28 results on '"Ji-Lin Chen"'
Search Results
2. Molecular network mechanism in cerebral ischemia-reperfusion rats treated with human urine stem cells
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Lang-Chun Zhang, Na Li, Ji-Lin Chen, Jie Sun, Min Xu, Wen-Qiang Liu, Zhong-Fu Zuo, Lan-Lan Shi, Ting-Hua Wang, and Xiang-Yin Luo
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Cerebral ischemia reperfusion ,Human urine stem cells ,Bioinformatics ,Science (General) ,Q1-390 ,Social sciences (General) ,H1-99 - Abstract
Objective: To explore the effect of human urine-derived stem cells (husc) in improving the neurological function of rats with cerebral ischemia-reperfusion (CIR), and report new molecular network by bioinformatics, combined with experiment validation. Methods: After CIR model was established, and husc were transplanted into the lateral ventricle of rats,neurological severe score (NSS) andgene network analysis were performed. Firstly, we input the keywords “Cerebral reperfusion” and “human urine stem cells” into Genecard database and merged data with findings from PubMed so as to get their targets genes, and downloaded them to make Venny intersection plot. Then, Gene ontology (GO) analysis, kyoto encyclopedia of genes and genomes (KEGG) pathway analysis and protein-protein interaction (PPI) were performed to construct molecular network of core genes. Lastly, the expressional level of core genes was validated via quantitative real-time polymerase chain reaction (qRT-PCR), and localized by immunofluorescence. Results: Compared with the Sham group, the neurological function of CIR rats was significantly improved after the injection of husc into the lateral ventricle; at 14 days, P = 0.028, which was statistically significant. There were 258 overlapping genes between CIR and husc, and integrated with 252 genes screened from PubMed and CNKI. GO enrichment analysis were mainly involved neutrophil degranulation, neutrophil activation in immune response and platelet positive regulation of degranulation, Hemostasis, blood coagulation, coagulation, etc. KEGG pathway analysis was mainly involved in complement and coagulation cascades, ECM-receptor. Hub genes screened by Cytoscape consist ofCD44, ACTB, FN1, ITGB1, PLG, CASP3, ALB, HSP90AA1, EGF, GAPDH. Lastly, qRT-PCR results showed statistic significance (P
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- 2024
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3. Interplay between lncRNA RP11-367G18.1 variant 2 and YY1 plays a vital role in hypoxia-mediated gene expression and tumorigenesis
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Pei-Hua Peng, Ji-Lin Chen, Heng-Hsiung Wu, Wen-Hao Yang, Li-Jie Lin, Joseph Chieh-Yu Lai, Jeng-Shou Chang, Jia-Ling Syu, Han-Tsang Wu, Fei-Ting Hsu, Wei-Chung Cheng, and Kai-Wen Hsu
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Hypoxia ,lncRNA RP11-367G18.1 variant 2 ,YY1 ,Neoplasms. Tumors. Oncology. Including cancer and carcinogens ,RC254-282 ,Cytology ,QH573-671 - Abstract
Abstract Background The hypoxia-responsive long non-coding RNA, RP11-367G18.1, has recently been reported to induce histone 4 lysine 16 acetylation (H4K16Ac) through its variant 2; however, the underlying molecular mechanism remains poorly understood. Methods RNA pull-down assay and liquid chromatography-tandem mass spectrometry were performed to identify RP11-367G18.1 variant 2-binding partner. The molecular events were examined utilizing western blot analysis, real-time PCR, luciferase reporter assay, chromatin immunoprecipitation, and chromatin isolation by RNA purification assays. The migration, invasion, soft agar colony formation, and in vivo xenograft experiments were conducted to evaluate the impact of RP11-367G18.1 variant 2–YY1 complex on tumor progression. Results In this study, RNA sequencing data revealed that hypoxia and RP11-367G18.1 variant 2 co-regulated genes were enriched in tumor-related pathways. YY1 was identified as an RP11-367G18.1 variant 2-binding partner that activates the H4K16Ac mark. YY1 was upregulated under hypoxic conditions and served as a target gene for hypoxia-inducible factor-1α. RP11-367G18.1 variant 2 colocalized with YY1 and H4K16Ac in the nucleus under hypoxic conditions. Head and neck cancer tissues had higher levels of RP11-367G18.1 and YY1 which were associated with poor patient outcomes. RP11-367G18.1 variant 2–YY1 complex contributes to hypoxia-induced epithelial–mesenchymal transition, cell migration, invasion, and tumorigenicity. YY1 regulated hypoxia-induced genes dependent on RP11-367G18.1 variant 2. Conclusions RP11-367G18.1 variant 2–YY1 complex mediates the tumor-promoting effects of hypoxia, suggesting that this complex can be targeted as a novel therapeutic strategy for cancer treatment.
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- 2023
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4. RP11‐367G18.1 V2 enhances clear cell renal cell carcinoma progression via induction of epithelial–mesenchymal transition
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I‐Hung Shao, Pei‐Hua Peng, Heng‐Hsiung Wu, Ji‐Lin Chen, Joseph Chieh‐Yu Lai, Jeng‐Shou Chang, Han‐Tsang Wu, Kou‐Juey Wu, See‐Tong Pang, and Kai‐Wen Hsu
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clear cell renal cell carcinoma ,epithelial–mesenchymal transition ,H4K16Ac ,hypoxia ,lncRNA RP11‐367G18.1 ,Neoplasms. Tumors. Oncology. Including cancer and carcinogens ,RC254-282 - Abstract
Abstract Purpose Metastasis is the end stage of renal cell carcinoma (RCC), and clear cell renal cell carcinoma (ccRCC) is the most common malignant subtype. The hypoxic microenvironment is a common feature in ccRCC and plays an essential role in the regulation of epithelial–mesenchymal transition (EMT). Accumulating evidence manifests that long non‐coding RNAs (lncRNAs) participate in RCC tumorigenesis and regulate hypoxia‐induced EMT. Here, we identified a lncRNA RP11‐367G18.1 induced by hypoxia, that was overexpressed in ccRCC tissues. Methods A total of 216 specimens, including 149 ccRCC tumor samples and 67 related normal kidney parenchyma tissue samples, were collected. To investigate the biological fucntions of RP11.367G18.1 in ccRCC, migration, invasion, soft agar colony formation, xenograft tumorigenicity assays, and tail vein and orthotopic metastatic mouse models were performed. The relationship between RP11‐367G18.1 and downstream signaling was analyzed utilizing reporter assay, RNA pull‐down, chromatin immunopreciptation, and chromatin isolation by RNA purification assays. Results Hypoxic conditions and overexpression of HIF‐1α increased the level of RP11‐367G18.1. RP11‐367G18.1 induced EMT and enhanced cell migration and invasion through variant 2. Inhibition of RP11‐367G18.1 variant 2 reversed hypoxia‐induced EMT phenotypes. An in vivo study revealed that RP11‐367G18.1 variant 2 was required for hypoxia‐induced tumor growth and metastasis in ccRCC. Mechanistically, RP11‐367G18.1 variant 2 interacted with p300 histone acetyltransferase to regulate lysine 16 acetylation on histone 4 (H4K16Ac), thus contributing to hypoxia‐regulated gene expression. Clinically, RP11‐367G18.1 variant 2 was upregulated in ccRCC tissues, particularly metastatic ccRCC tissues, and it is linked to poor overall survival. Conclusion These findings demonstrate the prognostic value and EMT‐promoting role of RP11‐367G18.1 and indicate that this lncRNA may provide a therapeutic target for ccRCC.
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- 2023
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5. Network pharmacology mechanism of Scutellarin to inhibit RGC pyroptosis in diabetic retinopathy
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Na Li, Xi-Liang Guo, Min Xu, Ji-Lin Chen, Yu-Fei Wang, Jie-Sun, Yu-Gao Xiao, An-Shun Gao, Lan-Chun Zhang, Xue-Zheng Liu, and Ting-Hua Wang
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Medicine ,Science - Abstract
Abstract To investigate the effect of scutellarin (SCU) in diabetic retinopathy (DR) and explore the associated molecular network mechanism. The animal model of DR was established from diabetic mellitus (DM) rats by intraperitoneally injected streptozotocin (STZ) at dosage 55 mg/kg. Meanwhile, SCU was intraperitoneally administrated to protect retina from cell pyroptosis induced by DM, and cell pyroptosis was detected by using HE, Nissl staining, and immunofluorescence recognition. Moreover, the hub gene involving in pyroptosis in DR was screened by bioinformatics and network pharmacology, designated as Venny intersection screen, GO and KEGG analysis, PPI protein interaction, and molecular docking. Lastly, the expressional change of hub genes were validated with experimental detection. Cell pyroptosis of the DR, specifically in retina ganglion cells (RGC), was induced in DM rats; SCU administration results in significant inhibition in the cell pyroptosis in DR. Mechanically, 4084 genes related to DR were screened from GeneCards and OMIM databases, and 120 SCU therapeutic targets were obtained, by using GeneCards, TCMSP with Swiss Target Prediction databases. Moreover, 357 targets related to pyroptosis were found using GenenCards database, and Drug, disease and phenotypic targets were analyzed online using the Draw Venn Diagram website, and 12 cross targets were obtained. Through GO function and KEGG pathway enrichment analysis, 659 BP related items, 7 CC related items, 30 MF related items, and 70 signal pathways were screened out; Of these, eleven proteins screened from cross-target PPI network were subsequently docked with the SCU, and their expressions including caspase-1, IL-1β, IL-18, GSDMD and NLRP3 in RGC indicated by immunofluorescence, and the mRNA expression for caspase-1 in DR indicated by quantitative PCR, were successfully validated. SCU can effectively protect RGC pyroptosis in DR, and underlying mechanisms are involved in the inhibition of caspase-1, GSDMD, NLRP3, IL-1β and IL-18. Our findings therefore provide crucial evidence to support the clinic practice of SCU for the treatment of DR, and explained the underlying molecular network mechanism.
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- 2023
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6. Correlation of an immune-related 8-gene panel with pathologic response to neoadjuvant chemotherapy in patients with primary breast cancers
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Ling-Ming Tseng, Chi-Cheng Huang, Yi-Fang Tsai, Ji-Lin Chen, Ta-Chung Chao, Jiun-I Lai, Pei-Ju Lien, Yen-Shu Lin, Chin-Jung Feng, Yen-Jen Chen, Jen-Hwey Chiu, Chih-Yi Hsu, and Chun-Yu Liu
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Neoadjuvant chemotherapy ,Breast cancer ,Pathologic complete response ,Neoplasms. Tumors. Oncology. Including cancer and carcinogens ,RC254-282 - Abstract
Neoadjuvant chemotherapy (NACT)-induced pathologic complete response (pCR) is associated with a favorable prognosis for breast cancer. Prior research links tumor-infiltrating lymphocytes with breast cancer chemotherapy response, suggesting the tumor-immune microenvironment's role. The aim of this study was to evaluate the immune-related genes that exhibit associations with the response to NACT. In this study, we analyzed a total of 37 patients (aged 27–67) who received NACT as the first-line treatment for primary breast cancer, followed by surgery. This group consisted of nine patients (24.3 %) with estrogen receptor (ER)-positive/HER2-negative status, ten patients (27.0 %) with ER-positive/HER2-positive status, five patients (13.5 %) with ER-negative/HER2-positive status, and thirteen patients (35.1 %) with triple-negative breast cancer (TNBC). Among these patients, twelve (32.4 %) achieved a pCR, with eight (66.6 %) having HER2-positive tumors, and the remaining four having TNBC. To identify immune-related genes linked with pCR in subjects with breast cancer prior to NACT, we collected fresh tissues for next-generation sequencing. Patients with pCR had higher expressions of eight genes, KLRK1, IGJ, CD69, CD40LG, MS4A1, CD1C, KLRB1, and CA4, compared to non-pCR patients. The 8-gene signature was associated with good prognosis and linked to better relapse-free survival in patients receiving chemotherapy. The expression of these genes was involved in better drug response, displaying a positive correlation with the infiltration of immune cells. In conclusion, we have identified eight immune-related genes that are associated with a favorable prognosis and positive responses to drugs. This 8-gene signature could potentially provide prognostic insights for breast cancer patients undergoing NACT.
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- 2023
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7. METTL4-mediated nuclear N6-deoxyadenosine methylation promotes metastasis through activating multiple metastasis-inducing targets
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Kai-Wen Hsu, Joseph Chieh-Yu Lai, Jeng-Shou Chang, Pei-Hua Peng, Ching-Hui Huang, Der-Yen Lee, Yu-Cheng Tsai, Chi-Jung Chung, Han Chang, Chao-Hsiang Chang, Ji-Lin Chen, See-Tong Pang, Ziyang Hao, Xiao-Long Cui, Chuan He, and Kou-Juey Wu
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METTL4 ,6mA ,Hypoxia ,lncRNA ,ZMIZ1 ,Metastasis ,Biology (General) ,QH301-705.5 ,Genetics ,QH426-470 - Abstract
Abstract Background DNA N6-methyldeoxyadenosine (6mA) is rarely present in mammalian cells and its nuclear role remains elusive. Results Here we show that hypoxia induces nuclear 6mA modification through a DNA methyltransferase, METTL4, in hypoxia-induced epithelial-mesenchymal transition (EMT) and tumor metastasis. Co-expression of METTL4 and 6mA represents a prognosis marker for upper tract urothelial cancer patients. By RNA sequencing and 6mA chromatin immunoprecipitation-exonuclease digestion followed by sequencing, we identify lncRNA RP11-390F4.3 and one novel HIF-1α co-activator, ZMIZ1, that are co-regulated by hypoxia and METTL4. Other genes involved in hypoxia-mediated phenotypes are also regulated by 6mA modification. Quantitative chromatin isolation by RNA purification assay shows the occupancy of lncRNA RP11-390F4.3 on the promoters of multiple EMT regulators, indicating lncRNA-chromatin interaction. Knockdown of lncRNA RP11-390F4.3 abolishes METTL4-mediated tumor metastasis. We demonstrate that ZMIZ1 is an essential co-activator of HIF-1α. Conclusions We show that hypoxia results in enriched 6mA levels in mammalian tumor cells through METTL4. This METTL4-mediated nuclear 6mA deposition induces tumor metastasis through activating multiple metastasis-inducing genes. METTL4 is characterized as a potential therapeutic target in hypoxic tumors.
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- 2022
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8. Interfering B cell receptor signaling via SHP-1/p-Lyn axis shows therapeutic potential in diffuse large B-cell lymphoma
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Ji-Lin Chen, Pei-Yi Chu, Chun-Teng Huang, Tzu-Ting Huang, Wan-Lun Wang, Yu-Hsuan Lee, Yuan-Ya Chang, Ming-Shen Dai, Chung-Wai Shiau, and Chun-Yu Liu
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Diffuse large B cell lymphoma ,SHP-1 ,Apoptosis ,Therapeutics. Pharmacology ,RM1-950 ,Biochemistry ,QD415-436 - Abstract
Abstract Background Diffuse large B cell lymphoma (DLBCL) is an aggressive and molecularly heterogeneous non-Hodgkin’s lymphoma. The B cell receptor (BCR) signaling pathway in DLBCL emerges as a new drug target. Protein phosphatase SHP-1 negatively regulates several oncogenic tyrosine kinases and plays a tumor suppressive role. Methods The direct SHP-1 agonists were used to evaluate the potential therapeutic implication of SHP-1 in DLBCL. Immunohistochemical staining for SHP-1 was quantified by H-score. The SHP-1 phosphatase activity was determined using tyrosine phosphatase assay. In vitro studies, including MTT, western blot analysis and cell apoptosis, were utilized to examined biological functions of SHP-1. Results Oral administration of SHP-1 agonist showed the potent anti-tumor effects compared to a selective Bruton’s tyrosine kinase (BTK) inhibitor ibrutinib in mice bearing U2932 xenografts. SHP-1 agonist increased SHP-1 activity as well as downregulated p-Lyn in vivo. Here, we demonstrated that immunohistochemical staining for SHP-1 expression was positive in 76% of DLBCL samples. SHP-1 agonist exerted anti-proliferative and apoptotic effects compared with ibrutinib in DLBCL cells. Mechanistically, SHP-1 agonist decreased BCR signaling, especially p-Lyn, and led to apoptosis. Conclusions These data suggest that SHP-1 negatively regulates phosphorylation of Lyn, and targeting SHP-1/p-Lyn using SHP-1 agonist has therapeutic potential for treatment of DLBCL.
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- 2022
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9. Lu Tong Ke Li protects neurons from injury by regulating inflammation in rats with brain trauma
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Jie Chen, Ting‐Ting Li, Ting‐Bao Chen, Rui‐Ze Niu, Ji‐Lin Chen, Yong Chen, and Jin Huang
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Chinese medicine ,Inflammation genes ,Lu Tong Ke Li ,Neuroprotection ,Traumatic brain injury ,Neurosciences. Biological psychiatry. Neuropsychiatry ,RC321-571 - Abstract
Abstract Currently, there is no effective therapy for traumatic brain injury (TBI). Therefore, this study was conducted to determine the protective effect of Lu Tong Ke Li (LTKL), a Chinese medicine, for TBI in experimental animals. The TBI rat model was induced using the modified Feeney's protocol. The rats were divided into four groups: Sham group, Control group, LTKL lower‐dose group (LTL, 2 g/kg/day, p.o.), and LTKL higher‐dose group (LTH, 4 g/kg/day, p.o.). The Neurological Severity Score (NSS) was used to examine neurological function. Magnetic resonance imaging was performed to check the brain tissue lesions in rats. Cell apoptosis in the damaged area was evaluated using the Terminal deoxynucleotidyl transferase deoxy‐UTP‐nick end labeling assay. Reverse‐transcription polymerase chain reaction was used to investigate the expression of inflammatory cytokines, including tumor necrosis factor‐α (TNF‐α), interleukin 1β (IL‐1β), and interleukin 10 (IL‐10). The TBI rat model was successfully constructed. Neurological function was enhanced at 14, 21, and 28 days post TBI in the LTH groups, indicated by gradually decreased NSS scores. Administration of LTH led to fewer brain defects in the damaged area, and the number of apoptosis cells in the brain injury area markedly decreased. LTKL treatment led to upregulation of IL‐10 expression and downregulation of TNF‐α and IL‐1β expressions at the molecular level. LTKL can improve the neurobehavior of TBI. The neuroprotective effect was probably related to regulation of inflammation cytokines. Our results provide crucial evidence of the potentially useful application of LTKL in the therapy of TBI in clinic practice in the future.
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- 2022
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10. Using bioinformatics approaches to identify survival-related oncomiRs as potential targets of miRNA-based treatments for lung adenocarcinoma
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Chia-Hsin Liu, Shu-Hsuan Liu, Yo-Liang Lai, Yi-Chun Cho, Fang-Hsin Chen, Li-Jie Lin, Pei-Hua Peng, Chia-Yang Li, Shu-Chi Wang, Ji-Lin Chen, Heng-Hsiung Wu, Min-Zu Wu, Yuh-Pyng Sher, Wei-Chung Cheng, and Kai-Wen Hsu
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oncomiR ,antagomiR ,Lung adenocarcinoma ,miRNA treatment ,Biotechnology ,TP248.13-248.65 - Abstract
Lung cancer is a major cause of cancer-associated deaths worldwide, and lung adenocarcinoma (LUAD) is the most common lung cancer subtype. Micro RNAs (miRNAs) regulate the pattern of gene expression in multiple cancer types and have been explored as potential drug development targets. To develop an oncomiR-based panel, we identified miRNA candidates that show differential expression patterns and are relevant to the worse 5-year overall survival outcomes in LUAD patient samples. We further evaluated various combinations of miRNA candidates for association with 5-year overall survival and identified a four-miRNA panel: miR-9-5p, miR-1246, miR-31-3p, and miR-3136-5p. The combination of these four miRNAs outperformed any single miRNA for predicting 5-year overall survival (hazard ratio [HR]: 3.47, log-rank p-value = 0.000271). Experiments were performed on lung cancer cell lines and animal models to validate the effects of these miRNAs. The results showed that singly transfected antagomiRs largely inhibited cell growth, migration, and invasion, and the combination of all four antagomiRs considerably reduced cell numbers, which is twice as effective as any single miRNA-targeted transfected. The in vivo studies revealed that antagomiR-mediated knockdown of all four miRNAs significantly reduced tumor growth and metastatic ability of lung cancer cells compared to the negative control group. The success of these in vivo and in vitro experiments suggested that these four identified oncomiRs may have therapeutic potential.
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- 2022
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11. The neuroprotective effects of Lutongkeli in traumatic brain injury rats by anti-apoptosis mechanism
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Qiu-Xia Xiao, Lu-Lu Xue, Zhang-Yu Su, Jin Huang, Ji-Lin Chen, Liu-Lin Xiong, and Ting-Hua Wang
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Brain Injuries ,Traumatic ,Lutongkeli ,Network Pharmacology ,Apoptosis ,Neuroprotection ,Surgery ,RD1-811 - Abstract
ABSTRACT Purpose: To explore the neuroprotective effects of Lutongkeli (LTKL) in traumatic brain injury (TBI) and detect the related mechanism. Methods: TBI model was established with LTKL administration (2 and 4 g/kg/d, p.o.). Motor function of rats was examined by Rotarod test. Nissl staining was used to show neuron morphology. Furthermore, the disease-medicine common targets were obtained with the network pharmacology and analyzed with Kyoto Encyclopedia of Genes and Genomes. Lastly, the predicted targets were validated by real-time polymerase chain reaction. Results: After LTKL administration, neural behavior was significantly improved, and the number of spared neurons in brain was largely increased. Moreover, 68 bioactive compounds were identified, corresponding to 148 LTKL targets; 2,855 genes were closely associated with TBI, of which 87 overlapped with the LTKL targets and were considered to be therapeutically relevant. Functional enrichment analysis suggested LTKL exerted its pharmacological effects in TBI by modulating multiple pathways including apoptosis, inflammation, etc. Lastly, we found LTKL administration could increase the mRNA level of Bcl-2 and decrease the expression of Bax and caspase-3. Conclusions: This study reported the neuroprotective effect of LTKL against TBI is accompanied with anti-apoptosis mechanism, which provides a scientific explanation for the clinical application of LTKL in the treatment of TBI.
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- 2022
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12. Gene Network Mechanism of Zhilong Huoxue Tongyu Capsule in Treating Cerebral Ischemia–Reperfusion
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Na Li, Jie Sun, Ji-Lin Chen, Xue Bai, and Ting-Hua Wang
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ZhiLong HuoXue TongYu capsule ,cerebral ischemia–reperfusion ,network pharmacology ,molecular docking ,gene network analysis ,Therapeutics. Pharmacology ,RM1-950 - Abstract
Objective: To investigate the effect of Zhilong Huoxue Tongyu capsule (ZLH) in the treatment of cerebral ischemia–reperfusion injury and determine the underlying molecular network mechanism.Methods: The treatment effect of Zhilong Huoxue Tongyu capsule (ZLH) was evaluated for cerebral ischemia–reperfusion injury in middle cerebral artery occlusion (MACO) rat, and the underlying molecular network mechanism was explored by using molecular network analysis based on network pharmacology, bioinformatics including protein–protein interaction (PPI) network, Gene Ontology (GO), and Kyoto Encyclopedia of Genes and Genomes (KEGG), as well as molecular docking.Results: The neurological function of rats in the ZLH group was significantly improved compared to those in the NS group (p = 0.000), confirming the positive effect of ZLH for the treatment of brain ischemia. There were 126 intersecting genes screened in ischemia–reperfusion cerebrum that are associated with several important biological processes, such as lipopolysaccharide, and the most important cell component, such as raft, as well as the most important molecular function pointed as cytokine receptor binding. The most important KEGG signaling pathway was the AGE-RAGE signaling pathway in diabetic complications. Moreover, according to the STRING interaction in the PPI network, 10 hub genes including MAPK14, FOS, MAPK1, JUN, MYC, RELA, ESR1, STAT1, AKT1, and IL6 were selected and exhibited in Cytoscape and molecular docking. Lastly, the relation between PPI, GO, and KEGG was analyzed. These findings indicated that multiple hub network genes have been involved in behavior improvement in cerebral ischemia–reperfusion rats subjected to ZLH treatment.Conclusion: Zhilong Huoxue Tongyu capsule improves cerebral ischemia–reperfusion and is associated with multiple network gene expressions.
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- 2022
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13. Expression pattern and prognostic impact of glycoprotein non-metastatic B (GPNMB) in triple-negative breast cancer
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Yu-Hsiang Huang, Pei-Yi Chu, Ji-Lin Chen, Chun-Teng Huang, Chi-Cheng Huang, Yi‐Fang Tsai, Yu-Ling Wang, Pei-Ju Lien, Ling-Ming Tseng, and Chun-Yu Liu
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Medicine ,Science - Abstract
Abstract Glycoprotein non-metastatic B (GPNMB) is a transmembrane protein overexpressed in numerous cancers including triple-negative breast cancers (TNBC). It has been linked to promote cancer aggressiveness and implicated as a novel target for GPNMB-expressing cancers. In current study, we aimed to explore the clinical significance of GPNMB in TNBC. Among 759 specimens, immunohistochemistry (IHC) exhibited GPNMB expressions were variable in different subtypes and significantly higher in TNBC. Kaplan–Meier analysis revealed GPNMB overexpression in TNBC was associated with worse prognosis especially distant metastasis (P = 0.020, HR = 2.515, CI 1.154–5.480). Multivariate analysis showed GPNMB expression was an independent prognostic factor in terms of recurrence and distant metastasis (P = 0.008, HR = 3.22, CI 1.36–7.61; P = 0.017, HR = 3.08, CI 1.22–7.74). In silico analysis showed high mRNA expression of GPNMB was associated with distant metastasis and GPNMB was overexpressed in TNBC. Furthermore, GPNMB positively correlated with epithelial–mesenchymal transition (EMT) regulators, mesenchymal marker vimentin, MMP and integrins. The protein levels of Twist and MMP2 were upregulated by GPNMB overexpression in TNBC cells. GPNMB-enhanced cell invasion was attenuated by broad spectrum MMP inhibitor (GM 6001) and the selective inhibitor of MMP-2 (ARP100). In summary, GPNMB expression is prevalent in TNBC and may be implicated as a prognostic biomarker in patients with TNBC.
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- 2021
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14. Impacts of smoking status on the clinical outcomes of coronary non-target lesions in patients with coronary heart disease: a single-center angiographic study
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Hao-Bo Xu, Juan Wang, Ji-Lin Chen, Chao Guo, Jian-Song Yuan, Xin Duan, Feng-Huan Hu, Wei-Xian Yang, Xiao-Liang Luo, Rong Liu, Jin-Gang Cui, Sheng-Wen Liu, Xiao-Jin Gao, Yu-Shi Chun, Shu-Bin Qiao, and Xiu-Yuan Hao and Xin Chen
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Medicine - Abstract
Abstract. Background. Coronary atherosclerotic plaque could go through rapid progression and induce adverse cardiac events. This study aimed to evaluate the impacts of smoking status on clinical outcomes of coronary non-target lesions. Methods. Consecutive patients with coronary heart disease who underwent two serial coronary angiographies were included. All coronary non-target lesions were recorded at first coronary angiography and analyzed using quantitative coronary angiography at both procedures. Patients were grouped into non-smokers, quitters, and smokers according to their smoking status. Clinical outcomes including rapid lesion progression, lesion re-vascularization, and myocardial infarction were recorded at second coronary angiography. Multivariable Cox regression analysis was used to investigate the association between smoking status and clinical outcomes. Results. A total of 1255 patients and 1670 lesions were included. Smokers were younger and more likely to be male compared with non-smokers. Increase in percent diameter stenosis was significantly lower (2.7 [0.6, 7.1] % vs. 3.5 [0.9, 8.9]%) and 3.4 [1.1, 7.7]%, P = 0.020) in quitters than those in smokers and non-smokers. Quitters tended to have a decreased incidence of rapid lesions progression (15.8% [76/482] vs. 21.6% [74/342] and 20.6% [89/431], P = 0.062), lesion re-vascularization (13.1% [63/482] vs. 15.5% [53/432] and 15.5% [67/431], P = 0.448), lesion-related myocardial infarction (0.8% [4/482] vs. 2.6% [9/342] and 1.4% [6/431], P = 0.110) and all-cause myocardial infarction (1.9% [9/482] vs. 4.1% [14/342] and 2.3% [10/431], P = 0.128) compared with smokers and non-smokers. In multivariable analysis, smoking status was not an independent predictor for rapid lesion progression, lesion re-vascularization, and lesion-related myocardial infarction except that a higher risk of all-cause myocardial infarction was observed in smokers than non-smokers (hazards ratio: 3.00, 95% confidence interval: 1.04–8.62, P = 0.042). Conclusion. Smoking cessation mitigates the increase in percent diameter stenosis of coronary non-target lesions, meanwhile, smokers are associated with increased risk for all-cause myocardial infarction compared with non-smokers.
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- 2020
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15. Significance of Kynurenine 3-Monooxygenase Expression in Colorectal Cancer
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Chun-Yu Liu, Tzu-Ting Huang, Ji-Lin Chen, Pei-Yi Chu, Chia-Han Lee, Hsin-Chen Lee, Yu-Hsuan Lee, Yuan-Ya Chang, Shung-Haur Yang, Jeng-Kai Jiang, Wei-Shone Chen, Yee Chao, and Hao-Wei Teng
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kynurenine 3-monooxygenase ,colorectal cancer ,overall survival ,metastasis ,stemness ,Neoplasms. Tumors. Oncology. Including cancer and carcinogens ,RC254-282 - Abstract
Colorectal cancer (CRC) is a leading cause of cancer-related deaths. Because of the lack of reliable prognostic and predictive biomarkers for CRC, most patients are often diagnosed at a late stage. The tryptophan–kynurenine pathway plays a crucial role in promoting cancer progression. Kynurenine is considered an oncometabolite in colon cancer, and its downstream metabolites are also associated with CRC. Kynurenine 3-monooxygenase (KMO), a pivotal enzyme that catalyzes kynurenine metabolism, is essential for several cellular processes. In the current study, we explored the role of KMO in CRC. Immunohistochemical results showed that KMO was upregulated in CRC tissues relative to paired healthy tissue and polyps. Moreover, CRC patients with higher KMO expression were associated with higher metastasis and poorer survival rates. Knockdown of KMO decreased the expression of cancer stem cell markers, as well as the sphere-forming, migration, and invasion abilities of CRC cells. Additionally, blockade of the enzymatic activity of KMO using an inhibitor suppressed sphere formation and cell motility in CRC cells. These findings suggest the clinical relevance of KMO in CRC tumorigenesis and aggressiveness.
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- 2021
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16. Targeting SET to restore PP2A activity disrupts an oncogenic CIP2A-feedforward loop and impairs triple negative breast cancer progressionResearch in context
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Chun-Yu Liu, Tzu-Ting Huang, Yi-Ting Chen, Ji-Lin Chen, Pei-Yi Chu, Chun-Teng Huang, Wan-Lun Wang, Ka-Yi Lau, Ming-Shen Dai, Chung-Wai Shiau, and Ling-Ming Tseng
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Medicine ,Medicine (General) ,R5-920 - Abstract
Background: Triple-negative breast cancer (TNBC) remains difficult to be targeted. SET and cancerous inhibitor of protein phosphatase 2A (CIP2A) are intrinsic protein-interacting inhibitors of protein phosphatase 2A (PP2A) and frequently overexpressed in cancers, whereas reactivating PP2A activity has been postulated as an anti-cancer strategy. Here we explored this strategy in TNBC. Methods: Data from The Cancer Genome Atlas (TCGA) database was analyzed. TNBC cell lines were used for in vitro studies. Cell viability was examined by MTT assay. The apoptotic cells were examined by flow cytometry and Western blot. A SET-PP2A protein-protein interaction antagonist TD19 was used to disrupt signal transduction. In vivo efficacy of TD19 was tested in MDA-MB-468-xenografted animal model. Findings: TCGA data revealed upregulation of SET and CIP2A and positive correlation of these two gene expressions in TNBC tumors. Ectopic SET or CIP2A increased cell viability, migration, and invasion of TNBC cells. Notably ERK inhibition increased PP2A activity. ERK activation is known crucial for Elk-1 activity, a transcriptional factor regulating CIP2A expression, we hypothesized an oncogenic feedforward loop consisting of pERK/pElk-1/CIP2A/PP2A. This loop was validated by knockdown of PP2A and ectopic expression of Elk-1, showing reciprocal changes in loop members. In addition, ectopic expression of SET increased pAkt, pERK, pElk-1 and CIP2A expressions, suggesting a positive linkage between SET and CIP2A signaling. Moreover, TD19 disrupted this CIP2A-feedforward loop by restoring PP2A activity, demonstrating in vitro and in vivo anti-cancer activity. Mechanistically, TD19 downregulated CIP2A mRNA via inhibiting pERK-mediated Elk-1 nuclear translocation thereby decreased Elk-1 binding to the CIP2A promoter. Interpretation: These findings suggested that a novel oncogenic CIP2A-feedforward loop contributes to TNBC progression and targeting SET to disrupt this oncogenic CIP2A loop showed therapeutic potential in TNBC.
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- 2019
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17. ER stress‐related ATF6 upregulates CIP2A and contributes to poor prognosis of colon cancer
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Chun‐Yu Liu, Chia‐Chi Hsu, Tzu‐Ting Huang, Chia‐Han Lee, Ji‐Lin Chen, Shung‐Haur Yang, Jeng‐Kai Jiang, Wei‐Shone Chen, Kuan‐Der Lee, and Hao‐Wei Teng
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ATF6 ,CIP2A ,colon cancer ,ER stress ,Neoplasms. Tumors. Oncology. Including cancer and carcinogens ,RC254-282 - Abstract
Endoplasmic reticulum (ER) stress is an adaptive response to various stress conditions and plays emerging roles in cancer. Activating transcription factor 6 (ATF6), one of the three major ER stress transducers, has been shown to contribute to chemoresistance by altering cancer cell survival. Cancerous inhibitor of protein phosphatase 2A (CIP2A) is an oncogene, and its expression has been correlated with the prognosis of patients with cancer. In this study, we aimed to explore the relationship between ER stress‐related ATF signaling and CIP2A. We found that CIP2A expression was positively correlated with ATF6 expression by analyzing publicly available RNA sequence data of patients with colorectal cancer (The Cancer Genome Atlas, TCGA). In addition, we demonstrated that tunicamycin‐induced ER stress in vitro upregulated ATF6 and CIP2A. Mechanistically, we found that ATF6 directly bound to the CIP2A promoter and induced CIP2A gene expression, which contributed to colon cancer cell survival. Furthermore, knockdown of CIP2A reduced the viability of cells under ER stress. Most importantly, immunohistochemical analysis of a tissue microarray from a colon cancer patient cohort showed that higher expression levels of ATF6 and CIP2A were associated with a trend toward poor prognosis. Taken together, our results show that ER stress‐related ATF6 upregulates CIP2A and contributes to the prognosis of colon cancer. Targeting CIP2A may disrupt ER stress‐mediated colon cancer cell survival and thus improve the prognosis of patients with colon cancer.
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- 2018
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18. Kynurenine 3-monooxygenase upregulates pluripotent genes through β-catenin and promotes triple-negative breast cancer progression
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Tzu-Ting Huang, Ling-Ming Tseng, Ji-Lin Chen, Pei-Yi Chu, Chia-Han Lee, Chun-Teng Huang, Wan-Lun Wang, Ka-Yi Lau, Mei-Fang Tseng, Yuan-Ya Chang, Tzu-Yi Chiang, Yune-Fang Ueng, Hsin-Chen Lee, Ming-Shen Dai, and Chun-Yu Liu
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Medicine ,Medicine (General) ,R5-920 - Abstract
Background: Triple-negative breast cancer (TNBC) is aggressive and has a poor prognosis. Kynurenine 3-monooxygenase (KMO), a crucial kynurenine metabolic enzyme, is involved in inflammation, immune response and tumorigenesis. We aimed to study the role of KMO in TNBC. Methods: KMO alteration and expression data from public databases were analyzed. KMO expression levels in TNBC samples were analyzed using immunohistochemistry. Knockdown of KMO in TNBC cells was achieved by RNAi and CRISPR/Cas9. KMO functions were examined by MTT, colony-forming, transwell migration/invasion, and mammosphere assays. The molecular events were analyzed by cDNA microarrays, Western blot, quantitative real-time PCR and luciferase reporter assays. Tumor growth and metastasis were detected by orthotopic xenograft and tail vein metastasis mouse models, respectively. Findings: KMO was amplified and associated with worse survival in breast cancer patients. KMO expression levels were higher in TNBC tumors compared to adjacent normal mammary tissues. In vitro ectopic KMO expression increased cell growth, colony and mammosphere formation, migration, invasion as well as mesenchymal marker expression levels in TNBC cells. In addition, KMO increased pluripotent gene expression levels and promoter activities in vitro. Mechanistically, KMO was associated with β-catenin and prevented β-catenin degradation, thereby enhancing the transcription of pluripotent genes. KMO knockdown suppressed tumor growth and the expression levels of β-catenin, CD44 and Nanog. Furthermore, mutant KMO (known with suppressed enzymatic activity) could still promote TNBC cell migration/invasion. Importantly, mice bearing CRISPR KMO-knockdown TNBC tumors showed decreased lung metastasis and prolonged survival. Interpretation: KMO regulates pluripotent genes via β-catenin and plays an oncogenic role in TNBC progression. Keywords: KMO, Triple negative breast cancer, β-catenin
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- 2020
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19. Differential Diagnosis, Clinical Characteristics, and Interventions of Braid-Like Coronary Artery: Case Series Analysis Based on Optical Coherence Tomography
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Wen-Xiu Leng, Huan-Huan Wang, Hai Ming Liu, Ying Song, Lian-Jun Xu, Jing-Jing Xu, Xue-Yan Zhao, Xiao-Yan Tan, Rong Li, Zhan Gao, Li-Jian Gao, Jue Chen, Jin-Qing Yuan, Yue-Jin Yang, and Ji-Lin Chen
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Diseases of the circulatory (Cardiovascular) system ,RC666-701 - Abstract
Aim. Based on optical coherence tomography (OCT), we aimed to determine the diagnosis, clinical characteristics, and interventions of braid-like coronary arteries, which are rare and tend to be diagnosed as a woven coronary artery (WCA) anomaly. Methods and Results. We identified braid-like lesions on coronary angiography (CAG) in 7 patients (6 men; median age 47 years; age range 26 to 57 years). All patients were heavy smokers. Four patients were diagnosed with an old myocardial infarction and the other 3 with unstable angina. The braid-like lesions were located in the left anterior descending arteries in 2 patients and in the right coronary arteries in the other 5. TIMI grade 2 flow was observed in all involved vessels. OCT findings of all lesions were consistent with recanalization of organized thrombi, which consisted of septa that divided the lumen into multiple small cavities communicating with each other. No separate three-layered structure could be defined. Based on the significance of the stenosis and its related symptoms, drug-eluting stents were implanted in all of the lesions. All patients experienced symptomatic improvement after the intervention and were followed up event-free for 12 months. Conclusions. Braid-like coronary arteries are likely to undergo recanalization of organized thrombi rather than WCA according to our OCT findings. The majority of cases affect men who smoke heavily. Percutaneous stent implantation may be beneficial in selected patients when feasible.
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- 2020
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20. Mevalonate Pathway Enzyme HMGCS1 Contributes to Gastric Cancer Progression
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I-Han Wang, Tzu-Ting Huang, Ji-Lin Chen, Li-Wei Chu, Yueh-Hsin Ping, Kai-Wen Hsu, Kuo-Hung Huang, Wen-Liang Fang, Hsin-Chen Lee, Chian-Feng Chen, Chen-Chung Liao, Rong-Hong Hsieh, and Tien-Shun Yeh
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HMGCS1 ,mevalonate pathway ,gastric cancer progression ,integrated stress response ,pluripotency ,Neoplasms. Tumors. Oncology. Including cancer and carcinogens ,RC254-282 - Abstract
The 3-hydroxy-3-methylglutaryl-CoA synthase 1 (HMGCS1) is a potential regulatory node in the mevalonate pathway that is frequently dysregulated in tumors. This study found that HMGCS1 expression is upregulated in stomach adenocarcinoma samples of patients and tumorspheres of gastric cancer cells. HMGCS1 elevates the expression levels of the pluripotency genes Oct4 and SOX-2 and contributes to tumorsphere formation ability in gastric cancer cells. HMGCS1 also promotes in vitro cell growth and progression and the in vivo tumor growth and lung metastasis of gastric cancer cells. After blocking the mevalonate pathway by statin and dipyridamole, HMGCS1 exerts nonmetabolic functions in enhancing gastric cancer progression. Furthermore, the level and nuclear translocation of HMGCS1 in gastric cancer cells are induced by serum deprivation. HMGCS1 binds to and activates Oct4 and SOX-2 promoters. HMGCS1 also enhances the integrated stress response (ISR) and interacts with the endoplasmic reticulum (ER) stress transducer protein kinase RNA-like endoplasmic reticulum kinase (PERK). Our results reveal that HMGCS1 contributes to gastric cancer progression in both metabolic and nonmetabolic manners.
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- 2020
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21. Effect of Final Kissing Balloon Dilatation after One-stent Technique at Left-main Bifurcation: A Single Center Data
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Zhan Gao, Bo Xu, Yue-Jin Yang, Shu-Bin Qiao, Yong-Jian Wu, Tao Chen, Liang Xu, Jin-Qing Yuan, Jue Chen, Xue-Wen Qin, Min Yao, Hai-Bo Liu, Shi-Jie You, Ye-Lin Zhao, Hong-Bing Yan, Ji-Lin Chen, and Run-Lin Gao
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Angioplasty ,Balloon ,Bifurcation ,Percutaneous Coronary Angioplasty ,Unprotected Left-main ,Medicine - Abstract
Background: Whether final kissing balloon (FKB) dilatation after one-stent implantation at left-main (LM) bifurcation site remains unclear. Therefore, this large sample and long-term follow-up study comparatively assessed the impact of FKB in patients with unprotected LM disease treated with one-stent strategy. Methods: Total 1528 consecutive patients underwent LM percutaneous coronary intervention in one center from January 2004 to December 2010 were enrolled; among them, 790 patients treated with one drug-eluting stent crossover LM to left anterior descending (LAD) with FKB (n = 230) or no FKB (n = 560) were comparatively analyzed. Primary outcome was the rate of major adverse cardiovascular events, defined as a composite of death, myocardial infarction (MI) and target vessel revascularization (TVR). Results: Overall, The prevalence of true bifurcation lesions, which included Medina classification (1,1,1), (1,0,1), or (0,1,1), was similar between-groups (non-FKB: 37.0% vs. FKB: 39.6%, P = 0.49). At mean 4 years follow-up, rates of major adverse cardiovascular events (non-FKB: 10.0% vs. FKB: 7.8%, P = 0.33), death, MI and TVR were not significantly different between-groups. In multivariate propensity-matched regression analysis, FKB was not an independent predictor of adverse outcomes. Conclusions: For patients treated with one-stent crossover LM to LAD, clinical outcomes appear similar between FKB and non-FKB strategy.
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- 2015
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22. Comparing of Light Transmittance Aggregometry and Modified Thrombelastograph in Predicting Clinical Outcomes in Chinese Patients Undergoing Coronary Stenting with Clopidogrel
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Xiao-Fang Tang, Ya-Ling Han, Jia-Hui Zhang, Jing Wang, Yin Zhang, Bo Xu, Zhan Gao, Shu-Bin Qiao, Jue Chen, Yuan Wu, Ji-Lin Chen, Run-Lin Gao, Yue-Jin Yang, and Jin-Qing Yuan
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Clopidogrel ,High On-treatment Platelet Reactivity ,Light Transmittance Aggregometry ,Thrombelastography ,Medicine - Abstract
Background: Several platelet function tests are currently used to measure responsiveness to antiplatelet therapy. This study was to compare two tests, light transmittance aggregometry (LTA) and modified thrombelastography (mTEG), for predicting clinical outcomes in Chinese patients after percutaneous coronary intervention (PCI). Methods: Prospective, observational, single-center study of 789 Chinese patients undergoing PCI was enrolled. This study was investigated the correlations between the two tests and performed receiver operating characteristic curve (ROC) analysis for major adverse cardiovascular events (MACEs) at 1-year follow-up. Results: MACEs occurred in 32 patients (4.1%). Correlations were well between the two tests in the adenosine diphosphate induced platelet reactivity (Spearman r = 0.733, P < 0.001). ROC-curve analysis demonstrated that LTA (area under the curve [AUC]: 0.677; 95% confidence interval [CI]: 0.643-0.710; P = 0.0009), and mTEG (AUC: 0.684; 95% CI: 0.650-0.716; P = 0.0001) had moderate ability to discriminate between patients with and without MACE. MACE occurred more frequently in patients with high on-treatment platelet reactivity (HPR) when assessed by LTA (7.4% vs. 2.7%; P < 0.001), and by TEG (6.7% vs. 2.6%; P < 0.001). Kaplan-Meier analysis demonstrated that HPR based on the LTA and mTEG was associated with almost 3-fold increased risk of MACE at 1-year follow-up. Conclusions: The correlation between LTA and mTEG is relatively high in Chinese patients. HPR measured by LTA and mTEG were significantly associated with MACE in Chinese patients undergoing PCI.
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- 2015
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23. Combination of palbociclib with enzalutamide shows in vitro activity in RB proficient and androgen receptor positive triple negative breast cancer cells.
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Chun-Yu Liu, Ka-Yi Lau, Chia-Chi Hsu, Ji-Lin Chen, Chia-Han Lee, Tzu-Ting Huang, Yi-Ting Chen, Chun-Teng Huang, Po-Han Lin, and Ling-Ming Tseng
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Medicine ,Science - Abstract
Triple negative breast cancer (TNBC) lacks specific drug targets and remains challenging. Palbociclib, a cyclin-dependent kinases 4 and 6 (CDK4/6) inhibitor is approved for metastatic estrogen receptor (ER)-positive and human epithermal growth factor 2 (HER2)-negative breast cancer. The nature of cell cycle inhibition by palbociclib suggests its potential in TNBC cells. Retinoblastoma (RB, a known substrate of CDK4/6) pathway deregulation is a frequent occurrence in TNBC and studies have revealed that pharmacological CDK4/6 inhibition induces a cooperative cytostatic effect with doxorubicin in RB-proficient TNBC models. In addition, recent studies reported that anti-androgen therapy shows preclinical efficacy in androgen-receptor (AR)-positive TNBC cells. Here we examined the effect of palbociclib in combination with an anti-androgen enzalutamide in TNBC cells.MDA-MB-453, BT-549, MDA-MB-231 and MDA-MB-468 TNBC cell lines were used for in vitro studies. Protein expressions were assessed by Western blot analysis. Cytostatic effect was examined by MTT assay. Cell cycle and apoptosis were examined by flow cytometry.Palbociclib showed inhibitory effect in RB-proficient TNBC cells, and enzalutamide inhibited cell viability in AR-positive TNBC cells. Enzalutamide treatment could enhance the palbociclib-induced cytostatic effect in AR-positive/RB-proficient TNBC cells. In addition, palbociclib-mediated G1 arrest in AR-positive/RB-proficient TNBC cells was attenuated by RB knockdown.Our study provided a preclinical rationale in selecting patients who might have therapeutic benefit from combining CDK4/6 inhibitors with AR antagonists.
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- 2017
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24. Costs and Benefits Associated With Transradial Versus Transfemoral Percutaneous Coronary Intervention in China
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Chen Jin, Wei Li, Shu‐Bin Qiao, Jin‐Gang Yang, Yang Wang, Pei‐Yuan He, Xin‐Ran Tang, Qiu‐Ting Dong, Xiang‐Dong Li, Hong‐Bing Yan, Yong‐Jian Wu, Ji‐Lin Chen, Run‐Lin Gao, Jin‐Qing Yuan, Ke‐Fei Dou, Bo Xu, Wei Zhao, Xue Zhang, Ying Xian, and Yue‐Jin Yang
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coronary artery disease ,cost ,health services research ,interventional cardiology ,outcomes research ,percutaneous coronary intervention ,Diseases of the circulatory (Cardiovascular) system ,RC666-701 - Abstract
BackgroundTransradial percutaneous coronary intervention (PCI) has been increasingly adopted in clinical practice, given its potential advantages over transfemoral intervention; however, the impact of different access strategies on costs and clinical outcomes remains poorly defined, especially in the developing world. Methods and ResultsUsing data from a consecutive cohort of 5306 patients undergoing PCI in China in 2010, we compared total hospital costs and in‐hospital outcomes for transradial intervention (TRI) and transfemoral intervention. Patients receiving TRI (n=4696, 88.5%) were slightly younger (mean age 57.4 versus 59.5 years), less often women (21.6% versus 33.1%), more likely to undergo PCI for single‐vessel disease, and less likely to undergo PCI for triple‐vessel or left main diseases. The unadjusted total hospital costs were 57 900 Chinese yuan (¥57 900; equivalent to 9190 US dollars [$9190]) for TRI and ¥67 418 ($10,701) for transfemoral intervention. After adjusting for all observed patient and procedural characteristics using the propensity score inverse probability weighting method, TRI was associated with a lower total cost (adjusted difference ¥8081 [$1283]). More than 80% of the cost difference was related to lower PCI‐related costs (adjusted difference −¥5162 [−$819]), which were likely driven by exclusive use of vascular closure devices in transfemoral intervention, and lower hospitalization costs (−¥1399 [−$222]). Patients receiving TRI had shorter length of stay and were less likely to experience major adverse cardiac events or post‐PCI bleeding. These differences were consistent among clinically relevant subgroups with acute myocardial infarction, acute coronary syndrome, and stable angina. ConclusionsAmong patients undergoing PCI, TRI was associated with lower cost and favorable clinical outcomes compared with transfemoral intervention.
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- 2016
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25. SET Overexpression is Associated with Worse Recurrence-Free Survival in Patients with Primary Breast Cancer Receiving Adjuvant Tamoxifen Treatment
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Yu-Hsiang Huang, Pei-Yi Chu, Ji-Lin Chen, Chun-Teng Huang, Chia-Han Lee, Ka-Yi Lau, Wan-Lun Wang, Yu-Ling Wang, Pei-Ju Lien, Ling-Ming Tseng, and Chun-Yu Liu
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breast cancer ,tamoxifen ,SET ,CIP2A ,PP2A ,Medicine - Abstract
Adjuvant tamoxifen reduces the recurrence rate of estrogen receptor (ER)-positive breast cancer. Previous in vitro studies have suggested that tamoxifen can affect the cancerous inhibitor of protein phosphatase 2A (CIP2A)/protein phosphatase 2A (PP2A)/phosphorylation Akt (pAkt) signaling in ER-negative breast cancer cells. In addition to CIP2A, SET nuclear proto-oncogene (SET) oncoprotein is another intrinsic inhibitor of PP2A, participating in cancer progression. In the current study, we explored the clinical significance of SET, CIP2A, PP2A, and Akt in patients with ER-positive breast cancer receiving adjuvant tamoxifen. A total of 218 primary breast cancer patients receiving adjuvant tamoxifen with a median follow-up of 106 months were analyzed, of which 17 (7.8%) experienced recurrence or metastasis. In an immunohistochemical (IHC) stain, SET overexpression was independently associated with worse recurrence-free survival (RFS) (hazard ratio = 3.72, 95% confidence interval 1.26–10.94, p = 0.017). In silico analysis revealed mRNA expressions of SET, PPP2CA, and AKT1 significantly correlated with worse RFS. In vitro, SET overexpression reduced tamoxifen-induced antitumor effects and drove luciferase activity in an Estrogen receptor element (ERE)-dependent manner. In conclusion, SET is a prognostic biomarker in patients with primary ER-positive breast cancer receiving adjuvant tamoxifen and may contribute to the failure of the tamoxifen treatment by modulating the ER signaling. Our study warrants further investigation into the potential role of SET in ER-positive breast cancer.
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- 2018
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26. Entecavir add-on Peg-interferon therapy plays a positive role in reversing hepatic fibrosis in treatment-naïve chronic hepatitis B patients: a prospective and randomized controlled trial
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Jing-Mao Yang, Li-Ping Chen, Ya-Jie Wang, Bei Lyu, Hong Zhao, Zhi-Yin Shang, Jun Li, Zhen-Yu Fan, Sheng-Di Wu, Xiao Ming, Xian Li, Shao-Ping Huang, Ji-Lin Cheng, and Yuan-Yuan Ji
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Medicine - Abstract
Abstract. Background. The efficacy of entecavir (ETV) add-on peg-interferon therapy compared with ETV monotherapy in treatment-naïve hepatitis B virus (HBV) patients remains controversial. We investigated whether adding peg-interferon to ongoing ETV treatment leads to a better curative effect or not. Methods. All patients have been recruited between August 2013 and January 2015 from the Shanghai Public Health Clinical Center and Zhongshan Hospital (China). Eligible HBV patients (n = 144) were randomly divided (1:1) to receive either ETV monotherapy (n = 70) or peg-interferon add-on therapy from week 26 to 52 (n = 74). Patients were followed-up for at least 2 years. Indexes including hepatitis B surface antigen (HBsAg) and hepatitis B e antigen (HBeAg) seroconversion rate, sustained virologic response, transient elastography value, and histological scores were evaluated every 3 months until the end of the study. The rate of patients with HBsAg loss was defined as the primary endpoint criteria. Results. At week 26, no patient achieved HBsAg seroconversion in either group. At week 52, one patient in the monotherapy group was HBsAg-negative but there was none in the combination therapy group. The monotherapy group showed significantly better liver function recovery results than the combination therapy group. At week 78, one patient in the combination group had HBsAg seroconverted. At week 104, only three patients in the combination therapy group were HBsAg-negative compared with one patient in monotherapy. The mean alanine aminotransferase and aspartate aminotransferase levels and transient elastography values decreased significantly compared with baseline. Both groups showed a favorable decrease in alpha-fetoprotein (monotherapy: 4.5 [2.8, 7.1] vs. 2.2 [1.8, 3.1] ng/mL, P
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- 2020
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27. Mechanism of gene network in the treatment of intracerebral hemorrhage by natural plant drugs in Lutong granules.
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Jie Sun, Na Li, Min Xu, Li Li, Ji Lin Chen, Yong Chen, Jian Guo Xu, and Ting Hua Wang
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Medicine ,Science - Abstract
PurposeTo study the effects of Lu-tong Granules (LTG) in ICH etermine the underlying mechanism of molecular network.MethodsModern bioinformatics and network pharmacology methods were used to predict molecular network mechanisms between ICH and LTG. Animal experiments were carried out to verify the effect of LTG for the treatment of ICH, combined with behavior test and morphologic detection.ResultsForty-three active components in LTG and involved 192 gene targets were identified successfully. Moreoner, they were intersected with 1132 genes of ICH,88 intersection targets were obtained. subsequently, Cytoscape was used to screen Hub genes, in which,6 core molecules, including AKT1, IL6, VEGFA, CASP3, JUN and MMP9 were recognized. Furthermore, we constructed Six core compounds by " disease-drug-active ingredient-target-KEGG " (D-D-A-T-K) network, showed including quercetin, luteolin, β sitosterol, stigmasterol, kaempferol and formononetin, and PPI protein network interaction showed that AKT1:OS3 and CNA2:DKN1A had the highest correlation. Whereas the enrichment of GO and KEGG indicated that LTG was most likely to play a therapeutic role in ICH through AGE-RAGE signaling pathway in diabetic complications. Integrated analysis also showed that the first 10 pathways of KEGG are integrated into 59 genes, among which 6 core genes are closely involved. Lastly, molecular docking showed that there was a good binding activity between the core components and the core genes, and animal experiments confirmed effect of LTG in the treatment of ICH, by using TTC staining and behavior test.ConclusionLTG are effective for the treatment of ICH, the underlying mechanism could be involved in gene network including anti-inflammatory response, nerve repair, analgesia, anti-epilepsy and other aspects.
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- 2022
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28. Mechanism of gene network in the treatment of intracerebral hemorrhage by natural plant drugs in Lutong granules
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Jie Sun, Na Li, Min Xu, Li Li, Ji Lin Chen, Yong Chen, Jian Guo Xu, and Ting Hua Wang
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Medicine ,Science - Abstract
Purpose To study the effects of Lu-tong Granules (LTG) in ICH etermine the underlying mechanism of molecular network Methods Modern bioinformatics and network pharmacology methods were used to predict molecular network mechanisms between ICH and LTG. Animal experiments were carried out to verify the effect of LTG for the treatment of ICH, combined with behavior test and morphologic detection. Results Forty-three active components in LTG and involved 192 gene targets were identified successfully. Moreoner, they were intersected with 1132 genes of ICH,88 intersection targets were obtained. subsequently, Cytoscape was used to screen Hub genes, in which,6 core molecules, including AKT1, IL6, VEGFA, CASP3, JUN and MMP9 were recognized. Furthermore, we constructed Six core compounds by " disease-drug-active ingredient-target-KEGG " (D-D-A-T-K) network, showed including quercetin, luteolin, β sitosterol, stigmasterol, kaempferol and formononetin, and PPI protein network interaction showed that AKT1:OS3 and CNA2:DKN1A had the highest correlation. Whereas the enrichment of GO and KEGG indicated that LTG was most likely to play a therapeutic role in ICH through AGE-RAGE signaling pathway in diabetic complications. Integrated analysis also showed that the first 10 pathways of KEGG are integrated into 59 genes, among which 6 core genes are closely involved. Lastly, molecular docking showed that there was a good binding activity between the core components and the core genes, and animal experiments confirmed effect of LTG in the treatment of ICH, by using TTC staining and behavior test. Conclusion LTG are effective for the treatment of ICH, the underlying mechanism could be involved in gene network including anti-inflammatory response, nerve repair, analgesia, anti-epilepsy and other aspects.
- Published
- 2022
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