104 results on '"Guanglin, Chen"'
Search Results
2. Molecular mechanism of specific HLA-A mRNA recognition by the RNA-binding-protein hMEX3B to promote tumor immune escape
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Kanglong Yang, Guanglin Chen, Fan Yu, Xianyang Fang, Jiahai Zhang, Zhiyong Zhang, Yunyu Shi, and Liang Zhang
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Biology (General) ,QH301-705.5 - Abstract
Abstract Immunotherapy, including immune checkpoint inhibitors and adoptive cell transfer, has obtained great progress, but their efficiencies vary among patients due to the genetic and epigenetic differences. Human MEX3B (hMEX3B) protein is an RNA-binding protein that contains two KH domains at the N-terminus and a RING domain at its C-terminus, which has the activity of E3 ubiquitin ligase and is essential for RNA degradation. Current evidence suggests that hMEX3B is involved in many important biological processes, including tumor immune evasion and HLA-A regulation, but the sequence of substrate RNA recognized by hMEX3B and the functional molecular mechanisms are unclear. Here, we first screened the optimized hMEX3B binding sequence on the HLA-A mRNA and reported that the two tandem KH domains can bind with their substrate one hundred times more than the individual KH domains. We systematically investigated the binding characteristics between the two KH domains and their RNA substrates by nuclear magnetic resonance (NMR). Based on this information and the small-angle X-ray scattering (SAXS) data, we used molecular dynamics simulations to obtain structural models of KH domains in complex with their corresponding RNAs. By analyzing the models, we noticed that on the KH domains’ variable loops, there were two pairs of threonines and arginines that can disrupt the recognition of the RNA completely, and this influence had also been verified both in vitro and in vivo. Finally, we presented a functional model of the hMEX3B protein, which indicated that hMEX3B regulated the degradation of its substrate mRNAs in many biological processes. Taken together, our research illustrated how the hMEX3B protein played a key role in translation inhibition during the immune response to tumor cells and provided an idea and a lead for the study of the molecular mechanism and function of other MEX3 family proteins.
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- 2024
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3. A Remote Fatigue Driving Detection System for Ship Supervision based on Physiological Response Features.
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Jinming Tong, Wei Cheng, Chen Li, Xuming Wang, and Guanglin Chen
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- 2023
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4. Application of Computer Image Processing Technology in Visual Communication System
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Guanglin Chen, Sinong Ding, and Wei Liu
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Electronic computers. Computer science ,QA75.5-76.95 ,Cybernetics ,Q300-390 - Abstract
This research paper aims to enhance the operation of visual communication systems by incorporating computer image processing technology. The study investigates the potential applications of visual communication systems by utilizing imaging equipment to capture distorted fringe images of height-modulated objects from different angles. Phase information closely associated with the object is then extracted from the images and utilized to obtain the object’s three-dimensional surface topography following calibration. The paper applies multi-frequency phase-shift profilometry and Fourier transforms profilometry to construct further a visual communication system based on computer graphics processing technology. The article contributes to visual communication systems by proposing a novel approach that incorporates computer image processing technology. This approach enhances the performance of visual communication systems, resulting in a more effective means of communication. The study’s experimental analysis demonstrates computer image processing technology’s superiority and ability to enhance the visual communication system’s application. The study’s key findings indicate that computer image processing technology can effectively enhance the effectiveness of visual communication systems. The incorporation of imaging equipment and phase extraction methods leads to the production of accurate three-dimensional surface topography data. Furthermore, multi-frequency phase-shift profilometry and Fourier transform profilometry aid in constructing a visual communication system based on computer graphics processing technology, which leads to an overall enhancement of the visual communication system’s application.
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- 2023
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5. An adaptive robust service composition and optimal selection method for cloud manufacturing based on the enhanced multi-objective artificial hummingbird algorithm.
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Qianfu Zhang, Shaobo Li 0001, Ruiqiang Pu, Peng Zhou, Guanglin Chen, Kaixin Li, and Dongchao Lv
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- 2024
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6. Effects of cadmium sulfide nanoparticles on sulfate bioreduction and oxidative stress in Desulfovibrio desulfuricans
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Guoqing Cheng, Huili Ding, Guanglin Chen, Hongjie Shi, Xu Zhang, Minglong Zhu, and Wensong Tan
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Desulfovibrio desulfuricans ,Cadmium sulfide nanoparticles ,Sulfate reduction ,Extracellular polymeric substances (EPS) ,Oxidative stress ,Technology ,Chemical technology ,TP1-1185 ,Biotechnology ,TP248.13-248.65 - Abstract
Highlight Efficiency of bioreduction of sulfate and biomass can be increased by CdS NPs. It is important for the EPS of RSB to improve the sulfate reduction efficiency. Utilization efficiency of extracellular electrons by RSB can be enhanced through EPS. Humic acid can alleviate the oxidative stress induced by CdS NPs to SRB.
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- 2022
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7. Tricyclic Diterpenoids Selectively Suppress Androgen Receptor-Positive Prostate Cancer Cells
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Inderpal Sekhon, Guanglin Chen, Keyara Piri, Seiji Shinkawa, Dennis Ashong, Qiang Zhang, Guangdi Wang, and Qiao-Hong Chen
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QW07 ,diterpenoid ,androgen receptor antagonist ,N-terminal domain ,prostate cancer ,Organic chemistry ,QD241-441 - Abstract
Androgen receptor (AR) is a viable therapeutic target for lethal castration-resistant prostate cancer (CRPC), because the continued progression of CRPC is mainly driven by the reactivation of AR transcriptional activity. The current FDA-approved AR antagonists binding to ligand binding domain (LBD) become ineffective in CRPC with AR gene amplification, LBD mutation, and the evolution of LBD-truncated AR splice variants. Encouraged by the fact that tricyclic aromatic diterpenoid QW07 has recently been established as a potential N-terminal AR antagonist, this study aims to explore the structure–activity relationship of tricyclic diterpenoids and their potential to suppress AR-positive cell proliferation. Dehydroabietylamine, abietic acid, dehydroabietic acid, and their derivatives were selected, since they have a similar core structure as QW07. Twenty diterpenoids were prepared for the evaluation of their antiproliferative potency on AR-positive prostate cancer cell models (LNCaP and 22Rv1) using AR-null cell models (PC-3 and DU145) as comparisons. Our data indicated that six tricyclic diterpenoids possess greater potency than enzalutamide (FDA-approved AR antagonist) towards LNCaP and 22Rv1 AR-positive cells, and four diterpenoids are more potent than enzalutamide against 22Rv1 AR-positive cells. The optimal derivative possesses greater potency (IC50 = 0.27 µM) and selectivity than QW07 towards AR-positive 22Rv1 cells.
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- 2023
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8. Gestational diabetes mellitus is associated with the neonatal gut microbiota and metabolome
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Ting Chen, Yufeng Qin, Minjian Chen, Yuqing Zhang, Xu Wang, Tianyu Dong, Guanglin Chen, Xian Sun, Ting Lu, Richard Allen White, Peng Ye, Hein M. Tun, and Yankai Xia
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Gestational diabetes mellitus ,Microbiota ,Metabolome ,Medicine - Abstract
Abstract Background Gestational diabetes mellitus (GDM) is a metabolic disease that occurs in pregnant women and increases the risk for the development of diabetes. The relationship between GDM and meconium microbiota and metabolome remains incompletely understood. Methods Four hundred eighteen mothers (147 women with GDM and 271 normal pregnant women) and their neonates from the GDM Mother and Child Study were included in this study. Meconium microbiota were profiled by 16S rRNA gene sequencing. Meconium and maternal serum metabolome were examined by UPLC-QE. Results Microbial communities in meconium were significantly altered in neonates from the GDM mothers. A reduction in alpha diversity was observed in neonates of GDM mothers. At the phylum level, the abundance of Firmicutes and Proteobacteria changed significantly in neonates of GDM mothers. Metabolomic analysis of meconium showed that metabolic pathways including taurine and hypotaurine metabolism, pyrimidine metabolism, beta-alanine metabolism, and bile acid biosynthesis were altered in GDM subjects. Several changed metabolites varying by the similar trend across the maternal serum and neonatal meconium were observed. Conclusion Altogether, these findings suggest that GDM could alter the serum metabolome and is associated with the neonatal meconium microbiota and metabolome, highlighting the importance of maternal factors on early-life metabolism.
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- 2021
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9. Core Structure–Activity Relationship Studies of 5,7,20-O-Trimethylsilybins in Prostate Cancer Cell Models
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Sitong Wu, Guanglin Chen, Eva Y. Chen, Leyla S. Farshidpour, Qiang Zhang, Guangdi Wang, and Qiao-Hong Chen
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silybin ,flavonolignan ,5,7,20-O-trimethylsilybin ,prostate cancer ,androgen receptor ,Medicine ,Pharmacy and materia medica ,RS1-441 - Abstract
Silibinin, also known as silybin, is isolated from milk thistle (Silybum marianum). Silibinin has been demonstrated to be a good lead compound due to its potential to prevent and treat prostate cancer. Its moderate potency and poor pharmacokinetic profile hindered it from moving forward to therapeutic use. Our research group has been working on optimizing silibinin for the potential treatment of castration-resistant prostate cancer. Our previous studies established 5,7,20-O-trimethylsilybins as promising lead compounds as they can selectively suppress androgen receptor (AR)-positive LNCaP cell proliferation. Encouraged by the promising data, the present study aims to investigate the relationships between the core structure of 5,7,20-O-trimethylsilybin and their antiproliferative activities towards AR-positive (LNCaP) and AR-negative prostate cancer cell lines (PC-3 and DU145). The structure–activity relationships among the four different core structures (including flavanonol-type flavonolignan (silibinin), flavone-type flavonolignan (hydnocarpin D), chalcone-type flavonolignan, and taxifolin (a flavonolignan precursor) indicate that 5,7,20-O-trimethylsilybins are the most promising scaffold to selectively suppress AR-positive LNCaP prostate cancer cell proliferation. Further investigation on the antiproliferative potency of their optically enriched versions of the most promising 5,7,20-O-trimethylsilybins led to the conclusion that (10R,11R) derivatives (silybin A series) are more potent than (10S,11S) derivatives (silybin B series) in suppressing AR positive LNCaP cell proliferation.
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- 2023
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10. Design and Application of Scenario-Based Perception of Smart Wearable Device Interaction Method.
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Guanglin Chen
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WEARABLE technology ,SMART devices ,USER experience ,VIRTUAL reality - Abstract
At the moment, Internet technology is still in a rapid development phase, with more highperformance, low-power processor chips entering the market and the commercialization of the smart wearable device industry accelerating. Virtual reality, intelligent clouds, and other technologies are at the heart of today's wearable technologies. It is a design product that employs cutting-edge technology to provide sturdy functioning and superior safety. However, the current study on smart wearable devices is more related to engineering technology, and there is relatively little research on the interaction behavior and user experience among users, devices, and environments. Incorporating the design object, application context, user experience, and other factors into the design of smart wearable devices can help promote the transformation of smart wearable devices from technology-driven to user experience-driven. Therefore, it is important to introduce the concepts of context-awareness and interaction design in the design of smart wearable devices. Through contextual cognitive theory, the study studies the contextual cognitive features of users, deconstructs and analyzes the interaction and experience of smart wearable devices, and discovers the relevant elements influencing user experience. The theoretical research results are then integrated with the interaction design system to connect the relationships among users, behaviors, scenes, and technologies, and a context-aware system for smart wearable devices based on scene perception is constructed. The influence of different aspects on the recognition accuracy of the system is analyzed, and the results show that the system proposed in this paper has very superior performance in gesture recognition. [ABSTRACT FROM AUTHOR]
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- 2024
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11. Comp34 displays potent preclinical antitumor efficacy in triple-negative breast cancer via inhibition of NUDT3-AS4, a novel oncogenic long noncoding RNA
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Qiongyu Hao, Piwen Wang, Pranabananda Dutta, Seyung Chung, Qun Li, Kun Wang, Jieqing Li, Wei Cao, Wenhong Deng, Qing Geng, Katrina Schrode, Magda Shaheen, Ke Wu, Donghui Zhu, Qiao-Hong Chen, Guanglin Chen, Yahya Elshimali, Jay Vadgama, and Yong Wu
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Cytology ,QH573-671 - Abstract
Abstract The abnormal PI3K/AKT/mTOR pathway is one of the most common genomic abnormalities in breast cancers including triple-negative breast cancer (TNBC), and pharmacologic inhibition of these aberrations has shown activity in TNBC patients. Here, we designed and identified a small-molecule Comp34 that suppresses both AKT and mTOR protein expression and exhibits robust cytotoxicity towards TNBC cells but not nontumorigenic normal breast epithelial cells. Mechanically, long noncoding RNA (lncRNA) AL354740.1-204 (also named as NUDT3-AS4) acts as a microRNA sponge to compete with AKT1/mTOR mRNAs for binding to miR-99s, leading to decrease in degradation of AKT1/mTOR mRNAs and subsequent increase in AKT1/mTOR protein expression. Inhibition of lncRNA-NUDT3-AS4 and suppression of the NUDT3-AS4/miR-99s association contribute to Comp34-affected biologic pathways. In addition, Comp34 alone is effective in cells with secondary resistance to rapamycin, the best-known inhibitor of mTOR, and displays a greater in vivo antitumor efficacy and lower toxicity than rapamycin in TNBC xenografted models. In conclusion, NUDT3-AS4 may play a proproliferative role in TNBC and be considered a relevant therapeutic target, and Comp34 presents promising activity as a single agent to inhibit TNBC through regulation of NUDT3-AS4 and miR-99s.
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- 2020
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12. Structural and dynamic properties of the YTH domain in complex with N$lt;sup$gt;6$lt;/sup$gt;-methyladenosine RNA studied by accelerated molecular dynamics simulations.
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Mingwei Li, Guanglin Chen, and Zhiyong Zhang
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- 2023
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13. Multi-Center Analysis of Predictive Factors of Enteral Autonomy and Risk Factors of Complications of Pediatric Intestinal Failure in China
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Weiwei Jiang, Guanglin Chen, Ying Wang, Wei Zhong, Chonggao Zhou, Jie Zhang, Xiaofeng Lv, Chunxia Du, Zhongxian Zhu, Qiming Geng, and Weibing Tang
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pediatric intestinal failure ,enteral autonomy ,intestinal failure-associated liver disease ,catheter-related bloodstream infections ,China ,Pediatrics ,RJ1-570 - Abstract
ObjectivesThe aim of this study was to identify predictors for enteral autonomy and intestinal failure (IF)-related complications and evaluate the outcomes of a multi-center pediatric cohort in China.MethodsThe medical records of pediatric patients with IF treated at four medical centers in China from January 1, 2012 to November 31, 2020 were retrospectively reviewed. Enteral autonomy was defined as sustained growth and cessation of parenteral nutrition for >90 days. Multivariate logistic regression analysis was used to identify factors predictive of enteral autonomy and the risk factors of complications, such as IF-associated liver disease (IFALD) and catheter-related bloodstream infection (CRBSI).ResultsThe study cohort of 92 pediatric patients with IF included 71 (77%) who underwent surgery and 21 (23%) who received non-surgical treatment. Eventually, 63 (68.5%) patients achieved enteral autonomy by the end of the follow-up period. Multivariate logistic regression analysis indicated that longer duration of parenteral nutrition (PN), sepsis, and non-breastfeeding were risk factors for enteral autonomy. When considering the detailed intraoperative data, the presence of an ileocecal valve (ICV) and greater residual small bowel (RSB) length were reaffirmed as predictors of achieving enteral autonomy. Medium/long-chain (MCT/LCT) lipids or sepsis were identified as negative predictors for IFALD. Univariate analysis revealed that the use of MCT/LCT lipids was associated with a greater likelihood of CRBSI.ConclusionIn this cohort, enteral autonomy was achieved at a percentage of 68.5%, and the risk factors for not achieving enteral autonomy were a longer duration of PN, sepsis, and non-breastfeeding. The presence of an ICV and a greater RSB length were important predictors of achieving enteral autonomy.
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- 2022
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14. Boussinesq Simulation of Coastal Wave Interaction with Bottom-Mounted Porous Structures
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Kezhao Fang, Minghan Huang, Guanglin Chen, Jinkong Wu, Hao Wu, and Tiantian Jiang
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porous structure ,coastal wave ,Boussinesq equations ,numerical simulation ,Naval architecture. Shipbuilding. Marine engineering ,VM1-989 ,Oceanography ,GC1-1581 - Abstract
A Boussinesq-type wave model is developed in this paper to simulate the interaction of coastal waves with bottom-mounted porous structures. The governing equations are rewritten in the conservative form to facilitate the use of hybrid finite volume (FV) and finite difference (FD) method. Higher-order slope terms are also inserted into the equations to account for rapidly varying bathymetry. The convective flux is approximated using the FV method, while the remaining terms are discretized using the FD method in a uniform rectangle grid system. The time integration is implemented using the third order Runge–Kutta method with an adaptive time step. A single GPU parallel computation is also implemented to save computation costs. The numerical model is validated against a series of experimental datasets, including data acquired in a new laboratory experiment. The predictions are in overall agreement with the measurements, proving that the model is capable of handling wave interaction with porous structures in the coastal region for a wide range of scenarios.
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- 2022
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15. Forecasting Network Interface Flow Using a Broad Learning System Based on the Sparrow Search Algorithm.
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Xiaoyu Li, Shaobo Li 0001, Peng Zhou, and Guanglin Chen
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- 2022
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16. 3-O-Carbamoyl-5,7,20-O-trimethylsilybins: Synthesis and Preliminary Antiproliferative Evaluation
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Sitong Wu, Guanglin Chen, Qiang Zhang, Guangdi Wang, and Qiao-Hong Chen
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silibinin ,carbamoylation ,prostate cancer ,cell proliferation ,androgen receptor ,Organic chemistry ,QD241-441 - Abstract
To search for novel androgen receptor (AR) modulators for the potential treatment of castration-resistant prostate cancer (CRPC), naturally occurring silibinin was sought after as a lead compound because it possesses a moderate potency towards AR-positive prostate cancer cells and its chemical scaffold is dissimilar to all currently marketed AR antagonists. On the basis of the structure–activity relationships that we have explored, this study aims to incorporate carbamoyl groups to the alcoholic hydroxyl groups of silibinin to improve its capability in selectively suppressing AR-positive prostate cancer cell proliferation together with water solubility. To this end, a feasible approach was developed to regioselectively introduce a carbamoyl group to the secondary alcoholic hydroxyl group at C-3 without causing the undesired oxidation at C2–C3, providing an avenue for achieving 3-O-carbamoyl-5,7,20-O-trimethylsilybins. The application of the synthetic method can be extended to the synthesis of 3-O-carbamoyl-3′,4′,5,7-O-tetramethyltaxifolins. The antiproliferative potency of 5,7,20-O-trimethylsilybin and its nine 3-carbamoyl derivatives were assessed in an AR-positive LNCaP prostate cancer cell line and two AR-null prostate cancer cell lines (PC-3 and DU145). Our preliminary bioassay data imply that 5,7,20-O-trimethylsilybin and four 3-O-carbamoyl-5,7,20-O-trimethylsilybins emerge as very promising lead compounds due to the fact that they can selectively suppress AR-positive LNCaP cell proliferation. The IC50 values of these five 5,7,20-O-trimethylsilybins against the LNCaP cells fall into the range of 0.11–0.83 µM, which exhibit up to 660 times greater in vitro antiproliferative potency than silibinin. Our findings suggest that carbamoylated 5,7,20-O-trimethylsilybins could serve as a natural product-based scaffold for new antiandrogens for lethal castration-resistant prostate cancer.
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- 2021
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17. Tricyclic Diterpenoids Selectively Suppress Androgen Receptor-Positive Prostate Cancer Cells
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Chen, Inderpal Sekhon, Guanglin Chen, Keyara Piri, Seiji Shinkawa, Dennis Ashong, Qiang Zhang, Guangdi Wang, and Qiao-Hong
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QW07 ,diterpenoid ,androgen receptor antagonist ,N-terminal domain ,prostate cancer - Abstract
Androgen receptor (AR) is a viable therapeutic target for lethal castration-resistant prostate cancer (CRPC), because the continued progression of CRPC is mainly driven by the reactivation of AR transcriptional activity. The current FDA-approved AR antagonists binding to ligand binding domain (LBD) become ineffective in CRPC with AR gene amplification, LBD mutation, and the evolution of LBD-truncated AR splice variants. Encouraged by the fact that tricyclic aromatic diterpenoid QW07 has recently been established as a potential N-terminal AR antagonist, this study aims to explore the structure–activity relationship of tricyclic diterpenoids and their potential to suppress AR-positive cell proliferation. Dehydroabietylamine, abietic acid, dehydroabietic acid, and their derivatives were selected, since they have a similar core structure as QW07. Twenty diterpenoids were prepared for the evaluation of their antiproliferative potency on AR-positive prostate cancer cell models (LNCaP and 22Rv1) using AR-null cell models (PC-3 and DU145) as comparisons. Our data indicated that six tricyclic diterpenoids possess greater potency than enzalutamide (FDA-approved AR antagonist) towards LNCaP and 22Rv1 AR-positive cells, and four diterpenoids are more potent than enzalutamide against 22Rv1 AR-positive cells. The optimal derivative possesses greater potency (IC50 = 0.27 µM) and selectivity than QW07 towards AR-positive 22Rv1 cells.
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- 2023
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18. Modeling the Effects of Phosphorylation on Phase Separation of the FUS Low-Complexity Domain
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Mingwei Li, Guanglin Chen, and Zhiyong Zhang
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Biophysics - Published
- 2023
19. Brachial Plexopathy from Metaldehyde Poisoning – A Case Report
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See-Teng Tan, Guanglin Chen, Wai Ching, Deanna Lee, and You-Jiang Tan
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Neurology ,Neurology (clinical) - Abstract
We describe the case of a middle-aged female with schizophrenia, who developed acute sensorimotor deficits of the right upper limb within a week of ingesting large amounts of metaldehyde in a suicide attempt. A right-sided brachial plexopathy was diagnosed clinically and supported by electrophysiologic assessments and targeted magnetic resonance imaging scans. Although metaldehyde’s neurotoxicity typically affects the central nervous system, focal involvement of the peripheral nervous system remains unreported in medical literature, and its pathogenic processes await further elucidation. Therefore, we recommend the continued observation for the subsequent development of sensorimotor deficits during the first week of metaldehyde poisoning.
- Published
- 2021
20. 1-Chromonyl-5-Imidazolylpentadienone Demonstrates Anti-Cancer Action against TNBC and Exhibits Synergism with Paclitaxel
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Karan Modi, Scott Lawson, Guanglin Chen, Deepthi Tumuluri, Inga Rekhtman, Michael Kurtz, G. Cristina Brailoiu, Qiao-Hong Chen, and Ashakumary Lakshmikuttyamma
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curcumin ,triple-negative breast cancer ,paclitaxel ,IL-6 ,Biology (General) ,QH301-705.5 ,Chemistry ,QD1-999 - Abstract
Curcumin has been well studied for its anti-oxidant, anti-inflammatory, and anti-cancer action. Its potential as a therapy is limited due to its low bioavailability and rapid metabolism. To overcome these challenges, investigators are developing curcumin analogs, nanoparticle formulations, and combining curcumin with other compounds or dietary components. In the present study, we used a 1-chromonyl-5-imidazolylpentadienone named KY-20-22 that contains both the pharmacophore of curcumin and 1,4 benzopyrone (chromone) moiety typical for flavonoids, and also included specific moieties to enhance the bioavailability. When we tested the in vitro effect of KY-20-22 in triple-negative breast cancer (TNBC) cell lines, we found that it decreased the cell survival and colony formation of MDA-MB-231 and MDA-MB-468 cells. An increase in mitochondrial reactive oxygen species was also observed in TNBC cells exposed to KY-20-22. Furthermore, KY-20-22 decreased epithelial–mesenchymal formation (EMT) as evidenced by the modulation of the EMT markers E-cadherin and N-cadherin. Based on the fact that KY-20-22 regulates interleukin-6, a cytokine involved in chemotherapy resistance, we combined it with paclitaxel and found that it synergistically induced anti-proliferative action in TNBC cells. The results from this study suggested that 1-chromonyl-5-imidazolylpentadienone KY-20-22 exhibited anti-cancer action in MDA-MB-231 and MDA-MB-468 cells. Future studies are required to evaluate the anti-cancer ability and bioavailability of KY-20-22 in the TNBC animal model.
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- 2020
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21. New Zampanolide Mimics: Design, Synthesis, and Antiproliferative Evaluation
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Guanglin Chen, Ziran Jiang, Qiang Zhang, Guangdi Wang, and Qiao-Hong Chen
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natural product ,anticancer agent ,synthesis ,zampanolide ,Organic chemistry ,QD241-441 - Abstract
Zampanolide is a promising microtubule-stabilizing agent (MSA) with a unique chemical structure. It is superior to the current clinically used MSAs due to the covalent nature of its binding to β-tubulin and high cytotoxic potency toward multidrug-resistant cancer cells. However, its further development as a viable drug candidate is hindered by its limited availability. More importantly, conversion of its chemically fragile side chain into a stabilized bioisostere is envisioned to enable zampanolide to possess more drug-like properties. As part of our ongoing project aiming to develop its mimics with a stable side chain using straightforward synthetic approaches, 2-fluorobenzyl alcohol was designed as a bioisosteric surrogate for the side chain based on its binding conformation as confirmed by the X-ray structure of tubulin complexed with zampanolide. Two new zampanolide mimics with the newly designed side chain have been successfully synthesized through a 25-step chemical transformation for each. Yamaguchi esterification and intramolecular Horner−Wadsworth−Emmons condensation were used as key reactions to construct the lactone core. The chiral centers at C17 and C18 were introduced by the Sharpless asymmetric dihydroxylation. Our WST-1 cell proliferation assay data in both docetaxel-resistant and docetaxel-naive prostate cancer cell lines revealed that compound 6 is the optimal mimic and the newly designed side chain can serve as a bioisostere for the chemically fragile N-acetyl hemiaminal side chain in zampanolide.
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- 2020
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22. Strategies for anti-oxidative stress and anti-acid stress in bioleaching of LiCoO2 using an acidophilic microbial consortium
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Dehong Liu, Hongjie Shi, Guanglin Chen, Xu Zhang, Tingyue Gu, Minglong Zhu, and Wensong Tan
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Molecular Medicine ,General Medicine ,Microbiology - Published
- 2022
23. O-Aminoalkyl-O-Trimethyl-2,3-Dehydrosilybins: Synthesis and In Vitro Effects Towards Prostate Cancer Cells
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Bao Vue, Sheng Zhang, Andre Vignau, Guanglin Chen, Xiaojie Zhang, William Diaz, Qiang Zhang, Shilong Zheng, Guangdi Wang, and Qiao-Hong Chen
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silybin ,prostate cancer ,2,3-dehydrosilybin ,cell proliferation ,cell apoptosis ,Organic chemistry ,QD241-441 - Abstract
As part of our ongoing silybin project, this study aims to introduce a basic nitrogen-containing group to 7-OH of 3,5,20-O-trimethyl-2,3-dehydrosilybin or 3-OH of 5,7,20-O-trimethyl-2,3-dehydrosilybin via an appropriate linker for in vitro evaluation as potential anti-prostate cancer agents. The synthetic approaches to 7-O-substituted-3,5,20-O-trimethyl-2,3-dehydrosilybins through a five-step procedure and to 3-O-substituted-5,7,20-O-trimethyl-2,3- dehydrosilybins via a four-step transformation have been developed. Thirty-two nitrogen-containing derivatives of silybin have been achieved through these synthetic methods for the evaluation of their antiproliferative activities towards both androgen-sensitive (LNCaP) and androgen-insensitive prostate cancer cell lines (PC-3 and DU145) using the WST-1 cell proliferation assay. These derivatives exhibited greater in vitro antiproliferative potency than silibinin. Among them, 11, 29, 31, 37, and 40 were identified as five optimal derivatives with IC50 values in the range of 1.40⁻3.06 µM, representing a 17- to 52-fold improvement in potency compared to silibinin. All these five optimal derivatives can arrest the PC-3 cell cycle in the G0/G1 phase and promote PC-3 cell apoptosis. Derivatives 11, 37, and 40 are more effective than 29 and 31 in activating PC-3 cell apoptosis.
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- 2018
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24. Multi-scale analysis of nickel ion tolerance mechanism for thermophilic Sulfobacillus thermosulfidooxidans in bioleaching
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Guanglin Chen, Hongjie Shi, Huili Ding, Xu Zhang, Tingyue Gu, Minglong Zhu, and Wensong Tan
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Ions ,Electric Power Supplies ,Environmental Engineering ,Nickel ,Health, Toxicology and Mutagenesis ,Environmental Chemistry ,Lithium ,Pollution ,Waste Management and Disposal - Abstract
Bioleaching is intensively investigated for recovering valuable metals such as Li, Co, Ni and Cu. Nickel ion stress threatens the health of microorganisms when Ni
- Published
- 2023
25. Targeted 19F-tags to detect amino acids in complex mixtures using NMR spectroscopy
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Keeton Montgomery, Aya Elhabashy, Guanglin Chen, Qiao-Hong Chen, and V.V. Krishnan
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Inorganic Chemistry ,Organic Chemistry ,Environmental Chemistry ,Physical and Theoretical Chemistry ,Biochemistry - Published
- 2023
26. Comp34 displays potent preclinical antitumor efficacy in triple-negative breast cancer via inhibition of NUDT3-AS4, a novel oncogenic long noncoding RNA
- Author
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Kun Wang, Katrina M. Schrode, Qiongyu Hao, Piwen Wang, Jieqing Li, Yong Wu, Seyung Chung, Qun Li, Wenhong Deng, Jay Vadgama, Qiao-Hong Chen, Wei Cao, Ke Wu, Pranabananda Dutta, Magda Shaheen, Donghui Zhu, Qing Geng, Guanglin Chen, and Yahya Elshimali
- Subjects
Cancer Research ,Transcription, Genetic ,AKT1 ,Diseases ,Triple Negative Breast Neoplasms ,Cytotoxicity ,Triple-negative breast cancer ,Cancer ,Tumor ,Chemistry ,Drug discovery ,lcsh:Cytology ,TOR Serine-Threonine Kinases ,Long non-coding RNA ,Gene Expression Regulation, Neoplastic ,Disease Progression ,Neoplastic Stem Cells ,Long Noncoding ,RNA, Long Noncoding ,Transcription ,Biotechnology ,Signal Transduction ,Curcumin ,Oncology and Carcinogenesis ,Immunology ,Antineoplastic Agents ,Article ,Cell Line ,Cellular and Molecular Neuroscience ,Breast cancer ,Genetic ,Cell Line, Tumor ,Breast Cancer ,microRNA ,Genetics ,medicine ,Humans ,lcsh:QH573-671 ,Protein kinase B ,PI3K/AKT/mTOR pathway ,Cell Proliferation ,Sirolimus ,Neoplastic ,Base Sequence ,Cell Biology ,medicine.disease ,MicroRNAs ,Gene Expression Regulation ,Cancer research ,RNA ,Biochemistry and Cell Biology ,Proto-Oncogene Proteins c-akt - Abstract
The abnormal PI3K/AKT/mTOR pathway is one of the most common genomic abnormalities in breast cancers including triple-negative breast cancer (TNBC), and pharmacologic inhibition of these aberrations has shown activity in TNBC patients. Here, we designed and identified a small-molecule Comp34 that suppresses both AKT and mTOR protein expression and exhibits robust cytotoxicity towards TNBC cells but not nontumorigenic normal breast epithelial cells. Mechanically, long noncoding RNA (lncRNA) AL354740.1-204 (also named as NUDT3-AS4) acts as a microRNA sponge to compete with AKT1/mTOR mRNAs for binding to miR-99s, leading to decrease in degradation of AKT1/mTOR mRNAs and subsequent increase in AKT1/mTOR protein expression. Inhibition of lncRNA-NUDT3-AS4 and suppression of the NUDT3-AS4/miR-99s association contribute to Comp34-affected biologic pathways. In addition, Comp34 alone is effective in cells with secondary resistance to rapamycin, the best-known inhibitor of mTOR, and displays a greater in vivo antitumor efficacy and lower toxicity than rapamycin in TNBC xenografted models. In conclusion, NUDT3-AS4 may play a proproliferative role in TNBC and be considered a relevant therapeutic target, and Comp34 presents promising activity as a single agent to inhibit TNBC through regulation of NUDT3-AS4 and miR-99s.
- Published
- 2020
27. Structural and dynamic properties of the YTH domain in complex with N6-methyladenosine RNA studied by accelerated molecular dynamics simulations.
- Author
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Mingwei Li, Guanglin Chen, and Zhiyong Zhang
- Subjects
- *
MOLECULAR dynamics , *HOMOLOGY (Biology) , *GENE expression , *NON-coding RNA , *ADENOSINE derivatives , *RNA methylation - Abstract
Background: N6-methyladenosine (m6A) modifications of mRNA and long non-coding RNA (lncRNAs) are known to play a significant role in regulation of gene expression and organismal development. Besides writer and eraser proteins of this dynamic modification, the YT521-B homology (YTH) domain can recognize the modification involved in numerous cellular processes. The function of proteins containing YTH domain and its binding mode with N6-methyladenosine RNA has attracted considerable attention. However, the structural and dynamic characteristics of the YTH domain in complex with m6A RNA is still unknown. Method: This work presents results of accelerated molecular dynamics (aMD) simulations at the timescale of microseconds. Principal component analysis (PCA), molecular mechanics generalized Born surface area (MM/GBSA) calculations, contact analysis and contact-based principal component analysis (conPCA) provide new insights into structure and dynamics of the YTH-RNA complex. Results: The aMD simulations indicate that the recognition loop has a larger movement away from the binding pocket in the YTH-A3 RNA than that in the YTH-m6A3 RNA. In aMD trajectories of the apo YTH, there is a significant close-open transition of the recognition loop, that is to say, the apo YTH can take both the closed and open structure. We have found that the YTH domain binds more favorably to the methylated RNA than the non-methylated RNA. The per-residue free energy decomposition and conPCA suggest that hydrophobic residues including W380, L383-V385, W431-P434, M437, and M441-L442, may play important roles in favorable binding of the m6A RNA to the YTH domain, which is also supported by aMD simulations of a double mutated system (L383A/M437A). Conclusion: The results are in good agreement with higher structural stability of the YTH-m6A RNA than that of the YTH-A3 RNA. The addition of a methylation group on A3 can enhance its binding to the hydrophobic pocket in the YTH domain. Our simulations support a 'conformational selection' mechanism between the YTH-RNA binding. This work may aid in our understanding of the structural and dynamic characteristics of the YTH protein in complex with the methylated RNA. [ABSTRACT FROM AUTHOR]
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- 2023
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28. The Long-Term Clinical Efficacy of Smart Plug in the Treatment of Aqueous Tear Deficiency Dry Eye: Results of a 5-Year Study
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Dennis S.C. Lam, Xingkai Zhang, Yueting Ma, Vishal Jhanji, Zhaoxia Kuang, Guanglin Chen, Yingying Su, Ye Yuan, and Yong Yao
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medicine.medical_specialty ,Lacrimal Canaliculitis ,business.industry ,Tear drainage ,Aqueous tear deficiency ,eye diseases ,Surgery ,Canaliculitis ,medicine ,Natural tears ,sense organs ,Clinical efficacy ,business ,Fluorescence staining ,Smart plug - Abstract
Background: Dry eye syndrome, which affects 10% to 20% of adults, is a disorder of the tear film and is associated with symptoms of ocular discomfort. Smart Plug is a mechanical treatment in which the tear drainage system is blocked in order to aid in the preservation of natural tears on the ocular surface. Purpose: To evaluate the long-term clinical efficacy of Smart Plug in the treatment of aqueous tear deficiency dry eye. Patients and Methods: Retrospective study. Three hundred and two patients with aqueous tear deficiency dry eye were enrolled and all the patients accepted the punctual plug of Smart plug from Jan. 2011 to Jan. 2016. The clinical symptoms, Schirmer’s I test, Fluorescein staining (FL), tear break up time (TBUT), and complications were observed and analyzed. Results: Three hundred and two patients (604 eyes) were treated with Smart Plug (22 cases accepted upper and lower punctual plug, 280 cases only lower punctual plug). There were 109 males (36.1%) and 193 females (63.9%) with a mean age of 44.54 years old (Range from 25 to 83 years). Ten cases required the upper Smart Plug after lower punctual plug insertion because of no significantly improved symptoms. Smart plug was removed in 3 patients (1%) due to tearing. Six patients had mild postoperative tearing and no special treatment was required. Lacrimal canaliculitis occurred postoperatively in 8 cases (2.6%) (6 lower and 2 upper), and the affected plug was removed and treated with topical antibiotic eye drops. The BUT, SIT and FL scores of all patients were significantly improved from (2.11 ± 1.01, 4.20 ± 1.07, 6.06 ± 1.97) to (4.34 ± 1.22, 9.01 ± 1.56, 2.33 ± 1.28) respectively after at least 36 months of follow-up (All P P < 0.05). Conclusion: During a mean follow-up of 4.3 years, Smart plug is an effective method for the treatment of aqueous tear deficiency dry eye in spite of its postoperative complications such as canaliculitis and tearing.
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- 2020
29. Multi-Scale Analysis of Nickel Tolerance Mechanism for Thermophilic Sulfobacillus Thermosulfidooxidans in Bioleaching
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Guanglin Chen, Hongjie Shi, Huili Ding, Xu Zhang, Tingyue Gu, Minglong Zhu, and Wensong Tan
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History ,Polymers and Plastics ,Business and International Management ,Industrial and Manufacturing Engineering - Published
- 2022
30. Structural and dynamic properties of the YTH domain in complex with N$lt;sup$gt;6$lt;/sup$gt;-methyladenosine RNA studied by accelerated molecular dynamics simulations
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Zhiyong Zhang, Guanglin Chen, and Mingwei Li
- Subjects
Applied Mathematics ,Modeling and Simulation ,Biochemistry, Genetics and Molecular Biology (miscellaneous) ,Computer Science Applications - Published
- 2023
31. Effects of CdS NPs on Sulfate Bioreduction and Oxidative Stress to Desulfovibrio Desulfuricans
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Guoqing Cheng, Huili Ding, Guanglin Chen, Hongjie Shi, Xu Zhang, Minglong Zhu, and Wensong Tan
- Abstract
Sulfate-containing wastewater has a serious threat to the environment and human health. Microbial technology has great potential for the treatment of sulfate-containing wastewater. It was found that nano-photocatalysts could be used as extracellular electron donors to promote the growth and metabolic activity of non-photosynthetic microorganisms. However, nano-photocatalysts could also induce oxidative stress and damage cells. In this paper, the mechanism and regulation strategy of cadmium sulfide nanoparticles(CdS NPs)on the growth of sulfate reducing bacteria and the sulfate reduction process were investigated. The results shows that the sulfate reduction efficiency could be increased by 6.43% through CdS NPs under light conditions. However, the growth of C09 was seriously inhibited by 55.00% due to the oxidative stress induced by CdS NPs on cells. The biomass and sulfate reduction efficiency could be enhanced by 6.84% and 5.85%, respectively, through external addition of humic acid (HA). At the same time, the mechanism of the CdS NPs strengthening the sulfate reduction process by sulfate bacteria was also studied. Which can provide important theoretical guidance and technical support for the development of microbial technology combined with extracellular electron transfer (EET) for the treatment of sulfate-containing wastewater.
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- 2021
32. Strategies for anti-oxidative stress and anti-acid stress in bioleaching of LiCoO
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Dehong, Liu, Hongjie, Shi, Guanglin, Chen, Xu, Zhang, Tingyue, Gu, Minglong, Zhu, and Wensong, Tan
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Oxidative Stress ,Microbial Consortia ,Spermine ,Hydrogen Peroxide ,Lithium ,Acids - Abstract
High metal ion concentrations and low pH cause severely inhibit the activity of an acidophilic microbial consortium (AMC) in bioleaching. This work investigated the effects of exogenous spermine on biofilm formation and the bioleaching efficiency of LiCoO
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- 2021
33. Improvement of TFRC Congestion Control Algorithm Based on LSTM
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Guanglin Chen, Chenyu Chu, and Peide Lou
- Published
- 2021
34. 5-Substituted 3, 3', 4', 7-tetramethoxyflavonoids - A novel class of potent DNA triplex specific binding ligands
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Vanessa M. Rangel, Landy Gu, Guanglin Chen, Qiao-Hong Chen, and Liang Xue
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Biological Products ,Binding Sites ,Molecular Structure ,Organic Chemistry ,Clinical Biochemistry ,Drug Discovery ,Pharmaceutical Science ,Molecular Medicine ,DNA ,Ligands ,Molecular Biology ,Biochemistry - Abstract
Herein, we present a class of potent triplex DNA binding ligands derived from the natural product quercetin, which is the first of its kind that has ever been reported in the literature. The binding of 5-substituted quercetin derivatives (3, 3', 4', 7-tetramethoxyflavonoids) to triplex and duplex DNA was investigated using several biophysical tools, including thermal denaturation monitored by UV, circular dichroism, differential scanning calorimetry, and isothermal titration calorimetry. Experimental data reveal that several 5-substituted 3, 3', 4', 7-tetramethoxyflavonoids have remarkable effects on binding to DNA triple helices, and they do not influence the double-helical DNA structures. A few derivatives such as compounds 5 and 7 have comparable (if not better) binding affinities to neomycin, a well-known DNA triplex binding ligand, under the same conditions. The amino-containing side chains at the 5-position of 3, 3', 4', 7-tetramethoxyflavonoids are crucial for the observed binding affinity and specificity.
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- 2021
35. Synthesis and biological evaluation of niclosamide PROTACs
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Erick, Munoz, Guanglin, Chen, Ahamed, Hossain, Sitong, Wu, Esveidy, Oceguera Nava, Jasmine, Hang, Tong, Lee, Qiang, Zhang, Guangdi, Wang, and Qiao-Hong, Chen
- Subjects
Male ,Ubiquitin-Protein Ligases ,Organic Chemistry ,Clinical Biochemistry ,Prostatic Neoplasms ,Pharmaceutical Science ,Ligands ,Biochemistry ,Receptors, Androgen ,Proteolysis ,Drug Discovery ,Humans ,Niclosamide ,Molecular Medicine ,Molecular Biology - Abstract
Roughly 268,000 new cases of prostate cancer and 34,000 deaths from prostate cancer are projected by the American Cancer Society to occur in the United States in 2022. Androgen receptor is a key protein in the proliferation and survival of prostate cancer cells and has been revealed to be overexpressed in 30% to 50% of castration-resistant prostate cancer patients. One promising approach to reducing the level of this protein is Proteolysis Targeting Chimeras (PROTACs) that is an emerging drug discovery technology. PROTACs are hetero-bifunctional molecules where one end binds to a protein of interest and the other to an E3 ligase ligand, initiating the Ubiquitin-Proteasome Pathway for protein degradation. Two PROTACs with niclosamide as androgen receptor ligand and VHL-032 as the E3 ligase ligand have been designed and synthesized for suppressing proliferation of androgen receptor-positive prostate cancer cells via degrading androgen receptor. The in vitro antiproliferative assessment suggested that they can selectively suppress PC-3, LNCaP, and 22Rv1 prostate cancer cell proliferation, but cannot inhibit DU145 cell proliferation. However, the mechanism of both compounds in suppressing prostate cancer cell proliferation is not through the AR PROTAC mechanism because they did not degrade AR in our Western Blotting assay up to 1 µM.
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- 2022
36. Gestational diabetes mellitus is associated with the neonatal gut microbiota and metabolome
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Yankai Xia, Hein M. Tun, Yuqing Zhang, Tianyu Dong, Xian Sun, Yufeng Qin, Xu Wang, Ting Chen, Lu Ting, Guanglin Chen, Minjian Chen, Peng Ye, and Richard A. White
- Subjects
0301 basic medicine ,Meconium ,Taurine ,endocrine system diseases ,Firmicutes ,Physiology ,030209 endocrinology & metabolism ,Gut flora ,Gestational diabetes mellitus ,03 medical and health sciences ,chemistry.chemical_compound ,0302 clinical medicine ,Metabolomics ,fluids and secretions ,Pregnancy ,Diabetes mellitus ,RNA, Ribosomal, 16S ,medicine ,Metabolome ,Humans ,biology ,business.industry ,Microbiota ,Infant, Newborn ,nutritional and metabolic diseases ,General Medicine ,medicine.disease ,biology.organism_classification ,female genital diseases and pregnancy complications ,Gastrointestinal Microbiome ,Gestational diabetes ,Diabetes, Gestational ,030104 developmental biology ,chemistry ,Medicine ,Female ,business ,Research Article - Abstract
Background Gestational diabetes mellitus (GDM) is a metabolic disease that occurs in pregnant women and increases the risk for the development of diabetes. The relationship between GDM and meconium microbiota and metabolome remains incompletely understood. Methods Four hundred eighteen mothers (147 women with GDM and 271 normal pregnant women) and their neonates from the GDM Mother and Child Study were included in this study. Meconium microbiota were profiled by 16S rRNA gene sequencing. Meconium and maternal serum metabolome were examined by UPLC-QE. Results Microbial communities in meconium were significantly altered in neonates from the GDM mothers. A reduction in alpha diversity was observed in neonates of GDM mothers. At the phylum level, the abundance of Firmicutes and Proteobacteria changed significantly in neonates of GDM mothers. Metabolomic analysis of meconium showed that metabolic pathways including taurine and hypotaurine metabolism, pyrimidine metabolism, beta-alanine metabolism, and bile acid biosynthesis were altered in GDM subjects. Several changed metabolites varying by the similar trend across the maternal serum and neonatal meconium were observed. Conclusion Altogether, these findings suggest that GDM could alter the serum metabolome and is associated with the neonatal meconium microbiota and metabolome, highlighting the importance of maternal factors on early-life metabolism.
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- 2021
37. A novel curcumin analog inhibits canonical and non-canonical functions of telomerase through STAT3 and NF-κB inactivation in colorectal cancer cells
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Seyung S Chung, Pranabananda Dutta, Nathaniel Chard, Jaydutt V. Vadgama, Guanglin Chen, Yong Wu, and Qiao-Hong Chen
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0301 basic medicine ,cancer stem cells ,Telomerase ,Caspase 3 ,colorectal cancer ,NF-κB ,STAT3 ,03 medical and health sciences ,chemistry.chemical_compound ,0302 clinical medicine ,Cancer stem cell ,Telomerase reverse transcriptase ,curcumin analog ,biology ,Clusterin ,CD44 ,3. Good health ,030104 developmental biology ,Oncology ,chemistry ,Apoptosis ,030220 oncology & carcinogenesis ,biology.protein ,Cancer research ,Curcumin ,Research Paper - Abstract
Curcumin is a biologically active polyphenol that exists in Indian spice turmeric. It has been reported that curcumin exerted anti-inflammatory, anti-oxidant and anti-cancer effects in numerous in vitro and in vivo studies. However, it is not well-understood the molecular mechanism of curcumin for the cancer stem cells and telomerase in colorectal cancer. In this study, compound 19, a nitrogen-containing curcumin analog, was used to treat human colorectal cancer cells. Compound 19 showed a greater anti-proliferative activity than curcumin while displayed no significant toxicity toward normal human colon epithelial cells. Compound 19 exerted anti-inflammatory activities by deactivating STAT3 and NF-κB. In cancer stem cell populations, CD44, Oct-4 and ALDHA1 expressions were abolished upon treating with compound 19. Cancer stem cell biomarkers CD51 and CD133 positive populations were reduced and telomerase activities were decreased with the reduced STAT3 binding to hTERT promoters. This means compound 19 dually inhibits canonical and non-canonical functions of telomerase. Furthermore, compound 19 treatments induced cell cycle arrest at G1 phase and apoptosis. Human apoptosis-related array screening revealed that activated caspase 3, catalase, clusterin and cytochrome C led to apoptosis. Taken together, our data suggest that compound 19 can be a novel therapeutic agent for metastatic colorectal cancer by concurrently targeting STAT3 and NF-κB signaling pathways.
- Published
- 2019
38. Targeting of PP2Cδ By a Small Molecule C23 Inhibits High Glucose-Induced Breast Cancer Progression In Vivo
- Author
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Xiaoting Yu, Yong Wu, Roshni Iyer, Qiao-Hong Chen, Kevin T Kemp nd, Ying-Li Wu, Guanglin Chen, Qiongyu Hao, Xianghua Yi, Kytai T. Nguyen, Ke Wu, Guangdi Wang, Donghui Zhu, Shilong Zheng, Zhimin Huang, Jaydutt V. Vadgama, and Yahya Elshimali
- Subjects
Models, Molecular ,0301 basic medicine ,Physiology ,Clinical Biochemistry ,Cell ,Biochemistry ,Mice ,chemistry.chemical_compound ,Enzyme Inhibitors ,Phosphorylation ,General Environmental Science ,biology ,NF-kappa B ,Acetylation ,Protein Phosphatase 2C ,Original Research Communications ,medicine.anatomical_structure ,Disease Progression ,Female ,Growth inhibition ,Curcumin ,Antineoplastic Agents ,Breast Neoplasms ,03 medical and health sciences ,Hsp27 ,Cell Line, Tumor ,Heat shock protein ,medicine ,Animals ,Humans ,Molecular Biology ,Protein kinase C ,Glycogen Synthase Kinase 3 beta ,030102 biochemistry & molecular biology ,Cell growth ,Cancer ,NF-κB ,Cell Biology ,medicine.disease ,Xenograft Model Antitumor Assays ,Disease Models, Animal ,Glucose ,030104 developmental biology ,chemistry ,Hyperglycemia ,biology.protein ,Cancer research ,General Earth and Planetary Sciences ,Tumor Suppressor Protein p53 ,Reactive Oxygen Species - Abstract
Aims: Epidemiologic evidence indicates that diabetes may increase risk of breast cancer (BC) and mortality in patients with cancer. The pathophysiological relationships between diabetes and cancer are not fully understood, and personalized treatments for diabetes-associated BC are urgently needed. Results: We observed that high glucose (HG), via activation of nuclear phosphatase PP2Cδ, suppresses p53 function, and consequently promotes BC cell proliferation, migration, and invasion. PP2Cδ expression is higher in tumor tissues from BC patients with hyperglycemia than those with normoglycemia. The mechanisms underlying HG stimulation of PP2Cδ involve classical/novel protein kinase-C (PKC) activation and GSK3β phosphorylation. Reactive oxygen species (ROS)/NF-κB pathway also mediates HG induction of PP2Cδ. Furthermore, we identified a 1,5-diheteroarylpenta-1,4-dien-3-one (Compound 23, or C23) as a novel potent PP2Cδ inhibitor with a striking cytotoxicity on MCF-7 cells through cell-based screening assay for growth inhibition and activity of a group of curcumin mimics. Beside directly inhibiting PP2Cδ activity, C23 blocks HG induction of PP2Cδ expression via heat shock protein 27 (HSP27) induction and subsequent ablation of ROS/NF-κB activation. C23 can thus significantly block HG-triggered inhibition of p53 activity, leading to the inhibition of cancer cell proliferation, migration, and invasion. In addition, hyperglycemia promotes BC development in diabetic nude mice, and C23 inhibits the xenografted BC tumor growth. Conclusions and Innovation: Our findings elucidate mechanisms that may have contributed to diabetes-associated BC progression, and provide the first evidence to support the possible alternative therapeutic approach to BC patients with diabetes. Antioxid. Redox Signal. 30, 1983-1998.
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- 2019
39. Synthesis and antiproliferative evaluation of new zampanolide mimics
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James D. White, Guangdi Wang, Guanglin Chen, Manee Patanapongpibul, Qiang Zhang, Ziran Jiang, Qiao-Hong Chen, and Shilong Zheng
- Subjects
Antineoplastic Agents ,010402 general chemistry ,01 natural sciences ,Biochemistry ,Article ,Structure-Activity Relationship ,chemistry.chemical_compound ,DU145 ,In vivo ,Tumor Cells, Cultured ,Side chain ,Humans ,Structure–activity relationship ,Physical and Theoretical Chemistry ,Cell Proliferation ,Dose-Response Relationship, Drug ,Molecular Structure ,010405 organic chemistry ,Cell growth ,Organic Chemistry ,Combinatorial chemistry ,0104 chemical sciences ,chemistry ,Cancer cell ,Macrolides ,Bioisostere ,Drug Screening Assays, Antitumor ,Lead compound - Abstract
(–)–Zampanolide is a marine microtubule-stabilizing macrolide that has been shown by in vitro experiments to be a promising anticancer lead compound. Through its unique covalent-binding with β-tubulin, zampanolide exhibits cytotoxic potency towards multi-drug resistant cancer cells that is superior to paclitaxel. However, the limited availability of zampanolide impedes its further in vivo evaluation as a viable drug candidate. Zampanolide is envisioned to become more drug-like if its chemically fragile side chain can be stabilized; hence, this project aims to develop mimics of zampanolide with a stable side chain using straightforward synthetic methods. To this end, twelve novel zampanolide mimics (51-62) with conjugated and planar side chains have been synthesized via a 24-step sequence for each mimic from commercially available 2-butyn-1-ol as starting material. A Horner-Wadsworth-Emmons reaction incorporates the α,β-unsaturated ketone side chain and also closes the core macrocycle. WST-1 cell proliferation assays in three docetaxel-sensitive and two docetaxel-resistant human prostate cancer cell models confirm that a suitably designed side chain can serve as a bioisostere for the N-acyl hemiaminal side chain in zampanolide. Mimic 52 with a 17R chiral center was identified as the optimal candidate with IC(50) values of 0.29–0.46 μM against both docetaxel-sensitive (PC-3 and DU145) and docetaxel-resistant prostate cancer cell lines (PC-3/DTX and DU145/DTX). Zampanolide mimic 52 exhibited equivalent antiproliferative potency towards both docetaxel-sensitive and docetaxel-resistant cell lines, with relative resistance in the range of 0.9–1.6.
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- 2019
40. The effects of two mixed intravenous lipid emulsions on clinical outcomes in infants after gastrointestinal surgery: a prospective, randomized study
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Qiming Geng, Huan Chen, Wei Li, Xiaoqun Xu, Guanglin Chen, Weibing Tang, Jie Zhang, Weiwei Jiang, Hongxing Li, Xiaofeng Lv, and Changgui Lu
- Subjects
Male ,Fat Emulsions, Intravenous ,Parenteral Nutrition ,medicine.medical_specialty ,medicine.medical_treatment ,Aspartate transaminase ,law.invention ,Sepsis ,03 medical and health sciences ,0302 clinical medicine ,Randomized controlled trial ,law ,030225 pediatrics ,Pediatric surgery ,medicine ,Humans ,Prospective Studies ,Digestive System Surgical Procedures ,Postoperative Care ,biology ,business.industry ,Infant, Newborn ,General Medicine ,medicine.disease ,Surgery ,Treatment Outcome ,Cytokine ,Parenteral nutrition ,Alanine transaminase ,Pediatrics, Perinatology and Child Health ,biology.protein ,Female ,030211 gastroenterology & hepatology ,medicine.symptom ,business ,Weight gain ,Follow-Up Studies - Abstract
There are many advantages of a SMOF emulsion (SMOF-lipid), such as liver-protective properties and anti-inflammatory effects. The objective of this study was to compare the clinical outcomes of SMOF-lipid with medium-chain triglycerides (MCT) /long-chain triglycerides (LCT) in infants after intestinal surgery. This was a prospective, randomized study. Neonates receiving intravenous nutrient solution, including lipid emulsion after gastrointestinal surgery, were included in this study. The patients were randomly assigned to the SMOF-lipid or MCT/LCT groups. Infants who received intravenous lipid emulsion continuously for > 2 weeks were considered to have completed the study. Differences in weight gain, nutrition indices, alanine transaminase (ALT), aspartate transaminase (AST), and direct bilirubin (DB), and inflammation cytokine markers (interleukin [IL]-6 and tumor necrosis factor [TNF]-α) were measured. The final sample included 160 infants. One hundred fourteen infants received intravenous SMOF-lipid (74) or MCT/LCT (86) > 2 weeks and 46 infants received intravenous SMOF-lipid (22) or MCT/LCT (24) > 4 weeks. There were no significant differences in weight gain, nutrition indices, inflammation cytokine markers, and sepsis between the groups at the end of 2 and 4 weeks; however, in the SMOF group, the ALT, AST, and DB levels were significantly lower than the MCT/LCT group at the end of 4 weeks. The mixture and balanced emulsion of SMOF-lipid was well-tolerated in infants who have undergone gastrointestinal surgery, and liver-protective properties were demonstrated following long-term venous nutrition, especially > 4 weeks.
- Published
- 2018
41. Circular RNA CCDC66 targets DCX to regulate cell proliferation and migration by sponging miR‐488‐3p in Hirschsprung's disease
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Hua Zhang, Hua Xie, Hongxing Li, Xiaoqun Xu, Yang Su, Guanglin Chen, Zhongxian Zhu, Lei Peng, Weibing Tang, Zechao Wen, Qiyang Shen, and Chunxia Du
- Subjects
Doublecortin Domain Proteins ,Male ,0301 basic medicine ,Doublecortin Protein ,Physiology ,Immunoprecipitation ,Clinical Biochemistry ,Biology ,03 medical and health sciences ,0302 clinical medicine ,Cell Movement ,Circular RNA ,medicine ,Humans ,Hirschsprung Disease ,Eye Proteins ,Hirschsprung's disease ,Cell Proliferation ,Luciferase reporter ,Competing endogenous RNA ,Cell growth ,Neuropeptides ,Infant ,RNA-Binding Proteins ,RNA, Circular ,Cell Biology ,medicine.disease ,In vitro ,Cell biology ,MicroRNAs ,HEK293 Cells ,030104 developmental biology ,Gene Expression Regulation ,030220 oncology & carcinogenesis ,Female ,Microtubule-Associated Proteins ,Function (biology) - Abstract
It has been suggested that circular RNAs play critical roles in natural growth and disease development. Nevertheless, whether the circular RNAs were related in Hirschsprung's disease (HSCR) remains unknown. Thus, we discovered the cir-CCDC66 was downregulated in HSCR compared with the normal gut tissues. The cir-CCDC66 reduction might inhibit cells' proliferation and migration in vitro. Then, we found that DCX transcript was putative cir-CCDC66 competing endogenous RNA. Furthermore, the function of cir-CCDC66 as a sponge for miR-488-3p to regulate DCX RNA expression was demonstrated by immunoprecipitation and luciferase reporter assays. In conclusion, this is the first report revealing that cir-CCDC66 modulates DCX expression through sponging miR-488-3p and thus participates in the onset of HSCR.
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- 2018
42. Risk factors for the occurrence and recurrence of acute cerebellar ataxia: a retrospective observational study
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Hongxing Li, Weibing Tang, Chunxia Du, Jie Zhang, Weiwei Jiang, Zhongxian Zhu, Hua Xie, Wei Li, Jie Tang, Huan Chen, Qiming Geng, Guanglin Chen, Xiaofeng Lv, and Changgui Lu
- Subjects
medicine.medical_specialty ,Multivariate analysis ,Cerebellar Ataxia ,Dermatology ,Logistic regression ,03 medical and health sciences ,0302 clinical medicine ,Recurrence ,Risk Factors ,Internal medicine ,Medicine ,Craniocerebral Trauma ,Humans ,030212 general & internal medicine ,Risk factor ,skin and connective tissue diseases ,Child ,Neuroradiology ,Retrospective Studies ,Univariate analysis ,business.industry ,food and beverages ,Retrospective cohort study ,General Medicine ,eye diseases ,stomatognathic diseases ,Psychiatry and Mental health ,Acute Disease ,Neurology (clinical) ,Neurosurgery ,business ,030217 neurology & neurosurgery ,Abdominal surgery - Abstract
There is little evidence to support a correlation between abdominal surgery and acute cerebellar ataxia (ACA). We reviewed the records of children with ACA treated at our institution to analyze risk factors for ACA. Clinical data of 442 children with ACA treated at Children’s Hospital of Nanjing Medical University between November 2015 and June 2019 were retrospectively analyzed. Univariate and multivariate analyses were performed to determine risk factors for the occurrence and recurrence of ACA. In total, 442 children with ACA were included in this study. Multivariate logistic regression analysis showed age (p = 0.009), infection (p
- Published
- 2021
43. Additional file 2 of Gestational diabetes mellitus is associated with the neonatal gut microbiota and metabolome
- Author
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Chen, Ting, Yufeng Qin, Minjian Chen, Yuqing Zhang, Wang, Xu, Tianyu Dong, Guanglin Chen, Sun, Xian, Lu, Ting, White, Richard Allen, Ye, Peng, Tun, Hein M., and Yankai Xia
- Abstract
Additional file 2: Figure S1. PCoA (based on weighted unifrac distances) of the gut microbiome by delivery mode. Figure S2. The abundances of the dominant families between two groups when stratified by delivery mode (a: vaginal delivery, b: C-section). Figure S3. Correlation networks of significantly differentiated genera in neonates born to control mothers (A) and GDM mothers (B). Red and green edges represented positive and negative correlations, respectively. Yellow and blue nodes indicate genera enriched in the control and the GDM group, respectively. In addition, node size denotes the mean relative abundance of the genus within each group.
- Published
- 2021
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- View/download PDF
44. Prospective study reveals a microbiome signature that predicts the occurrence of post-operative enterocolitis in Hirschsprung disease (HSCR) patients
- Author
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Guanglin Chen, Lingling Zhou, Yang Li, Zhengke Zhi, Bo Hang, Weibing Tang, Jian-Hua Mao, Yankai Xia, Antoine M. Snijders, Hongxing Li, Hang Chang, Lei Peng, Yang Su, Chen Yuan, Pin Wang, and Yuqing Zhang
- Subjects
0301 basic medicine ,Lipopolysaccharides ,Male ,Hirschsprung disease ,Breastfeeding ,Disease ,the enteric microbiome ,Gastroenterology ,Oral and gastrointestinal ,Pathogenesis ,0302 clinical medicine ,Postoperative Complications ,2.1 Biological and endogenous factors ,Prospective Studies ,Post operative ,Intestinal Mucosa ,Aetiology ,Prospective cohort study ,Enterocolitis ,Pediatric ,Incidence (epidemiology) ,Infectious Diseases ,Breast Feeding ,exclusive breastfeeding ,cardiovascular system ,030211 gastroenterology & hepatology ,Female ,medicine.symptom ,Microbiology (medical) ,medicine.medical_specialty ,Colon ,Biology ,Microbiology ,03 medical and health sciences ,Clinical Research ,Internal medicine ,medicine ,Humans ,Hirschsprung Disease ,Microbiome ,Hirschsprung-associated enterocolitis ,Bacteria ,Prevention ,Infant ,Gastrointestinal Microbiome ,030104 developmental biology ,Good Health and Well Being ,Case-Control Studies ,Research Paper/Report ,Congenital Structural Anomalies ,Digestive Diseases - Abstract
Hirschsprung disease (HSCR) is a birth defect with an approximate incidence of 1/5,000 live births, and up to one-third of HSCR patients develop Hirschsprung-associated enterocolitis (HAEC), the leading cause of HSCR-related death. Very little is known about the pathogenesis, prevention, and early diagnosis of HAEC. Here, we used a prospective study to investigate the enteric microbiome composition at the time of surgery as a predictor for developing postoperative HAEC. We identified a microbiome signature containing 21 operational taxonomic units (OTUs) that can potentially predict postoperative HAEC with ~85% accuracy. Furthermore, we identified exclusive breastfeeding as a novel protective factor for total HAEC (i.e., preoperative and postoperative HAEC combined). In addition, we discovered that breastfeeding was associated with a lowered risk for HAEC potentially mediated by modulating the gut microbiome composition characterized by a lower abundance of Gram-negative bacteria and lower LPS concentrations. In conclusion, modulating the gut microbiome by encouraging breastfeeding might prevent HAEC progression in HSCR patients.
- Published
- 2020
45. Structure-activity relationship and pharmacokinetic studies of 3-O-substitutedflavonols as anti-prostate cancer agents
- Author
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Aaron Gonzalez, Ryan Fong, Guanglin Chen, Pravien Rajaram, Qiang Zhang, Shanchun Guo, Maizie Lee, Guangdi Wang, Xiang Li, Changde Zhang, Shilong Zheng, and Qiao-Hong Chen
- Subjects
Male ,0301 basic medicine ,Flavonols ,Antineoplastic Agents ,Article ,Pyrrolidine ,Rats, Sprague-Dawley ,Structure-Activity Relationship ,03 medical and health sciences ,Prostate cancer ,chemistry.chemical_compound ,0302 clinical medicine ,Drug Discovery ,medicine ,Animals ,Humans ,Potency ,Structure–activity relationship ,Cells, Cultured ,Cell Proliferation ,Pharmacology ,Dose-Response Relationship, Drug ,Molecular Structure ,Chemistry ,Organic Chemistry ,Prostatic Neoplasms ,General Medicine ,medicine.disease ,Rats ,Bioavailability ,030104 developmental biology ,Mechanism of action ,030220 oncology & carcinogenesis ,Cancer cell ,Cancer research ,Drug Screening Assays, Antitumor ,medicine.symptom ,Linker - Abstract
Thirty-eight 3-O-substituted-3′,4′-dimethoxyflavonols and twenty-five 3-O-substituted-3′,4′,7-trimethoxyflavonols have been synthesized for systematic investigation on the structure-activity relationships of 3-O-substituted-3′,4′-dimethoxyflavonols in three human prostate cancer cell models. Our findings indicate that incorporation of an appropriate amino group to 3-OH of 3′,4′-dimethoxyflavonol and 3′,4′,7-trimethoxyflavonol through a 3- to 5-carbon linker can substantially improve the in vitro antiproliferative potency in three human prostate cancer cell models, but not in two non-neoplastic human epithelial cell models (MCF 10A and PWR-1E). 1-Methylpiperazine, pyrrolidine, and dibutylamine are optimal terminal amine groups that, in combination with a 3- to 5-carbon linker, are notably beneficial to the anti-proliferative potency of 3-O-substituted-3′,4′-dimethoxyflavonols. It is worth noting that 3-O-(4-methylpiperazin-1-yl)propyl-3′,4′,7-trimethoxyflavonol (76) induces PC-3 cell death in a completely different way from 3-O-pyrrolidinopentyl-3′,4′,7-trimethoxyflavonol (81) even though they belong to 3-O-substituted-3′,4′,7-trimethoxyflavonols and exhibit similar potency in inhibiting PC-3 cell proliferation, suggesting that the mechanism of action for each specific 3-O-substitutedflavonol varies with different amino moiety. 3-O-(N,N-Dibutylamino)propyl-3′,4′-dimethoxyflavonol (42) emerged as the most promising derivative due to its substantially improved potency in cell models, superior bioavailability in rats, and good selectivity of inhibiting prostate cancer cell proliferation over non-neoplastic human epithelial cell proliferation.
- Published
- 2018
46. New Zampanolide Mimics: Design, Synthesis, and Antiproliferative Evaluation
- Author
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Guangdi Wang, Qiang Zhang, Ziran Jiang, Guanglin Chen, and Qiao-Hong Chen
- Subjects
Male ,natural product ,synthesis ,zampanolide ,Pharmaceutical Science ,Antineoplastic Agents ,Docetaxel ,01 natural sciences ,Article ,Analytical Chemistry ,lcsh:QD241-441 ,03 medical and health sciences ,chemistry.chemical_compound ,0302 clinical medicine ,lcsh:Organic chemistry ,stomatognathic system ,Biomimetics ,Drug Discovery ,Side chain ,Tumor Cells, Cultured ,Humans ,Physical and Theoretical Chemistry ,Cell Proliferation ,chemistry.chemical_classification ,Natural product ,010405 organic chemistry ,Organic Chemistry ,Prostatic Neoplasms ,Combinatorial chemistry ,3. Good health ,0104 chemical sciences ,anticancer agent ,chemistry ,Chemistry (miscellaneous) ,Covalent bond ,Drug Resistance, Neoplasm ,030220 oncology & carcinogenesis ,Drug Design ,Hemiaminal ,Molecular Medicine ,Bioisostere ,Macrolides ,Sharpless asymmetric dihydroxylation ,Yamaguchi esterification ,Lactone - Abstract
Zampanolide is a promising microtubule-stabilizing agent (MSA) with a unique chemical structure. It is superior to the current clinically used MSAs due to the covalent nature of its binding to &beta, tubulin and high cytotoxic potency toward multidrug-resistant cancer cells. However, its further development as a viable drug candidate is hindered by its limited availability. More importantly, conversion of its chemically fragile side chain into a stabilized bioisostere is envisioned to enable zampanolide to possess more drug-like properties. As part of our ongoing project aiming to develop its mimics with a stable side chain using straightforward synthetic approaches, 2-fluorobenzyl alcohol was designed as a bioisosteric surrogate for the side chain based on its binding conformation as confirmed by the X-ray structure of tubulin complexed with zampanolide. Two new zampanolide mimics with the newly designed side chain have been successfully synthesized through a 25-step chemical transformation for each. Yamaguchi esterification and intramolecular Horner&ndash, Wadsworth&ndash, Emmons condensation were used as key reactions to construct the lactone core. The chiral centers at C17 and C18 were introduced by the Sharpless asymmetric dihydroxylation. Our WST-1 cell proliferation assay data in both docetaxel-resistant and docetaxel-naive prostate cancer cell lines revealed that compound 6 is the optimal mimic and the newly designed side chain can serve as a bioisostere for the chemically fragile N-acetyl hemiaminal side chain in zampanolide.
- Published
- 2019
47. Preparation, structure, and release behavior of PLLA/silk fibroin micro-fiber films with controlled structure
- Author
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Cao Jianda, Guanglin Chen, Ma Hui, Wu Wen, Wanli Han, and Zhang Huanxia
- Subjects
Poly l lactic acid ,010407 polymers ,Materials science ,business.product_category ,Polymers and Plastics ,Materials Science (miscellaneous) ,Sodium ,fungi ,chemistry.chemical_element ,Fibroin ,01 natural sciences ,Industrial and Manufacturing Engineering ,0104 chemical sciences ,Core (optical fiber) ,chemistry ,Chemical engineering ,Microfiber ,General Agricultural and Biological Sciences ,business ,Coaxial electrospinning - Abstract
Micro-fiber films of poly(l-lactic acid)/silk fibroin as sheath and polyoxyethylene/ sodium l-ascorbic acid-2-phosphate as core were prepared successfully by coaxial electrospinning, and the struct...
- Published
- 2018
48. Identification of two novel PCDHA9 mutations associated with Hirschsprung's disease
- Author
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Hongxing Li, Yankai Xia, Yang Su, Hua Zhang, Qiyang Shen, Chunxia Du, Hua Xie, Lei Peng, Xiaofeng Lv, Weibing Tang, Changgui Lu, Zhongxian Zhu, Zechao Wen, and Guanglin Chen
- Subjects
Male ,0301 basic medicine ,DNA Mutational Analysis ,Mutation, Missense ,Protocadherin ,Gene mutation ,Biology ,medicine.disease_cause ,Enteric Nervous System ,Mice ,03 medical and health sciences ,symbols.namesake ,Intestinal mucosa ,Pregnancy ,Diseases in Twins ,Genetics ,medicine ,Animals ,Humans ,Hirschsprung Disease ,Hirschsprung's disease ,Cells, Cultured ,Exome sequencing ,Myenteric plexus ,Sanger sequencing ,Mice, Inbred ICR ,Mutation ,Siblings ,Twins, Monozygotic ,General Medicine ,Cadherins ,Embryo, Mammalian ,medicine.disease ,Molecular biology ,Pedigree ,030104 developmental biology ,Amino Acid Substitution ,symbols ,Female - Abstract
Hirschsprung's disease (HSCR) is a complex disorder with multiple pathogenic gene mutations. Protocadherin alpha 9 (PCDHA9) was identified as a potential candidate gene for HSCR by whole-exome sequencing in a Chinese family. Sanger sequencing in 298 HSCR cases revealed two sporadic Chinese patients with a novel missence PCDHΑ9 mutation (NM_031857; c.1280C > T[p.Ala427Val]) and one sporadic Chinese patient with another novel missence PCDHΑ9 mutation (c.1425C > G[p.Phe475Leu]).The silico predictions and 3D modeling suggest the deleterious effect of identified mutations on protein function. Immunohistochemistry analysis showed PCDHΑ9 was predominantly expressed in the myenteric plexus of human colon tissues. For mouse embryos, PCDHΑ9 was expressed in the stomach but rarely seen in the intestine during E10.5-12.5, then obviously expressed in the intestinal mucosa at E13.5 and extensively expressed in intestinal muscularis and mucosa at E14.5. Moreover, the down-regulation of PCDHΑ9 in the SH-SY5Y cell line promoted the proliferation and migration rate but inhibited the apoptotic rate. In summary, PCDHΑ9 is potentially related to HSCR and the clustered protocadherins (Pcdhs) may involve in the enteric nervous system (ENS) ontogeny.
- Published
- 2018
49. Identification of candidate genes for necrotizing enterocolitis based on microarray data
- Author
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Weibing Tang, Hongxing Li, Guanglin Chen, Hua Zhang, Yang Li, Zechao Wen, Yankai Xia, Qiyang Shen, Lingling Zhou, Chunxia Du, and Yang Su
- Subjects
0301 basic medicine ,Candidate gene ,Computational biology ,Disease ,Biology ,03 medical and health sciences ,0302 clinical medicine ,Enterocolitis, Necrotizing ,Intestine, Small ,Gene expression ,Genetics ,medicine ,Humans ,Gene Regulatory Networks ,Protein Interaction Maps ,Gene ,Genetic Association Studies ,ACACB ,Microarray analysis techniques ,Gene Expression Profiling ,Infant, Newborn ,Computational Biology ,General Medicine ,Microarray Analysis ,medicine.disease ,digestive system diseases ,030104 developmental biology ,030220 oncology & carcinogenesis ,Necrotizing enterocolitis ,Identification (biology) ,Metabolic Networks and Pathways - Abstract
Necrotizing enterocolitis (NEC) is one of the most serious diseases that could threaten the life of neonates. However the current opinions about the pathogenesis or how to prevent or treat the disease are still ambiguous. The purpose of the present study was to identify the key genes of this disease and provide new insights into the mechanism of NEC. The gene expression data of GSE46619, including 5 specimens from NEC patients and 4 samples from surgical-control infants, were collected from Gene Expression Omnibus (GEO) database. The differentially expressed genes (DEGs) were screened with regard to NEC versus surgical-control group using Limma package in R software and Gene Ontology (GO) enrichment analysis and pathway enrichment analysis were conducted by means of Database for Annotation, Visualization and Integrated Discovery (DAVID) website subsequently. Furthermore the protein-protein interaction (PPI) network for DEGs was constructed using Cytoscape software and the most highly connected module was extracted using MCODE plugin from the PPI network. Moreover, the significantly enriched sub-pathways were identified using iSubpathwayMiner package in R software. A total of 2629 DEGs were screened out between NEC and control samples, including 367 up-regulated genes and 2262 down-regulated genes and they involved in different GO terms and pathways which may be associated with NEC onset and progression. PPI network and module analysis revealed that several genes were defined as hub genes including AGT, IL8 and KNG1. The sub-pathway analysis screened out 189 significantly enriched sub-pathways, including Tryptophan metabolism, Fatty acid metabolism, and Arachidonic acid metabolism. Genes in the corresponding sub-pathway, such as ACACB and CAT were regarded as critical genes in NEC. QRT-PCR was also conducted to identify the expression of the five key genes (AGT, IL8, KNG1, ACACB and CAT) in NEC samples. These findings have identified several hub genes (e.g., AGT, IL8, KNG1, ACACB and CAT) which were presumed to serve critical roles in NEC.
- Published
- 2018
50. Long non-coding RNA LOC100507600 functions as a competitive endogenous RNA to regulate BMI1 expression by sponging miR128-1-3p in Hirschsprung's disease
- Author
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Zhongxian Zhu, Zechao Wen, Hongxing Li, Yankai Xia, Qiyang Shen, Lei Peng, Chunxia Du, Weibing Tang, Hua Zhang, Yang Su, Hua Xie, and Guanglin Chen
- Subjects
Male ,0301 basic medicine ,Cell ,Apoptosis ,Endogeny ,Biology ,03 medical and health sciences ,0302 clinical medicine ,Downregulation and upregulation ,Cell Movement ,Cell Line, Tumor ,medicine ,Humans ,Hirschsprung Disease ,RNA, Small Interfering ,Child ,Molecular Biology ,Polycomb Repressive Complex 1 ,Reporter gene ,Antagomirs ,RNA ,Cell Biology ,Long non-coding RNA ,Blot ,MicroRNAs ,HEK293 Cells ,030104 developmental biology ,medicine.anatomical_structure ,ROC Curve ,BMI1 ,Area Under Curve ,030220 oncology & carcinogenesis ,Cancer research ,Female ,RNA Interference ,RNA, Long Noncoding ,Reports ,Developmental Biology - Abstract
Recently studies reported that long non-coding RNAs (lncRNAs) may take part in a lot of congenital diseases, meanwhile, Hirschsprung's disease (HSCR) is a major congenital digestive tract malformation. Nevertheless whether lncRNAs participate in the occurrence of HSCR and how it contributes to this disease are still unknown. LOC100507600 was selected from our gene expression microarray data obtained from bowel tissues from HSCR patients and negative controls. Subsequently, we used qRT-PCR to prove the result in 64 pairs of HSCR disease bowel stenosis tissues and negative controls. Transwell assay, CCK-8 assay and flow cytometry were employed to explore whether cellular functions change after knocking down the LOC100507600 in SH-SY5Y cell and human 293T cell. Dual-luciferase reporter assay was used to confirm the competitive relationship between BMI1 and LOC100507600 through their association with hsa-miR128–1-3p. Protein extraction and Western blotting were used to further confirm the relationship between LOC100507600 and BMI1. We found that LOC100507600 was obvious reduced in tissues from HSCR patients with noteworthy correlation with BMI1. Furthermore, Downregulation of LOC100507600 repressed cell migration and proliferation and didn't affect cell apoptosis or cycle. Dual-luciferase reporter assay, qRT-PCR and Western blotting assay verified that LOC100507600 serves as a competitive endogenous RNA of miR128–1-3p and down-regulates BMI1 expression by sponging miR128–1-3p in HSCR. In sum, our study researches the potential diagnostic value of LOC100507600 in HSCR and deduces that LOC100507600 can contributes to HSCR as a competitive endogenous RNA to regulate BMI1 expression by sponging miR128–1-3p.
- Published
- 2018
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