• Nutrition Research and Practice
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• 제14권5호
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• pp.478-489
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• 2020

BACKGROUND/OBJECTIVES: Morusin, a marker component of Morus alba L., possesses anti-cancer activity. The objective of this study was to determine autophagy-inducing effect of morusin in non-small cell lung cancer (NSCLC) cells and investigate the underlying mechanism. SUBJECTS/METHODS: Autophagy induction and the expression of autophagy-related proteins were analyzed by LC3 immunofluorescence and western blot, respectively. The role of autophagy and AMP-activated protein kinase (AMPK) was determined by treating NSCLC cells with bafilomycin A1, an autophagy inhibitor, and compound C, an AMPK inhibitor. Cytotoxicity and apoptosis induction were determined by MTT assay, trypan blue exclusion assay, annexin V-propidium iodide (PI) double staining assay, and cell cycle analysis. RESULTS: Morusin increased the formation of LC3 puncta in the cytoplasm and upregulated the expression of autophagy-related 5 (Atg5), Atg12, beclin-1, and LC3II in NSCLC cells, demonstrating that morusin could induce autophagy. Treatment with bafilomycin A1 markedly reduced cell viability but increased proportions of sub-G1 phase cells and annexin V-positive cells in H460 cells. These results indicate that morusin can trigger autophagy in NSCLC cells as a defense mechanism against morusin-induced apoptosis. Furthermore, we found that AMPK and its downstream acetyl-CoA carboxylase (ACC) were phosphorylated, while mammalian target of rapamycin (mTOR) and its downstream p70S6 kinase (p70S6K) were dephosphorylated by morusin. Morusin-induced apoptosis was significantly increased by treatment with compound C in H460 cells. These results suggest that morusin-induced AMPK activation could protect NSCLC cells from apoptosis probably by inducing autophagy. CONCLUSIONS: Our findings suggest that combination treatment with morusin and autophagy inhibitor or AMPK inhibitor might enhance the clinical efficacy of morusin for NSCLC.

• Journal of Korean Neurosurgical Society
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• 제67권1호
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• pp.94-102
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• 2024

Objective : The spontaneous intracerebral hemorrhage (ICH) remains a significant cause of mortality and morbidity throughout the world. The purpose of this retrospective study is to develop multiple models for predicting ICH outcomes using machine learning (ML). Methods : Between January 2014 and October 2021, we included ICH patients identified by computed tomography or magnetic resonance imaging and treated with surgery. At the 6-month check-up, outcomes were assessed using the modified Rankin Scale. In this study, four ML models, including Support Vector Machine (SVM), Decision Tree C5.0, Artificial Neural Network, Logistic Regression were used to build ICH prediction models. In order to evaluate the reliability and the ML models, we calculated the area under the receiver operating characteristic curve (AUC), specificity, sensitivity, accuracy, positive likelihood ratio (PLR), negative likelihood ratio (NLR), diagnostic odds ratio (DOR). Results : We identified 71 patients who had favorable outcomes and 156 who had unfavorable outcomes. The results showed that the SVM model achieved the best comprehensive prediction efficiency. For the SVM model, the AUC, accuracy, specificity, sensitivity, PLR, NLR, and DOR were 0.91, 0.92, 0.92, 0.93, 11.63, 0.076, and 153.03, respectively. For the SVM model, we found the importance value of time to operating room (TOR) was higher significantly than other variables. Conclusion : The analysis of clinical reliability showed that the SVM model achieved the best comprehensive prediction efficiency and the importance value of TOR was higher significantly than other variables.

• International Journal of Oral Biology
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• 제45권1호
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• pp.1-7
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• 2020

Oral lichen planus (OLP) is a chronic inflammatory disease observed in approximately 0.5-2.2% of the population, and it is recognized as a premalignant lesion that can progress into oral squamous cell carcinoma (OSCC). The rate of malignant transformation is approximately 1.09-2.3%, and the risk factors for malignant transformation are age, female, erosive type, and tongue site location. Malignant transformation of OLP is likely related to the low frequency of apoptotic phenomena. Therefore, apoptosis-related genetic factors, like p53, BCL-2, and BAX are reviewed. Increased p53 expression and altered expression of BCL-2 and BAX were observed in OLP patients, and the malignant transformation rate in these patients was relatively higher. The involvement of microRNA (miRNA) in the malignant transformation of OLP is also reviewed. Because autophagy is involved in cell survival and death through the regulation of various cellular processes, autophagy-related genetic factors may function as factors for malignant transformation. In OLP, decreased levels of ATG9B mRNA and a higher expression of IGF1 were observed, suggesting a reduction in cell death and autophagic response. Activated IGF1-PI3K/AKT/mTor cascade may play an important role in a signaling pathway related to the malignant transformation of OLP to OSCC. Recent research has shown that miRNAs, such as miR-199 and miR-122, activate the cascade, increasing the prosurvival and proproliferative signals.

• 한국식품영양과학회지
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• 제41권8호
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• pp.1079-1085
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• 2012

본 연구는 녹두묵을 이용한 항비만 임상선행연구를 바탕으로 녹두에 풍부한 vitexin의 항비만 효과의 기작을 살펴보고자 하였다. 녹두 vitexin은 $200{\mu}M$ 농도까지 3T3-L1 지방 전구세포의 독성효과는 없었으며 50, 100, $200{\mu}M$ 농도에서 지방합성이 억제되었고 $100{\mu}M$ 농도에서 지방분해효과로 추측할 수 있는 결과가 나타났다. 또한 $200{\mu}M$에서 염증성 아디포사이토카인 유전자발현을 증폭시키는 상위신호체계(p38, ERK)가 억제된 반면 AMPK의 경우는 $100{\mu}M$ 농도까지 증가하였고 $PPAR{\gamma}$ 단백질 발현도 $200{\mu}M$에서 증폭하였으며 TNF-${\alpha}$와 aP2 mRNA 발현은 $25{\mu}M$에 증가하였다가 감소하였다. 이러한 결과를 바탕으로 결론을 내리면 vitexin $100{\sim}200{\mu}M$ 사이의 농도가 항비만 기작을 규명하는 in vivo 실험을 위한 적절한 농도로 여겨진다. 그러나 본 연구에서는 vitexin 처리에 따른 C/EBP, SREBP1, $PPAR{\gamma}$ mRNA 농도의 변화는 관찰되지 않아 3T3-L1 세포자살(apoptosis) 신호체계 및 mTOR와의 연계성체계 혹은 기타 adipogenesis 억제 유전자로 SIRT1 등의 연구가 향후에 더 필요할 것으로 사료된다.

• 한국대기환경학회지
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• 제26권5호
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• pp.567-580
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• 2010

Organic carbon (OC) and elemental carbon (EC) concentrations were determined for $PM_{10}$, $PM_{2.5}$ and $PM_{1.0}$ aerosols particles collected at Gosan Superstation on Jeju Island from August 2007 to September 2008. Aerosols were collected on quartz filters for 24 hours and then OC and EC were analyzed by TOR/IMPROVED method. Mean concentrations of OC and EC were $4.66\;{\mu}g/m^3$ and $1.69\;{\mu}g/m^3$ for $PM_{10}$, $3.95\;{\mu}g/m^3$ and $1.69\;{\mu}g/m^3$ for $PM_{2.5}$, and $3.16\;{\mu}g/m^3$ and $1.42\;{\mu}g/m^3$ for $PM_{1.0}$, respectively. The concentrations of OC and EC comprised 16.4% and 6.0% of $PM_{10}$, 22.9% and 9.8% of $PM_{2.5}$, and 23.0% and 10.0% of $PM_{1.0}$. OC and EC showed a clear seasonal variation with the highest in winter and the lowest in summer. The correlations between the two were also the best during the winter ($R^2$=0.87, 0.94, and 0.95 for $PM_{10}$, $PM_{2.5}$ and $PM_{1.0}$). The ratio of OC/EC exhibited the maximum (7.24) during an Asian dust event due to an increase of OC, which was possibly derived from soil. The mass fraction of both OC and EC was the highest in fall. When OC and EC concentrations were highly elevated, EC1 (the first EC fraction determined at $550^{\circ}C$) and pyrolyzed OC (POC) were dominant subcomponents in winter and OC3 (the third OC fraction determined at $450^{\circ}C$) and POC in spring.

• Asian Pacific Journal of Cancer Prevention
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• 제13권6호
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• pp.2533-2539
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• 2012

Annona muricata L (Annonaceae), commonly known as soursop has a long, rich history in herbal medicine with a lengthy recorded indigenous use. It had also been found to be a promising new anti-tumor agent in numerous in vitro studies. The present investigation concerns chemopreventive effects in a two-stage model of skin papillomagenesis. Chemopreventive effects of an ethanolic extract of A. muricata leaves (AMLE) was evaluated in 6-7 week old ICR mice given a single topical application of 7,12-dimethylbenza(${\alpha}$)anthracene (DMBA 100ug/100ul acetone) and promotion by repeated application of croton oil (1% in acetone/twice a week) for 10 weeks. Morphological tumor incidence, burden and volume were measured, with histological evaluation of skin tissue. Topical application of AMLE at 30, 100 and 300mg/kg significantly reduced DMBA/croton oil induced mice skin papillomagenesis in (i) peri-initiation protocol (AMLE from 7 days prior to 7 days after DMBA), (ii) promotion protocol (AMLE 30 minutes after croton oil), or (iii) both peri-initiation and promotion protocol (AMLE 7 days prior to 7 day after DMBA and AMLE 30 minutes after croton oil throughout the experimental period), in a dose dependent manner (p<0.05) as compared to carcinogen-treated control. Furthermore, the average latent period was significantly increased in theAMLE-treated group. Interestingly, At 100 and 300 mg/kg, AMLE completely inhibited the tumor development in all stages. Histopathological study revealed that tumor growth from the AMLE-treated groups showed only slight hyperplasia and absence of keratin pearls and rete ridges. The results, thus suggest that the A.muricata leaves extract was able to suppress tumor initiation as well as tumor promotion even at lower dosage.

• 약학회지
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• 제49권5호
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• pp.370-374
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• 2005

Lactoferrin is a multifunctional protein that is found in milk, neutrophils, and other biological fluids, and its receptors have also been identified in the central nervous system. Recently, it was reported that bovine milk-derived lacto­ferrin (BLF) produced analgesia via a $\mu$-opioid receptor-mediated response in the spinal cord. However the precise mech­anism of this analgesic effect is remains unclear. In Randall-Selitto paw pressure study, each single administration of morphine (10 mg/kg) and BLF (50, 100 and 200 mg/kg) induced analgesia, however, NMDA receptor antagonist MK-801 (0.1, 0.2 and 0.3 mg/kg), inhibited analgesia induced by BLF (100 mg/kg). Intracerebroventricular infusion (I.C.V.) of N­methyl-D-aspartic acid (NMDA) ($0.3\;{\mu}g/8.0\;{\mu}l/hr/day$), as a NMDA receptor agonist, reversed inhibition of MK-801 (0.3 mg/kg) on analgesia induced by BLF (100 mg/kg). These results suggest that BLF have analgesic effect, through NMDA recep­tor activation.

• 한국수정란이식학회지
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• 제33권3호
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• pp.119-127
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• 2018

The purpose of this study is to examined the electrofusion and activation conditions for the production of porcine somatic cell nuclear transfer (SCNT) embryos. In this study, immature oocytes were cultured in TCM-199 with and without hormones for 22 hours. Skin fibroblasts cells of porcine were transferred into the perivitelline space of enucleated in vitro matured oocytes. Cell fusion was performed with two different pulses that each one pulse (DC) of 1.1 kV/cm or 1.5 kV/cm for $30{\mu}sec$. After fusion subsequent activation were divided into three groups; non-treatment (control) and treatment with 2 mM 6-DMAP or $7.5{\mu}g/ml$ cytochalasin B for 4 hours. Transferred embryos were cultured in PZM-3 (Porcine Zygote Medium-3) in $5%\;CO_2$ and 95% air at $39^{\circ}C$ for 7 day. Apoptosis-related genes (Caspase-3, BCL-2, mTOR, and MMP-2) were analyzed by immunofluorescence staining. There was no significant difference between two different electrofusion stimuli in the cleavage rate; $64.9{\pm}4.8%$ in 1.1 kV/cm and $62.7{\pm}4.0%$ in 1.5 kV/cm. However, blastocyst formation rate (%) was significantly different among three different activation groups (no treatment, 2 mM 6-DMAP or $7.5{\mu}g/ml$ cytochalasin B) combined with electrofusion of 1.1 kV/cm. The blastocyst formation rate was $12.6{\pm}2.5$, $20.0{\pm}5.0$, and $34.9{\pm}4.3%$ in control, 2 mM 6-DMAP, and $7.5{\mu}g/ml$ cytochalasin B, respectively. Immunofluorescence data showed that expression levels of caspase-3 in SCNT embryos undeveloped to blastocyst stage were higher than those in the blastocyst stage embryos. Expression levels of Bcl-2 in blastocyst stage embryos were higher than those in the arrested SCNT embryos. These results showed that the combination of an electric pulse (1.1 kV/cm for $30{\mu}sec$) and $7.5{\mu}g/ml$ cytochalasin B treatment was effective for production of the porcine SCNT embryos.

• 한국수산과학회지
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• 제30권3호
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• pp.442-450
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• 1997

본 연구는 부경대학교 해양탐사선인 탐양호를 이용하여 1995년 2월 14일에서 17일까지 실시하였다 수온, 염분 및 용존산소를 이용한 T-S diagram 및 $T-O_2$ diagram 으로부터 수괴는 5개의 Type으로 구분되었다. 특히 T-S diagram에서는 잘 구분되지 않았던 Type IV와 Type V는 $T-O_2$ diagram에서 뚜렷이 구분되었다. 하지만 기존 수괴와 명확히 일치하지 않는 것은 본 조사가 동계에 실시되어 표층수온의 감소로 인하여 수괴의 수직혼합이 강하게 일어나서 생긴 현상으로 사료된다. 영양염류의 수괴별 농도분포를 보면, Type I, Type II, Type III은 서로 거의 비슷한 농도를 보였지만 Type IV에서 Type V로 갈수록 증가되었다. 그리고 동일 수괴에서 농도범위가 넓게 나왔는데, 이는 수온약층의 약화로 인하여 발생한 것으로 생각된다. N/P ratio은 모든 water type에서 Redfield ratio 이하로 나타났는데, 이것은 질산염이 식물플랑크톤 성장의 제한인자로 작용하고 있음을 보여주고 있다. chlorophyll $\alpha$의 농도는 $0\~8\;{\mu}g/\ell$의 범위로, Type I에서 최대였고 Type IV와 Type V에서는 거의 검출되지 않았다. 입자성 유기탄소와 유기질소의 농도는 각각 $0.49\~20.03\;{\mu}g-at/\ell$와 $0.09\~5.34\;{\mu}g-at/\ell$ 범위로서, 수심의 증가에 따라 그 농도가 감소하고, 연안에서 외양쪽으로 갈수록 낮아지는 경향이었다. Water type별 농도는 Type I > Type II > Type III > Type IV > Type V의 순서로 수심의 증가에 따라 농도가 증가하는 경향이었다. 즉 이들 입자성 유기물질은 수괴별로 어떤 뚜렷한 경향을 보이지는 않았으며, 수심에 따라서 농도가 변화되는 것으로 생각된다. POC/PON의 원자비는 3.23으로 Redfield ratio 이하로 나타났다. 이것은 POC보다 PON이 더 난분해성이라 침강하는 동안 POC는 분해되지만 수직혼합에 의해 PON은 다시 재부유하기 때문인 것으로 사료된다. POC/chlorophyll $\alpha$의 평균값은 1962로 매우 높은 값을 나타내었으며, non-living detritus가 POC의 대부분을 차지하고 있는 것으로 판단된다.

• 한국수산과학회지
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• 제35권6호
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• pp.545-550
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• 2002

금강 하구에서 분리한 용혈독소를 생산하는 V. mimicus와 유사하지만 분류되지 않은 기수성 Vibrio속으로 추정되는 균주 Vibrio sp. E10 (V. kunsan)의 세균학적 특징은 다음과 같다. 기본적인 생화학적 시험과 전자현미경 상의 형태에서는 V. mimicus와 유사하였지만 TCBS 배지 상의 colony 형태는 V. vulnifirus와 유사하였으므로 V. mimicus와는 차이를 보였다. Human과 sheep blood agar에서의 뚜렷한 용혈환과 rat에 피부혈관투과항진 작용으로 용혈독성이 있었으며, mouse에 대한 치사독성이 있었으므로 병원성이 확인되었다. 생육 가능한 환경 조건은 염도 0$\~$$4.5\%$, pH 6.2$\~$9.2, 온도 $14\~42^{\circ}C$이 었다. Vibrio sp. E10의 16S rDNA 염기서열은 10여종의 V. cholerae와 1종의 Vibrio mimicus의 염기서열과 $99\%$의 상동성을 보여 유사 종으로 판명되었다. 그러나 세균 자동동정기를 이용한 동정 결과, genus는 Vibrio 속으로 동정되었으나 species는 일치하는 균종이 없었다. 알려진 Vi-brio속 중에서 유사성이 높았던 V. mimicus와 비교해 볼 때 18종류의 항목이, V. cholerae와는 11종류의 항목이 다른 반응을 나타내어 미분류 균종으로 확인되었다.