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Iron oxide nanoparticles in magnetic drug targeting and ferroptosis-based cancer therapy
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作者 Quazi T.H.Shubhra 《Medical Review》 2023年第5期444-447,共4页
Iron oxide(IO)nanoparticles(NPs)have gained significant attention in the field of biomedicine,particularly in drug targeting and cancer therapy.Their potential in magnetic drug targeting(MDT)and ferroptosis-based canc... Iron oxide(IO)nanoparticles(NPs)have gained significant attention in the field of biomedicine,particularly in drug targeting and cancer therapy.Their potential in magnetic drug targeting(MDT)and ferroptosis-based cancer therapy is highly promising.IO NPs serve as an effective drug delivery system(DDS),utilizing external magnetic fields(EMFs)to target cancer cells while minimizing damage to healthy organs.Additionally,IO NPs can generate reactive oxygen species(ROS)and induce ferroptosis,resulting in cytotoxic effects on cancer cells.This article explores how IO NPs can potentially revolutionize cancer research,focusing on their applications in MDT and ferroptosis-based therapy. 展开更多
关键词 magnetic nanoparticles ferroptosis drug targeting CANCER
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Recent advances in promising drugs for primary prevention of gastroesophageal variceal bleeding with cirrhotic portal hypertension
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作者 Ji-Yao Sheng Zi-Fan Meng +1 位作者 Qiao Li Yong-Sheng Yang 《Hepatobiliary & Pancreatic Diseases International》 SCIE CAS CSCD 2024年第1期4-13,共10页
Background:Gastroesophageal variceal bleeding is one of the most severe complications of patients with cirrhosis.Although primary prevention drugs,including non-selectiveβ-blockers,have effectively reduced the incide... Background:Gastroesophageal variceal bleeding is one of the most severe complications of patients with cirrhosis.Although primary prevention drugs,including non-selectiveβ-blockers,have effectively reduced the incidence of bleeding,their efficacy is limited due to side effects and related contraindications.With recent advances in precision medicine,precise drug treatment provides better treatment efficacy.Data sources:Literature search was conducted in PubMed,MEDLINE and Web of Science for relevant articles published up to May 2022.Information on clinical trials was obtained from https://clinicaltrials.gov/and http://www.chictr.org.cn/.Results:The in-depth understanding of the pathogenesis and advances of portal hypertension has enabled the discovery of multiple molecular targets for promising drugs.According to the site of action,these drugs could be classified into four classes:intrahepatic,extrahepatic,both intrahepatic and extrahepatic targets and others.All these classes of drugs offer advantages over traditional treatments in prevention of gastroesophageal variceal bleeding in patients with cirrhotic portal hypertension.Conclusions:This review classified and summarized the promising drugs,which prevent gastroesophageal variceal bleeding by targeting specific markers of pathogenesis of portal hypertension,demonstrating the significance of using the precision medicine strategy to discover and develop promising drugs for the primary prevention of gastroesophageal variceal bleeding in patients with cirrhotic portal hypertension. 展开更多
关键词 Cirrhotic portal hypertension Target drug Primary prevention BLEEDING
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In silico antiplasmodial effects of phytocompounds derived from Andrographis paniculata on validated drug targets of different stages of Plasmodium falciparum
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作者 Funmilayo I.D.Afolayan Sayo Ebenezer Oladokun 《Infectious Diseases Research》 2024年第2期1-11,共11页
Background:Andrographis paniculata has been widely reported as an herbal plant for malaria treatment.The increasing rate of resistance to recommended antimalarial drugs has justified the need for a continuous search f... Background:Andrographis paniculata has been widely reported as an herbal plant for malaria treatment.The increasing rate of resistance to recommended antimalarial drugs has justified the need for a continuous search for new and more potent drugs that target all stages of the Plasmodium falciparum life cycle from natural plant sources.This study aimed to determine the antiplasmodial effect of phytocompounds derived from A.paniculata on the stages of plasmodium falciparum.Methods:Phytocompounds from A.paniculata were identified by Gas Chromatography-Mass Spectrophotometry(GCMS)analysis.The phytocompounds were screened for their druggability using Lipinski’s rule of five and subjected to Absorption,Distribution,Metabolism,Excretion,Toxicity(ADMET)and druglikeness analysis.The phytocompounds were docked against some validated drug targets at different stages of Plasmodium falciparum(hepatic,asexual,sexual,and vector targets)using PyRx software to analyze the inhibitory potential and protein-ligand interaction.Thereafter,the stability and flexibility of the best complexes were assessed through molecular dynamics simulations at 50ns using WebGRO.Result:The 7a-Isopropenyl-4,5-dimethyloctahydroinden-4-yl exhibited a higher binding affinity and better stability throughout the simulation period with P.falciparum dihydrofolate reductase-thymidylate synthase and Plasmodium falciparum M1 alanyl aminopeptidase for asexual blood stage and gametocyte stage of Plasmodium falciparum,respectively than the existing drugs.Meanwhile,N-Ethyl-3-methoxy-4-methylphenethylamine was also found to have a higher binding affinity and more stability throughout the simulation period with P.falciparum purine nucleoside phosphorylase and Plasmodium falciparum gametocyte surface protein for Hepatic schizonts stage of Plasmodium falciparum and gametocyte transmission blocking stage,respectively,than the existing drugs.Conclusion:The 7a-Isopropenyl-4,5-dimethyloctahydroinden-4-yl and N-Ethyl-3-methoxy-4 methylphenethylamine from A.paniculata are predicted as an antimalarial drug candidate.Thus,it is recommended that in vitro and in vivo bioassays be conducted on these hit compounds to validate these predictions. 展开更多
关键词 Plasmodium falciparum drug targets Andrographis paniculata molecular docking molecular dynamics
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Cancer stem cells, stemness markers and selected drug targeting: metastatic colorectal cancer and cyclooxygenase-2/prostaglandin E2 connection to WNT as a model system
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作者 Reem Ali ALHulais Stephen John Ralph 《Journal of Cancer Metastasis and Treatment》 2019年第1期18-40,共23页
Few studies have reported on the analyses of drugs targeting enriched populations of cancer stem cells (CSCs) as a means for identifying potent anti-CSC agents. This review evaluates recent information on the identifi... Few studies have reported on the analyses of drugs targeting enriched populations of cancer stem cells (CSCs) as a means for identifying potent anti-CSC agents. This review evaluates recent information on the identification and functions of specific CSC surface markers, with particular emphasis on colorectal cancers and the screening of drugs to eliminate such cells. Many of these CSC markers are found commonly expressed on CSCs from different cancer types as well as embryonic stem cells. These markers are often related to hypoxic activation of the WNT/b-catenin pathway, cyclooxygenase-2/prostaglandin E signalling and their relationship to LGR5. By effectively using drugs that inhibit these pathways to kill the CSC population, or otherwise forcing them out of dormancy into active cell division, cancers should become more susceptible to chemotherapy. Such combinational therapies targeting both CSCs and proliferating tumor cells should greatly improve upon the current basis for treatment. 展开更多
关键词 Cancer stem cells colorectal cancer MARKERS selective drug targeting
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Hydrodynamic modeling of ferrofluid flow in magnetic targeting drug delivery
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作者 刘菡萏 徐威 +1 位作者 王石刚 柯遵纪 《Applied Mathematics and Mechanics(English Edition)》 SCIE EI 2008年第10期1341-1349,共9页
Among the proposed techniques for delivering drugs to specific locations within human body, magnetic drug targeting prevails due to its non-invasive character and its high targeting efficiency. Magnetic targeting drug... Among the proposed techniques for delivering drugs to specific locations within human body, magnetic drug targeting prevails due to its non-invasive character and its high targeting efficiency. Magnetic targeting drug delivery is a method of carrying drug-loaded magnetic nanoparticles to a target tissue target under the applied magnetic field. This method increases the drug concentration in the target while reducing the adverse side-effects. Although there have been some theoretical analyses for magnetic drug targeting, very few researchers have addressed the hydrodynamic models of magnetic fluids in the blood vessel. A mathematical model is presented to describe the hydrodynamics of ferrofiuids as drug carriers flowing in a blood vessel under the applied magnetic field. In this model, magnetic force and asymmetrical force are added, and an angular momentum equation of magnetic nanoparticles in the applied magnetic field is modeled. Engineering approximations are achieved by retaining the physically most significant items in the model due to the mathematical complexity of the motion equations. Numerical simulations are performed to obtain better insight into the theoretical model with computational fluid dynamics. Simulation results demonstrate the important parameters leading to adequate drug delivery to the target site depending on the magnetic field intensity, which coincident with those of animal experiments. Results of the analysis provide important information and suggest strategies for improving delivery in clinical application. 展开更多
关键词 magnetic targeting drug delivery FERROFLUIDS magnetic nanoparticles hydrodynamic modeling CFD simulation
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Process Modeling of Ferrofluids Flow for Magnetic Targeting Drug Delivery
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作者 LIU Handan WANG Shigang XU Wei 《Chinese Journal of Mechanical Engineering》 SCIE EI CAS CSCD 2009年第3期440-445,共6页
Among the proposed techniques for delivering drugs to specific sites within the human body, magnetic targeting drug delivery surpasses due to its non-invasive character and its high targeting efficiency. Although ther... Among the proposed techniques for delivering drugs to specific sites within the human body, magnetic targeting drug delivery surpasses due to its non-invasive character and its high targeting efficiency. Although there have been some analyses theoretically for magnetic drug targeting, very few researchers have addressed the hydrodynamic models of magnetic fluids in the blood vessel of human body. This paper presents a mathematical model to describe the hydrodynamics of ferrofluids as drug carriers flowing in a blood vessel under the applied magnetic field. A 3D flow field of magnetic particles in a blood vessel model is numerically simulated in order to further understand clinical application of magnetic targeting drug delivery. Simulation results show that magnetic nanoparticles can be enriched in a target region depending on the applied magnetic field intensity. Magnetic resonance imaging confirms the enrichment of ferrofluids in a desired body tissue of Sprague-Dawley rats. The simulation results coincide with those animal experiments. Results of the analysis provide the important information and can suggest strategies for improving delivery in favor of the clinical application. 展开更多
关键词 Magnetic targeting drug delivery FERROFLUIDS magnetic nano-particels process modeling HYDRODYNAMICS computational fluid dynamics(CFD) numerical simulation Magnetic resonance imaging
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Is it time to rethink the Alzheimer's disease drug development strategy by targeting its silent phase?
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作者 Benoit Souchet Mickael Audrain +3 位作者 Baptiste Billoir Laurent Lecanu Satoru Tada Jérome Braudeau 《Neural Regeneration Research》 SCIE CAS CSCD 2018年第2期224-225,共2页
Alzheimer's disease (AD) is the most frequent cause of dementia in the western world. In clinical terms, AD is characterized by progres- sive cognitive decline that usually begins with memory impairment. As the dis... Alzheimer's disease (AD) is the most frequent cause of dementia in the western world. In clinical terms, AD is characterized by progres- sive cognitive decline that usually begins with memory impairment. As the disease progresses, AD inevitably affects all intellectual functions including executive functions, leading to complete dependence for basic activities of daily life and premature death. 展开更多
关键词 AD Is it time to rethink the Alzheimer’s disease drug development strategy by targeting its silent phase
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Anti-cancer drugs targeting using nanocarrier niosomes-a review
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作者 Sidharth Mehta 《TMR Cancer》 2020年第4期169-174,共6页
In the last few decades numbers of review and research articles have been published on niosomes. This shows the relevant interest of academias & researchers in niosomes because of the advantages sponsored by them ... In the last few decades numbers of review and research articles have been published on niosomes. This shows the relevant interest of academias & researchers in niosomes because of the advantages sponsored by them over other colloidal drug delivery systems. Niosomes formation occurs when non-ionic surfactant vesicles assemble themselves. Various antineoplastic agents are used in chemotherapy, but they have some drawbacks that these agents cause cell death in normal tissues as well. There are two approaches to overcome this limitation. First, to modify the structure of existing drugs, but this will not possible because it changes the properties of drugs. Second, the development of nano-carriers like liposomes, dendrimers, nanoparticles, niosomes et al. Among all, niosomes (non-ionic surfactant vesicles) have more advantages besides all nano-carriers. Drugs either hydrophilic in nature or hydrophobic in nature, both can be incorporated in niosomes. And by embedding specific ligands over vesicular surface enables us to target the drug to specific cancer cells. 展开更多
关键词 NANOCARRIERS NIOSOMES Anticancer drugs Targeted drug delivery Non-ionic surfactants vesicles Anti neoplastic agents
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Network biology:A promising approach for drug target identification against neurodevelopmental disorders
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作者 WAYEZ NAQVI ANANYA SINGH +1 位作者 PREKSHI GARG PRACHI SRIVASTAVA 《BIOCELL》 SCIE 2023年第8期1675-1687,共13页
Biological entities are involved in complicated and complex connections;hence,discovering biological information using network biology ideas is critical.In the past few years,network biology has emerged as an integrat... Biological entities are involved in complicated and complex connections;hence,discovering biological information using network biology ideas is critical.In the past few years,network biology has emerged as an integrative and systems-level approach for understanding and interpreting these complex interactions.Biological network analysis is one method for reducing enormous data sets to clinically useful knowledge for disease diagnosis,prognosis,and treatment.The network of biological entities can help us predict drug targets for several diseases.The drug targets identified through the systems biology approach help in targeting the essential biological pathways that contribute to the progression and development of the disease.The novel strategical approach of system biologyassisted pharmacology coupled with computer-aided drug discovery(CADD)can help drugs fight multifactorial diseases efficiently.In the present review,we have summarized the role and application of network biology for not only unfolding the mechanism of complex neurodevelopmental disorders but also identifying important drug targets for diseases like ADHD,Autism,Epilepsy,and Intellectual Disability.Systems biology has emerged as a promising approach to identifying drug targets and aiming for targeted drug discovery for the precise treatment of neurodevelopmental disorders. 展开更多
关键词 Network biology Neurodevelopmental disorders drug target PHARMACOLOGY System biology assisted CADD
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Drug–Target Interaction Prediction Model Using Optimal Recurrent Neural Network
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作者 G.Kavipriya D.Manjula 《Intelligent Automation & Soft Computing》 SCIE 2023年第2期1675-1689,共15页
Drug-target interactions prediction(DTIP)remains an important requirement in thefield of drug discovery and human medicine.The identification of interaction among the drug compound and target protein plays an essential ... Drug-target interactions prediction(DTIP)remains an important requirement in thefield of drug discovery and human medicine.The identification of interaction among the drug compound and target protein plays an essential pro-cess in the drug discovery process.It is a lengthier and complex process for pre-dicting the drug target interaction(DTI)utilizing experimental approaches.To resolve these issues,computational intelligence based DTIP techniques were developed to offer an efficient predictive model with low cost.The recently devel-oped deep learning(DL)models can be employed for the design of effective pre-dictive approaches for DTIP.With this motivation,this paper presents a new drug target interaction prediction using optimal recurrent neural network(DTIP-ORNN)technique.The goal of the DTIP-ORNN technique is to predict the DTIs in a semi-supervised way,i.e.,inclusion of both labelled and unlabelled instances.Initially,the DTIP-ORNN technique performs data preparation process and also includes class labelling process,where the target interactions from the database are used to determine thefinal label of the unlabelled instances.Besides,drug-to-drug(D-D)and target-to-target(T-T)interactions are used for the weight initia-tion of the RNN based bidirectional long short term memory(BiLSTM)model which is then utilized to the prediction of DTIs.Since hyperparameters signifi-cantly affect the prediction performance of the BiLSTM technique,the Adam optimizer is used which mainly helps to improve the DTI prediction outcomes.In order to ensure the enhanced predictive outcomes of the DTIP-ORNN techni-que,a series of simulations are implemented on four benchmark datasets.The comparative result analysis shows the promising performance of the DTIP-ORNN method on the recent approaches. 展开更多
关键词 drug target interaction deep learning recurrent neural network parameter tuning semi-supervised learning
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Nanodiamonds with powerful ability for drug delivery and biomedical applications:Recent updates on in vivo study and patents 被引量:5
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作者 Swati Chauhan Neha Jain Upendra Nagaich 《Journal of Pharmaceutical Analysis》 SCIE CAS CSCD 2020年第1期1-12,共12页
Nanodiamonds are novel nanosized carbon building blocks possessing varied fascinating mechanical,chemical,optical and biological properties,making them significant active moiety carriers for biomedical application.The... Nanodiamonds are novel nanosized carbon building blocks possessing varied fascinating mechanical,chemical,optical and biological properties,making them significant active moiety carriers for biomedical application.These are known as the most‘captivating’crystals attributed to their chemical inertness and unique properties posing them useful for variety of applications in biomedical era.Alongside,it becomes increasingly important to find,ascertain and circumvent the negative aspects associated with nanodiamonds.Surface modification or functionalization with biological molecules plays a significant role in managing the toxic behavior since nanodiamonds have tailorable surface chemistry.To take advantage of nanodiamond potential in drug delivery,focus has to be laid on its purity,surface chemistry and other considerations which may directly or indirectly affect drug adsorption on nanodiamond and drug release in biological environment.This review emphasizes on the basic properties,synthesis techniques,surface modification techniques,toxicity issues and biomedical applications of nanodiamonds.For the development of nanodiamonds as an effective dosage form,researchers are still engaged in the in-depth study of nanodiamonds and their effect on life interfaces. 展开更多
关键词 NANOMEDICINE Biochemical application DIAMONDOIDS Surface functionalization drug targeting
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A proteomic landscape of pharmacologic perturbations for functional relevance
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作者 Zhiwei Liu Shangwen Jiang +8 位作者 Bingbing Hao Shuyu Xie Yingluo Liu Yuqi Huang Heng Xu Cheng Luo Min Huang Minjia Tan Jun-Yu Xu 《Journal of Pharmaceutical Analysis》 SCIE CAS CSCD 2024年第1期128-139,共12页
Pharmacological perturbation studies based on protein-level signatures are fundamental for drug discovery. In the present study, we used a mass spectrometry (MS)-based proteomic platform to profile the whole proteome ... Pharmacological perturbation studies based on protein-level signatures are fundamental for drug discovery. In the present study, we used a mass spectrometry (MS)-based proteomic platform to profile the whole proteome of the breast cancer MCF7 cell line under stress induced by 78 bioactive compounds. The integrated analysis of perturbed signal abundance revealed the connectivity between phenotypic behaviors and molecular features in cancer cells. Our data showed functional relevance in exploring the novel pharmacological activity of phenolic xanthohumol, as well as the noncanonical targets of clinically approved tamoxifen, lovastatin, and their derivatives. Furthermore, the rational design of synergistic inhibition using a combination of histone methyltransferase and topoisomerase was identified based on their complementary drug fingerprints. This study provides rich resources for the proteomic landscape of drug responses for precision therapeutic medicine. 展开更多
关键词 PROTEOMICS drug PERTURBATION drug target drug combination
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Risk Factors of Depression Screened by Two-Sample Mendelian Randomization Analysis:A Systematic Review
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作者 WANG Han Lin XUE Yan Feng +2 位作者 CUI Bao Qiu LIU Hong SHEN Xin Xin 《Biomedical and Environmental Sciences》 SCIE CAS CSCD 2024年第1期85-95,共11页
Objective This study explored the potentially modifiable factors for depression and major depressive disorder(MDD)from the MR-Base database and further evaluated the associations between drug targets with MDD.Methods ... Objective This study explored the potentially modifiable factors for depression and major depressive disorder(MDD)from the MR-Base database and further evaluated the associations between drug targets with MDD.Methods We analyzed two-sample of Mendelian randomization(2SMR)using genetic variant depression(n=113,154)and MDD(n=208,811)from Genome-Wide Association Studies(GWAS).Separate calculations were performed with modifiable risk factors from MR-Base for 1,001 genomes.The MR analysis was performed by screening drug targets with MDD in the DrugBank database to explore the therapeutic targets for MDD.Inverse variance weighted(IVW),fixed-effect inverse variance weighted(FE-IVW),MR-Egger,weighted median,and weighted mode were used for complementary calculation.Results The potential causal relationship between modifiable risk factors and depression contained 459 results for depression and 424 for MDD.Also,the associations between drug targets and MDD showed that SLC6A4,GRIN2A,GRIN2C,SCN10A,and IL1B expression are associated with an increased risk of depression.In contrast,ADRB1,CHRNA3,HTR3A,GSTP1,and GABRG2 genes are candidate protective factors against depression.Conclusion This study identified the risk factors causally associated with depression and MDD,and estimated 10 drug targets with significant impact on MDD,providing essential information for formulating strategies to prevent and treat depression. 展开更多
关键词 Risk factors drug targets DEPRESSION Major depressive disorder Two-sample Mendelian randomization
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Comprehensive analysis of the role of ubiquitin-specific peptidases in colorectal cancer:A systematic review
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作者 Eman Al-Balushi Amina Al Marzouqi +10 位作者 Shima Tavoosi Amir Hossein Baghsheikhi Arash Sadri Leyla Sharifi Aliabadi Mohammad-Mahdi Salarabedi Syed Azizur Rahman Nabeel Al-Yateem Alireza Mosavi Jarrahi Aram Halimi Mohammad Ahmadvand Wael M Abdel-Rahman 《World Journal of Gastrointestinal Oncology》 SCIE 2024年第1期197-213,共17页
BACKGROUND Colorectal cancer(CRC)is the third most frequent and the second most fatal cancer.The search for more effective drugs to treat this disease is ongoing.A better understanding of the mechanisms of CRC develop... BACKGROUND Colorectal cancer(CRC)is the third most frequent and the second most fatal cancer.The search for more effective drugs to treat this disease is ongoing.A better understanding of the mechanisms of CRC development and progression may reveal new therapeutic strategies.Ubiquitin-specific peptidases(USPs),the largest group of the deubiquitinase protein family,have long been implicated in various cancers.There have been numerous studies on the role of USPs in CRC;however,a comprehensive view of this role is lacking.AIM To provide a systematic review of the studies investigating the roles and functions of USPs in CRC.METHODS We systematically queried the MEDLINE(via PubMed),Scopus,and Web of Science databases.RESULTS Our study highlights the pivotal role of various USPs in several processes implicated in CRC:Regulation of the cell cycle,apoptosis,cancer stemness,epithelial–mesenchymal transition,metastasis,DNA repair,and drug resistance.The findings of this study suggest that USPs have great potential as drug targets and noninvasive biomarkers in CRC.The dysregulation of USPs in CRC contributes to drug resistance through multiple mechanisms.CONCLUSION Targeting specific USPs involved in drug resistance pathways could provide a novel therapeutic strategy for overcoming resistance to current treatment regimens in CRC. 展开更多
关键词 Ubiquitin-specific peptidases Colorectal cancer Deubiquitinase protein family drug target discovery Biomarker discovery
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Brain delivering RNA-based therapeutic strategies by targeting mTOR pathway for axon regeneration after central nervous system injury 被引量:3
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作者 Ming-Xi Li Jing-Wen Weng +2 位作者 Eric S.Ho Shing Fung Chow Chi Kwan Tsang 《Neural Regeneration Research》 SCIE CAS CSCD 2022年第10期2157-2165,共9页
Injuries to the central nervous system(CNS)such as stroke,brain,and spinal cord trauma often result in permanent disabilities because adult CNS neurons only exhibit limited axon regeneration.The brain has a surprising... Injuries to the central nervous system(CNS)such as stroke,brain,and spinal cord trauma often result in permanent disabilities because adult CNS neurons only exhibit limited axon regeneration.The brain has a surprising intrinsic capability of recovering itself after injury.However,the hostile extrinsic microenvironment significantly hinders axon regeneration.Recent advances have indicated that the inactivation of intrinsic regenerative pathways plays a pivotal role in the failure of most adult CNS neuronal regeneration.Particularly,substantial evidence has convincingly demonstrated that the mechanistic target of rapamycin(mTOR)signaling is one of the most crucial intrinsic regenerative pathways that drive axonal regeneration and sprouting in various CNS injuries.In this review,we will discuss the recent findings and highlight the critical roles of mTOR pathway in axon regeneration in different types of CNS injury.Importantly,we will demonstrate that the reactivation of this regenerative pathway can be achieved by blocking the key mTOR signaling components such as phosphatase and tensin homolog(PTEN).Given that multiple mTOR signaling components are endogenous inhibitory factors of this pathway,we will discuss the promising potential of RNA-based therapeutics which are particularly suitable for this purpose,and the fact that they have attracted substantial attention recently after the success of coronavirus disease 2019 vaccination.To specifically tackle the blood-brain barrier issue,we will review the current technology to deliver these RNA therapeutics into the brain with a focus on nanoparticle technology.We will propose the clinical application of these RNA-mediated therapies in combination with the brain-targeted drug delivery approach against mTOR signaling components as an effective and feasible therapeutic strategy aiming to enhance axonal regeneration for functional recovery after CNS injury. 展开更多
关键词 axon sprouting axon regeneration brain targeted drug delivery CNS injury ischemic stroke mTOR nanoparticle neural circuit reconstruction PTEN RNA-based therapeutics
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Fluorescence imaging of drug target proteins using chemical probes 被引量:1
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作者 Hao Zhu Itaru Hamachi 《Journal of Pharmaceutical Analysis》 SCIE CAS CSCD 2020年第5期426-433,共8页
Fluorescence imaging can provide valuable information on the expression,distribution,and activity of drug target proteins.Chemical probes are useful small-molecule tools for fluorescence imaging with high structural f... Fluorescence imaging can provide valuable information on the expression,distribution,and activity of drug target proteins.Chemical probes are useful small-molecule tools for fluorescence imaging with high structural flexibility and biocompatibility.In this review,we briefly introduce two classes of fluorescent probes for the visualization of drug target proteins.Enzymatically activatable probes make use of the specific enzymatic transformations that generally produce a fluorogenic response upon reacting with target enzymes.Alternatively,specific imaging can be conferred with a ligand that drives the probes to target proteins,where the labeling relies on noncovalent binding,covalent inhibition,or traceless labeling by ligand-directed chemistry. 展开更多
关键词 Fluorescence imaging drug target Chemical probe Ligand-directed chemistry
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Design and preparation of a new multi-targeted drug delivery system using multifunctional nanoparticles for co-delivery of siRNA and paclitaxel 被引量:1
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作者 Sara Hosayni Nasab Amin Amani +1 位作者 Hossein Ali Ebrahimi Ali Asghar Hamidi 《Journal of Pharmaceutical Analysis》 SCIE CAS CSCD 2021年第2期163-173,共11页
Drug resistance is a great challenge in cancer therapy using chemotherapeutic agents. Administration of these drugs with siRNA is an efficacious strategy in this battle. Here, the present study tried to incorporate si... Drug resistance is a great challenge in cancer therapy using chemotherapeutic agents. Administration of these drugs with siRNA is an efficacious strategy in this battle. Here, the present study tried to incorporate siRNA and paclitaxel(PTX) simultaneously into a novel nanocarrier. The selectivity of carrier to target cancer tissues was optimized through conjugation of folic acid(FA) and glucose(Glu) onto its surface. The structure of nanocarrier was formed from ternary magnetic copolymers based on FeCopolyethyleneimine(FeCo-PEI) nanoparticles and polylactic acid-polyethylene glycol(PLA-PEG) gene delivery system. Biocompatibility of FeCo-PEI-PLA-PEG-FA(NPsA), FeCo-PEI-PLA-PEG-Glu(NPsB) and FeCo-PEI-PLA-PEG-FA/Glu(NPsAB) nanoparticles and also influence of PTX-loaded nanoparticles on in vitro cytotoxicity were examined using MTT assay. Besides, siRNA-FAM internalization was investigated by fluorescence microscopy. The results showed the blank nanoparticles were significantly less cytotoxic at various concentrations. Meanwhile, siRNA-FAM/PTX encapsulated nanoparticles exhibited significant anticancer activity against MCF-7 and BT-474 cell lines. NPsAB/siRNA/PTX nanoparticles showed greater effects on MCF-7 and BT-474 cells viability than NPsA/siRNA/PTX and NPsB/siRNA/PTX.Also, they induced significantly higher anticancer effects on cancer cells compared with NPsA/siRNA/PTX and NPsB/siRNA/PTX due to their multi-targeted properties using FA and Glu. We concluded that NPsAB nanoparticles have a great potential for co-delivery of both drugs and genes for use in gene therapy and chemotherapy. 展开更多
关键词 PACLITAXEL SIRNA Targeted drug delivery Magnetic nanoparticles Polymeric drug delivery
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Self-assembled Nanoparticles based on Folic Acid Modifi ed Carboxymethyl Chitosan Conjugated with Targeting Antibody 被引量:2
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作者 虎征宇 ZHENG Hua +6 位作者 LI Dan XIONG Xiong TAN Mingyuan HUANG Dan GUO Xing 张雪琼 严晗 《Journal of Wuhan University of Technology(Materials Science)》 SCIE EI CAS 2016年第2期446-453,共8页
Nanoparticles conjugated with antibody were designed as active drug delivery system to reduce the toxicity and side effects of drugs for acute myeloid leukemia(AML).Moreover,methotrexate(MTX)was chosen as modeldru... Nanoparticles conjugated with antibody were designed as active drug delivery system to reduce the toxicity and side effects of drugs for acute myeloid leukemia(AML).Moreover,methotrexate(MTX)was chosen as modeldrug and encapsulate within folic acid modified carboxymethylchitosan(FACMCS)nanoparticles through self-assembling.The chemicalstructure,morphology,release and targeting of nanoparticles were characterized by routine detection.It is demonstrated that the mean diameter is about 150 nm,the release rate increases with the decreasing of p H,the binding rate of CD33 antibody and FA-CMCS nanoparticles is about 5:2,and nanoparticles can effectively bind onto HL60 cells in vitro.The experimentalresults indicate that the FA-CMCS nanoparticles conjugated with antibody may be used as a potentialp Hsensitive drug delivery system with leukemic targeting properties. 展开更多
关键词 chitosan nanoparticles targeted drug delivery cancer controlled release self-assembly pH-sensitive
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Modeling and targeting an essential metabolic pathway of Plasmodium falciparum in apicoplast using Petri nets
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作者 Sakshi Gupta Gajendra Pratap Singh Sunita Kumawat 《Applied Mathematics(A Journal of Chinese Universities)》 SCIE CSCD 2022年第1期91-110,共20页
Petri net(PN) is one of the promising computational and mathematical formalisms used to represent and study the behavior of complex metabolic networks. The various available analysis techniques of PN could be used to ... Petri net(PN) is one of the promising computational and mathematical formalisms used to represent and study the behavior of complex metabolic networks. The various available analysis techniques of PN could be used to validate and analyze the network in different scenarios. Plasmodium falciparum is one of the threatening parasites which causes malaria, a deadly disease affecting a large number of today’s world population. The development of antimalarial drug resistance is an emerging global threat, highlighting the need to discover novel antimalarial targets. The fatty acid biosynthesis of malarial parasite is one of the essential metabolic pathways required for its growth and is present in apicoplast, a non-photosynthetic plastid. The malarial parasite obtains fatty acids by using type two fatty acid synthase(FAS II) enzyme,which is different from type one enzyme used by human host, making it an ideal drug target.This article proposes and studies the PN model of the parasite’s FAS II pathway to analyze the mechanism of potential drug targets in this pathway. The proposed PN model can serve as a base for further findings in the field of antimalarial drug targets to decrease the malaria mortality rate. 展开更多
关键词 Petri net MALARIA Plasmodium falciparum type II fatty acid biosynthesis drug target property analysis
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Regulatory effects of GRK2 on GPCRs and possible use as a drug target
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作者 Chen-chen HAN Yang MA +2 位作者 Yi-fan LI Yang WANG Wei WEI 《中国药理学与毒理学杂志》 CAS CSCD 北大核心 2017年第10期959-960,共2页
G protein-coupled receptor kinase 2(GRK2),as a key Ser/Thr protein kinase,belong to the member of the G protein-coupled receptor kinase(GRK)family.The C-terminus of GRK2 including a plekstrin homology domain and the N... G protein-coupled receptor kinase 2(GRK2),as a key Ser/Thr protein kinase,belong to the member of the G protein-coupled receptor kinase(GRK)family.The C-terminus of GRK2 including a plekstrin homology domain and the N-terminus of GRK2 including the RGS homology domain with binding sites for several proteins and lipids such as G protein-coupled receptors(GPCRs),G protein,phospholipase C,phosphatidylinositol 4,5-bisphosphate,extracellular signal-regulated kinase,protein kinase A and Gβγ,which can regulate the activity of GRK2.GRK2 can regulate GPCR desensitization and internalization by phosphorylating the GPCR,promoting the affinity of binding to arrestins,and uncoupling the receptors from G proteins,which play an important role in maintaining the balance between the receptors and signal transduction.Previous studies have indicated that cardiac GRK2overexpression can promote the phosphorylation ofβ-adrenergic receptor(βAR)leading toβAR desensitization and internalization,which play a pivotal role in inducing heart failure(HF)-related dysfunction and myocyte death.GRK2,as a regulator of cell function,is overexpression in hypertension.Overexpression GRK2 can inhibit Akt/e NOS signaling pathway and decreased the production and activation of e NOS leading to endothelial dysfunction.Collagen-induced arthritis induces the upregulation of GRK2 expression in fibroblast-like synoviocytes.In this review,we mainly discussed the evidence for the association between GRK2 overexpression and various diseases,which suggests that GRK2 may be an effective drug target for preventing and treating heart failure,hypertension and inflammatory disease. 展开更多
关键词 G protein-coupled receptor kinase 2 G protein-coupled receptor signal transduction drug targets DISEASE
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