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Cardiac sympathetic overactivation is a critical driver in the progression of acute myocardial infarction (AMI). The left middle cervical ganglion (LMCG) is an important extracardiac sympathetic ganglion. However, the regulatory effects of LMCG on AMI have not yet been fully documented. In the present study, we detected that the LMCG was innervated by abundant sympathetic components and exerted an excitatory effect on the cardiac sympathetic nervous system in response to stimulation. In canine models of AMI, targeted ablation of LMCG reduced the sympathetic indexes of heart rate variability and serum norepinephrine, resulting in suppressed cardiac sympathetic activity. Moreover, LMCG ablation could improve ventricular electrophysiological stability, evidenced by the prolonged ventricular effective refractory period, elevated action potential duration, increased ventricular fibrillation threshold, and enhanced connexin43 expression, consequently showing antiarrhythmic effects. Additionally, compared with the control group, myocardial infarction size, circulating cardiac troponin I, and myocardial apoptosis were significantly reduced, accompanied by preserved cardiac function in canines subjected to LMCG ablation. Finally, we performed the left stellate ganglion (LSG) ablation and compared its effects with LMCG destruction. The results indicated that LMCG ablation prevented ventricular electrophysiological instability, cardiac sympathetic activation, and AMI-induced ventricular arrhythmias with similar efficiency as LSG denervation. In conclusion, this study demonstrated that LMCG ablation suppressed cardiac sympathetic activity, stabilized ventricular electrophysiological properties and mitigated cardiomyocyte death, resultantly preventing ischemia-induced ventricular arrhythmias, myocardial injury, and cardiac dysfunction. Neuromodulation therapy targeting LMCG represented a promising strategy for the treatment of AMI.
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Infarto del Miocardio , Animales , Perros , Arritmias Cardíacas , Corazón/inervación , Fibrilación Ventricular/etiología , Fibrilación Ventricular/prevención & control , Ganglios Simpáticos/metabolismoRESUMEN
The tire rubber antioxidant N-(1,3-dimethylbutyl)-N'-phenyl-p-phenylenediamine (6PPD) and its quinone product (6PPDQ) are prevalent emerging contaminants, yet their biotransformation profiles remain poorly understood, hampering the assessment of environmental and health risks. This study investigated the phase-I metabolism of 6PPD and 6PPDQ across aquatic and mammalian species through in vitro liver microsome (LM) incubations and in silico simulations. A total of 40 metabolites from seven pathways were identified using the highly sensitive nano-electrospray ionization mass spectrometry. Notably, 6PPDQ was consistently detected as a 6PPD metabolite with an approximate 2% yield, highlighting biotransformation as a neglected indirect exposure pathway for 6PPDQ in organisms. 6PPDQ was calculated to form through a facile two-step phenyl hydroxylation of 6PPD, catalyzed by cytochrome P450 enzymes. Distinct species-specific metabolic kinetics were observed, with fish LM demonstrating retarded biotransformation rates for 6PPD and 6PPDQ compared to mammalian LM, suggesting the vulnerability of aquatic vertebrates to these contaminants. Intriguingly, two novel coupled metabolites were identified for 6PPD, which were predicted to exhibit elevated toxicity compared to 6PPDQ and result from C-N oxidative coupling by P450s. These unveiled metabolic profiles offer valuable insights for the risk assessment of 6PPD and 6PPDQ, which may inform future studies and regulatory actions.
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Chronic hyperglycaemia is a chief feature of diabetes mellitus and complicates with many systematic anomalies. Non-human primates (NHPs) are excellent for studying hyperglycaemia or diabetes and associated comorbidities, but lack behavioural observation. In the study, behavioural, brain imaging and histological analysis were performed in a case of spontaneously hyperglycaemic (HGM) Macaca fascicularis. The results were shown that the HGM monkey had persistent body weight loss, long-term hyperglycaemia, insulin resistance, dyslipidemia, but normal concentrations of insulin, C-peptide, insulin autoantibody, islet cell antibody and glutamic acid decarboxylase antibody. Importantly, an impaired working memory in a delayed response task and neurological dysfunctions were found in the HGM monkey. The tendency for atrophy in hippocampus was observed by magnetic resonance imaging. Lenticular opacification, lens fibres disruptions and vacuole formation also occurred to the HGM monkey. The data suggested that the spontaneous HGM monkey might present diabetes-like characteristics and associated neurobehavioral anomalies in this case. This study first reported cognitive deficits in a spontaneous hyperglycaemia NHPs, which might provide evidence to use macaque as a promising model for translational research in diabetes and neurological complications.
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Catarata , Hiperglucemia , Macaca fascicularis , Animales , Hiperglucemia/metabolismo , Catarata/patología , Masculino , Trastornos del Conocimiento/etiología , Trastornos del Conocimiento/patología , Enfermedades del Sistema Nervioso , Hipocampo/patología , Hipocampo/metabolismoRESUMEN
Air pollution has a significant global impact on natural resources and public health. Accurate prediction of air pollution is crucial for effective prevention and control measures. However, due to regional variations, different cities may have varying primary pollutants, posing new challenges for accurate prediction. In this paper, we propose a novel method called FP-RF, which integrates clustering algorithms to categorize multiple cities according to their air quality index values. Subsequently, we apply functional principal component analysis to extract the primary components of air pollution within each cluster. Furthermore, an enhanced random forest algorithm is utilized to predict air quality grades for each city. We conduct experimental evaluations using authentic historical data from Anhui Province spanning from 2018 to 2023. The results unequivocally establish the effectiveness of our model, with an average accuracy rate of 98.6% in forecasting six pollution grades and 96.04% accuracy in predicting 16 prefecture-level cities, surpassing performance compared to other baseline models.
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Contaminantes Atmosféricos , Contaminación del Aire , Monitoreo del Ambiente , Predicción , Contaminación del Aire/estadística & datos numéricos , Monitoreo del Ambiente/métodos , Contaminantes Atmosféricos/análisis , Ciudades , Algoritmos , China , Modelos Teóricos , Análisis de Componente PrincipalRESUMEN
Respiratory tract infections are associated with the most common diseases transmitted among people and remain a huge threat to global public health. Rapid and sensitive diagnosis of causative agents is critical for timely treatment and disease control. Here, we developed a novel method based on recombinase polymerase amplification (RPA) combined with CRISPR-Cas12a to detect three viral pathogens, including SARS-CoV-2, influenza A, and influenza B, which cause similar symptom complexes of flu cold in the respiratory tract. The detection method can be completed within 1 h, which is faster than other standard detection methods, and the limit of detection is approximately 102 copies/µL. Additionally, this detection system is highly specific and there is no cross-reactivity with other common respiratory tract pathogens. Based on this assay, we further developed a more simplified RPA/CRISPR-Cas12a system combined with lateral flow assay on a manual microfluidic chip, which can simultaneously detect these three viruses. This low-cost detection system is rapid and sensitive, which could be applied in the field and resource-limited areas without bulky and expensive instruments, providing powerful tools for the point-of-care diagnostic.
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COVID-19 , Gripe Humana , Orthomyxoviridae , Humanos , Recombinasas , SARS-CoV-2 , Sistemas CRISPR-Cas , Nucleotidiltransferasas , Técnicas de Amplificación de Ácido NucleicoRESUMEN
In this paper, we propose a reflective terahertz (THz) Bessel metalens that utilizes polarization-insensitive sub-wavelength metal resonator-dielectric-metal structures. The Bessel metalens is configured with the superposition of hyperboloidal and conical phase profiles, resulting in a high-efficiency and long non-diffractive length Bessel beam. Our experimental results demonstrate that the proposed Bessel metalens has a focusing efficiency of 72.1% and a non-diffractive length of 239λ. This device has promising aspects in the fields of THz imaging systems and other miniaturized and integrated scenes that require non-diffractive Bessel beams.
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Developing non-noble-metal electrocatalysts for hydrogen evolution reactions with high activity and stability is the key issue in green hydrogen generation based on electrolytic water splitting. It has been recognized that the stacking of large CoP particles limits the intrinsic activity of as-synthesized CoP catalyst for hydrogen evolution reaction. In the present study, N-MoxC/CoP-0.5 with excellent electrocatalytic activity for hydrogen evolution reaction was prepared using N-MoxC as decoration. A reasonable overpotential of 106 mV (at 10 mA cm-2) and a Tafel slope of 59 mV dec-1in 1.0 M KOH solution was achieved with N-MoxC/CoP-0.5 electrocatalyst, which exhibits superior activity even after working for 37 h. Uniformly distributed ultrafine nanoclusters of the N-MoxC/CoP-0.5 hybrids could provide sufficient interfaces for enhanced charge transfer. The effective capacity of the hydrogen evolution reaction could be preserved in the complex, and the enlarged electrocatalytic surface area could be expected to offer more active sites for the reaction.
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AIMS: This study aimed to screen a bacterial strain with high detoxifying capability for aflatoxin B1 (AFB1), verify its biotransformation efficiency, and detoxification process. METHODS AND RESULTS: A total of 350 samples collected from different environmental niche were screened using coumarin as the sole carbon source. High Performance Liquid Chromatography (HPLC) was used to detect residues of AFB1, and 16S rRNA sequencing was performed on the isolated strain with the highest AFB1 removal ratio for identification. The detoxified products of this strain were tested for toxicity in Escherichia coli as well as LO2, Caco-2, and HaCaT human cell lines. HPLC-MS was applied to further confirm the AFB1 removal and detoxification process. CONCLUSIONS: We identified a strain from plant leaf designated as DT with high AFB1-detoxifying ability that is highly homologous to Bacillus aryabhattai. The optimum detoxification conditions of this strain were 37°C and pH 8.0, resulting in 82.92% removal ratio of 2 µg mL-1 AFB1 in 72 h. The detoxified products were nontoxic for E. coli and significantly less toxic for the LO2, Caco-2, and HaCaT human cell lines. HPLC-MS analysis also confirmed the significant drop of the AFB1 characteristic peak. Two possible metabolic products, C19H15O8 (m/z 371) and C19H19O8 (m/z 375), were observed by mass spectrometry. Potential biotransformation pathway was based on the cleavage of double bond in the terminal furan of AFB1. These generated components had different chemical structures with AFB1, manifesting that the attenuation of AFB1 toxicity would be attributed to the destruction of lactone structure of AFB1 during the conversion process.
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Aflatoxina B1 , Escherichia coli , Humanos , Aflatoxina B1/metabolismo , Células CACO-2 , Escherichia coli/genética , Escherichia coli/metabolismo , ARN Ribosómico 16S/genéticaRESUMEN
BACKGROUND: Gastric cancer (GC) has a poor prognosis and limited therapeutic options. As a new promising cancer therapeutic approach, chimeric antigen receptor (CAR)-T cells represent a potential GC treatment. We investigated the antitumor activity of CAR-T cells target-B7H3 in GC. METHODS: In our study, expression of B7H3 was examined in GC tissues and explored the tumoricidal potential of B7H3-targeting CAR-T cells in GC. B7H3-directed CAR-T cells with a humanized antigen-recognizing domain was generated. The anti-tumor effects of this CAR-T cell were finally investigated in vitro and in vivo. RESULTS: Our results show that B7H3-directed CAR-T cells efficiently killed GC tumor cells. In addition, we found that B7H3 is correlated with tumor cell stemness, and anti-B7H3 CAR-T can simultaneously target stem cell-like GC cells to improve the treatment outcome. CONCLUSIONS: Our study indicates that B7H3 is an attractive target for GC therapy, and B7H3 has high potential for clinical application.
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The aim of this study was to establish a time-resolved fluorescent immunoassay (TRFIA) for the detection of serum Galectin-3 (Gal-3) and apply this method to evaluate the clinical significance of serum Gal-3 in predicting Idiopathic Membranous Nephropathy (IMN) progression. The Gal-3-TRFIA was established using the double antibody sandwich method, with the capture antibodies coated on a 96-well microplate and the detection antibodies chelated with Europium (III) (Eu3+). Serum Gal-3 was detected in 81 patients with IMN and 123 healthy controls to further evaluate the value of the Gal-3 in staging of IMN. The sensitivity of the Gal-3-TRFIA assay was 0.85 ng/mL, and the detection range was 0.85-1000 ng/mL. The Gal-3 intra-batch and inter-batch coefficients of variation were 3.45% and 5.12%, respectively. The correlation coefficient (R) between the Gal-3-TRFIA assay and commercially available enzyme-linked immunosorbent assay kits was 0.83. The serum Gal-3 concentration was higher in patients with IMN (65.57 ± 55.90 ng/mL) compared to healthy controls (16.29 ± 9.91 ng/mL, P < 0.0001). In this study, a wide detection range Gal-3-TRFIA assay was developed using lanthanide (Eu3+) chelates for the detection of Gal-3 concentrations in serum. Gal-3 concentration is elevated in patients with IMN.
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Fluoroinmunoensayo/métodos , Galectina 3/sangre , Glomerulonefritis Membranosa/sangre , Glomerulonefritis Membranosa/diagnóstico , Anticuerpos/sangre , Progresión de la Enfermedad , Ensayo de Inmunoadsorción Enzimática , Galectina 3/inmunología , Humanos , Estudios Prospectivos , Sensibilidad y Especificidad , Factores de TiempoRESUMEN
Acquisition of the direct electrochemical response of protein is the cornerstone for the development of the third generation of electrochemical biosensors. In this work, we developed a nanocluster-assisted protein-film voltammetry technique (NCA-PFV) which can achieve the acquisition of the electrochemical signal and maintain the activity without affecting of the protein's structure. With this strategy, a lipid bilayer membrane is used to immobilize the membrane protein so as to maintain its natural state. Copper nanoclusters with a size smaller than most proteins are then used to function at sub-protein scale and to mediate the electron hopping from the electroactive center of the electrode. As a model, the direct electrochemical signal of cyclooxygenase (COX) is successfully obtained, with a pair of well-defined redox peaks located at -0.39 mV and -0.31 mV, which characterize the heme center of the enzyme. Its catalytic activity towards the substrate arachidonic acid (AA) is also retained. The detection range for AA is 10-1000 µM and the detection limit is 2.4 µM. Electrochemical monitoring of the regulation of the catalytic activity by an inhibitor DuP-697 is also achieved. This work provides a powerful tool for the fabrication of enzyme-based electrochemical biosensors, and is also of great significance for promoting the development and application of next-generation electrochemical biosensors.
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Técnicas Biosensibles/métodos , Cobre/química , Electroquímica/métodos , Hemo/análisis , Nanopartículas/análisis , Prostaglandina-Endoperóxido Sintasas/química , Ácido Araquidónico/química , Carbono/química , Catálisis , Electrodos , Hemo/química , Humanos , Membrana Dobles de Lípidos/química , Microscopía Electrónica de Transmisión , Nanopartículas/química , Oxidación-ReducciónRESUMEN
BACKGROUND: The profiles of liver function abnormalities in COVID-19 patients need to be clarified. METHODS: In this retrospective study, consecutive COVID-19 patients over 60 years old in Renmin Hospital of Wuhan University from January 1 to February 6 were included. Data of demographics, clinical characteristics, comorbidities, laboratory tests, medications and outcomes were collected and analysed. Sequential alterations of serum alanine aminotransferase (ALT) were monitored. RESULTS: A total of 330 patients were included and classified into two groups with normal (n = 234) or elevated ALT (n = 96). There were fewer females (40.6% vs 54.7%, P = .020) and more critical cases (30.2% vs 19.2%, P = .026) in patients with elevated ALT compared with the normal group. Higher levels of bacterial infection indices (eg, white blood cell count, neutrophil count, C-reactive protein and procalcitonin) were observed in the elevated group. Spearman correlation showed that both ALT and AST levels were positively correlated with those indices of bacterial infection. No obvious effects of medications on ALT abnormalities were found. In patients with elevated ALT, most ALT elevations were mild and transient. 59.4% of the patients had ALT concentrations of 41-100 U/L, while only a few patients (5.2%) had high serum ALT concentrations above 300 U/L. ALT elevations occurred at 13 (10-17) days and recovered at 28 (18-35) days from disease onset. For most patients, the elevation of serum ALT levels occurred at 6-20 days after disease onset and reached their peak values within a similar time frame. The recovery of serum ALT levels to normal frequently occurred at 16-20 days or 31-35 days after disease onset. CONCLUSIONS: Liver function abnormalities were observed in 29.1% of elderly people COVID-19 patients, which were slightly and transient in most cases. Liver function abnormalities in COVID-19 may be correlated with bacterial infection.
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COVID-19 , Hepatopatías , Anciano , Femenino , Humanos , Hígado , Pruebas de Función Hepática , Persona de Mediana Edad , Estudios Retrospectivos , SARS-CoV-2RESUMEN
In this paper, a polyimide (PI)/Si/SiO2-based piezoresistive microcantilever biosensor was developed to achieve a trace level detection for aflatoxin B1. To take advantage of both the high piezoresistance coefficient of single-crystal silicon and the small spring constant of PI, the flexible piezoresistive microcantilever was designed using the buried oxide (BOX) layer of a silicon-on-insulator (SOI) wafer as a bottom passivation layer, the topmost single-crystal silicon layer as a piezoresistor layer, and a thin PI film as a top passivation layer. To obtain higher sensitivity and output voltage stability, four identical piezoresistors, two of which were located in the substrate and two integrated in the microcantilevers, were composed of a quarter-bridge configuration wheatstone bridge. The fabricated PI/Si/SiO2 microcantilever showed good mechanical properties with a spring constant of 21.31 nN/µm and a deflection sensitivity of 3.54 × 10-7 nm-1. The microcantilever biosensor also showed a stable voltage output in the Phosphate Buffered Saline (PBS) buffer with a fluctuation less than 1 µV @ 3 V. By functionalizing anti-aflatoxin B1 on the sensing piezoresistive microcantilever with a biotin avidin system (BAS), a linear aflatoxin B1 detection concentration resulting from 1 ng/mL to 100 ng/mL was obtained, and the toxic molecule detection also showed good specificity. The experimental results indicate that the PI/Si/SiO2 flexible piezoresistive microcantilever biosensor has excellent abilities in trace-level and specific detections of aflatoxin B1 and other biomolecules.
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Aflatoxina B1/análisis , Técnicas Biosensibles , Óxidos , Dióxido de SilicioRESUMEN
The chemical constituents from the stems and leaves of Clausena excavata were isolated and purified by column chromatography with silica gel, ODS, Sephadex LH-20 and RP-HPLC. The chemical structures of the isolated compounds were identified on the basis of physicochemical properties, spectroscopic analysis, as well as the comparisons with the data reported in literature. Nineteen compounds were isolated from the 90% ethanol extract of the stems and leaves of C. excavata, which were identified as methyl orsellinate(1), syringaresinol(2), lenisin A(3), scopoletin(4), osthenol(5), N-benzoyltyrarnine methyl ether(6), N-p-coumaroyltyramine(7), aurantiamide acetate(8), 1H-indole-3-carboxaldehyde(9), furostifoline(10), clausenalansine E(11), 3-formylcarbazole(12), clausine L(13), clausine E(14), methyl carbazole-3-carboxylate(15), glycosinin(16), murrayafoline A(17), clausine H(18) and 2,7-dihydroxy-3-formyl-1-(3'-methyl-2'-butenyl)carbazole(19). Among these isolated compounds, compounds 1-11 were isolated from C. excavata for the first time, and compounds 1, 2 and 10 were isolated from the genus Clausena for the first time. In addition, this study evaluated the anti-rheumatoid arthritis activities of compounds 1-19 by measuring their anti-proliferative effects on synoviocytes in vitro according to MTS method. Compounds 10-19 displayed remarkable anti-rheumatoid arthritis activities, which exhibited the inhibitory effects on the proliferation of MH7 A synovial fibroblast cells with the IC_(50) values ranging from(27.63±0.18) to(235.67±2.16) µmol·L~(-1).
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Clausena , Sinoviocitos , Proliferación Celular , Cromatografía de Fase Inversa , Hojas de la PlantaRESUMEN
We report a tunable terahertz (THz) metamaterial absorber (MA) actuated by thermomechanical bimaterial microcantilevers. The THz MA, which is suspended on a silicon substrate by the bimaterial microcantilevers, is a sandwich structure with a bottom Al ground plane, middle air and SiNx dielectric layers, and a top Al rotationally symmetric open split ring resonator. Upon application of a current, a Ti heating resistor integrated on the SiNx dielectric layer induces the bimaterial microcantilevers to bend, causing the air layer thickness to change, modulating the absorption of the THz MA. The tunable THz MA exhibited a relative modulation depth of absorption of 28.1% at 0.69 THz and a thermomechanical sensitivity of 0.12°/K. This tunable THz MA has potential applications in filtering, modulation, control, and THz imaging.
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Two new prenylated chromones, artoheterophines A (1) and B (2), five known prenylated chromones (3-7), as well as five known biogenetically related prenylated flavonoids (8-12) were isolated and characterized from the stems and leaves of A. heterophyllus. Their chemical structures were unambiguously determined through comprehensive spectral data analyses. The antiproliferative and anti-inflammatory effects of all these isolated prenylated chromones and flavonoids were evaluated in vitro. As a result, compounds 1-12 showed notable inhibitory effects against various human cancer cell lines with IC50 values ranging from 0.36 ± 0.02 to 22.09 ± 0.16 µM. Meanwhile, compounds 1-12 exhibited significant inhibitory activities on nitric oxide (NO) production holding IC50 values in the range of 0.48 ± 0.05-19.87 ± 0.21 µM. These research results suggest that the isolation and characterization of these prenylated chromones (1-7) and flavonoids (8-12) holding significant antiproliferative and anti-inflammatory activities could be significant to the discovery and development of new natural anti-tumor and anti-inflammatory drugs. The findings also provides a phytochemical evidence for further development and utilization of the stems and leaves of A. heterophyllus in health and pharmaceutical products.
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Antiinflamatorios/uso terapéutico , Cromonas/química , Flavonoides/química , Antiinflamatorios/farmacología , Proliferación Celular , Humanos , Estructura Molecular , Relación Estructura-ActividadRESUMEN
A phytochemical investigation on the stems and leaves of Wikstroemia chuii resulted in the isolation of three new daphnane diterpenes, wikstroechuins A-C (1-3), together with eight known analogues (4-11). The structures of new daphnane diterpenes (1-3) were determined on the basis of extensive spectroscopic methods and the known daphnane diterpenes (4-11) were identified by comparing their observable spectroscopic data with those reported spectral data in the literature. The anti-inflammatory effects as well as anti-HIV activities in vitro of all isolated daphnane diterpenes 1-11 were assessed. As a consequence, daphnane diterpenes 1-11 displayed remarkable inhibitory activities on NO (nitric oxide) production induced by lipopolysaccharide in mouse macrophage RAW 264.7 cells showing IC50 values in the range of 0.12 ± 0.03 to 10.58 ± 0.16 µM. Meanwhile, daphnane diterpenes 1-11 displayed significant anti-HIV-1 reverse transcriptase (RT) effects showing EC50 values ranging from 0.09509 to 8.62356 µM. These research results indicated that the discovery of these new daphnane diterpenes with remarkable anti-inflammatory and anti-HIV activities from W. chuii, especially these new ones, could be extremely meaningful to the discovery of new anti-inflammatory agents and anti-HIV drugs as well as their potential practical values in the health and pharmaceutical products.
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Fármacos Anti-VIH/farmacología , Antiinflamatorios no Esteroideos/farmacología , Diterpenos/farmacología , Inhibidores de la Transcriptasa Inversa/farmacología , Wikstroemia/química , Animales , Fármacos Anti-VIH/química , Fármacos Anti-VIH/aislamiento & purificación , Antiinflamatorios no Esteroideos/química , Antiinflamatorios no Esteroideos/aislamiento & purificación , Diterpenos/química , Diterpenos/aislamiento & purificación , Relación Dosis-Respuesta a Droga , VIH/efectos de los fármacos , Transcriptasa Inversa del VIH/antagonistas & inhibidores , Transcriptasa Inversa del VIH/metabolismo , Lipopolisacáridos/antagonistas & inhibidores , Lipopolisacáridos/farmacología , Macrófagos/efectos de los fármacos , Macrófagos/metabolismo , Ratones , Pruebas de Sensibilidad Microbiana , Estructura Molecular , Óxido Nítrico/antagonistas & inhibidores , Óxido Nítrico/biosíntesis , Hojas de la Planta/química , Células RAW 264.7 , Inhibidores de la Transcriptasa Inversa/química , Inhibidores de la Transcriptasa Inversa/aislamiento & purificación , Relación Estructura-ActividadRESUMEN
INTRODUCTION: Our recent study found that selective ablation of the distal part of the ligament of Marshall (LOMLSPV ) could suppress ventricular arrhythmias (VAs) during acute myocardial infarction (AMI). This study was to investigate the possible underlying mechanisms. METHODS: Dogs were randomly divided into the sham-operated group (SO; n = 6), AMI group (AMI; n = 8) and the group undergoing LOMLSPV ablation ahead of AMI (LOMD+AMI; n = 8). Incidence of VAs, serum levels of malondialdehyde (MDA) and superoxide dismutase (SOD), expression of connexin (Cx43), Bcl-2, Bax, caspase-3, tumor necrosis factor (TNF)-α, interleukin-6 (IL-6), and high mobility group box (HMGB)1 were compared. Anatomic and immunostaining examinations of LOM LSPV were performed. RESULTS: Compared with the AMI group, incidence of VAs was reduced in the LOMD+AMI group. Compared with the SO group, Cx43, SOD, and Bcl-2 were decreased, MDA, Bax, caspase-3, TNF-α, IL-6, and HMGB1 were increased in the MI group, and all the alterations were significantly restrained in the LOMD+AMI group. A visual nerve fiber communication between the left stellate ganglion (LSG) and LOM and abundant sympathetic nerve bundles distribution in LOMLSPV were revealed. CONCLUSIONS: LOMLSPV ablation could suppress VAs during AMI. The possible mechanism may be associated with disconnection of the sympathetic conduit from LSG to the ventricles. Preservation of Cx43, inhibition of cardiac oxidative stress, apoptosis, and inflammation may be involved.
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Arritmias Cardíacas/prevención & control , Ablación por Catéter , Ligamentos/cirugía , Infarto del Miocardio/cirugía , Potenciales de Acción , Animales , Apoptosis , Proteínas Reguladoras de la Apoptosis/metabolismo , Arritmias Cardíacas/metabolismo , Arritmias Cardíacas/patología , Arritmias Cardíacas/fisiopatología , Conexina 43/metabolismo , Modelos Animales de Enfermedad , Perros , Frecuencia Cardíaca , Mediadores de Inflamación/metabolismo , Ligamentos/inervación , Ligamentos/metabolismo , Ligamentos/patología , Masculino , Infarto del Miocardio/metabolismo , Infarto del Miocardio/patología , Infarto del Miocardio/fisiopatología , Miocardio/metabolismo , Miocardio/patología , Estrés Oxidativo , Ganglio Estrellado/fisiopatologíaRESUMEN
BACKGROUND: Atrial ganglionated plexus (GP) ablation was proved to have therapeutic effects on vasovagal syncope. The study aimed to investigate whether selective ablation of only right anterior GP (ARGP) and right inferior GP (IRGP) was effective in a canine model of vasovagal syncope. METHODS: Seventeen mongrel dogs were divided into control (N = 10) and ablation group (N = 7). Bilateral thoracotomy was performed at the fourth intercostal space and ARGP and IRGP were ablated in the ablation group. A bolus of veratridine (15 ug/kg) was injected into the left atrium to induce vasovagal reflex. Surface electrocardiogram and blood pressure (BP) were continuously monitored. Heart rate (HR) variability was calculated to represent cardiac autonomic tone. RESULTS: Veratridine injection induced vasovagal reflex in all dogs. HR decreased from 149 ± 17 to 89 ± 33 beats/min (P < 0.001) in the control group, while in the ablation group HR decreased from 141 ± 35 to 125 ± 34 beats/min (P = 0.032). The postveratridine HR in the ablation group was significantly higher than that in the control group (P = 0.045). A significantly less intense HR decrease was observed in the ablation group compared with control (-17 ± 16 vs -61 ± 34 beats/min, P = 0.006). Significant BP decreases were induced in both the groups (all P < 0.01), while no evident differences in postveratridine BP and the extent of BP decreases were found between the groups. HR variability revealed significant decrease in cardiac vagal tone after ablation [high-frequency power, 0.50 (0.17-1.05) vs 6.28 (0.68-8.99) ms2 , P = 0.005]. CONCLUSIONS: Selective ablation of ARGP + IRGP weakened cardiac parasympathetic control and significantly attenuated the cardioinhibitory response in an animal model of vasovagal reflex. This ablation strategy might be effective for vasovagal syncope with evident cardioinhibitory response.
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Ablación por Catéter/métodos , Ganglios Autónomos/cirugía , Atrios Cardíacos/cirugía , Sistema de Conducción Cardíaco/fisiopatología , Síncope Vasovagal/cirugía , Animales , Modelos Animales de Enfermedad , Perros , Electrocardiografía , Ganglios Autónomos/fisiopatología , Atrios Cardíacos/fisiopatología , Síncope Vasovagal/fisiopatología , Toracotomía , VeratridinaRESUMEN
High sensitivity of seeds to water loss is a widespread phenomenon in the world's plant species. The molecular basis of this trait is poorly understood but thought to be associated with critical changes in membrane function. We profiled membrane lipids of seeds in eight species with varying levels of desiccation tolerance and found a close association between reducing seed viability and increasing phosphatidic acid (PA). We applied hydration-dehydration cycles to Arabidopsis seeds, which are normally desiccation tolerant, to mimic the onset of desiccation sensitivity with progression towards germination and examined the role of phospholipase D (PLD) in desiccation stress-induced production of PA. We found that PLDα1 became more abundant and migrated from the cytosol to the membrane during desiccation, whereas PLDδ did not change, and that all desiccation-induced PA was derived from PLDα1 hydrolysis. When PLDα1 was suppressed, the germination level after each hydration-dehydration cycle improved significantly. We further demonstrated that PLDα1-mediated PA formation modulates desiccation sensitivity as applying its inhibitor improved seed desiccation tolerance and its suppression in protoplasts enhanced survival under dehydration. The insights provided by comparative lipidomics enable us to propose a new membrane-based model for seed desiccation stress and survival.