The Synergistic Bactericidal Mechanism of Simultaneous Treatment with a 222-Nanometer Krypton-Chlorine Excilamp and a 254-Nanometer Low-Pressure Mercury Lamp

Kang, Jun-Won,Kang, Dong-Hyun American Society for Microbiology 2019 Applied and environmental microbiology Vol.85 No.1

<P>Contamination of pathogenic microorganisms in water plays an important role in inducing outbreaks of food-borne illness by causing cross-contamination in foods. Thus, proper disinfection of water before use in food production is essential to prevent outbreaks of food-borne illness. As technologies capable of selecting UV radiation wavelengths (such as UV-LEDs and excilamps) have been developed, wavelength combination treatment with UV radiation, which is widely used in water disinfection systems, is actively being studied. In this regard, we have confirmed synergistic bactericidal effects in combination with 222-nm and 254-nm wavelengths and have identified mechanisms for this. This study clearly analyzed the mechanism of synergistic bactericidal effect by wavelength combination treatment, which has not been attempted in other studies. Therefore, it is also expected that these results will play an important role as baseline data for future research on, as well as industrial applications for, the disinfection strategy of effective wavelength combinations.</P><P>The purpose of this study was to investigate the synergistic bactericidal effect of 222-nm KrCl excilamp and 254-nm low-pressure (LP) Hg lamp simultaneous treatment against <I>Escherichia coli</I> O157:H7, <I>Salmonella enterica</I> subsp. <I>enterica</I> serovar Typhimurium, and <I>Listeria monocytogenes</I> in tap water and to identify the synergistic bactericidal mechanism. Sterilized tap water inoculated with pathogens was treated individually or simultaneously with a 254-nm LP Hg lamp or 222-nm KrCl excilamp. Overall, for all pathogens, an additional reduction was found compared to the sum of the log unit reductions of the individual treatments resulting from synergy in the simultaneous treatment with both kinds of lamps. In order to identify the mechanism of this synergistic bactericidal action, the form and cause of membrane damage were analyzed. Total reactive oxygen species (ROS) and superoxide generation as well as the activity of ROS defense enzymes then were measured, and the overall mechanism was described as follows. When the 222-nm KrCl excilamp and the 254-nm LP Hg lamp were treated simultaneously, inactivation of ROS defense enzymes by the 222-nm KrCl excilamp induced additional ROS generation following exposure to 254-nm LP Hg lamp (synergistic) generation, resulting in synergistic lipid peroxidation in the cell membrane. As a result, there was a synergistic increase in cell membrane permeability leading to a synergistic bactericidal effect. This identification of the fundamental mechanism of the combined disinfection system of the 222-nm KrCl excilamp and 254-nm LP Hg lamp, which exhibited a synergistic bactericidal effect, can provide important baseline data for further related studies or industrial applications in the future.</P><P><B>IMPORTANCE</B> Contamination of pathogenic microorganisms in water plays an important role in inducing outbreaks of food-borne illness by causing cross-contamination in foods. Thus, proper disinfection of water before use in food production is essential to prevent outbreaks of food-borne illness. As technologies capable of selecting UV radiation wavelengths (such as UV-LEDs and excilamps) have been developed, wavelength combination treatment with UV radiation, which is widely used in water disinfection systems, is actively being studied. In this regard, we have confirmed synergistic bactericidal effects in combination with 222-nm and 254-nm wavelengths and have identified mechanisms for this. This study clearly analyzed the mechanism of synergistic bactericidal effect by wavelength combination treatment, which has not been attempted in other studies. Therefore, it is also expected that these results will play an important role as baseline data for future research on, as well as industrial applications for, the disinfection strategy of effective wavelength combinations.</P>

UVB로 손상된 피부 섬유아세포에서 병풀과 배초향의 보호작용에 대한 상승효과

김민하,이승준,허희진,정종욱,성지혜,정헌상,이준수 한국식품영양과학회 2022 한국식품영양과학회지 Vol.51 No.7

Ultraviolet B (UVB) irradiation is a major cause of the photoaging of human skin. Centella asiatica (CA) has been used as an effective anti-photoaging agent, mainly because it increases type Ⅰ collagen levels. On the other hand Agastache rugosa (AR) is a source of bioactive compounds that protect human skin fibroblasts against UVB irradiation by restoring the antioxidant defense. In this study, we investigated the synergistic protective effects of CA and AR in combination (CA-AR) against UVB-induced damage in human skin fibroblasts (Hs68 cells). Cell viabilities and protective effects were examined using an MTT assay with or without UVB irradiation (30 mJ/cm2). CA, AR, and CA-AR did not have a cytotoxic effect. The synergistic effects of CA and AR were analyzed using combination indices (CI) and isobologram models, and the optimal CA to AR ratio was 3:7. CA, AR, and CA-AR 3:7 increased cell viability by 87%, 80%, and 98%, respectively in UVB irradiated Hs68 cells, and at this ratio. CA-AR 3:7 had CI values ranging from 0.03 to 0.41 and was 71∼97% more effective than CA or AR alone against UVB-induced photoaging. These results suggest that the CA-AR combination has potential use in functional foods and cosmeceutical preparations.

SNA를 이용한 NCW 시너지효과요소의 정량화에 관한 연구

정치영,강성진 한국국방경영분석학회 2012 한국국방경영분석학회지 Vol.38 No.1

NCW offers BSEs(Battelspace-Entities) the capabilities of sharing information through C4ISR network and it also improves their combat powers based on information superiority with awareness of common situation in battlefield and self-synchronization. Although the concept of NCW was developed at the end of 1990 and there were various studies for NCW from the development of its concept, the effort for measuring the synergistic effect of NCW is insufficient at the present time. Therefore, in this paper we reviewed literatures concerning the effectiveness measurement of NCW and identified NCW's synergistic effectiveness factors to measure the synergistic effectiveness. We also proposed quantification functions that could quantify the NCW's synergistic effectiveness factors using SNA. The result we proposed in this paper is primary tasks to quantify the NCW's synergistic effectiveness, so it will contribute to the successful realization of NCW in the future.

Lipopolysaccharide로 유도된 RAW264.7 세포에서 발효도라지추출물의 항염증 상승효과 물질 탐색

송희원,이소연,한은혜,유희종,임미경 한국식품영양과학회 2019 한국식품영양과학회지 Vol.48 No.2

The root extracts of Platycodon grandiflorum (PG) have been widely used as a phlegm-relieving herb. Platycodin D, derived from the root of P. grandiflorum, is known as an effective ingredient and possesses a variety of pharmacological effects such as anti-asthma, anti-inflammation, anti-obesity, anti-cancer, antimicrobial and immunomodulatory activities. This study aimed to find substances that could have an additive or synergistic effect on anti-inflammatory activities when combined with fermented P. grandiflorum extracts (FPG) containing increased platycodin D contents due to fermentation. Nitric oxide (NO) assays were performed using 14 natural product extracts, 6 minerals, and 11 vitamins. Among them, four substances, namely tartary buckwheat extracts, angelica (root) complex extracts, soybean extracts, and vitamin C, were selected for combination with FPG. As a result, soybean extracts and vitamin C exhibited additive or synergistic anti-inflammatory effects in combinatorial treatment with FPG, whereas tartary buckwheat extracts and angelica complex extracts did not exert synergistic effects. The combinatorial treatment of 200 μg/mL of FPG with soybean extracts or vitamin C inhibited NO production in LPS-stimulated RAW264.7 cells by 85.5%, and 76.3%, respectively, compared to treatment with FPG alone. In addition, combinatorial treatment of FPG with tartary buckwheat extracts or angelica complex extracts did not affect cell viability, however combinatorial treatment of 1,600 μg/mL of FPG with soybean extracts or vitamin C reduced cell viability. Therefore, these findings may be used as a basis for developing products with enhanced anti-inflammatory functionality using fermented P. grandiflorum extracts. 도라지(Platycodon grandiflorum)는 우리나라 및 중국, 일본에서 자생하고 있는 다년생 초본류로서 항염, 천식, 항비만, 항암, 고지혈증 개선, 피부염 개선 등 다양한 효능을 보유하고 있으며, 예로부터 약용 및 식용으로 널리 이용되었다. 본 연구에서는 도라지를 이용한 건강식품 개발의 효율성을 높이기 위하여 도라지의 유효성분으로 알려진 platycodin D 함량을 높이고, 도라지추출물과 혼합하여 상가・상승효과를 낼 수 있는 물질을 발굴하고자 하였다. 따라서 본 연구에서는 14종의 천연물 추출물과 6종의 미네랄, 11종의 비타민에 대한 NO 생성 억제능을 확인하였으며, 이로부터 대두추출물, 달단메밀추출물, 당귀등복합추출물, 비타민 C 4종을 선별하였다. 이들을 발효를 통해 platycodin D 함량이 4배 증가한 발효도라지추출물과 조합하여 RAW264.7 세포에 농도별로 처리하여 LPS에 의해 유도된 NO를 생성 억제율을 측정하였다. 실험 결과 대두추출물과 비타민 C는 발효도라지추출물 200, 400 μg/mL와 조합한 농도에서 발효도라지추출물 단독 처리군 대비 각각 85.5%, 79.3%, 76.3%, 60.9% 증가한 NO 생성 억제율을 보여 발효도라지추출물과 대두추출물 또는 비타민 C의 복합물에 의한 상승효과를 확인할 수 있었다. 반면에 달단메밀추출물은 발효도라지추출물과 상승・상가효과는 보이지 않았으며, 당귀등복합추출물의 경우에는 NO 생성 억제 효능이 1,600 μg/mL 농도의 발효도라지추출물에서만 38.8% 증가하였다. 또한 MTT assay를 수행하여 발효도라지추출물과 대두추출물, 달단메밀추출물, 당귀등복합추출물, 비타민 C 복합물에 의한 세포생존율을 확인한 결과 발효도라지추출물과 달단메밀추출물, 당귀등복합추출물의 조합에서는 세포생존율에 영향을 미치지 않았으나, 발효도라지추출물 1,600 μg/mL 농도에서 대두추출물과 비타민 C와의 복합물에서 세포생존율이 각각 71.8%, 82.9%로 감소하였다. 따라서 발효도라지추출물 농도는 최소한 1,600 μg/mL 이하로 설정하되, 200~400 μg/ mL의 발효도라지추출물과 1 mg/mL의 대두추출물 또는 100 μg/mL의 비타민 C와의 조합이 항염작용의 상가・상승효과를 낼 수 있는 최적의 조합으로 생각된다. 이러한 연구 결과는 기능성이 증진된 제품 개발을 위한 기초자료로 활용될 수 있을 것으로 생각된다.

Mevalocidin과 Clomazone 혼합물의 경엽처리시 제초활성 발현특성

김진석,김보관,최정섭,김은애,김재덕,고영관 한국잔디학회 2022 Weed & Turfgrass Science Vol.11 No.2

This study was conducted to know that how the herbicidal interactions and its characteristics were exhibited in various plants, when the clomazone inhibiting the non-mevalonate pathway in chloroplast was mixture-treated with the mevalocidin which was supposed to inhibit the mevalonate pathway in cytoplasm. The herbicidal activity of mevalocidin in Lemna paucicostata, which its major symptoms were frond disorganization, membrane breakdown and necrosis (grey colorization), was not significantly increased or decreased by the clomazone inducing the whitening and growth inhibition, showing an interaction near additive effect. In the case of foliar treatment to various plants, the herbicidal interactions of two herbicide were different according to plant species and herbicidal symptoms. For example, synergistic effect was occurred in Echinochloa spp. and Panicum dichotomiflorum, additive effect in Orysa sativa, and antagonistic effect in Solanum nigrum and Calystegia japonica. Particularly the degree of synergistic interaction in Echinochloa spp. was higher in the condition of vigorous growth (in a higher growth temperature) than in relatively lower growth. On the other hand, synergistic effect was occurred in wilting and desiccation, additive effect in whitening, and antagonistic effect in growth inhibition. In average, the mixture of clomazone and mevalocidin did not increase the total herbicidal efficacy as much as expected, but tended to broaden the herbicidal spectrum. In this experiment, various interactions observed differently according to plant species and herbicidal symptoms would be related to chemical absorption, translocation, metabolism, binding affinity at action sites, cross-talks of metabolic biosynthesis pathway in cell, cultural environmental factors, and so on. Therefore, an additional research would be needed for clarifying the underlying interaction mechanisms. 본 연구는 엽록체내의 non-mevalonate 생합성 경로를 저해한다고 알려진 clomazone과 세포질의 mevalonate 생합성 경로를 저해하는 것으로 추정되는 mevalocidin을 혼합처리 했을 때, 여러 식물종에서 어떠한 상호작용과 제초활성의 발현특징을 가지는지 알아보기 위하여 수행되었다. 좀개구리밥(Lemna paucicostata)에 혼합처리 하였을 때, mevalocidin에 의한 엽상체 해체, 막파괴 및 괴사(회색) 등의 제초활성은 백화와 생육저해를 일으키는 clomazone처리에 의해 상승되거나경감되지는 않았고 거의 독립적으로 작용하는 특징을 보였다. 온실에서의 경엽처리 경우엔 두 약제간의 상호작용성이식물종간 또는 제초증상별로 다르게 나타나는 복잡성을 보였다. 식물종의 경우 피와 미국개기장의 제초활성에는 상승작용, 벼에 대해서는 상가작용, 까마중과 메꽃에 대해서는 길항작용을 나타냈다. 특히 피의 경우엔 생육온도가 상대적으로 낮은 조건보다는 높은 조건에서 상승작용이 보다 증가되는 경향이었다. 제초증상의 경우, 경엽 위조고사 작용에대해서는 상승작용, 백화증상에 대해서는 길항작용, 생육억제에 대해서는 독립작용을 나타내는 경향을 보였다. 전반적으로 두 화합물간의 혼합처리에 의해서 제초활성 스펙트럼은 넓어지는 경향이 관찰되었으나 종합적인 제초활성에 있어서는 기대보다 현저히 증진되지는 않았다. 이러한 다양한 상호작용들이 관찰되는 원인들에 대해서는 화합물 측면에서의 흡수, 이행, 대사, 작용점에서의 결합능력, 식물체내 생합성 경로간의 상호작용, 재배환경 등 여러 요인과 연계되어 있을 것으로 간주되며 보다 정확한 원인파악을 위해서는 추가연구가 필요할 것으로 사료된다.

Nootkatone, an AMPK activator derived from grapefruit, inhibits KRAS downstream pathway and sensitizes non-small-cell lung cancer A549 cells to adriamycin

Hung, Le Van Manh,Moon, Jeong Yong,Ryu, Ji-yeon,Cho, Somi Kim Elsevier 2019 Phytomedicine Vol.63 No.-

<P><B>Abstract</B></P> <P><B>Background</B></P> <P>Non-small-cell lung cancer (NSCLC) accounts for approximately 85% of all lung cancer cases and it is intrinsically resistant to anticancer drugs. Nootkatone (NKT), which is the main fragrant component of grapefruit, has been identified as a bioactive compound with a wide range of beneficial applications. NKT can activate AMP-activated protein kinase (AMPK) in liver and muscle cells, however, little is known about the role of NKT in cancer, particularly its role in NSCLC with high rates of liver kinase B1 (LKB1) and KRAS mutations.</P> <P><B>Purpose</B></P> <P>The anti-cancer activities of NKT in NSCLC A549 cells and ADR-resistant A549/ADR cells were investigated and compared to those of metformin, an AMPK activator that is used clinically as an AMPK activator.</P> <P><B>Methods</B></P> <P>Cell viability, proliferation and NKT sensitization were determined by the MTT assay. Mechanisms of NKT against anti-cancer activities including AMPK activation, cell cycle arrest, and synergistic cytotoxic effect were evaluated by Western blot analysis, and flow cytometry. In <I>in vivo</I> experiments, athymic BALB/c male nude mice were used for experiments. After the successful generation of tumor models through subcutaneous injection of A549/ADR cells, NKT and/or ADR were administered and mice were kept for weekly measurements for up to 7 weeks. The animals were then sacrificed, and the tumors were removed from all animals and weighed.</P> <P><B>Results</B></P> <P>NKT activated AMPK via LKB1-independent and CAMKK2-dependent pathways, leading to inhibition of cell growth and induction of G1 cell arrest. The effect of NKT is comparable but superior to that of metformin, an AMPK activator in clinical use. Importantly, NKT inhibited the activation of oncogenic AKT and ERK proteins, while metformin inhibited AKT but failed to impact ERK, the major oncogenic protein of NSCLC cells with KRAS mutation. The synergistic activity of NKT and ADR was more effective than that of metformin and ADR. <I>In vivo</I> data confirmed synergistic effects of NKT and ADR without systemic side effects.</P> <P><B>Conclusion</B></P> <P>We demonstrate for the first time that NKT can sensitize ADR-resistant A549/ADR cells to ADR <I>in vitro</I> and <I>in vivo.</I> Metformin, on the other hand, failed to show any synergistic effect with ADR in A549/ADR cells.</P> <P><B>Graphical abstract</B></P> <P>[DISPLAY OMISSION]</P>

pH-Responsive Assembly of Gold Nanoparticles and “Spatiotemporally Concerted” Drug Release for Synergistic Cancer Therapy

Nam, Jutaek,La, Wan-Geun,Hwang, Sekyu,Ha, Yeong Su,Park, Nokyoung,Won, Nayoun,Jung, Sungwook,Bhang, Suk Ho,Ma, Yoon-Ji,Cho, Yong-Min,Jin, Min,Han, Jin,Shin, Jung-Youn,Wang, Eun Kyung,Kim, Sang Geol,Ch American Chemical Society 2013 ACS NANO Vol.7 No.4

<P>A challenge in using plasmonic nanostructure–drug conjugates for thermo–chemo combination cancer therapy lies in the huge size discrepancy; the size difference can critically differentiate their biodistributions and hamper the synergistic effect. Properly tuning the plasmonic wavelength for photothermal therapy typically results in the nanostructure size reaching ∼100 nm. We report a new combination cancer therapy platform that consists of relatively small 10 nm pH-responsive spherical gold nanoparticles and conjugated doxorubicins. They are designed to form aggregates in mild acidic environment such as in a tumor. The aggregates serve as a photothermal agent that can selectively exploit external light by their collective plasmon modes. Simultaneously, the conjugated doxorubicins are released. The spatiotemporal concertion is confirmed at the subcellular, cellular, and organ levels. Both agents colocalize in the cell nuclei. The conjugates accumulate in cancer cells by the rapid phagocytic actions and effective blockage of exocytosis by the increased aggregate size. They also effectively accumulate in tumors up to 17 times over the control because of the enhanced permeation and retention. The conjugates exhibit a synergistic effect enhanced by nearly an order of magnitude in cellular level. The synergistic effect is demonstrated by the remarkable reductions in both the therapeutically effective drug dosage and the photothermal laser threshold. Using an animal model, effective tumor growth suppression is demonstrated. The conjugates induce apoptosis to tumors without any noticeable damage to other organs. The synergistic effect <I>in vivo</I> is confirmed by qRT-PCR analysis over the thermal stress and drug-induced growth arrest.</P><P><B>Graphic Abstract</B> <IMG SRC='http://pubs.acs.org/appl/literatum/publisher/achs/journals/content/ancac3/2013/ancac3.2013.7.issue-4/nn400223a/production/images/medium/nn-2013-00223a_0008.gif'></P><P><A href='http://pubs.acs.org/doi/suppl/10.1021/nn400223a'>ACS Electronic Supporting Info</A></P>

Synergistic versus Additive Effect of Active Molecular Chitosan with Biochemical Compounds of Sorghum bicolor

( Da Gyung Lee ),( Jhulee Park ),( Hae Jung Yoo ),( Seo Ju Oh ),( Joo Young Jang ),( Shaheen Amna ),( Jae Kweon Park ) 한국키틴키토산학회 2016 한국키틴키토산학회지 Vol.21 No.3

The synergistic or additive effect of active molecular chitosan (AMC) with Sorghum bicolor ethanol extract (ES) and fermentative supernatant was invesigated in this study. ES had 29% less content of phenolic compounds, 78% less contents of total carbohydrates containing reducing sugars, and 56% less tannin contents than that of S. bicolor fermentative supernatant (SF). It has shown the significantly higher antioxidant activity than SF and other fermantative substances (S and Y). These results suggest that flavonoid in the ES may be the key molecule as it contains 28% higher concentration of flavonoids than SF and Y substances and hence ES showed the remarkablely higher specific activity of whitenning effect. Further more SF was selected for heat stability studies, tyrosinase inhibitory, and antibacterial activity in the presence or absence of active molecular chitosan (AMC). Although less significant synergistic antibacterial activity of SF toward Candida albicans in the presence of AMC was observed, both substances still can be useful as antioxidant or whitenning substances in combination with AMC. whereas a strong antibacterial activity of AMC toward Candica albicans was observed, and also is one of the ingredients in functional food and cosmaceutical compounds with potential health-promoting properties.

Effect of Gas Bubbles on the Recovery Efficiency of Paclitaxel from Biomass of Taxus chinensis in Ultrasonic Extraction

전효진,김진현 한국생물공학회 2023 Biotechnology and Bioprocess Engineering Vol.28 No.4

The synergistic effect of introducing both ultrasonic cavitation bubbles and gas bubbles to the extraction of paclitaxel from Taxus chinensis biomass was investigated. The addition of gas bubbles to ultrasonic extraction significantly improved the extraction efficiency, confirming that ultrasonic cavitation bubbles and gas bubbles have a synergistic effect. Furthermore, an ultrasonic power of 250 W and a gas flow rate of 1.750 L/min could recover up to 94% of the paclitaxel from the biomass. In addition, as the ultrasonic power and gas flow rate increased, the extraction rate constant, the effective diffusion coefficient, and the mass transfer coefficient also increased. The efficiency of paclitaxel extraction was improved by the efficient crushing of the biomass facilitated by the synergistic effect of the ultrasonic cavitation bubbles and the gas bubbles.

Synergistic Effect of the Novel Benzochalcone Derivative DK-78 and Doxorubicin on MCF7-VN Breast Cancer Stem Cells

조문제,박상규,김소미,고동수 한국응용생명화학회 2013 Applied Biological Chemistry (Appl Biol Chem) Vol.56 No.5

Several naturally occurring or synthesized forms of chalcone have been shown to possess multiple biological properties,including antitumor activities. A novel synthetic flavonoid, the benzochalcone derivative DK-78, was administered with the anticancer drug doxorubicin to two breast cancer cell lines (MCF7-VN and MDA-MB-231), and was evaluated for a synergistic cytotoxic effect. DK-78 reduced the expression of mesenchymal marker proteins and reduced cell migration and attachment. Sequential treatment with DK-78 and doxorubicin showed synergistic effects.