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Genomic Screening for Targets Regulated by Berberine in Breast Cancer Cells
Wen, Chun-Jie,Wu, Lan-Xiang,Fu, Li-Juan,Yu, Jing,Zhang, Yi-Wen,Zhang, Xue,Zhou, Hong-Hao Asian Pacific Journal of Cancer Prevention 2013 Asian Pacific journal of cancer prevention Vol.14 No.10
Berberine, a common isoquinoline alkaloid, has been shown to possess anti-cancer activities. However, the underlying molecular mechanisms are still not completely understood. In the current study, we investigated the effects of berberine on cell growth, colony formation, cell cycle distribution, and whether it improved the anticancer efficiency of cisplatin and doxorubicin in human breast cancer estrogen receptor positive (ER+) MCF-7 cells and estrogen receptor negative (ER-) MDA-MB-231 cells. Notably, berberine treatment significantly inhibited cell growth and colony formation in the two cell lines, berberine in combination with cisplatin exerting synergistic growth inhibitory effects. Accompanied by decreased growth, berberine induced G1 phase arrest in MCF-7 but not MDA-MB-231 cells. To provide a more detailed understanding of the mechanisms of action of berberine, we performed genome-wide expression profiling of berberine-treated cells using cDNA microarrays. This revealed that there were 3,397 and 2,706 genes regulated by berberine in MCF-7 and MDA-MB-231 cells, respectively. Fene oncology (GO) analysis identified that many of the target genes were involved in regulation of the cell cycle, cell migration, apoptosis, and drug responses. To confirm the microarray data, qPCR analysis was conducted for 10 selected genes based on previously reported associations with breast cancer and GO analysis. In conclusion, berberine exhibits inhibitory effects on breast cancer cells proliferation, which is likely mediated by alteration of gene expression profiles.
Zhang, Ya-Xiong,Kang, Shi-Yang,Chen, Gang,Fang, Wen-Feng,Wu, Xuan,You, Hua-Jing,He, Da-Cheng,Cao, Ya-Lin,Liang, Wen-Hua,Zhang, Li Asian Pacific Journal of Cancer Prevention 2014 Asian Pacific journal of cancer prevention Vol.15 No.17
Background: A prior study showed blood type A/AB to be associated with an increased risk of nasopharyngeal carcinoma (NPC) compared to subjects with blood type O. However, the relationship between ABO blood groups and prognosis of NPC patients is still questionable. In addition, whether Epstein-Barr virus (EBV) infection is associated with prognosis of NPC patients with different ABO blood groups is unclear. Materials and Methods: We conducted univariate and multivariable Cox regression analyses based on a consecutive cohort of 1,601 patients to investigate the above issues. Results: There was no significant difference in overall survival (OS) between different ABO blood groups (p=0.629), neither between A vs. non-A blood groups (p=0.895) nor AB vs. non-AB blood group (p=0.309) in univariate analyses and after adjusting for other factors. Interaction tests revealed that high immunoglobulin A against Epstein-Barr virus viral capsid antigen (VcA-IgA) level was associated with a favorable prognosis in male patients with UICC stage II disease who had an A blood type (p=0.008), compared with those with non-A blood type. In addition, male patients with an A blood group with a high blood lymphocyte level showeda tendency towards better survival in UICC stage III (p=0.096). Conclusions: ABO blood group status is not associated with the prognosis of patients with NPC. Additionally, blood group A male NPC patients with high VcA-IgA level or high blood lymphocyte counts might be correlated with a favorable prognosis in UICC stage II or III, respectively.
Identification of novel rheumatoid arthritis-associated MiRNA-204-5p from plasma exosomes
Wu Long-Fei,Zhang Qin,Mo Xing-Bo,Lin Jun,Wu Yang-Lin,Lu Xin,He Pei,Wu Jian,Guo Yu-Fan,Wang Ming-Jun,Ren Wen-Yan,Deng Hong-Wen,Lei Shu-Feng,Deng Fei-Yan 생화학분자생물학회 2022 Experimental and molecular medicine Vol.54 No.-
Rheumatoid arthritis (RA) is an autoimmune disease characterized by infiltration of immune cells in the synovium. However, the crosstalk of immune cells and synovial fibroblasts is still largely unknown. Here, global miRNA screening in plasma exosomes was carried out with a custom microarray (RA patients vs. healthy controls = 9:9). A total of 14 exosomal miRNAs were abnormally expressed in the RA patients. Then, downregulated expression of exosomal miR-204-5p was confirmed in both the replication (RA patients vs. healthy controls = 30:30) and validation groups (RA patients vs. healthy controls = 56:60). Similar to the findings obtained in humans, a decreased abundance of exosomal miR-204-5p was observed in mice with collagen-induced arthritis (CIA). Furthermore, Spearman correlation analysis indicated that plasma exosomal miR-204-5p expression was inversely correlated with disease parameters of RA patients, such as rheumatoid factor, erythrocyte sedimentation rate, and C-reactive protein. In vitro, our data showed that human T lymphocytes released exosomes containing large amounts of miR-204-5p, which can be transferred into synovial fibroblasts, inhibiting cell proliferation. Overexpression of miR-204-5p in synovial fibroblasts suppressed synovial fibroblast activation by targeting genes related to cell proliferation and invasion. In vivo assays found that administration of lentiviruses expressing miR-204-5p markedly alleviated the disease progression of the mice with CIA. Collectively, this study identified a novel RA-associated plasma exosomal miRNA-204-5p that mediates the communication between immune cells and synovial fibroblasts and can be used as a potential biomarker for RA diagnosis and treatment.
Wen-Yi Zhang,Xin-Ze Xiao,Chao Lv,Jia Zhao,Gong Wang,Xuan Gu,Ran Zhang,Bin-Bin Xu,Dan-Dan Zhang,Ai-Wu Li,Yong-Lai Zhang,Hong-Bo Sun 한국고분자학회 2013 Macromolecular Research Vol.21 No.3
Reported here is the fabrication of photopolymer hierarchical micronanostructures through a combinative process of electrospinning and subsequent photolithography. Electrospun SU-8 (epoxy-based negative photoresist)nanofiber films have been patterned into gratings with periods of 100, 200, 300, and 400 μm, respectively. Deposition of a silver nanolayer on these interlaced nanofiber films would lead to the formation of various plasmonic nanostructures,and therefore, giving rise to abundant surface-enhanced Raman scattering (SERS) “hot spots”. In the detection of Rhodamine 6G (R6G), probing molecule, the resultant SERS substrates show both high sensitivity and good reproducibility. The SERS enhancement factor could reach as high as ~108, indicating high efficiency. The fabrication of patterned, highly efficient SERS substrates may hold a great promise for the integration of SERS substrates in various microdevices such as microfluidic chips.
Wen, Chun-Jie,Wu, Lan-Xiang,Fu, Li-Juan,Shen, Dong-Ya,Zhang, Xue,Zhang, Yi-Wen,Yu, Jing,Zhou, Hong-Hao Asian Pacific Journal of Cancer Prevention 2014 Asian Pacific journal of cancer prevention Vol.15 No.1
Estrogens are considered the major breast cancer risk factor, and the carcinogenic potential of estrogens might be attributed to DNA modification caused by derivatives formed during metabolism. $17{\beta}$-estradiol ($E_2$), the main steroidal estrogen present in women, is metabolized via two major pathways: formation of 2-hydroxyestradiol (2-OH $E_2$) and 4-hydroxyestradiol ($4-OH\;E_2$) through the action of cytochrome P450 (CYP) 1A1 and 1B1, respectively. Previous reports suggested that $2-OH\;E_2$ has putative protective effects, while $4-OH\;E_2$ is genotoxic and has potent carcinogenic activity. Thus, the ratio of $2-OH\;E_2/4-OH\;E_2$ is a critical determinant of the toxicity of $E_2$ in mammary cells. In the present study, we investigated the effects of berberine on the expression profile of the estrogen metabolizing enzymes CYP1A1 and CYP1B1 in breast cancer MCF-7 cells. Berberine treatment produced significant induction of both forms at the level of mRNA expression, but with increased doses produced 16~ to 52~fold greater induction of CYP1A1 mRNA over CYP1B1 mRNA. Furthermore, berberine dramatically increased CYP1A1 protein levels but did not influence CYP1B1 protein levels in MCF-7 cells. In conclusion, we present the first report to show that berberine may provide protection against breast cancer by altering the ratio of CYP1A1/CYP1B1, could redirect $E_2$ metabolism in a more protective pathway in breast cancer MCF-7 cells.
Geping Wu,Guanghai Yang,Ruxin Zhang,Guangyin Xu,Ling Zhang,Wu Wen,Jianbing Lu,Jianyong Liu,Yan Yu 대한천식알레르기학회 2015 Allergy, Asthma & Immunology Research Vol.7 No.5
Purpose: Allergic rhinitis (AR) is an inflammatory disorder of the upper airway. Exosomes or extracellular vesicles are nanosized vesicles of endosomal origin released from inflammatory and epithelial cells that have been implicated in allergic diseases. In this study, we characterized the microRNA (miRNA) content of exosomes in AR. Methods: Extracellular vesicles were isolated from nasal mucus from healthy control subjects (n=10) and patients with severe AR (n=10). Vesicle RNA was analyzed by using a TaqMan microRNA assays Human Panel-Early Access kit (Applied Biosystems, Foster City, CA, USA) containing probes for 366 human miRNAs, and selected findings were validated with quantitative RT-PCR. Target prediction and pathway analysis for the differentially expressed miRNAs were performed using DIANA-mirPath. Results: Twenty-one vesicle miRNAs were up -regulated and 14 miRNAs were under-regulated significantly (P<0.05) in nasal mucus from AR patients when compared to healthy controls. Bioinformatic analysis by DIANA-mirPath demonstrated that 32 KEGG biological processes were significantly enriched (P<0.05, FDR corrected) among differentially expressed vesicle miRNA signatures. Among them, the B-cell receptor signaling pathway (P=3.709E-09), the natural killer cell-mediated cytotoxicity (P=8.466E-05), the T-cell receptor signaling pathway (P=0.00075), the RIG-I-like receptor signaling pathway (P=0.00127), the Wnt signaling pathway (P=0.00130), endocytosis (P=0.00440), and salivary secretion (P=0.04660) were the most prominent pathways enriched in quantiles with differential vesicle miRNA patterns. Furthermore, miR-30-5p, miR-199b-3p, miR-874, miR-28-3p, miR-203, and miR-875-5p, involved in B-cell receptor and salivary secretion signaling pathways, were selected for validation using independent samples from 44 AR patients and 20 healthy controls. MiR-30-5p and miR-199b-3p were significantly increased in extracellular vesicles from nasal mucus when compared to healthy controls, while miR-874 and miR-28-3p were significantly down-regulated. In addition, miRNA-203 was significantly increased in AR patients, while miRNA-875-5p was found to be significantly decreased in AR patients. Conclusions: This study demonstrated that vesicle miRNA may be a regulator for the development of AR.
Xiang-Feng Wu,Yi-Jin Wang,Zuo-Lin Cao,Yan-Mei Feng,Hui Li,Chen-Xu Zhang,Jun-Zhang Su,Jia-Rui Zhang,Yi-Wei Wang,Kai-Yuan Wang,Guo-Wen Sun 대한화학회 2018 Bulletin of the Korean Chemical Society Vol.39 No.7
The novel AgCl/Ag2SO3 hybrids as an efficient photocatalyst had been fabricated by an in situ synthetic method. The correlations between the structure and the photocatalytic properties of the as-fabricated hybrids were analyzed. Experimental results exhibited that with increasing the amount of Ag2SO3, the degradation rate of the as-obtained samples was firstly increased and then decreased under the visible light irradiation. When the mass ratio of AgCl to Ag2SO3 was 1:2, in 30?min, it displayed the highest degradation rate of 99.2% for rhodamine-B, which was obviously higher than 46.1, 60.5, and 14.6% of pure AgCl, Ag2SO3, and TiO2 (P25), respectively. Similar results could be found in degradation of methyl orange. It had the maximum of 97.4% in 90?min, which was higher than 55.2, 48.7, and 12.7% of pure AgCl, Ag2SO3, and P25, respectively. Moreover, the as-prepared hybrids possessed the enhanced separation and transfer of photo-generated electron?hole pairs compared to the pure samples. In addition, the holes and superoxide radicals played the dominant role and the hydroxyl radicals played the secondary role during the process of photocatalytic degradation.
Wen, Wanqing,Zheng, Wei,Okada, Yukinori,Takeuchi, Fumihiko,Tabara, Yasuharu,Hwang, Joo-Yeon,Dorajoo, Rajkumar,Li, Huaixing,Tsai, Fuu-Jen,Yang, Xiaobo,He, Jiang,Wu, Ying,He, Meian,Zhang, Yi,Liang, Jun IRL Press 2014 Human molecular genetics Vol.23 No.20
<P>Recent genetic association studies have identified 55 genetic loci associated with obesity or body mass index (BMI). The vast majority, 51 loci, however, were identified in European-ancestry populations. We conducted a meta-analysis of associations between BMI and ∼2.5 million genotyped or imputed single nucleotide polymorphisms among 86 757 individuals of Asian ancestry, followed by <I>in silico</I> and <I>de novo</I> replication among 7488–47 352 additional Asian-ancestry individuals. We identified four novel BMI-associated loci near the <I>KCNQ1</I> (rs2237892, <I>P</I> = 9.29 × 10<SUP>−13</SUP>), <I>ALDH2/MYL2</I> (rs671, <I>P</I> = 3.40 × 10<SUP>−11</SUP>; rs12229654, <I>P</I> = 4.56 × 10<SUP>−9</SUP>), <I>ITIH4</I> (rs2535633, <I>P</I> = 1.77 × 10<SUP>−10</SUP>) and <I>NT5C2</I> (rs11191580, <I>P</I> = 3.83 × 10<SUP>−8</SUP>) genes. The association of BMI with rs2237892, rs671 and rs12229654 was significantly stronger among men than among women. Of the 51 BMI-associated loci initially identified in European-ancestry populations, we confirmed eight loci at the genome-wide significance level (<I>P</I> < 5.0 × 10<SUP>−8</SUP>) and an additional 14 at <I>P</I> < 1.0 × 10<SUP>−3</SUP> with the same direction of effect as reported previously. Findings from this analysis expand our knowledge of the genetic basis of obesity.</P>