Cancer is the second leading cause of death globally.Its treatment remains a major challenge due to the disease's complexity,heterogeneity,and adaptive nature.Among the array of available treatments,targeted thera...Cancer is the second leading cause of death globally.Its treatment remains a major challenge due to the disease's complexity,heterogeneity,and adaptive nature.Among the array of available treatments,targeted therapy emerges as a paramount approach to address this substantial unmet clinical need,owing to its precise tumor targeting capabilities and potential for mitigating tumor progression risks.Drug conjugates are in high demand for targeted therapy due to their unique ligand specificity and potent cytotoxicity,thereby significantly enhancing therapeutic efficacy and reducing the incidence of adverse effects.Therefore,as a burgeoning field in biomedical research,it is timely to outline the latest advances in drug conjugates-driven cancer treatment.Herein,we aim to present the emerging breakthroughs in this exciting field at the intersection of target ligands,linkers,payloads,and cancer treatments.This review focuses on several drug conjugates-related strategies,including antibody-drug conjugates(ADCs),peptide-drug conjugates(PDCs),small molecule-drug conjugates(SMDCs),aptamer-drug conjugates(ApDCs)and radionuclide-drug conjugates(RDCs).Finally,we discuss the fundamentals behind drug conjugate-based anticancer therapeutics,along with their inherent advantages and associated challenges,as well as recent research advances.展开更多
Despite advances in current anti-cancer therapies,challenges such as drug resistance,toxicity,and tumor heterogeneity persist.The limitations of traditional single-target drugs and simple combination therapies are bec...Despite advances in current anti-cancer therapies,challenges such as drug resistance,toxicity,and tumor heterogeneity persist.The limitations of traditional single-target drugs and simple combination therapies are becoming increasingly apparent1.To address these issues,a novel treatment strategy,the artificially intelligent synergistic engineered drug(AISED)paradigm,merits further exploration.This paradigm is based on the systematic engineered integration of multiple active ingredients into a unified single entity through artificial intelligence(AI).This strategy is aimed at developing new anti-cancer drug designs involving multiple ingredients,multiple molecular targets,and multiple biological effects,for multiple cancer types,thereby providing a novel theoretical paradigm for overcoming existing treatment bottlenecks.展开更多
Neural injuries can cause considerable functional impairments,and both central and peripheral nervous systems have limited regenerative capacity.The existing conventional pharmacological treatments in clinical practic...Neural injuries can cause considerable functional impairments,and both central and peripheral nervous systems have limited regenerative capacity.The existing conventional pharmacological treatments in clinical practice show poor targeting,rapid drug clearance from the circulatory system,and low therapeutic efficiency.Therefore,in this review,we have first described the mechanisms underlying nerve regeneration,characterized the biomaterials used for drug delivery to facilitate nerve regeneration,and highlighted the functionalization strategies used for such drug-delivery systems.These systems mainly use natural and synthetic polymers,inorganic materials,and hybrid systems with advanced drug-delivery abilities,including nanoparticles,hydrogels,and scaffoldbased systems.Then,we focused on comparing the types of drug-delivery systems for neural regeneration as well as the mechanisms and challenges associated with targeted delivery of drugs to facilitate neural regeneration.Finally,we have summarized the clinical application research and limitations of targeted delivery of these drugs.These biomaterials and drug-delivery systems can provide mechanical support,sustained release of bioactive molecules,and enhanced intercellular contact,ultimately reducing cell apoptosis and enhancing functional recovery.Nevertheless,immune reactions,degradation regulation,and clinical translations remain major unresolved challenges.Future studies should focus on optimizing biomaterial properties,refining delivery precision,and overcoming translational barriers to advance these technologies toward clinical applications.展开更多
In recent years,different drugs therapies for treatment pulmonary fibrosis(PF) have gained much attention due to development of drug delivery technology and urgent clinical needs.PF treatment existed a variety of curr...In recent years,different drugs therapies for treatment pulmonary fibrosis(PF) have gained much attention due to development of drug delivery technology and urgent clinical needs.PF treatment existed a variety of currently clinical problem but PF could be treated with different drugs potentially though drug delivery technology.This review systematically expounds its basic theory,various drug delivery technologies,and future development directions.In the introduction,the relationship between the pathological mechanism of PF and drug delivery,the basic principles of the drug delivery system and the biological barriers faced by pulmonary drug delivery are analyzed.This review details delivery of small molecule drug,macromolecular drug and cells,including chemical synthesis and natural small molecule drug delivery,as well as RNA and cell-based delivery.Finally,the challenges and perspectives of these drugs to treat PF delivery technologies are discussed and key aspects in the development of PF drugs are considered.We hoped that this review can provide comprehensive and in-depth theoretical reference and technical support for the drug treatment of PF.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
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
The prolonged and intricate history of oncological treatments has transitioned significantly since the introduction of chemotherapy.Substantial therapeutic benefits in cancer therapy have been achieved by the integrat...The prolonged and intricate history of oncological treatments has transitioned significantly since the introduction of chemotherapy.Substantial therapeutic benefits in cancer therapy have been achieved by the integration of conventional treatments with molecular biosciences and omics technologies.Human epidermal growth factor receptor,hormone receptors,and angiogenesis factors are among the established therapies in tumor reduction and managing side effects.Novel targeted therapies like KRAS G12C,Claudin-18 isoform 2(CLDN18.2),Trophoblast cell-surface antigen 2(TROP2),and epigenetic regulators emphasize their promise in advancing precision medicine.However,in many cases,the resistance mechanisms associated with these interventions render them ineffective in carrying out their functions.The purpose of this review is to provide a comprehensive and up-to-date examination of both established and emerging drug targets and mechanisms of treatment resistance in oncology.This review seeks to elucidate recent advancements,address persisting challenges,and explore opportunities for innovative developments in cancer target research.Additionally,it explores the growing role of artificial intelligence in reshaping cancer drug discovery and development frameworks as potential avenues for future research.In conclusion,innovative approaches in oncology,supported by pharmacological research,ongoing clinical trials,molecular biosciences,and artificial intelligence,are poised to significantly transform cancer treatment.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
Background:The development of materials for cardiovascular surgery that would improve the effectiveness of surgical interventions remains an important task.Surgical intervention during the implantation of vascular pro...Background:The development of materials for cardiovascular surgery that would improve the effectiveness of surgical interventions remains an important task.Surgical intervention during the implantation of vascular prostheses and stents,and the body’s reaction to artificial materials,could lead to chronic inflammation,a local increase in the concentration of proinflammatory factors,and stimulation of unwanted tissue growth.The introduction of nonsteroidal anti-inflammatory drugs into implantable devices could be used to obtain vascular implants that do not induce inflammation and do not induce neointimal tissue outgrowth.Methods:The scaffolds were made by electrospinning from mixtures of polyurethane(PU)with diclofenac(DF).The kinetics of DF release from the scaffolds composed of 3%PU/10%HSA/3%DMSO/DF and 3%PU/DF were studied.The biocompatibility and anti-inflammatory effects of the obtained scaffolds on human gingival fibroblasts and umbilical vein endothelial cells were studied.Results:Both types of scaffolds are characterized by fast DF release.The viability of cells cultured on scaffolds is 2 times worse than that of cells cultured on plastic.The level of the proinflammatory cytokine IL-6 in the culture medium of cells cultured on DF-containing scaffolds was lower than that of cells cultured on scaffolds without DF.Conclusion:The introduction of DF into scaffolds minimizes the inflammation caused by cell reactions to an artificial material.展开更多
Pure drug nanomedicines(PDNs)encompass active pharmaceutical ingredients(APIs),including macromolecules,biological compounds,and functional components.They overcome research barriers and conversion thresholds associat...Pure drug nanomedicines(PDNs)encompass active pharmaceutical ingredients(APIs),including macromolecules,biological compounds,and functional components.They overcome research barriers and conversion thresholds associated with nanocarriers,offering advantages such as high drug loading capacity,synergistic treatment effects,and environmentally friendly production methods.This review provides a comprehensive overview of the latest advancements in PDNs,focusing on their essential components,design theories,and manufacturing techniques.The physicochemical properties and in vivo behaviors of PDNs are thoroughly analyzed to gain an in-depth understanding of their systematic characteristics.The review introduces currently approved PDN products and further explores the opportunities and challenges in expanding their depth and breadth of application.Drug nanocrystals,drug-drug cocrystals(DDCs),antibody-drug conjugates(ADCs),and nanobodies represent the successful commercialization and widespread utilization of PDNs across various disease domains.Self-assembled pure drug nanoparticles(SAPDNPs),a next-generation product,still require extensive translational research.Challenges persist in transitioning from laboratory-scale production to mass manufacturing and overcoming the conversion threshold from laboratory findings to clinical applications.展开更多
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
Artificial intelligence(AI)researchers and cheminformatics specialists strive to identify effective drug precursors while optimizing costs and accelerating development processes.Digital molecular representation plays ...Artificial intelligence(AI)researchers and cheminformatics specialists strive to identify effective drug precursors while optimizing costs and accelerating development processes.Digital molecular representation plays a crucial role in achieving this objective by making molecules machine-readable,thereby enhancing the accuracy of molecular prediction tasks and facilitating evidence-based decision making.This study presents a comprehensive review of small molecular representations and AI-driven drug discovery downstream tasks utilizing these representations.The research methodology begins with the compilation of small molecule databases,followed by an analysis of fundamental molecular representations and the models that learn these representations from initial forms,capturing patterns and salient features across extensive chemical spaces.The study then examines various drug discovery downstream tasks,including drug-target interaction(DTI)prediction,drug-target affinity(DTA)prediction,drug property(DP)prediction,and drug generation,all based on learned representations.The analysis concludes by highlighting challenges and opportunities associated with machine learning(ML)methods for molecular representation and improving downstream task performance.Additionally,the representation of small molecules and AI-based downstream tasks demonstrates significant potential in identifying traditional Chinese medicine(TCM)medicinal substances and facilitating TCM target discovery.展开更多
Objective To determine the proportions of drug-resistant tuberculosis(TB),its trends,and the drug resistance-conferring mutations among patients with pulmonary TB aged 10-24 years in China.Methods The data of patients...Objective To determine the proportions of drug-resistant tuberculosis(TB),its trends,and the drug resistance-conferring mutations among patients with pulmonary TB aged 10-24 years in China.Methods The data of patients with pulmonary TB were retrieved from a national drug-resistant TB survey for analysis.Joinpoint regression software was used to analyze time trends.We also used whole genome sequencing to analyze the lineages and drug resistance-conferring mutations of 621 isolates.Results Among 4,235 patients with pulmonary TB,the proportion of new cases of multidrug-resistant tuberculosis(MDR-TB)was 3.18%(95%confidence interval[CI]:2.37-4.15)for adolescents and 3.76%(95%CI:3.03-4.60)for young adults;for previously treated patients,MDR-TB accounted for 11.25%(95%CI:5.28-20.28)of adolescents and 11.05%(95%CI:6.88-16.55)of young adults.The proportion of patients with MDR-TB remained stable among both new and previously treated patients aged 10-24 years during the study period.Through whole genome sequencing,we found that the most common mutations in the MDR-TB strains were Ser315Thr in the katG gene(71.74%)and Ser450Leu in the rpoB gene(50.00%).Conclusion This study revealed a high proportion of MDR-TB among adolescents and young adults,indicating that urgent and comprehensive measures are needed to reduce the emergence and transmission of drug-resistant TB among this population in China.展开更多
Malignant pleural effusion(MPE) is a serious disease caused by malignant tumors with high morbidity and mortality.Chemotherapy,immunotherapy,and antiangiogenic therapy are common treatments for MPE at present.However,...Malignant pleural effusion(MPE) is a serious disease caused by malignant tumors with high morbidity and mortality.Chemotherapy,immunotherapy,and antiangiogenic therapy are common treatments for MPE at present.However,traditional chemotherapeutic drugs have many side effects and can easily lead to drug resistance in patients.The complex tumor microenvironment(TME) of MPE directly reduces the antitumor efficacy of immunotherapy.Fortunately,drug delivery systems(DDSs) based on biomaterials have the ability to overcome some of the drawbacks of conventional treatments by improving drug stability,increasing the accuracy of tumor cell targeting,reducing toxic side effects,and remodeling TME,ultimately improving drug efficacy.Therefore,the purpose of this review is to provide an overview and discussion of the latest progress in biomaterial-based DDSs for the treatment of MPE.We discuss the application of biomaterials in the treatment of MPE from multiple perspectives,including chemotherapy,immunotherapy,combination therapy,and pleurodesis,where microspheres,cell membrane-derived microparticles(MPs),micelles,nanoparticles,and liposomes,are involved.The application of these biomaterials has been proven to have great potential in the treatment of MPE,providing a new idea for follow-up research.展开更多
The mechanisms underlying the pathophysiology of ischemic stroke are complex and multifactorial and include excitotoxicity,oxidative stress,inflammatory responses,and blood–brain barrier disruption.While vascular rec...The mechanisms underlying the pathophysiology of ischemic stroke are complex and multifactorial and include excitotoxicity,oxidative stress,inflammatory responses,and blood–brain barrier disruption.While vascular recanalization treatments such as thrombolysis and mechanical thrombectomy have achieved some success,reperfusion injury remains a significant contributor to the exacerbation of brain injury.This emphasizes the need for developing neuroprotective strategies to mitigate this type of injury.The purpose of this review was to examine the application of nanotechnology in the treatment of ischemic stroke,covering research progress in nanoparticlebased drug delivery,targeted therapy,and antioxidant and anti-inflammatory applications.Nanobased drug delivery systems offer several advantages compared to traditional therapies,including enhanced blood–brain barrier penetration,prolonged drug circulation time,improved drug stability,and targeted delivery.For example,inorganic nanoparticles,such as those based on CeO_(2),have been widely studied for their strong antioxidant capabilities.Biomimetic nanoparticles,such as those coated with cell membranes,have garnered significant attention owing to their excellent biocompatibility and targeting abilities.Nanoparticles can be used to deliver a wide range of neuroprotective agents,such as antioxidants(e.g.,edaravone),anti-inflammatory drugs(e.g.,curcumin),and neurotrophic factors.Nanotechnology significantly enhances the efficacy of these drugs while minimizing adverse reactions.Although nanotechnology has demonstrated great potential in animal studies,its clinical application still faces several challenges,including the long-term safety of nanoparticles,the feasibility of large-scale production,quality control,and the ability to predict therapeutic effects in humans.In summary,nanotechnology holds significant promise for the treatment of ischemic stroke.Future research should focus on further exploring the mechanisms of action of nanoparticles,developing multifunctional nanoparticles,and validating their safety and efficacy through rigorous clinical trials.Moreover,interdisciplinary collaboration is essential for advancing the use of nanotechnology in stroke treatment.展开更多
Given that platinum-based drugs are widely used clinically as chemotherapeutic agents,their severe toxic side effects have attracted significant attention.Consequently,the development of novel nanoprodrugs based on lo...Given that platinum-based drugs are widely used clinically as chemotherapeutic agents,their severe toxic side effects have attracted significant attention.Consequently,the development of novel nanoprodrugs based on low-toxicity tetravalent platinum(Pt(Ⅳ))com plexes holds substantial research value.Herein,we discovered that coumarin derivatives exhibit inherent antitumor efficacy and significantly enhance superoxide anion radicals(·O_(2)^(-))generation in aqueous solutions under ultrasound(US)irradiation.Given that·O_(2)^(-)is known to mediate the reduction of Pt(Ⅳ)to divalent platinum(Pt(Ⅱ)),we engineered an US-responsive dual-drug nanoprodrug(P-cisPt(Ⅳ)@5-MOP).This nanoprodrug was prepared by covalently conjugating Pt(Ⅳ)and methoxy polyethylene glycol hydroxyl(m PEG-OH)to a poly(_(L)-glutamic acid)(PLG)carrier,followed by encapsulating coumarin derivatives.Under low-intensity US irradiation(1.5 W/cm^(2),1 MHz,10 min),P-cisPt(Ⅳ)@5-MOP achieved a Pt(Ⅳ)reduction rate of 91.4%.Furthermore,upon US exposure,its half-maximal inhibitory concentration(IC_(50))against 4T1 breast cancer cells decreased dramatically from 25.7μmol/L to 0.1μmol/L.Remarkably,this system combined with US therapy yielded a tumor inhibition rate of 90.9%,with 40%of tumor-bea ring mice achieving com plete eradication of tumors,while exhibiting low systemic toxicity.Collectively,this work not only identifies a novel sonosensitizer capable of generating·O_(2)^(-)but also develops a new class of ultrasound-activatable Pt(Ⅳ)nanoprodrug.展开更多
In recent years,the problem of veterinary drug residues in animal-derived foods has attracted worldwide attention.Developing rapid,simple,highly sensitive,and high-throughput veterinary drug residue detection technolo...In recent years,the problem of veterinary drug residues in animal-derived foods has attracted worldwide attention.Developing rapid,simple,highly sensitive,and high-throughput veterinary drug residue detection technologies has become an urgent need.This paper provides a comprehensive review of the pretreatment and analytical techniques for veterinary drug residue analysis,comparing the detection principles,operational procedures,and respective advantages and disadvantages of various detection technologies.It further explores the future development directions of veterinary drug residue detection technologies.展开更多
In recent years,development of strategies to treat central nervous system(CNS) diseases has attracted extensive attention.A major obstacle in this field is the blood-brain barrier(BBB),which significantly limits the e...In recent years,development of strategies to treat central nervous system(CNS) diseases has attracted extensive attention.A major obstacle in this field is the blood-brain barrier(BBB),which significantly limits the efficient delivery of therapeutic agents to the brain and hinders the treatment of CNS diseases.Overcoming the restrictive nature of the BBB has thus emerged as a key objective in CNS drug development.Nanomaterials have garnered growing interest due to their unique physicochemical properties and potential to traverse the BBB,enabling targeted drug delivery to brain tissue and improving therapeutic efficacy.In this review,we present current insights into the structure and function of the BBB and highlight a range of nanomaterial-based strategies for BBB penetration,including receptor-mediated transport(RMT),adsorptive-mediated transcytosis,reversible BBB disruption,and intranasal administration.Finally,we summarize recent advances in enhancing BBB permeability for CNS therapeutics and discuss persisting challenges,offering perspectives for future research in this field.展开更多
Objective:To evaluate the effects of a piceatannol-loaded self-nanoemulsifying drug delivery system(PIC-SNEDDS)on wound healing in diabetic rats and its mechanisms of wound healing action.Methods:Diabetes was induced ...Objective:To evaluate the effects of a piceatannol-loaded self-nanoemulsifying drug delivery system(PIC-SNEDDS)on wound healing in diabetic rats and its mechanisms of wound healing action.Methods:Diabetes was induced in rats using streptozotocin,after which full-thickness excisional wounds were created.Piceatannol was administered topically either as a raw hydrogel or formulated into a PIC-SNEDDS,which was prepared using an optimized oil-surfactant mixture and incorporated into a hydrogel for application.Wound healing activity was assessed through measurements of wound contraction,oxidative stress biomarkers,and collagen content,along with histological and immunohistochemical evaluation of inflammatory,angiogenic,and remodeling markers.Results:PIC-SNEDDS markedly enhanced diabetic wound healing by promoting epithelial regeneration,granulation tissue formation,epidermal proliferation,and keratinization.The formulation also reduced the expression of pro-inflammatory markers(interleukin-6,nuclear factor-kappa B,and tumor necrosis factor-α)while increasingα-smooth muscle actin,transforming growth factor-β1,vascular endothelial growth factor-A,and hydroxyproline levels.Additionally,it improved antioxidant status by lowering malondialdehyde levels and boosting superoxide dismutase and catalase activity,along with upregulation of COL1A1 mRNA expression.Conclusions:PIC-SNEDDS promotes the healing of diabetic wounds and exhibits anti-inflammatory,antioxidant,pro-collagen,and angiogenic properties.展开更多
Objectives:B-cell maturation antigen(BCMA)-targeted antibody–drug conjugates(ADCs)have emerged as promising therapies for relapsed/refractory multiple myeloma(RRMM),but the overall efficacy and safety profile is uncl...Objectives:B-cell maturation antigen(BCMA)-targeted antibody–drug conjugates(ADCs)have emerged as promising therapies for relapsed/refractory multiple myeloma(RRMM),but the overall efficacy and safety profile is unclear.This study aimed to synthesize the available evidence on the safety and efficacy of BCMA-ADCs in development for RRMM.Methods:A systematic search was conducted using six bibliographic databases and ClinicalTrials.gov up to November 2024.Studies were eligible if they were human clinical trials or animal studies evaluating BCMA-ADCs and reported efficacy and safety outcomes.Data extraction and quality assessments were conducted using validated tools,including ROBINS-I and SYRCLE’s risk of bias tool.Results:A total of 21 studies were included:16 clinical trials and five animal studies.Key findings included that belantamab mafodotin demonstrated variable but generally durable response rates(32%–85%)and a broad range of progression-free survival(PFS)(2.8–36.6 months),albeit with ocular toxicities in 51%–96%.Among newer candidates,MEDI2228 showed median PFS 5.1–6.6 months with 14%discontinuation for ocular symptoms,while AMG 224 had an overall response rate(ORR)of 23%(9/40)with anemia 21%,thrombocytopenia 24%,and ocular adverse events(AEs)21%.Animal studies supported the tumor-eradicating potential of all BCMA-ADC candidates,although safety signals such as hepatic and renal toxicity were noted with HDP-101.The risk of bias assessment revealed generally moderate to serious concerns in human trials,while the overall quality of the animal studies was acceptable.Conclusions:BCMA-targeted ADC candidates show encouraging efficacy in RRMM,particularly belantamab mafodotin.However,frequent AEs,especially ocular and hematologic toxicities,underscore the need for optimization in ADC design.Further research should prioritize enhancing safety while maintaining clinical benefit.展开更多
基金the Project of China-Japan Joint International Laboratory of Advanced Drug Delivery System Research and Translation of Liaoning Province(No.2024JH2/102100007)the open fund of National Key Laboratory of Advanced DrugFormulations for Overcoming Delivery Barriers(No.2024-KFB-003)+1 种基金the National Natural Science Foundation of China(No.82104109)Scientific Research Project of Liaoning Department of Education(No.LJ212410163045).
文摘Cancer is the second leading cause of death globally.Its treatment remains a major challenge due to the disease's complexity,heterogeneity,and adaptive nature.Among the array of available treatments,targeted therapy emerges as a paramount approach to address this substantial unmet clinical need,owing to its precise tumor targeting capabilities and potential for mitigating tumor progression risks.Drug conjugates are in high demand for targeted therapy due to their unique ligand specificity and potent cytotoxicity,thereby significantly enhancing therapeutic efficacy and reducing the incidence of adverse effects.Therefore,as a burgeoning field in biomedical research,it is timely to outline the latest advances in drug conjugates-driven cancer treatment.Herein,we aim to present the emerging breakthroughs in this exciting field at the intersection of target ligands,linkers,payloads,and cancer treatments.This review focuses on several drug conjugates-related strategies,including antibody-drug conjugates(ADCs),peptide-drug conjugates(PDCs),small molecule-drug conjugates(SMDCs),aptamer-drug conjugates(ApDCs)and radionuclide-drug conjugates(RDCs).Finally,we discuss the fundamentals behind drug conjugate-based anticancer therapeutics,along with their inherent advantages and associated challenges,as well as recent research advances.
文摘Despite advances in current anti-cancer therapies,challenges such as drug resistance,toxicity,and tumor heterogeneity persist.The limitations of traditional single-target drugs and simple combination therapies are becoming increasingly apparent1.To address these issues,a novel treatment strategy,the artificially intelligent synergistic engineered drug(AISED)paradigm,merits further exploration.This paradigm is based on the systematic engineered integration of multiple active ingredients into a unified single entity through artificial intelligence(AI).This strategy is aimed at developing new anti-cancer drug designs involving multiple ingredients,multiple molecular targets,and multiple biological effects,for multiple cancer types,thereby providing a novel theoretical paradigm for overcoming existing treatment bottlenecks.
基金the support from Base for Interdisciplinary Innovative Talent Training,Shanghai Jiao Tong UniversityYouth Science and Technology Innovation Studio of Shanghai Jiao Tong University School of Medicine。
文摘Neural injuries can cause considerable functional impairments,and both central and peripheral nervous systems have limited regenerative capacity.The existing conventional pharmacological treatments in clinical practice show poor targeting,rapid drug clearance from the circulatory system,and low therapeutic efficiency.Therefore,in this review,we have first described the mechanisms underlying nerve regeneration,characterized the biomaterials used for drug delivery to facilitate nerve regeneration,and highlighted the functionalization strategies used for such drug-delivery systems.These systems mainly use natural and synthetic polymers,inorganic materials,and hybrid systems with advanced drug-delivery abilities,including nanoparticles,hydrogels,and scaffoldbased systems.Then,we focused on comparing the types of drug-delivery systems for neural regeneration as well as the mechanisms and challenges associated with targeted delivery of drugs to facilitate neural regeneration.Finally,we have summarized the clinical application research and limitations of targeted delivery of these drugs.These biomaterials and drug-delivery systems can provide mechanical support,sustained release of bioactive molecules,and enhanced intercellular contact,ultimately reducing cell apoptosis and enhancing functional recovery.Nevertheless,immune reactions,degradation regulation,and clinical translations remain major unresolved challenges.Future studies should focus on optimizing biomaterial properties,refining delivery precision,and overcoming translational barriers to advance these technologies toward clinical applications.
基金funded by the National Natural Science Foundation of China (No.NSFC82400096)Science and Technology Department of Sichuan Province (No.2025ZNSFSC1538)Xihua University Internal Talent Introduction Project with Scientific Research Funding (No.ZX20250087)。
文摘In recent years,different drugs therapies for treatment pulmonary fibrosis(PF) have gained much attention due to development of drug delivery technology and urgent clinical needs.PF treatment existed a variety of currently clinical problem but PF could be treated with different drugs potentially though drug delivery technology.This review systematically expounds its basic theory,various drug delivery technologies,and future development directions.In the introduction,the relationship between the pathological mechanism of PF and drug delivery,the basic principles of the drug delivery system and the biological barriers faced by pulmonary drug delivery are analyzed.This review details delivery of small molecule drug,macromolecular drug and cells,including chemical synthesis and natural small molecule drug delivery,as well as RNA and cell-based delivery.Finally,the challenges and perspectives of these drugs to treat PF delivery technologies are discussed and key aspects in the development of PF drugs are considered.We hoped that this review can provide comprehensive and in-depth theoretical reference and technical support for the drug treatment of PF.
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.
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The prolonged and intricate history of oncological treatments has transitioned significantly since the introduction of chemotherapy.Substantial therapeutic benefits in cancer therapy have been achieved by the integration of conventional treatments with molecular biosciences and omics technologies.Human epidermal growth factor receptor,hormone receptors,and angiogenesis factors are among the established therapies in tumor reduction and managing side effects.Novel targeted therapies like KRAS G12C,Claudin-18 isoform 2(CLDN18.2),Trophoblast cell-surface antigen 2(TROP2),and epigenetic regulators emphasize their promise in advancing precision medicine.However,in many cases,the resistance mechanisms associated with these interventions render them ineffective in carrying out their functions.The purpose of this review is to provide a comprehensive and up-to-date examination of both established and emerging drug targets and mechanisms of treatment resistance in oncology.This review seeks to elucidate recent advancements,address persisting challenges,and explore opportunities for innovative developments in cancer target research.Additionally,it explores the growing role of artificial intelligence in reshaping cancer drug discovery and development frameworks as potential avenues for future research.In conclusion,innovative approaches in oncology,supported by pharmacological research,ongoing clinical trials,molecular biosciences,and artificial intelligence,are poised to significantly transform cancer treatment.
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 Russian state-funded project for ICBFM SB RAS(grant number 125012300656-5)。
文摘Background:The development of materials for cardiovascular surgery that would improve the effectiveness of surgical interventions remains an important task.Surgical intervention during the implantation of vascular prostheses and stents,and the body’s reaction to artificial materials,could lead to chronic inflammation,a local increase in the concentration of proinflammatory factors,and stimulation of unwanted tissue growth.The introduction of nonsteroidal anti-inflammatory drugs into implantable devices could be used to obtain vascular implants that do not induce inflammation and do not induce neointimal tissue outgrowth.Methods:The scaffolds were made by electrospinning from mixtures of polyurethane(PU)with diclofenac(DF).The kinetics of DF release from the scaffolds composed of 3%PU/10%HSA/3%DMSO/DF and 3%PU/DF were studied.The biocompatibility and anti-inflammatory effects of the obtained scaffolds on human gingival fibroblasts and umbilical vein endothelial cells were studied.Results:Both types of scaffolds are characterized by fast DF release.The viability of cells cultured on scaffolds is 2 times worse than that of cells cultured on plastic.The level of the proinflammatory cytokine IL-6 in the culture medium of cells cultured on DF-containing scaffolds was lower than that of cells cultured on scaffolds without DF.Conclusion:The introduction of DF into scaffolds minimizes the inflammation caused by cell reactions to an artificial material.
基金supported by the National Natural Science Foundation of China(Nos.82073782 and 82241002)。
文摘Pure drug nanomedicines(PDNs)encompass active pharmaceutical ingredients(APIs),including macromolecules,biological compounds,and functional components.They overcome research barriers and conversion thresholds associated with nanocarriers,offering advantages such as high drug loading capacity,synergistic treatment effects,and environmentally friendly production methods.This review provides a comprehensive overview of the latest advancements in PDNs,focusing on their essential components,design theories,and manufacturing techniques.The physicochemical properties and in vivo behaviors of PDNs are thoroughly analyzed to gain an in-depth understanding of their systematic characteristics.The review introduces currently approved PDN products and further explores the opportunities and challenges in expanding their depth and breadth of application.Drug nanocrystals,drug-drug cocrystals(DDCs),antibody-drug conjugates(ADCs),and nanobodies represent the successful commercialization and widespread utilization of PDNs across various disease domains.Self-assembled pure drug nanoparticles(SAPDNPs),a next-generation product,still require extensive translational research.Challenges persist in transitioning from laboratory-scale production to mass manufacturing and overcoming the conversion threshold from laboratory findings to clinical applications.
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.
基金supported by the Shenzhen Key Laboratory of Intelligent Bioinformatics(No.ZDSYS20220422103800001)the Shenzhen Science and Technology Program(No.JCYJ20230807140709020)+2 种基金National Natural Science Foundation of China(Nos.62402489,U22A2041,and 62373172)the China Postdoctoral Science Foundation(No.2023M743688)Guangdong Basic and Applied Basic Research Foundation(Nos.2024A1515011960 and 2023A1515110570)。
文摘Artificial intelligence(AI)researchers and cheminformatics specialists strive to identify effective drug precursors while optimizing costs and accelerating development processes.Digital molecular representation plays a crucial role in achieving this objective by making molecules machine-readable,thereby enhancing the accuracy of molecular prediction tasks and facilitating evidence-based decision making.This study presents a comprehensive review of small molecular representations and AI-driven drug discovery downstream tasks utilizing these representations.The research methodology begins with the compilation of small molecule databases,followed by an analysis of fundamental molecular representations and the models that learn these representations from initial forms,capturing patterns and salient features across extensive chemical spaces.The study then examines various drug discovery downstream tasks,including drug-target interaction(DTI)prediction,drug-target affinity(DTA)prediction,drug property(DP)prediction,and drug generation,all based on learned representations.The analysis concludes by highlighting challenges and opportunities associated with machine learning(ML)methods for molecular representation and improving downstream task performance.Additionally,the representation of small molecules and AI-based downstream tasks demonstrates significant potential in identifying traditional Chinese medicine(TCM)medicinal substances and facilitating TCM target discovery.
基金funded by the National Key Research and Development Program of China(grant number 2022YFC2305204).
文摘Objective To determine the proportions of drug-resistant tuberculosis(TB),its trends,and the drug resistance-conferring mutations among patients with pulmonary TB aged 10-24 years in China.Methods The data of patients with pulmonary TB were retrieved from a national drug-resistant TB survey for analysis.Joinpoint regression software was used to analyze time trends.We also used whole genome sequencing to analyze the lineages and drug resistance-conferring mutations of 621 isolates.Results Among 4,235 patients with pulmonary TB,the proportion of new cases of multidrug-resistant tuberculosis(MDR-TB)was 3.18%(95%confidence interval[CI]:2.37-4.15)for adolescents and 3.76%(95%CI:3.03-4.60)for young adults;for previously treated patients,MDR-TB accounted for 11.25%(95%CI:5.28-20.28)of adolescents and 11.05%(95%CI:6.88-16.55)of young adults.The proportion of patients with MDR-TB remained stable among both new and previously treated patients aged 10-24 years during the study period.Through whole genome sequencing,we found that the most common mutations in the MDR-TB strains were Ser315Thr in the katG gene(71.74%)and Ser450Leu in the rpoB gene(50.00%).Conclusion This study revealed a high proportion of MDR-TB among adolescents and young adults,indicating that urgent and comprehensive measures are needed to reduce the emergence and transmission of drug-resistant TB among this population in China.
基金financial support from the Noncommunicable Chronic Diseases-National Science and Technology Major Project (Nos.2024ZD0522800,2024ZD0522803)the National Natural Science Foundation of China (Nos.U21A20417,31930067,31800797)+2 种基金the Natural Science Foundation of Sichuan Province (No.2024NSFSC0046)the Sichuan Science and Technology Program (No.2022YFS0333)the 1·3·5 Project for Disciplines of Excellence,West China Hospital,Sichuan University (No.ZYGD24003)。
文摘Malignant pleural effusion(MPE) is a serious disease caused by malignant tumors with high morbidity and mortality.Chemotherapy,immunotherapy,and antiangiogenic therapy are common treatments for MPE at present.However,traditional chemotherapeutic drugs have many side effects and can easily lead to drug resistance in patients.The complex tumor microenvironment(TME) of MPE directly reduces the antitumor efficacy of immunotherapy.Fortunately,drug delivery systems(DDSs) based on biomaterials have the ability to overcome some of the drawbacks of conventional treatments by improving drug stability,increasing the accuracy of tumor cell targeting,reducing toxic side effects,and remodeling TME,ultimately improving drug efficacy.Therefore,the purpose of this review is to provide an overview and discussion of the latest progress in biomaterial-based DDSs for the treatment of MPE.We discuss the application of biomaterials in the treatment of MPE from multiple perspectives,including chemotherapy,immunotherapy,combination therapy,and pleurodesis,where microspheres,cell membrane-derived microparticles(MPs),micelles,nanoparticles,and liposomes,are involved.The application of these biomaterials has been proven to have great potential in the treatment of MPE,providing a new idea for follow-up research.
基金supported by the National Natural Science Foundation of China,Nos.82301093(to QC)and 22334004(to HY)the Fuzhou University Fund for Testing Precious Equipment,No.2025T038(to QC)。
文摘The mechanisms underlying the pathophysiology of ischemic stroke are complex and multifactorial and include excitotoxicity,oxidative stress,inflammatory responses,and blood–brain barrier disruption.While vascular recanalization treatments such as thrombolysis and mechanical thrombectomy have achieved some success,reperfusion injury remains a significant contributor to the exacerbation of brain injury.This emphasizes the need for developing neuroprotective strategies to mitigate this type of injury.The purpose of this review was to examine the application of nanotechnology in the treatment of ischemic stroke,covering research progress in nanoparticlebased drug delivery,targeted therapy,and antioxidant and anti-inflammatory applications.Nanobased drug delivery systems offer several advantages compared to traditional therapies,including enhanced blood–brain barrier penetration,prolonged drug circulation time,improved drug stability,and targeted delivery.For example,inorganic nanoparticles,such as those based on CeO_(2),have been widely studied for their strong antioxidant capabilities.Biomimetic nanoparticles,such as those coated with cell membranes,have garnered significant attention owing to their excellent biocompatibility and targeting abilities.Nanoparticles can be used to deliver a wide range of neuroprotective agents,such as antioxidants(e.g.,edaravone),anti-inflammatory drugs(e.g.,curcumin),and neurotrophic factors.Nanotechnology significantly enhances the efficacy of these drugs while minimizing adverse reactions.Although nanotechnology has demonstrated great potential in animal studies,its clinical application still faces several challenges,including the long-term safety of nanoparticles,the feasibility of large-scale production,quality control,and the ability to predict therapeutic effects in humans.In summary,nanotechnology holds significant promise for the treatment of ischemic stroke.Future research should focus on further exploring the mechanisms of action of nanoparticles,developing multifunctional nanoparticles,and validating their safety and efficacy through rigorous clinical trials.Moreover,interdisciplinary collaboration is essential for advancing the use of nanotechnology in stroke treatment.
基金financially supported by the National Natural Science Foundation of China(Nos.52533015,52495013,52403211,52573183,52273157,52073279 and 52025035)Jilin Province,China(Nos.20250601009RC and 20230508102RC)Youth Innovation Promotion Association of the Chinese Academy of Sciences(No.2022224)。
文摘Given that platinum-based drugs are widely used clinically as chemotherapeutic agents,their severe toxic side effects have attracted significant attention.Consequently,the development of novel nanoprodrugs based on low-toxicity tetravalent platinum(Pt(Ⅳ))com plexes holds substantial research value.Herein,we discovered that coumarin derivatives exhibit inherent antitumor efficacy and significantly enhance superoxide anion radicals(·O_(2)^(-))generation in aqueous solutions under ultrasound(US)irradiation.Given that·O_(2)^(-)is known to mediate the reduction of Pt(Ⅳ)to divalent platinum(Pt(Ⅱ)),we engineered an US-responsive dual-drug nanoprodrug(P-cisPt(Ⅳ)@5-MOP).This nanoprodrug was prepared by covalently conjugating Pt(Ⅳ)and methoxy polyethylene glycol hydroxyl(m PEG-OH)to a poly(_(L)-glutamic acid)(PLG)carrier,followed by encapsulating coumarin derivatives.Under low-intensity US irradiation(1.5 W/cm^(2),1 MHz,10 min),P-cisPt(Ⅳ)@5-MOP achieved a Pt(Ⅳ)reduction rate of 91.4%.Furthermore,upon US exposure,its half-maximal inhibitory concentration(IC_(50))against 4T1 breast cancer cells decreased dramatically from 25.7μmol/L to 0.1μmol/L.Remarkably,this system combined with US therapy yielded a tumor inhibition rate of 90.9%,with 40%of tumor-bea ring mice achieving com plete eradication of tumors,while exhibiting low systemic toxicity.Collectively,this work not only identifies a novel sonosensitizer capable of generating·O_(2)^(-)but also develops a new class of ultrasound-activatable Pt(Ⅳ)nanoprodrug.
基金Supported by Tangshan Science and Technology Planning Project(25150202E).
文摘In recent years,the problem of veterinary drug residues in animal-derived foods has attracted worldwide attention.Developing rapid,simple,highly sensitive,and high-throughput veterinary drug residue detection technologies has become an urgent need.This paper provides a comprehensive review of the pretreatment and analytical techniques for veterinary drug residue analysis,comparing the detection principles,operational procedures,and respective advantages and disadvantages of various detection technologies.It further explores the future development directions of veterinary drug residue detection technologies.
基金funded by the Fundamental Research Funds for the Central Universities (No.2242022R42012)。
文摘In recent years,development of strategies to treat central nervous system(CNS) diseases has attracted extensive attention.A major obstacle in this field is the blood-brain barrier(BBB),which significantly limits the efficient delivery of therapeutic agents to the brain and hinders the treatment of CNS diseases.Overcoming the restrictive nature of the BBB has thus emerged as a key objective in CNS drug development.Nanomaterials have garnered growing interest due to their unique physicochemical properties and potential to traverse the BBB,enabling targeted drug delivery to brain tissue and improving therapeutic efficacy.In this review,we present current insights into the structure and function of the BBB and highlight a range of nanomaterial-based strategies for BBB penetration,including receptor-mediated transport(RMT),adsorptive-mediated transcytosis,reversible BBB disruption,and intranasal administration.Finally,we summarize recent advances in enhancing BBB permeability for CNS therapeutics and discuss persisting challenges,offering perspectives for future research in this field.
基金funded by the Deanship of Scientific Research at King Abdulaziz University,Jeddah,under Grant No.G:534-140-1443.
文摘Objective:To evaluate the effects of a piceatannol-loaded self-nanoemulsifying drug delivery system(PIC-SNEDDS)on wound healing in diabetic rats and its mechanisms of wound healing action.Methods:Diabetes was induced in rats using streptozotocin,after which full-thickness excisional wounds were created.Piceatannol was administered topically either as a raw hydrogel or formulated into a PIC-SNEDDS,which was prepared using an optimized oil-surfactant mixture and incorporated into a hydrogel for application.Wound healing activity was assessed through measurements of wound contraction,oxidative stress biomarkers,and collagen content,along with histological and immunohistochemical evaluation of inflammatory,angiogenic,and remodeling markers.Results:PIC-SNEDDS markedly enhanced diabetic wound healing by promoting epithelial regeneration,granulation tissue formation,epidermal proliferation,and keratinization.The formulation also reduced the expression of pro-inflammatory markers(interleukin-6,nuclear factor-kappa B,and tumor necrosis factor-α)while increasingα-smooth muscle actin,transforming growth factor-β1,vascular endothelial growth factor-A,and hydroxyproline levels.Additionally,it improved antioxidant status by lowering malondialdehyde levels and boosting superoxide dismutase and catalase activity,along with upregulation of COL1A1 mRNA expression.Conclusions:PIC-SNEDDS promotes the healing of diabetic wounds and exhibits anti-inflammatory,antioxidant,pro-collagen,and angiogenic properties.
文摘Objectives:B-cell maturation antigen(BCMA)-targeted antibody–drug conjugates(ADCs)have emerged as promising therapies for relapsed/refractory multiple myeloma(RRMM),but the overall efficacy and safety profile is unclear.This study aimed to synthesize the available evidence on the safety and efficacy of BCMA-ADCs in development for RRMM.Methods:A systematic search was conducted using six bibliographic databases and ClinicalTrials.gov up to November 2024.Studies were eligible if they were human clinical trials or animal studies evaluating BCMA-ADCs and reported efficacy and safety outcomes.Data extraction and quality assessments were conducted using validated tools,including ROBINS-I and SYRCLE’s risk of bias tool.Results:A total of 21 studies were included:16 clinical trials and five animal studies.Key findings included that belantamab mafodotin demonstrated variable but generally durable response rates(32%–85%)and a broad range of progression-free survival(PFS)(2.8–36.6 months),albeit with ocular toxicities in 51%–96%.Among newer candidates,MEDI2228 showed median PFS 5.1–6.6 months with 14%discontinuation for ocular symptoms,while AMG 224 had an overall response rate(ORR)of 23%(9/40)with anemia 21%,thrombocytopenia 24%,and ocular adverse events(AEs)21%.Animal studies supported the tumor-eradicating potential of all BCMA-ADC candidates,although safety signals such as hepatic and renal toxicity were noted with HDP-101.The risk of bias assessment revealed generally moderate to serious concerns in human trials,while the overall quality of the animal studies was acceptable.Conclusions:BCMA-targeted ADC candidates show encouraging efficacy in RRMM,particularly belantamab mafodotin.However,frequent AEs,especially ocular and hematologic toxicities,underscore the need for optimization in ADC design.Further research should prioritize enhancing safety while maintaining clinical benefit.
