Sensitive and accurate detection of biological analytes,such as proteins,genes,small molecules,ions,cells,etc.,has been a significant project in life science.Signal amplification is one of the most effective approache...Sensitive and accurate detection of biological analytes,such as proteins,genes,small molecules,ions,cells,etc.,has been a significant project in life science.Signal amplification is one of the most effective approaches to improve the sensitivity of bioanalysis.Taking advantage of specific base pairing,programmable operation,and predictable assembly,DNA is flexible and suitable to perform the signal amplification procedure.In recent years,signal amplification strategies by means of DNA technology have been widely integrated into the construction of electrochemiluminescence(ECL)biosensors,achieving desirable analytical performance in clinical diagnosis,biomedical research,and drug development.To the best of our knowledge,these DNA signal amplification technologies mainly include classical polymerase chain reaction,and various amplification approaches conducted under mild conditions,such as rolling circle amplification(RCA)or hyperbranched RCA,cleaving enzyme-assisted amplification,DNAzyme-involved amplification,toehold-mediated DNA strand displacement amplification without enzyme participation,and so on.This review overviews the recent advancements of DNA signal amplification strategies for bioanalysis in the ECL realm,sketching the creative trajectory from strategies design to ultrasensitive ECL platform construction and resulting applications.展开更多
Attenuated total reflection surface-enhanced infrared absorption spectroscopy(ATR-SEIRAS)has recently been proven to be a powerful tool for bioanalysis.It enables in situ and in real-time observation of dynamic proces...Attenuated total reflection surface-enhanced infrared absorption spectroscopy(ATR-SEIRAS)has recently been proven to be a powerful tool for bioanalysis.It enables in situ and in real-time observation of dynamic processes occurring on specific interface,revealing rich structural and functional information of biomolecules at sub monolayer level.The aim of this general review was to give an overview of the cutting edge applications of ATRSEIRAS.We start with description of the basic configuration of the standard ATR-SEIRAS platform.The enhanced mechanisms and methods to fabricate enhanced substrates are then presented.We discuss the recent developments,challenges and applications of ATR-SEIRAS in bioanalysis,mainly focusing on DNA analysis,protein behavior and cell properties.Finally,further development of the ATRSEIRAS technique with enhanced sensitivity,improved time and spatial resolutions will be prospected.展开更多
Cells, basic units of living structures and functions, build up a complicated small world, and their order and complexity resemble a small universe. The detailed understanding and elucidation of the matter transport a...Cells, basic units of living structures and functions, build up a complicated small world, and their order and complexity resemble a small universe. The detailed understanding and elucidation of the matter transport and energy conversion mechanisms within a single cell will expand our knowledge about the origin and evolution of life, the disease mechanisms and much more. In past decades, single-cell analysis has been rapidly and significantly improved and various methodologies have been developed to reveal the complexity of mass, energy, and information within single cells. In this review, we focused on the methods developed in recent years for single-cell analysis, including electrochemical method, optical method, and mass spectrometry method. We reviewed the recent advances and representative studies in this research field, and also discussed the strengths and limitations of each method. Finally, we presented the existing technical challenges and further directions for single-cell analysis.展开更多
Developing photoelectrochemical(PEC)bioassays based on the principle of a photocathodic measurement of enzymatic product H_(2)O_(2) is highly attractive because it can naturally avoid interfering signals arising from ...Developing photoelectrochemical(PEC)bioassays based on the principle of a photocathodic measurement of enzymatic product H_(2)O_(2) is highly attractive because it can naturally avoid interfering signals arising from reductive species inherent to biofluids.However,fluctuant oxygen levels in the analyte solution can compromise the accuracy of photocathodic bioanalysis and restrict its application because oxygen reduction potential is similar to H_(2)O_(2).Herein,we addressed this restriction by constructing a triphase biophotocathode with air–liquid–solid joint interfaces by immobilizing an oxidase enzyme film on the tip part of superhydrophobic p-type semiconductor nanowire arrays.Such a triphase biophotocathode has a reaction zone with steady and air phasedependent oxygen concentration which stabilizes and increases the oxidase kinetics,and enables the photocathodic measurement principle in reliable PEC bioassay development with high selectivity,good accuracy,and a wide linear detection range.Moreover,the biophotocathode shows good stability during repeated testing under light illumination.This reliable PEC bioassay system has broad potential in the fields of disease diagnosis,medical research,and environmental monitoring.展开更多
Liquid biopsy is a technology that exhibits potential to detect cancer early,monitor therapies,and predict cancer prognosis due to its unique characteristics,including noninvasive sampling and real-time analysis.Circu...Liquid biopsy is a technology that exhibits potential to detect cancer early,monitor therapies,and predict cancer prognosis due to its unique characteristics,including noninvasive sampling and real-time analysis.Circulating tumor cells(CTCs)and extracellular vesicles(EVs)are two important components of circulating targets,carrying substantial disease-related molecular information and playing a key role in liquid biopsy.Aptamers are single-stranded oligonucleotides with superior affinity and specificity,and they can bind to targets by folding into unique tertiary structures.Aptamer-based microfluidic platforms offer new ways to enhance the purity and capture efficiency of CTCs and EVs by combining the advantages of microfluidic chips as isolation platforms and aptamers as recognition tools.In this review,we first briefly introduce some new strategies for aptamer discovery based on traditional and aptamer-based microfluidic approaches.Then,we subsequently summarize the progress of aptamer-based microfluidics for CTC and EV detection.Finally,we offer an outlook on the future directional challenges of aptamer-based microfluidics for circulating targets in clinical applications.展开更多
Microfluidic,as the systems for using microchannel(micron-or sub-micron scale)to process or manipulate microflow,is being widely applied in enzyme biotechnology and biocatalysis.Microfluidic immobilized enzyme reactor...Microfluidic,as the systems for using microchannel(micron-or sub-micron scale)to process or manipulate microflow,is being widely applied in enzyme biotechnology and biocatalysis.Microfluidic immobilized enzyme reactor(MIER)is a tool with great value for the study of catalytic property and optimal reaction parameter in a flourishing and highly producing manner.In view of its advantages in efficiency,economy,and addressable recognition especially,MIER occupies an important position in the investigation of life science,including molecular biology,bioanalysis and biosensing,biocatalysis etc.Immobilization of enzymes can generally improve their stability,and upon most occasions,the immobilized enzyme is endowed with recyclability.In this review,the enzyme immobilization techniques applied in MIER will be discussed,followed by summarizing the novel developments in the field of MIER for biocatalysis,bioconversion and bioanalysis.The preponderances and deficiencies of the current state-of-the-art preparation ways of MIER are peculiarly discussed.In addition,the prospects of its future study are outlined.展开更多
The new antiepileptic drugs perampanel,retigabine,rufinamide and stiripentol have been recently approved for different epilepsy types.Being them an innovation in the antiepileptics armamentarium,a lot of investigation...The new antiepileptic drugs perampanel,retigabine,rufinamide and stiripentol have been recently approved for different epilepsy types.Being them an innovation in the antiepileptics armamentarium,a lot of investigations regarding their pharmacological properties are yet to be performed.Besides,considering their broad anticonvulsant activities,an extension of their therapeutic indications may be worthy of investigation,especially regarding other seizure types as well as other central nervous system disorders.Although different liquid chromatographic(LC)methods coupled with ultraviolet,fluorescence,mass or tandem-mass spectrometry detection have already been developed for the determination of perampanel,retigabine,rufinamide and stiripentol,new and more cost-effective methods are yet required.Therefore,this review summarizes the main analytical aspects regarding the liquid chromatographic methods developed for the analysis of perampanel,retigabine(and its main active metabolite),rufinamide and stiripentol in biological samples and pharmaceutical dosage forms.Furthermore,the physicochemical and stability properties of the target compounds will also be addressed.Thus,this review gathers,for the first time,important background information on LC methods that have been developed and applied for the determination of perampanel,retigabine,rufinamide and stiripentol,which should be considered as a starting point if new(bio)analytical techniques are aimed to be implemented for these drugs.展开更多
During the last decade high-throughput in vitro absorption,distribution,metabolism and excretion(HTADME)screening has become an essential part of any drug discovery effort of synthetic molecules.The conduct of HT-ADME...During the last decade high-throughput in vitro absorption,distribution,metabolism and excretion(HTADME)screening has become an essential part of any drug discovery effort of synthetic molecules.The conduct of HT-ADME screening has been"industrialized"due to the extensive development of software and automation tools in cell culture,assay incubation,sample analysis and data analysis.The HT-ADME assay portfolio continues to expand in emerging areas such as drug-transporter interactions,early soft spot identification,and ADME screening of peptide drug candidates.Additionally,thanks to the very large and high-quality HT-ADME data sets available in many biopharma companies,in silico prediction of ADME properties using machine learning has also gained much momentum in recent years.In this review,we discuss the current state-of-the-art practices in HT-ADME screening including assay portfolio,assay automation,sample analysis,data processing,and prediction model building.In addition,we also offer perspectives in future development of this exciting field.展开更多
Formulation/pharmaceutical excipients play a major role in formulating drug candidates,with the objectives of ease of administration,targeted delivery and complete availability.Many excipients used in pharmaceutical f...Formulation/pharmaceutical excipients play a major role in formulating drug candidates,with the objectives of ease of administration,targeted delivery and complete availability.Many excipients used in pharmaceutical formulations are orphanized in preclinical drug discovery.These orphan excipients could enhance formulatability of highly lipophilic compounds.Additionally,they are safe in preclinical species when used below the LD50 values.However,when the excipients are used in formulating compounds with diverse physico-chemical properties,they pose challenges by modulating study results through their bioanalytical matrix effects.Excipients invariably present in study samples and not in the calibration curve standards cause over-/under-estimation of exposures.Thus,the mechanism by which excipients cause matrix effects and strategies to nullify these effects needs to be revisited.Furthermore,formulation excipients cause drug interactions by moderating the pathways of drug metabolizing enzymes and drug transport proteins.Although it is not possible to get rid of excipient driven interactions,it is always advised to be aware of these interactions and apply the knowledge to draw meaningful conclusions from study results.In this review,we will comprehensively discuss a)orphan excipients that have wider applications in preclinical formulations,b)bioanalytical matrix effects and possible approaches to mitigating these effects,and c)excipient driven drug interactions and strategies to alleviate the impacts of drug interactions.展开更多
Journal of Pharmaceutical Analysis welcomes submissions of fulllength reviews, original research papers and short communication.The act of submitting a manuscript to the Journal carries with it the right to publish th...Journal of Pharmaceutical Analysis welcomes submissions of fulllength reviews, original research papers and short communication.The act of submitting a manuscript to the Journal carries with it the right to publish that paper.Journal of Pharmaceutical Analysis is published to attract and disseminate innovative and expert findings in the fields:(1) Analysis of traditional Chinese medicine (medicinal materials,patent medicine, prescription, injection)(2) Pharmaceutical analysis of complex system(3) Quality control and methods of biotech drug(4) Action mechanism and metabolisms(5)Quantitative and qualitative analysis in the drug screening process(6) Tracer analysis in molecular pharmacology(7) Quantitative analysis in biopharmaceutics (8) Clinical laboratory and展开更多
Sample preparation is considered as the bottleneck step in bioanalysis because each biological matrix has its own unique challenges and complexity.Competent sample preparation to extract the desired analytes and remov...Sample preparation is considered as the bottleneck step in bioanalysis because each biological matrix has its own unique challenges and complexity.Competent sample preparation to extract the desired analytes and remove redundant components is a crucial step in each bioanalytical approach.The matrix effect is a key hurdle in bioanalytical sample preparation,which has gained extensive consideration.Novel sample preparation techniques have advantages over classical techniques in terms of accuracy,automation,ease of sample preparation,storage,and shipment and have become increasingly popular over the past decade.Our objective is to provide a broad outline of current developments in various bioanalytical sample preparation techniques in chromatographic and spectroscopic examinations.In addition,how these techniques have gained considerable attention over the past decade in bioanalytical research is mentioned with preferred examples.Modern trends in bioanalytical sample preparation techniques,including sorbent-based microextraction techniques,are primarily emphasized.展开更多
Sepsis-induced acute lung injury(ALI)is a leading cause of death among septic complications.Tao-Hong-Si-Wu decoction(TSD),a classical recipe from traditional Chinese medicine used for treating ischemic stroke,has been...Sepsis-induced acute lung injury(ALI)is a leading cause of death among septic complications.Tao-Hong-Si-Wu decoction(TSD),a classical recipe from traditional Chinese medicine used for treating ischemic stroke,has been recently reported to alleviate inflammation and inflammation-stimulated injuries related to the pathology of ALI.Here,we first observed the therapeutic effect of TSD on sepsis-induced ALI.Based on integrated metabolomics and network pharmacology analysis(NPA)techniques,we aim to understand the mechanism of TSD alleviating ALI.TSD’s effects were observed in rats modeled by cecal ligation and puncture(CLP)and rat macrophages stimulated by lipopolysaccharide(LPS).Metabolomics analyses were applied to determine the ingredients in the medicine and key metabolites correlated to the NPA for the prediction of TSD targets.Gene and protein expressions of the key predicted targets were evaluated in the lung tissue and macrophages of septic model rat by quantitative polymerase chain reaction(PCR)and enzyme-linked immunosorbent assays,respectively.TSD improved survival rate and protected against lung injury in CLP rats.Eleven endogenous metabolites were related to TSD’s actions.TSD significantly suppressed IL-6 and TNF-αsecretions and their gene expressions both in the lung tissue of the model rats and in LPS-stimulated macrophages.TSD also restored decreased lung protein expression of VEGFA in septic model rats.Targeted proteins and their affecting metabolites were finally validated in an external test set of rats.This study shows that metabolomics coupled with NPA is a promising approach to explore potential targets of medicine with complex compositions.展开更多
Advanced bioanalysis,including accurate quantitation,has driven the need to understand biology and medicine at the molecular level.Bioconjugated silica nanoparticles have the potential to address this emerging challen...Advanced bioanalysis,including accurate quantitation,has driven the need to understand biology and medicine at the molecular level.Bioconjugated silica nanoparticles have the potential to address this emerging challenge.Particularly intriguing diagnostic and therapeutic applications in cancer and infectious disease as well as uses in gene and drug delivery,have also been found for silica nanoparticles.In this review,we describe the synthesis,bioconjugation,and applications of silica nanoparticles in different bioanalysis formats,such as selective tagging,barcoding,and separation of a wide range of biomedically important targets.Overall,we envisage that further development of these nanoparticles will provide a variety of advanced tools for molecular biology,genomics,proteomics and medicine.展开更多
Electrochemiluminescence(ECL),also called electrogenerated chemiluminescence,is luminescence that is produced by chemical reactions triggered by electrochemical method.ECL imaging is a novel imaging technique,which ca...Electrochemiluminescence(ECL),also called electrogenerated chemiluminescence,is luminescence that is produced by chemical reactions triggered by electrochemical method.ECL imaging is a novel imaging technique,which can simultaneously provide two kinds of signals of both electrochemistry and optical image.Over the past two decades,ECL imaging has been not only a powerful tool for investigating the fundamental scientific questions such as ECL mechanisms and reaction kinetics,but also a versatile analytical technique for detection of a wide range of analytes including small molecules,DNA,proteins,and cells.In the first part of this review,we briefly describe the reaction mechanisms of ECL generation.Then the review focuses on the research progress on the ECL imaging approach.It is basically introduced from the following five aspects:(i)visualization of electroactive sites on surfaces,(ii)imaging analysis at the single-bead and single-cell levels,(iii)array bioanalysis,(iv)multi-color ECL imaging,and(v)paper chip based on ECL imaging.Finally,some perspectives and future directions in this active research area are presented.展开更多
Electrochemiluminescence(ECL)-based imaging analysis is a dominant method to inspect the electrode composition,to study electrochemical reaction kinetics at a microscopic level,and also a rapid emerging technology in ...Electrochemiluminescence(ECL)-based imaging analysis is a dominant method to inspect the electrode composition,to study electrochemical reaction kinetics at a microscopic level,and also a rapid emerging technology in bioanalysis with high spatiotemporal resolutions,high-throughput and visualization characteristics.In comparison with other imaging microscopes,an optical excitation is not involved in imaging,thus the approach is free from background noise resulting in a low detec-tion limit.In this review work,the principle of ECL,its unique natures compared to other luminescence techniques were briefed at first.Then after,the progress and basic principles of ECL imaging were summarized.Furthermore,recent and representative advances of ECL imaging for visualizing and sensing applications were reviewed.Finally,the perspectives in ECL imaging for further perspective were discussed.展开更多
The continuous tuning of plasmonic nanoassembly's structure is the key to manipulate their optical and catalytic properties.Herein,we report a strategy of using macroscopic deformation to continuously tune the str...The continuous tuning of plasmonic nanoassembly's structure is the key to manipulate their optical and catalytic properties.Herein,we report a strategy of using macroscopic deformation to continuously tune the structure and optical activity of massive plasmonic nanoassemblies that are embedded in elastic polymer matrix.Plasmonic gold nanoparticles(Au NPs)are assembled to nanochains(Au NCs)with defined length and further embedded into polyvinylpyrrolidone(PVP)matrix.The nanostructure and plasmonic properties of massive Au NCs in this Au NCs-PVP film can be simultaneously and continuously tuned,simply by reversible mechanical deformation of this elastic film.In this way,the surface-enhanced Raman scattering(SERS)enhancement factor of this film as a SERS substrate can be mechanically modulated in the range of 10^(0)to 6.8×10^(7).Meanwhile,the PVP matrix also serves as a selective diffusion barrier to eliminate the fluorescence interference of large biomolecules,which enables the Au NCs-PVP film as a convenient SER S substrate for quick and direct analysis of small molecule analytes in biological samples and food,avoiding the complicate and time-consuming sample pretreatment process.展开更多
Membrane proteins are vital components of the cell membrane and play crucial roles in various cellular activities.Analysis of membrane proteins is of paramount importance for studying molecular events inside cells and...Membrane proteins are vital components of the cell membrane and play crucial roles in various cellular activities.Analysis of membrane proteins is of paramount importance for studying molecular events inside cells and organisms and holds promising prospects for early disease diagnosis and treatment assessment.Benefiting from obvious merits including high affinity,high specificity and ease of modification,aptamers have been regarded as ideal molecular recognition elements in membrane protein analysis and molecular diagnostics strategies.This review summarised recent advances in membrane protein-specific aptamer screening,aptamer-based static and dynamic membrane protein analysis,and aptamer-based molecular diagnostic techniques.Prospects and challenges were also discussed.展开更多
基金financially supported by the National Natural Science Foundation of China(21834004 and 21904063)the Natural Science Foundation of Jiangsu Province(BK20190279)the Fundamental Research Funds for the Central Universities(021314380151)
文摘Sensitive and accurate detection of biological analytes,such as proteins,genes,small molecules,ions,cells,etc.,has been a significant project in life science.Signal amplification is one of the most effective approaches to improve the sensitivity of bioanalysis.Taking advantage of specific base pairing,programmable operation,and predictable assembly,DNA is flexible and suitable to perform the signal amplification procedure.In recent years,signal amplification strategies by means of DNA technology have been widely integrated into the construction of electrochemiluminescence(ECL)biosensors,achieving desirable analytical performance in clinical diagnosis,biomedical research,and drug development.To the best of our knowledge,these DNA signal amplification technologies mainly include classical polymerase chain reaction,and various amplification approaches conducted under mild conditions,such as rolling circle amplification(RCA)or hyperbranched RCA,cleaving enzyme-assisted amplification,DNAzyme-involved amplification,toehold-mediated DNA strand displacement amplification without enzyme participation,and so on.This review overviews the recent advancements of DNA signal amplification strategies for bioanalysis in the ECL realm,sketching the creative trajectory from strategies design to ultrasensitive ECL platform construction and resulting applications.
基金This work was supported by grants from the National Natural Science Foundation of China(21327902,21635004,21675079,21627806).
文摘Attenuated total reflection surface-enhanced infrared absorption spectroscopy(ATR-SEIRAS)has recently been proven to be a powerful tool for bioanalysis.It enables in situ and in real-time observation of dynamic processes occurring on specific interface,revealing rich structural and functional information of biomolecules at sub monolayer level.The aim of this general review was to give an overview of the cutting edge applications of ATRSEIRAS.We start with description of the basic configuration of the standard ATR-SEIRAS platform.The enhanced mechanisms and methods to fabricate enhanced substrates are then presented.We discuss the recent developments,challenges and applications of ATR-SEIRAS in bioanalysis,mainly focusing on DNA analysis,protein behavior and cell properties.Finally,further development of the ATRSEIRAS technique with enhanced sensitivity,improved time and spatial resolutions will be prospected.
基金supported by the National Natural Science Foundation of China(21327902)the Excellent Research Program of Nanjing University(ZYJH004)。
文摘Cells, basic units of living structures and functions, build up a complicated small world, and their order and complexity resemble a small universe. The detailed understanding and elucidation of the matter transport and energy conversion mechanisms within a single cell will expand our knowledge about the origin and evolution of life, the disease mechanisms and much more. In past decades, single-cell analysis has been rapidly and significantly improved and various methodologies have been developed to reveal the complexity of mass, energy, and information within single cells. In this review, we focused on the methods developed in recent years for single-cell analysis, including electrochemical method, optical method, and mass spectrometry method. We reviewed the recent advances and representative studies in this research field, and also discussed the strengths and limitations of each method. Finally, we presented the existing technical challenges and further directions for single-cell analysis.
基金supported by the National Key R&D Program of China(no.2019YFA0709200)National Natural Science Foundation of China(nos.21988102,51772198,and 22002101).
文摘Developing photoelectrochemical(PEC)bioassays based on the principle of a photocathodic measurement of enzymatic product H_(2)O_(2) is highly attractive because it can naturally avoid interfering signals arising from reductive species inherent to biofluids.However,fluctuant oxygen levels in the analyte solution can compromise the accuracy of photocathodic bioanalysis and restrict its application because oxygen reduction potential is similar to H_(2)O_(2).Herein,we addressed this restriction by constructing a triphase biophotocathode with air–liquid–solid joint interfaces by immobilizing an oxidase enzyme film on the tip part of superhydrophobic p-type semiconductor nanowire arrays.Such a triphase biophotocathode has a reaction zone with steady and air phasedependent oxygen concentration which stabilizes and increases the oxidase kinetics,and enables the photocathodic measurement principle in reliable PEC bioassay development with high selectivity,good accuracy,and a wide linear detection range.Moreover,the biophotocathode shows good stability during repeated testing under light illumination.This reliable PEC bioassay system has broad potential in the fields of disease diagnosis,medical research,and environmental monitoring.
基金This work was supported by the National Natural Science Foundation of China(Grant Nos.:82003710 and 82173808)the Natural Science Foundation of Guangdong Province(Grant Nos.:2020A1515010075 and 2021B1515020100)+3 种基金the Project of Educational Commission of Guangdong Province(Grant No.:2021ZDZX2012)the Guangzhou Basic and Applied Basic Research Project(Grant No.:2023A04J1163)the National Key Clinical Specialty Construction Project(Clinical Pharmacy)High-Level Clinical Key Specialty(Clinical Pharmacy)in Guangdong Province,China.
文摘Liquid biopsy is a technology that exhibits potential to detect cancer early,monitor therapies,and predict cancer prognosis due to its unique characteristics,including noninvasive sampling and real-time analysis.Circulating tumor cells(CTCs)and extracellular vesicles(EVs)are two important components of circulating targets,carrying substantial disease-related molecular information and playing a key role in liquid biopsy.Aptamers are single-stranded oligonucleotides with superior affinity and specificity,and they can bind to targets by folding into unique tertiary structures.Aptamer-based microfluidic platforms offer new ways to enhance the purity and capture efficiency of CTCs and EVs by combining the advantages of microfluidic chips as isolation platforms and aptamers as recognition tools.In this review,we first briefly introduce some new strategies for aptamer discovery based on traditional and aptamer-based microfluidic approaches.Then,we subsequently summarize the progress of aptamer-based microfluidics for CTC and EV detection.Finally,we offer an outlook on the future directional challenges of aptamer-based microfluidics for circulating targets in clinical applications.
文摘Microfluidic,as the systems for using microchannel(micron-or sub-micron scale)to process or manipulate microflow,is being widely applied in enzyme biotechnology and biocatalysis.Microfluidic immobilized enzyme reactor(MIER)is a tool with great value for the study of catalytic property and optimal reaction parameter in a flourishing and highly producing manner.In view of its advantages in efficiency,economy,and addressable recognition especially,MIER occupies an important position in the investigation of life science,including molecular biology,bioanalysis and biosensing,biocatalysis etc.Immobilization of enzymes can generally improve their stability,and upon most occasions,the immobilized enzyme is endowed with recyclability.In this review,the enzyme immobilization techniques applied in MIER will be discussed,followed by summarizing the novel developments in the field of MIER for biocatalysis,bioconversion and bioanalysis.The preponderances and deficiencies of the current state-of-the-art preparation ways of MIER are peculiarly discussed.In addition,the prospects of its future study are outlined.
基金supported by Banco Santander/Totta(Portugal)through the fellowship BID/ICI-FCS/CICS/Santander UniversidadesUBI/2017by Foundation for Science and Technology(FCT)through the fellowship SFRH/BD/136028/2018+3 种基金by FEDER funds through the POCI-COMPETE 2020-Operational Program Competitiveness and Internationalization in Axis I(Project No.POCI-01-0145FEDER-007491)National Funds by FCT(Project No.UIDB/00709/2020and Project No.UIDP/00709/2020)the support provided by FEDER funds through the“Programa Operacional do Centro”(Project No.CENTRO-010145-FEDER-000013)。
文摘The new antiepileptic drugs perampanel,retigabine,rufinamide and stiripentol have been recently approved for different epilepsy types.Being them an innovation in the antiepileptics armamentarium,a lot of investigations regarding their pharmacological properties are yet to be performed.Besides,considering their broad anticonvulsant activities,an extension of their therapeutic indications may be worthy of investigation,especially regarding other seizure types as well as other central nervous system disorders.Although different liquid chromatographic(LC)methods coupled with ultraviolet,fluorescence,mass or tandem-mass spectrometry detection have already been developed for the determination of perampanel,retigabine,rufinamide and stiripentol,new and more cost-effective methods are yet required.Therefore,this review summarizes the main analytical aspects regarding the liquid chromatographic methods developed for the analysis of perampanel,retigabine(and its main active metabolite),rufinamide and stiripentol in biological samples and pharmaceutical dosage forms.Furthermore,the physicochemical and stability properties of the target compounds will also be addressed.Thus,this review gathers,for the first time,important background information on LC methods that have been developed and applied for the determination of perampanel,retigabine,rufinamide and stiripentol,which should be considered as a starting point if new(bio)analytical techniques are aimed to be implemented for these drugs.
文摘During the last decade high-throughput in vitro absorption,distribution,metabolism and excretion(HTADME)screening has become an essential part of any drug discovery effort of synthetic molecules.The conduct of HT-ADME screening has been"industrialized"due to the extensive development of software and automation tools in cell culture,assay incubation,sample analysis and data analysis.The HT-ADME assay portfolio continues to expand in emerging areas such as drug-transporter interactions,early soft spot identification,and ADME screening of peptide drug candidates.Additionally,thanks to the very large and high-quality HT-ADME data sets available in many biopharma companies,in silico prediction of ADME properties using machine learning has also gained much momentum in recent years.In this review,we discuss the current state-of-the-art practices in HT-ADME screening including assay portfolio,assay automation,sample analysis,data processing,and prediction model building.In addition,we also offer perspectives in future development of this exciting field.
文摘Formulation/pharmaceutical excipients play a major role in formulating drug candidates,with the objectives of ease of administration,targeted delivery and complete availability.Many excipients used in pharmaceutical formulations are orphanized in preclinical drug discovery.These orphan excipients could enhance formulatability of highly lipophilic compounds.Additionally,they are safe in preclinical species when used below the LD50 values.However,when the excipients are used in formulating compounds with diverse physico-chemical properties,they pose challenges by modulating study results through their bioanalytical matrix effects.Excipients invariably present in study samples and not in the calibration curve standards cause over-/under-estimation of exposures.Thus,the mechanism by which excipients cause matrix effects and strategies to nullify these effects needs to be revisited.Furthermore,formulation excipients cause drug interactions by moderating the pathways of drug metabolizing enzymes and drug transport proteins.Although it is not possible to get rid of excipient driven interactions,it is always advised to be aware of these interactions and apply the knowledge to draw meaningful conclusions from study results.In this review,we will comprehensively discuss a)orphan excipients that have wider applications in preclinical formulations,b)bioanalytical matrix effects and possible approaches to mitigating these effects,and c)excipient driven drug interactions and strategies to alleviate the impacts of drug interactions.
文摘Journal of Pharmaceutical Analysis welcomes submissions of fulllength reviews, original research papers and short communication.The act of submitting a manuscript to the Journal carries with it the right to publish that paper.Journal of Pharmaceutical Analysis is published to attract and disseminate innovative and expert findings in the fields:(1) Analysis of traditional Chinese medicine (medicinal materials,patent medicine, prescription, injection)(2) Pharmaceutical analysis of complex system(3) Quality control and methods of biotech drug(4) Action mechanism and metabolisms(5)Quantitative and qualitative analysis in the drug screening process(6) Tracer analysis in molecular pharmacology(7) Quantitative analysis in biopharmaceutics (8) Clinical laboratory and
基金the National Natural Science Foundation of China(Grant No.:81741144)Ministry of Science and Technology of the People's Republic of China(Grant No.:2018ZX09J18107-002)for their financial assistance.
文摘Sample preparation is considered as the bottleneck step in bioanalysis because each biological matrix has its own unique challenges and complexity.Competent sample preparation to extract the desired analytes and remove redundant components is a crucial step in each bioanalytical approach.The matrix effect is a key hurdle in bioanalytical sample preparation,which has gained extensive consideration.Novel sample preparation techniques have advantages over classical techniques in terms of accuracy,automation,ease of sample preparation,storage,and shipment and have become increasingly popular over the past decade.Our objective is to provide a broad outline of current developments in various bioanalytical sample preparation techniques in chromatographic and spectroscopic examinations.In addition,how these techniques have gained considerable attention over the past decade in bioanalytical research is mentioned with preferred examples.Modern trends in bioanalytical sample preparation techniques,including sorbent-based microextraction techniques,are primarily emphasized.
基金supported by the National Natural Science Foundation of China(81873986)Anhui Natural Science Foundation(2008085QH364)+1 种基金the funding of Anhui Medical University(2020xkjT019,2021lcxk026)Scientific Research Platform Improvement Project of Anhui Medical University(2022xkjT045)
文摘Sepsis-induced acute lung injury(ALI)is a leading cause of death among septic complications.Tao-Hong-Si-Wu decoction(TSD),a classical recipe from traditional Chinese medicine used for treating ischemic stroke,has been recently reported to alleviate inflammation and inflammation-stimulated injuries related to the pathology of ALI.Here,we first observed the therapeutic effect of TSD on sepsis-induced ALI.Based on integrated metabolomics and network pharmacology analysis(NPA)techniques,we aim to understand the mechanism of TSD alleviating ALI.TSD’s effects were observed in rats modeled by cecal ligation and puncture(CLP)and rat macrophages stimulated by lipopolysaccharide(LPS).Metabolomics analyses were applied to determine the ingredients in the medicine and key metabolites correlated to the NPA for the prediction of TSD targets.Gene and protein expressions of the key predicted targets were evaluated in the lung tissue and macrophages of septic model rat by quantitative polymerase chain reaction(PCR)and enzyme-linked immunosorbent assays,respectively.TSD improved survival rate and protected against lung injury in CLP rats.Eleven endogenous metabolites were related to TSD’s actions.TSD significantly suppressed IL-6 and TNF-αsecretions and their gene expressions both in the lung tissue of the model rats and in LPS-stimulated macrophages.TSD also restored decreased lung protein expression of VEGFA in septic model rats.Targeted proteins and their affecting metabolites were finally validated in an external test set of rats.This study shows that metabolomics coupled with NPA is a promising approach to explore potential targets of medicine with complex compositions.
基金US NIH grants,NSF NIRT and State of Florida Center of Excellence for nano-biosensors。
文摘Advanced bioanalysis,including accurate quantitation,has driven the need to understand biology and medicine at the molecular level.Bioconjugated silica nanoparticles have the potential to address this emerging challenge.Particularly intriguing diagnostic and therapeutic applications in cancer and infectious disease as well as uses in gene and drug delivery,have also been found for silica nanoparticles.In this review,we describe the synthesis,bioconjugation,and applications of silica nanoparticles in different bioanalysis formats,such as selective tagging,barcoding,and separation of a wide range of biomedically important targets.Overall,we envisage that further development of these nanoparticles will provide a variety of advanced tools for molecular biology,genomics,proteomics and medicine.
基金We gratefully acknowledge the Nature Science Foundation of China(21335001,21575126)the Nature Science Foundation of Zhejiang Province(LR14B050001).
文摘Electrochemiluminescence(ECL),also called electrogenerated chemiluminescence,is luminescence that is produced by chemical reactions triggered by electrochemical method.ECL imaging is a novel imaging technique,which can simultaneously provide two kinds of signals of both electrochemistry and optical image.Over the past two decades,ECL imaging has been not only a powerful tool for investigating the fundamental scientific questions such as ECL mechanisms and reaction kinetics,but also a versatile analytical technique for detection of a wide range of analytes including small molecules,DNA,proteins,and cells.In the first part of this review,we briefly describe the reaction mechanisms of ECL generation.Then the review focuses on the research progress on the ECL imaging approach.It is basically introduced from the following five aspects:(i)visualization of electroactive sites on surfaces,(ii)imaging analysis at the single-bead and single-cell levels,(iii)array bioanalysis,(iv)multi-color ECL imaging,and(v)paper chip based on ECL imaging.Finally,some perspectives and future directions in this active research area are presented.
基金the National Natural Science Foundation of China[Nos.21675148,21874126,an 21804127]Ministry of Science and Technology of the People’s Republic of China[No.2016YFA0201300]the Chinese Academy of Sciences(CAS)-the Academy of Sciences for the Developing World(TWAS)President’s Fellowship Programme[No.2016CTF032].
文摘Electrochemiluminescence(ECL)-based imaging analysis is a dominant method to inspect the electrode composition,to study electrochemical reaction kinetics at a microscopic level,and also a rapid emerging technology in bioanalysis with high spatiotemporal resolutions,high-throughput and visualization characteristics.In comparison with other imaging microscopes,an optical excitation is not involved in imaging,thus the approach is free from background noise resulting in a low detec-tion limit.In this review work,the principle of ECL,its unique natures compared to other luminescence techniques were briefed at first.Then after,the progress and basic principles of ECL imaging were summarized.Furthermore,recent and representative advances of ECL imaging for visualizing and sensing applications were reviewed.Finally,the perspectives in ECL imaging for further perspective were discussed.
基金the National Natural Science Foundation of China(Nos.21722406,21975240,21778052)by the Fundamental Research Funds for the Central Universities(No.WK2060190102).We thank Dr.Xiaowei Chen and Prof.Liangbin Li for their help on the SR-SAXS instrument.
文摘The continuous tuning of plasmonic nanoassembly's structure is the key to manipulate their optical and catalytic properties.Herein,we report a strategy of using macroscopic deformation to continuously tune the structure and optical activity of massive plasmonic nanoassemblies that are embedded in elastic polymer matrix.Plasmonic gold nanoparticles(Au NPs)are assembled to nanochains(Au NCs)with defined length and further embedded into polyvinylpyrrolidone(PVP)matrix.The nanostructure and plasmonic properties of massive Au NCs in this Au NCs-PVP film can be simultaneously and continuously tuned,simply by reversible mechanical deformation of this elastic film.In this way,the surface-enhanced Raman scattering(SERS)enhancement factor of this film as a SERS substrate can be mechanically modulated in the range of 10^(0)to 6.8×10^(7).Meanwhile,the PVP matrix also serves as a selective diffusion barrier to eliminate the fluorescence interference of large biomolecules,which enables the Au NCs-PVP film as a convenient SER S substrate for quick and direct analysis of small molecule analytes in biological samples and food,avoiding the complicate and time-consuming sample pretreatment process.
基金supported by the National Key Research and Development Project,China(No.2020YFA0909000)the National Natural Science Foundation of China(No.22107027)+1 种基金the Natural Science Foundation of Hunan Province,China(No.2023JJ20003)the Scientific Research Program of Furong Laboratory,China(No.2023SK2088).
文摘Membrane proteins are vital components of the cell membrane and play crucial roles in various cellular activities.Analysis of membrane proteins is of paramount importance for studying molecular events inside cells and organisms and holds promising prospects for early disease diagnosis and treatment assessment.Benefiting from obvious merits including high affinity,high specificity and ease of modification,aptamers have been regarded as ideal molecular recognition elements in membrane protein analysis and molecular diagnostics strategies.This review summarised recent advances in membrane protein-specific aptamer screening,aptamer-based static and dynamic membrane protein analysis,and aptamer-based molecular diagnostic techniques.Prospects and challenges were also discussed.
