Epigenetic alterations are involved in the overexpression of glutathione S-transferase π-1 in human colorectal cancers.

Zhang, Rui,Kang, Kyoung Ah,Piao, Mei Jing,Kim, Ki Cheon,Zheng, Jian,Yao, Cheng Wen,Cha, Ji Won,Maeng, Young Hee,Chang, Weon Young,Moon, Pyong-Gon,Baek, Moon-Chang,Hyun, Jin Won Lychnia 2014 International journal of oncology Vol.45 No.3

<P>Glutathione S-transferase pi-1 (GSTP-1) is a member of the glutathione S-transferase enzyme superfamily, which catalyzes the conjugation of electrophiles to glutathione during the process of detoxification. In this study, the epigenetic alterations of GSTP-1 expression in human colorectal cancers and the underlying mechanisms were investigated. In 10 colon cancer patients, proteomic analysis revealed that expression of GSTP-1 protein was higher in tumor tissues than in paired adjacent normal tissues. Likewise, in 7 of 10 colon cancer patients, GSTP-1 protein expression was more than 1.5-fold higher in tumor tissues than in adjacent normal tissues, as determined by western blotting. Immunohistochemical data confirmed that GSTP-1 protein was expressed at higher levels in colon cancer tissues compared to normal mucosa. GSTP-1 enzyme activity was closely correlated with GSTP-1 protein expression in colon cancer patients. Consistent with this, GSTP-1 mRNA, protein and activity levels were higher in the colorectal cancer cell lines Caco-2, HCT-116, HT-29, SNU-407 and SNU-1033 compared to the normal colon cell line FHC. Methylation-specific PCR results indicated that the high levels of GSTP-1 in human colorectal cancer cell lines were likely due to the lower degree of promoter methylation in colon cancer cell lines compared to the normal colon cell line, consistent with findings in colon cancer patients. Moreover, the levels of specific activator-protein complexes and histone marks were higher in human colorectal cancer cells compared to the normal human colon cell line, whereas the repressor protein complexes exhibited the opposite pattern. Furthermore, chromatin immunoprecipitation assays demonstrated that expression levels of the transcription factors AP-1 and SP-1 were correlated with the upregulation of GSTP-1 expression in colorectal cancer cells. Finally, knockdown of GSTP-1 promoted the sensitivity of SNU-407 cells to the anticancer agent 5-fluorouracil. These data indicate that GSTP-1 may serve as a clinically useful biomarker of colon cancer and a target for anti-colon cancer drugs.</P>

A miR-155–Peli1–c-Rel pathway controls the generation and function of T follicular helper cells

Liu, Wen-Hsien,Kang, Seung Goo,Huang, Zhe,Wu, Cheng-Jang,Jin, Hyun Yong,Maine, Christian J.,Liu, Yi,Shepherd, Jovan,Sabouri-Ghomi, Mohsen,Gonzalez-Martin, Alicia,Xu, Shunbin,Hoffmann, Alexander,Zheng, The Rockefeller University Press 2016 The Journal of experimental medicine Vol.213 No.9

<P>MicroRNA (miRNA) deficiency impairs the generation of T follicular helper (Tfh) cells, but the contribution of individual miRNAs to this phenotype remains poorly understood. In this study, we performed deep sequencing analysis of miRNAs expressed in Tfh cells and identified a five-miRNA signature. Analyses of mutant mice deficient of these miRNAs revealed that miR-22 and miR-183/96/182 are dispensable, but miR-155 is essential for the generation and function of Tfh cells. miR-155 deficiency led to decreased proliferation specifically at the late stage of Tfh cell differentiation and reduced CD40 ligand (CD40L) expression on antigen-specific CD4<SUP>+</SUP> T cells. Mechanistically, miR-155 repressed the expression of Peli1, a ubiquitin ligase that promotes the degradation of the NF-κB family transcription factor c-Rel, which controls cellular proliferation and CD40L expression. Therefore, our study identifies a novel miR-155–Peli1–c-Rel pathway that specifically regulates Tfh cell generation and function.</P>

Effect of 7, 8-dihydroxyflavone on the up-regulation of Nrf2-mediated heme oxygenase-1 expression in hamster lung fibroblasts.

Ryu, Min Ju,Kang, Kyoung Ah,Piao, Mei Jing,Kim, Ki Cheon,Zheng, Jian,Yao, Cheng Wen,Cha, Ji Won,Hyun, Chang Lim,Chung, Ha Sook,Park, Jong Cook,Cho, Suk Ju,Hyun, Jin Won Springer 2014 In vitro cellular & developmental biology Animal Vol.50 No.6

<P>The cytoprotective mechanism of 7, 8-dihydroxyflavone (DHF) against oxidative stress-induced cell damage with respect to its stimulatory effect on the expression of heme oxygenase-1 (HO-1), a potent antioxidant enzyme, was investigated in the present study. Up-regulation of HO-1 expression by DHF was both dose and time dependent in lung fibroblast V79-4 cells. DHF also increased the protein expression level of the transcription factor nuclear factor erythroid-2-related factor 2 (Nrf2), and induced the translocation of Nrf2 from the cytosol into the nucleus, leading to elevated HO-1 expression. The siNrf2 RNA-transfection attenuated HO-1 expression induced by DHF treatment. In addition, DHF induced the activation of extracellular signal-regulated kinase (ERK), while U0126 (a specific pharmacological inhibitor of ERK kinase) abrogated DHF-activated Nrf2 and HO-1 expression. This suggests that DHF increased the levels of Nrf2 and HO-1 via ERK-dependent pathways. Furthermore, DHF significantly prevented the reduction of cell viability in response to oxidative stress; however, U0126 attenuated the protective effect of DHF. Taken together, these results demonstrate that DHF protected cells from oxidative stress via the activation of an ERK/Nrf2/HO-1 signaling pathway.</P>

Dictyopteris undulata Extract Induces Apoptosis in Human Colon Cancer Cells

Kim, Areum Daseul,Kang, Kyoung Ah,Piao, Jing Mei,Kim, Ki Cheon,Zheng, Jian,Yao, Cheng Wen,Cha, Ji Won,Hyun, Chang Lim,Boo, Sun Jin,Lee, Nam Ho,Na, Soo Young,Hyun, Jin Won 한국생물공학회 2014 Biotechnology and Bioprocess Engineering Vol.19 No.3

The present study investigated the cytotoxic and apoptotic effects of an ethanol extract derived from the marine brown alga Dictyopteris undulata against human colon adenocarcinoma cells. The Dictyopteris undulata extract (DUE) showed cytotoxic activity against SW480 cells in a dose-dependent manner, with 50% inhibition of cell viability at a concentration of $40{\mu}g/mL$. DUE also induced programmed cell death in SW480 cells, as evidenced by apoptotic body formation, DNA fragmentation, an increase in the population of apoptotic sub-$G_1$ phase cells, and mitochondrial membrane depolarization. Moreover, DUE significantly modulated the expression of apoptosis-associated proteins, resulting in a decrease in B cell lymphoma-2 expression and an increase in Bcl-2-associated X protein expression, as well as the activation of caspase-9 and caspase-3. Furthermore, DUE showed apoptotic cell death in two other colon cancer cell lines, SNU407 and HT29. These observations suggest that DUE may prove useful as a therapeutic agent for the attenuation of colon cancer.

Precise visualization and ROS-dependent photodynamic therapy of colorectal cancer with a novel mitochondrial viscosity photosensitive fluorescent probe

Runsha Xiao,Fan Zheng,Kuo Kang,Lei Xiao,Anyao Bi,Yiting Chen,Qi Zhou,Xueping Feng,Zhikang Chen,Hao Yin,Wei Wang,Zihua Chen,Xiaomiao Cheng,Wenbin Zeng 한국생체재료학회 2023 생체재료학회지 Vol.27 No.00

Background Colorectal cancer (CRC) is a prominent global cancer with high mortality rates among human beings. Efficient diagnosis and treatment have always been a challenge for CRC management. Fluorescence guided cancer therapy, which combines diagnosis with therapy into one platform, has brought a new chance for achieving precise cancer theranostics. Among this, photosensitizers, applied in photodynamic therapy (PDT), given the integration of real-time imaging capacity and efficacious treatment feasibility, show great potential to serve as remarkable tools. Although much effort has been put into constructing photosensitizers for locating and destroying CRC cells, it is still in high need to develop novel photosensitizers to attain specific detection and fulfil effective therapy. Methods Probe HTI was rational synthesized for the diagnosis and treatment of CRC. Spectrometric determination was carried out first, followed by the 1O2 generation ability test. Then, HTI was displayed in distinguishing CRC cells from normal cells Further, the PDT effect of the photosensitizer was studied in vitro. Additionally, HTI was used in CRC BALB/c nude mice model to validate its viscosity labelling and tumor suppression characteristics. Results We successfully fabricated a mitochondrial targeting probe, HTI, together with remarkable viscosity sensitivity, ultralow background interference, and excellent 1O2 generation capacity. HTI was favorably applied to the viscosity detection, displaying a 11-fold fluorescent intensity enhancement in solvents from 1.57 cp to 2043 cp. Then, it was demonstrated that HTI could distinguish CRC cells from normal cells upon the difference in mitochondrial viscosity. Moreover, HTI was qualified for producing 1O2 with high efficiency in cells, supported by the sparkling signals of DCFH after incubation with HTI under light irradiation. More importantly, the viscosity labelling and tumor suppression performance in CRC CDX model was determined, enriching the multifunctional validation of HTI in vivo. Conclusions In this study, HTI was demonstrated to show a sensitive response to mitochondrial viscosity and possess a high 1O2 generation capacity. Both in vitro cell imaging and in vivo tumor treatment trials proved that HTI was effectively served as a robust scaffold for tumor labeling and CRC cells clearance. This breakthrough discovery held immense potential for advancing the early diagnosis and management of CRC through PDT. By leveraging HTI’s properties, medical professionals could benefit from improved diagnostic accuracy and targeted treatment in CRC management, ultimately leading to enhanced patient outcomes.

Phloroglucinol inhibits ultraviolet B radiation-induced oxidative stress in the mouse skin

Piao, Mei Jing,Ahn, Mee Jung,Kang, Kyoung Ah,Kim, Ki Cheon,Zheng, Jian,Yao, Cheng Wen,Cha, Ji Won,Hyun, Chang Lim,Kang, Hee Kyoung,Lee, Nam Ho,Hyun, Jin Won Informa Healthcare 2014 International journal of radiation biology Vol.90 No.10

<P><I>Purpose</I>: Previously we demonstrated that phloroglucinol (1,3,5-trihydroxybenzene) protected human HaCaT keratinocytes against ultraviolet B (UVB, 280-320 nm)-induced oxidative stress <I>in vitro</I> by scavenging intracellular reactive oxygen species (ROS). The current study investigated whether phloroglucinol could similarly protect the mouse skin against UVB-induced oxidative tissue damage <I>in vivo</I>.</P><P><I>Materials and methods</I>: Male 7-week-old Balb/c mice were divided into the following untreated normal control, phloroglucinol only-treated, vehicle plus UVB (30 or 60 mJ/cm<SUP>2</SUP>)-exposed, and phloroglucinol (10 or 50 mg/ml) plus UVB (30 or 60 mJ/cm<SUP>2</SUP>)-treated groups. Following UVB exposure, phloroglucinol or phosphate buffered saline vehicle was applied to the dorsal skin of each mouse daily for 3 days. Studies were conducted at 24 h after the last of the UVB exposures. Histopathological analyses of dorsal skin lesions were performed on all mice. In addition, the levels of UVB-provoked injury to cellular components, including DNA, proteins, and lipids were detected by levels of 8-oxoguanine (8-oxoG), protein carbonyls, and 8-isoprostane. Apoptosis were assessed by using western blot for B-cell lymphoma-2-associated X protein (Bax) and activated caspase-3 expression, by using immunohistochemistry.</P><P><I>Results</I>: UVB radiation increased the thickness of the epidermis and the dermis, and also stimulated the accumulation of mast cells in the irradiated skin. However, treatment with phloroglucinol significantly decreased all of these parameters. Furthermore, phloroglucinol decreased UVB-provoked injury to cellular components, including DNA, proteins, and lipids; down-regulated the expression of phospho-histone H2A.X in the injured skin; and reduced the UVB-generated levels of 8-oxoG, protein carbonyls, and 8-isoprostane, which are all markers of oxidative stress. In addition, phloroglucinol attenuated the UVB-induced expression of the pro-apoptotic proteins, Bax protein, and activated caspase-3.</P><P><I>Conclusion</I>: These results suggest that phloroglucinol safeguards the mouse skin against UVB-induced oxidative stress and apoptosis.</P>

Screening Peptides Binding Specifically to Colorectal Cancer Cells from a Phage Random Peptide Library

Wang, Jun-Jiang,Liu, Ying,Zheng, Yang,Liao, Kang-Xiong,Lin, Feng,Wu, Cheng-Tang,Cai, Guan-Fu,Yao, Xue-Qing Asian Pacific Journal of Cancer Prevention 2012 Asian Pacific journal of cancer prevention Vol.13 No.1

The aim of this study was to screen for polypeptides binding specifically to LoVo human colorectal cancer cells using a phage-displayed peptide library as a targeting vector for colorectal cancer therapy. Human normal colorectal mucous epithelial cells were applied as absorber cells for subtraction biopanning with a c7c phage display peptide library. Positive phage clones were identified by enzyme-linked immunosorbent assay and immunofluorescence detection; amino acid sequences were deduced by DNA sequencing. After 3 rounds of screening, 5 of 20 phage clones screened positive, showing specific binding to LoVo cells and a conserved RPM motif. Specific peptides against colorectal cancer cells could be obtained from a phage display peptide library and may be used as potential vectors for targeting therapy for colorectal cancer.

Fucodiphlorethol G Purified from Ecklonia cava Suppresses Ultraviolet B Radiation-Induced Oxidative Stress and Cellular Damage

( Ki Cheon Kim ),( Mei Jing Piao ),( Jian Zheng ),( Cheng Wen Yao ),( Ji Won Cha ),( Madduma Hewage Susara Ruwan Kumara ),( Xia Han ),( Hee Kyoung Kang ),( Nam Ho Lee ),( Jin Won Hyun ) 한국응용약물학회 2014 Biomolecules & Therapeutics(구 응용약물학회지) Vol.22 No.4

Fucodiphlorethol G (6`-[2,4-dihydroxy-6-(2,4,6-trihydroxyphenoxy)phenoxy]biphenyl-2,2`,4,4`,6-pentol) is a compound purifi ed from Ecklonia cava, a brown alga that is widely distributed offshore of Jeju Island. This study investigated the protective effects of fucodiphlorethol G against oxidative damage-mediated apoptosis induced by ultraviolet B (UVB) irradiation. Fucodiphlorethol G attenuated the generation of 2, 2-diphenyl-1-picrylhydrazyl radicals and intracellular reactive oxygen species in response to UVB irradiation. Fucodiphlorethol G suppressed the inhibition of human keratinocyte growth by UVB irradiation. Additionally, the wavelength of light absorbed by fucodiphlorethol G was close to the UVB spectrum. Fucodiphlorethol G reduced UVB radiation-induced 8-isoprostane generation and DNA fragmentation in human keratinocytes. Moreover, fucodiphlorethol G reduced UVB radiationinduced loss of mitochondrial membrane potential, generation of apoptotic cells, and active caspase-9 expression. Taken together, fucodiphlorethol G protected human keratinocytes against UVB radiation-induced cell damage and apoptosis by absorbing UVB radiation and scavenging reactive oxygen species.

The ethyl acetate fraction of <i>Sargassum muticum</i> attenuates ultraviolet B radiation-induced apoptotic cell death via regulation of MAPK- and caspase-dependent signaling pathways in human HaCaT keratinocytes

Piao, Mei Jing,Kim, Ki Cheon,Zheng, Jian,Yao, Cheng Wen,Cha, Ji Won,Boo, Sun Jin,Yoon, Weon Jong,Kang, Hee Kyoung,Yoo, Eun Sook,Koh, Young Sang,Ko, Mi Hee,Lee, Nam Ho,Hyun, Jin Won Informa Healthcare USA, Inc. 2014 PHARMACEUTICAL BIOLOGY Vol.52 No.9

<P><I>Context</I>: Our previous work demonstrated that an ethyl acetate extract derived from <I>Sargassum muticum</I> (Yendo) Fenshol (SME) protected human HaCaT keratinocytes against ultraviolet B (UVB)-induced oxidative stress by increasing antioxidant activity in the cells, thereby inhibiting apoptosis.</P><P><I>Objective</I>: The aim of the current study was to further elucidate the anti-apoptotic mechanism of SME against UVB-induced cell damage.</P><P><I>Materials and methods</I>: The expression levels of several apoptotic-associated and mitogen-activated kinase (MAPK) signaling proteins were determined by western blot analysis of UVB-irradiated HaCaT cells with or without prior SME treatment. In addition, the loss of mitochondrial membrane potential (Δ<I>ψ</I><SUB>m</SUB>) was detected using flow cytometry or confocal microscopy and the mitochondria membrane-permeate dye, JC-1. Apoptosis was assessed by quantifying DNA fragmentation and apoptotic body formation. Furthermore, cell viability was evaluated using the MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) assay.</P><P><I>Results</I>: SME absorbed electromagnetic radiation in the UVB range (280-320 nm) of the UV/visible light spectrum. SME also increased Bcl-2 and Mcl-1 expression in UVB-irradiated cells and decreased the Bax expression. Moreover, SME inhibited the UVB-induced disruption of mitochondrial membrane potential and prevented UVB-mediated increases in activated caspase-9 and caspase-3 (an apoptotic initiator and executor, respectively) levels. Notably, treatment with a pan-caspase inhibitor enhanced the anti-apoptotic effects of SME in UVB-irradiated cells. Finally, SME reduced the UVB-mediated phosphorylation of p38 MAPK and JNK, and prevented the UVB-mediated dephosphorylation of Erk1/2 and Akt.</P><P><I>Discussion and conclusion</I>: The present results indicate that SME safeguards HaCaT keratinocytes from UVB-mediated apoptosis by inhibiting a caspase-dependent signaling pathway.</P>

Liaohe National Park based on big data visualization Visitor Perception Study

Qi-Wei Jing,Zi-Yang Liu(유자양),Cheng-Kang Zheng 한국컴퓨터정보학회 2023 韓國컴퓨터情報學會論文誌 Vol.28 No.4

국립공원은 세계 자연 보존 연맹(WWF)이 수립한 보호지역 관리 체계의 중요 유형 중 하나이며, 또한 자연 및 문화 유산의 효과적인 보호와 지속적인 이용을 실현하는 세계 각국의 관리 모델이다. 이러한 공원은 보호, 과학 연구, 교육, 레크리에이션 및 지역 개발을 비롯한 중요한 역할을 담당하다. 대용량 데이터의 배경 아래, 본 연구는 전 세계 연안 습지의 대표적인 대상인 중국 랴오하 국립공원을 사례 지역으로 삼아 파이썬 기술을 사용하여 중국의 주요 관광 OTA 사이트 중 하나인 망픈웨이(Mafengwo), 셰어이(Gonglve), 큐난우(Chujingyou), 메이툰(Meituan) 및 대중점평넷(Dianping)의 관광객 여행기와 댓글을 데이터 소스로 수집하였다. 텍스트 시간 범위는 2015년부터 2022년까지이며, 총 2,998개의 댓글과 166,588개의 단어를 포함하다. ROST 콘텐츠 마이닝 및 Gephi 소프트웨어를 사용하여 랴오하 국립공원 방문객의 만족도, 인지 과정, 공선 네트워크, 감정 성향 등을 시각적 분석하였다. 결과는 다음과 같다. 야생 동물 및 식물 자원, 강과 바다가 결합 된 자연 경관, 습지 생태는 랴오하 국립공원 방문객의 인식에서 충분히 반영되었다. 방문객은 랴오하 국립공원에 대해 강한 긍정적인 감정을 가지고 있지만, 시설 서비스, 대중교육, 방문객 참여 경험 등에서 여전히 개선할 여지가 있다. National parks are one of the important types of protected area management systems established by IUCN and a management model for implementing effective conservation and sustainable use of natural and cultural heritage in countries around the world, and they assume important roles in conservation, scientific research, education, recreation and driving community development. In the context of big data, this study takes Chinas Liaohe National Park, a typical representative of global coastal wetlands, as a case study, and using Python technology to collect tourists travelogues and reviews from major OTA websites in China as a source. The text spans from 2015 to 2022 and contains 2998 reviews with 166,588 words in total. The results show that wildlife resources, natural landscape, wetland ecology and the fishing and hunting culture of northern China are fully reflected in the perceptions of visitors to Liaohe National Park; visitors have strong positive feelings toward Liaohe National Park, but there is still much room for improvement in supporting services and facilities, public education and visitor experience and participation.