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The rapidly changing climate is exacerbating the environmental stress that negatively impacts crop health and yield. Timely sensing of plant response to stress is beneficial to timely adjust planting conditions, promoting the healthy growth of plants, and improving plant productivity. Hydrogen peroxide (H2O2) is an important molecule of signal transduction in plants. However, the common methods for detecting H2O2 in plants are associated with certain drawbacks, such as long extraction time, cumbersome steps, dependence on large instruments, and difficulty in realizing in-field sensing. Therefore, it is urgent to establish more efficient detection methods to realize the rapid detection of H2O2 content in plants. In this research, poly (methyl vinyl ether-alt-maleic acid) (PMVE/MA) hydrogel microneedle (MN) patch for rapid extraction of leaf sap are prepared, and the extraction mechanism of PEG-crosslinked PMVE/MA hydrogel MN patch is studied. A method of rapid detection of H2O2 content in plants based on MN patch with optical detection technology is constructed. The hydrogel MN patch can be used for timely H2O2 analysis. This application enables new opportunities in plant engineering, and can be extended to the safety and health monitoring of other plants and animals.
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Electroporation is a proven technique that can record action potential of cardiomyocytes and serve for biomolecular delivery. To ensure high cell viability, micro-nanodevices cooperating with low-voltage electroporation are frequently utilized in research, and the effectiveness of delivery for intracellular access is typically assessed using an optical imaging approach like flow cytometry. However, the efficiency of in situ biomedical studies is hampered by the intricacy of these analytical approaches. Here, we develop an integrated cardiomyocyte-based biosensing platform to effectively record action potential and evaluate the electroporation quality in terms of viability, delivery efficiency, and mortality. The ITO-MEA device of the platform possesses sensing/stimulating electrodes which combines with the self-developed system to achieve intracellular action potential recording and delivery by electroporation trigger. Moreover, the image acquisition processing system analyzes various parameters effectively to assess delivery performance. Therefore, this platform has the potential for drug delivery therapy and pathology research for cardiology.
Assuntos
Eletroporação , Miócitos Cardíacos , Terapia com Eletroporação , Eletrodos , Sobrevivência CelularRESUMO
BACKGROUND: Mesenchymal stem cell (MSC)-derived exosomes play significant roles in ameliorating cardiac damage after myocardial ischemia-reperfusion (I/R) injury. Long non-coding RNA alpha-2-macroglobulin antisense RNA 1 (Lnc A2M-AS1) was found that might protect against myocardial I/R. However, whether Lnc A2M-AS1 delivery via MSC-derived exosomes could also regulate myocardial I/R injury remains unknown. METHODS: Exosomes were isolated by ultracentrifugation, and qualified by transmission electron microscopy (TEM), nanoparticle tracking analysis (NTA), and Western blot. Hypoxia/reoxygenation (H/R) treatment in human cardiomyocytes was used to mimic the process of myocardial I/R in vitro. The viability and apoptosis of cardiomyocytes were detected using cell counting kit-8, flow cytometry, and Western blot assays. The contents of lactate dehydrogenase (LDH), malondialdehyde (MDA), and superoxide dismutase (SOD) were evaluated using corresponding commercial kits. The quantitative real-time polymerase chain reaction and Western blot were used to determine the expression levels of Lnc A2M-AS1, microRNA (miR)-556-5p, and X-linked inhibitor of apoptosis protein (XIAP). The binding interaction between miR-556-5p and Lnc A2M-AS1 or XIAP was confirmed by the dual-luciferase reporter, RIP and pull-down assays. RESULTS: Exosomes isolated from hMSCs (hMSCs-exo) attenuated H/R-induced apoptosis and oxidative stress in cardiomyocytes. Lnc A2M-AS1 was lowly expressed in AMI patients and H/R-induced cardiomyocytes. Besides, Lnc A2M-AS1 was detectable in hMSCs-exo, exosomes derived from Lnc A2M-AS1-transfected hMSCs weakened H/R-induced apoptosis and oxidative stress, and enhanced the protective action of hMSCs-exo on H/R-induced cardiomyocytes. Further mechanism analysis showed that Lnc A2M-AS1 acted as a sponge for miR-556-5p to increase XIAP expression level. Importantly, miR-556-5p overexpression or XIAP knockdown reversed the action of exosomal Lnc A2M-AS1 on H/R-induced cardiomyocytes. CONCLUSION: Lnc A2M-AS1 delivery via MSC-derived exosomes ameliorated H/R-induced cardiomyocyte apoptosis and oxidative stress via regulating miR-556-5p/XIAP, opening a new window into the pathogenesis of myocardial I/R injury.
Assuntos
Exossomos , Células-Tronco Mesenquimais , MicroRNAs , Traumatismo por Reperfusão Miocárdica , RNA Longo não Codificante , Humanos , MicroRNAs/genética , MicroRNAs/metabolismo , Miócitos Cardíacos/metabolismo , RNA Longo não Codificante/genética , RNA Longo não Codificante/metabolismo , RNA Antissenso/metabolismo , Apoptose , Hipóxia , Estresse Oxidativo , Traumatismo por Reperfusão Miocárdica/genética , Traumatismo por Reperfusão Miocárdica/prevenção & controle , Traumatismo por Reperfusão Miocárdica/metabolismo , Reperfusão , Células-Tronco Mesenquimais/metabolismo , Células-Tronco Mesenquimais/patologia , Exossomos/genética , Exossomos/metabolismo , Exossomos/patologia , alfa-Macroglobulinas/metabolismoRESUMO
Inflammatory bowel disease (IBD) is a worldwide issue, and the increased incidence has brought a heavy burden to patients and society. Gut microbiota is involved in the pathogenesis of IBD, and targeting the microbiota, such as probiotics, has emerged as a potential therapy for the treatment of IBD. Here, the effect of Bifidobacterium animalis ssp. lactis LKM512 (LKM512), an anti-aging probiotic, on dextran sulfate sodium salt (DSS)-induced IBD in larval zebrafish was determined. Supplementation of LKM512 promoted the survival rate of the larvae, together with increased locomotor activities and body length. In addition, LKM512 treatment enhanced mucus secretion and alleviated intestinal injury, and these results were associated with the upregulation of mucin-related and downregulation of inflammatory markers. Moreover, LKM512 increased the diversity of the microbiota and ameliorated the dysbiosis by increasing the abundance of Bacteroidetes and Firmicutes and reducing the abundance of Proteobacteria. Specifically, the abundance of beneficial bacteria, including the short-chain fatty-acids (SCFAs)-producing genera Lachnospiraceae_NK4A136_group, Muribaculaceae, and Alloprevotella, was increased by LKM512, while the abundance of harmful genera, such as Pseudomonas, Halomonas, and Escherichia-Shigella, was reduced by LKM512. Consistent with these findings, the microbial functions related to metabolism were partly reversed by LKM512, and importantly, fermentation of short-chain fatty acids-related functions were enhanced by LKM512. Therefore, LKM512 might be one potential probiotic for the prevention and treatment of IBD, and further studies that clarify the mechanism of LKM512 would promote the application of LKM512.
Assuntos
Bifidobacterium animalis , Doenças Inflamatórias Intestinais , Microbiota , Animais , Humanos , Peixe-Zebra , Bifidobacterium/metabolismo , Fezes/microbiologia , Doenças Inflamatórias Intestinais/tratamento farmacológico , Sulfato de DextranaRESUMO
Cerebral ischaemia/reperfusion (I/R) injury is caused by blood flow restoration after an ischaemic insult, and effective treatments targeting I/R injury are still insufficient. Oxidative stress plays a critical role in the pathogenesis of cerebral I/R injury. This study investigated whether vitamin D receptor (VDR) could inhibit oxidative stress caused by cerebral I/R injury and explored the detailed mechanism. VDR was highly expressed in brain tissues of mice with cerebral I/R injury. Pretreatment with the active vitamin D calcitriol and synthetic vitamin D analogue paricalcitol (PC) reduced autophagy and apoptosis, improved neurological deficits and decreased infarct size in mice after cerebral I/R. Calcitriol or PC upregulated VDR expression to prevent cerebral I/R injury by affecting oxidative stress. Silencing of VDR reversed the protective effects of calcitriol or PC on brain tissues in mice with cerebral I/R. The bioinformatics analysis revealed that VDR interacted with SMAD family member 3 (SMAD3). It was validated through the chromatin immunoprecipitation assay that SMAD3 can bind to the VDR promoter and VDR can bind to the SMAD3 promoter. Collectively, these findings provide evidence that reciprocal activation between SMAD3 and VDR transcription factors defines vitamin D-mediated oxidative stress to prevent cerebral I/R injury.
Assuntos
Isquemia Encefálica , Traumatismo por Reperfusão , Animais , Camundongos , Receptores de Calcitriol/genética , Receptores de Calcitriol/metabolismo , Calcitriol/farmacologia , Calcitriol/uso terapêutico , Vitamina D/farmacologia , Vitamina D/uso terapêutico , Estresse Oxidativo , Traumatismo por Reperfusão/tratamento farmacológico , Isquemia Encefálica/tratamento farmacológicoRESUMO
Recently, the introduction of surface acoustic wave (SAW) technique for microfluidics has drawn a lot of attention. The pattern and mutual communication in cell layers, tissues, and organs play a critical role in tissue homeostasis and regeneration and may contribute to disease occurrence and progression. Tissue engineering aims to repair and regenerate damaged organs, depending on biomimetic scaffolds and advanced fabrication technology. However, traditional bioengineering synthesis approaches are time-consuming, heterogeneous, and unmanageable. It is hard to pattern cells in scaffolds effectively with no impact on cell viability and function. Here, we summarize a biocompatible, easily available, label-free, and non-invasive tool, surface acoustic wave (SAW) technique, which is getting a lot of attention in tissue engineering. SAW technique can realize accurate sorting, manipulation, and cells' pattern and rapid formation of spheroids. By integrating several SAW devices onto lab-on-a-chip platforms, tissue engineering lab-on-a-chip system was proposed. To the best of our knowledge, this is the first report to summarize the application of this novel technique in the field of tissue engineering.
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Dispositivos Lab-On-A-Chip , Engenharia Tecidual/instrumentação , Animais , Desenho de Equipamento , Humanos , Som , Esferoides Celulares/citologia , Células-Tronco/citologia , Engenharia Tecidual/métodosRESUMO
Brain microvascular endothelial cells (BMECs) injury is one of the main causes of cerebrovascular diseases. Circular RNA (circRNA) has been found to be involved in the regulation of cerebrovascular diseases progression. However, the role and mechanism of circ_0003423 in cerebrovascular diseases is still unclear. In our study, oxidized low density lipoprotein (ox-LDL)-induced HBMEC-IM cells were used to construct cerebrovascular cell injury model in vitro. Quantitative real-time PCR was used to determine the expression levels of circ_0003423, miR-589-5p and Ten-eleven translocation 2 (TET2). The interactions between miR-589-5p and circ_0003423 or TET2 were confirmed by dual-luciferase reporter assay, RIP assay and RNA pull-down assay. Cell viability, angiogenesis and apoptosis were measured using cell counting kit 8 assay, tube formation assay and flow cytometry. Cell oxidative stress was evaluated by detecting the levels of reactive oxygen species and lactate dehydrogenase. The protein levels were examined by western blot analysis. Our results showed that circ_0003423 was a downregulated circRNA in ox-LDL-induced HBMEC-IM cells. In the terms of mechanism, circ_0003423 was found to be a sponge of miR-589-5p. Function analysis showed that circ_0003423 overexpression could relieve ox-LDL-induced HBMEC-IM cell injury, and this effect could be reversed by miR-589-5p mimic. In addition, TET2 was confirmed to be a target of miR-589-5p, and its overexpression could alleviate ox-LDL-induced HBMEC-IM cell injury. Moreover, the rescue experiments also confirmed that TET2 silencing could abolish the inhibition effect of anti-miR-589-5p on ox-LDL-induced HBMEC-IM cell injury. In summary, our data showed that circ_0003423 alleviated ox-LDL-induced HBMEC-IM cells injury through regulating the miR-589-5p/TET2 axis.
Assuntos
Encéfalo/metabolismo , Proteínas de Ligação a DNA/biossíntese , Dioxigenases/biossíntese , Lipoproteínas LDL/toxicidade , MicroRNAs/biossíntese , Microvasos/metabolismo , RNA Circular/biossíntese , Encéfalo/irrigação sanguínea , Encéfalo/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Sobrevivência Celular/fisiologia , Endotélio Vascular/efeitos dos fármacos , Endotélio Vascular/metabolismo , Células Endoteliais da Veia Umbilical Humana/efeitos dos fármacos , Células Endoteliais da Veia Umbilical Humana/metabolismo , Humanos , Microvasos/efeitos dos fármacosRESUMO
To perform the drug screening, planar cultured cell models are commonly applied to test efficacy and toxicity of drugs. However, planar cultured cells are different from the human 3D organs or tissues in vivo. To simulate the human 3D organs or tissues, 3D spheroids are developed by culturing a small aggregate of cells which reside around the extracellular matrix and interact with other cells in liquid media. Here we apply lung carcinoma cell lines to engineer the 3D lung cancer spheroid-based biosensor using the interdigitated electrodes for drug efficacy evaluation. The results show 3D spheroid had higher drug resistance than the planar cell model. The anticarcinogen inhibition on different 3D lung cancer spheroid models (A549, H1299, H460) can be quantitatively evaluated by electric impedance sensing. Besides, we delivered combination of anticarcinogens treatments to A549 spheroids which is commonly used in clinic treatment, and found the synergistic effect of cisplatin plus etoposide had higher drug response. To simultaneously test the drug efficacy and side effects on multi-organ model with circulatory system, a connected multiwell interdigitated electrode arraywas applied to culture different organoid spheroids. Overall, the organization of 3D cancer spheroids-based biosensor, which has higher predictive value for drug discovery and personalized medicine screening, is expected to be well applied in the area of pharmacy and clinical medicine.
Assuntos
Técnicas Biossensoriais/instrumentação , Ensaios de Seleção de Medicamentos Antitumorais/instrumentação , Ensaios de Triagem em Larga Escala/instrumentação , Esferoides Celulares/efeitos dos fármacos , Anticarcinógenos/farmacologia , Antineoplásicos/farmacologia , Biônica , Linhagem Celular Tumoral , Cisplatino/farmacologia , Humanos , Dispositivos Lab-On-A-ChipRESUMO
Okadaic acid (OA), a representative diarrhetic shellfish poisoning toxin, mainly produced by toxigenic dinoflagellates, has significant hazard to public health. Traditional methods for detection of OA can not give the consideration to the need of rapid, high sensitive, quantitative and in-situ detection at the same time. Herein, a new effective detection method of OA was developed based on fluorescence immunosensor and flow cytometry (FCM). In this assay, Streptavidin-coated magnetic beads (MBs) were used as the supporter to immobilize the biotinylated OA. Modified MBs competed with the free OA in the sample solution to bind with the anti-OA monoclonal antibody (OA-MAb). The R-phycoerythrin (R-PE) dye labeled IgG was served as a secondary antibody to perform fluorescence detection. A portable flow cytometry was applied for the in-situ fluorescence quantification. The results showed that the OA concentration was inversely proportional to the R-PE fluorescence intensity. The detection method took within 50 min with a limit of detection (LOD) was 0.05 µg/L and range from 0.2 to 20 µg/L for OA detection. Moreover, the matrix effect and the recovery rate were assessed during real sample measurement, showing a high recovery. Performance features such as high sensitivity, low LOD, speediness and simplicity of the analysis protocol, shows this biosensing-systems as a promising tool for routine use.
Assuntos
Técnicas Biossensoriais , Citometria de Fluxo , Separação Imunomagnética , Toxinas Marinhas/análise , Ácido Okadáico/análise , Animais , Calibragem , Dispositivos Lab-On-A-Chip , Limite de Detecção , Sensibilidade e Especificidade , Frutos do MarRESUMO
Okadaic acid (OA) is a marine toxin ingested by shellfish. In this work, a simple, sensitive and label-free gap-based electrical competitive bioassay has been developed for this biotoxin detection. The gap-electrical biosensor is constructed by modifying interdigitated microelectrodes with gold nanoparticles (AuNPs) and using the self-catalytic growth of AuNPs as conductive bridges. In this development, the AuNPs growth is realized in the solution of glucose and chloroauric acid, with glucose oxidation used as the catalysis for growth of the AuNPs. The catalytic reaction product H2O2 in turn reduces chloroauric acid to make the AuNPs grow. The conductance signal amplification is directly determined by the growth efficiency of AuNPs and closely related to the catalytic activity of AuNPs upon their interaction with OA molecule and OA aptamer. In the absence of OA molecule, the OA aptamer can absorb onto the surfaces of AuNPs due to electrostatic interaction, and the catalytically active sites of AuNPs are fully blocked. Thus the AuNPs growth would not happen. In contrast, the presence of OA molecule can hinder the interaction of OA aptamer and AuNPs. Then the AuNPs sites are exposed and the catalytic growth induces the conductance signal change. The results demonstrated that developed biosensor was able to specifically respond to OA ranging from 5 ppb to 80 ppb, providing limit of detection of 1 ppb. The strategy is confirmed to be effective for OA detection, which indicates the label-free OA biosensor has great potential to offer promising alternatives to the traditional analytical and immunological methods for OA detection.
Assuntos
Técnicas Biossensoriais/instrumentação , Condutividade Elétrica , Ouro/química , Nanopartículas Metálicas/química , Ácido Okadáico/análise , Glucose/química , Oxirredução , Silanos/químicaRESUMO
Cell-based bioassays were effective method to assess the compound toxicity by cell viability, and the traditional label-based methods missed much information of cell growth due to endpoint detection, while the higher throughputs were demanded to obtain dynamic information. Cell-based biosensor methods can dynamically and continuously monitor with cell viability, however, the dynamic information was often ignored or seldom utilized in the toxin and drug assessment. Here, we reported a high-efficient and high-content cytotoxic recording method via dynamic and continuous cell-based impedance biosensor technology. The dynamic cell viability, inhibition ratio and growth rate were derived from the dynamic response curves from the cell-based impedance biosensor. The results showed that the biosensors has the dose-dependent manners to diarrhetic shellfish toxin, okadiac acid based on the analysis of the dynamic cell viability and cell growth status. Moreover, the throughputs of dynamic cytotoxicity were compared between cell-based biosensor methods and label-based endpoint methods. This cell-based impedance biosensor can provide a flexible, cost and label-efficient platform of cell viability assessment in the shellfish toxin screening fields.
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Técnicas Biossensoriais/métodos , Citotoxinas/toxicidade , Testes de Toxicidade/métodos , Animais , Bivalves , Contagem de Células , Proliferação de Células/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Impedância Elétrica , Células Hep G2 , Humanos , Concentração Inibidora 50 , Toxinas Biológicas/toxicidadeRESUMO
Small molecules in plants - such as metabolites, phytohormones, reactive oxygen species (ROS), and inorganic ions - participate in the processes of plant growth and development, physiological metabolism, and stress response. Wearable electrochemical sensors, known for their fast response, high sensitivity, and minimal plant damage, serve as ideal tools for dynamically tracking these small molecules. Such sensors provide producers or agricultural researchers with noninvasive or minimally invasive means of obtaining plant signals. In this review we explore the applications of wearable electrochemical sensors in detecting plant small molecules, enabling scientific assessment of plant conditions, quantification of environmental stresses, and facilitation of plant health monitoring and disease prediction.
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Técnicas Biossensoriais , Dispositivos Eletrônicos Vestíveis , Plantas/metabolismo , Espécies Reativas de Oxigênio/metabolismo , Desenvolvimento Vegetal , AgriculturaRESUMO
In point-of-care diagnostics, the continuous monitoring of sweat constituents provides a window into individual's physiological state. For species like horses, with abundant sweat glands, sweat composition can serve as an early health indicator. Considering the salience of such metrics in the domain of high-value animal breeding, a sophisticated wearable sensor patch tailored is introduced for the dynamic assessment of equine sweat, offering insights into pH, potassium ion (K+), and temperature profiles during episodes of heat stress and under normal physiological conditions. The device integrates a laser-engraved graphene (LEG) sensing electrode array, a non-invasive iontophoretic module for stimulated sweat secretion, an adaptable signal processing unit, and an embedded wireless communication framework. Profiting from an admirable Truth Table capable of logical evaluation, the integrated system enabled the early and timely assessment for heat stress, with high accuracy, stability, and reproducibility. The sensor patch has been calibrated to align with the unique dermal and physiological contours of equine anatomy, thereby augmenting its applicability in practical settings. This real-time analysis tool for equine perspiration stands to revolutionize personalized health management approaches for high-value animals, marking a significant stride in the integration of smart technologies within the agricultural sector.
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Dispositivos Eletrônicos Vestíveis , Cavalos , Animais , Suor/química , Lasers , Transtornos de Estresse por Calor/diagnóstico , Desenho de Equipamento , Técnicas Eletroquímicas/métodos , Técnicas Eletroquímicas/instrumentação , Reprodutibilidade dos Testes , Técnicas Biossensoriais/métodos , Técnicas Biossensoriais/instrumentaçãoRESUMO
Real-time monitoring of glucose concentration changes in plants and access to plant physiological information timely are of great significance to the development of precision agriculture. Here, we innovatively present an electrochemical sensing device that combines microneedle sensors and 3D printing technology to achieve real-time monitoring of glucose in plants in a minimally invasive manner. The device consists of two components: the inner part features a highly efficient sensing interface based on platinum wire (MPt-Au-Nafion-GOx-Pu), while the outer part consists of polymer microneedles formed by 3D printing. Additionally, the polymer hollow microneedle features a slender tip diameter of only 300 µm, minimizing plant damage during the detection procedure. The device shows good detection performance, with a limit of detection (LOD) of 33.3 µM and a detection sensitivity of 17 nA/µM·cm2. It can detect glucose concentrations in the range of 100 µM to 100 mM, providing a unique solution for timely agronomic management of crops tool. By performing 12 h real-time monitoring and salt stress treat on tomato and aloe vera, the results verified the feasibility of integrated device applied to real-time glucose detection in plants.
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Técnicas Biossensoriais , Glucose , Glicemia , Automonitorização da Glicemia , Agulhas , Técnicas Biossensoriais/métodosRESUMO
Spermidine exerts protective roles in obesity, while the mechanism of spermidine in adipose tissue thermogenesis remains unclear. The present study first investigated the effect of spermidine on cold-stimulation and ß3-adrenoceptor agonist-induced thermogenesis in lean and high-fat diet-induced obese mice. Next, the role of spermidine on glucose and lipid metabolism in different types of adipose tissue was determined. Here, we found that spermidine supplementation did not affect cold-stimulated thermogenesis in lean mice, while significantly promoting the activation of adipose tissue thermogenesis under cold stimulation and ß3-adrenergic receptor agonist treatment in obese mice. Spermidine treatment markedly enhanced glucose and lipid metabolism in adipose tissues, and these results were associated with the activated autophagy pathway. Moreover, spermidine up-regulated fibroblast growth factor 21 (FGF21) signaling and its downstream pathway, including PI3K/AKT and AMPK pathways in vivo and in vitro. Knockdown of Fgf21 or inhibition of PI3K/AKT and AMPK pathways in brown adipocytes abolished the thermogenesis-promoting effect of spermidine, suggesting that the effect of spermidine on adipose tissue thermogenesis might be regulated by FGF21 signaling via the PI3K/AKT and AMPK pathways. The present study provides new insight into the mechanism of spermidine on obesity and its metabolic complications, thereby laying a theoretical basis for the clinical application of spermidine.
Assuntos
Tecido Adiposo Marrom , Espermidina , Camundongos , Animais , Espermidina/farmacologia , Espermidina/metabolismo , Espermidina/uso terapêutico , Tecido Adiposo Marrom/metabolismo , Proteínas Quinases Ativadas por AMP/metabolismo , Camundongos Obesos , Fosfatidilinositol 3-Quinases/metabolismo , Proteínas Proto-Oncogênicas c-akt/metabolismo , Tecido Adiposo/metabolismo , Fatores de Crescimento de Fibroblastos/genética , Fatores de Crescimento de Fibroblastos/metabolismo , Obesidade/metabolismo , Glucose/metabolismo , Termogênese , Tecido Adiposo Branco/metabolismo , Camundongos Endogâmicos C57BLRESUMO
Extensive preclinical evidence demonstrates a causative link between insulin signaling dysfunction and the pathogenesis of Alzheimer's disease (AD), and diabetic drugs may represent a promising approach to fighting AD. However, it remains to be determined which antidiabetic drugs are more effective in preventing cognitive impairment. Thus, the present study investigated the effect of dipeptidyl peptidase-4 (DPP-4) inhibitor linagliptin on cognitive impairment in middle-aged mice by comparing it with the effect of metformin. We found that DPP-4 activity increased in the hippocampus of middle-aged mice, and DPP-4 was mainly expressed by microglia rather than astrocytes and oligodendrocytes. DPP-4 directly regulated M1/M2 microglia polarization following LPS or IL-4 stimulation, while DPP-4 inhibitor, linagliptin, suppressed M1-polarized activation and induced M2-polarized activation. Both linagliptin and metformin enhanced cognitive ability, increased hippocampal synaptic plasticity and neurogenesis, and decreased age-related oxidative stress and inflammation by regulating microglia polarization in the hippocampus of middle-aged mice. The combination of linagliptin and metformin showed a maximum protective effect compared to the individual drugs alone. Loss of macrophage inflammatory protein-1α (MIP-1α), a DPP-4 substrate, abrogated the cognitive protection and anti-inflammation effects of linagliptin. Therefore, the current investigation exhibits a potential utility for DPP-4 inhibition in attenuating microglia-mediated inflammation and preventing mild cognitive impairment (MCI) in middle-aged mice, and the effect was partly mediated by MIP-1α.
Assuntos
Doença de Alzheimer , Disfunção Cognitiva , Inibidores da Dipeptidil Peptidase IV , Metformina , Camundongos , Animais , Linagliptina/farmacologia , Linagliptina/uso terapêutico , Quimiocina CCL3/farmacologia , Microglia , Inibidores da Dipeptidil Peptidase IV/farmacologia , Inibidores da Dipeptidil Peptidase IV/uso terapêutico , Hipoglicemiantes/farmacologia , Hipoglicemiantes/uso terapêutico , Disfunção Cognitiva/tratamento farmacológico , Metformina/farmacologia , Metformina/uso terapêutico , InflamaçãoRESUMO
Heart failure (HF) is a life-threatening syndrome. Timely and accurate bedside monitoring of the occurrence and progression of HF via measurements of multiple HF-related biomarkers remains a challenge. Here, we report a triple cascade quantum-strip (TCQS) sensing strategy for the rapid and selective multiplex-tracing of three clinically validated HF biomarkers (BNP/NT-proBNP/ST2) in serum. High selectivity to the three biomarkers is achieved by controlling the individual recognition ability of three target-specific quantum immunoprobes and tuning their simultaneous use to BNP/NT-proBNP/ST2 recognition without mutual interference, which allows the three biomarkers to be directly enriched from serum samples. Benefiting from the fast release-binding kinetics of target-bound immunoprobes on TCQS, recognizable fluorescent signals can be rapidly read out through combining with a self-designed smartphone-based portable reader. This rapid and simple profiling strategy results in good specificity and sensitivity with LODs of 0.097, 0.072, and 0.948 ng/mL for BNP, NT-proBNP, and ST2, respectively, which match the need of clinical applications. Real serum samples are tested with an accuracy of 92.86% for HF diagnosis, validating the capability of the smartphone-read TCQS for practical applications. In particular, the simultaneous detection of the TCQS sensing strategy for BNP/NT-proBNP/ST2 will facilitate the accurate monitoring of HF occurrence, risk stratification, progression, and prognosis as a powerful POCT tool.
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Insuficiência Cardíaca , Proteína 1 Semelhante a Receptor de Interleucina-1 , Humanos , Insuficiência Cardíaca/diagnóstico , Peptídeo Natriurético Encefálico , Prognóstico , Biomarcadores , Limite de DetecçãoRESUMO
Dityrosine (Dityr) has been detected in commercial food as a product of protein oxidation and has been shown to pose a threat to human health. This study aims to investigate whether Dityr causes a decrease in lactic acid metabolism in the gastrocnemius muscle during endurance exercise. C57BL/6 mice were administered Dityr or saline by gavage for 13 weeks and underwent an endurance exercise test on a treadmill. Dityr caused a severe reduction in motion displacement and endurance time, along with a significant increase in lactic acid accumulation in the blood and gastrocnemius muscle in mice after exercise. Dityr induced significant mitochondrial defects in the gastrocnemius muscle of mice. Additionally, Dityr induced serious oxidative stress in the gastrocnemius muscle, accompanied by inflammation, which might be one of the causes of mitochondrial dysfunction. Moreover, significant apoptosis in the gastrocnemius muscle increased after exposure to Dityr. This study confirmed that Dityr induced oxidative stress in the gastrocnemius muscle, which further caused significant mitochondrial damage in the gastrocnemius muscle cell, resulting in decreased capacity of lactic acid metabolism and finally affected performance in endurance exercise. This may be one of the possible mechanisms by which highly oxidized foods cause a decreased muscle energy metabolism.
Assuntos
Mitocôndrias , Músculo Esquelético , Tirosina/análogos & derivados , Humanos , Animais , Camundongos , Camundongos Endogâmicos C57BL , Músculo Esquelético/metabolismo , Mitocôndrias/metabolismo , Estresse OxidativoRESUMO
Inflammation in patients with coronary artery disease (CAD) has been linked to adverse clinical outcomes. A useful biomarker for measuring inflammation levels, high-sensitivity C-reactive protein (hs-CRP) in the blood can be used to detect the presence of low-grade inflammation. This study sought to assess the predictive value of baseline hs-CRP levels for adverse clinical events in CAD patients undergoing percutaneous coronary intervention (PCI). To investigate this topic, a meta-analysis was performed. We conducted a systematic search of PubMed, Embase, and the Cochrane Library for original articles reporting the correlation between hs-CRP levels and adverse clinical events in CAD patients undergoing PCI. We followed the Preferred Reporting Items for Systematic Reviews and Meta-analyses guidelines and conducted a meta-analysis by extracting relevant data. Our pooled calculations yielded hazard ratios or odds ratios with 95% confidence intervals. A total of 28 studies comprising 60544 patients were included in this analysis. High baseline hs-CRP levels predicted increased risk for major adverse cardiac events (P = 0.037), major adverse cardiac and cerebrovascular events (P = 0.020), all-cause mortality (P = 0.001), cardiovascular mortality (P < 0.001), death and/or myocardial infarction (P = 0.017) in patients, as well as restenosis (P < 0.001). However, there was no association between elevated baseline hs-CRP levels and thrombosis. In conclusion, in CAD patients undergoing PCI, baseline hs-CRP levels are reliable predictors of major adverse cardiac events, major adverse cardiac and cerebrovascular events, all-cause mortality, cardiovascular mortality, death and/or myocardial infarction, and restenosis. Therefore, hs-CRP can effectively assist in prognosis determination for CAD patients undergoing PCI.
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In vivo monitoring of animal physiological information plays a crucial role in promptly alerting humans to potential diseases in animals and aiding in the exploration of mechanisms underlying human diseases. Currently, implantable electrochemical microsensors have emerged as a prominent area of research. These microsensors not only fulfill the technical requirements for monitoring animal physiological information but also offer an ideal platform for integration. They have been extensively studied for their ability to monitor animal physiological information in a minimally invasive manner, characterized by their bloodless, painless features, and exceptional performance. The development of implantable electrochemical microsensors for in vivo monitoring of animal physiological information has witnessed significant scientific and technological advancements through dedicated efforts. This review commenced with a comprehensive discussion of the construction of microsensors, including the materials utilized and the methods employed for fabrication. Following this, we proceeded to explore the various implantation technologies employed for electrochemical microsensors. In addition, a comprehensive overview was provided of the various applications of implantable electrochemical microsensors, specifically in the monitoring of diseases and the investigation of disease mechanisms. Lastly, a concise conclusion was conducted on the recent advancements and significant obstacles pertaining to the practical implementation of implantable electrochemical microsensors.