240 research outputs found
sj-docx-1-tah-10.1177_20406207221085197 – Supplemental material for A multicenter phase II study on the efficacy and safety of hetrombopag in patients with severe aplastic anemia refractory to immunosuppressive therapy
No full textSupplemental material, sj-docx-1-tah-10.1177_20406207221085197 for A multicenter phase II study on the efficacy and safety of hetrombopag in patients with severe aplastic anemia refractory to immunosuppressive therapy by Guangxin Peng, Guangsheng He, Hong Chang, Sujun Gao, Xinjian Liu, Tong Chen, Pei Li, Bing Han, Miao Miao, Zheng Ge, Xiaoyan Ge, Fei Li, Yingmei Li, Shunqing Wang, Yi Wang, Yaqi Shen, Tao Zhang, Jianjun Zou and Fengkui Zhang in Therapeutic Advances in Hematology</p
The cell free DNA methylome captures distinctions between localized and metastatic prostate tumors
No full textWe provide analysis of 60 and 175 plasma DNA methylomes from patients with localized and metastatic prostate cancer, respectively, using the highly sensitive cell-free methylated DNA immunoprecipitation coupled with next generation sequencing (cfMeDIP-seq) technology
The Transcriptomic Heterogeneity in Prostate Cancer
No full textProstate cancer affects millions of people worldwide. The current risk stratification and disease management strategies are not sufficient. Understanding the molecular basis of prostate cancer can help address these clinical needs. While the genome is extensively investigated, the transcriptome of prostate cancer is much less well characterized. I have worked to unravel the transcriptomic heterogeneity in prostate cancer. I investigated the transcriptome of primary tumors with ultra-deep total RNA-seq and identified widespread RNA circularization in prostate cancer for the first time: the average tumor expressed 7,232 distinct circular transcripts and circRNAs showed a highly tissue specific expression pattern. The parental genes of circRNAs showed distinct characteristics and the circular transcriptome harbors unique prognostic information. The degree of circRNA production is directly correlated to disease progression in multiple patient cohorts. Loss of function screening identified 11.3% of highly abundant circRNAs as essential for cell proliferation; for ~90% of these, their parental linear transcripts were not essential. Individual circRNAs can have distinct functions, with circCSNK1G3 promoting cell growth partially through regulating microRNA miR-181. In two side projects, I interrogated the tumor transcriptome from two different aspects: First, I tackled the intra-tumoral heterogeneity at single cell resolution and identified multiple transcriptomic reprogramming associated with tumor progression in primary tumors (Appendix I). Second, I worked to outline the transcriptional regulatory mechanism of the histone demethylation protein LSD1 on the pioneer transcription factor FOXA1 in prostate cancer (Appendix II). Together, my work reiterated the importance of transcriptomic study in prostate cancer: it provided novel insights into prostate cancer biology, offered multiple opportunities for future investigation and pinpointed actionable targets for advanced tumors.Ph.D
The cell free DNA methylome captures distinctions between localized and metastatic prostate tumors
No full textWe provide analysis of 60 and 175 plasma DNA methylomes from patients with localized and metastatic prostate cancer, respectively, using the highly sensitive cell-free methylated DNA immunoprecipitation coupled with next generation sequencing (cfMeDIP-seq) technology
Abstract 5497: LSD1 modulates androgen receptor cistrome in prostate cancer via regulation of FOXA1 chromatin binding
No full textAbstract
Patients with castration-resistant prostate cancer (PCa) benefit from CYP17A1 inhibitors and more potent AR antagonists, but still relapse with tumors expressing high levels of AR and AR regulated genes, indicating restoration of AR activity. Therefore, there remains a pressing need for further development of novel AR targeted therapies.
One major mechanism that contributes to the PCa development is reprogramming of AR cistrome by transcriptional factors and chromatin modifiers. In this process, AR is recruited to a subset of newly established enhancers that can drive the expression of proliferation genes. FOXA1 is one such transcriptional factor that determines cell-lineage and is characterized as a “pioneer” factor to facilitate the access of additional transcription factors (such as AR or ER) to the regions with compact chromatin. A recent study by comparing the AR cistrome in normal prostate and PCa tissues suggests that FOXA1 is responsible for driving AR reprograming. Whole genome analyses in PCa cells have revealed that FOXA1 can recognize enhancer regions with active histone marks (H3K4me1,2) and then further open up the sites to allow subsequent AR binding. However, the molecular mechanism on how FOXA1 is guided to the target region in PCa is still elusive and studying this mechanism exhibits significant translational potential on modulating AR activity in PCa.
Lysine Specific Demethylase 1 (LSD1/KDM1A) is an important epigenetic modifier that can function as a repressor by demethylating H3K4me1,2. However, LSD1 also often associates with enhancers and can function as an activator in some contexts. Our previous studies showed that LSD1 binding significantly overlaps with FOXA1 and the overlapping sites that are marked by high levels of H3K4me2 enrich for AR activated genes. LSD1 also interacts with FOXA1 and this interaction enhances binding of both proteins at AR-mediated enhancers. These findings suggest that LSD1 may regulate the availability of enhancers to AR via interaction with FOXA1 and hence may reprogram AR cistrome in PCa cells. In this study, we performed ChIP-seq analyses of FOXA1 and AR in PCa cells treated with LSD1 inhibitors. The results showed that the global FOXA1 binding was drastically diminished by inhibiting LSD1, indicating that its demethylase activity is required for FOXA1 binding. Importantly, inhibiting LSD1 also results in distinct AR binding patterns with the expression of many classic AR-activated genes being impaired and new AR-activated genes emerged. We are currently carrying out xenograft studies to examine the impact on tumor progression and AR cistrome by LSD1 inhibitor. Overall, our results suggest that the LSD1-FOXA1 interaction functions as an important modulator of AR cistrome and targeting LSD1 in conjunction with AR antagonists may be a promising therapeutic approach to treat PCa.
Citation Format: Shuai Gao, Sujun Chen, Dong Han, Wanting Han, Steven P. Balk, Housheng Hansen He, Changmeng Cai. LSD1 modulates androgen receptor cistrome in prostate cancer via regulation of FOXA1 chromatin binding [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 5497. doi:10.1158/1538-7445.AM2017-5497</jats:p
Species profiles and normalized reactivity of volatile organic compounds from gasoline evaporation in China
No full textIn China, fast increase in passenger cars and gasoline consumption with yet quite limited vapor recovery during gasoline distribution has procured growing concern about gasoline evaporation as an important emission source of volatile organic compounds (VOCs), particularly in megacities hard-hit by air quality problems. This study presents VOC species profiles related to major pathways of gasoline evaporative loss in China, including headspace displacement, refueling operations and spillage/leakage. Apart from liquid gasoline and headspace vapors, gasoline vapors emitted when refueling cars in service stations or tank trucks in oil marketing depots were also sampled in situ with vapor recovery units (VRUs) turning on/off. Alkanes, alkenes and aromatic hydrocarbons accounted for 55-66, 21-35 and 4-8% in refueling vapors, 59-72, 18-28 and 4-10% in headspace vapors and 33-51, 8-15 and 38-48% in liquid gasoline samples, respectively. During refueling with VRUs turning on, total VOCs in vapors were less than one fifth of that with VRUs turning off, and aromatic hydrocarbons had higher weight percentages of about 8% in contrast with that of about 4% during refueling with VRUs turning off. Refueling vapors, especially for that with VRUs turning off, showed a larger fraction of light hydrocarbons including C-3-O-5 light alkenes when compared to headspace vapors, probably due to splashing and disturbance during filling operation. In refueling or headspace vapors the ratios of i-pentane/benzene, i-pentane/toluene, and MTBE (methyl tert-butyl ether)/benzene ranged 8.7-57, 2.7-4.8, and 1.9-6.6, respectively; and they are distinctively much higher than those previously reported in vehicle exhausts. Calculated normalized reactivity or ozone formation potential of the gasoline vapors in China ranged 3.3-4.4 g O-3 g(-1) VOC, about twice that of gasoline headspace vapors reported in USA as a result of larger fractions of alkenes in China's gasoline vapors. The results suggested that reducing VOC emission from gasoline distribution sector would particularly benefit ground-level ozone control in China. (C) 2013 Elsevier Ltd. All rights reserved.Environmental SciencesMeteorology & Atmospheric SciencesSCI(E)EI5ARTICLE110-1187
Leveraging hepatitis B vaccination to consolidate functional cure: reigniting the humoral axis in chronic HBV infection
No full textContext-Sensitive Correlation and Fuzzy Collaborative Clustering Based Unsupervised Change Detection
No full textIdentification of Biomarkers, Pathways, Immune Properties of Mitophagy Genes, and Prediction Models for Intervertebral Disc Degeneration
No full textYongxiong Huang,1,2,* Xianshuai Qiu,3,* Jinlian Liu,4 Jiangtao Wan,5 Cheng Yu,1 Chun Liu,1 Yang Duan,1 Chong Chen,2 Jingxing Dai,6 Jun Ouyang,6 Ming Liu,3 Shaoxiong Min,1,5 Sujun Qiu1 1Department of Spine Surgery, Zhujiang Hospital, Southern Medical University, Guangzhou, 510280, People’s Republic of China; 2Department of Spine Surgery, Guangdong Provincial People’s Hospital, Southern Medical University, Guangzhou, 510000, People’s Republic of China; 3Department of Orthopedics and Sports Medicine Center, Heyou Hospital, Foshan, 528333, People’s Republic of China; 4Department of Pathophysiology, Guangdong Provincial Key Laboratory of Shock and Microcirculation, School of Basic Medical Sciences, Southern Medical University, Guangzhou, 510515, People’s Republic of China; 5Shenzhen Key Laboratory of Spine Surgery, Department of Spine Surgery, Peking University Shenzhen Hospital, Shenzhen, 518036, People’s Republic of China; 6Guangdong Provincial Key Laboratory of Medical Biomechanics & National Key Discipline of Human Anatomy, School of Basic Medical Sciences, Southern Medical University, Guangzhou, 510515, People’s Republic of China*These authors contributed equally to this workCorrespondence: Sujun Qiu, Department of Spine Surgery, Zhujiang Hospital, Southern Medical University, Guangzhou, 510280, People’s Republic of China, Email [email protected] Shaoxiong Min, Shenzhen Key Laboratory of Spine Surgery, Department of Spine Surgery, Peking University Shenzhen Hospital, Shenzhen, 518036, People’s Republic of China, Email [email protected]: Intervertebral disc degeneration (IDD) is the leading cause of low back pain (LBP). The mechanism of IDD development and progression is not fully understood. Peripheral biomarkers are increasingly vital non-radioactive methods in early detection and diagnosis for IDD. Nevertheless, less attention has been paid to the role of mitophagy genes in the progress of IDD. This study aimed to identify the mitophagy disease-causing genes in the process of IDD and mitophagy diagnostic biomarkers for IDD.Methods: Mitophagy-related differentially expressed genes (MRDEGs) related to IDD were investigated by analyzing the microarray datasets of IDD cases from GEO, PathCards and Molecular Signatures Databases. We used R software, WGCNA, PPI, mRNA-miRNA, mRNA-TF, GO, KEGG, GSEA, GSVA and Cytoscape to analyze and visualize the data. We further used ssGSEA for immunoinfiltration analysis to obtain different immune cell infiltration. LASSO model was developed to screen for genes that met the diagnostic gene model requirements. Finally, qRT-PCR, Western blotting and HE were used to verify hub genes and their expression from clinical IDD samples.Results: We identified 14 MRDEGs and 12 hub genes. GO, KEGG, GSEA and GSVA analyses demonstrated that hub genes were critical for the development of IDD. LASSO diagnostic model consisted of six hub genes, among which SQSTM1, ATG7 and OPTN were significantly different between the two IDD disease subtypes. At the same time, SQSTM1 also had a high correlation with immune characteristic subtypes. The results of qRT-PCR and Western blotting also indicated that these genes were significantly differentially expressed in nucleus pulposus cells (NPCs) of the IDD group.Conclusion: We explored an association between MRDEGs-associated signature in IDD and validated that hub genes like SQSTM1 might serve as biomarkers for diagnostic and therapeutic targets for IDD. Meanwhile, this study can provide new insights into the functional characteristics and mechanism of mitophagy in the development of IDD. Keywords: intervertebral disc degeneration, mitophagy-related differentially expressed genes, immune infiltration, diagnostic model, SQSTM1, nucleus pulposus cell
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