season in spite of drought with deficiency of 8% and -2%. The results of this study represents current agricultural reservoirs have vulnerability for the upcoming drought.

Oral Administration of Lactobacillus plantarum HY7714 Protects Hairless Mouse Against Ultraviolet B-Induced Photoaging

  • Kim, Hyun Mee;Lee, Dong Eun;Park, Soo Dong;Kim, Yong-Tae;Kim, Yu Jin;Jeong, Ji Woong;Jang, Sung Sik;Ahn, Young-Tae;Sim, Jae-Hun;Huh, Chul-Sung;Chung, Dae Kyun;Lee, Jung-Hee
    • Journal of Microbiology and Biotechnology
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    • v.24 no.11
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    • pp.1583-1591
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    • 2014
  • Ultraviolet (UV) irradiation alters multiple molecular pathways in the skin, thereby inducing skin damage, including photoaging. In recent years, probiotics have gained interest due to their beneficial effects on skin health, such as inhibiting atopic dermatitis and improving skin immunity or inflammation. However, little is known about the effects of probiotics on UVB-induced photoaging. In this study, we evaluated the effect of Lactobacillus plantarum HY7714 against UVB-induced photoaging in human dermal fibroblasts and hairless mice. The results showed that L. plantarum HY7714 treatment effectively rescued UVB-reduced procollagen expression through the inhibition of UVB-induced matrix metalloproteinase (MMP)-1 expression in human dermal fibroblasts. Data from a western blot showed that L. plantarum HY7714 inhibited the phosphorylation of Jun N-terminal kinase, thereby suppressing the UVB-induced phosphorylation and expression of c-Jun. Oral administration of L. plantarum HY7714 clearly inhibited the number, depth, and area of wrinkles in hairless mouse skin. Histological data showed that L. plantarum HY7714 significantly inhibited UVB-induced epidermal thickness in mice. Western blot and zymography data also revealed that L. plantarum HY7714 effectively inhibited MMP-13 expression as well as MMP-2 and -9 activities in dermal tissue. Collectively, these results provide further insight regarding the skin biological actions of L. plantarum HY7714, a potential skin anti-photoaging agent.

Transcriptomic Approach for Understanding the Adaptation of Salmonella enterica to Contaminated Produce

  • Park, Sojung;Nam, Eun woo;Kim, Yeeun;Lee, Seohyeon;Kim, Seul I;Yoon, Hyunjin
    • Journal of Microbiology and Biotechnology
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    • v.30 no.11
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    • pp.1729-1738
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    • 2020
  • Salmonellosis is a form of gastroenteritis caused by Salmonella infection. The main transmission route of salmonellosis has been identified as poorly cooked meat and poultry products contaminated with Salmonella. However, in recent years, the number of outbreaks attributed to contaminated raw produce has increased dramatically. To understand how Salmonella adapts to produce, transcriptomic analysis was conducted on Salmonella enterica serovar Virchow exposed to fresh-cut radish greens. Considering the different Salmonella lifestyles in contact with fresh produce, such as motile and sessile lifestyles, total RNA was extracted from planktonic and epiphytic cells separately. Transcriptomic analysis of S. Virchow cells revealed different transcription profiles between lifestyles. During bacterial adaptation to fresh-cut radish greens, planktonic cells were likely to shift toward anaerobic metabolism, exploiting nitrate as an electron acceptor of anaerobic respiration, and utilizing cobalamin as a cofactor for coupled metabolic pathways. Meanwhile, Salmonella cells adhering to plant surfaces showed coordinated upregulation in genes associated with translation and ribosomal biogenesis, indicating dramatic cellular reprogramming in response to environmental changes. In accordance with the extensive translational response, epiphytic cells showed an increase in the transcription of genes that are important for bacterial motility, nucleotide transporter/metabolism, cell envelope biogenesis, and defense mechanisms. Intriguingly, Salmonella pathogenicity island (SPI)-1 and SPI-2 displayed up- and downregulation, respectively, regardless of lifestyles in contact with the radish greens, suggesting altered Salmonella virulence during adaptation to plant environments. This study provides molecular insights into Salmonella adaptation to plants as an alternative environmental reservoir.