Uncontrolled microglial activation is decisively involved in the neuroinflammatory pathogenesis of brain diseases. Consequently, suppression of microglial overactivation appears to be a strategy for the prevention of ...Uncontrolled microglial activation is decisively involved in the neuroinflammatory pathogenesis of brain diseases. Consequently, suppression of microglial overactivation appears to be a strategy for the prevention of nerve injury. In this paper, a novel vanadium complex, vanadyl N-(p-N,Ndimethylaminophenylcarbamoylmethyl)iminodiacetate(VO(p-dmada)), was synthesized from vanadyl sulfate and N,N-dimethyl-p-phenylenediamine, which was structurally characterized by Fourier transform infrared spectrum and ESI-MS analysis. The effect of VO(p-dmada) on neuroinflammation was investigated by using the models of lipopolysaccharide(LPS)-induced BV2 microglial cells and BALB/c mice.Our data demonstrated that VO(p-dmada) significantly suppressed microglial activation by downregulating inflammatory mediators and associated proteins, and inactivating nuclear factor-κ B(NF-κ B) signaling pathway. VO(p-dmada) also upregulated peroxisome proliferator activated receptor gamma(PPARγ) by reducing transglutaminase 2 and heat shock protein 60 expression. Co-treatment with PPARγ antagonist GW9662 significantly impeded the inhibitory effect of VO(p-dmada) on LPS-induced neuroinflammation.These cumulative findings demonstrated that VO(p-dmada) is a potential new drug for the treatment of neuroinflammation-related neurodegenerative diseases.展开更多
Transdermal drug delivery(TDD)systems have evolved,with skin electronics emerging as a technology capable of enabling efficient drug administration.However,conventional skin electronics often rely on rigid materials a...Transdermal drug delivery(TDD)systems have evolved,with skin electronics emerging as a technology capable of enabling efficient drug administration.However,conventional skin electronics often rely on rigid materials and expensive fabrication processes,limiting flexibility and skin-adhesion.In this study,we developed cellulose nanofiber(CNFs)-based adhesive electronics by integrating a three-dimensional octopus-inspired architecture(OIA)and a conductive layer.The OIA imprinted on CNFs enhanced adhesion by leveraging the synergistic effect of its adhesive structure and the ability to remain stable even after absorbing active ingredient solutions.Unlike conventional fiber-based TDD platforms,the optimized CNFs-OIA retains its architecture,enabling suction-based adhesion to improve skin attachment.To further enhance the TDD efficiency,we integrated a conductive layer into the CNFs-OIA.This conductive interface generates microcurrents that reduce the electrical resistance of the stratum corneum and facilitates the ionization of active ingredients,thereby improving skin penetration.展开更多
Future drug discovery and toxicology testing could benefit significantly from more predictive and multi-parametric readouts from in vitro models.Despite the recent advances in the field of microfluidics,and more recen...Future drug discovery and toxicology testing could benefit significantly from more predictive and multi-parametric readouts from in vitro models.Despite the recent advances in the field of microfluidics,and more recently organ-on-a-chip technology,there is still a high demand for real-time monitoring systems that can be readily embedded with microfluidics.In addition,multi-parametric monitoring is essential to improve the predictive quality of the data used to inform clinical studies that follow.Here we present a microfluidic platform integrated with in-line electronic sensors based on the organic electrochemical transistor.Our goals are twofold,first to generate a platform to host cells in a more physiologically relevant environment(using physiologically relevant fluid shear stress(FSS))and second to show efficient integration of multiple different methods for assessing cell morphology,differentiation,and integrity.These include optical imaging,impedance monitoring,metabolite sensing,and a wound-healing assay.We illustrate the versatility of this multi-parametric monitoring in giving us increased confidence to validate the improved differentiation of cells toward a physiological profile under FSS,thus yielding more accurate data when used to assess the effect of drugs or toxins.Overall,this platform will enable high-content screening for in vitro drug discovery and toxicology testing and bridges the existing gap in the integration of in-line sensors in microfluidic devices.展开更多
基金financially supported by grants from the National Natural Science Foundation of China(No.21877081)the China Postdoctoral Science Foundation(No.2021M692210)+2 种基金Guangdong Provincial Key S&T Program(No.2018B030336001)the Shenzhen Science and Technology Innovation Commission(No.JCYJ20200109110001818)the Shenzhen-Hong Kong Institute of brain Science-Shenzhen Fundamental Research institutions(No.2022SHIBS0003)。
文摘Uncontrolled microglial activation is decisively involved in the neuroinflammatory pathogenesis of brain diseases. Consequently, suppression of microglial overactivation appears to be a strategy for the prevention of nerve injury. In this paper, a novel vanadium complex, vanadyl N-(p-N,Ndimethylaminophenylcarbamoylmethyl)iminodiacetate(VO(p-dmada)), was synthesized from vanadyl sulfate and N,N-dimethyl-p-phenylenediamine, which was structurally characterized by Fourier transform infrared spectrum and ESI-MS analysis. The effect of VO(p-dmada) on neuroinflammation was investigated by using the models of lipopolysaccharide(LPS)-induced BV2 microglial cells and BALB/c mice.Our data demonstrated that VO(p-dmada) significantly suppressed microglial activation by downregulating inflammatory mediators and associated proteins, and inactivating nuclear factor-κ B(NF-κ B) signaling pathway. VO(p-dmada) also upregulated peroxisome proliferator activated receptor gamma(PPARγ) by reducing transglutaminase 2 and heat shock protein 60 expression. Co-treatment with PPARγ antagonist GW9662 significantly impeded the inhibitory effect of VO(p-dmada) on LPS-induced neuroinflammation.These cumulative findings demonstrated that VO(p-dmada) is a potential new drug for the treatment of neuroinflammation-related neurodegenerative diseases.
基金support from the National Research Foundation of Korea(RS-2024-00352352)the Market-led K-sensor technology program(RS-2022-00154781,Development of large-area wafer-level flexible/stretchable hybrid sensor platform technology for form factor-free highly integrated convergence sensor),funded By the Ministry of Trade,Industry&Energy(MOTIE,Korea)+1 种基金support of the industry-academia cooperation research of Mimetics Co.,Ltdsupported by theSungKyunKwanUniversity and the BK21 FOUR(Graduate School Innovation)funded by the Ministry of Education(MOE,Korea)and National Research Foundation of Korea(NRF)。
文摘Transdermal drug delivery(TDD)systems have evolved,with skin electronics emerging as a technology capable of enabling efficient drug administration.However,conventional skin electronics often rely on rigid materials and expensive fabrication processes,limiting flexibility and skin-adhesion.In this study,we developed cellulose nanofiber(CNFs)-based adhesive electronics by integrating a three-dimensional octopus-inspired architecture(OIA)and a conductive layer.The OIA imprinted on CNFs enhanced adhesion by leveraging the synergistic effect of its adhesive structure and the ability to remain stable even after absorbing active ingredient solutions.Unlike conventional fiber-based TDD platforms,the optimized CNFs-OIA retains its architecture,enabling suction-based adhesion to improve skin attachment.To further enhance the TDD efficiency,we integrated a conductive layer into the CNFs-OIA.This conductive interface generates microcurrents that reduce the electrical resistance of the stratum corneum and facilitates the ionization of active ingredients,thereby improving skin penetration.
基金V.F.C.acknowledges support from a Marie Curie post-doctoral fellowship FP7-PEOPLE-2013-IEF,Project No.624673A.-M.P.and M.B.acknowledge support from Marie Curie ITN OrgBIO Project No.607896.
文摘Future drug discovery and toxicology testing could benefit significantly from more predictive and multi-parametric readouts from in vitro models.Despite the recent advances in the field of microfluidics,and more recently organ-on-a-chip technology,there is still a high demand for real-time monitoring systems that can be readily embedded with microfluidics.In addition,multi-parametric monitoring is essential to improve the predictive quality of the data used to inform clinical studies that follow.Here we present a microfluidic platform integrated with in-line electronic sensors based on the organic electrochemical transistor.Our goals are twofold,first to generate a platform to host cells in a more physiologically relevant environment(using physiologically relevant fluid shear stress(FSS))and second to show efficient integration of multiple different methods for assessing cell morphology,differentiation,and integrity.These include optical imaging,impedance monitoring,metabolite sensing,and a wound-healing assay.We illustrate the versatility of this multi-parametric monitoring in giving us increased confidence to validate the improved differentiation of cells toward a physiological profile under FSS,thus yielding more accurate data when used to assess the effect of drugs or toxins.Overall,this platform will enable high-content screening for in vitro drug discovery and toxicology testing and bridges the existing gap in the integration of in-line sensors in microfluidic devices.
