ABSTRACT
BACKGROUND: Traumatic brain injury (TBI) could induce multiple forms of cell death, ferroptosis, a novel form of cell death distinct from apoptosis and autophagy, plays an important role in disease progression in TBI. Therapies targeting ferroptosis are beneficial for recovery from TBI. Paeoniflorin (Pae) is a water-soluble monoterpene glycoside and the active ingredient of Paeonia lactiflora pall. It has been shown to exert anti-inflammatory and antioxidant effects. However The effects and mechanisms of paeoniflorin on secondary injury after TBI are unknown. PURPOSE: To investigate the mechanism by which Pae regulates ferroptosis after TBI. METHODS: The TBI mouse model and cortical primary neurons were utilized to study the protective effect of paeoniflorin on the brain tissue after TBI. The neuronal cell ferroptosis model was established by treating cortical primary neurons with erastin. Liproxstatin-1(Lip-1) was used as a positive control drug. Immunofluorescence staining, Nissl staining, biochemical analyses, pharmacological analyses, and western blot were used to evaluate the effects of paeoniflorin on TBI. RESULTS: Pae significantly ameliorated neuronal damage after TBI, inhibited mitochondrial damage, increased glutathione peroxidase 4 (GPX4) activity, decreased malondialdehyde (MDA) production, restored neurological function and inhibited cerebral edema. Pae promotes the degradation of P53 in the form of proteasome, promotes its ubiquitination, and reduces the stability of P53 by inhibiting its acetylation, thus alleviating the P53-mediated inhibition of cystine/glutamate antiporter solute carrier family 7 member 11 (SLC7A11) by P53. CONCLUSION: Pae inhibits ferroptosis by promoting P53 ubiquitination out of the nucleus, inhibiting P53 acetylation, and modulating the SLC7A11-GPX4 pathway.
ABSTRACT
BACKGROUND: Recent studies increasingly suggest that microbial infections and the immune responses they elicit play significant roles in the pathogenesis of chronic inflammatory skin diseases. This study uses Mendelian randomization (MR) and Bayesian weighted Mendelian randomization (BWMR) to explore the causal relationships between immune antibody responses and four common skin diseases: psoriasis, atopic dermatitis (AD), rosacea, and vitiligo. METHODS: We utilized summary statistics from genome-wide association studies (GWAS) for antibody responses to 13 infectious pathogens and four skin diseases. Single nucleotide polymorphisms (SNPs) were selected as instrumental variables (IVs) to assess causal relationships using multiple MR methods, including inverse variance weighted (IVW), MR Egger, and weighted median. BWMR was also employed to confirm findings and address potential pleiotropy. RESULTS: The IVW analysis identified significant associations between specific antibody responses and the skin diseases studied. Key findings include protective associations of anti-Epstein-Barr virus (EBV) IgG seropositivity and Helicobacter pylori UREA antibody levels with psoriasis and AD. anti-chlamydia trachomatis IgG seropositivity, anti-polyomavirus 2 IgG seropositivity, and varicella zoster virus glycoprotein E and I antibody levels were negatively associated with rosacea, while EBV Elevated levels of the early antigen (EA-D) antibody levels and HHV-6 IE1B antibody levels were positively associated with rosacea. H. pylori Catalase antibody levels were protectively associated with vitiligo, whereas anti-herpes simplex virus 2 (HSV-2) IgG seropositivity was positively associated with vitiligo. The BWMR analysis confirmed these associations. CONCLUSION: This study underscores the significant role of H. pylori and other pathogens in these skin diseases, suggesting both protective and exacerbating effects depending on the specific condition. Understanding these pathogen-immune interactions can lead to the development of more effective, personalized treatments and preventative strategies, ultimately improving patient outcomes and quality of life.
Subject(s)
Bayes Theorem , Genome-Wide Association Study , Mendelian Randomization Analysis , Polymorphism, Single Nucleotide , Humans , Dermatitis, Atopic/immunology , Dermatitis, Atopic/genetics , Dermatitis, Atopic/microbiology , Dermatitis, Atopic/blood , Rosacea/immunology , Rosacea/genetics , Vitiligo/genetics , Vitiligo/immunology , Antibody Formation/genetics , Psoriasis/immunology , Psoriasis/genetics , Skin Diseases/immunology , Skin Diseases/geneticsABSTRACT
Inorganic/organic heterojunctions show promising applications as high-performance sensing platforms for photoelectrochemical (PEC) immunosensors. This work reports constructing a PEC biosensor for CA15-3 based on a self-assembled perylene diimide (PDI) nanowire sensitized In2O3@MgIn2S4 S-scheme heterojunction platform. P-type semiconductor Cu2O nanoparticles were designed as a signal burst source and were used as immunoassay labels. The carboxyl group on self-assembled PDI nanowires eliminates the step of additional surface functionalization for covalent immobilization of the capture elements. The π-π stacking of PDI enhances electron generation efficiency, while the carboxylic acid groups on PDI promote electron transfer. The performance of the constructed sensor was validated using CA15-3 as a model. The experimental results showed that the sensor based on In2O3@MgIn2S4/PDI has excellent selectivity, stability, and reproducibility, and can sensitively detect CA15-3 in the range of 0.001-100 U·mL-1 with the detection limit of 0.00056 U·mL-1. The sensor has a broad application prospect. It is hoped that this research work based on the unique advantages of the organic compound PDI will inspire other researchers to design light-responsive materials and promote the development of the field of photoelectrochemical sensing.
ABSTRACT
Three new diterpenoid alkaloids (1, 2, 3) and seventeen known (4-20) compounds were isolated from the whole plant of Delphinium sherriffii Munz (Ranunculaceae). Their structures were elucidated by various spectroscopic analyses, including IR, HR-ESI-MS, 1D and 2D NMR spectra. All compounds were evaluated for the inhibitory activity of Sf9 cells and compound 5 exhibited the strongest cytotoxicity (IC50 = 8.97 µM) against Sf9 cell line.
ABSTRACT
BACKGROUND: Keloid is a disease characterized by proliferation of fibrous tissue after the healing of skin tissue, which seriously affects the daily life of patients. However, the clinical treatment of keloids still has limitations, that is, it is not effective in controlling keloids, resulting in a high recurrence rate. Thus, it is urgent to identify new signatures to improve the diagnosis and treatment of keloids. METHOD: Bulk RNA seq and scRNA seq data were downloaded from the GEO database. First, we used WGCNA and MEGENA to co-identify keloid/immune-related DEGs. Subsequently, we used three machine learning algorithms (Randomforest, SVM-RFE, and LASSO) to identify hub immune-related genes of keloid (KHIGs) and investigated the heterogeneous expression of KHIGs during fibroblast subpopulation differentiation using scRNA-seq. Finally, we used HE and Masson staining, quantitative reverse transcription-PCR, western blotting, immunohistochemical, and Immunofluorescent assay to investigate the dysregulated expression and the mechanism of retinoic acid in keloids. RESULTS: In the present study, we identified PTGFR, RBP5, and LIF as KHIGs and validated their diagnostic performance. Subsequently, we constructed a novel artificial neural network molecular diagnostic model based on the transcriptome pattern of KHIGs, which is expected to break through the current dilemma faced by molecular diagnosis of keloids in the clinic. Meanwhile, the constructed IG score can also effectively predict keloid risk, which provides a new strategy for keloid prevention. Additionally, we observed that KHIGs were also heterogeneously expressed in the constructed differentiation trajectories of fibroblast subtypes, which may affect the differentiation of fibroblast subtypes and thus lead to dysregulation of the immune microenvironment in keloids. Finally, we found that retinoic acid may treat or alleviate keloids by inhibiting RBP5 to differentiate pro-inflammatory fibroblasts (PIF) to mesenchymal fibroblasts (MF), which further reduces collagen secretion. CONCLUSION: In summary, the present study provides novel immune signatures (PTGFR, RBP5, and LIF) for keloid diagnosis and treatment, and identifies retinoic acid as potential anti-keloid drugs. More importantly, we provide a new perspective for understanding the interactions between different fibroblast subtypes in keloids and the remodeling of their immune microenvironment.
Subject(s)
Keloid , RNA-Seq , Keloid/genetics , Keloid/diagnosis , Keloid/pathology , Keloid/immunology , Keloid/drug therapy , Humans , Transcriptome/genetics , Gene Expression Profiling , Fibroblasts/metabolism , Fibroblasts/pathology , Fibroblasts/immunology , Gene Regulatory Networks , Tretinoin/pharmacology , Tretinoin/therapeutic use , Single-Cell Analysis/methods , Cell Differentiation/genetics , Sequence Analysis, RNA/methods , Machine Learning , Single-Cell Gene Expression AnalysisABSTRACT
The development of advanced neural modulation techniques is crucial to neuroscience research and neuroengineering applications. Recently, optical-based, nongenetic modulation approaches have been actively investigated to remotely interrogate the nervous system with high precision. Here, we show that a thin-film, silicon (Si)-based diode device is capable to bidirectionally regulate in vitro and in vivo neural activities upon adjusted illumination. When exposed to high-power and short-pulsed light, the Si diode generates photothermal effects, evoking neuron depolarization and enhancing intracellular calcium dynamics. Conversely, low-power and long-pulsed light on the Si diode hyperpolarizes neurons and reduces calcium activities. Furthermore, the Si diode film mounted on the brain of living mice can activate or suppress cortical activities under varied irradiation conditions. The presented material and device strategies reveal an innovated optoelectronic interface for precise neural modulations.
Subject(s)
Neurons , Optogenetics , Silicon , Animals , Silicon/chemistry , Neurons/physiology , Mice , Optogenetics/methods , Calcium/metabolism , Light , Brain/physiologyABSTRACT
Importance: Peceleganan spray is a novel topical antimicrobial agent targeted for the treatment of skin wound infections. However, its efficacy and safety remain unclear. Objective: To assess the safety and efficacy of peceleganan spray for the treatment of wound infections. Design, Setting, and Participants: This multicenter, open-label, phase 3 randomized clinical trial recruited and followed up 570 adult patients diagnosed with secondary open wound infections from 37 hospitals in China from August 23, 2021, to July 16, 2022. Interventions: Patients were randomized to 2 groups with a 2:1 allocation. One group received treatment with 2% peceleganan spray (n = 381) and the other with 1% silver sulfadiazine (SSD) cream (n = 189). Main Outcomes and Measures: The primary efficacy outcome was the clinical efficacy rate (the number of patients fulfilling the criteria for efficacy of the number of patients receiving the treatment) on the first day following the end of treatment (day 8). The secondary outcomes included the clinical efficacy rate on day 5 and the bacterial clearance rate (cases achieving negative bacteria cultures after treatment of all cases with positive bacteria cultures before treatment) on days 5 and 8. The safety outcomes included patients' vital signs, physical examination results, electrocardiographic findings, blood test results, and adverse reactions. Results: Among the 570 patients randomized to 1 of the 2 groups, 375 (98.4%) in the 2% peceleganan treatment group and 183 (96.8%) in the 1% SSD control group completed the trial (n = 558). Of these, 361 (64.7%) were men, and the mean (SD) age was 48.6 (15.3) years. The demographic characteristics were similar between groups. On day 8, clinical efficacy was achieved by 339 patients (90.4%) in the treatment group and 144 (78.7%) in the control group (P < .001). On day 5, clinical efficacy was achieved by 222 patients (59.2%) in the treatment group and 90 (49.2%) in the control group (P = .03). On day 8, bacterial clearance was achieved by 80 of 334 patients (24.0%) in the treatment group and in 75 of 163 (46.0%) in the control group (P < .001). On day 5, bacterial clearance was achieved by 55 of 334 patients (16.5%) in the treatment group and 50 of 163 (30.7%) in the control group (P < .001). The adverse events related to the application of peceleganan spray and SSD cream were similar. Conclusions and Relevance: This randomized clinical trial found that peceleganan spray is a safe topical antimicrobial agent with a satisfactory clinical efficacy rate for the treatment of skin wound infections, while the effectiveness of bacterial clearance remains uncertain. Trial Registration: Chinese Clinical Trial Registry Identifier: ChiCTR2100047202.
Subject(s)
Wound Infection , Humans , Male , Female , Middle Aged , Adult , Wound Infection/drug therapy , Anti-Infective Agents, Local/therapeutic use , Anti-Infective Agents, Local/administration & dosage , China , Silver Sulfadiazine/therapeutic use , Silver Sulfadiazine/administration & dosage , Treatment Outcome , Aged , Anti-Bacterial Agents/therapeutic use , Anti-Bacterial Agents/administration & dosageABSTRACT
Present study aimed to compare the effects of SSIT intervention with varying rest distributions on hormonal, physiological, and performance adaptations in soccer players. Thirty-six players were randomly divided into three SSIT groups, each performing 4 sets of 6-10 repetitions of 6-second all-out running with rest intervals at ratios of 1:3, 1:6, and 1:9. Prior to and following the 7-week training period, aerobic fitness indices and anaerobic power were evaluated using a graded exercise test with a gas collection system and a lower-body Wingate test, respectively. Also, sport-specific bio-motor abilities were determined by measuring vertical jump, 20-m sprint, and T-test change of direction speed, Yo-Yo IR1 and maximal kicking distance. Hormonal status was also monitored by evaluating testosterone and cortisol levels. Following the 7-week training period, all SSIT interventions resulted in significant enhancements (p < 0.05) in soccer-related performance, physiological parameters, and hormonal adaptations, exhibiting effect sizes that ranged from small to large. Comparative analysis indicated that the 1:9 SSIT results in greater adaptive responses (p < 0.05) in the vertical jump, peak power, testosterone, and cortisol compared to the 1:3 SSIT group. By contrast, the 1:3 SSIT group induced more adaptive responses (p < 0.05) in the mean power output, maximum oxygen consumption (VÌO2max), and Yo-Yo IR1 compared to the 1:9 SSIT group. Hence, for enhancing physical performance, especially vertical jump height, anaerobic peak power, and hormonal adaptations, the 1:9 SSIT ratio is preferable. Conversely, shorter rest intervals (specifically, the 1:3 SSIT ratio) are better suited for eliciting heightened adaptive responses in mean power output, VÌO2max, and Yo-Yo IR1 over the 7-week training period among young male soccer players.
Subject(s)
Adaptation, Physiological , Athletic Performance , High-Intensity Interval Training , Hydrocortisone , Oxygen Consumption , Rest , Running , Soccer , Testosterone , Humans , Soccer/physiology , Hydrocortisone/blood , Athletic Performance/physiology , Testosterone/blood , Running/physiology , Male , Adolescent , High-Intensity Interval Training/methods , Rest/physiology , Oxygen Consumption/physiology , Exercise TestABSTRACT
A smartphone-based electrochemical aptasensing platform was developed for the point-of-care testing (POCT) of carcinoembryonic antigen (CEA) based on the ferrocene (Fc) and PdPt@PCN-224 dual-signal labeled strategy. The prepared PdPt@PCN-224 nanocomposite showed a strong catalytic property for the reduction of H2O2. Phosphate group-labeled aptamer could capture PdPt@PCN-224 by Zr-O-P bonds to form PdPt@PCN-224-P-Apt. Therefore, a dual signal labeled probe was formed by the hybridization between Fc-DNA and PdPt@PCN-224-P-Apt. The presence of CEA forced PdPt@PCN-224-P-Apt to leave the electrode surface due to the specific affinity, leading to the decrease of the reduction current of H2O2. At the same time, the Fc-DNA strand changed to hairpin structure, which made Fc closer to the electrode and resulted in the increase of the oxidation current of Fc. Thus, CEA can be accurately determined through both signals: the decrease of H2O2 reduction current and the increase of Fc oxidation current, which could avoid the false positive signal. Under the optimal conditions, the prepared aptasensor exhibited a wide linear range from 1 pg·mL-1 to 100 ng·mL-1 and low detection limits of 0.98 pg·mL-1 and 0.27 pg·mL-1 with Fc and PdPt@PCN-224 as signal labels, respectively. The aptasensor developed in this study has successfully demonstrated its capability to detect CEA in real human serum samples. These findings suggest that the proposed sensing platform will hold great potential for clinical tumor diagnosis and monitoring.
Subject(s)
Aptamers, Nucleotide , Biosensing Techniques , Carcinoembryonic Antigen , Electrochemical Techniques , Ferrous Compounds , Hydrogen Peroxide , Limit of Detection , Palladium , Point-of-Care Testing , Smartphone , Carcinoembryonic Antigen/blood , Carcinoembryonic Antigen/analysis , Aptamers, Nucleotide/chemistry , Electrochemical Techniques/methods , Electrochemical Techniques/instrumentation , Humans , Biosensing Techniques/methods , Hydrogen Peroxide/chemistry , Palladium/chemistry , Ferrous Compounds/chemistry , Metallocenes/chemistry , Platinum/chemistryABSTRACT
Large-scale neural population recordings with single-cell resolution across the primate brain remain challenging. Here we introduce the Neuroscroll probe that isolates single neuronal activities simultaneously from 1,024 densely spaced channels that are flexibly distributed across the shank of the probe. The Neuroscroll probe length is easily tunable for individual probes from 10 mm to 90 mm, covering the brain size of non-human primates and humans, and the probes remain intact and functional after repeated bending deformations. The Neuroscroll probes provided reliable recordings from large neural populations with high chronic stability up to 105 weeks in rats. Recording with each Neuroscroll probe yielded hundreds of well-isolated single units simultaneously from multiple brain regions distributed across the entire depth of the rhesus macaque brain. With the thousand simultaneously recorded channels, unprecedented probe length, excellent mechanical stability and flexible recording site distribution, the Neuroscroll probes enable a wide range of new experimental paradigms in system neuroscience studies with great versatility.
Subject(s)
Brain , Macaca mulatta , Neurons , Animals , Brain/physiology , Neurons/physiology , Rats , Electrodes, Implanted , Male , Action Potentials/physiologyABSTRACT
OBJECTIVE: To compare an Extreme Gradient Boosting (XGboost) model with a multivariable logistic regression (LR) model for their ability to predict sepsis after extremely severe burns. METHODS: For this observational study, patient demographic and clinical information were collected from medical records. The two models were evaluated using area under curve (AUC) of the receiver operating characteristic (ROC) curve. RESULTS: Of the 103 eligible patients with extremely severe burns, 20 (19%) were in the sepsis group, and 83 (81%) in the non-sepsis group. The LR model showed that age, admission time, body index (BI), fibrinogen, and neutrophil to lymphocyte ratio (NLR) were risk factors for sepsis. Comparing AUC of the ROC curves, the XGboost model had a higher predictive performance (0.91) than the LR model (0.88). The SHAP visualization tool indicated fibrinogen, NLR, BI, and age were important features of sepsis in patients with extremely severe burns. CONCLUSIONS: The XGboost model was superior to the LR model in predictive efficacy. Results suggest that, fibrinogen, NLR, BI, and age were correlated with sepsis after extremely severe burns.
Subject(s)
Burns , ROC Curve , Sepsis , Humans , Sepsis/etiology , Sepsis/blood , Sepsis/complications , Sepsis/diagnosis , Male , Female , Burns/complications , Logistic Models , Middle Aged , Adult , Risk Factors , Neutrophils/immunology , Fibrinogen/metabolism , Fibrinogen/analysis , Prognosis , Retrospective Studies , Area Under Curve , AgedABSTRACT
Simultaneous sensitive and precise determination of multibiomarkers is of great significance for improving detection efficiency, reducing diagnosis and treatment expenses, and elevating survival rates. However, the development of simple and portable biosensors for simultaneous determination of multiplexed targets in biological fluids still faces challenges. Herein, a unique and versatile immobilization-free dual-target electrochemical biosensing platform, which combines distinguishable magnetic signal reporters with buoyancy-magnetism separation, was designed and constructed for simultaneous detection of carcinoembryonic (CEA) and α-fetoprotein (AFP) in intricate biological fluids. To construct such distinguishable magnetic signal reporters with signal transduction, amplification, and output, secondary antibodies of CEA and AFP were respectively functionalized on methylene blue (MB) and 6-(ferrocenyl)hexanethiol (FeC) modified Fe3O4@Au magnetic nanocomposites. Meanwhile, a multifunctional flotation probe with dual target recognition, capture, and isolation capability was prepared by conjugating primary antibodies (Ab1-CEA, Ab1-AFP) to hollow buoyant microspheres. The target antigens of CEA and AFP can trigger a flotation-mediated sandwich-type immunoreaction and capture a certain amount of the distinguishable magnetic signal reporter, which enables the conversion of the target CEA and AFP quantities to the signal of the potential-resolved MB and FeC. Thus, the MB and FeC currents of magnetically adsorbed distinguishable magnetic reporters can be used to determine the CEA and AFP targets simultaneously and precisely. Accordingly, the proposed strategy exhibited a delightful linear response for CEA and AFP in the range of 100 fg·mL-1-100 ng·mL-1 with detection limits of 33.34 and 17.02 fg·mL-1 (S/N = 3), respectively. Meanwhile, no significant nonspecific adsorption and cross-talk were observed. The biosensing platform has shown satisfactory performance in the determination of real clinical samples. More importantly, the proposed approach can be conveniently extended to universal detection just by simply substituting biorecognition events. Thus, this work opens up a new promising perspective for dual and even multiple targets and offers promising potential applications in clinical diagnosis.
Subject(s)
Biosensing Techniques , Carcinoembryonic Antigen , Electrochemical Techniques , alpha-Fetoproteins , alpha-Fetoproteins/analysis , alpha-Fetoproteins/immunology , Carcinoembryonic Antigen/analysis , Carcinoembryonic Antigen/immunology , Biosensing Techniques/methods , Humans , Immunoassay/methods , Gold/chemistry , Limit of DetectionABSTRACT
Purpose: The occurrence of hyponatremia is a prevalent complication following transnasal transsphenoidal surgery for pituitary adenoma surgery, which adversely affects patient prognosis, hospitalization duration, and rehospitalization risk. The primary objective of this study is to strengthen the correlation between clinical factors associated with pituitary adenoma and postoperative hyponatremia. Additionally, the study aims to develop a predictive model for postoperative hyponatremia in patients with pituitary adenoma, with the ultimate goal of establishing a basis for reducing the occurrence of postoperative hyponatremia following surgical interventions. Methods: The chi-square test or Fisher test was employed for nominal data, while the t-test or Mann-Whitney test was utilized for continuous data analysis. In cases where the data exhibited statistical differences, binary logistic analysis was conducted to examine the risk and protective factors associated with postoperative hyponatremia. XGBoost was employed to construct predictive models for hyponatremia in this study. The patients were partitioned into training and test sets, and the most suitable parameters were determined through five-fold cross-validation and subsequently utilized for training on the training set. The discriminatory capability was assessed on the internal validation set. Results and conclusions: Out of the total 280 patients included in this investigation, 82 patients experienced early postoperative hyponatremia. Among these individuals, male gender (P = 0.02, odds ratio = 1.98) was identified as a risk factor for early postoperative hyponatremia, while preoperative chloride levels (P = 0.021, odds ratio = 0.866) and surgery time (P = 0.039, odds ratio = 0.990) were identified as protective factors against postoperative hyponatremia. The XGBoost model exhibited a sensitivity of 94.2%, a specificity of 61.5%, a positive predictive value of 51.6%, a negative predictive value of 96%, and identified male gender, preoperative sodium, and preoperative cortisol as the most significant predictors. Our findings indicate that gender may have influence in the development of early postoperative hyponatremia in patients with pituitary adenomas.
ABSTRACT
Polycyclic aromatic hydrocarbons (PAHs) are excellent alternative luminophores for electrochemiluminescence (ECL) immunoassays. However, they are inevitably limited by the aggregation-caused quenching effect. In this study, aimed at eliminating the aggregation quenching of PAHs, luminescent metal-organic frameworks (MOFs) with 1,3,6,8-tetra(4-carboxybenzene)pyrene (H4TBAPy) as the ligand were exploited as a novel nano-emitter for the construction of ECL immunoassays. The luminophore exhibits efficient aggregation-induced emission enhancement, good acid-base resistance property and unusual ECL reactivity. In addition, the simultaneous use of potassium persulfate and hydrogen peroxide as dual co-reactants resulted in a synergistic enhancement of the cathodic ECL efficiency. The use of magnetic iron-nickel alloys as the multifunctional sensing platform can further enhance the ECL activity, and its enriched zero-valent iron as a co-reactant accelerator effectively drives ECL analytical performance. Profiting from the excellent characteristics, signal-on ECL immunoassays have been constructed. With carcinoembryonic antigen as the model analysis target, a detection limit of 0.63 pg/mL was obtained within the linear range of 1 pg/mL to 50 ng/mL, accompanied by excellent analytical performance. This report opens a new window for the rational design of efficient ECL illuminators, and the proposed ECL immunoassays may find promising applications in the detection of disease markers.
Subject(s)
Biosensing Techniques , Metal Nanoparticles , Metal-Organic Frameworks , Polycyclic Aromatic Hydrocarbons , Pyrenes , Immunoassay , Iron , Luminescent Measurements , Electrochemical Techniques , Limit of DetectionABSTRACT
Dual-potential ratiometric electrochemiluminescence (ECL) is in favor of resistance to environmental interference. However, two kinds of emitters or coreactants, and a wide scan potential range (>2 V) are mandatory. This work developed a new dual-potential ratiometric ECL sensor for detection of carcinoembryonic antigen (CEA) using single emitter (luminol) and single coreactant (H2O2) with a mild potential range from -0.1 to 0.6 V. Luminol could produce a strong cathodic ECL (Ec) induced by hydroxyl radicals (HOâ§) from the reduction of H2O2, and a relatively weak anodic ECL (Ea). After the ferrocene modified CEA aptamer (Apt-Fc) was attached, Fc could promote Ea by catalyzing the oxidation of H2O2, and reduce Ec by consuming HOâ§. With the cycling amplification of the exonuclease I, CEA could substantially reduce the amount of Apt-Fc, resulting in the decrease of Ea and the rise of Ec. So, the ratio of Ec to Ea (Ec/Ea) was used as the detection signal, realizing the sensitive determination of CEA from 0.1 pg mL-1 to 10 ng mL-1 with a LOD of 41.85 fg mL-1 (S/N = 3). The developed sensor demonstrated excellent specificity, stability and reproducibility, with satisfactory results in practical detection.
Subject(s)
Aptamers, Nucleotide , Carcinoembryonic Antigen , Electrochemical Techniques , Hydrogen Peroxide , Luminescent Measurements , Luminol , Carcinoembryonic Antigen/analysis , Carcinoembryonic Antigen/blood , Electrochemical Techniques/methods , Humans , Luminescent Measurements/methods , Hydrogen Peroxide/chemistry , Hydrogen Peroxide/analysis , Luminol/chemistry , Aptamers, Nucleotide/chemistry , Limit of Detection , Biosensing Techniques/methods , Metallocenes/chemistry , Ferrous Compounds/chemistryABSTRACT
Subarachnoid hemorrhage (SAH) is primarily attributed to the rupture of intracranial aneurysms and is associated with a high incidence of disability and mortality. SAH disrupts the bloodâbrain barrier, leading to the release of iron ions from blood within the subarachnoid space, subsequently inducing neuronal ferroptosis. A recently discovered protein, known as ferroptosis suppressor protein 1 (FSP1), exerts anti-ferroptotic effects by facilitating the conversion of oxidative coenzyme Q 10 (CoQ10) to its reduced form, which effectively scavenges reactive oxygen radicals and mitigates iron-induced ferroptosis. In our investigation, we observed an increase in FSP1 levels following SAH. However, the depletion of CoQ10 caused by SAH hindered the biological function of FSP1. Therefore, we created neuron-targeted liposomal CoQ10 by introducing the neuron-targeting peptide Tet1 onto the surface of liposomal CoQ10. Our objective was to determine whether this formulation could activate the FSP1 system and subsequently inhibit neuronal ferroptosis. Our findings revealed that neuron-targeted liposomal CoQ10 effectively localized to neurons at the lesion site after SAH. Furthermore, it facilitated the upregulation of FSP1, reduced the accumulation of malondialdehyde and reactive oxygen species, inhibited neuronal ferroptosis, and exerted neuroprotective effects both in vitro and in vivo. Our study provides evidence that supplementation with CoQ10 can effectively activate the FSP1 system. Additionally, we developed a neuron-targeted liposomal CoQ10 formulation that can be selectively delivered to neurons at the site of SAH. This innovative approach represents a promising therapeutic strategy for neuronal ferroptosis following SAH. STATEMENT OF SIGNIFICANCE: Subarachnoid hemorrhage (SAH) is primarily attributed to the rupture of intracranial aneurysms and is associated with a high incidence of disability and mortality. Ferroptosis suppressor protein 1 (FSP1), exerts anti-ferroptotic effects by facilitating the conversion of oxidative coenzyme Q 10 (CoQ10) to its reduced form, which effectively scavenges reactive oxygen radicals and mitigates iron-induced ferroptosis. In our investigation, we observed an increase in FSP1 levels following SAH. However, the depletion of CoQ10 caused by SAH hindered the biological function of FSP1. Therefore, we created neuron-targeted liposomal CoQ10. We find that it effectively localized to neurons at the lesion site after SAH and activated the FSP1/CoQ10 system. This innovative approach represents a promising therapeutic strategy for neuronal ferroptosis following SAH and other central nervous system diseases characterized by disruption of the blood-brain barrier.