ABSTRACT
Recent studies have revealed that glioma-associated mesenchymal stem cells play instrumental roles in tumorigenesis and tumour progression and cannot be ignored as a cellular component of the glioma microenvironment. Nevertheless, the origin of these cells and their roles are poorly understood. The only relevant studies have shown that glioma-associated mesenchymal stem cells play a large role in promoting tumour proliferation, invasion and angiogenesis. This review provides a comprehensive summary of their discovery and definition, origin, differences from other tissue-derived mesenchymal stem cells, spatial distribution, functions and prognostic and therapeutic opportunities to deepen the understanding of these cells and provide new insight into the treatment of glioma.
Subject(s)
Brain Neoplasms , Glioma , Mesenchymal Stem Cells , Humans , Brain Neoplasms/pathology , Cell Proliferation , Glioma/pathology , Tumor MicroenvironmentABSTRACT
This Letter presents a method for fast-scanning speed LiDAR based on front focal length modulation in the transmitter, which compensates for the influence of the laser divergence angle on the scanning speed at close range of the long-range LiDAR. According to the thin lens equation for Gaussian beams, the laser divergence angle is affected by the distance from the lens to the object (the waist of the laser beam). The scanning speed of the LiDAR is correlated to the laser divergence angle during LiDAR operation, and the scanning speed can be improved by expanding the laser divergence angle by enlarging the front focal length of the transmitter. Through experimental analysis, the laser dispersion angle modulation of LiDAR can improve the scanning speed under the premise of guaranteeing the target detection performance in close-range detection.
ABSTRACT
Recent advancements in signal amplifiers, such as biofunctionalized gold nanoparticles (AuNPs) have improved the surface plasmon resonance (SPR) performance. However, the correlation between the sizes of DNA-Au conjugates and the SPR chips remains elusive. We investigated how the size of AuNPs functioned with DNA detection probes (D-AuNPs) affect SPR signals in sandwich DNA hybridization assays. The effects of three sizes (5, 13, and 29 nm) of D-AuNPs with an equal surface probe density were systematically compared to delineate the relationship between signal amplification and steric hindrance. Sporadically adsorbed target DNA on sparse capture probe-coated chips led to a growth of signal amplification with larger D-AuNPs. In contrast, on dense capture probe-coated SPR chips, when the target DNA concentration was above 1.5 nM, the medium-sized 13-nm AuNPs displayed 1.7- and 1.3-fold enhancement factors than 5-nm and 29-nm ones, respectively. Our results indicate the steric hindrance disturbs the capture of D-AuNPs on dense target DNA-modified chips, rendering the surface density of captured D-AuNPs a determining factor of the sensor response. Alternatively, the sensor sensitivity to D-AuNP surface density is crucial on chips with sparse target DNA. These insights should stimulate and guide future research on surface functionalization toward SPR sensors and AuNPs.
ABSTRACT
Cell-based kinetic studies of ligand or candidate drug binding to membrane proteins have produced affinity and kinetic values that are different from measurements using purified proteins. However, ligand binding to fixated cells whose membrane constituents (e.g., proteins and their glycosylated forms) are partially connected by a cross-linking reagent has not been compared to that to live cells. Under the same experimental conditions for the LigandTracer method, we measured the interactions of fluorophore-labeled lectins and antibody molecules with glycans at HFF cells and the human epithelial growth receptor 2 at SKBR3 cells, respectively. In conjunction with surface plasmon resonance microscopy, the effects of labels and cell/sub-cell heterogeneity on binding kinetics were investigated. Our results revealed that, for cell constituents whose structures and functions are not closely dependent on cell viability, the ligand binding kinetics at fixated cells is only slightly different from that at live cells. The altered kinetics is explained on the basis of a less mobile receptor confined in a local environment created by partially interconnected protein molecules. We show that cell/sub-cell heterogeneity and labels on the ligands can alter the binding reaction more significantly. Thus, fixating cells not only simplifies experimental procedures for drug screening and renders assays more robust but also provides reliable kinetic information about drug binding to cell constituents whose structures are not changed by chemical fixation.
Subject(s)
Microscopy , Surface Plasmon Resonance , Humans , Surface Plasmon Resonance/methods , Kinetics , Ligands , Protein Binding , Membrane ProteinsABSTRACT
Cattle are recognized as the principal reservoir for Escherichia coli O157:H7 and preharvest food safety efforts often focus on decreasing shedding of this pathogen in cattle feces. Enogen® corn (EC; Syngenta Seeds, LLC) is genetically modified to produce enhanced concentrations of α-amylase in the corn kernel endosperm. Research has demonstrated improvements in feed efficiency for cattle fed EC and research has not yet explored whether improved digestion impacts foodborne pathogen populations in cattle. Therefore, this study explored effects of finishing diets containing EC on Escherichia coli O157:H7 prevalence in cattle. A 2 × 2 factorial experiment was conducted with steers (n = 960) fed diets consisting of 2 types of silage (EC or Control) and grain (EC or Control), fed daily ad libitum. Steers were grouped into 12 blocks by incoming body weight, blocks were randomly assigned to one of four pens, and pens were randomly assigned to one diet. Cattle were sampled using rectoanal mucosal swabs in cohorts of 298-337 cattle per day, for a total of 3 sampling days (15-16 days apart). Escherichia coli O157:H7 prevalence rates ranged from not detected (0/75) to 10.0% (8/80) depending on sampling day. Tests for the silage × corn interaction, and the main effects of silage and corn, were not significant (p > 0.05); however, EC reduced the odds of Escherichia coli O157:H7 prevalence by 43% compared to the control corn diet (p = 0.07). Diets containing EC tended to decrease Escherichia coli O157:H7 prevalence in feedlot cattle; however, this reduction was not significant. Before a conclusion can be drawn about impact of EC on Escherichia coli O157:H7 in cattle, further research is necessary to (1) determine if this tendency is due to increased alpha amylase activity and (2) elucidate impact on Escherichia coli O157:H7 prevalence and concentration, as well as a possible mechanism of action.
Subject(s)
Cattle Diseases , Escherichia coli Infections , Escherichia coli O157 , Animals , Cattle , alpha-Amylases , Animal Feed/analysis , Colony Count, Microbial , Diet/veterinary , Escherichia coli Infections/epidemiology , Escherichia coli Infections/prevention & control , Escherichia coli Infections/veterinary , Feces , Zea maysABSTRACT
Milk is an important source of food, and it is also a nutrient-rich medium, which can harbor multiple microorganisms. Staphylococcus aureus is an important foodborne pathogen in food-producing animals, and there have been many reports on its infection and antimicrobial resistance (AMR), which has significant global public health concerns. This study was designed to isolate, characterize, and analyze the AMR pattern of S. aureus from milk samples collected in Chennai, India. A total of 259 raw milk samples from 3 groups: dairy farms, local vendors, and retail outlets were analyzed, and it was found that 34% (89/259) were positive for S. aureus. Positive isolates were further characterized by pulsed-field gel electrophoresis and isolates recovered from different sources, study areas, and locations showed high genetic diversity with no similarity. The presence of AMR has been further assessed by phenotypic methods as per CLSI-M100 performance standards, and all the isolates were susceptible to ampicillin/sulbactam, mupirocin, and tylosin. Additionally, all of the isolates were resistant to ampicillin. There were 28 isolates categorized as multidrug-resistant, which showed resistance to more than 2-3 classes of antimicrobials. This is the first report of inducible clindamycin resistance and mupirocin sensitivity pattern from S. aureus isolates recovered from milk. This study established the occurrence varied with genetic diversity in the isolates prevalent in the study area and divergence pattern of AMR S. aureus. The AMR in these isolates and with methicillin-resistant S. aureus could pose a serious threat to food safety and economic implications.
Subject(s)
Methicillin-Resistant Staphylococcus aureus , Staphylococcal Infections , Animals , Staphylococcus aureus/genetics , Anti-Bacterial Agents/pharmacology , Milk , Mupirocin , Prevalence , Microbial Sensitivity Tests , India/epidemiology , Staphylococcal Infections/epidemiology , Staphylococcal Infections/veterinary , AmpicillinABSTRACT
Magnesium phosphate (MgP) has garnered growing interest in hard tissue replacement processes due to having similar biological characteristics to calcium phosphate (CaP). In this study, an MgP coating with the newberyite (MgHPO4·3H2O) was prepared on the surface of pure titanium (Ti) using the phosphate chemical conversion (PCC) method. The influence of reaction temperature on the phase composition, microstructure, and properties of coatings was systematically researched with the use of an X-ray diffractometer (XRD), a scanning electron microscope (SEM), a laser scanning confocal microscope (LSCM), a contact angle goniometer, and a tensile testing machine. The formation mechanism of MgP coating on Ti was also explored. In addition, the corrosion resistance of the coatings on Ti was researched by assessing the electrochemical behavior in 0.9% NaCl solution using an electrochemical workstation. The results showed that temperature did not obviously affect the phase composition of the MgP coatings, but affected the growth and nucleation of newberyite crystals. In addition, an increase in reaction temperature had a great impact on properties including surface roughness, thickness, bonding strength, and corrosion resistance. Higher reaction temperatures resulted in more continuous MgP, larger grain size, higher density, and better corrosion resistance.
Subject(s)
Alloys , Titanium , Temperature , Titanium/chemistry , Alloys/chemistry , Phosphates/chemistry , Corrosion , Surface Properties , Coated Materials, Biocompatible/chemistryABSTRACT
OBJECTIVE: The rapid spread of the Omicron variant of COVID-19 in China had resulted in campus lockdown in many universities since February 2022, profoundly affecting students' daily lives. Campus lockdown conditions differ considerably from home quarantine, so that the eating patterns of university students may be different. Thus, the current study aimed to: (1) investigate university students' eating patterns during campus lockdown; (2) identify factors associated with their disordered eating. METHOD: An online survey about recent life changes, disordered eating, stress, depression, and anxiety was carried out from April 8th to May 16th, 2022. A total of 2541 responses from 29 provinces/cities of China were received. RESULTS: 2213 participants were included in the main analysis, and other 86 participants were analyzed separately as a subgroup due to their diagnosis of eating disorder. Participants who were undergoing campus lockdown (the lockdown group) showed less disordered eating than those who had never been in campus lockdown (the never-lockdown group), as well as those who had experienced campus lockdown before (the once-lockdown group). However, they perceived more stress and felt more depressed. Being female, higher BMI, gaining weight, increasing exercise, spending more time on social media, higher level of depression and anxiety were all related to disordered eating in the lockdown group. CONCLUSIONS: Disordered eating among Chinese university students was less prevalent during campus lockdown due to the strict and regular diet. However, there is a potential risk of "revenge eating" after campus lockdown ends. Thus, there should be further tracking and related prevention. LEVEL OF EVIDENCE: IV, uncontrolled trials without any interventions.
Subject(s)
COVID-19 , Feeding and Eating Disorders , Humans , Female , Male , COVID-19/prevention & control , SARS-CoV-2 , Universities , Communicable Disease Control , Feeding and Eating Disorders/epidemiology , StudentsABSTRACT
BACKGROUND: Natural service breeding is common in U.S. cow-calf operations. Diseases impacting bull reproductive performance have significant economic consequences for producers. Anaplasmosis may be an underappreciated cause of poor reproductive performance in bulls. The primary systemic effects of bovine anaplasmosis including anemia, fever, and weight loss, can all result in unsatisfactory reproductive performance. The objective of this pilot study was to evaluate breeding soundness examination (BSE) outcomes and clinical changes in bulls during and upon resolution of clinical anaplasmosis. Anaplasma marginale-challenged bulls were observed for clinical disease and infection progression and changes in breeding soundness compared to uninfected control bulls for 16 weeks. RESULTS: All Anaplasma marginale-challenged bulls were PCR-positive, seropositive, and showed clinical signs by 3-, 17-, and 24-days post-challenge, respectively. Clinical signs of anaplasmosis included pallor, icterus, fever (≥ 40.2 °C), and weight loss. Acute anemia was observed in all challenged bulls with PCV nadirs ≤ 18% and peak percent parasitized erythrocyte ≥ 50%. Decreased scrotal circumference and poor semen quality (e.g., increased percentage of abnormal spermatozoa, decreased progressively motile sperm), were initially observed within days after onset of clinical anaplasmosis signs and continued weeks beyond disease resolution. Control bulls remained negative for A. marginale. CONCLUSION: This pilot study demonstrates that clinical anaplasmosis reduces breeding soundness in beef bulls. Anaplasmosis should be considered as a differential for bulls with decreased semen quality, especially within endemic areas. A 90 day or greater retest window is recommended for bulls of unsatisfactory breeding potential recently recovered from clinical anaplasmosis.
Subject(s)
Anaplasmosis , Cattle Diseases , Female , Cattle , Animals , Male , Semen Analysis/veterinary , Pilot Projects , Semen , Scrotum , Weight LossABSTRACT
Best management practices that reduce potential phosphorus (P) loss and provide flexibility in P fertilizer management are needed to help producers protect water quality while maintaining crop yield. This study examined the impacts of P fertilizer management (no P, fall broadcast P, and spring injected P) and cover crop use on annual concentrations and loads of sediment, total P, and dissolved reactive P (DRP) in edge-of-field runoff from a no-till corn (Zea mays)-soybean (Glycine max) rotation in the Central Great Plains, USA, from September 2015 through September 2019. The spring injected P fertilizer treatment generally had 19% less total P and 33% less DRP loss compared to the fall broadcast treatment, confirming the importance of P fertilizer management as a practice for reducing P loss. The addition of a cover crop had an inconsistent effect on total P loss, with no effect in 2016 and 2017, increasing loss in 2018 by 56%, and decreasing it in 2019 by 40%. The inconsistent impact of cover crops on total P loss was related to cover crop effects on sediment loss. Although cover crop impacts on total P losses were inconsistent, the addition of a cover crop increased DRP loss in three of four years. Cover crop use consistently reduced sediment loss, with greater sediment reduction when P fertilizer was applied. Results from this study highlight the benefit of cover crops for reducing sediment loss and the continued need for proper fertilizer management to reduce P loss from agricultural fields.
Subject(s)
Fertilizers , Phosphorus , Agriculture , Fertilizers/analysis , Phosphorus/analysis , Glycine max , Water Movements , Water Quality , Zea maysABSTRACT
PURPOSE: Abnormalities in appetite hormones have been implicated in bulimia nervosa (BN). Orexigenic hormone asprosin has been reported to be associated with food intake and weight gain, but no relevant studies have yet been reported in BN. This study investigated asprosin concentrations and their association with eating disorder symptoms in patients with BN. METHODS: This study recruited a total of 26 BN patients and 23 healthy controls (HC). Symptom severity for eating disorders, depression, and anxiety was determined by the Eating Disorder Examination Questionnaire 6.0, Beck Depression Inventory, Version 2, and Beck Anxiety Inventory, respectively. In addition, the study employed sandwich enzyme-linked immunoassay technology to determine plasma asprosin and glucose concentrations in all participants. RESULTS: The results revealed that plasma asprosin concentrations were significantly higher in BN patients than in HC (P = 0.037), but the difference disappeared after adjusting for the covariate BMI (F = 2.685, P = 0.108). Correlation analysis showed that asprosin concentration was positively correlated with overeating (r = 0.451, P = 0.021) and eating loss of control (r = 0.483, P = 0.012) in BN patients. Linear regression analysis indicated that an increase in asprosin concentration was associated with an increase in the times of overeating (F = 6.303, P = 0.019, R2 = 0.208). Multiple linear regression showed that increases in asprosin concentration and BDI-II total score could explain the frequent eating loss of control (F = 5.766, P = 0.009, R2 = 0.334). CONCLUSIONS: The present study is the first report of plasma asprosin concentration in BN patients and found that overeating and eating loss of control increased with the increase of asprosin concentration. Additionally, asprosin level and degree of depression may explain the frequency of loss of control. LEVEL OF EVIDENCE: Level III: Evidence obtained from case-control studies.
Subject(s)
Anorexia Nervosa , Bulimia Nervosa , Bulimia , Bulimia/diagnosis , Bulimia Nervosa/diagnosis , Glucose , Hormones , Humans , HyperphagiaABSTRACT
Single-atom active-site catalysts have attracted significant attention in the field of photocatalytic CO2 conversion. However, designing active sites for CO2 reduction and H2 O oxidation simultaneously on a photocatalyst and combining the corresponding half-reaction in a photocatalytic system is still difficult. Here, we synthesized a bimetallic single-atom active-site photocatalyst with two compatible active centers of Mn and Co on carbon nitride (Mn1 Co1 /CN). Our experimental results and density functional theory calculations showed that the active center of Mn promotes H2 O oxidation by accumulating photogenerated holes. In addition, the active center of Co promotes CO2 activation by increasing the bond length and bond angle of CO2 molecules. Benefiting from the synergistic effect of the atomic active centers, the synthesized Mn1 Co1 /CN exhibited a CO production rate of 47â µmol g-1 h-1 , which is significantly higher than that of the corresponding single-metal active-site photocatalyst.
ABSTRACT
Benzimidazo[2,1-a]isoquinolin-6(5H)-one constitutes a structurally unique class of tetracyclic N-heterocycles that are found throughout a myriad of biologically active natural products, pharmaceutical compounds, and functional materials. Various synthetic routes for the preparation of benzimidazo[2,1-a]isoquinolin-6(5H)-ones have been reported. In particular, the use of N-methacryloyl-2-phenylbenzoimidazoles to construct benzimidazo[2,1-a]isoquinolin-6(5H)-ones through various radical strategies have attracted widespread attention due to the versatility and simple preparation of raw materials, as well as the step-economy and mild reaction conditions. Using representative examples, we highlight significant progress in the synthesis of benzimidazo[2,1-a]isoquinolin-6(5H)-ones, including the selection of the catalytic system, substrate scope, mechanistic understanding, and applications. The contents of this review focus on the development of C-, S-, P-, and Si-centered radical addition-intramolecular cyclization strategies.
ABSTRACT
An efficient, selective, and step economical radical cyclization of 1,6-dienes with alkyl nitriles initiated by α-C(sp3)-H functionalization under the Sc(OTf)3 and Ag2CO3 system is described here. The selective divergent cyclization relies on the substitution effect at the α-position of the acrylamide moiety and nitriles, which is terminated by hydrogen abstraction, direct cyclization with the aryl ring, or further cyclization with the CîN bond and hydrolysis, respectively.
ABSTRACT
An interference-free photoelectrochemical (PEC) immunoassay was developed for cardiac troponin I (cTnI) detection. Covalent linkage of cTnI antibody to carboxymethylated (CM-) dextran pre-immobilized onto a gold nanoparticles (AuNPs)-modified TiO2 nanotube array (NTA) affords five consecutive analyte captures with surface regenerations in between. Changes in the photocurrents at this photoanode before and after cTnI captures can be well fitted with the Langmuir isotherm from 0.220 pM to 2.20 nM cTnI. Owing to the inherently high sensitivity of the PEC detection, the detection limit (2.20 pg/mL) is lower than the range attainable with the enzyme-linked immunosorbent assay (ELISA) (6.00-40.0 pg/mL). Furthermore, CM-dextran prevents species in complex biological matrices from nonspecifically adsorbing onto the sensor surface, a feature not attainable with uncoated semiconductor electrodes or those coated with non-hydrogel-based chemical modifiers. The excellent anti-fouling property of dextran hydrogel allowed us to validate the accuracy of our regenerable sensors through a comparison of PEC immunoassays of patient sera to those of ELISA.
Subject(s)
Dextrans/chemistry , Electrochemical Techniques , Gold/chemistry , Immunoassay/methods , Photochemical Processes , Titanium/chemistry , Biomarkers , Electrodes , Humans , Nanotubes/chemistry , Troponin I/chemistryABSTRACT
A hyperspectral irradiance monitor (HIM) is designed to measure the direct solar spectral irradiance on the ground, which can be used for research on climate change and vicarious calibration. The spectrometer uses a Féry prism to disperse and converge light, and a linear image sensor (NMOS) measures the spectral irradiance ranging from 400 nm to 1100 nm. The instrument utilizes two flat mirrors to fold the optical path, and optical software is used to optimize the key parameters. The dispersion equation of the prism and two characteristic wavelengths of the laser are utilized for the spectral calibration, for which the uncertainty of the spectral calibration is less than 0.8 nm. A standard lamp is used for the spectral irradiance calibration, for which the uncertainty of the spectral irradiance calibration is less than 2.78% (k=2). The instrument runs stably in the field.
ABSTRACT
Shiga toxin-producing Escherichia coli (STEC) are major foodborne pathogens and seven serogroups, O26, O45, O103, O111, O121, O145, and O157, often called top-7 STEC, account for the majority of the STEC-associated human illnesses in the United States. Two Shiga toxins, Shiga toxins 1 and 2, encoded by stx1 and stx2 genes, are major virulence factors that are involved in STEC infections. Foodborne STEC infections have been linked to a variety of foods of both animal and plant origin, including products derived from cereal grains. In recent years, a few STEC outbreaks have been linked to contaminated wheat flour. The microbiological quality of the wheat grains is a major contributor to the safety of wheat flour. The objective of the study was to utilize polymerase chain reaction (PCR)- and culture-based methods to detect and isolate STEC in wheat grains. Wheat grain samples (n = 625), collected from different regions of the United States, were enriched in modified buffered peptone water with pyruvate (mBPWp) or E. coli (EC) broth, and they were then subjected to PCR- and culture-based methods to detect and isolate STEC. Wheat grains enriched in EC broth yielded more samples positive for stx genes (1.6% vs. 0.32%) and STEC serogroups (5.8% vs. 2.4%) than mBPWp. The four serogroups of top-7 detected and isolated were O26, O45, O103, and O157 and none of the isolates was positive for the Shiga toxin genes. A total of five isolates that carried the stx2 gene were isolated and identified as serogroups O8 (0.6%) and O130 (0.2%). The EC broth was a better medium to enrich wheat grains than mBPWp for the detection and isolation of STEC. The overall prevalence of virulence genes and STEC serogroups in wheat grains was low. The stx2-positive serogroups isolated, O8 and O130, are not major STEC pathogens and have only been implicated in sporadic infections in animals and humans.
Subject(s)
Escherichia coli Infections , Escherichia coli Proteins , Shiga-Toxigenic Escherichia coli , Animals , Escherichia coli Infections/epidemiology , Escherichia coli Proteins/genetics , Feces , Flour , Humans , Multiplex Polymerase Chain Reaction , Shiga-Toxigenic Escherichia coli/genetics , Triticum , United States/epidemiologyABSTRACT
PURPOSE: Asprosin is a centrally acting appetite-promoting hormone and promotes glucose production in the liver. This study is the first to investigate the difference in asprosin in the plasma between anorexia nervosa (AN) and healthy controls, and to explore the relationship between asprosin changes and plasma glucose levels and AN symptoms. METHODS: Plasma asprosin and glucose concentrations were detected in AN patients (n = 46) and healthy control subjects (n = 47). Eating Disorder Inventory-2 (EDI-2) was used to assess subjects' eating disorder symptoms and related personality traits. The patient's concomitant levels of depression and anxiety were also measured using the beck depression inventory and beck anxiety inventory, respectively. RESULTS: Results indicate that AN patients had a higher asprosin concentration in their plasma compared to healthy controls (p = 0.033). Among AN patients, plasma asprosin levels correlated positively with EDI-2 interoceptive awareness subscale score (p = 0.030) and negatively with duration of illness (p = 0.036). Multiple linear regression analyses showed that increases in asprosin levels (p = 0.029), glucose levels (p = 0.024) and body mass index (p = 0.003) were associated with an increase of the score of EDI-2 bulimia subscale. CONCLUSIONS: Our findings suggest that the increase in plasma asprosin concentration in patients with AN may be a compensation for the body's energy shortage, and asprosin may be involved in the development of bulimia and lack of interoceptive awareness in AN patients. LEVEL OF EVIDENCE: Level III, case-control analytic study.
Subject(s)
Anorexia Nervosa , Bulimia Nervosa , Bulimia , Peptide Hormones , Pharmaceutical Preparations , Fibrillin-1 , Humans , Microfilament Proteins , Peptide Fragments , Psychiatric Status Rating ScalesABSTRACT
We previously demonstrated that circulating extracellular vesicles (EVs) from patients with valvular heart disease (VHD; vEVs) contain inflammatory components and inhibit endothelium-dependent vasodilation. Neutrophil chemotaxis plays a key role in renal dysfunction, and dexmedetomidine (DEX) can reduce renal dysfunction in cardiac surgery. However, the roles of vEVs in neutrophil chemotaxis and effects of DEX on vEVs are unknown. Here, we investigated the impact of vEVs on neutrophil chemotaxis in kidneys and the influence of DEX on vEVs. Circulating EVs were isolated from healthy subjects and patients with VHD. The effects of EVs on chemokine generation, forkhead box protein O3a (FOXO3a) pathway activation and neutrophil chemotaxis on cultured human umbilical vein endothelial cells (HUVECs) and kidneys in mice and the influence of DEX on EVs were detected. vEVs increased FOXO3a expression, decreased phosphorylation of Akt and FOXO3a, promoted FOXO3a nuclear translocation, and activated the FOXO3a signaling pathway in vitro. DEX pretreatment reduced vEV-induced CXCL4 and CCL5 expression and neutrophil chemotaxis in cultured HUVECs via the FOXO3a signaling pathway. vEVs were also found to suppress Akt phosphorylation and activate FOXO3a signaling to increase plasma levels of CXCL4 and CCL5 and neutrophil accumulation in kidney. The overall mechanism was inhibited in vivo with DEX pretreatment. Our data demonstrated that vEVs induced CXCL4-CCL5 to stimulate neutrophil infiltration in kidney, which can be inhibited by DEX via the FOXO3a signaling. Our findings reveal a unique mechanism involving vEVs in inducing neutrophils chemotaxis and may provide a novel basis for using DEX in reducing renal dysfunction in valvular heart surgery.
Subject(s)
Chemotaxis, Leukocyte/immunology , Extracellular Vesicles/immunology , Heart Valve Diseases/immunology , Human Umbilical Vein Endothelial Cells/immunology , Kidney/immunology , Neutrophils/immunology , Renal Insufficiency/immunology , Adrenergic alpha-2 Receptor Agonists/pharmacology , Adult , Animals , Case-Control Studies , Chemokine CCL5/drug effects , Chemokine CCL5/immunology , Chemokine CCL5/metabolism , Chemotaxis, Leukocyte/drug effects , Dexmedetomidine/pharmacology , Extracellular Vesicles/drug effects , Extracellular Vesicles/metabolism , Female , Forkhead Box Protein O3/drug effects , Forkhead Box Protein O3/immunology , Forkhead Box Protein O3/metabolism , Heart Valve Diseases/metabolism , Human Umbilical Vein Endothelial Cells/drug effects , Human Umbilical Vein Endothelial Cells/metabolism , Humans , Inflammation , Kidney/drug effects , Kidney/metabolism , Male , Mice , Middle Aged , Neutrophils/drug effects , Phosphorylation , Platelet Factor 4/drug effects , Platelet Factor 4/immunology , Platelet Factor 4/metabolism , Proto-Oncogene Proteins c-akt/drug effects , Proto-Oncogene Proteins c-akt/metabolism , Renal Insufficiency/metabolism , VasodilationABSTRACT
We developed a dual-modal colorimetric and photothermal assay for glutathione (GSH) using MnO2 nanosheets prepared with environmentally friendly materials. The nanosheets were synthesized by using ascorbic acid present abundantly in lemon and orange juices to reduce KMnO4. The as-prepared MnO2 nanosheets display oxidase-like activity and can catalyze the oxidation reaction of 3,3',5,5'-tetramethylbenzidine (TMB), yielding a blue oxidative product (oxTMB) that exhibits a UV-Vis absorption peak at 652 nm. In the presence of GSH, the MnO2 nanosheets are reduced and decomposed, resulting in a decrease in the peak intensity. The colorimetric assay offers a wide dynamic range (0.1-100 µM) and a detection limit of 100 nM. The MnO2 nanosheets are also efficient in converting photoenergy to thermal energy, with a photothermal conversion efficiency of 23.3%. The temperature change, after near-infrared (NIR) irradiation at 808 nm, can be easily measured by an inexpensive pen-type thermometer. This effect can also be used for GSH quantification and expands the GSH concentration detection to the range from 6.0 to 200 µM. The viability of our dual-modal assay for clinical applications was demonstrated with successful analyses of GSH in human serum samples. Graphical abstract.