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Assessment of the Cytotoxic and Apoptotic Effects of Chaetominine in a Human Leukemia Cell Line
( Jing Yun Yao ),( Rui Hua Jiao ),( Chang Qing Liu ),( Yu Peng Zhang ),( Wan Guo Yu ),( Yan Hua Lu ),( Ren Xiang Tan ) 한국응용약물학회 2016 Biomolecules & Therapeutics(구 응용약물학회지) Vol.24 No.2
Chaetominine is a quinazoline alkaloid originating from the endophytic fungus Aspergillus fumigatus CY018. In this study, we showed evidence that chaetominine has cytotoxic and apoptotic effects on human leukemia K562 cells and investigated the pathway involved in chaetominine-induced apoptosis in detail. Chaetominine inhibited K562 cell growth, with an IC50 value of 35 nM, but showed little inhibitory effect on the growth of human peripheral blood mononuclear cells. The high apoptosis rates, morphological apoptotic features, and DNA fragmentation caused by chaetominine indicated that the cytotoxicity was partially caused by its pro-apoptotic effect. Under chaetominine treatment, the Bax/Bcl-2 ratio was upregulated (from 0.3 to 8), which was followed by a decrease in mitochondrial membrane potential, release of cytochrome c from mitochondria into the cytosol, and stimulation of Apaf-1. Furthermore, activation of caspase-9 and caspase-3, which are the main executers of the apoptotic process, was observed. These results demonstrated that chaetominine induced cell apoptosis via the mitochondrial pathway. Chaetominine inhibited K562 cell growth and induced apoptotic cell death through the intrinsic pathway, which suggests that chaetominine might be a promising therapeutic for leukemia.
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Han Ying-Hao,Mao Ying-Ying,Yu Nan-Nan,Jin Mei-Hua,Jin Ying-Hua,Wang Ai-Guo,Zhang Yong-Qing,Shen Gui-Nan,Cui Yu-Dong,Yu Li-Yun,Lee Dong-Seok,Jo Yu-Jin,Sun Hu-Nan,Kwon Jeongwoo,권태호 한국응용생명화학회 2020 Applied Biological Chemistry (Appl Biol Chem) Vol.63 No.3
In this study, we used RNA sequencing (RNA-seq) to analyze and compare bulk cell samples from wild-type (WT) dermal mesenchymal stem cells (DMSCs) (n = 3) and Prx II knockout DMSCs (n = 3). The purpose of the study was to elucidate the role of Prx II on allogeneic immune rejection of transplanted DMSCs. The results revealed differential expression of 472 genes (176 up-regulated and 296 down-regulated; p ≤ 0.05) between the PrxII+/+ (WT) and PrxII−/− sample groups. When highly regulated genes were categorized according to the Gene Ontology (GO) molecular function classification and the Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis, the PrxII−/− samples showed a robust downward trend in allograft rejection. The study identified 43 all immunologically rejected differentially expressed genes, of which 41 showed lower expression in the PrxII−/− vs. PrxII+/+ (WT) samples. These findings suggest that Prx II gene knockout may down-regulate the allograft rejection that occurs during DMSCs transplantation and improve the survival rate of DMSCs in the host. This study provides a new perspective on the clinical treatment of stem cell transplantation.
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Yu, Yang,Xiang, Hua,He, Xiang-Ming,Yang, Hong-Jian,Zong, Xiang-Yun Asian Pacific Journal of Cancer Prevention 2013 Asian Pacific journal of cancer prevention Vol.14 No.4
From January 1, 2008 to March 31, 2010, 101 patients with stage II-III breast cancer were enrolled in this study and subjected to an anthracycline-based neoadjuvant chemotherapy regimen with or without docetaxel. Surgery was performed after 2-6 cycles of chemotherapy, and the clinical response was determined by pathological and histochemical assessments. The clinical response rate, as indicated by complete response (CR), partial response (PR), stable disease (SD), and progressive disease (PD), were 6.9, 52.5, 36.6, and 4.0%, respectively. A multivariable correlation analysis indicated that the overall clinical response rate correlated with the number of metastatic lymph nodes, number of chemotherapy cycles, and vessel invasion status. Importantly, the CR rate was only associated with the number of chemotherapy cycles. Nonparametric tests failed to detect a correlation between HER2 or Topo $II{\alpha}$ status and clinical response to neoadjuvant chemotherapy in these patients. When they were stratified by HER2 or HR status, for HER2-positive patients the CR rate was associated with vessel invasion and Topo $II{\alpha}$ status. Based on our findings, we propose that HR, HER-2 and Topo $II{\alpha}$ are not putative predictive biomarkers of chemotherapy outcome for breast cancer patients. Topo $II{\alpha}$ expression level was only inversely correlated with CR rate among HR-positive patients. Importantly, the achievement of CR was largely related to the number of chemotherapy cycles.
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Yu, Wan-Guo,He, Hao,Yao, Jing-Yun,Zhu, Yi-Xiang,Lu, Yan-Hua The Korean Society of Applied Pharmacology 2015 Biomolecules & Therapeutics(구 응용약물학회지) Vol.23 No.6
Consumption of herbal tea [flower buds of Cleistocalyx operculatus (Roxb.) Merr. et Perry (Myrtaceae)] is associated with health beneficial effects against multiple diseases including diabetes, asthma, and inflammatory bowel disease. Emerging evidences have reported that High mobility group box 1 (HMGB1) is considered as a key "late" proinflammatory factor by its unique secretion pattern in aforementioned diseases. Dimethyl cardamonin (2',4'-dihydroxy-6'-methoxy-3',5'-dimethylchalcone, DMC) is a major ingredient of C. operculatus flower buds. In this study, the anti-inflammatory effects of DMC and its underlying molecular mechanisms were investigated on lipopolysaccharide (LPS)-induced macrophages. DMC notably suppressed the mRNA expressions of TNF-${\alpha}$, IL-$1{\beta}$, IL-6, and HMGB1, and also markedly decreased their productions in a time- and dose-dependent manner. Intriguingly, DMC could notably reduce LPS-stimulated HMGB1 secretion and its nucleo-cytoplasmic translocation. Furthermore, DMC dose-dependently inhibited the activation of phosphatidylinositol 3-kinase (PI3K), phosphoinositide-dependent kinase 1 (PDK1), and protein kinase C alpha (PKC${\alpha}$). All these data demonstrated that DMC had anti-inflammatory effects through reducing both early (TNF-${\alpha}$, IL-$1{\beta}$, and IL-6) and late (HMGB1) cytokines expressions via interfering with the PI3K-PDK1-PKC${\alpha}$ signaling pathway.
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( Yun Peng Wang ),( Pei Pei Hao ),( Mi Jin Lee ),( Goung Ran Yu ),( Hua Lee ),( Seong Hun Kim ),( Dae Ghon Kim ) 대한간학회 2012 춘·추계 학술대회 (KASL) Vol.2012 No.1
Background: CTHRC1 is a 30 kDa secreted protein that has the ability to inhibit collagen matrix synthesis. CTHRC1 expression in breast cancer and colorectal cancer is associated with cancer tissue invasion and metastasis. But, the functional significance of CTHRC1 expression in hepatocellular carcinoma (HCC) is unknown. So the purpose of this study is to investigate whether CTHRC1 is a biomolecular marker in human hepatocellular carcinoma. Methods: CTHRC1 protein expression was investigated by Immunoblotting analysis in HCC cell lines and HCC tumor tissues, respectively. The expressions of CTHRC1 in HCC tissues were also evaluated by immunohistochemical staining according to tumor differentiaton and stage. CTHRC1 levels were assessed in serum of HCC patients by Western blot analysis. Colony formation was assessed in SH-J1 and HLK3 cells. Results: Endogenous and ectopic expression of CTHRC1 was mainly localized in the cytoplasm of the tumor cells. The immunohistochemical staining showed that the expression of CTHRC1 was negligible in normal liver tissue, but most tumors were immunoreactive. CTHRC1 was highly expressed in tumor tissues compares with non - tumor tissues, but barely expressed in HCC cells. We also found that secreted CTHRC1 was abundantly present in the serum of the patients with early and advanced HCCs, and absent with normal liver. Colony generation assay revealed that CTHRC1 overexpression increased colony number by two-folds. Conclusions: These results suggest that CTHRC1 protein maybe useful as a potential biomolecular maker for HCC.
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Yu, Jian-Qin,Zhou, Qing,Zhu, Hua,Zheng, Fei-Yun,Chen, Zhi-Wen Asian Pacific Journal of Cancer Prevention 2015 Asian Pacific journal of cancer prevention Vol.16 No.6
Objectives: To explore the expression of astrocyte elevated gene-1 (AEG-1) in cervical cancer and analyze its correlation with microvascular density (MVD), nuclear factor kappaB (NF-kB p65) and vascular endothelial growth factor (VEGF). Materials and Methods: Immunohistochemical MaxVision method was adopted to detect the expression level of AEG-1, NF-kB p65 and VEGF in 45 samples of invading cervical cancer and 12 samples of cervicitis from The First Affiliated Hospital of Wenzhou Medical University. Tumor microvascular endothelial marker CD34 combined with Weidner was used to determine the MVD in cervical cancer tissue. The positive expression and staining conditions of AEG-1, NF-kB p65 and VEGF in cervical cancer tissues were observed under a light microscope. Correlations between expression of AEG-1 protein and those of NF-Kb p65 and VEGF, as well as MVD, were analyzed using Pearson correlation. Results: The expression levels of AEG-1 were $0.186{\pm}0.043$ in cervical cancer and $0.051{\pm}0.002$ in chronic cervicitis (p<0.01). Moreover, expression of AEG-1 was related to vascular invasion and lymphatic metastasis of cervical cancer (p<0.01), but not with age of the patients, differentiation degree, tumour size, pathological type and parametrial infiltration (p>0.05). Pearson correlation analysis showed that the expression of AEG-1 was linked with NF-kB p65 (r=0.501, p=0.000), VEGF (r=0.718, p=0.000) as well as MVD in cervical cancer tissue (r=0.815, p=0.000). Conclusions: AEG-1 is highly expressed in cervical cancer and promotes angiogenesis, which might be related to the fact that AEG-1 activating the signal pathway of NF-kB could up-regulate the level of VEGF expression.
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( Yun Peng Wang ),( Pei Pei Hao ),( Mi Jin Lee ),( Goung Ran Yu ),( Hua Lee ),( Seong Hun Kim ),( Dae Ghon Kim ) 대한간학회 2012 춘·추계 학술대회 (KASL) Vol.2012 No.-
Background: CTHRC1 is a 30 kDa secreted protein that has the ability to inhibit collagen matrix synthesis. CTHRC1 expression in breast cancer and colorectal cancer is associated with cancer tissue invasion and metastasis. But, the functional significance of CTHRC1 expression in hepatocellular carcinoma (HCC) is unknown. So the purpose of this study is to investigate whether CTHRC1 is a biomolecular marker in human hepatocellular carcinoma. Methods: CTHRC1 protein expression was investigated by Immunoblotting analysis in HCC cell lines and HCC tumor tissues, respectively. The expressions of CTHRC1 in HCC tissues were also evaluated by immunohistochemical staining according to tumor differentiaton and stage. CTHRC1 levels were assessed in serum of HCC patients by Western blot analysis. Colony formation was assessed in SH-J1 and HLK3 cells. Results: Endogenous and ectopic expression of CTHRC1 was mainly localized in the cytoplasm of the tumor cells. The immunohistochemical staining showed that the expression of CTHRC1 was negligible in normal liver tissue, but most tumors were immunoreactive. CTHRC1 was highly expressed in tumor tissues compares with non - tumor tissues, but barely expressed in HCC cells. We also found that secreted CTHRC1 was abundantly present in the serum of the patients with early and advanced HCCs, and absent with normal liver. Colony generation assay revealed that CTHRC1 overexpression increased colony number by two-folds. Conclusions: These results suggest that CTHRC1 protein maybe useful as a potential biomolecular maker for HCC.
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Chang-Yun Liu,Ji-Lan Lin,Shu-Yan Feng,Chun-Hui Che,Hua-Pin Huang,Zhang-Yu Zou 대한신경과학회 2022 Journal of Clinical Neurology Vol.18 No.1
Background and Purpose Mutations in the FIG4 gene have been linked to amyotrophic lateral sclerosis (ALS) type 11 in Caucasian populations. The purpose of this study was to identify FIG4 variants in a cohort of 15 familial ALS (FALS) indexes and 275 sporadic ALS (SALS) patients of Han Chinese origin. Methods All 23 exons of FIG4 were sequenced using targeted next-generation sequencing. An extensive literature review was performed to detect genotype-phenotype associations of FIG4 mutations. Results No FIG4 variants were identified in the FALS patients. One novel heterozygous missense variant (c.352G>T [p.D118Y]) and one novel heterozygous nonsense variant (c.2158G>T [p.E720X]) in FIG4 were identified in two SALS patients. The p.E720X variant is interpreted as likely pathogenic while the p.D118Y variant is a variant of uncertain significance. The patient carrying the p.E720X mutation developed lower-limb-onset slowly progressive ALS, and survived for 11.5 years. The patient harboring the FIG4 p.D118Y variant also presented with progressive ALS, with the score on the ALS Functional Rating Scale–Revised (ALSFRS-R) decreasing by 0.4 per month. The rate of decrease in the ALSFRS-R scores from symptom onset to diagnosis seemed to be lower in the patients carrying FIG4 variants than the no-FIG4-mutation ALS patients in this study. Conclusions Our findings suggest that ALS patients carrying FIG4 mutations are not common in the Chinese population and are more likely to exhibit slow progression.
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Finite Element Analysis and Test Study on Restraint of High-energy Pipe Whip in Conventional Island
Ling-yun Peng,Yu-ke Deng,Hua-ting Chen,Ying-jie Kang,Xiang-xiu Li 대한토목학회 2019 KSCE JOURNAL OF CIVIL ENGINEERING Vol.23 No.4
The effects of high-energy pipe whipping after rupturing are very important in an AP1000 nuclear power plant's conventional island and restraints of pipe whipping should be considered in the design. It is the first time in the country when reinforced concrete shear walls are used as restraint services. In this paper, the behaviors of walls and restraint services subjected to pipe whipping are analyzed through static and dynamic methods in the finite element software (ABAQUS), in which all kinds of nonlinearities are considered. In addition, a test study on the restraint of pipe whipping is conducted. The results show that the wall and the restraint service can prevent pipe whipping effectively under the design load, and anchor plates arranged around the wall opening can improve the local concrete compression performance of concrete to reduce the damage of concrete. Meanwhile, the study also provides the valuable reference for wall designing to prevent from pipe whipping.
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