478 results on '"Hong-Hao Zhou"'
Search Results
2. WGCNA-Based DNA Methylation Profiling Analysis on Allopurinol-Induced Severe Cutaneous Adverse Reactions: A DNA Methylation Signature for Predisposing Drug Hypersensitivity
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Lin Cheng, Bao Sun, Yan Xiong, Lei Hu, Lichen Gao, Ji Li, Hongfu Xie, Xiaoping Chen, Wei Zhang, and Hong-Hao Zhou
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drug hypersensitivity ,epigenetics ,DNA methylation ,allopurinol-induced severe cutaneous adverse reactions (SCARs) ,weighted gene co-expression network analysis (WGCNA) ,ATG13 ,Medicine - Abstract
Background: The role of aberrant DNA methylation in allopurinol-induced severe cutaneous adverse reactions (SCARs) is incompletely understood. To fill the gap, we analyze the DNA methylation profiling in allopurinol-induced Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) patients and identify the DNA methylation signature for predisposing allopurinol hypersensitivity. Methods: Genome-scale methylation analysis was conducted using the Illumina® HumanMethylation450 BeadChip. Weighted Gene Co-Expression Network Analysis (WGCNA) was utilized to analyze the data. Results: A total of 21,497 annotated promoter regions were analyzed. Ten modules were identified between allopurinol hypersensitivity and tolerance, with turquoise and yellow modules being the most significant correlation. ATG13, EPM2AIP1, and SRSF11 were the top three hub genes in the turquoise module. MIR412, MIR369, and MIR409 were the top three hub genes in the yellow module. Gene Ontology (GO) analysis revealed that the turquoise module was related to the metabolic process in intracellular organelles and the binding of various compounds, proteins, or nucleotides. The yellow module, however, was related to stimulus sensory perception in cytoskeletal elements and the activity of the receptor or transducer. Conclusion: DNA methylation plays a vital role in allopurinol-induced SCARs. DNA methylation profiling of SJS/TEN is significantly related to autophagy and microRNAs (miRNAs).
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- 2022
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3. Tumour immune cell infiltration and survival after platinum-based chemotherapy in high-grade serous ovarian cancer subtypes: A gene expression-based computational study
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Rong Liu, Rong Hu, Ying Zeng, Wei Zhang, and Hong-Hao Zhou
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Medicine ,Medicine (General) ,R5-920 - Abstract
Background: Increasing evidence supports that the immune infiltration of tumours is associated with prognosis. Here, we sought to assess the relevance of the cellular composition of the immune infiltrate to survival after platinum-based chemotherapy amongst patients with high-grade serous ovarian cancer and evaluate these effects by molecular subtype. Methods: We searched publicly available databases and identified 13 studies with more than 2000 patients. We estimated the proportions of 22 immune cell subsets by using a computational approach (CIBERSORT). Then, we investigated the associations between each immune cell subset and progression-free survival (PFS) and overall survival (OS), with cellular proportions modelled as quartiles. Findings: A high fraction of M1 [hazard ratio (HR) = 0.92, 95% confidence interval (CI) = 0.86–0.99] and M0 (HR = 0.93, 95% CI = 0.87–0.99) macrophages emerged as the most closely associated with favourable OS. Neutrophils were associated with poor OS (HR = 1.06, 95% CI = 1.00–1.13) and PFS (HR = 1.10, 95% CI = 1.02–1.13). Amongst the immunoreactive tumours, the M0 macrophages and the CD8+ T cells were associated with improved OS, whereas the M2 macrophages conferred worse OS. Interestingly, PD-1 was associated with good OS (HR=0.89, 95% CI = 0.80–1.00) and PFS (HR=0.89, 95% CI = 0.79–1.01) in this subtype. Four subgroups of tumours with distinct survival patterns were identified using immune cell proportions with unsupervised clustering. Interpretation: Further investigations of the quantitative cellular immune infiltrations in tumours may contribute to therapeutic advances. Keywords: Tumour-immune infiltration, Platinum, High grade serous ovarian cancer, Overall survival, Progression-free survival
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- 2020
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4. Clinical Features of Primary Familial Brain Calcification in 17 Families
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Yuan-Tao Huang, Li-Hua Zhang, Mei-Fang Li, Lin Cheng, Jian Qu, Yu Cheng, Xi Li, Guo-Ying Zou, and Hong-Hao Zhou
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Medicine - Published
- 2018
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5. Genome-scale analysis identifies NEK2, DLGAP5 and ECT2 as promising diagnostic and prognostic biomarkers in human lung cancer
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Yuan-Xiang Shi, Ji-Ye Yin, Yao Shen, Wei Zhang, Hong-Hao Zhou, and Zhao-Qian Liu
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Medicine ,Science - Abstract
Abstract This study aims to identify promising biomarkers for the early detection of lung cancer and evaluate the prognosis of lung cancer patients. Genome-wide mRNA expression data obtained from the Gene Expression Omnibus (GSE19188, GSE18842 and GSE40791), including 231 primary tumor samples and 210 normal samples, were used to discover differentially expressed genes (DEGs). NEK2, DLGAP5 and ECT2 were found to be highly expressed in tumor samples. These results were experimentally confirmed by quantitative reverse transcription-polymerase chain reaction (qRT-PCR). The elevated expression of the three candidate genes was also validated using the Cancer Genome Atlas (TCGA) datasets, which consist of 349 tumor and 58 normal tissues. Furthermore, we performed receiver operating characteristics (ROC) analysis to assess the diagnostic value of these lung cancer biomarkers, and the results suggested that NEK2, DLGAP5 and ECT2 expression levels could robustly distinguish lung cancer patients from normal subjects. Finally, Kaplan-Meier analysis revealed that elevated NEK2, DLGAP5 and ECT2 expression was negatively correlated with both overall survival (OS) and relapse-free survival (RFS). Taken together, these findings indicate that these three genes might be used as promising biomarkers for the early detection of lung cancer, as well as predicting the prognosis of lung cancer patients.
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- 2017
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6. Effect of carboxylesterase 1 S75N on clopidogrel therapy among acute coronary syndrome patients
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Fei-Yan Xiao, Jian-Quan Luo, Min Liu, Bi-Lian Chen, Shan Cao, Zhao-Qian Liu, Hong-Hao Zhou, Gan Zhou, and Wei Zhang
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Medicine ,Science - Abstract
Abstract Carboxylesterase 1 (CES1) hydrolyzes the prodrug clopidogrel to an inactive carboxylic acid metabolite. The effects of CES1 S75N (rs2307240,C>T) on clopidogrel response among 851 acute coronary syndrome patients who came from the north, central and south of China were studied. The occurrence ratios of each endpoint in the CC group were significantly higher than in the CT + TT group for cerebrovascular events (14% vs 4.8%, p
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- 2017
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7. Gene-gene and gene-environment interactions influence platinum-based chemotherapy response and toxicity in non-small cell lung cancer patients
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Jia-Jia Cui, Lei-Yun Wang, Tao Zhu, Wei-Jing Gong, Hong-Hao Zhou, Zhao-Qian Liu, and Ji-Ye Yin
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Medicine ,Science - Abstract
Abstract Platinum-based chemotherapy is a major therapeutic regimen of lung cancer. Various single nucleotide polymorphisms (SNPs) reported were associated with platinum-based chemotherapy response and drug toxicity. However, neither of the studies explored this association from SNP-SNP interaction perspective nor taking into effects of SNP-environment consideration simultaneously. We genotyped 504 polymorphisms and explore the association of gene-gene and gene-environment interactions with platinum-based chemotherapy response and toxicity in 490 NSCLC patients. 16 SNPs were found significantly associated with platinum-based chemotherapy, and they were picked out as study object in the validation cohort. We recruited 788 patients in the validation cohort. We found that HSPD1 rs17730989-SUMF1 rs2633851 interaction was associated with platinum-based chemotherapy-induced hematologic toxicity (adjusted OR = 0.233, P = 0.018). In addition, the combined effect of ABCG2 rs2231142-CES5A rs3859104 was significantly associated with overall toxicity (adjusted OR = 8.044, P = 4.350 × 10−5). Besides, the model of ARHGAP26 rs3776332-ERCC6 rs2228528-SLC2A1 rs4658-histology was associated with platinum-based chemotherapeutic response. Gene-gene and gene-environment interactions have been identified to contribute to chemotherapy sensitivity and toxicity. They can potentially predict drug response and toxicity of platinum-based chemotherapy in NSCLC patients.
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- 2017
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8. Genetic Polymorphisms and Platinum-based Chemotherapy Treatment Outcomes in Patients with Non-Small Cell Lung Cancer: A Genetic Epidemiology Study Based Meta-analysis
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Li-Ming Tan, Cheng-Feng Qiu, Tao Zhu, Yuan-Xiang Jin, Xi Li, Ji-Ye Yin, Wei Zhang, Hong-Hao Zhou, and Zhao-Qian Liu
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Medicine ,Science - Abstract
Abstract Data regarding genetic polymorphisms and platinum-based chemotherapy (PBC) treatment outcomes in patients with NSCLC are published at a growing pace, but the results are inconsistent. This meta-analysis integrated eligible candidate genes to better evaluate the pharmacogenetics of PBC in NSCLC patients. Relevant studies were retrieved from PubMed, Chinese National Knowledge Infrastructure and WANFANG databases. A total of 111 articles comprising 18,196 subjects were included for this study. The associations of genetic polymorphisms with treatment outcomes of PBC including overall response rate (ORR), overall survival (OS) and progression-free survival (PFS) were determined by analyzing the relative risk (RR), hazard ration (HR), corresponding 95% confidence interval (CI). Eleven polymorphisms in 9 genes, including ERCC1 rs11615 (OS), rs3212986 (ORR), XPA rs1800975 (ORR), XPD rs1052555 (OS, PFS), rs13181 (OS, PFS), XPG rs2296147 (OS), XRCC1 rs1799782 (ORR), XRCC3 rs861539 (ORR), GSTP1 rs1695 (ORR), MTHFR rs1801133 (ORR) and MDR1 rs1045642 (ORR), were found significantly associated with PBC treatment outcomes. These variants were mainly involved in DNA repair (EXCC1, XPA, XPD, XPG, XRCC1 and XRCC3), drug influx and efflux (MDR1), metabolism and detoxification (GSTP1) and DNA synthesis (MTHFR), and might be considered as potential prognostic biomarkers for assessing objective response and progression risk in NSCLC patients receiving platinum-based regimens.
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- 2017
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9. Bioavailability and pharmacokinetic comparison of tanshinones between two formulations of Salvia miltiorrhiza in healthy volunteers
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Lu Xing, Zhi-Rong Tan, Jin-Le Cheng, Wei-Hua Huang, Wei Zhang, Wen Deng, Chun-Su Yuan, and Hong-Hao Zhou
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Medicine ,Science - Abstract
Abstract Salvia miltiorrhiza (SM) is widely used to treat microcirculatory disturbance-related diseases; its lipophilic components play important roles in this application. Cryptotanshinone (CTS), tanshinone I (TSI) and tanshinone IIA (TSA) are the most widely-studied lipophilic ingredients, but low oral bioavailability limits their clinical application. It has been proven that micronization could improve the bioavailability of some drugs, so we’ve conducted this randomized study to investigate whether micronized granular powder (GP) of SM could improve the bioavailability of tanshinones compared with traditional decoction (TD). An oral dose of TD or GP of SM was administrated to subjects and blood samples were collected at predetermined time points. The plasma concentrations of tanshinones were detected by a validated method and pharmacokinetic parameters were calculated using a non-compartmental model. GP of SM resulted in a significant increase in mean maximum plasma concentration (C max ), elimination half-life and area under concentration-time curve (AUC) of tanshinones, with the plasma AUC of CTS, TSI and TSA in GP 5–184, 4–619 and 5–130 times higher than TD. In addition, the individual variances of C max and AUC were much lower after GP administration. Summarily, tanshinones in micronized GP of SM had higher oral bioavailability and lower individual variances, thus we speculate that it may indicate a better clinical efficacy and be a better choice than current treatments.
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- 2017
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10. Long noncoding RNA expression signature to predict platinum-based chemotherapeutic sensitivity of ovarian cancer patients
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Rong Liu, Ying Zeng, Cheng-Fang Zhou, Ying Wang, Xi Li, Zhao-Qian Liu, Xiao-Ping Chen, Wei Zhang, and Hong-Hao Zhou
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Medicine ,Science - Abstract
Abstract Dysregulated long noncoding RNAs (lncRNAs) are potential markers of several tumor prognoses. This study aimed to develop a lncRNA expression signature that can predict chemotherapeutic sensitivity for patients with advanced stage and high-grade serous ovarian cancer (HGS-OvCa) treated with platinum-based chemotherapy. The lncRNA expression profiles of 258 HGS-OvCa patients from The Cancer Genome Atlas were analyzed. Results revealed that an eight-lncRNA signature was significantly associated with chemosensitivity in the multivariate logistic regression model, which can accurately predict the chemosensitivity of patients [Area under curve (AUC) = 0.83]. The association of a chemosensitivity predictor with molecular subtypes indicated the excellent prognosis performance of this marker in differentiated, mesenchymal, and immunoreactive subtypes (AUC > 0.8). The significant correlation between ZFAS1 expression and chemosensitivity was confirmed in 233 HGS-OvCa patients from the Gene Expression Omnibus datasets (GSE9891, GSE63885, and GSE51373). In vitro experiments demonstrated that the ZFAS1 expression was upregulated by cisplatin in A2008, HeyA8, and HeyC2 cell lines. This finding suggested that ZFAS1 may participate in platinum resistance. Therefore, the evaluation of the eight-lncRNA signature may be clinically implicated in the selection of platinum-resistant HGS-OvCa patients. The role of ZFAS1 in platinum resistance should be further investigated.
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- 2017
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11. Comparison of Nine Statistical Model Based Warfarin Pharmacogenetic Dosing Algorithms Using the Racially Diverse International Warfarin Pharmacogenetic Consortium Cohort Database.
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Rong Liu, Xi Li, Wei Zhang, and Hong-Hao Zhou
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Medicine ,Science - Abstract
Multiple linear regression (MLR) and machine learning techniques in pharmacogenetic algorithm-based warfarin dosing have been reported. However, performances of these algorithms in racially diverse group have never been objectively evaluated and compared. In this literature-based study, we compared the performances of eight machine learning techniques with those of MLR in a large, racially-diverse cohort.MLR, artificial neural network (ANN), regression tree (RT), multivariate adaptive regression splines (MARS), boosted regression tree (BRT), support vector regression (SVR), random forest regression (RFR), lasso regression (LAR) and Bayesian additive regression trees (BART) were applied in warfarin dose algorithms in a cohort from the International Warfarin Pharmacogenetics Consortium database. Covariates obtained by stepwise regression from 80% of randomly selected patients were used to develop algorithms. To compare the performances of these algorithms, the mean percentage of patients whose predicted dose fell within 20% of the actual dose (mean percentage within 20%) and the mean absolute error (MAE) were calculated in the remaining 20% of patients. The performances of these techniques in different races, as well as the dose ranges of therapeutic warfarin were compared. Robust results were obtained after 100 rounds of resampling.BART, MARS and SVR were statistically indistinguishable and significantly out performed all the other approaches in the whole cohort (MAE: 8.84-8.96 mg/week, mean percentage within 20%: 45.88%-46.35%). In the White population, MARS and BART showed higher mean percentage within 20% and lower mean MAE than those of MLR (all p values < 0.05). In the Asian population, SVR, BART, MARS and LAR performed the same as MLR. MLR and LAR optimally performed among the Black population. When patients were grouped in terms of warfarin dose range, all machine learning techniques except ANN and LAR showed significantly higher mean percentage within 20%, and lower MAE (all p values < 0.05) than MLR in the low- and high- dose ranges.Overall, machine learning-based techniques, BART, MARS and SVR performed superior than MLR in warfarin pharmacogenetic dosing. Differences of algorithms' performances exist among the races. Moreover, machine learning-based algorithms tended to perform better in the low- and high- dose ranges than MLR.
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- 2015
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12. The prognostic value of altered eIF3a and its association with p27 in non-small cell lung cancers.
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Jie Shen, Ji-Ye Yin, Xiang-Ping Li, Zhao-Qian Liu, Ying Wang, Juan Chen, Jian Qu, Xiao-Jing Xu, Howard Lewis McLeod, Yi-Jing He, Kun Xia, Yuan-Wei Jia, and Hong-Hao Zhou
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Medicine ,Science - Abstract
BACKGROUND: Over-expressed eukaryotic initiation factor 3a (eIF3a) in non-small cell lung cancer (NSCLC) contributed to cisplatin sensitivity. However, the role of eIF3a in oncogenesis was still controversial. This study was designed to investigate the prognostic impact of eIF3a and p27 in radically resected NSCLC patients. METHODS: The expression levels of subcellular eIF3a and p27 were evaluated immunohistochemically in 537 radically resected NSCLC samples, and another cohort of 210 stage II NSCLC patients. Disease specific survival (DSS) and disease free survival (DFS) were analyzed by Kaplan-Meier method and Cox regression model. RESULTS: The subcellular expression of eIF3a was strongly correlated with status of p27 (Spearman rank coefficient correlation for cytoplasmic eIF3a and p27=0.653, for nuclear staining=0.716). Moreover, survival analysis revealed favorable prognostic impact of nuclear eIF3a, p27, and the combination high nuclear staining on NSCLC (Hazards Ratio=0.360, 95%CI=0.109-0.782, P=0.028). In addition, interaction research between biomarkers and chemotherapy status disclosed cisplatin-based regimen trend to prolong DSS of stage II NSCLC patients with high eIF3a-C (P=0.036)and low p27-N (P=0.031). CONCLUSIONS: Our findings suggested altered eIF3a expression closely correlated with p27 status, and the association was of prognostic value for resected NSCLC. Altered expression of eIF3a and p27 predicted prognosis of NSCLC independently.
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- 2014
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13. Endothelial nitric oxide synthase gene G894T polymorphism and myocardial infarction: a meta-analysis of 34 studies involving 21,068 subjects.
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Jian-Quan Luo, Jia-Gen Wen, Hong-Hao Zhou, Xiao-Ping Chen, and Wei Zhang
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Medicine ,Science - Abstract
BACKGROUND: Researches have revealed that the endothelial nitric oxide synthase (eNOS) gene G894T polymorphism is associated with the risk of Myocardial infarction (MI), but the results remain conflicting. OBJECTIVE AND METHODS: A meta-analysis was conducted to investigate the association between eNOS G894T polymorphism and MI. Published studies from PubMed, Embase, CNKI and CBM databases were retrieved. The pooled odds ratios (ORs) for the association between eNOS G894T polymorphism and MI and their corresponding 95% confidence intervals (CIs) were estimated using the random- or fixed- effect model. RESULTS: A total of 34 studies including 8229 cases and 12839 controls were identified for the meta-analysis. The eNOS G894T polymorphism was significantly associated with MI under a homozygous genetic model (OR = 1.41, 95% CI = 1.08-1.84; P = 0.012), a recessive genetic model (OR = 1.35, 95% CI = 1.06-1.70; P = 0.014), a dominant genetic model (OR = 1.18, 95% CI = 1.04-1.34; P = 0.009). In the subgroup analysis by ethnicity (non-Asian and Asian), no significant association was observed between eNOS G894T polymorphism and MI risk among non-Asians (P>0.05), but a positive significant association was found among Asians (P
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- 2014
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14. The association of transporter genes polymorphisms and lung cancer chemotherapy response.
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Ying Wang, Ji-Ye Yin, Xiang-Ping Li, Juan Chen, Chen-Yue Qian, Yi Zheng, Yi-Lan Fu, Zi-Yu Chen, Hong-Hao Zhou, and Zhao-Qian Liu
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Medicine ,Science - Abstract
Lung cancer is one of the most common cancers and is the leading cause of death worldwide. Platinum-based chemotherapy is the main treatment method in lung cancer patients. Our previous studies indicated that single nucleotide polymorphisms (SNPs) in some transporter genes played important role in platinum-based chemotherapy efficacy. The aim of this study was to investigate the association of SNPs in transporter genes and platinum-based chemotherapy efficacy. The main polymorphisms on transporters OCT2, LRP, AQP2, AQP9 and TMEM205 genes were genotyped in 338 lung cancer patients. The rs195854 in genotypic model, rs896412 in genotypic and recessive models for all subjects showed significant association with chemotherapy response. In stratification analysis, TMEM205 rs896412, OCT2 rs1869641 and rs195854, AQP9 rs1516400 and AQP2 rs7314734 showed significant relation to chemotherapy response. In conclusion, the genetic polymorphisms in OCT2, AQP2, AQP9 and TMEM205 may contribute to chemotherapy response in lung cancer patients.
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- 2014
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15. Protective effects of let-7a and let-7b on oxidized low-density lipoprotein induced endothelial cell injuries.
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Mei-Hua Bao, Yi-Wen Zhang, Xiao-Ya Lou, Yu Cheng, and Hong-Hao Zhou
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Medicine ,Science - Abstract
Lectin-like low-density lipoprotein receptor 1 (LOX-1) is a receptor for oxidized low density lipoprotein (oxLDL) in endothelial cells. The activation of LOX-1 by oxLDL stimulates the apoptosis and dysfunction of endothelial cells, and contributes to atherogenesis. However, the regulatory factors for LOX-1 are still unclear. MicroRNAs are small, endogenous, non-coding RNAs that regulate gene expressions at a post-transcriptional level. The let-7 family is the second microRNA been discovered, which plays important roles in cardiovascular diseases. Let-7a and let-7b were predicted to target LOX-1 3'-UTR and be highly expressed in endothelial cells. The present study demonstrated that LOX-1 was a target of let-7a and let-7b. They inhibited the expression of LOX-1 by targeting the positions of 310-316 in LOX-1 3'-UTR. Over-expression of let-7a and let-7b inhibited the oxLDL-induced endothelial cell apoptosis, NO deficiency, ROS over-production, LOX-1 upregulation and endothelial nitric oxide synthase (eNOS) downregulation. Moreover, we found that oxLDL treatment induced p38MAPK phosphorylation, NF-κB nuclear translocation, IκB degradation and PKB dephosphorylation. Let-7a or let-7b over-expression attenuated these alterations significantly. The present study may provide a new insight into the protective properties of let-7a and let-7b in preventing the endothelial dysfunction associated with cardiovascular disease, such as atherosclerosis.
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- 2014
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16. Polymorphism of ORM1 is associated with the pharmacokinetics of telmisartan.
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Wang-Qing Chen, Yan Shu, Qing Li, Lin-Yong Xu, Mary W Roederer, Lan Fan, Lan-Xiang Wu, Fa-Zhong He, Jian-Quan Luo, Zhi-Rong Tan, Yi-Jing He, Hong-Hao Zhou, Xiang Chen, and Wei Zhang
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Medicine ,Science - Abstract
BACKGROUND:The pharmacokinetics (PKs) and pharmacodynamics (PDs) of telmisartan varies among the individuals, and the main causes remain unknown. The aim of this study was to evaluate the impact of ORM1, as well as ABCC2, ABCB1, ABCG2 and SLCO1B3 polymorphisms, on the disposition of the drug and BP change after taking 40 mg telmisartan in 48 healthy Chinese males. METHOD:A total of 48 healthy males were included in this trial. Every volunteer ingested a single dose of 40 mg telmisartan, and the plasma drug concentration and blood pressure (BP) were measured up to 48 h. RESULT:In this study, the area under the plasma concentration-time curve (AUC) in the heterozygotes of ORM1 113AG was higher than that in the wild-type homozygotes, AUC(0-48) (113AA vs. 113AG, 1,549.18±859.84 ng·h/ml vs. 2,313.54±1,257.71 ng·h/ml, P = 0.033), AUC(0-∞) (113AA vs. 113AG, 1,753.13±1,060.60 ng·h/ml vs. 2,686.90±1,401.87 ng·h/ml, P = 0.016), and the change(%) of the diastolic blood pressure (DBP) from the baseline BP value also showed a significant difference between the ORM1 113AG and 113AA genotypes at 5 h after taking telmisartan (P = 0.026). This study also showed that the allele of ABCC2 C3972T would affected the disposition of telmsiartan and the DBP change significantly after taking the drug. However, the common SNPs of ABCG2 C421, ABCB1 C3435T, and SLCO1B3 T334G showed no impacts on the PKs of telmisartan or BP change(%) in our trial. CONCLUSION:The ORM1 A113G polymorphism was associated with the PKs variability after taking telmsiartan, as well as ABCC2 C3972T. The heterozygotes of ORM1 113AG showed a larger AUC and a notable BP change(%) from the baseline compared with the wild-type. TRIAL REGISTRATION:Chinese Clinical Trial Registry ChiCTR-TNC-10000898.
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- 2013
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17. Different involvement of promoter methylation in the expression of organic cation/carnitine transporter 2 (OCTN2) in cancer cell lines.
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Qiang Qu, Jian Qu, Min Zhan, Lan-Xiang Wu, Yi-Wen Zhang, Xiao-Ya Lou, Li-Juan Fu, and Hong-Hao Zhou
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Medicine ,Science - Abstract
Organic cation/carnitine transporter 2 (OCTN2) is responsible for the cellular uptake of the antineoplastic agent, oxaliplatin. Epigenetic modification is a possible mechanism of altered drug-transporter expression in cancers, leading to altered efficacy of chemotherapeutic drugs. However, the mechanisms governing OCTN2 regulation are not completely understood. In this study, the low levels of OCTN2 in HepG2 and LS174T cells were elevated by the demethylating reagent, decitabine (DCA). To further reveal the epigenetic mechanism of down-regulation of OCTN2, we found that Region-1 within the OCTN2 promoter (spanning -354 to +85) was a determinant of OCTN2 expression in a luciferase reporter assay. Moreover, methylation-specific PCR (MSP) and bisulfite genomic sequencing showed that the degree of individual methylated CpG sites within this region was inversely correlated with the levels of OCTN2 in different cancer cells. Application of DCA to HepG2 and LS174T cells reversed the hypermethylation status of the OCTN2 promoter and increased OCTN2 expression, enhancing cellular uptake of oxaliplatin. Thus, we identified that promoter methylation is responsible for epigenetic down-regulation of OCTN2 in HepG2 and LS174T cells. Given the essential role of OCTN2 in cancer cell uptake of chemotherapeutics, and thus treatment efficacy, pretreatment with a demethylating reagent is a possible strategy for optimizing pharmacotherapies against cancers.
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- 2013
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18. Meta-analysis on pharmacogenetics of platinum-based chemotherapy in non small cell lung cancer (NSCLC) patients.
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Ji-Ye Yin, Qiong Huang, Ying-Chun Zhao, Hong-Hao Zhou, and Zhao-Qian Liu
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Medicine ,Science - Abstract
AIM: To determine the pharmacogenetics of platinum-based chemotherapy in Non Small Cell Lung Cancer (NSCLC) patients. METHODS: Publications were selected from PubMed, Cochrane Library and ISI Web of Knowledge. A meta-analysis was conducted to determine the association between genetic polymorphisms and platinum-based chemotherapy by checking odds ratio (OR) and 95% confidence interval (CI). RESULTS: Data were extracted from 24 publications, which included 11 polymorphisms in 8 genes for meta-analysis. MDR1 C3435T (OR = 1.97, 95% CI: 1.11-3.50, P = 0.02), G2677A/T (OR = 2.61, 95% CI: 1.44-4.74, P = 0.002) and GSTP1 A313G (OR = 0.32, 95% CI: 0.17-0.58, P = 0.0002) were significantly correlated with platinum-based chemotherapy in Asian NSCLC patients. CONCLUSION: Attention should be paid to MDR1 C3435T, G2677A/T and GSTP1 A313G for personalized chemotherapy treatment for NSCLC patients in Asian population in the future.
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- 2012
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19. Gut microbiota and host Cyp450s co-contribute to pharmacokinetic variability in mice with non-alcoholic steatohepatitis: Effects vary from drug to drug
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Hong-Hao Zhou, Song-Xia Zhang, Zhi-Rong Tan, Li-jie Chen, Wei Zhang, Yao Chen, Yu-ligh Liou, Ying Xu, Jing Guo, and Xiao-ping Chen
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Drug ,Midazolam ,Tolbutamide ,media_common.quotation_subject ,Pharmacology ,Gut flora ,digestive system ,Mice ,Pharmacokinetics ,Non-alcoholic Fatty Liver Disease ,medicine ,Animals ,Omeprazole ,media_common ,Multidisciplinary ,biology ,business.industry ,Phenacetin ,biology.organism_classification ,medicine.disease ,Gastrointestinal Microbiome ,Chlorzoxazone ,Pharmaceutical Preparations ,Steatohepatitis ,business ,Metoprolol ,medicine.drug - Abstract
Pharmacokinetic variability in disease state is common in clinical practice, but its underlying mechanism remains unclear. Recently, gut microbiota has been considered to be pharmacokinetically equivalent to the host liver. Although some studies have explored the roles of gut microbiota and host Cyp450s in drug pharmacokinetics, few have explored their effects on pharmacokinetic variability, especially in disease states.In this study, we aim to investigate the effects of gut microbiota and host Cyp450s on pharmacokinetic variability in mice with non-alcoholic steatohepatitis (NASH), and to elucidate the contribution of gut microbiota and host Cyp450s to pharmacokinetic variability in this setting.The pharmacokinetic variability of mice with NASH was explored under intragastric and intravenous administrations of a cocktail mixture of omeprazole, phenacetin, midazolam, tolbutamide, chlorzoxazone, and metoprolol, after which the results were compared with those obtained from the control group. Thereafter, the pharmacokinetic variabilities of all drugs and their relations to the changes in gut microbiota and host Cyp450s were compared and analyzed.The exposures of all drugs, except metoprolol, significantly increased in the NASH group under intragastric administration. However, no significant increase in the exposure of all drugs, except tolbutamide, was observed in the NASH group under intravenous administration. The pharmacokinetic variabilities of phenacetin, midazolam, omeprazole, and chlorzoxazone were mainly associated with decreased elimination activity in the gut microbiota. By contrast, the pharmacokinetic variability of tolbutamide was mainly related to the change in the host Cyp2c65. Notably, gut microbiota and host Cyp450s exerted minimal effects on the pharmacokinetic variability of metoprolol.Gut microbiota and host Cyp450s co-contribute to the pharmacokinetic variability in mice with NASH, and the degree of contribution varies from drug to drug. The present findings provide new insights into the explanation of pharmacokinetic variability in disease states.
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- 2022
20. Genome-wide analysis identify novel germline genetic variations in ADCY1 influencing platinum-based chemotherapy response in non-small cell lung cancer
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Xi Li, Hong-Hao Zhou, Ji-Ye Yin, Heng Xu, Yingjie Xu, Chen-Xue Mao, Jun-Yan Liu, Haihua Xiao, Yuan-Kang Zhou, Zhan Wang, Min Li, Wei Zhuo, Desheng Xiao, Lin Wu, Wen Yang, Pinhua Pan, Xiang-Ping Li, Yang Gao, Juan Chen, Shuo Hu, Wei Zhang, Kazuhiko Hanada, Ting Zou, and Zhao-Qian Liu
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Oncology ,medicine.medical_specialty ,Microarray ,Genome-wide association study ,Biology ,medicine.disease ,Pharmacogenomics ,Internal medicine ,Genetic variation ,Expression quantitative trait loci ,medicine ,Carcinoma ,General Pharmacology, Toxicology and Pharmaceutics ,Lung cancer ,Genetic association - Abstract
To explore the pharmacogenomic markers that affect the platinum-based chemotherapy response in non-small-cell lung carcinoma (NSCLC), we performed a two-cohort of genome-wide association studies (GWAS), including 34 for WES-based and 433 for microarray-based analyses, as well as two independent validation cohorts. After integrating the results of two studies, the genetic variations related to the platinum-based chemotherapy response were further determined by fine-mapping in 838 samples, and their potential functional impact were investigated by eQTL analysis and in vitro cell experiments. We found that a total of 68 variations were significant at P
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- 2022
21. Targeting PLA2G16, a lipid metabolism gene, by Ginsenoside Compound K to suppress the malignant progression of colorectal cancer
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Ling-Jie Zheng, Zhou Ying'en, Jing Yu, Ling Chen, Xiaonv Xie, Hong-Hao Zhou, Wenhui Meng, Dong-Sheng Ouyang, Li Yang, Zhi-Rong Tan, Lihua Zhang, and Junjia Luo
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0301 basic medicine ,Medicine (General) ,Science (General) ,Ginsenosides ,Colorectal cancer ,Pharmaceutical Science ,Mice, Nude ,medicine.disease_cause ,Metastasis ,03 medical and health sciences ,Mice ,Q1-390 ,0302 clinical medicine ,R5-920 ,In vivo ,Cell Line, Tumor ,medicine ,Animals ,Humans ,neoplasms ,Hippo signaling pathway ,ComputingMethodologies_COMPUTERGRAPHICS ,Multidisciplinary ,business.industry ,Cell growth ,Lipid metabolism ,medicine.disease ,Lipid Metabolism ,digestive system diseases ,Blot ,Ginsenoside Compound K ,Lipid metabolism gene ,030104 developmental biology ,030220 oncology & carcinogenesis ,PLA2G16 ,Lipidomics ,Cancer research ,Carcinogenesis ,business ,Colorectal Neoplasms - Abstract
Graphical abstract, Highlights • PLA2G16 is up-regulated in CRC, and high expression of PLA2G16 is associated with the advanced stages. • PLA2G16 promotes the malignant progression of CRC through the Hippo signaling pathway. • GCK exerts its anti-CRC effects by inhibiting the protein expression of PLA2G16. • Provide a new insights towards the development of effective therapeutic strategies for CRC treatment by targeting PLA2G16., Introduction Colorectal cancer (CRC) is a common malignant tumor with a high global incidence, metastasis rate and low cure rate. Changes in lipid metabolism-related genes can affect the occurrence and development of CRC, and may be a potential therapeutic target for CRC. Therefore, starting from lipid metabolism-related genes to find natural medicines for tumor treatment may become a new direction in CRC research. Objectives This study aimed to investigate the effect of PLA2G16, a key gene involved in lipid metabolism, on the biological function of CRC, and whether the anti-CRC effect of GCK is related to PLA2G16. Methods To explore the role of PLA2G16 in CRC in vitro and in vivo, we performed cell proliferation, migration, invasion and nude mice tumorigenesis assays. As for the mechanism, we designed RNA-seq analysis and verified by western blotting and immunofluorescence experiments. Subsequently, we found the anti-CRC effect of GCK is related to PLA2G16 through western blotting and rescue experiments. Results We showed that PLA2G16 was significantly higher in CRC tissues than the adjacent normal appearing tissues, and high PLA2G16 expression correlates with unfavorable prognosis of CRC patients. Further, PLA2G16 promoted the malignant progression of CRC by inhibiting the Hippo signaling pathway determined by RNA-seq analysis, and GCK exerted anti-CRC effects by inhibiting the protein expression of PLA2G16 in vitro and in vivo. Conclusion Our results suggested that PLA2G16 promote the malignant progression of CRC by inhibiting the Hippo signaling pathway and the anti-CRC effect of GCK is through inhibiting the protein expression of PLA2G16.
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- 2022
22. Lrp6 Genotype affects Individual Susceptibility to Nonalcoholic Fatty Liver Disease and Silibinin Therapeutic Response via Wnt/β-catenin-Cyp2e1 Signaling
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Ying Xu, Hong-Hao Zhou, Wei Zhang, Xiu-Xian Lin, Hong Yang, Shi-Fang Peng, Qing Zhao, Jing Guo, Dong Guo, Li-jie Chen, Guang-Hui Lian, Song-Xia Zhang, Yao Chen, Yan Shu, Dan Chen, and Jian Xiao
- Subjects
nonalcoholic fatty liver disease ,Normal diet ,genotype ,Silibinin ,Applied Microbiology and Biotechnology ,digestive system ,chemistry.chemical_compound ,Nonalcoholic fatty liver disease ,medicine ,Genetic predisposition ,cytochrome P450 2e1 ,Molecular Biology ,low-density lipoprotein receptor-related protein 6 ,Ecology, Evolution, Behavior and Systematics ,Liver injury ,reactive oxygen species ,business.industry ,Wnt signaling pathway ,LRP6 ,nutritional and metabolic diseases ,Cell Biology ,medicine.disease ,digestive system diseases ,chemistry ,Catenin ,Cancer research ,business ,Developmental Biology ,Research Paper - Abstract
Background: Nonalcoholic fatty liver disease (NAFLD) is a serious threat to human health worldwide, with a high genetic susceptibility. Rs2302685, a functional germline variant of LRP6, has been recently found to associate with NAFLD risk. This study was aimed to clarify the underlying mechanism associated with rs2302685 risk and its impact on pharmacotherapy in treatment of NAFLD. Methods: Venous blood samples were collected from NAFLD and non-NAFLD patients for SNP genotyping by using mass spectrometry. The Lrp6-floxdel mouse (Lrp6 (+/-)) was generated to model the partial function associated with human rs2302685. The liver injury and therapeutic effects of silibinin were compared between Lrp6 (+/-) and Lrp6 (+/+) mice received a methionine-choline deficient (MCD) diet or normal diet. The effect of Lrp6 functional alteration on Wnt/β-catenin-Cyp2e1 signaling activities was evaluated by a series of cellular and molecular assays. Results: The T allele of LRP6 rs2302685 was confirmed to associate with a higher risk of NAFLD in human subjects. The carriers of rs2302685 had reduced level of AST and ALT as compared with the noncarriers. The Lrp6 (+/-) mice exhibited a less severe liver injury induced by MCD but a reduced response to the treatment of silibinin in comparison to the Lrp6 (+/+) mice, suggesting Lrp6 as a target of silibinin. Wnt/β-catenin-Cyp2e1 signaling together with ROS generation could be exacerbated by the overexpression of Lrp6, while decreased in response to Lrp6 siRNA or silibinin treatment under NAFLD modeling. Conclusions: The Lrp6 function affects individual susceptibility to NAFLD and the therapeutic effect of silibinin through the Wnt/β-catenin-Cyp2e1 signaling pathway. The present work has provided an underlying mechanism for human individual susceptibility to NAFLD associated with Lrp6 polymorphisms as well as a rationale for the effective use of silibinin in NAFLD patients.
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- 2021
23. Metabolomics of Artichoke Bud Extract in Spontaneously Hypertensive Rats
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Shi-long Jiang, Shuo Hu, Wei Zhuo, Jingbo Peng, Zhao-Qian Liu, Zhi-Quan Yang, Tong Liu, Zhi-Bin Wang, Xu Wang, Xiao-Yuan Mao, Hong-Hao Zhou, Jiwei Guo, and Shao-Bo Liu
- Subjects
Adenosine monophosphate ,Antioxidant ,General Chemical Engineering ,medicine.medical_treatment ,Methylmalonic acid ,Albumin ,General Chemistry ,Pharmacology ,medicine.disease_cause ,Article ,Chemistry ,chemistry.chemical_compound ,Blood pressure ,chemistry ,Enalapril Maleate ,medicine ,Uric acid ,QD1-999 ,Oxidative stress - Abstract
Hypertension adversely affects the quality of life in humans across modern society. Studies have attributed increased reactive oxygen species production to the pathophysiology of hypertension. So far, a specific drug to control the disease perfectly has not been developed. However, artichoke, an edible vegetable, plays an essential role in treating many diseases due to its potent antioxidant activities. The objective of this study is to evaluate the effect of artichoke bud extract (ABE) on heart tissue metabolomics of hypertensive rats. Spontaneously hypertensive rats and Wistar-Kyoto (WKY) rats were divided into six groups, then exposed to different doses comprising ABE, Enalapril Maleate, or 1% carboxylmethyl cellulose for 4 weeks. Their blood pressures were recorded at 0, 2, 3, and 4 weeks after the start of the test period. Thereafter, all rats were anesthetized, and blood was collected from their cardiac apexes. Then, we measured the levels for 15 kinds of serum biochemical parameters. An established orthogonal partial least square-discriminant analysis model completed the metabolomic analysis. Hypertensive rats in the ABE group exhibited well-controlled blood pressure, relative to those in the model group. Specifically, artichoke significantly lowered serum levels for total protein (TP), albumin (ALB), and uric acid (UA) in the hypertensive rats. This effect involved the action of eight metabolites, including guanine, 1-methylnicotinamide, p-aminobenzoic acid, NAD, NADH, uridine 5'-monophosphate, adenosine monophosphate, and methylmalonic acid. Collectively, these findings suggest that ABE may play a role in affecting oxidative stress and purine, nicotinate, and nicotinamide metabolism.
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- 2021
24. A Two-Stage Study Identifies Two Novel Polymorphisms in PRKAG2 Affecting Metformin Response in Chinese Type 2 Diabetes Patients
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Xi Li, Simin Zhang, Linong Ji, Zhao-Qian Liu, Ji-Ye Yin, Hong-Hao Zhou, Wei Zhang, Xueyao Han, Rang-Ru Liu, Xiao-Ping Chen, Jun-Yan Liu, and Di Xiao
- Subjects
0301 basic medicine ,Oncology ,medicine.medical_specialty ,endocrine system diseases ,Single-nucleotide polymorphism ,Type 2 diabetes ,Glibenclamide ,03 medical and health sciences ,0302 clinical medicine ,Pharmacogenomics and Personalized Medicine ,Internal medicine ,Genetic variation ,Medicine ,Allele ,Genotyping ,Original Research ,Glycemic ,Pharmacology ,business.industry ,genetic variants ,nutritional and metabolic diseases ,metformin response ,medicine.disease ,PRKAG2 ,Metformin ,030104 developmental biology ,030220 oncology & carcinogenesis ,Molecular Medicine ,type 2 diabetes ,business ,medicine.drug - Abstract
Di Xiao,1,2,* Jun-Yan Liu,3,* Si-Min Zhang,4,* Rang-Ru Liu,1,5 Ji-Ye Yin,1,6 Xue-Yao Han,4 Xi Li,1,6 Wei Zhang,1,6,7 Xiao-Ping Chen,1,6 Hong-Hao Zhou,1,6,7 Li-Nong Ji,4 Zhao-Qian Liu1,6,7 1Department of Clinical Pharmacology, Xiangya Hospital, Central South University, Changsha, Peopleâs Republic of China; 2Department of pharmacy, Xiangya Hospital, Central South University, Changsha, Peopleâs Republic of China; 3Department of orthopaedics, Xiangya Hospital, Central South University, Changsha, Peopleâs Republic of China; 4Department of Endocrinology and Metabolism, The Peopleâs Hospital of Peking University, Beijing, Peopleâs Republic of China; 5Key Laboratory of Tropical Diseases and Translational Medicine of the Ministry of Education & Hainan Provincial Key Laboratory of Tropical Medicine, Hainan Medical College, Haikou, Peopleâs Republic of China; 6Institute of Clinical Pharmacology, Hunan Key Laboratory of Pharmacogenetics, Central South University, Changsha, Peopleâs Republic of China; 7National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, Changsha, Peopleâs Republic of China*These authors contributed equally to this workCorrespondence: Zhao-Qian Liu; Li-Nong Ji Email liuzhaoqian63@126.com; jiln@gmail.comObjective: Individual differences in glycemic response to metformin in antidiabetic treatment exist widely. Although some associated genetic variations have been discovered, they still cannot accurately predict metformin response. In the current study, we set out to investigate novel genetic variants affecting metformin response in Chinese type 2 diabetes (T2D) patients.Methods: A two-stage study enrolled 500 T2D patients who received metformin, glibenclamide or a combination of both were recruited from 2009 to 2012 in China. Change of HbA1c, adjusted by clinical covariates, was used to evaluate glycemic response to metformin. Selected single nucleotide polymorphisms (SNPs) were genotyped using the Infinium iSelect and/or Illumina GoldenGate genotyping platform. A linear regression model was used to evaluate the association between SNPs and response.Results: A total of 3739 SNPs were screened in Stage 1, of which 50 were associated with drug response. Except for one genetic variant preferred to affect glibenclamide, the remaining SNPs were subsequently verified in Stage 2, and two SNPs were successfully validated. These were PRKAG2 rs2727528 (discovery group: β=â 0.212, P=0.046; validation group: β=â 0.269, P=0.028) and PRKAG2 rs1105842 (discovery group: β=0.205, P=0.048; validation group: β=0.273, P=0.025). C allele carriers of rs2727528 and C allele carriers of rs1105842 would have a larger difference of HbA1c level when using metformin.Conclusion: Two variants rs2727528 and rs1105842 in PRKAG2, encoding γ 2 subunit of AMP-activated protein kinase (AMPK), were found to be associated with metformin response in Chinese T2D patients. These findings may provide some novel information for personalized pharmacotherapy of metformin in China.Keywords: type 2 diabetes, metformin response, genetic variants, PRKAG2
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- 2021
25. Ferroptosis‐related gene signature predicts prognosis and immunotherapy in glioma
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Qin-Xuan Xia, Rong-Jun Wan, Hong-Hao Zhou, Wang Peng, and Xiao-Yuan Mao
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0301 basic medicine ,Oncology ,medicine.medical_specialty ,Programmed cell death ,medicine.medical_treatment ,Brain tumor ,risk score ,gene signature ,Cohort Studies ,03 medical and health sciences ,0302 clinical medicine ,Predictive Value of Tests ,Physiology (medical) ,Glioma ,Internal medicine ,Databases, Genetic ,medicine ,Humans ,Pharmacology (medical) ,Pharmacology ,Framingham Risk Score ,Brain Neoplasms ,business.industry ,Gene Expression Profiling ,Original Articles ,Immunotherapy ,Gene signature ,Prognosis ,medicine.disease ,ferroptosis ,Immune checkpoint ,Gene Expression Regulation, Neoplastic ,Psychiatry and Mental health ,030104 developmental biology ,Cohort ,Original Article ,business ,030217 neurology & neurosurgery - Abstract
Aims Glioma is a highly invasive brain tumor, which makes prognosis challenging and renders patients resistant to various treatments. Induction of cell death is promising in cancer therapy. Ferroptosis, a recently discovered regulated cell death, can be induced for killing glioma cells. However, the prognostic prediction of ferroptosis‐related genes (FRGs) in glioma remains elusive. Methods The mRNA expression profiles and gene variation and corresponding clinical data of glioma patients and NON‐TUMOR control were downloaded from public databases. Risk score based on a FRGs signature was constructed in REMBRANDT cohort and validated in other datasets including CGGA‐693, CGGA‐325, and TCGA. Results Our results demonstrated that the majority of FRGs was differentially expressed among GBM, LGG, and NON‐TUMOR groups (96.6%). Furthermore, the glioma patients with low‐risk score exhibited a more satisfactory clinical outcome. The better prognosis was also validated in the glioma patients with low‐risk score no matter to which grade they were affiliated. Functional analysis revealed that the high‐risk score group was positively correlated with the enrichment scores for immune checkpoint blockade‐related positive signatures, indicating the critical role of glioma immunotherapy via risk score. Conclusion A novel FRGs‐related risk score can predict prognosis and immunotherapy in glioma patients., A random survival forest model was constructed to obtain the risk score based on 59 ferroptosis genes in glioma patients in REMBRANDT cohort and it was validated in other datasets including CGGA‐325, CGGA‐693, and TCGA cohorts. Finally, a novel ferroptosis‐related risk score can predict prognosis and immunotherapy in glioma patients.
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- 2021
26. LINC-PINT impedes DNA repair and enhances radiotherapeutic response by targeting DNA-PKcs in nasopharyngeal cancer
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Tao Liu, Hong-Hao Zhou, Zhen Guo, Wei Zhang, Zhao-Qian Liu, Wei-Hua Huang, Jing Xiong, Chen Xiaoping, Xiong Li, Youhong Wang, Heng Xu, Liang An, and Yong Zhou
- Subjects
Cancer Research ,DNA Repair ,DNA repair ,DNA damage ,Immunology ,DNA-Activated Protein Kinase ,Biology ,DNA damage response ,Article ,Metastasis ,Cellular and Molecular Neuroscience ,Radioresistance ,Cell Line, Tumor ,medicine ,Humans ,Radiosensitivity ,DNA-PKcs ,Cell Proliferation ,QH573-671 ,Nasopharyngeal Neoplasms ,Cell Biology ,medicine.disease ,Cancer therapeutic resistance ,Cancer cell ,Cancer research ,RNA, Long Noncoding ,Signal transduction ,Cytology ,DNA Damage - Abstract
Radioresistance continues to be the leading cause of recurrence and metastasis in nasopharyngeal cancer. Long noncoding RNAs are emerging as regulators of DNA damage and radioresistance. LINC-PINT was originally identified as a tumor suppressor in various cancers. In this study, LINC-PINT was significantly downregulated in nasopharyngeal cancer tissues than in rhinitis tissues, and low LINC-PINT expressions showed poorer prognosis in patients who received radiotherapy. We further identified a functional role of LINC-PINT in inhibiting the malignant phenotypes and sensitizing cancer cells to irradiation in vitro and in vivo. Mechanistically, LINC-PINT was responsive to DNA damage, inhibiting DNA damage repair through ATM/ATR-Chk1/Chk2 signaling pathways. Moreover, LINC-PINT increased radiosensitivity by interacting with DNA-dependent protein kinase catalytic subunit (DNA-PKcs) and negatively regulated the expression and recruitment of DNA-PKcs. Therefore, these findings collectively support the possibility that LINC-PINT serves as an attractive target to overcome radioresistance in NPC.
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- 2021
27. Author Correction: MiR-488 inhibits proliferation and cisplatin sensibility in non-small-cell lung cancer (NSCLC) cells by activating the eIF3a-mediated NER signaling pathway
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Hong-Hao Zhou, Ji-Ye Yin, Wei Zhang, Yi-Xin Chen, Zhao-Qian Liu, Hsuan-Shun Huang, Na-Yiyuan Wu, Xiang-Ping Li, and Chao Fang
- Subjects
Cisplatin ,Multidisciplinary ,business.industry ,Science ,non-small cell lung cancer (NSCLC) ,medicine.disease ,Text mining ,Cancer research ,Medicine ,Signal transduction ,business ,medicine.drug - Published
- 2021
28. Associations between Vascular Endothelial Growth Factor Gene Polymorphisms and Different Types of Diabetic Retinopathy Susceptibility: A Systematic Review and Meta-Analysis
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Hong-Hao Zhou, Wen-Xu Hong, Xiaoping Chen, Chun-Mei Gong, Junxia Yan, and Li-Ming Hu
- Subjects
Adult ,Male ,Vascular Endothelial Growth Factor A ,Oncology ,medicine.medical_specialty ,Endocrinology, Diabetes and Metabolism ,Single-nucleotide polymorphism ,Review Article ,Polymorphism, Single Nucleotide ,Diseases of the endocrine glands. Clinical endocrinology ,Endocrinology ,Polymorphism (computer science) ,Internal medicine ,Diabetes mellitus ,medicine ,Humans ,Genetic Predisposition to Disease ,Genetic Association Studies ,Aged ,Aged, 80 and over ,Diabetic Retinopathy ,business.industry ,Vitreoretinopathy, Proliferative ,Odds ratio ,Diabetic retinopathy ,Publication bias ,Middle Aged ,RC648-665 ,medicine.disease ,eye diseases ,Confidence interval ,Diabetes Mellitus, Type 1 ,Diabetes Mellitus, Type 2 ,Meta-analysis ,Female ,business - Abstract
Background. Vascular endothelial growth factor (VEGF) gene polymorphisms have been shown to be associated with the risk of diabetic retinopathy (DR), but the results were inconsistent. The aim of this study was to systematically assess the associations between VEGF gene polymorphisms and different types of DR (nonproliferative DR and proliferative DR). Methods. Electronic databases PubMed, Embase, Web of Science, CNKI, and WANFANG DATA were searched for articles on the associations between VEGF gene polymorphisms and different types of DR up to November 6, 2019. Pooled odds ratios (ORs) and 95% confidence intervals (CIs) were calculated, and subgroup analyses were conducted by ethnicity. Sensitivity analysis was conducted to assess the stability of the results. Publication bias was assessed by using the Egger regression asymmetry test and visualization of funnel plots. A systematic review was conducted for polymorphisms with a high degree of heterogeneity ( I 2 > 75 % ) or studied in only one study. Results. A total of 13 and 18 studies analyzed the associations between VEGF SNPs and nonproliferative DR (NPDR) as well as proliferative DR (PDR), respectively. There were significant associations between rs2010963 and NPDR in Asian (dominant model: OR = 1.29 , 95 % CI = 1.04 − 1.60 ); and rs2010963 is associated with PDR in total population (dominant model: OR = 1.20 , 95 % CI = 1.03 − 1.41 ), either Asian (recessive model: OR = 1.57 , 95 % CI = 1.04 − 2.35 ) or Caucasian (recessive model: OR = 1.83 , 95 % CI = 1.28 − 2.63 ). Rs833061 is associated with PDR in Asian (recessive model: OR = 1.58 , 95 % CI = 1.11 − 2.26 ). Rs699947 is associated with NPDR in the total population (dominant model: OR = 2.04 , 95 % CI = 1.30 − 3.21 ) and associated with PDR in Asian (dominant model: OR = 1.72 , 95 % CI = 1.05 − 2.84 ). Conclusions. Rs2010963, rs833061, and rs699947 are associated with NPDR or PDR, which may be involved in the occurrence and development of DR.
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- 2021
29. Targeting translation regulators improves cancer therapy
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Ji-Ye Yin, Ji Peng, Lin Lei, Zhao-Qian Liu, Shi-Long Jiang, Hong-Hao Zhou, Jun-Luan Mo, and Wen-Xu Hong
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Ribosomal Proteins ,0106 biological sciences ,Cancer therapy ,Antineoplastic Agents ,Computational biology ,Biology ,01 natural sciences ,Metastasis ,03 medical and health sciences ,Therapeutic approach ,Neoplasms ,Translational regulation ,Genetics ,medicine ,Animals ,Humans ,030304 developmental biology ,0303 health sciences ,Cancer ,Translation (biology) ,medicine.disease ,Gene Expression Regulation, Neoplastic ,Clinical trial ,Protein Biosynthesis ,Signal transduction ,010606 plant biology & botany - Abstract
Deregulation of protein synthesis may be involved in multiple aspects of cancer, such as gene expression, signal transduction and drive specific cell biological responses, resulting in promoting cancer growth, invasion and metastasis. Study the molecular mechanisms about translational control may help us to find more effective anti-cancer drugs and develop novel therapeutic opportunities. Recently, the researchers had focused on targeting translational machinery to overcome cancer, and various small molecular inhibitors targeting translation factors or pathways have been tested in clinical trials and exhibited improving outcomes in several cancer types. There is no doubt that an insight into the class of translation regulation protein would provide new target for pharmacologic intervention and further provide opportunities to develop novel anti-tumor therapeutic interventions. In this review, we summarized the developments of translational control in cancer survival and progression et al, and highlighted the therapeutic approach targeted translation regulation to overcome the cancer.
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- 2021
30. LncRNA linc00312 suppresses radiotherapy resistance by targeting DNA-PKcs and impairing DNA damage repair in nasopharyngeal carcinoma
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Youhong Wang, Chun-Su Yuan, Hui Wang, Zhen Guo, Hong-Hao Zhou, Wei-Hua Huang, Wei Zhang, and Heng Xu
- Subjects
Cancer Research ,Ku80 ,DNA Repair ,DNA repair ,DNA damage ,Immunology ,Mice, Nude ,Biology ,Article ,Cellular and Molecular Neuroscience ,Transduction (genetics) ,Prognostic markers ,Mice ,Radioresistance ,medicine ,Animals ,Humans ,Non-homologous-end joining ,lcsh:QH573-671 ,Head and neck cancer ,DNA-PKcs ,Cell Proliferation ,Nasopharyngeal Carcinoma ,lcsh:Cytology ,Cell Biology ,medicine.disease ,Prognosis ,Comet assay ,enzymes and coenzymes (carbohydrates) ,Nasopharyngeal carcinoma ,Cancer research ,Long non-coding RNAs ,Female ,RNA, Long Noncoding ,DNA Damage - Abstract
Radioresistance is the main obstacle in the clinical management of nasopharyngeal carcinoma (NPC). linc00312 is deregulated in a number of human cancers, including NPC. However, the detailed functions and underlying mechanisms of linc00312 in regulating radiosensitivity of NPC remains unknown. In this study, cox regression analysis was used to assess the association between linc00312 and NPC patients’ survival after radiotherapy. Our results reveal that linc00312 is significantly down-regulated in NPC tissues and patients with higher expression of linc00312 are significantly associated with longer overall survival and better short-term radiotherapy efficacy. Overexpression of linc00312 could increase the sensitivity of NPC cells to ionizing radiation, as indicated by clonogenic survival assay, comet assay, and flow cytometry. Mechanistically, RNA pull down and RNA immunoprecipitation were performed to investigate the binding proteins of linc00312. linc00312 directly binds to DNA-PKcs, hinders the recruitment of DNA-PKcs to Ku80, and inhibits phosphorylation of AKT–DNA–PKcs axis, therefore inhibiting the DNA damage signal sensation and transduction in the NHEJ repair pathway. In addition, linc00312 impairs DNA repair and cell cycle control by suppressing MRN–ATM–CHK2 signal and ATR–CHK1 signal. In summary, we identified DNA-PKcs as the binding protein of linc00312 and revealed a novel mechanism of linc00312 in the DNA damage response, providing evidence for a potential therapeutic strategy in NPC.
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- 2021
31. Construction and validation of an immunity-related prognostic signature for breast cancer
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Tao Zhu, Xi Li, Hong-Hao Zhou, Wei Zhang, Zhao-Qian Liu, Shuo Hu, and Juyan Zheng
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Oncology ,Aging ,medicine.medical_specialty ,Breast Neoplasms ,Transcriptome ,breast cancer ,Immune system ,Breast cancer ,Immunity ,Internal medicine ,Tumor Microenvironment ,Humans ,Medicine ,tumor immunology ,prognostic signature ,Gene ,IRGs ,transcription factor ,business.industry ,Proportional hazards model ,Cell Biology ,Prognosis ,medicine.disease ,immunity-related gene ,Female ,business ,CD8 ,Research Paper - Abstract
Breast cancer is one of the most lethal malignancies among women, and understanding the effects of host immunity on disease progression offers the potential to improve immunotherapies against it. Here, we constructed an immunity-related gene (IRG)-based prognostic signature to stratify breast cancer patients and predict their survival. We identified differentially-expressed genes by analyzing the breast cancer transcriptome data from The Cancer Genome Atlas. Univariate Cox regression revealed 179 survival-correlated IRGs, 12 of which we used to construct an immunity-based prognostic signature that stratified breast cancer patients into high- and low-risk groups. The signature was an independent predictor for survival and was validated in an independent dataset. We also investigated the correlations between our prognostic signature and immune infiltrates and found that signature-derived risk scores correlated negatively with infiltration of B cells, CD4+ T cells, CD8+ T cells, neutrophils and dendritic cells. Our results show that the proposed prognostic signature reflects the tumor immune microenvironment, which makes it a potential indicator for survival that warrants further research to assess its clinical utility.
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- 2020
32. LRP1 polymorphisms associated with warfarin stable dose in Chinese patients: a stepwise conditional analysis
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Xi Li, Hong Zhu, Han Yan, Xin-Ming Zhou, Wei Zhang, Dan Li, Hong-Hao Zhou, Yi Chen, Zhiying Luo, and Guo-Bao Song
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0301 basic medicine ,Pharmacology ,Vitamin ,medicine.medical_specialty ,Multivariate analysis ,business.industry ,Conditional analysis ,Warfarin ,030204 cardiovascular system & hematology ,Gastroenterology ,LRP1 ,03 medical and health sciences ,chemistry.chemical_compound ,030104 developmental biology ,0302 clinical medicine ,chemistry ,Internal medicine ,Genetics ,medicine ,Molecular Medicine ,In patient ,VKORC1 ,business ,CYP2C9 ,medicine.drug - Abstract
Aim: The aim of this study was to investigate whether variability in warfarin stable dose (WSD) could be influenced by vitamin K-related polymorphisms in patients with heart valve replacement. Patients & methods: Twenty-nine vitamin K-related SNPs in 208 patients who initially took warfarin and achieved WSD were genotyped. Results: After conducting conditional analysis for both VKORC1 -1639G>A and CYP2C9*3, LRP1 rs1800139 and LRP1 rs1800154 were significantly associated with WSD (p = 0.007 and p = 0.015, respectively). Multivariate analysis showed that LRP1 rs1800139 accounted for 5.9% WSD variability. Conclusion: Our results suggest that a novel vitamin K-related gene, LRP1, exerts a relevant influence on WSD, independent of VKORC1 -1639G>A and CYP2C9*3.
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- 2020
33. circSETD3 Contributes to Acquired Resistance to Gefitinib in Non-Small-Cell Lung Cancer by Targeting the miR-520h/ABCG2 Pathway
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Hong-Hao Zhou, Shuai He, Lan-Xiang Wu, Yi Dai, Dezhang Zhao, Chunjie Wen, Yutang Huang, and Jingjing Shi
- Subjects
0301 basic medicine ,Abcg2 ,ABCG2 ,Article ,03 medical and health sciences ,Splicing factor ,0302 clinical medicine ,Gefitinib ,Downregulation and upregulation ,Drug Discovery ,medicine ,heterocyclic compounds ,skin and connective tissue diseases ,Lung cancer ,neoplasms ,biology ,business.industry ,lcsh:RM1-950 ,Transporter ,miR-520h ,medicine.disease ,respiratory tract diseases ,SRSF1 ,lcsh:Therapeutics. Pharmacology ,030104 developmental biology ,030220 oncology & carcinogenesis ,biology.protein ,Cancer research ,Molecular Medicine ,Efflux ,business ,acquired resistance to gefitinib ,Intracellular ,circSETD3 ,medicine.drug - Abstract
Gefitinib is a first-line treatment for patients with non-small-cell lung cancer (NSCLC), but acquired resistance is a major obstacle to its therapeutic efficacy, and the underlying mechanisms are not fully elucidated. Recent studies have indicated that circular RNAs play a crucial role in chemoresistance, but their expression and function in NSCLC cells with acquired resistance to gefitinib are largely unknown. In this study, we determined that circSETD3 was significantly upregulated in gefitinib-resistant NSCLC cell lines and the plasma of gefitinib-resistant NSCLC patients. circSETD3 markedly decreased the gefitinib sensitivity of NSCLC cells both in vitro and in nude mice xenografts. It could directly bind to miR-520h and lead to the upregulation of ATP-binding cassette subfamily G member 2 (ABCG2), an efflux transporter of gefitinib, resulting in a reduced intracellular gefitinib concentration. Moreover, we reported that the downregulation of serine/arginine splicing factor 1 (SRSF1) contributed to, at least in part, the increased expression of circSETD3 in NSCLC cells with acquired resistance to gefitinib. Taken together, our findings indicated that circSETD3 may serve as a prognostic biomarker and a potential therapeutic target for acquired resistance to gefitinib in NSCLC., Graphical Abstract, Wu and colleagues identified circSETD3, which could regulate acquired resistance to gefitinib in NSCLC. They characterized the SRSF1/circSETD3/miR-520h/ABCG2 axis, which decreased intracellular concentration of gefitinib after drug resistance. They also demonstrated the effect of circSETD3 on acquired resistance to gefitinib in vivo.
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- 2020
34. Optimization of whole-cell immobilization system constructed with two-species microorganism and its ability of tetracycline wastewater treatment
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Zhou Xiangyu, Lu Shen, Weimin Zeng, Xian-Ping Wu, Yichao Gu, and Hong-Hao Zhou
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Environmental Engineering ,Chromatography ,biology ,Strain (chemistry) ,Chemistry ,Tetracycline ,Microorganism ,Chemical oxygen demand ,Bacillus cereus ,010501 environmental sciences ,biology.organism_classification ,Penicillium chrysogenum ,01 natural sciences ,Wastewater ,medicine ,Environmental Chemistry ,Sewage treatment ,General Agricultural and Biological Sciences ,0105 earth and related environmental sciences ,medicine.drug - Abstract
Microbial technology is an effective and low-cost way for the treatment of water contaminated with tetracycline. In this study, 6 strains were isolated form a piggery wastewater. Strain C4 with good performance of chemical oxygen demand (COD) degradation was shown to be the best effective in the experiment of 50 mg L−1 tetracycline removal. Strain C4 was identified as Bacillus cereus; it was immobilized with fungi Penicillium chrysogenum Y5 to construct the whole-cell immobilization system. The optimal combination conditions were shown that inactivated strain Y5 compared with the living one was better as the immobilization skeleton and the inoculated strain C4 at the logarithmic growth phase were more suitable. The combination pellets could obviously improve the percentage of COD degradation and tetracycline removal to 88% and 90%, respectively. Scanning electron microscope results confirmed that lots of strain C4 cells could successfully adsorbed on the surface of fungus. It can be found from Fourier transform infrared spectroscopy analysis that hydroxyl, carbonyl, carboxyl and amino groups are rich in the immobilization pellets and this would benefit the removal of tetracycline in the wastewater.
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- 2020
35. Genetic association of hypoxia inducible factor 1-alpha (HIF1A) Pro582Ser polymorphism with risk of diabetes and diabetic complications
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Wei Zhang, Huan Ren, Ying Jiang, Man-Yun Chen, Xiao-Ping Chen, Jian-Quan Luo, YongChao Gao, and Hong-Hao Zhou
- Subjects
Adult ,Male ,Aging ,medicine.medical_specialty ,Adolescent ,Polymorphism, Single Nucleotide ,Risk Assessment ,Gastroenterology ,polymorphism ,Diabetes Complications ,Young Adult ,Polymorphism (computer science) ,Internal medicine ,Diabetes mellitus ,Genetic model ,diabetic complications ,medicine ,Pro582Ser ,Humans ,Genetic Predisposition to Disease ,Allele ,Aged ,Genetic association ,diabetes ,business.industry ,Cell Biology ,Odds ratio ,HIF1A ,Middle Aged ,Hypoxia-Inducible Factor 1, alpha Subunit ,medicine.disease ,Confidence interval ,Female ,business ,Research Paper - Abstract
Diabetes is an age-related chronic disease associated with a number of complications, emerging as one of the major causes of morbidity and mortality worldwide. Several studies indicated that hypoxia-inducible factor 1-alpha (HIF1A) genetic polymorphisms may be associated with diabetes and diabetic complications. However, this association remains ambiguous. Thus, we performed a meta-analysis to provide more precise conclusion on this issue. Odds ratios (OR) with corresponding 95% confidence intervals (CI) were applied to assess the strength of the relationships. There was a protective association between HIF1A Pro582Ser polymorphism and diabetes under the heterozygous genetic model (OR = 0.70, 95% CI = 0.55-0.91; P = 0.007). Similar associations were observed in diabetic complications risk under the allelic (OR = 0.69, 95% CI = 0.57-0.83; P < 0.001), homozygous (OR = 0.51, 95% CI = 0.30-0.87; P = 0.014), recessive (OR = 0.73, 95% CI = 0.59-0.90; P = 0.004) and dominant (OR = 0.40, 95% CI = 0.25-0.65; P < 0.001) genetic models. No effects of the HIF1A Ala588Thr polymorphism were found in risk of diabetes and diabetic complications. Taken together, these findings revealed the protective effect of HIF1A Pro582Ser polymorphism against diabetes and diabetic complications.
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- 2020
36. Panax notoginseng saponins prevent colitis-associated colorectal cancer development: the role of gut microbiota
- Author
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Wei Zhang, Tai Rao, Wei-Hua Huang, Man-Yun Chen, Ling Chen, Hong-Hao Zhou, and Li Shao
- Subjects
Male ,Panax notoginseng ,Gut flora ,digestive system ,01 natural sciences ,Inflammatory bowel disease ,Feces ,Mice ,03 medical and health sciences ,chemistry.chemical_compound ,0302 clinical medicine ,RNA, Ribosomal, 16S ,Drug Discovery ,medicine ,Animals ,Microbiome ,Colitis ,biology ,010405 organic chemistry ,Azoxymethane ,business.industry ,Akkermansia ,General Medicine ,Saponins ,medicine.disease ,biology.organism_classification ,digestive system diseases ,Gastrointestinal Microbiome ,0104 chemical sciences ,Disease Models, Animal ,Complementary and alternative medicine ,chemistry ,030220 oncology & carcinogenesis ,Cancer research ,Colitis-Associated Neoplasms ,Colorectal Neoplasms ,business ,Dysbiosis - Abstract
Gut microbiota dysbiosis is a risk factor for colorectal cancer (CRC) in inflammatory bowel disease (IBD). In this study, the effects of Panax notoginseng saponins (PNS) on colitis-associated CRC progression were evaluated on an azoxymethane (AOM)/dextran sulfate sodium (DSS) mouse model. In vivo, PNS significantly relieved AOM/DSS-induced colon tumorigenesis and development by reducing the disease activity index (DAI) scores and colon tumor load. The 16S rRNA data of fecal samples showed that the microbiome community was obviously destructed, while PNS could recover the richness and diversity of gut microbiota. Especially, PNS could increase the abundance of Akkermansia spp. which was significantly decreased in model group and negatively correlated with the progression of CRC. Moreover, ginsenoside compound K (GC-K) was evaluated on the effects of human CRC cells, which was the main bio-transformed metabolite of PNS by gut microbiota. Our data showed that PNS played important role in the prevention of the progression of CRC, due to their regulation on the microbiome balance and microbial bio-converted product with anti-CRC activity.
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- 2020
37. LRP1 and APOA1 Polymorphisms: Impact on Warfarin International Normalized Ratio-Related Phenotypes
- Author
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Wei Zhang, Han Yan, Xin-Ming Zhou, Xi Li, Hong Zhu, Guo-Bao Song, Dan Li, Zhiying Luo, Yi Chen, and Hong-Hao Zhou
- Subjects
Adult ,Male ,0301 basic medicine ,Vitamin ,endocrine system ,medicine.medical_specialty ,Pharmacogenomic Variants ,Single-nucleotide polymorphism ,030204 cardiovascular system & hematology ,Polymorphism, Single Nucleotide ,Gastroenterology ,03 medical and health sciences ,chemistry.chemical_compound ,0302 clinical medicine ,Therapeutic index ,health services administration ,Internal medicine ,medicine ,Humans ,heterocyclic compounds ,International Normalized Ratio ,cardiovascular diseases ,Blood Coagulation ,Genetic association ,Pharmacology ,Apolipoprotein A-I ,business.industry ,fungi ,Warfarin ,Anticoagulants ,Middle Aged ,LRP1 ,Phenotype ,030104 developmental biology ,Coagulation ,chemistry ,Female ,Drug Monitoring ,Cardiology and Cardiovascular Medicine ,business ,Low Density Lipoprotein Receptor-Related Protein-1 ,medicine.drug - Abstract
Warfarin international normalized ratio (INR)-related phenotypes such as the percentage of INR time in the therapeutic range (PTTR) and INR variability are associated with warfarin adverse reactions. However, INR-related phenotypes greatly vary among patients, and the underlying mechanism remains unclear. As a key cofactor for coagulation proteins, vitamin K can affect warfarin INR values. The aim of this study was to address the influence of vitamin K-related single-nucleotide polymorphisms (SNPs) on warfarin INR-related phenotypes. A total of 262 patients who were new recipients of warfarin therapy and followed up for 3 months were enrolled. Twenty-nine SNPs were genotyped by matrix-assisted laser desorption/ionization time-of-flight mass array. Sixteen warfarin INR-related phenotypes were observed. After association analysis, 11 SNPs were significantly associated with at least one INR-related phenotype, and 6 SNPs were associated with at least 2 INR-related phenotypes (P < 0.05). In these SNPs, rs1800139, rs1800154, rs1800141, and rs486020 were the most representative. rs1800139, rs1800154, and rs1800141 locate in LRP1 and were found to be correlated with 1-month and 2-month INR variability (P < 0.05). Besides, the APOA1 rs486020 was significantly associated with the first month PTTR (P = 0.009), and patients with C-allele had higher PTTR than those with G-alleles almost during the entire monitoring period. In conclusion, the study revealed that the polymorphisms of LRP1 and APOA1 gene may play important roles in the variation of warfarin INR-related phenotypes. Our results provide new information for improving warfarin anticoagulation management.
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- 2020
38. The Novel Zinc Finger Protein 587B Gene, ZNF587B, Regulates Cell Proliferation and Metastasis in Ovarian Cancer Cells in vivo and in vitro
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Wei-Hua Huang, Zeen Sun, Yujie Liu, Qianying Ouyang, Jie Liu, Jieqiong Tan, Hong-Hao Zhou, Ying-Zi Liu, Feiyue Zeng, and Zhao-Qian Liu
- Subjects
0301 basic medicine ,Zinc finger ,Gene knockdown ,Small interfering RNA ,Chemistry ,Cell growth ,Transfection ,medicine.disease ,03 medical and health sciences ,030104 developmental biology ,0302 clinical medicine ,Oncology ,Cell culture ,Apoptosis ,030220 oncology & carcinogenesis ,medicine ,Cancer research ,Ovarian cancer - Abstract
Background The zinc finger protein 587B (ZNF587B) is a novel cisplatin-sensitive gene that was identified in our previous research by using a genome-scale CRISPR-Cas9 knockout library in ovarian cancer (OC) cell lines. ZNF587B belongs to the C2H2-type zinc finger protein (ZFP) family. Many ZFP protein could inhibit tumor development and malignancy. However, the function of ZNF587B remains unknown. Methods Quantitative PCR (qPCR) was utilized to compare ZNF587B mRNA expression levels in OC and normal ovarian cell lines. The small interfering RNA (siRNA) and full-length ZNF587B eukaryotic expression plasmid were constructed and transfected into OC cells later. Colony formation, 5-ethynyl-2'-deoxyuridine (EdU) assay, transwell assay, and xenograft experiment were conducted to evaluate the effect of ZNF587B on OC cells. Results ZNF587B was downregulated by approximately 43% and 17% in the OC cell lines SKOV3 and A2780, respectively, compared with that in the normal ovarian cell line IOSE80. Overexpression of ZNF587B reduced cell proliferation, colony formation, migration, and invasion, which could be reversed by knockdown of ZNF587B via siRNA. Xenograft experiments also confirmed that ZNF587B could suppress tumor growth. Survival data of OC patients in the SurvExpress database showed that with respect to overall survival, low-risk patients grouped by the prognostic index had a higher expression of ZNF587B and a better prognosis than high-risk group (HR = 1.77, 95% CI: 0.55-0.70, p = 0.023). Moreover, overexpression of ZNF587B promoted OC cells apoptosis when pretreated with cisplatin. Conclusion ZNF587B is a novel potential tumor suppressor of OC and may be a therapeutic target for OC.
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- 2020
39. Pharmacogenomics of 5-fluorouracil in colorectal cancer: review and update
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Li-Ming Tan, Pan Xie, Xi Li, Zhao-Qian Liu, Hong-Hao Zhou, Jin-Hong Liu, Jun-Luan Mo, and Wei Zhang
- Subjects
0301 basic medicine ,Drug ,Oncology ,Cancer Research ,medicine.medical_specialty ,Colorectal cancer ,media_common.quotation_subject ,Disease ,Drug resistance ,03 medical and health sciences ,0302 clinical medicine ,Internal medicine ,Autophagy ,Animals ,Humans ,Medicine ,media_common ,biology ,business.industry ,General Medicine ,medicine.disease ,Clinical trial ,030104 developmental biology ,Drug Resistance, Neoplasm ,Pharmacogenetics ,Fluorouracil ,030220 oncology & carcinogenesis ,Pharmacogenomics ,Methylenetetrahydrofolate reductase ,biology.protein ,Molecular Medicine ,Colorectal Neoplasms ,business ,Signal Transduction ,medicine.drug - Abstract
Colorectal cancer (CRC) is a disease with high morbidity and mortality rates. 5-fluorouracil (5-FU) is the first-line recommended drug for chemotherapy in patients with CRC, and it has a good effect on a variety of other solid tumors as well. Unfortunately, however, due to the emergence of drug resistance the effectiveness of treatment may be greatly reduced. In the past decade, major progress has been made in the field of 5-FU drug resistance in terms of molecular mechanisms, pre-clinical (animal) models and clinical trials. In this article we systematically review and update current knowledge on 5-FU pharmacogenomics related to drug uptake and activation, the expression and activity of target enzymes (DPD, TS and MTHFR) and key signaling pathways in CRC. Furthermore, a summary of drug combination strategies aimed at targeting specific genes and/or pathways to reverse 5-FU resistance is provided. Based on this, we suggest that causal relationships between genes, pathways and drug sensitivity should be systematically considered from a multidimensional perspective. In the design of research methods, emerging technologies such as CRISPR-Cas, TALENS and patient-derived xenograft models should be applied as far as possible to improve the accuracy of clinically relevant results.
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- 2020
40. Integrative analyses identify a DNA damage repair gene signature for prognosis prediction in lower grade gliomas
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Zhao-Qian Liu, Dan Li, Xi Li, Jun-Luan Mo, Han Yan, Yi Chen, Feng-Mei Pang, Longbo Zhang, Jun Wu, and Hong-Hao Zhou
- Subjects
Male ,0301 basic medicine ,Cancer Research ,DNA Repair ,PLK3 ,03 medical and health sciences ,0302 clinical medicine ,Glioma ,Biomarkers, Tumor ,medicine ,Humans ,Gene ,Alleles ,Survival analysis ,Neoplasm Staging ,Proportional Hazards Models ,biology ,business.industry ,Gene Expression Profiling ,Cancer ,General Medicine ,DNA Methylation ,Gene signature ,Prognosis ,medicine.disease ,Gene Expression Regulation, Neoplastic ,body regions ,Wee1 ,030104 developmental biology ,Oncology ,030220 oncology & carcinogenesis ,Mutation ,DNA methylation ,Cancer research ,biology.protein ,Female ,Neoplasm Grading ,business ,DNA Damage - Abstract
Background: The DNA damage repair (DDR) pathways play important roles for regulating cancer progression and therapeutic response. IDH mutations, well-known prognosis biomarkers for glioma, lead to hypermethylation of tumor cells and affect genes’ expression. Whether IDH mutations affect glioma prognosis through influencing the expression of DDR genes remains unclear. Methods: A total of 272 DDR genes were selected for differential expression and survival analysis. The identified genes were then utilized to construct the prognosis predicting model. Results: PARPBP, PLK3, POLL and WEE1 were found differential expressed between IDH mutations carriers and wild-type carriers, and were associated with survival of low grade glioma (LGG) patients. The predicting algorithm can predicts the prognosis of LGG patients. Conclusion: IDH mutations may affect LGG prognosis through regulation of DDR pathways.
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- 2020
41. Correction: Shao et al. AKT Axis, miR-21, and RECK Play Pivotal Roles in Dihydroartemisinin Killing Malignant Glioma Cells. Int. J. Mol. Sci. 2017, 18, 350
- Author
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Lan-Xiang Wu, Shuang Li, Hecun Zou, Jin Huang, Tao-Lan Zhang, Ying-Ying Shao, and Hong-Hao Zhou
- Subjects
Adult ,Male ,QH301-705.5 ,medicine.medical_treatment ,Dihydroartemisinin ,Apoptosis ,GPI-Linked Proteins ,Catalysis ,Inorganic Chemistry ,Cell Movement ,Glioma ,Cell Line, Tumor ,medicine ,Humans ,Physical and Theoretical Chemistry ,Biology (General) ,Molecular Biology ,Protein kinase B ,QD1-999 ,Spectroscopy ,Aged ,Cell Proliferation ,Neoplasm Staging ,Chemistry ,Organic Chemistry ,INT ,Correction ,General Medicine ,Middle Aged ,medicine.disease ,Artemisinins ,Computer Science Applications ,Gene Expression Regulation, Neoplastic ,MicroRNAs ,n/a ,Cancer research ,Female ,Proto-Oncogene Proteins c-akt - Abstract
Dihydroartemisinin (DHA), a semi-synthetic derivative of artemisinin, is known to play important roles in inhibiting proliferation rate, inducing apoptosis, as well as hindering the metastasis and invasion of glioma cells, but the underlying mechanisms are still unclear so far. In this study, methyl thiazolyl tetrazolium (MTT), colony-forming, wound healing, invasion, and apoptosis assays were performed to investigate the effect of DHA on malignant glioma cells. Results showed that DHA induced apoptosis of malignant glioma cells through Protein Kinase B (AKT) axis, induced death of malignant glioma cells by downregulating miR-21, and inhibited the invasion of malignant glioma cells corresponding with up-regulation of the reversion-inducing-cysteine-rich protein with kazal motifs (RECK). These results revealed that AKT axis, miR-21, and RECK play pivotal roles in DHA killing malignant glioma cells, suggesting that DHA is a potential agent for treating glioma.
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- 2021
42. Analytics of the clinical implementation of pharmacogenomics testing in 12 758 individuals
- Author
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Zhi Li, Zhao-Qian Liu, Dong-Sheng Ouyang, Gang Zhou, Fan Xiao, Lei-Yun Wang, Hong-Hao Zhou, Rong Liu, Yang Wang, Qing Li, Yan Chen, Wei Zhang, Yan Zhan, Le-Dong Xiao, Howard L. McLeod, Ji-Ye Yin, and Xing-Liang Xiong
- Subjects
China ,Medicine (General) ,business.industry ,MEDLINE ,Medicine (miscellaneous) ,Data science ,Letter to Editor ,Clopidogrel ,Pharmacogenomic Testing ,Cytochrome P-450 CYP2C19 ,R5-920 ,Analytics ,Vitamin K Epoxide Reductases ,Pharmacogenomics ,Humans ,Molecular Medicine ,Medicine ,Warfarin ,Precision Medicine ,business ,Cytochrome P-450 CYP2C9 - Published
- 2021
43. Inhibition of Nrf2-mediated glucose metabolism by brusatol synergistically sensitizes acute myeloid leukemia to Ara-C
- Author
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Zhi-Ping Jiang, Wei Zhang, Fang Yuan, Gan Zhou, Cao Shan, Cong Cheng, Xie-Lan Zhao, Hong-Hao Zhou, and Xiao-Ping Chen
- Subjects
0301 basic medicine ,THP-1 Cells ,Apoptosis ,chemistry.chemical_compound ,0302 clinical medicine ,Ubiquitin ,Glycolysis ,Mice, Inbred BALB C ,Quassins ,biology ,Cytarabine ,Myeloid leukemia ,General Medicine ,Tumor Burden ,Leukemia, Myeloid, Acute ,Liver ,030220 oncology & carcinogenesis ,Female ,medicine.drug ,Antimetabolites, Antineoplastic ,NF-E2-Related Factor 2 ,Glutamate-Cysteine Ligase ,Mice, Nude ,Antineoplastic Agents ,HL-60 Cells ,Brusatol ,RM1-950 ,Glucosephosphate Dehydrogenase ,Nrf2 ,03 medical and health sciences ,Downregulation and upregulation ,medicine ,Animals ,Humans ,Transcription factor ,Pharmacology ,Acute myeloid leukemia ,Cell Cycle Checkpoints ,Xenograft Model Antitumor Assays ,Glucose ,030104 developmental biology ,chemistry ,Cell culture ,Cancer research ,biology.protein ,Therapeutics. Pharmacology ,Drug synergism ,Sulforaphane - Abstract
Chemotherapy resistance remains to be the primary barrier to acute myeloid leukemia (AML) treatment failure. Nuclear factor-erythroid 2-related factor 2 (Nrf2) has been well established as a truly pleiotropic transcription factor. Inhibition of Nrf2 function increases the sensitivity of various chemotherapeutics and overcomes chemoresistance effectively. Brusatol (Bru) has been reported to decrease Nrf2 protein expression specifically by ubiquitin degradation of Nrf2. However, it remains elusive whether combination of Brusatol and Cytarabine (Ara-C) elicits a synergistic antitumor effect in AML. Our results demonstrated that combination of Ara-C and Brusatol synergistically exerted remarkable pro-apoptosis effect in HL-60 and THP-1 cells. Mechanistically, synergistic anti-tumor effect of Ara-C/Brusatol in AML cells is mediated by attenuating Nrf2 expression. To our surprise, Nrf2 inhibition by Brusatol causes downregulation of the expression of glycolysis-related proteins and decreased glucose consumption and lactate production, whereas the level of ROS production was unaffected. The activation of Nrf2 by Sulforaphane (SFP) could reverse the chemotherapeutic effect and changes of glycolysis of concomitant of Ara-C with Brusatol in AML cell lines. Additionally, Ara-C/Brusatol co-treatment decreased Glucose-6-phosphate dehydrogenase (G6PD) protein expression and increased the sensitivity of Ara-C. Moreover, the mouse xenograft in vivo experiment confirmed that combining Ara-C with Brusatol exerted stronger antileukemia than Ara-C alone. The efficacy, together with the mechanistic observations, reveals the potential of simultaneously giving these two drugs and provides a rational basis for targeting glucose catabolism in future clinical therapeutic approach.
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- 2021
44. Effect of NPC1L1 polymorphism on warfarin stable dose in Chinese patients under heart valve replacement surgery
- Author
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Xinmin Zhou, Zhiying Luo, Hong-Hao Zhou, Wei Zhang, Siqing Ma, and Ling Chen
- Subjects
medicine.medical_specialty ,China ,Genotype ,Physiology ,medicine.drug_class ,Single-nucleotide polymorphism ,Polymorphism, Single Nucleotide ,Intestinal absorption ,Polymorphism (computer science) ,Physiology (medical) ,Vitamin K Epoxide Reductases ,Medicine ,Humans ,International Normalized Ratio ,CYP2C9 ,Cytochrome P-450 CYP2C9 ,Pharmacology ,business.industry ,Anticoagulant ,Warfarin ,Membrane Transport Proteins ,Heart Valves ,Surgery ,VKORC1 ,business ,Pharmacogenetics ,medicine.drug - Abstract
Warfarin is the most often anticoagulant choice for preventable thromboembolism. Notably, vitamin K plays a vital role in the process of warfarin's anticoagulant effect. Therefore, we presume NPC1L1, a key transporter of vitamin K (VK) intestinal absorption, may modulate the anticoagulant effect of warfarin. Studies have shown that NPC1L1(-762T>C, rs2073548) and p53 (P72R, rs1042522) variations are implicated in influencing NPC1L1 expression. This study aimed to assess the association between these two variants and warfarin stable dose (WSD). A two-stage extreme phenotype design was used to explore the influence of these two variants (rs2073548, rs1042522) on WSD variance in 655 Chinese patients undergoing heart valve replacement surgery. NPC1L1 rs2073548, p53 rs1042522, VKORC1 rs9923231 and CYP2C9*1/*3 polymorphisms were genotyped by polymerase chain reaction-restriction fragment polymorphism (PCR-RFLP) or Sanger sequencing, respectively. WSD was identified when target monitoring international normalized ratio (INR) value at 2.0-3.0. In the discovery phase, NPC1L1 rs2073548 A allele carriers occupied a significantly higher rate in the low dose group (P = .019). However, in the validation group, warfarin dosage in patients with the rs2073548 AA, AG and GG genotypes were 2.91 ± 0.97 mg/day, 3.02 ± 1.00 mg/day and 3.00 ± 1.06 mg/day, respectively. Multiple linear regression analysis results suggested that CYP2C9*3 and VKORC1 rs9923231, but not NPC1L1 rs2073548, were independent predictors of WSD in Chinese heart valve replacement (HVR) surgical patients.
- Published
- 2021
45. Ferrostatin-1 obviates seizures and associated cognitive deficits in ferric chloride-induced posttraumatic epilepsy via suppressing ferroptosis
- Author
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Hong-Hao Zhou, Zhao-Jun Wang, Xi-Xi Yin, Xiao-Yuan Mao, Kang-Ni Chen, and Qi-Wen Guan
- Subjects
History ,Programmed cell death ,Polymers and Plastics ,Morris water navigation task ,Hippocampus ,Pharmacology ,Phenylenediamines ,Somatosensory system ,Biochemistry ,Ferric Compounds ,Industrial and Manufacturing Engineering ,Mice ,Cognition ,Chlorides ,Seizures ,Physiology (medical) ,medicine ,Animals ,Ferroptosis ,Humans ,Cognitive Dysfunction ,Business and International Management ,Cognitive deficit ,chemistry.chemical_classification ,Cyclohexylamines ,business.industry ,Glutathione peroxidase ,Therapeutic effect ,Tolerability ,chemistry ,medicine.symptom ,business - Abstract
Posttraumatic epilepsy (PTE) is a prevalent complication of brain trauma. Current anti-epileptic drugs available do not have satisfactory response to PTE. It is of desperate need to explore novel therapeutic approaches for curing PTE. Our prior work revealed that ferroptosis, a recently discovered mode of cell death, occurs in rodent model of PTE. In the present study, we aimed to further investigate the effect of ferrostatin-1 (Fer-1), a specific ferroptosis inhibitor, on seizure behavior and cognitive deficit in a mouse model of PTE. The preparation of PTE was performed by stereotaxical injection in the somatosensory cortex region of 50 mM FeCl 3 . Seizure activity was assessed via Racine scoring and electroencephalogram analysis. PTE-related cognitive function was evaluated by novel object recognition and Morris water maze tests. Ferroptosis-related indices including glutathione peroxidase (GPx) activity and protein expressions of 4-hydroxynonenal (4-HNE) were detected using a commercial kit and immunofluorescence, respectively. It was found that treatment with Fer-1 significantly exerted protective effects against acute seizure and memory decline, although no evident effect on epileptic progression. Fer-1 also exhibited good tolerability and safety as we observed that it hardly influenced the body weight. Furthermore, it was noted that administration of Fer-1 suppressed ferroptosis-related indices including GPx activity and protein expressions of 4-HNE in hippocampus. These data altogether indicate that Fer-1 has potent therapeutic effects against seizures and cognitive impairment following PTE-induced brain insult. Fer-1 may act as a promising drug for curing PTE patients.
- Published
- 2021
46. WNT3A rs752107(C > T) Polymorphism Is Associated With an Increased Risk of Essential Hypertension and Related Cardiovascular Diseases
- Author
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Huan Ren, Jian-Quan Luo, Fan Ouyang, Li Cheng, Xiao-Ping Chen, Hong-Hao Zhou, Wei-Hua Huang, and Wei Zhang
- Subjects
0301 basic medicine ,FZD1 ,medicine.medical_specialty ,heart failure ,Single-nucleotide polymorphism ,Cardiovascular Medicine ,030204 cardiovascular system & hematology ,Essential hypertension ,Gastroenterology ,03 medical and health sciences ,0302 clinical medicine ,genetic polymorphisms ,Internal medicine ,Genotype ,medicine ,ischemic stroke ,Diseases of the circulatory (Cardiovascular) system ,Original Research ,business.industry ,essential hypertension ,LRP6 ,LRP5 ,Wnt3a ,medicine.disease ,030104 developmental biology ,Frzb ,DKK1 ,RC666-701 ,Cardiology and Cardiovascular Medicine ,business - Abstract
Essential Hypertension (EH) results in the burden of cardiovascular disease (CVD) such as Heart Failure (HF) and Ischemic Stroke (IS). A rapidly emerging field involving the role of Wnt/β-catenin signaling pathway in cardiovascular development and dysfunction has recently drawn extensive attention. In the present study, we conducted a genetic association between genomic variants in Wnt/β-catenin signaling pathway and EH, HF, IS. A total of 95 SNPs in 12 Wnt signaling genes (WNT3A, WNT3, WNT4, DKK1, DKK2, LRP5, LRP6, CTNNB1, APC, FZD1, FRZB, SFRP1) were genotyped in 1,860 participants (440 patients with EH, 535 patients with HF, 421 patients with IS and 464 normal control subjects) using Sequenom MassArray technology. WNT3A rs752107(C > T) was strongly associated with an increased risk of EH, HF and IS. Compared with WNT3A rs752107 CC genotype, the CT genotype carriers had a 48% increased risk of EH (OR = 1.48, 95% CI = 1.12–1.96, P = 0.006), the TT genotype conferred a 139% increased risk of EH (OR = 2.39, 95% CI = 1.32–4.34, P = 0.003). Regarding HF and IS, the risk of HF in the T allele carriers (CT + TT) was nearly increased by 58% (OR = 1.58, 95% CI = 1.22–2.04, P = 4.40 × 10−4) and the risk of IS was increased by 37% (OR = 1.37, 95% CI = 1.04–1.79, P = 0.025). Expression quantitative trait loci (eQTL) analysis indicated that rs752107 C allele corresponded to a significant reduction of WNT3A expression. We described a genetic variant of WNT3A rs752107 in Wnt/β-catenin signaling strongly associated with the risk of EH, HF and IS for the first time.
- Published
- 2021
47. Influence of Tumor Immune Infiltration on Immune Checkpoint Inhibitor Therapeutic Efficacy: A Computational Retrospective Study
- Author
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Rong Liu, Fang Yang, Ji-Ye Yin, Ying-Zi Liu, Wei Zhang, and Hong-Hao Zhou
- Subjects
0301 basic medicine ,CD4-Positive T-Lymphocytes ,overall survival ,Immunology ,immune checkpoint inhibitor ,CD8-Positive T-Lymphocytes ,Major histocompatibility complex ,medicine.disease_cause ,Tumour-immune infiltration ,Transcriptome ,03 medical and health sciences ,0302 clinical medicine ,Immune system ,Lymphocytes, Tumor-Infiltrating ,Interferon ,medicine ,Tumor Microenvironment ,Immunology and Allergy ,Humans ,Progression-free survival ,Immune Checkpoint Inhibitors ,Melanoma ,Original Research ,Retrospective Studies ,Mutation ,response ,biology ,business.industry ,Computational Biology ,RC581-607 ,medicine.disease ,Prognosis ,Progression-Free Survival ,030104 developmental biology ,030220 oncology & carcinogenesis ,Cancer research ,biology.protein ,Immunologic diseases. Allergy ,business ,CD8 ,medicine.drug - Abstract
The tumor immune microenvironment (TIME) is likely an important determinant of sensitivity to immune checkpoint inhibitor (ICI) treatment. However, a comprehensive analysis covering the complexity and diversity of the TIME and its influence on ICI therapeutic efficacy is still lacking. Data from 782 samples from 10 ICI clinical trials were collected. To infer the infiltration of 22 subsets of immune cells, CIBERSORTx was applied to the bulk tumor transcriptomes. The associations between each cell fraction and the response to ICI treatment, progression-free survival (PFS) and overall survival (OS) were evaluated, modeling cellular proportions as quartiles. Activity of the interferon-γ pathway, the cytolytic activity score and the MHC score were associated with good prognosis in melanoma. Of the immune cells investigated, M1 macrophages, activated memory CD4+ T cells, T follicular helper (Tfh) cells and CD8+ T cells correlated with response and prolonged PFS and OS, while resting memory CD4+ T cells was associated with unfavorable prognosis in melanoma and urothelial cancer. Consensus clustering revealed four immune subgroups with distinct responses to ICI therapy and survival patterns. The cluster with high proportions of infiltrated CD8+ T cells, activated memory CD4+ T cells, and Tfh cells and low levels of resting memory CD4+ T cells exhibited a higher tumor mutation burden and neoantigen load in melanoma and conferred a higher probability of response and improved survival. Local systemic immune cellular differences were associated with outcomes after ICI therapy. Further investigations of the tumor-infiltrating cellular immune response will lay the foundation for achieving durable efficacy.
- Published
- 2021
48. DCBLD2 Affects the Development of Colorectal Cancer via EMT and Angiogenesis and Modulates 5-FU Drug Resistance
- Author
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Pan Xie, Fu-Qiang Yuan, Ma-Sha Huang, Wei Zhang, Hong-Hao Zhou, Xi Li, and Zhao-Qian Liu
- Subjects
0301 basic medicine ,QH301-705.5 ,Angiogenesis ,Colorectal cancer ,colorectal cancer ,Biology ,Metastasis ,Cell and Developmental Biology ,03 medical and health sciences ,0302 clinical medicine ,Western blot ,In vivo ,medicine ,5-FU ,Biology (General) ,drug sensitivity ,Original Research ,medicine.diagnostic_test ,Cell growth ,EMT ,Cancer ,Cell Biology ,medicine.disease ,DCBLD2 ,030104 developmental biology ,030220 oncology & carcinogenesis ,Cancer research ,Signal transduction ,Developmental Biology - Abstract
Background: DCBLD2 is highly expressed in various cancers, including colorectal cancer. DCBLD2 overexpression promotes tumor occurrence, development, and metastasis. However, DCBLD2 sensitivity to chemotherapy drugs and its mechanism on tumor development are unknown.Methods: DCBLD2 expression differences in cancer and normal tissues were obtained from GEO and TCGA databases. DCBLD2 influence on prognosis was also compared, and the database analysis results were verified via the analysis of clinical samples. GDSC database was used to analyze the effect of DCBLD2 expression difference on 5-FU drug sensitivity on tumor cells. CCK-8, clone formation, scratch, Transwell invasion and migration assays were used to assess DCBLD2 effects on the proliferation, metastasis, and 5-FU drug sensitivity on HCT116 and Caco-2 colorectal cancer cells. Angiogenesis and Matrigel plug assays were used to study the effect of DCBLD2 on angiogenesis. Q-RCR and Western Blot were used to analyze DCBLD2 impact on the EMT signaling pathway, and TAP-MS assay with Co-IP verification was used to identify the downstream target proteins binding to DCBLD2.Results: Both database and clinical sample validation results showed that the expression of DCBLD2 in colorectal cancer tissues was significantly higher than that in normal tissues, leading to poor prognosis of patients. GDSC database analysis showed that DCBLD2 overexpression caused tumor cell resistance to 5-FU. The results of in vitro and in vivo experiments showed that the inhibition of DCBLD2 reduced the proliferation, migration and invasion of colorectal cancer cells, inhibited the angiogenesis of endothelial cells, and enhanced the drug sensitivity to 5-FU. The results of q-RCR and Western Blot experiments showed that the inhibition of DCBLD2 can suppress the EMT signal. The results of TAP-MS assay showed that the proteins bound to DCBLD2 were enriched to the Focal adhesion pathway. The results of Co-IP assay show that DCBLD2 can combine with ITGB1, the key factor of Focal adhesion pathway.Conclusion: DCBLD2 may affect the development of colorectal cancer by regulating cell proliferation and motility, and modulate 5-FU resistance. Down-regulation of DCBLD2 can inhibit EMT signal and angiogenesis. DCBLD2 can combine with ITGB1, the key signal factor of the Focal adhesion pathway.
- Published
- 2021
49. Non-Coding RNA Polymorphisms (rs2910164 and rs1333049) Associated With Prognosis of Lung Cancer Under Platinum-Based Chemotherapy
- Author
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Yi-Xin Chen, Juan Chen, Ji-Ye Yin, Hong-Hao Zhou, Bai-Mei He, and Zhao-Qian Liu
- Subjects
Oncology ,medicine.medical_specialty ,medicine.medical_treatment ,non-coding RNA ,Single-nucleotide polymorphism ,RM1-950 ,Lower risk ,polymorphism ,Polymorphism (computer science) ,Internal medicine ,Genotype ,medicine ,Pharmacology (medical) ,platinum-based chemotherapy ,Lung cancer ,Original Research ,Pharmacology ,Chemotherapy ,Proportional hazards model ,business.industry ,Cancer ,medicine.disease ,lung cancer ,Therapeutics. Pharmacology ,prognosis ,business - Abstract
Purpose: Lung cancer is the largest cause of cancer deaths in the world. Platinum-based chemotherapy is a foundation of first-line chemotherapy. However, the prognosis of lung cancer treated with platinum-based chemotherapy is still a challenge. Single nucleotide polymorphism of non-coding RNA has the potential to be a biomarker, but its effectiveness has yet to be comprehensively assessed. In this study, we explored the association between polymorphisms of non-coding RNA and prognosis of lung cancer patients receiving platinum-based chemotherapy.Materials and Methods: For 446 lung cancer patients receiving platinum-based chemotherapy, 22 single nucleotide polymorphisms of microRNA and long noncoding RNA were genotyped by MALDI-TOF mass spectrometry. Cox regression analysis, Kaplan-Meier method, and long-rank test have been performed to assess the association of overall and progression-free survival with polymorphisms.Results: In the additive and dominant models, genetic polymorphism of ANRIL rs1333049 (G > C) was significantly associated with progression-free survival. Additive model: CC vs GC vs GG [HR = 0.84, p = 0.021, 95% CI (0.73–0.97)]; Recessive model: CC vs GG + GC [HR = 0.77, p = 0.026, 95% CI (0.61–0.97)]. In the dominant model, compared with the CC genotype patients, lower risk of death [HR = 0.81, p = 0.036, 95% CI (0.66–0.99)] and lower risk of progression [HR = 0.81, p = 0.040, 95% CI (0.67–0.99)] have been observed on the patients with CG or GG genotype in miR-146A rs2910164.Conclusion: Our research demonstrated the potential of using ANRIL rs1333049 (G > C) and miR-146A rs2910164 (C > G) as biomarkers to support the prediction of a better prognosis for lung cancer patients receiving platinum-based chemotherapy.
- Published
- 2021
50. Metformin reverses the schizophrenia-like behaviors induced by MK-801 in rats
- Author
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Hong-Hao Zhou, Zhao-Qian Liu, Xu Wang, Wei Zhang, Ji-Ye Yin, Xi Li, Chao Luo, and Xiao-Yuan Mao
- Subjects
Male ,0301 basic medicine ,Reflex, Startle ,endocrine system diseases ,medicine.drug_class ,Anxiety ,Pharmacology ,Neuroprotection ,Open field ,Rats, Sprague-Dawley ,03 medical and health sciences ,0302 clinical medicine ,Animals ,Medicine ,Cognitive Dysfunction ,Maze Learning ,Molecular Biology ,Glycogen Synthase Kinase 3 beta ,Behavior, Animal ,Prepulse Inhibition ,business.industry ,General Neuroscience ,nutritional and metabolic diseases ,medicine.disease ,Receptor antagonist ,Metformin ,Rats ,Dizocilpine ,Disease Models, Animal ,Memory, Short-Term ,Neuroprotective Agents ,030104 developmental biology ,Dopamine receptor ,Schizophrenia ,NMDA receptor ,Neurology (clinical) ,Dizocilpine Maleate ,Cognition Disorders ,business ,Proto-Oncogene Proteins c-akt ,030217 neurology & neurosurgery ,Antipsychotic Agents ,Developmental Biology ,medicine.drug - Abstract
Schizophrenia is known to be a complex and disabling psychiatric disorder. Dopamine receptor antagonists have a significant therapeutic effect in improving the positive symptoms that are associated with the illness. Therefore, dopamine receptor antagonists are commonly used in the treatment of schizophrenia; however, they do not achieve satisfactory results in improving negative symptoms and cognitive impairment. Metformin, widely known as an antidiabetic drug, has been found to enhance spatial memory formation and improve anxiety-like behaviors in rodents. Metformin's neuroprotective effect has been well documented in several neurological disorders including Alzheimer's disease, Parkinson's disease, strokes, Huntington's disease, and seizures. In the present study, we used a rat model to explore the effect of metformin on schizophrenia-like behaviors induced by MK-801 (dizocilpine), an N-methyl-D-aspartate (NMDA) receptor antagonist. We found that the pre-pulse inhibition (PPI) deficit caused by MK-801 could be alleviated by metformin. The hyperlocomotion in the open field test induced by chronic treatment of MK-801 was reversed by administration of metformin. Metformin has no effect on the baseline level of anxiety in normal naive rats, while metformin could relieve the anxiety-like behaviors in MK-801-treatment rats, though this effect is not reaching a significant level. Additionally, metformin could significantly ameliorate working memory impairments induced by MK-801. Moreover, the increased level of phosphorylation of Akt and GSK3β in the frontal cortex induced by MK-801 was normalized by metformin. In conclusion, our results demonstrate that metformin improved schizophrenia-like symptoms in rats, and is therefore a potential agent for the treatment of schizophrenia.
- Published
- 2019
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