• Biomolecules & Therapeutics
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• 제25권3호
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• pp.223-230
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• 2017

Platelets play an essential role in hemostasis through aggregation and adhesion to vascular injury sites but their unnecessary activation can often lead to thrombotic diseases. Upon exposure to physical or biochemical stimuli, remarkable platelet shape changes precede aggregation or adhesion. Platelets shape changes facilitate the formation and adhesion of platelet aggregates, but are readily reversible in contrast to the irrevocable characteristics of aggregation and adhesion. In this dynamic phenomenon, complex molecular signaling pathways and a host of diverse cytoskeleton proteins are involved. Platelet shape change is easily primed by diverse pro-thrombotic xenobiotics and stimuli, and its inhibition can modulate thrombosis, which can ultimately contribute to the development or prevention of thrombotic diseases. In this review, we discussed the current knowledge on the mechanisms of platelet shape change and also pathological implications and therapeutic opportunities for regulating the related cytoskeleton dynamics.

• Bulletin of the Korean Chemical Society
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• 제20권12호
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• pp.1428-1432
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• 1999

[Fe$^{II}$(BLPA)DBCH]BPh₄ (1), a new functional model for the extradiol-cleaving catechol dioxygenases, has been synthesized, where BLPA is bis(6-methyl-2-pyridylmethyl)(2-pyridylmethyl)amine and DBCH is 3,5-di-tert-butylcatecholate monoanion. ¹H NMR and EPR studies confirm that 1 has a high-spin Fe(II) (S = 2) center. The electronic spectrum of 1 exhibits one absorption band at 386 nm, showing the yellow color of the typical [Fe$^{II}$(BLPA)] complex. Upon exposure to O₂, 1 is converted to an intense blue species within a minute. This blue species exhibits two intense bands at 586 and 960 nm and EPR signals at g = 5.5 and 8.0 corresponding to the high-spin Fe(III) complex (S = 5/2, E/D = 0.11). This blue complex further reacts with O₂ to be converted to (μ-oxo)Fe$^{III}_2$ complex within a few hours. Interestingly, 1 affords intradiol cleavage (65%) and extradiol cleavage (20%) products after the oxygenation. It can be suggested that 1 undergoes two different oxygenation pathways. The one takes the substrate activation mechanism proposed for the intradiol cleavage products after the oxidation of the $Fe^II\;to\;Fe^{III}$. The other involves the direct attack of O₂ to $Fe^{II}$ center, forming the $Fe^{III}$-superoxo intermediate which can give rise to the extradiol cleavage products. 1 is the first functional Fe(II) complex for extradiol-cleaving dioxygenases giving extradiol cleavage products.

• 한국미생물·생명공학회지
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• 제50권4호
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• pp.441-456
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• 2022

Shiga toxins (Stxs) are major virulence factors from the enterohemorrhagic Escherichia coli (EHEC), a subset of Stx-producing Escherichia coli. Stxs are multi-functional, ribosome-inactivating proteins that underpin the development of hemolytic uremic syndrome (HUS) and central nervous system (CNS) damage. Currently, therapeutic options for the treatment of diseases caused by Stxs are limited and unsatisfactory. Furthermore, the pathophysiological mechanisms underpinning toxin-induced inflammation remain unclear. Numerous works have demonstrated that the various host ribotoxic stress-induced targets including p38 mitogen-activated protein kinase, its downstream substrate Mitogen-activated protein kinase-activated protein kinase 2, and apoptotic signaling via ER-stress sensors are activated in many different susceptible cell types following the regular retrograde transportation of the Stxs, eventually leading to disturbing intercellular communication. Therapeutic options targeting host cellular pathways induced by Stxs may represent a promising strategy for intervention in Stx-mediated acute renal dysfunction, retinal damage, and CNS damage. This review aims at fostering an in-depth understanding of EHEC Stxs-mediated pathogenesis through the toxin-host interactions.

• Restorative Dentistry and Endodontics
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• 제48권2호
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• pp.20.1-20.13
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• 2023

This mini-review was conducted to present an overview of the use of exosomes in regenerating the dentin-pulp complex (DPC). The PubMed and Scopus databases were searched for relevant articles published between January 1, 2013 and January 1, 2023. The findings of basic in vitro studies indicated that exosomes enhance the proliferation and migration of mesenchymal cells, as human dental pulp stem cells, via mitogen-activated protein kinases and Wingless-Int signaling pathways. In addition, they possess proangiogenic potential and contribute to neovascularization and capillary tube formation by promoting endothelial cell proliferation and migration of human umbilical vein endothelial cells. Likewise, they regulate the migration and differentiation of Schwann cells, facilitate the conversion of M1 pro-inflammatory macrophages to M2 anti-inflammatory phenotypes, and mediate immune suppression as they promote regulatory T cell conversion. Basic in vivo studies have indicated that exosomes triggered the regeneration of dentin-pulp-like tissue, and exosomes isolated under odontogenic circumstances are particularly strong inducers of tissue regeneration and stem cell differentiation. Exosomes are a promising regenerative tool for DPC in cases of small pulp exposure or for whole-pulp tissue regeneration.

• 환경영향평가
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• 제20권4호
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• pp.497-507
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• 2011

This research studied human health risk assessment of benzene from industrial complexes of Chungcheong Province (Seosan industrial complex) and Jeonla Province (Iksan industrial complex and Yeosoo industrial complex). The residents near the industrial complexes areas can be often exposed to volatile organic compounds (e.g., benzene, toluene, xylenes) through a number of exposure pathways, including inhalation of the organic pollutant via various environmental matrices (air, water and soil), contaminated water, and soil intake. Benzene is well known to be a common carcinogenic and toxic compound that is produced from industrial and oil refinery complexes. In this study, a number of samples from water, air, and soil were taken from the residential settings and public school zones located near the industrial complex sites. Based on the carcinogenic risk assessment, the risk estimates were slightly above $10{\times}10^{-6}$ at all three industrial sites. According to deterministic risk assessment, inhalation was the most important route. The distribution of benzene in the environment would be dependent on vapor pressure, and the physical property influencing the extent of the potential risks. Non-carcinogenic risk assessment of benzene shows that the values of Hazard Index(HI) were much lower than 1.0 at all industrial complexes. Therefore, benzene was not a cause of concern in terms of non-carcinogenic risk posed to the residents near the sites. When compared to probabilistic risk assessment, the CTE(central tendency exposure) cancer risk values of deterministic risk assessment were close to the mean values predicted by the probabilistic risk assessment. The RME(reasonable maximum exposure) values fell within the range of 95% to 99.9% estimated by the probabilistic risk assessment. Since the values of carcinogenic risk assessment were higher than $10{\times}10^{-6}$, further detailed monitoring and refined risk assessment for benzene may be warranted to estimate more reliable and potential inhalation risks to receptors near the industrial complexes.

• 생명과학회지
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• 제20권3호
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• pp.356-364
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• 2010

본 연구는 비교적 청정한 지역인 춘천시에 거주하는 일반인 모유 중 PBDEs의 노출 경로를 확인하기 위해 처음으로 시도된 연구이다. 본 연구지역의 모유 중 ${\sum}PBDEs$의 수준은 북아메리카지역에 비하여 낮은 수준이었으나 일부 아시아, 유럽국가와 유사하였다. 모유 내 PBDEs의 축적은 산모의 특성과 상관관계가 나타나지 않았으나, 상엽용 PBDEs 제품을 포함하여 여러 복합적 인자에 의하여 노출되고 있었으며, 식품 섭취와 같은 식이노출은 한국인에 있어 중요한 노출 경로의 하나로 판단되었다. 따라서 본 연구 결과는 한국인의 PBDEs 노출 경로 파악에 중요한 정보를 제공하여, 장차 PBDEs 및 관련 브롬계 난연제의 노출에 따른 인체 위해성 평가를 수행함에 있어 중요한 참고자료가 될 것이다. 또한, 한국 내의 PBDEs에 대한 인체노출 경로를 명확하게 하기 위한 연구는 계속적으로 이루어져야 할 것이다.

• 한국수자원학회논문집
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• 제55권6호
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• pp.421-435
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• 2022

기후변화로 인해 자연재해의 빈도가 증가하고 있어 미래 기후변화 시나리오를 바탕으로 가뭄 영향을 평가 및 전망하고 가뭄 위험도 감소를 위한 기후변화 적응 대책이 필요하다. 가뭄 위험도(risk)를 평가하기 위해서는 기후 요소뿐만 아니라 가뭄 발생 지역의 사회·경제적인 요소들 또한 고려해야 한다. 따라서 본 연구에서는 IPCC의 재난 위험도 분석 프레임워크에 따라 가뭄 위험도 평가 요소를 위해성(Hazard), 노출도(Exposure), 취약성(Vulnerability)으로 나누고 이에 맞는 각 지표를 선정하여 우리나라 중권역 단위의 가뭄 위험도를 정량화하였다. 미래 가뭄 위험도 평가를 위해 근 미래(2030-2050년)와 먼 미래(2080년-2099년)에 대해 기후변화 시나리오(RCP 2.6, RCP 8.5)와 사회경제 시나리오(SSP1, SSP2, SSP3)를 조합하여 가뭄 위험도를 살펴보고 이를 과거(1986-2005년)와 비교·분석하였다. 미래 시나리오에 따른 가뭄 위험도는 시간에 따라 전 유역에 걸쳐 먼 미래에 크게 상승하였다. 그리고 가뭄 위험도의 각 요소별 기여도와 순위 분석을 통해 미래 가뭄 위험도 상승에 대해 가뭄 위해성의 기여도가 전반적으로 크고, 유역별로 상승 요인이 다르다는 것을 확인했다. 이에 미래 기후변화 시나리오에 따른 유역별 해결 방안을 제시하여 향후 가뭄대책 수립을 위한 정책에 기반이 될 수 있도록 하였다.

• Toxicological Research
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• 제8권2호
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• pp.343-357
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• 1992

Tumor necrosis factor-${\alpha}$(TNF), a polypeptide hormone secreted primarily by activated macrophages, was originally identified on the basis of its ability to cause hemorrhagic necrosis and tumor regression in vivo. Subsequently, TNF has been shown to be an important component of the host responses to infection and cancer and may mediate the wasting syndrome known as cachexia. These systemic actions of TNF are reflected in its diverse effects on target cells in vitro. TNF initiates its diverse cellular actions by binding to specific cell surface receptors. Although TNF receptors have been identified on most of animal cells, regulation of these receptors and the mechanisms which transduce TNF receptor binding into cellular responses are not well understood. Therefore, in the present study, the mechanisms how TNF receptors are being regulated and how TNF receptor binding is being transduced into cellular responses were investigated in rat liver plasma membranes (PM) and ME-180 human cervical carcinoma cell lines. $^{125}I$-TNF bound to high ($K_d=1.51{\pm}0.35nM$)affinity receptors in rat liver PM. Solubilization of PM with 1% Triton X-100 increased both high affinity (from $0.33{\pm}0.04\;to\;1.67{\pm}0.05$ pmoles/mg protein) and low affinity (from $1.92{\pm}0.16\;to\;7.57{\pm}0.50$ pmoles/mg protein) TNF binding without affecting the affinities for TNF, suggesting the presence of a large latent pool of TNF receptors. Affinity labeling of receptors whether from PM or solubilized PM resulted in cross-linking of $^{125}I$-TNF into $M_r$ 130 kDa, 90 kDa and 66kDa complexes. Thus, the properties of the latent TNF receptors were similar to those initially accessible to TNF. To determine if exposure of latent receptors is regulated by TNF, $^{125}I$-TNF binding to control and TNF-pretreated membranes were assayed. Specific binding was increased by pretreatment with TNF (P<0.05), demonstrating that hepatic PM contains latent TNF receptors whose exposure is promoted by TNF. Homologous up-regulation of TNF receptors may, in part, be responsible for sustained hepatic responsiveness during chronic exposure to TNF. As a next step, the post-receptor events induced by TNF were examined. Although the signal transduction pathways for TNF have not been delineated clearly, the actions of many other hormones are mediated by the reversible phosphorylation of specific enzymes or target proteins. The present study demonstrated that TNF induces phosphorylation of 28 kDa protein (p28). Two dimensional soidum dodecyl sulfate-polyacrylamide gel electrophoresis(SDS-PAGE) resolved the 28kDa phosphoprotein into two isoforms having pIs of 6.2 and 6.1. The pIs and relative molecular weight of p28 were consistent with those of a previously characterized mRNA cap binding protein. mRNA cap binding proteins are a class of translation initiation factors that recognize the 7-methylguanosine cap structure found on the 5' end of eukaryotic mRNAs. In vitro, these proteins are defined by their specific elution from affinity columns composed of 7-methylguanosine 5'-triphosphate($m^7$GTP)-Sepharose. Affinity purification of mRNA cap binding proteins from control and TNF treated ME-180 cells proved that TNF rapidly stimulates phosphorylation of an mRNA cap binding protein. Phosphorylation occurred in several cell types that are important in vitro models of TNF action. The mRNA cap binding protein phosphorylated in response to TNF treatment was purifice, sequenced, and identified as the proto-oncogene product eukaryotic initiation factor-4E(eIF-4E). These data show that phosphorylation of a key component of the cellular translational machinery is a common early event in the diverse cellular actions of TNF.

• 자원환경지질
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• 제38권5호
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• pp.535-545
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• 2005

본 연구에서는 폐금속광산 지역에서의 비소가 인체에 미치는 위해영향을 정량적으로 평가하기 위하여 동일, 옥동, 동정, 도곡 및 화천광산 주변 지역에서 광미, 토양, 농작물 및 지하수를 채취하여 화학분석을 실시하였다. 이들 폐금속광산 주변에 폐기된 광미내 비소 함량은 매우 높게 나타났으며, 이러한 광미가 바람이나 강우에 의해 광미댐 하부에 있는 농경지나 하천으로 유입되어 주변 환경을 오염시킬 가능성이 크므로 이들 토양, 농작물, 자연수 시료들에 대한 화학분석자료를 바탕으로 인체위해성평가 모델링을 실시하였다. 폐금속광산 지역에서의 인체노출경로는 농사활동을 통한 토양의 섭취, 지하수(식수)의 섭취, 쌀의 섭취, 농사활동에 의한 토양의 피부접촉, 목욕에 의한 지하수의 피부접촉 등 5가지로 파악할 수 있었다. 각 노출경로별 비발암성위해도 평가 결과, 모든 광산에서 지하수를 식수로 섭취하는 노출경로와 쌀의 섭취를 통해 비소의 독성위해도가 가장 높은 것으로 나타났다. 특히, 동일광산과 옥동광산에서는 HI지수가 7.0 이상으로, 화천광산의 경우는 5.0 이상으로 매우 높게 나타나 이들 지역 주민들의 비소의 독성위해성이 높았다. 비소에 대한 발암위해도 평가 결과, 동일광산, 옥동광산 및 화천광산 지역의 쌀 섭취의 노출경로를 통한 비소에 의해 암이 발생할 확률은 만명중의 5명에서 8명 정도로 높게 나타났다. 지하수를 식수로 섭취하는 경우, 비소의 발암위해도도 이들 광산지역에서 만명중의 1명보다 높게 나타났다. 이는 미국 EPA에서 제시한 초과발암위해도보다도 크므로 이들 지역 주민들이 비소에 의해 오염된 농작물(쌀)이나 지하수를 식수로 지속적으로 장기간 섭취하게 된다면 비소가 건강에 미치는 위해영향이 크다고 판단된다.warfarin 용량 조절에 유용할 것으로 생각된다.대한 치료 순응도가 높아졌다. 후 동율동 전환율이나 좌심방 수축능 회복에 좋은 결과를 보여주었다 그러나 향후 대상환자들에 대한 중장기적인 추적 관찰이 필요하리라 생각한다.pm1.6$일째에 관상동맥조영술을 시행하여 모든 도관의 개존율$(100\%=57/57)$을 확인하였다 수술 전 중재 술을 시행한 1개소에서는 중재술 부위의 재협착소견이 보여 수술 후 조영술시 재풍선확장술로 치료하였다. 수술 후 추적관찰(평균 $25\pm26$개월)동안 1예에서 심부전으로 사망하였다. 생존한 환자 24예에서 술 후 평균 $9.6\pm3$개월째에 관상동맥조영술을 시행하였고 이식도관이 string 징후를 보인 1예를 제외하고 모두 개존(56/57)되어 있었으며, 약물용출형 스탠트를 시행하기 이전의 12예의 중재술 중 2예에서 $50\%$ 이상의 스텐트 협착이 있었으나 흉통의 재발은 없었다. 결론: 하이브리드 관상동맥 우회 술은 수술위험도를 낮추기 위하여 최소절개 관상동맥우회술과 병합하여 시도될 수 있을 뿐 아니라, 선택적 환자들에서는 정중 흉골절개 관상동맥우회술과 병합하여 수술관련 유병률을 낮추고 심근의 완전 재관류화를 도모할 수 있었다.호도에서 가장 적절한 방법으로 사료된다.비위생 점수가 유의적으로 높은 점수를 나타내었다. 조리종사자의 위생지식 점수와 위생관리 수행수준의 상관관계를 조사한 결과, 위생지식의 기기설비위생은 위생관리 수행수준의 합계(p<0.01)에서 유의적인 상관관계(p<0.01)를 나타내었으며, 위생지식의 식중독 및 미생물은 위생관리 수행수준의 개인위생(p<0.01)과 유의적인

• 대한의생명과학회지
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• 제9권4호
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• pp.241-248
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• 2003

Sodium salicylate, a plant stress hormone that plays an important role(s) in defenses against pathogenic microbial and herbivore attack, has been shown to induce a variety of cell responses such as anti-inflammation, cell cycle arrest and apoptosis in animal cells. p38MAPK plays a critical role(s) in the cell regulation by sodium salicylate. However, the signal pathway for sodium salicylate-induced p38MAPK activation is yet unclear. In this study, we show that although sodium salicylate enhances reactive oxygen species (ROS) production, N-acetyl-L-cysteine, a general ROS scavenger, did not prevent sodium salicylate-induced p38MAPK, indicating ROS-independent activation of p38MAPK by sodium salicylate. Sodium salicylate-activated p38MAPK appeared to be very rapidly down-regulated 2 min after removal of sodium salicylate. Interestingly, sodium salicylate-pretreated cells remained fully responsive to re-induction of p38MAPK activity by a second sodium salicylate stimulation or by other stresses, $H_2O$$_2$ and methyl jasmonate (MeJA), thereby indicating that sodium salicylate does not exhibit both homologous and heterologous desensitization. In contrast, pre-exposure to MeJA, $H_2O$$_2$, heat shock, or hyperosmotic stress reduced the responsiveness to subsequent homologous stimulation. Sodium salicylate was able to activate p38MAPK in cells desensitized by other heterologous p38MAPK activators. These results indicate that there is a sensing mechanism highly specific to sodium salicylate for activation of p38MAPK, distinct trom pathways used by other stressors such as MeJA, $H_2O$$_2$ heat shock, and hyperosmotic stress.