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The urgent need for sensitive and accurate assays to monitor acetylcholinesterase (AChE) activity and organophosphorus pesticides (OPs) arises from the imperative to safeguard human health and protect the ecosystem. Due to its cost-effectiveness, ease of operation, and rapid response, nanozyme-based colorimetry has been widely utilized in the determination of AChE activity and OPs. However, the rational design of nanozymes with high activity and specificity remains a great challenge. Herein, trace amount of Bi-doped core-shell Pd@Pt mesoporous nanospheres (Pd@PtBi2) have been successfully synthesized, exhibiting good peroxidase-like activity and specificity. With the incorporation of trace bismuth, there is a more than 4-fold enhancement in the peroxidase-like performance of Pd@PtBi2 compared to that of Pd@Pt. Besides, no significant improvement of oxidase-like and catalase-like activities of Pd@PtBi2 was found, which prevents interference from O2 and undesirable consumption of substrate H2O2. Based on the blocking impact of thiocholine, a colorimetric detection platform utilizing Pd@PtBi2 was constructed to monitor AChE activity with sensitivity and selectivity. Given the inhibition of OPs on AChE activity, a biosensor was further developed by integrating Pd@PtBi2 with AChE to detect OPs, capitalizing on the cascade amplification strategy. The OP biosensor achieved a detection limit as low as 0.06 ng mL-1, exhibiting high sensitivity and anti-interference ability. This work is promising for the construction of nanozymes with high activity and specificity, as well as the development of nanozyme-based colorimetric biosensors.
Assuntos
Técnicas Biossensoriais , Nanosferas , Agentes Neurotóxicos , Praguicidas , Humanos , Acetilcolinesterase/metabolismo , Compostos Organofosforados , Praguicidas/análise , Peróxido de Hidrogênio , Ecossistema , Oxirredutases , Peroxidase , ColorimetriaRESUMO
Microglia are resident immune cells in the central nervous system, playing critical roles in brain development and homeostasis. Increasing evidence has implicated microglia dysfunction in the pathogenesis of various brain disorders ranging from psychiatric disorders to neurodegenerative diseases. Using a human cell-based model to illuminate the functional mechanisms of microglia will promote pathological studies and drug development. The recently developed microglia-containing human brain organoids (MC-HBOs), in-vitro three-dimensional cell cultures that recapitulate key features of the human brain, have provided a new avenue to model brain development and pathology. However, MC-HBOs generated from different methods differ in the origin, proportion, and fidelity of microglia within the organoids, and may have produced inconsistent results. To help researchers to develop a robust and reproducible model that recapitulates in-vivo signatures of human microglia to study brain development and pathology, this review summarized the current methods used to generate MC-HBOs and provided opinions on the use of MC-HBOs for disease modeling and functional studies.
Assuntos
Microglia , Doenças Neurodegenerativas , Humanos , Microglia/fisiologia , Encéfalo/patologia , Sistema Nervoso Central/fisiologia , Organoides/patologiaRESUMO
Effective glucose surveillance provides a strong guarantee for the high-quality development of human health. Au nanomaterials possess compelling applications in nonenzymatic electrochemical glucose biosensors owing to superior catalytic performances and intriguing biocompatibility properties. However, it has been a grand challenge to accurately control the architecture and composition of Au nanomaterials to optimize their optical, electronic, and magnetic properties for further improving the performance of electrocatalytic sensing. Herein, ultra-low content Bi-anchored Au aerogels are synthesized via a one-step reduction strategy. Benefiting from the unique structure of aerogels as well as the synergistic effect between Au and Bi, the optimized Au200Bi aerogels greatly boost the activity of glucose oxidation compared with Au aerogels. Under plasmon resonance excitation, bimetallic Au200Bi aerogels with wider photics-dependent properties further show plasmon-promoted glucose electro-oxidation activity, which is derived from the photothermal and photoelectric effects caused by the local surface plasmon resonance. Thanks to the enhanced performance, a nonenzymatic electrochemical glucose biosensor is constructed to detect glucose with high sensitivity. This plasmon-promoted electrocatalytic activity through the synergetic strategy of bimetallic aerogels has potential applications in various research fields.
Assuntos
Técnicas Biossensoriais , Ouro , Bismuto , Catálise , Técnicas Eletroquímicas , Glucose , Ouro/química , HumanosRESUMO
Development of highly sensitive biosensors has received ever-increasing attention over the years. Due to the unique physicochemical properties, the functional nanomaterial-enabled signal amplification strategy has made some great breakthroughs in biosensing. However, the sensitivity and selectivity still need further improvement. Single-atom catalysts (SACs) containing atomically dispersed metal active sites demonstrate distinctive advantages in catalytic activity and selectivity for various catalytic reactions. As a consequence, the SAC-enabled signal amplification strategy holds great promise in biosensors, demonstrating satisfactory sensitivity and selectivity with the assistance of tunable metal-support interactions, coordination environments and geometric/electronic structures of active sites. In this tutorial review, we briefly discuss the structural advantages of SACs. Then, the catalytic mechanism at the atomic scale and signal amplification effects of SACs in the colorimetric, electrochemical, chemiluminescence, electrochemiluminescence, and photoelectrochemical biosensing applications are highlighted in detail. Finally, opportunities and challenges to be faced in the future development of the SAC-enabled signal amplification strategy for biosensing are discussed and outlooked.
Assuntos
Técnicas Biossensoriais , Carbono/química , Metais Pesados/química , Nanoestruturas/química , Catálise , SemicondutoresRESUMO
Benefiting from the maximum atom-utilization efficiency and distinct structural features, single-atom catalysts open a new avenue for the design of more functional catalysts, whereas their bioapplications are still in their infancy. Due to the advantages, platinum single atoms supported by cadmium sulfide nanorods (Pt SAs-CdS) are synthesized to build an ultrasensitive photoelectrochemical (PEC) biosensing platform. With the decoration of Pt SAs, the PEC signal of CdS is significantly boosted. Furthermore, theory calculations indicate the positively charged Pt SAs could change the charge distribution and increase the excited carrier density of CdS. Meanwhile, it also suggests that Cu2+ can severely hinder the photoexcitation and electron-hole separation of CdS. As a proof of concept, prostate-specific antigen is chosen as the target analyte to demonstrate the superiority of the Pt SAs-CdS-based PEC sensing system. As a result, the PEC biosensor based on Pt SAs-CdS exhibits outstanding detection sensitivity and promising applicability.
Assuntos
Técnicas Biossensoriais , Nanotubos , Técnicas Eletroquímicas , Humanos , Imunoensaio , Limite de Detecção , MasculinoRESUMO
Although single-atom catalysts with high enzyme-like activities have been found, the rational design of highly active peroxidase (POD)-like nanozymes is still a formidable challenge. Herein, highly active POD-like nanozymes were synthesized through loading Pt clusters on the Fe single-atom (FeSA-PtC) nanozymes. The POD-like activity of FeSA-PtC nanozymes is enhanced 4.5-fold and 7-fold, in comparison to that of FeSA and PtC nanozymes, respectively, which is attributed to the unexpected synergistic effect between Fe single atoms and Pt clusters. Based on the outstanding POD-like activity of FeSA-PtC nanozymes, a cascade signal amplification strategy was constructed by combining glucose oxidase for the colorimetric biosensing of prostate-specific antigens, exhibiting satisfactory sensitivity, high selectivity, a low detection limit of 1.8 pg/mL, and practical feasibility in serum sample detection. This work may serve as a tough foundation to guide the design of superior POD-like nanozymes and expand the application in biosensing.
Assuntos
Técnicas Biossensoriais , Colorimetria , Peróxido de Hidrogênio , Imunoensaio , PeroxidasesRESUMO
The rational construction of advanced sensing platforms to sensitively detect H2O2 produced by living cells is one of the challenges in both physiological and pathological fields. Owing to the extraordinary catalytic performances and similar metal coordination to natural metalloenzymes, single atomic site catalysts (SASCs) with intrinsic peroxidase (POD)-like activity have shown great promise for H2O2 detection. However, there still exists an obvious gap between them and natural enzymes because of the great challenge in rationally modulating the electronic and geometrical structures of central atoms. Note that the deliberate modulation of the metal-support interaction may give rise to the promising catalytic activity. In this work, an extremely sensitive electrochemical H2O2 biosensor based on single atomic Fe sites coupled with carbon-encapsulated Fe3C crystals (Fe3C@C/Fe-N-C) is proposed. Compared with the conventional Fe SASCs (Fe-N-C), Fe3C@C/Fe-N-C exhibits superior POD-like activity and electrochemical H2O2 sensing performance with a high sensitivity of 1225 µA/mM·cm2, fast response within 2 s, and a low detection limit of 0.26 µM. Significantly, sensitive monitoring of H2O2 released from living cells is also achieved. Moreover, the density functional theory calculations reveal that the incorporated Fe3C nanocrystals donate electrons to single atomic Fe sites, endowing them with improved activation ability of H2O2 and further enhancing the overall activity. This work provides a new design of synergistically enhanced single atomic sites for electrochemical sensing applications.
Assuntos
Técnicas Biossensoriais , Peróxido de Hidrogênio , Carbono , Catálise , OxirreduçãoRESUMO
Though nanozymes are successfully applied in various areas, the increasing demands facilitate the exploitation of nanozymes possessing higher activity and more functions. Natural enzyme-linked receptors (ELRs) are critical components for signal transductions in vivo by expressing activity variations after binding with ligands. Inspired by this, the defect-engineered carbon nitrides (DCN) are reported to serve as nanozyme-linked receptors (NLRs). For one thing, cyano defects increase the enzyme-like activity by a factor of 109.5. For another, DCN-based NLRs are constructed by employing cyano groups as receptors, and variable outputs are ensued upon the addition of ion ligands. Significantly, both the cascade effect and electronic effect are demonstrated to contribute to this phenomenon. Finally, NLRs are used for pattern recognition of metal ions, indicating the signal transduction ability of NLRs as well. This work not only provides great promise of defect engineering in nanozymes, but also contributes to the design of artificial ELRs.
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Design of highly active carbon nanozymes and further establishment of ultrasensitive biosensors remain a challenge. Herein, hierarchically porous carbon nanozymes with sulfur (S)/nitrogen (N) codoping (SNC) were developed. Compared with N-doped carbon (NC) nanozymes, SNC nanozymes have a smaller Michaelis-Menten constant and higher specific activities, demonstrating that the S-doping in SNC nanozymes could not only enhance their affinity toward substrates but also improve their catalytic performance. These results may be caused by the synergistic effect of heteroatoms (S and N). Because of the good enzyme-like activity, the proposed SNC nanozymes were exploited to the colorimetric detection of the total antioxidant capacity (TAC) using ascorbic acid as a typical model with a limit of detection of 0.08 mM. Because of its high sensitivity and selectivity and encouraging performance, the detection method presented practical feasibility for the TAC assay in commercial beverages. This work paves a way to design the highly active carbon nanozymes and expand their applications in the construction of high-performance biosensors.
Assuntos
Antioxidantes/análise , Ácido Ascórbico/análise , Técnicas Biossensoriais , Carbono/química , Nanoestruturas/química , Peroxidase/química , Antioxidantes/metabolismo , Ácido Ascórbico/metabolismo , Nitrogênio/química , Tamanho da Partícula , Peroxidase/metabolismo , Porosidade , Enxofre/química , Propriedades de SuperfícieRESUMO
Nanomaterials with enzyme-like activities, coined nanozymes, have been researched widely as they offer unparalleled advantages in terms of low cost, superior activity, and high stability. The complex structure and composition of nanozymes has led to extensive investigation of their catalytic sites at an atomic scale, and to an in-depth understanding of the biocatalysis occurring. Single-atom catalysts (SACs), characterized by atomically dispersed active sites, have provided opportunities for mimicking metalloprotease and for bridging the gap between natural enzymes and nanozymes. In this Minireview, we illustrate the unique properties of nanozymes and we discuss recent advances in the synthesis, characterization, and applications of SACs. Subsequently, we outline the impressive progress made in single-atom nanozymes and we discuss their applications in sensing, degradation of organic pollutants, and in therapeutic roles. Finally, we present the major challenges and opportunities remaining for a successful marriage of nanozymes and SACs.
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Materiais Biomiméticos/química , Nanoestruturas/química , CatáliseRESUMO
Recently, in situ detection of hydrogen peroxide (H2O2) generated from live cells have caused tremendous attention, because it is of great significance in the control of multiple biological processes. Herein, Fe-N-C single-atom nanozymes (Fe-N-C SAzymes) with intrinsic peroxidase-like activity were successfully prepared via high-temperature calcination using FeCl2, glucose, and dicyandiamide as precursors. The Fe-N-C SAzymes with FeNx as active sites were similar to natural metalloproteases, which can specifically enhance the peroxidase-like activity rather than oxidase-like activity. Accordingly, owing to the excellent catalytic efficiency of the Fe-N-C SAzymes, colorimetric biosensing of H2O2 in vitro was performed via a typical 3,3',5,5'-tetramethylbenzidine induced an allochroic reaction, demonstrating the satisfactory specificity and sensitivity. With regard to the practical application, in situ detection of H2O2 generated from the Hela cells by the Fe-N-C SAzymes was also performed, which can expand the applications of the newborn SAzymes.
Assuntos
Carbono/química , Peróxido de Hidrogênio/análise , Ferro/química , Nanocompostos/química , Nitrogênio/química , Células HeLa , HumanosRESUMO
Improvement in the sensitivity and portability of enzyme-linked immunosorbent assay (ELISA) still faced huge challenges recently. Inspired by the nanoprecipitation process for the carrier-free nanodrug in drug delivery systems, we developed an self-assembly strategy to prepare a kind of all-inclusive allochroic 3,3',5,5'-tetramethylbenzidine (TMB) nanoparticles for developing improved ELISA (named TLISA). During the self-assembly of TMB molecules, the antibody as signal recognition units and bovine serum albumin as the stabilizing agents could be accommodated simultaneously through hydrogen-bonding and van der Waals interactions to form all-inclusive signal tags, which can avoid the complex cross-linking procedures. Due to the ultrahigh loading capacity (817 mg/g) of TMB molecules, the sensitivity of TLISA toward inflammatory biomarkers interleukin-6 was 11.82 times higher than that of conventional ELISA, which paves an avenue to develop an ultrasensitive colorimetric immunoassay.
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Benzidinas/química , Interleucina-6/sangue , Nanopartículas/química , Soroalbumina Bovina/química , Ensaio de Imunoadsorção Enzimática , Humanos , Nanopartículas/metabolismo , Soroalbumina Bovina/metabolismoRESUMO
Single-atom catalysts (SACs) have attracted extensive attention in the catalysis field because of their remarkable catalytic activity, gratifying stability, excellent selectivity, and 100% atom utilization. With atomically dispersed metal active sites, Fe-N-C SACs can mimic oxidase by activating O2 into reactive oxygen species, O2- ⢠radicals. Taking advantages of this property, single-atom nanozymes (SAzymes) can become a great impetus to develop novel biosensors. Herein, the performance of Fe-N-C SACs as oxidase-like nanozymes is explored. Besides, the Fe-N-C SAzymes are applied in biosensor areas to evaluate the activity of acetylcholinesterase based on the inhibition toward nanozyme activity by thiols. Moreover, this SAzymes-based biosensor is further used for monitoring the amounts of organophosphorus compounds.
Assuntos
Acetilcolinesterase/análise , Carbono/química , Ferro/química , Nanoestruturas/química , Nitrogênio/química , Oxirredutases/metabolismo , Acetiltiocolina/metabolismo , Animais , Nanoestruturas/ultraestrutura , Espectrofotometria UltravioletaRESUMO
Purpose: Spinal cord injury (SCI) is an incurable and disabling event that is accompanied by complex inflammation-related pathological processes, such as the production of excessive reactive oxygen species (ROS) by infiltrating inflammatory immune cells and their release into the extracellular microenvironment, resulting in extensive apoptosis of endogenous neural stem cells. In this study, we noticed the neuroregeneration-promoting effect as well as the ability of the innovative treatment method of FTY720-CDs@GelMA paired with NSCs to increase motor function recovery in a rat spinal cord injury model. Methods: Carbon dots (CDs) and fingolimod (FTY720) were added to a hydrogel created by chemical cross-linking GelMA (FTY720-CDs@GelMA). The basic properties of FTY720-CDs@GelMA hydrogels were investigated using TEM, SEM, XPS, and FTIR. The swelling and degradation rates of FTY720-CDs@GelMA hydrogels were measured, and each group's ability to scavenge reactive oxygen species was investigated. The in vitro biocompatibility of FTY720-CDs@GelMA hydrogels was assessed using neural stem cells. The regeneration of the spinal cord and recovery of motor function in rats were studied following co-treatment of spinal cord injury using FTY720-CDs@GelMA hydrogel in combination with NSCs, utilising rats with spinal cord injuries as a model. Histological and immunofluorescence labelling were used to determine the regeneration of axons and neurons. The recovery of motor function in rats was assessed using the BBB score. Results: The hydrogel boosted neurogenesis and axonal regeneration by eliminating excess ROS and restoring the regenerative environment. The hydrogel efficiently contained brain stem cells and demonstrated strong neuroprotective effects in vivo by lowering endogenous ROS generation and mitigating ROS-mediated oxidative stress. In a follow-up investigation, we discovered that FTY720-CDs@GelMA hydrogel could dramatically boost NSC proliferation while also promoting neuronal regeneration and synaptic formation, hence lowering cavity area. Conclusion: Our findings suggest that the innovative treatment of FTY720-CDs@GelMA paired with NSCs can effectively improve functional recovery in SCI patients, making it a promising therapeutic alternative for SCI.
Assuntos
Cloridrato de Fingolimode , Hidrogéis , Células-Tronco Neurais , Ratos Sprague-Dawley , Traumatismos da Medula Espinal , Animais , Traumatismos da Medula Espinal/tratamento farmacológico , Traumatismos da Medula Espinal/terapia , Cloridrato de Fingolimode/farmacologia , Cloridrato de Fingolimode/química , Cloridrato de Fingolimode/administração & dosagem , Células-Tronco Neurais/efeitos dos fármacos , Hidrogéis/química , Hidrogéis/farmacologia , Hidrogéis/administração & dosagem , Ratos , Recuperação de Função Fisiológica/efeitos dos fármacos , Espécies Reativas de Oxigênio/metabolismo , Pontos Quânticos/química , Modelos Animais de Doenças , Feminino , Medula Espinal/efeitos dos fármacosRESUMO
In order to not only improve the stability of nanomicelles in blood circulation but also promote the cellular uptake in tumors and rapidly release the encapsulated drugs in tumor cells, a kind of acid/reduction dual-sensitive amphiphilic graft polyurethane with folic acid and detachable poly(ethylene glycol) (FA-PUSS-gimi-mPEG) was synthesized by grafting folic acid and monomethoxy poly(ethylene glycol) to the polyurethane side chain. FA-PUSS-gimi-mPEG could self-assemble in aqueous solution to form negatively charged nanomicelles, which endowed them good stability under normal physiological condition. Using ultraviolet-visible spectrometer (UV-vis) and dynamic light scattering (DLS), it was found that the hydrophilic poly(ethylene glycol) layer of FA-PUSS-gimi-mPEG micelles could be detached due to the cleavage of benzoic-imine bond under slightly acidic condition, which resulted in reversing the charge of the micellar surface and exposing folic acid to the micellar surface. FA-PUSS-gimi-mPEG micelles could load doxorubicin (DOX), moreover the drug release rate was faster at pH 5.0 and 10 mM glutathione (GSH) than that under normal physiological condition. The results of cell experiments further demonstrated that FA-PUSS-gimi-mPEG micelles had acid/reduction dual-sensitive property. The changes in the structure of FA-PUSS-gimi-mPEG micelles could enhance the cellular uptake under acid condition and the micelles could accelerate the drug release in tumor cells due to the presence of disulfide bonds in the polymer. Therefore, FA-PUSS-gimi-mPEG micelles could efficiently deliver anticancer drug into tumor cells and enhance the inhibition of cellular proliferation through multi-effect synergy.
Assuntos
Antineoplásicos , Poliuretanos , Poliuretanos/farmacologia , Micelas , Ácido Fólico/farmacologia , Ácido Fólico/química , Antineoplásicos/farmacologia , Antineoplásicos/química , Polietilenoglicóis/química , Doxorrubicina/farmacologia , Doxorrubicina/química , Portadores de Fármacos/química , Sistemas de Liberação de Medicamentos , Sobrevivência CelularRESUMO
Identifying genes whose expression is associated with schizophrenia (SCZ) risk by transcriptome-wide association studies (TWAS) facilitates downstream experimental studies. Here, we integrated multiple published datasets of TWAS (including FUSION, PrediXcan, summary-data-based Mendelian randomization (SMR), joint-tissue imputation approach with Mendelian randomization (MR-JTI)), gene coexpression, and differential gene expression analysis to prioritize SCZ candidate genes for functional study. Convergent evidence prioritized Propionyl-CoA Carboxylase Subunit Beta ( PCCB ), a nuclear-encoded mitochondrial gene, as an SCZ risk gene. However, the PCCB â™s contribution to SCZ risk has not been investigated before. Using dual luciferase reporter assay, we identified that SCZ-associated SNP rs35874192, an eQTL SNP for PCCB , showed differential allelic effects on transcriptional activities. PCCB knockdown in human forebrain organoids (hFOs) followed by RNA-seq revealed dysregulation of genes enriched with multiple neuronal functions including gamma-aminobutyric acid (GABA)-ergic synapse, as well as genes dysregulated in postmortem brains of SCZ patients or in cerebral organoids derived from SCZ patients. The metabolomic and mitochondrial function analyses confirmed the deceased GABA levels resulted from reduced tricarboxylic acid cycle in PCCB knockdown hFOs. Multielectrode array recording analysis showed that PCCB knockdown in hFOs resulted into SCZ-related phenotypes including hyper-neuroactivities and decreased synchronization of neural network. In summary, this study utilized hFOs-based multi-omics data and revealed that PCCB downregulation may contribute to SCZ risk through regulating GABAergic system, highlighting the mitochondrial function in SCZ.
RESUMO
Identifying genes whose expression is associated with schizophrenia (SCZ) risk by transcriptome-wide association studies (TWAS) facilitates downstream experimental studies. Here, we integrated multiple published datasets of TWAS, gene coexpression, and differential gene expression analysis to prioritize SCZ candidate genes for functional study. Convergent evidence prioritized Propionyl-CoA Carboxylase Subunit Beta (PCCB), a nuclear-encoded mitochondrial gene, as an SCZ risk gene. However, the PCCB's contribution to SCZ risk has not been investigated before. Using dual luciferase reporter assay, we identified that SCZ-associated SNPs rs6791142 and rs35874192, two eQTL SNPs for PCCB, showed differential allelic effects on transcriptional activities. PCCB knockdown in human forebrain organoids (hFOs) followed by RNA sequencing analysis revealed dysregulation of genes enriched with multiple neuronal functions including gamma-aminobutyric acid (GABA)-ergic synapse. The metabolomic and mitochondrial function analyses confirmed the decreased GABA levels resulted from inhibited tricarboxylic acid cycle in PCCB knockdown hFOs. Multielectrode array recording analysis showed that PCCB knockdown in hFOs resulted into SCZ-related phenotypes including hyper-neuroactivities and decreased synchronization of neural network. In summary, this study utilized hFOs-based multi-omics analyses and revealed that PCCB downregulation may contribute to SCZ risk through regulating GABAergic pathways, highlighting the mitochondrial function in SCZ.
Assuntos
Carbono-Carbono Ligases , Multiômica , Esquizofrenia , Humanos , Metabolômica , Organoides , Prosencéfalo , Esquizofrenia/genética , Carbono-Carbono Ligases/genéticaRESUMO
Reactive oxygen species (ROS)-involved tumor therapeutic strategy, chemodynamic therapy (CDT), has attracted extensive research interest in the scientific community. However, the therapeutic effect of CDT is insufficient and unsustainable owing to the limited endogenous H2 O2 level in the tumor microenvironment. Here, peroxidase (POD)-like RuTe2 nanozyme with the immobilization of glucose oxidase (GOx) and allochroic 3,3',5,5'-tetramethylbenzidine (TMB) molecule have been synthesized to construct RuTe2 -GOx-TMB nanoreactors (RGT NRs) as cascade reaction systems for tumor-specific and self-replenishing cancer therapy. GOx in sequential nanocatalysts can effectively deplete glucose in tumor cells. Meanwhile, a sustainable supply of H2 O2 for subsequent Fenton-like reactions catalyzed by RuTe2 nanozyme is achieved in response to the mild acidic tumor microenvironment. Through this cascade reaction, highly toxic hydroxyl radicals (·OH) are produced, which can further oxidize TMB to trigger tumor-specific "turn-on" photothermal therapy (PTT). In addition, PTT and massive ROS can stimulate the tumor immune microenvironment and activate the systematic anti-tumor immune responses, exerting a notable effect on hindering tumor recurrence and metastasis. This study paves a promising paradigm for synergistic starvation therapy, PTT, and CDT cancer therapy with high efficiency.
Assuntos
Neoplasias , Humanos , Espécies Reativas de Oxigênio , Neoplasias/tratamento farmacológico , Glucose , Glucose Oxidase/uso terapêutico , Peroxidase , Microambiente Tumoral , Peróxido de Hidrogênio , Linhagem Celular TumoralRESUMO
Effective strategies are needed to prevent the development of neuroinflammation, which is associated with nervous system disease,\\r\\nin patients. A previous study indicated that mitochonic acid 5 (MA5) may promote the survival of microglial cells via mitofusin 2 (Mfn2)associated mitophagy in response to lipopolysaccharide (LPS)induced inflammation. The current study investigated the role and underlying mechanisms of MA5 in the migration of BV2 cells following LPSmediated inflammation. The results of the present study revealed that MA5 promoted migration and upregulated the expression of Factin, CXC motif chemokine receptor (CXCR) 4 and CXCR7 in BV2 cells in response to LPSinduced inflammation. The results also indicate that MA5 did not promote migration or upregulate the expression of Factin, CXCR4 or CXCR7 following the inhibition of Mfn2. Overall, the results of the present study suggest that MA5 may promote the migration of microglial cells via Mfn2associated mitophagy following LPSinduced inflammation.
Assuntos
GTP Fosfo-Hidrolases , Microglia , Animais , Camundongos , Actinas/metabolismo , GTP Fosfo-Hidrolases/metabolismo , Inflamação/induzido quimicamente , Inflamação/metabolismo , Lipopolissacarídeos/toxicidade , Microglia/metabolismo , Mitofagia , Movimento CelularRESUMO
In the era of high-speed trains, it is very important to ensure the safety and stability of rail tracks under adverse conditions including seasonal freezing and thawing. Freeze-thaw cycles (FTCs) affecting the engineering performance of coarse-grained soil (CGS) is one of the major reasons for track deterioration. The reported results of a number of static freeze-thaw triaxial tests on the shear behaviour of CGS are analysed herein. It was observed that confining pressure (σ3) and FTCs have a significant influence on the shear behaviour of CGS. In this paper, an empirical mathematical model has been proposed to capture the dilatancy of CGS subjected to FTCs during shearing. The empirical constants a, b, and c proposed in the model are a function of σ3 and FTCs. The results of the model have been compared with the laboratory experiments and are found to be in good agreement.