Traumatic brain injury can be categorized into primary and secondary injuries.Secondary injuries are the main cause of disability following traumatic brain injury,which involves a complex multicellular cascade.Microgl...Traumatic brain injury can be categorized into primary and secondary injuries.Secondary injuries are the main cause of disability following traumatic brain injury,which involves a complex multicellular cascade.Microglia play an important role in secondary injury and can be activated in response to traumatic brain injury.In this article,we review the origin and classification of microglia as well as the dynamic changes of microglia in traumatic brain injury.We also clarify the microglial polarization pathways and the therapeutic drugs targeting activated microglia.We found that regulating the signaling pathways involved in pro-inflammatory and anti-inflammatory microglia,such as the Toll-like receptor 4/nuclear factor-kappa B,mitogen-activated protein kinase,Janus kinase/signal transducer and activator of transcription,phosphoinositide 3-kinase/protein kinase B,Notch,and high mobility group box 1 pathways,can alleviate the inflammatory response triggered by microglia in traumatic brain injury,thereby exerting neuroprotective effects.We also reviewed the strategies developed on the basis of these pathways,such as drug and cell replacement therapies.Drugs that modulate inflammatory factors,such as rosuvastatin,have been shown to promote the polarization of antiinflammatory microglia and reduce the inflammatory response caused by traumatic brain injury.Mesenchymal stem cells possess anti-inflammatory properties,and clinical studies have confirmed their significant efficacy and safety in patients with traumatic brain injury.Additionally,advancements in mesenchymal stem cell-delivery methods—such as combinations of novel biomaterials,genetic engineering,and mesenchymal stem cell exosome therapy—have greatly enhanced the efficiency and therapeutic effects of mesenchymal stem cells in animal models.However,numerous challenges in the application of drug and mesenchymal stem cell treatment strategies remain to be addressed.In the future,new technologies,such as single-cell RNA sequencing and transcriptome analysis,can facilitate further experimental studies.Moreover,research involving non-human primates can help translate these treatment strategies to clinical practice.展开更多
BACKGROUND Drug utilization research has an important role in assisting the healthcare administration to know,compute,and refine the prescription whose principal objective is to enable the rational use of drugs.Resear...BACKGROUND Drug utilization research has an important role in assisting the healthcare administration to know,compute,and refine the prescription whose principal objective is to enable the rational use of drugs.Research in developing nations relating to the cost of treatment is scarce when compared with developed countries.Thus,the drug utilization research studies from developing nations are most needed,and their number has been growing.AIM To evaluate patterns of utilization of antipsychotic drugs and direct medical cost analysis in patients newly diagnosed with schizophrenia.METHODS The present study was observational in type and based on a retrospective cohort to evaluate patterns of utilization of antipsychotic drugs using World Health Organization(WHO)core prescribing indicators and anatomical therapeutic chemical/defined daily dose indicators.We also calculated direct medical costs for a period of 6 months.RESULTS This study has found that atypical antipsychotics are the mainstay of treatment for schizophrenia in every age group and subcategories of schizophrenia.The evaluation based on WHO prescribing indicators showed a low average number of drugs per prescription and low prescribing frequency of antipsychotics from the National List of Essential Medicines 2015 and the WHO Essential Medicines List 2019.The total mean drug cost of our study was 1396 Indian rupees.The total mean cost due to the investigation in our study was 1017.34 Indian rupees.Therefore,the total mean direct medical cost incurred on patients in our study was 4337.28 Indian rupees.CONCLUSION The information from the present study can be used for reviewing and updating treatment policy at the institutional level.展开更多
Owing to the emergence of drug resistance and high morbidity,the need for novel antiviral drugs with novel targets is highly sought after.Marine-derived compounds mostly possess potent antiviral activity and serve as ...Owing to the emergence of drug resistance and high morbidity,the need for novel antiviral drugs with novel targets is highly sought after.Marine-derived compounds mostly possess potent antiviral activity and serve as a primary source for developing novel antiviral drugs,making the rapid discovery and evaluation of marine antiviral agents particularly crucial.Thus,future research should place greater emphasis on the identification of novel antiviral targets through the combination of artificial intelligence(AI)and structural pharmacology,as well as expanding the marine resource and target databases.展开更多
Poor solubility often results in low efficacy of antitumor drugs.Nevertheless,limited research has been conducted on the potential decrease in drug efficacy following the self-assembly of hydrophobic pure drugs into n...Poor solubility often results in low efficacy of antitumor drugs.Nevertheless,limited research has been conducted on the potential decrease in drug efficacy following the self-assembly of hydrophobic pure drugs into nanodrugs,and solutions to this problem are even rarer.Loading water-insoluble antitumor drugs into nanocarriers offers a promising solution.However,intricate carrier preparation,limited drug loading capacity,and carrier-associated safety remain key challenges.In this study,based on the discovery that hydrophobic gambogic acid(GA) self-assembles into nanostructures with diminished antitumor efficacy in aqueous environments,we developed a carrier-free nanodrug system,designated as GA-S-S-AS nanoparticles(NPs),characterized by straightforward preparation,high drug loading,fluorescence imaging,tumor-targeting,and responsive drug release in reducing environments.Specifically,the hydrophobic GA was covalently linked to the hydrophilic aptamer through a disulfide bond and then self-assembled into the nanodrugs.About 92 % of drug was encapsulated in self-assembled NPs,demonstrating remarkable stability under physiological conditions and controlled release of GA in the high-glutathione environment characteristic of tumor sites.Furthermore,by utilizing the synergistic interaction between the enhanced permeability and retention(EPR) effect and ligand-receptor active targeting mechanisms,the nanodrugs significantly increased the accumulation of GA at tumor locations.Consequently,the nanodrugs exhibited optimal therapeutic efficacy against the tumor both in vitro and in vivo,significantly inhibiting tumor growth.Furthermore,the nanodrugs demonstrated enhanced biosafety compared to free GA,effectively reducing GA-induced hepatotoxicity.Taken together,these findings underscore the significant potential of this multifunctional carrier-free nanodrugs for the targeted delivery of GA,thereby laying a foundation for future endeavors aimed at developing novel formulations of hydrophobic antitumor drugs.展开更多
To simultaneously enrich,separate,and determine five fluoroquinolone antibiotics(FQs)in marine crude drugs(MCDs),seawater and seafood,we conducted this study using vortex assisted dispersed liquid-liquid microextracti...To simultaneously enrich,separate,and determine five fluoroquinolone antibiotics(FQs)in marine crude drugs(MCDs),seawater and seafood,we conducted this study using vortex assisted dispersed liquid-liquid microextraction(DLLME),followed by capillary electrophoresis(CE)-UV.A single-variable optimization was employed to examine the factors influencing the separation effect of CE and the extraction efficiency of DLLME,including buffer solution,organic solvent,separation voltage,extractant,dispersant,and sample solution pH.Under the optimal conditions,the baseline separation of the five FQs was achieved within 6 min.The analytical performance of the method was assessed using six types of actual samples,including three MCDs of hippocampus,clam,and kelp,seawater,and two seafood of prawn and pomfret,demonstrating good linearity ranging from 0.1-5 or 0.01-5μg/mL.The limits of detection(LODs)and limits of quantification(LOQs)for the five FQs in MCDs were 0.0022-0.0292 and 0.0066-0.0973μg/mL,respectively.The LODs and LOQs in seawater and seafood were 0.0009-0.0262 and 0.0029-0.0874μg/mL,respectively.The matrix effects of this method were evaluated in the hippocampus,seawater,and prawn,and the results show that DLLME could effectively eliminate matrix interference.Satisfactory recovery rates were achieved in all the six tested actual samples.This developed DLLME-CE method was proven simple to operate,accurate and reliable,with high sensitivity,making it suitable for the analysis of multiple antibiotic residues in complex matrices.展开更多
Exploring multi-target drugs(MTDs)is a prevalent method against Alzheimer’s disease(AD).However,the current developed MTDs based on the“framework combination”technique or using flavonoids have not realized better h...Exploring multi-target drugs(MTDs)is a prevalent method against Alzheimer’s disease(AD).However,the current developed MTDs based on the“framework combination”technique or using flavonoids have not realized better healing effects owing to a complex metabolic process and low bioavailability.Here,we propose an alternative strategy to develop self-assembled nanoparticles(NPs)as MTDs using 9-fluorenylmethyloxycarbonyl-tryptophan(Fmoc-Trp),quercetin(Que),and Fe^(2+)as building blocks through coordination and electrostatic interaction to generate Fmoc-Trp-Fe^(2+)-Que(FTFQ)NPs.Whether in cell or in vivo,FTFQ NPs exhibited considerable biocompatibility attributing to the inherent biological affinity of assembly units.By combining the advantages of assemble approach and nanostructures,the obtained FTFQ NPs greatly enhanced the bioavailability of Que and displayed synergistic therapeutic effects through reducing Aβaggregation in direct/indirect means and eliminating the toxicity induced by ROS and Aβoligomer/fibrils.Furthermore,FTFQ NPs could obviously restore the AD zebrafish’s mobility and stimulus response ability.More importantly,developing self-assembly NPs as MTDs could be an efficient and general method to promote other novel MTDs by extending the assemble units to other drugs,peptides,and metal ions.Based on above benefits,these self-assembled NPs could be as potential MTDs and show great promising application in AD treatment.展开更多
The research and development of new traditional Chinese medicine(TCM)drugs have progressively established a novel system founded on the integration of TCM theory,human experience,and clinical trials(termed the“Three ...The research and development of new traditional Chinese medicine(TCM)drugs have progressively established a novel system founded on the integration of TCM theory,human experience,and clinical trials(termed the“Three Combinations”).However,considering TCM's distinctive features of“syndrome differentiation and treatment”and“multicomponent formulations and complex mechanisms”,current TCM drug development faces challenges such as insufficient understanding of the material basis and the overall mechanism of action and an incomplete evidence chain system.Moreover,significant obstacles persist in gathering human experience data,evaluating clinical efficacy,and controlling the quality of active ingredients,which impede the innovation process in TCM drug development.Network pharmacology,centered on the“network targets”theory,transcends the limitations of the conventional“single target”reductionist research model.It emphasizes the comprehensive effects of disease or syndrome biological networks as targets to elucidate the overall regulatory mechanism of TCM prescriptions.This approach aligns with the holistic perspective of TCM,offering a novel method consistent with TCM's holistic view for investigating the complex mechanisms of TCM and developing new TCM drugs.It is internationally recognized as a“next-generation drug research model”.To advance the research of new tools,methods,and standards for TCM evaluation and to overcome fundamental,critical,and cutting-edge technical challenges in TCM regulation,this consensus aims to explore the characteristics,progress,challenges,applicable pathways,and specific applications of network pharmacology as a new theory,method,and tool in TCM drug development.The goal is to enhance the quality of TCM drug research and development and accelerate the efficiency of developing new TCM products.展开更多
Therapeutic antibodies are valued for their high specificity and selectivity in immu-notherapy.However,the potential toxicity they may elicit underscores the necessity of assessing their preclinical efficacy and safet...Therapeutic antibodies are valued for their high specificity and selectivity in immu-notherapy.However,the potential toxicity they may elicit underscores the necessity of assessing their preclinical efficacy and safety using suitable animal models.In this context,we review the various categories and applications of humanized mice,which have been engrafted with human cells or tissues to mimic the human immune system.These models are extensively utilized in the nonclinical assessment and development of various antibody drugs,acting as a conduit to clinical research.However,several challenges remain,including the limited lifespan of humanized mice,inadequate en-graftment of human cells,and the rudimentary nature of the immune environment in these models.The development of humanized immune system models in mice pre-sents both opportunities and challenges,potentially leading to new insights into the evolution and application of antibody therapeutics.展开更多
Peptide-based therapies have attracted considerable interest in the treatment of cancer, diabetes, bacterial infections, and neurodegenerative diseases due to their promising therapeutic properties and enhanced safety...Peptide-based therapies have attracted considerable interest in the treatment of cancer, diabetes, bacterial infections, and neurodegenerative diseases due to their promising therapeutic properties and enhanced safety profiles. This review provides a comprehensive overview of the major trends in peptide drug discovery and development, emphasizing preclinical strategies aimed at improving peptide stability, specificity, and pharmacokinetic properties. It assesses the current applications and challenges of peptide-based drugs in these diseases, illustrating the pharmaceutical areas where peptide-based drugs demonstrate significant potential. Furthermore, this review analyzes the obstacles that must be overcome in the future,aiming to provide valuable insights and references for the continued advancement of peptidebased drugs.展开更多
Alzheimer 's disease(AD) is an alarming noncommunicable, multi-factorial, and non-treatable disease. Its underlying neurodegenerative events have not yet been fully explained and its early diagnosis is very diffic...Alzheimer 's disease(AD) is an alarming noncommunicable, multi-factorial, and non-treatable disease. Its underlying neurodegenerative events have not yet been fully explained and its early diagnosis is very difficult. The appearance of the disease is associated with clinical features such as the degeneration of several cholinergic nuclei of the brain.展开更多
The use of traditional herbal drugs derived from natural sources is on the rise due to their minimal side effects and numerous health benefits.However,a major limitation is the lack of standardized knowledge for ident...The use of traditional herbal drugs derived from natural sources is on the rise due to their minimal side effects and numerous health benefits.However,a major limitation is the lack of standardized knowledge for identifying and mapping the quality of these herbal medicines.This article aims to provide practical insights into the application of artificial intelligence for quality-based commercialization of raw herbal drugs.It focuses on feature extraction methods,image processing techniques,and the preparation of herbal images for compatibility with machine learning models.The article discusses commonly used image processing tools such as normalization,slicing,cropping,and augmentation to prepare images for artificial intelligence-based models.It also provides an overview of global herbal image databases and the models employed for herbal plant/drug identification.Readers will gain a comprehensive understanding of the potential application of various machine learning models,including artificial neural networks and convolutional neural networks.The article delves into suitable validation parameters like true positive rates,accuracy,precision,and more for the development of artificial intelligence-based identification and authentication techniques for herbal drugs.This article offers valuable insights and a conclusive platform for the further exploration of artificial intelligence in the field of herbal drugs,paving the way for smarter identification and authentication methods.展开更多
After spinal cord injury,impairment of the sensorimotor circuit can lead to dysfunction in the motor,sensory,proprioceptive,and autonomic nervous systems.Functional recovery is often hindered by constraints on the tim...After spinal cord injury,impairment of the sensorimotor circuit can lead to dysfunction in the motor,sensory,proprioceptive,and autonomic nervous systems.Functional recovery is often hindered by constraints on the timing of interventions,combined with the limitations of current methods.To address these challenges,various techniques have been developed to aid in the repair and reconstruction of neural circuits at different stages of injury.Notably,neuromodulation has garnered considerable attention for its potential to enhance nerve regeneration,provide neuroprotection,restore neurons,and regulate the neural reorganization of circuits within the cerebral cortex and corticospinal tract.To improve the effectiveness of these interventions,the implementation of multitarget early interventional neuromodulation strategies,such as electrical and magnetic stimulation,is recommended to enhance functional recovery across different phases of nerve injury.This review concisely outlines the challenges encountered following spinal cord injury,synthesizes existing neurostimulation techniques while emphasizing neuroprotection,repair,and regeneration of impaired connections,and advocates for multi-targeted,task-oriented,and timely interventions.展开更多
Background Present drug delivery systems such as oral administration and intravenous injection limit the drug efficacy of current anti-allergy drugs.Therefore,new drug delivery systems,including nanocarriers,transderm...Background Present drug delivery systems such as oral administration and intravenous injection limit the drug efficacy of current anti-allergy drugs.Therefore,new drug delivery systems,including nanocarriers,transdermal patches,and microneedles,are being investigated for their potential to deliver anti-allergy drugs.Purpose of review The review reveals the likely improvements by applying new drug delivery systems,including nanocarriers,transdermal patches and microneedles.Recent findings These new drug delivery systems utilize local administration and do not undergo metabolism pathways in the liver.Thus,they demonstrate high drug targeting,rapid onset action,precise dosage control,and minimal side effects.Limitations on large-scale production and high costs hinder the application of advanced drug delivery systems.Fortunately,forthcoming innovation and maturation will likely overcome the barriers and enable general patients to access anti-allergy drugs delivered by these advanced drug delivery systems,resulting in optimal body functions for everyday life.Conclusion Despite their limitations,new drug delivery systems are still promising solutions for delivering anti-allergy drugs due to their enhanced drug concentration,shortened onset time,and reduced systemic side effects.展开更多
The aim of this study is to evaluate the characteristics and patterns of adverse drug reactions(ADRs)associated with antineoplastic drugs and provide insights for safer chemotherapy practices.Based on 979 ADR cases re...The aim of this study is to evaluate the characteristics and patterns of adverse drug reactions(ADRs)associated with antineoplastic drugs and provide insights for safer chemotherapy practices.Based on 979 ADR cases reported in our hospital from January 1,2022,to December 31,2023,an analysis was conducted.Statistical analysis of the data revealed that 72.73%of these ADR incidents occurred in a hospital setting.The incidence of ADRs was higher in female patients compared to males,with the majority of cases(59.14%)observed in individuals aged 51-70 years.Intravenous administration was the predominant route linked to ADRs,accounting for 69.66%of the cases.Serious ADRs represented 9.30%of the total,including one instance where symptoms did not improve despite drug discontinuation or treatment.Cytotoxic antineoplastic drugs were responsible for 97.85%of all ADRs,with oxaliplatin being the most frequently implicated agent(19.82%).Gastrointestinal system involvement was the most common ADR manifestation,observed in 60.79%of cases.These findings underscored the necessity of enhanced monitoring for ADRs associated with cytotoxic antineoplastic drugs,particularly platinum-based agents.Comprehensive risk assessments and tailored treatment plans should be implemented during chemotherapy to minimize the occurrence of ADRs and safeguard patient safety.展开更多
Lung cancer is one of the malignant tumor diseases with high morbidity and high mortality in the world. Non-small cell lung cancer (NSCLC) is the most common pathological type of lung cancer. Currently, chemotherapy, ...Lung cancer is one of the malignant tumor diseases with high morbidity and high mortality in the world. Non-small cell lung cancer (NSCLC) is the most common pathological type of lung cancer. Currently, chemotherapy, targeted therapy, immunotherapy or combination therapy is the main treatment for NSCLC, but it is still inevitably faced with the challenges of acquired drug resistance and tumor progression. The birth of antibody conjugator provides a new choice for its treatment. Antibody conjugator is a new type of biotherapeutic drug which is connected by monoclonal antibody via linker and cytotoxic drug. It has the characteristics of precision, high efficiency and low toxicity, etc. In recent years, its research and development and clinical trials have been endless. It shows that this new type of drug has great potential in the field of tumor therapy. In this paper, the structural characteristics, mechanism of action, current application, research achievements, challenges, countermeasures and development of ADC in NSCLC treatment are reviewed.展开更多
The Reference Listed drug(RLD)plays a critical role in the development and research of generic medicinal products,serving as the comparator product used in the marketing authorization application of new generic medici...The Reference Listed drug(RLD)plays a critical role in the development and research of generic medicinal products,serving as the comparator product used in the marketing authorization application of new generic medicinal product and re-evaluation of generic medicinal product.In China,RLDs are sourced from various origins,but their quality and market availability can be constrained by multiple factors,including emergent issues such as nitrosamine impurities.Five classes of medicinal products have been reported to be at risk for containing nitrosamine impurities:sartan-based medicines,metformin-containing products,ranitidine medicines,rifampicin medicines,and Champix.This paper explores the control strategies implemented by drug regulatory agencies in the United States and the European Union to manage nitrosamine impurities and assesses their impact on the market availability and quality of RLDs in China.The aim is to offer valuable insights for generic drug manufacturers and regulatory bodies both domestically and internationally.展开更多
Nucleic acid drugs represent the third wave of innovation in drug research and development,succeeding small-molecule and antibody drugs.These drugs,particularly RNA interference(RNAi)therapies,have become a pivotal fo...Nucleic acid drugs represent the third wave of innovation in drug research and development,succeeding small-molecule and antibody drugs.These drugs,particularly RNA interference(RNAi)therapies,have become a pivotal focus in the pharmaceutical industry.RNAi drugs are extensively utilized in the treatment of chronic and rare diseases due to their exceptional gene-silencing efficiency,manageable side effects,and straightforward synthesis process.This study undertook a thorough analysis of the global landscape of RNAi drug patents,highlighting the latest technological advancements and trends.We meticulously identified and cataloged the key technologies that dominated this patent landscape.The goal was to provide valuable insights and references for researchers involved in the development of RNAi drugs within the domestic pharmaceutical sector.展开更多
Drug synergistic effects refer to combinations that have a greater impact than individual drugs,which are often but sometimes harmful.Predicting synergism via computational methods like intelligence(AI)is popular,yet ...Drug synergistic effects refer to combinations that have a greater impact than individual drugs,which are often but sometimes harmful.Predicting synergism via computational methods like intelligence(AI)is popular,yet experimental validation remains challenging.DNA-programmed labeling(DPAL)is a method for target based on drug-target binding,minimizing interference from photoreactive groups and tags,which has the advantages of high sensitivity and low impact on drug activities[1–3].In the present study,we utilized the DPAL method to reveal the synergistic targets of the three main components(bufalin,cinobufagin,and resibufogenin(BCR))of cinobufacini injection with anti-hepatocarcinoma activities.展开更多
With the continuous advancement of cancer treatment methods, plasma combined with drug therapy has garnered widespread attention as an emerging therapeutic strategy. This paper elaborates on the generation and charact...With the continuous advancement of cancer treatment methods, plasma combined with drug therapy has garnered widespread attention as an emerging therapeutic strategy. This paper elaborates on the generation and characteristics of plasma, as well as its mechanisms of action on cancer cells when used alone, including the production of reactive oxygen and nitrogen species, and damage to cancer cell membranes, and organelles. It emphasizes the synergistic mechanisms observed when plasma is combined with various anticancer drugs (e.g., chemotherapeutic agents, targeted drugs, and immunotherapies). The analysis focuses on enhancing drug uptake, promoting the activation of drug action targets, and improving the tumor microenvironment. These insights provide a theoretical basis for optimizing plasma-drug combination therapy for cancer.展开更多
Green synthesis of drugs is of paramount importance for current public health and a prerequisite to new drugs exploiting.Nowadays,novel strategies of disease diagnosis and therapies are in blooming development as rema...Green synthesis of drugs is of paramount importance for current public health and a prerequisite to new drugs exploiting.Nowadays,novel strategies of disease diagnosis and therapies are in blooming development as remarkable advances have been achieved which are all highly depended on drug development.Under the current requirements to high production capacity and novel synthesis methods of drugs,green synthesis based on strategies with different ways of empowering,advanced catalysts and unique reaction equipment are attracting huge attention and of great challenging.Higher quality products and environmentally friendly synthesis conditions are becoming more and more important for manufacturing process which has new requirements for catalyst materials and synthesis processes.Polyoxometalates(POMs)are class of transition metals-oxygen clusters with precise molecular structures and superior physicochemical properties which have made longstanding and important applications upon research community of functional materials,catalysis and medicine.In this review,the recent advances of polyoxometalates based strategies for green synthesis of drugs are summarized including POMs based catalysts,alternative reaction equipment based novel synthesis protocols.The significance of POMs to pharmaceutical and industrial field is highlighted and the related perspective for future development are well discussed.展开更多
基金supported by the Natural Science Foundation of Yunnan Province,No.202401AS070086(to ZW)the National Key Research and Development Program of China,No.2018YFA0801403(to ZW)+1 种基金Yunnan Science and Technology Talent and Platform Plan,No.202105AC160041(to ZW)the Natural Science Foundation of China,No.31960120(to ZW)。
文摘Traumatic brain injury can be categorized into primary and secondary injuries.Secondary injuries are the main cause of disability following traumatic brain injury,which involves a complex multicellular cascade.Microglia play an important role in secondary injury and can be activated in response to traumatic brain injury.In this article,we review the origin and classification of microglia as well as the dynamic changes of microglia in traumatic brain injury.We also clarify the microglial polarization pathways and the therapeutic drugs targeting activated microglia.We found that regulating the signaling pathways involved in pro-inflammatory and anti-inflammatory microglia,such as the Toll-like receptor 4/nuclear factor-kappa B,mitogen-activated protein kinase,Janus kinase/signal transducer and activator of transcription,phosphoinositide 3-kinase/protein kinase B,Notch,and high mobility group box 1 pathways,can alleviate the inflammatory response triggered by microglia in traumatic brain injury,thereby exerting neuroprotective effects.We also reviewed the strategies developed on the basis of these pathways,such as drug and cell replacement therapies.Drugs that modulate inflammatory factors,such as rosuvastatin,have been shown to promote the polarization of antiinflammatory microglia and reduce the inflammatory response caused by traumatic brain injury.Mesenchymal stem cells possess anti-inflammatory properties,and clinical studies have confirmed their significant efficacy and safety in patients with traumatic brain injury.Additionally,advancements in mesenchymal stem cell-delivery methods—such as combinations of novel biomaterials,genetic engineering,and mesenchymal stem cell exosome therapy—have greatly enhanced the efficiency and therapeutic effects of mesenchymal stem cells in animal models.However,numerous challenges in the application of drug and mesenchymal stem cell treatment strategies remain to be addressed.In the future,new technologies,such as single-cell RNA sequencing and transcriptome analysis,can facilitate further experimental studies.Moreover,research involving non-human primates can help translate these treatment strategies to clinical practice.
文摘BACKGROUND Drug utilization research has an important role in assisting the healthcare administration to know,compute,and refine the prescription whose principal objective is to enable the rational use of drugs.Research in developing nations relating to the cost of treatment is scarce when compared with developed countries.Thus,the drug utilization research studies from developing nations are most needed,and their number has been growing.AIM To evaluate patterns of utilization of antipsychotic drugs and direct medical cost analysis in patients newly diagnosed with schizophrenia.METHODS The present study was observational in type and based on a retrospective cohort to evaluate patterns of utilization of antipsychotic drugs using World Health Organization(WHO)core prescribing indicators and anatomical therapeutic chemical/defined daily dose indicators.We also calculated direct medical costs for a period of 6 months.RESULTS This study has found that atypical antipsychotics are the mainstay of treatment for schizophrenia in every age group and subcategories of schizophrenia.The evaluation based on WHO prescribing indicators showed a low average number of drugs per prescription and low prescribing frequency of antipsychotics from the National List of Essential Medicines 2015 and the WHO Essential Medicines List 2019.The total mean drug cost of our study was 1396 Indian rupees.The total mean cost due to the investigation in our study was 1017.34 Indian rupees.Therefore,the total mean direct medical cost incurred on patients in our study was 4337.28 Indian rupees.CONCLUSION The information from the present study can be used for reviewing and updating treatment policy at the institutional level.
文摘Owing to the emergence of drug resistance and high morbidity,the need for novel antiviral drugs with novel targets is highly sought after.Marine-derived compounds mostly possess potent antiviral activity and serve as a primary source for developing novel antiviral drugs,making the rapid discovery and evaluation of marine antiviral agents particularly crucial.Thus,future research should place greater emphasis on the identification of novel antiviral targets through the combination of artificial intelligence(AI)and structural pharmacology,as well as expanding the marine resource and target databases.
基金the National Natural Science Foundation of China (Nos.21907076 and 31901908)the Natural Science Foundation of Tianjin (No.22JCQNJC01570)。
文摘Poor solubility often results in low efficacy of antitumor drugs.Nevertheless,limited research has been conducted on the potential decrease in drug efficacy following the self-assembly of hydrophobic pure drugs into nanodrugs,and solutions to this problem are even rarer.Loading water-insoluble antitumor drugs into nanocarriers offers a promising solution.However,intricate carrier preparation,limited drug loading capacity,and carrier-associated safety remain key challenges.In this study,based on the discovery that hydrophobic gambogic acid(GA) self-assembles into nanostructures with diminished antitumor efficacy in aqueous environments,we developed a carrier-free nanodrug system,designated as GA-S-S-AS nanoparticles(NPs),characterized by straightforward preparation,high drug loading,fluorescence imaging,tumor-targeting,and responsive drug release in reducing environments.Specifically,the hydrophobic GA was covalently linked to the hydrophilic aptamer through a disulfide bond and then self-assembled into the nanodrugs.About 92 % of drug was encapsulated in self-assembled NPs,demonstrating remarkable stability under physiological conditions and controlled release of GA in the high-glutathione environment characteristic of tumor sites.Furthermore,by utilizing the synergistic interaction between the enhanced permeability and retention(EPR) effect and ligand-receptor active targeting mechanisms,the nanodrugs significantly increased the accumulation of GA at tumor locations.Consequently,the nanodrugs exhibited optimal therapeutic efficacy against the tumor both in vitro and in vivo,significantly inhibiting tumor growth.Furthermore,the nanodrugs demonstrated enhanced biosafety compared to free GA,effectively reducing GA-induced hepatotoxicity.Taken together,these findings underscore the significant potential of this multifunctional carrier-free nanodrugs for the targeted delivery of GA,thereby laying a foundation for future endeavors aimed at developing novel formulations of hydrophobic antitumor drugs.
基金Supported by the National Natural Science Foundation of China(No.22176210)the Major Innovation Fund of Shandong Province(No.2021ZDSYS23)。
文摘To simultaneously enrich,separate,and determine five fluoroquinolone antibiotics(FQs)in marine crude drugs(MCDs),seawater and seafood,we conducted this study using vortex assisted dispersed liquid-liquid microextraction(DLLME),followed by capillary electrophoresis(CE)-UV.A single-variable optimization was employed to examine the factors influencing the separation effect of CE and the extraction efficiency of DLLME,including buffer solution,organic solvent,separation voltage,extractant,dispersant,and sample solution pH.Under the optimal conditions,the baseline separation of the five FQs was achieved within 6 min.The analytical performance of the method was assessed using six types of actual samples,including three MCDs of hippocampus,clam,and kelp,seawater,and two seafood of prawn and pomfret,demonstrating good linearity ranging from 0.1-5 or 0.01-5μg/mL.The limits of detection(LODs)and limits of quantification(LOQs)for the five FQs in MCDs were 0.0022-0.0292 and 0.0066-0.0973μg/mL,respectively.The LODs and LOQs in seawater and seafood were 0.0009-0.0262 and 0.0029-0.0874μg/mL,respectively.The matrix effects of this method were evaluated in the hippocampus,seawater,and prawn,and the results show that DLLME could effectively eliminate matrix interference.Satisfactory recovery rates were achieved in all the six tested actual samples.This developed DLLME-CE method was proven simple to operate,accurate and reliable,with high sensitivity,making it suitable for the analysis of multiple antibiotic residues in complex matrices.
基金supported by the National Natural Science Foundation(No.22076024)the Natural Science Foundation of Fujian Province(No.2021J01552)Fuzhou University Testing Fund of Precious Apparatus(No.2020T005).
文摘Exploring multi-target drugs(MTDs)is a prevalent method against Alzheimer’s disease(AD).However,the current developed MTDs based on the“framework combination”technique or using flavonoids have not realized better healing effects owing to a complex metabolic process and low bioavailability.Here,we propose an alternative strategy to develop self-assembled nanoparticles(NPs)as MTDs using 9-fluorenylmethyloxycarbonyl-tryptophan(Fmoc-Trp),quercetin(Que),and Fe^(2+)as building blocks through coordination and electrostatic interaction to generate Fmoc-Trp-Fe^(2+)-Que(FTFQ)NPs.Whether in cell or in vivo,FTFQ NPs exhibited considerable biocompatibility attributing to the inherent biological affinity of assembly units.By combining the advantages of assemble approach and nanostructures,the obtained FTFQ NPs greatly enhanced the bioavailability of Que and displayed synergistic therapeutic effects through reducing Aβaggregation in direct/indirect means and eliminating the toxicity induced by ROS and Aβoligomer/fibrils.Furthermore,FTFQ NPs could obviously restore the AD zebrafish’s mobility and stimulus response ability.More importantly,developing self-assembly NPs as MTDs could be an efficient and general method to promote other novel MTDs by extending the assemble units to other drugs,peptides,and metal ions.Based on above benefits,these self-assembled NPs could be as potential MTDs and show great promising application in AD treatment.
基金supported by the National Medical Products Administration Commissioned Research Project (No.20211440216)the National Administration of Traditional Chinese Medicine Science and Technology Project (No.GZY-KJS-2024-03)+3 种基金the State Key Laboratory of Drug Regulatory Science Project (No.2023SKLDRS0104)the Basic Research Program Natural Science Fund-Frontier Leading Technology Basic Research Special Project of Jiangsu Province (No.BK20232014)the Programs Foundation for Leading Talents in National Administration of Traditional Chinese Medicine of China“Qihuang scholars”Projectthe Tianjin Administration for Market Regulation Science and Technology Key Projects (No.2022-W35)。
文摘The research and development of new traditional Chinese medicine(TCM)drugs have progressively established a novel system founded on the integration of TCM theory,human experience,and clinical trials(termed the“Three Combinations”).However,considering TCM's distinctive features of“syndrome differentiation and treatment”and“multicomponent formulations and complex mechanisms”,current TCM drug development faces challenges such as insufficient understanding of the material basis and the overall mechanism of action and an incomplete evidence chain system.Moreover,significant obstacles persist in gathering human experience data,evaluating clinical efficacy,and controlling the quality of active ingredients,which impede the innovation process in TCM drug development.Network pharmacology,centered on the“network targets”theory,transcends the limitations of the conventional“single target”reductionist research model.It emphasizes the comprehensive effects of disease or syndrome biological networks as targets to elucidate the overall regulatory mechanism of TCM prescriptions.This approach aligns with the holistic perspective of TCM,offering a novel method consistent with TCM's holistic view for investigating the complex mechanisms of TCM and developing new TCM drugs.It is internationally recognized as a“next-generation drug research model”.To advance the research of new tools,methods,and standards for TCM evaluation and to overcome fundamental,critical,and cutting-edge technical challenges in TCM regulation,this consensus aims to explore the characteristics,progress,challenges,applicable pathways,and specific applications of network pharmacology as a new theory,method,and tool in TCM drug development.The goal is to enhance the quality of TCM drug research and development and accelerate the efficiency of developing new TCM products.
基金supported by the Independent Research and Development Projects Foundation of Shanghai InnoStar Bio-Techology Co.,Ltd.(H23ZZYF01 and H24ZZYF01).
文摘Therapeutic antibodies are valued for their high specificity and selectivity in immu-notherapy.However,the potential toxicity they may elicit underscores the necessity of assessing their preclinical efficacy and safety using suitable animal models.In this context,we review the various categories and applications of humanized mice,which have been engrafted with human cells or tissues to mimic the human immune system.These models are extensively utilized in the nonclinical assessment and development of various antibody drugs,acting as a conduit to clinical research.However,several challenges remain,including the limited lifespan of humanized mice,inadequate en-graftment of human cells,and the rudimentary nature of the immune environment in these models.The development of humanized immune system models in mice pre-sents both opportunities and challenges,potentially leading to new insights into the evolution and application of antibody therapeutics.
基金supported by the National Natural Science Foundation of China (Nos. 82173674 and 82204195)。
文摘Peptide-based therapies have attracted considerable interest in the treatment of cancer, diabetes, bacterial infections, and neurodegenerative diseases due to their promising therapeutic properties and enhanced safety profiles. This review provides a comprehensive overview of the major trends in peptide drug discovery and development, emphasizing preclinical strategies aimed at improving peptide stability, specificity, and pharmacokinetic properties. It assesses the current applications and challenges of peptide-based drugs in these diseases, illustrating the pharmaceutical areas where peptide-based drugs demonstrate significant potential. Furthermore, this review analyzes the obstacles that must be overcome in the future,aiming to provide valuable insights and references for the continued advancement of peptidebased drugs.
文摘Alzheimer 's disease(AD) is an alarming noncommunicable, multi-factorial, and non-treatable disease. Its underlying neurodegenerative events have not yet been fully explained and its early diagnosis is very difficult. The appearance of the disease is associated with clinical features such as the degeneration of several cholinergic nuclei of the brain.
文摘The use of traditional herbal drugs derived from natural sources is on the rise due to their minimal side effects and numerous health benefits.However,a major limitation is the lack of standardized knowledge for identifying and mapping the quality of these herbal medicines.This article aims to provide practical insights into the application of artificial intelligence for quality-based commercialization of raw herbal drugs.It focuses on feature extraction methods,image processing techniques,and the preparation of herbal images for compatibility with machine learning models.The article discusses commonly used image processing tools such as normalization,slicing,cropping,and augmentation to prepare images for artificial intelligence-based models.It also provides an overview of global herbal image databases and the models employed for herbal plant/drug identification.Readers will gain a comprehensive understanding of the potential application of various machine learning models,including artificial neural networks and convolutional neural networks.The article delves into suitable validation parameters like true positive rates,accuracy,precision,and more for the development of artificial intelligence-based identification and authentication techniques for herbal drugs.This article offers valuable insights and a conclusive platform for the further exploration of artificial intelligence in the field of herbal drugs,paving the way for smarter identification and authentication methods.
基金supported by the National Key Research and Development Program of China,No.2023YFC3603705(to DX)the National Natural Science Foundation of China,No.82302866(to YZ).
文摘After spinal cord injury,impairment of the sensorimotor circuit can lead to dysfunction in the motor,sensory,proprioceptive,and autonomic nervous systems.Functional recovery is often hindered by constraints on the timing of interventions,combined with the limitations of current methods.To address these challenges,various techniques have been developed to aid in the repair and reconstruction of neural circuits at different stages of injury.Notably,neuromodulation has garnered considerable attention for its potential to enhance nerve regeneration,provide neuroprotection,restore neurons,and regulate the neural reorganization of circuits within the cerebral cortex and corticospinal tract.To improve the effectiveness of these interventions,the implementation of multitarget early interventional neuromodulation strategies,such as electrical and magnetic stimulation,is recommended to enhance functional recovery across different phases of nerve injury.This review concisely outlines the challenges encountered following spinal cord injury,synthesizes existing neurostimulation techniques while emphasizing neuroprotection,repair,and regeneration of impaired connections,and advocates for multi-targeted,task-oriented,and timely interventions.
文摘Background Present drug delivery systems such as oral administration and intravenous injection limit the drug efficacy of current anti-allergy drugs.Therefore,new drug delivery systems,including nanocarriers,transdermal patches,and microneedles,are being investigated for their potential to deliver anti-allergy drugs.Purpose of review The review reveals the likely improvements by applying new drug delivery systems,including nanocarriers,transdermal patches and microneedles.Recent findings These new drug delivery systems utilize local administration and do not undergo metabolism pathways in the liver.Thus,they demonstrate high drug targeting,rapid onset action,precise dosage control,and minimal side effects.Limitations on large-scale production and high costs hinder the application of advanced drug delivery systems.Fortunately,forthcoming innovation and maturation will likely overcome the barriers and enable general patients to access anti-allergy drugs delivered by these advanced drug delivery systems,resulting in optimal body functions for everyday life.Conclusion Despite their limitations,new drug delivery systems are still promising solutions for delivering anti-allergy drugs due to their enhanced drug concentration,shortened onset time,and reduced systemic side effects.
基金Collaborative Innovation Program of Jiangsu Pharmaceutical Vocational College(Grant No.20239120)。
文摘The aim of this study is to evaluate the characteristics and patterns of adverse drug reactions(ADRs)associated with antineoplastic drugs and provide insights for safer chemotherapy practices.Based on 979 ADR cases reported in our hospital from January 1,2022,to December 31,2023,an analysis was conducted.Statistical analysis of the data revealed that 72.73%of these ADR incidents occurred in a hospital setting.The incidence of ADRs was higher in female patients compared to males,with the majority of cases(59.14%)observed in individuals aged 51-70 years.Intravenous administration was the predominant route linked to ADRs,accounting for 69.66%of the cases.Serious ADRs represented 9.30%of the total,including one instance where symptoms did not improve despite drug discontinuation or treatment.Cytotoxic antineoplastic drugs were responsible for 97.85%of all ADRs,with oxaliplatin being the most frequently implicated agent(19.82%).Gastrointestinal system involvement was the most common ADR manifestation,observed in 60.79%of cases.These findings underscored the necessity of enhanced monitoring for ADRs associated with cytotoxic antineoplastic drugs,particularly platinum-based agents.Comprehensive risk assessments and tailored treatment plans should be implemented during chemotherapy to minimize the occurrence of ADRs and safeguard patient safety.
文摘Lung cancer is one of the malignant tumor diseases with high morbidity and high mortality in the world. Non-small cell lung cancer (NSCLC) is the most common pathological type of lung cancer. Currently, chemotherapy, targeted therapy, immunotherapy or combination therapy is the main treatment for NSCLC, but it is still inevitably faced with the challenges of acquired drug resistance and tumor progression. The birth of antibody conjugator provides a new choice for its treatment. Antibody conjugator is a new type of biotherapeutic drug which is connected by monoclonal antibody via linker and cytotoxic drug. It has the characteristics of precision, high efficiency and low toxicity, etc. In recent years, its research and development and clinical trials have been endless. It shows that this new type of drug has great potential in the field of tumor therapy. In this paper, the structural characteristics, mechanism of action, current application, research achievements, challenges, countermeasures and development of ADC in NSCLC treatment are reviewed.
基金Subject construction funding project of Institute for Chemical Drug Control(Grant No.2024HYZX42)in National Institutes for Food and Drug Control,Beijing,China。
文摘The Reference Listed drug(RLD)plays a critical role in the development and research of generic medicinal products,serving as the comparator product used in the marketing authorization application of new generic medicinal product and re-evaluation of generic medicinal product.In China,RLDs are sourced from various origins,but their quality and market availability can be constrained by multiple factors,including emergent issues such as nitrosamine impurities.Five classes of medicinal products have been reported to be at risk for containing nitrosamine impurities:sartan-based medicines,metformin-containing products,ranitidine medicines,rifampicin medicines,and Champix.This paper explores the control strategies implemented by drug regulatory agencies in the United States and the European Union to manage nitrosamine impurities and assesses their impact on the market availability and quality of RLDs in China.The aim is to offer valuable insights for generic drug manufacturers and regulatory bodies both domestically and internationally.
文摘Nucleic acid drugs represent the third wave of innovation in drug research and development,succeeding small-molecule and antibody drugs.These drugs,particularly RNA interference(RNAi)therapies,have become a pivotal focus in the pharmaceutical industry.RNAi drugs are extensively utilized in the treatment of chronic and rare diseases due to their exceptional gene-silencing efficiency,manageable side effects,and straightforward synthesis process.This study undertook a thorough analysis of the global landscape of RNAi drug patents,highlighting the latest technological advancements and trends.We meticulously identified and cataloged the key technologies that dominated this patent landscape.The goal was to provide valuable insights and references for researchers involved in the development of RNAi drugs within the domestic pharmaceutical sector.
基金supported by the National Natural Science Foundation of China(Grant No.:82003711)Open Research Fund of Basic Medicine College(Grant No.:JCKFKT-MS-001)+2 种基金Shanghai Natural Science Foundation(Grant No.:23ZR1477600)Young Elite Scientists Sponsorship Program by CAST(Program No.:2022QNRC001)Shanghai Sailing Program(Program No.:24YF2758300).
文摘Drug synergistic effects refer to combinations that have a greater impact than individual drugs,which are often but sometimes harmful.Predicting synergism via computational methods like intelligence(AI)is popular,yet experimental validation remains challenging.DNA-programmed labeling(DPAL)is a method for target based on drug-target binding,minimizing interference from photoreactive groups and tags,which has the advantages of high sensitivity and low impact on drug activities[1–3].In the present study,we utilized the DPAL method to reveal the synergistic targets of the three main components(bufalin,cinobufagin,and resibufogenin(BCR))of cinobufacini injection with anti-hepatocarcinoma activities.
文摘With the continuous advancement of cancer treatment methods, plasma combined with drug therapy has garnered widespread attention as an emerging therapeutic strategy. This paper elaborates on the generation and characteristics of plasma, as well as its mechanisms of action on cancer cells when used alone, including the production of reactive oxygen and nitrogen species, and damage to cancer cell membranes, and organelles. It emphasizes the synergistic mechanisms observed when plasma is combined with various anticancer drugs (e.g., chemotherapeutic agents, targeted drugs, and immunotherapies). The analysis focuses on enhancing drug uptake, promoting the activation of drug action targets, and improving the tumor microenvironment. These insights provide a theoretical basis for optimizing plasma-drug combination therapy for cancer.
基金supported by the National Natural Science Foundation of China(No.21801153)Natural Science Foundation of Shandong Province(No.ZR2023MB065)+1 种基金Academic promotion program of Shandong First Medical University(No.2019LJ003)High-level Overseas Talent Workstation of Shandong Province.
文摘Green synthesis of drugs is of paramount importance for current public health and a prerequisite to new drugs exploiting.Nowadays,novel strategies of disease diagnosis and therapies are in blooming development as remarkable advances have been achieved which are all highly depended on drug development.Under the current requirements to high production capacity and novel synthesis methods of drugs,green synthesis based on strategies with different ways of empowering,advanced catalysts and unique reaction equipment are attracting huge attention and of great challenging.Higher quality products and environmentally friendly synthesis conditions are becoming more and more important for manufacturing process which has new requirements for catalyst materials and synthesis processes.Polyoxometalates(POMs)are class of transition metals-oxygen clusters with precise molecular structures and superior physicochemical properties which have made longstanding and important applications upon research community of functional materials,catalysis and medicine.In this review,the recent advances of polyoxometalates based strategies for green synthesis of drugs are summarized including POMs based catalysts,alternative reaction equipment based novel synthesis protocols.The significance of POMs to pharmaceutical and industrial field is highlighted and the related perspective for future development are well discussed.
