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Telomeric repeat containing RNA (TERRA) is a noncoding RNA that is transcribed from telomeres. Previous study showed that TERRA trans anneals by invading into the telomeric duplex to form an R-loop in mammalian cells. Here, we elucidate the molecular mechanism underlying TERRA recruitment and invasion into telomeres in the context of shelterin proteins, RAD51 and RNase H using single molecule (sm) assays. We demonstrate that TERRA trans annealing into telomeric DNA exhibits dynamic movement that is stabilized by TRF2. TERRA annealing to the telomeric duplex results in the formation of a stable triplex structure which differs from a conventional R-loop. We identified that the presence of a sub-telomeric DNA and a telomeric overhang in the form of a G-quadruplex significantly enhances TERRA annealing to telomeric duplex. We also demonstrate that RAD51-TERRA complex invades telomere duplex more efficiently than TERRA alone. Additionally, TRF2 increases TERRA affinity to telomeric duplex and protects it from RNase H digestion. In contrast, TRF1 represses TERRA annealing to telomeric duplex and fails to provide protection against RNase H digestion. Our findings provide an in-depth molecular mechanism underpinning TERRA recruitment and annealing to the telomere.
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Riboswitches are regulatory elements found in bacterial mRNAs that control downstream gene expression through ligand-induced conformational changes. Here, we used single-molecule FRET to map the conformational landscape of the translational SAM/SAH riboswitch and probe how co-transcriptional ligand-induced conformational changes affect its translation regulation function. Riboswitch folding is highly heterogeneous, suggesting a rugged conformational landscape that allows for sampling of the ligand-bound conformation even in the absence of ligand. The addition of ligand shifts the landscape, favoring the ligand-bound conformation. Mutation studies identified a key structural element, the pseudoknot helix, that is crucial for determining ligand-free conformations and their ligand responsiveness. We also investigated ribosomal binding site accessibility under two scenarios: pre-folding and co-transcriptional folding. The regulatory function of the SAM/SAH riboswitch involves kinetically favoring ligand binding, but co-transcriptional folding reduces this preference with a less compact initial conformation that exposes the Shine-Dalgarno sequence and takes min to redistribute to more compact conformations of the pre-folded riboswitch. Such slow equilibration decreases the effective ligand affinity. Overall, our study provides a deeper understanding of the complex folding process and how the riboswitch adapts its folding pattern in response to ligand, modulates ribosome accessibility and the role of co-transcriptional folding in these processes.
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Riboswitch , Conformación de Ácido Nucleico , Pliegue del ARN , Emparejamiento Base , Ribosomas , LigandosRESUMEN
In eukaryotes, the origin recognition complex (ORC) is required for the initiation of DNA replication. The smallest subunit of ORC, Orc6, is essential for prereplication complex (pre-RC) assembly and cell viability in yeast and for cytokinesis in metazoans. However, unlike other ORC components, the role of human Orc6 in replication remains to be resolved. Here, we identify an unexpected role for hOrc6, which is to promote S-phase progression after pre-RC assembly and DNA damage response. Orc6 localizes at the replication fork and is an accessory factor of the mismatch repair (MMR) complex. In response to oxidative damage during S phase, often repaired by MMR, Orc6 facilitates MMR complex assembly and activity, without which the checkpoint signaling is abrogated. Mechanistically, Orc6 directly binds to MutSα and enhances the chromatin-association of MutLα, thus enabling efficient MMR. Based on this, we conclude that hOrc6 plays a fundamental role in genome surveillance during S phase.
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Reparación de la Incompatibilidad de ADN , Complejo de Reconocimiento del Origen , Fase S , Proteínas de Unión al ADN/metabolismo , Humanos , Proteínas MutL/metabolismo , Complejo de Reconocimiento del Origen/genética , Complejo de Reconocimiento del Origen/metabolismo , Unión ProteicaRESUMEN
BACKGROUND: Starting enzyme replacement therapy (ERT) before severe irreversible muscular damage occurs is important in infantile-onset Pompe disease (IOPD). This long-term follow-up study demonstrates our diagnostic and treatment strategies for IOPD and compares our clinical outcomes with those of other medical centres. METHODS: In this long-term follow-up study, we analysed the outcomes of very early ERT with premedication hydrocortisone in patients with IOPD. Out of 1 228 539 infants screened between 1 January 2010 and 28 February 2021, 33 newborns had confirmed IOPD in Taipei Veterans General Hospital. Twenty-six were regularly treated and monitored at Taipei Veterans General Hospital. Echocardiographic parameters, biomarkers, IgG antibodies against alglucosidase alpha, pulmonary function variables and developmental status were all assessed regularly over an average follow-up duration of 6.18±3.14 years. We compared the long-term treatment outcomes of our patients with those of other research groups. RESULTS: The average age at ERT initiation was 9.75±3.17 days for patients with classic IOPD. The average of the latest antialglucosidase alpha IgG titre was 669.23±1159.23. All enrolled patients had normal heart sizes, motor milestones, cognitive function and pulmonary function that were near-normal to normal. Compared with patients in other studies, our patients had better outcomes in all aspects. CONCLUSION: Very early ERT using our rapid diagnostic and treatment strategy enabled our patients with IOPD to have better outcomes than patients in other medical centres.
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Enfermedad del Almacenamiento de Glucógeno Tipo II , Lactante , Humanos , Recién Nacido , Enfermedad del Almacenamiento de Glucógeno Tipo II/diagnóstico , Enfermedad del Almacenamiento de Glucógeno Tipo II/tratamiento farmacológico , Enfermedad del Almacenamiento de Glucógeno Tipo II/epidemiología , Tamizaje Neonatal , Estudios de Seguimiento , Terapia de Reemplazo Enzimático , EcocardiografíaRESUMEN
BACKGROUND AND PURPOSE: Patients with hypervascular spinal tumors may have severe blood loss during tumor resection, which increases the risks of perioperative morbidity and mortality. However, the preoperative evaluation of tumor vascularity may be challenging; moreover, the reliability of the data obtained in conventional preoperative noninvasive imaging is debatable. In this study, we compared conventional magnetic resonance imaging (MRI) and subtraction computed tomography angiography (CTA) in terms of their performance in vascularity evaluation. The catheter digital subtraction angiography (DSA) technique was used as a reference standard. METHODS: This study included 123 consecutive patients with spinal tumor who underwent subtraction CTA, catheter DSA, and subsequent surgery between October 2015 and October 2021. Data regarding qualitative and semiquantitative subtraction CTA parameters and conventional MRI signs were collected for comparison with tumor vascularity graded through catheter DSA. The diagnostic performance of qualitative CTA, quantitative CTA, and conventional MRI in assessing spinal tumor vascularity was analyzed. RESULTS: Qualitative subtraction CTA was the best noninvasive imaging modality in terms of diagnostic performance (area under the receiver operating characteristic curve [AUROC], 0.95). Quantitative CTA was relatively inferior (AUROC, 0.87). MRI results had low reliability (AUROC, 0.51 to 0.59). Intratumoral hemorrhage and prominent foraminal venous plexus were found to be the specific signs for hypervascularity (specificity 93.2%). CONCLUSIONS: Qualitative subtraction CTA offers the highest diagnostic value in evaluating spinal tumor vascularity, compared to quantitative CTA and MRI. Although conventional MRI may not be a reliable approach, certain MRI signs may have high specificity, which may be crucial for assessing spinal tumor vascularity.
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BACKGROUND: Impaired renal function is frequently observed in patients with heart failure and reduced ejection fraction (HFrEF). The differential effect of sacubitril/valsartan and angiotensin-converting enzyme inhibitors/angiotensin-receptor blockers (ACEIs/ARBs) on the clinical and renal outcomes in patients with HFrEF and chronic kidney disease (CKD) remains unknown. AIMS: This study aimed to explore the differential effect of sacubitril/valsartan and ACEI/ARB on the clinical and renal outcomes as well as renal function over a 12-month follow-up period in HFrEF patients with and without CKD. METHODS: Patients with HfrEF (LVEF ≤35%) and NYHA class ≥II were enrolled from the Chang Gung Research Database between 2017 and 2020. Baseline characteristics were compared between patients prescribed sacubitril/valsartan and ACEI/ARB. After propensity score matching, the following clinical and renal outcomes were compared between the two groups in patients with and without CKD over a 12-month follow-up period: acute kidney injury (AKI), emergent dialysis/renal death, HF hospitalization, cardiovascular mortality, and all-cause mortality. RESULTS: This study enrolled 3735 HFrEF patients with a mean left ventricular EF of 27.56 ± 5.86%, who had been prescribed sacubitril/valsartan (N = 1708) or ACEI/ARB (N = 2027). After propensity score matching, the clinical and renal outcomes did not differ between the sacubitril/valsartan and ACEI/ARB groups in patients without CKD. In patients with CKD, the ACEI/ARB group had a significantly higher incidence of all-cause mortality than the sacubitril/valsartan group (14.89% vs. 10.50%; hazard ratio 1.46; 95% confidence interval 1.06-2.00; p = 0.02), and the incidence of AKI, HF hospitalization, and CV mortality did not differ between the two groups. CONCLUSIONS: Sacubitril/valsartan had a lower all-cause mortality compared to ACEI/ARB in symptomatic HFrEF patients with CKD. Further prospective randomized studies are warranted to confirm our findings.
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BACKGROUND: Pulmonary vein isolation (PVI) is a cornerstone therapy for paroxysmal atrial fibrillation (PAF). The variations in nonlinear heart rate variability (HRV) between patients with and without recurrences remain unclear. We aimed to characterize the nonlinear HRV before and after PVI in patients with and without recurrence. METHODS: Twenty-five drug-refractory PAF patients (56.0 ± 9.1 years old, 20 males) who received PVI were enrolled. Holter electrocardiography were performed before, 1-3, and 6-12 months after PVI. After 8.2 ± 2.5 months of follow-ups after PVI, patients were divided into two groups: the recurrence (n = 8) and non-recurrence (n = 17) groups. Linear and nonlinear HRV variables were analyzed, including the Poincaré Plot analysis and the Detrended Fluctuation Analysis (DFA). RESULTS: The non-recurrence group, but not the recurrence group, had decreased high-frequency component (HF), the root mean square of successive RR interval differences (RMSSD), and the Poincaré Plot index SD1 1-3 months after PVI and increased DFAslope2 6-12 months after PVI. The non-recurrence group's LF/HF ratio and DFAslope1 decreased significantly 1-3 and 6-12 months after PVI, respectively, whereas there was no significant change in the recurrence group after PVI. CONCLUSIONS: Significantly reduced vagal tone 1-3 months after PVI, increased long-term fractal complexity 6-12 months after PVI, and decreased sympathetic tone as well as short-term fractal complexity 1-3 and 6-12 months after PVI led to a better AF-free survival after PVI. These findings suggest that neuromodulation and heart rate dynamics play crucial roles in AF recurrence following PVI.
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Fibrilación Atrial , Ablación por Catéter , Venas Pulmonares , Masculino , Humanos , Persona de Mediana Edad , Anciano , Fibrilación Atrial/cirugía , Venas Pulmonares/cirugía , Fractales , Electrocardiografía , Resultado del TratamientoRESUMEN
BACKGROUND: Vitamin K antagonists and different direct oral anticoagulants (DOACs) have different renal clearance rates. However, the impact of different stages of chronic renal impairment on the efficacy and safety of warfarin, dabigatran, rivaroxaban, apixaban, and edoxaban in atrial fibrillation (AF) patients remains unclear. METHODS: This study enrolled AF patients from the Chang Gung Research Database. The study endpoints included thromboembolic events, major/fatal bleeding, gastrointestinal (GI) bleeding and intracranial hemorrhage (ICH). The risks of time to study endpoints between groups were compared using a Cox proportional hazards regression model with adjustment. RESULTS: This study enrolled 3525 patients with moderate renal impairment (30 ≤ creatinine clearance (CrCl) < 60 mL/min), 2846 patients with mild renal impairment (60 ≤ CrCl < 90 mL/min) and 1153 patients with CrCl ≥ 90 mL/min. Over the 3.3 ± 0.9 years follow-up period, the cumulative thromboembolic events rates and the cumulative event rates of major/fatal bleeding and ICH did not differ among the warfarin and different DOAC groups at different stages of chronic renal impairment. The annual incidences of thromboembolic events, major/fatal bleeding, GI bleeding, and ICH were similar among the warfarin and different DOAC groups at different stages of renal impairment. CONCLUSION: There did not appear to be major differences in bleeding or thromboembolic risk compared to warfarin in AF patients across a range of degree of renal failure when appropriate dose reductions of the DOACs are made.
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While most SAM riboswitches strongly discriminate between SAM and SAH, the SAM/SAH riboswitch responds to both ligands with similar apparent affinities. We have determined crystal structures of the SAM/SAH riboswitch bound to SAH, SAM and other variant ligands at high resolution. The riboswitch forms an H-type pseudoknot structure with coaxial alignment of the stem-loop helix (P1) and the pseudoknot helix (PK). An additional three base pairs form at the non-open end of P1, and the ligand is bound at the interface between the P1 extension and the PK helix. The adenine nucleobase is stacked into the helix and forms a trans Hoogsteen-Watson-Crick base pair with a uridine, thus becoming an integral part of the helical structure. The majority of the specific interactions are formed with the adenosine. The methionine or homocysteine chain lies in the groove making a single hydrogen bond, and there is no discrimination between the sulfonium of SAM or the thioether of SAH. Single-molecule FRET analysis reveals that the riboswitch exists in two distinct conformations, and that addition of SAM or SAH shifts the population into a stable state that likely corresponds to the form observed in the crystal. A model for translational regulation is presented whereby in the absence of ligand the riboswitch is largely unfolded, lacking the PK helix so that translation can be initiated at the ribosome binding site. But the presence of ligand stabilizes the folded conformation that includes the PK helix, so occluding the ribosome binding site and thus preventing the initiation of translation.
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Pliegue del ARN , Riboswitch , S-Adenosilhomocisteína/química , S-Adenosilmetionina/química , Emparejamiento Base , Transferencia Resonante de Energía de Fluorescencia , S-Adenosilhomocisteína/metabolismo , S-Adenosilmetionina/metabolismoRESUMEN
Background: The safety and efficacy of dual antiplatelet therapy (DAPT) in medically treated acute myocardial infarction (AMI) patients with baseline thrombocytopenia (platelet count < 150 × 103/uL) are unclear. Methods: In this multi-institute retrospective cohort study, we included 468 patients with medically treated AMI with baseline thrombocytopenia and separated them into single antiplatelet therapy (SAPT) and DAPT groups according to the discharge anti-thrombotic strategy. The primary outcome was net clinical adverse events (NACEs), defined as a composite of death, ischemic events (myocardial infarction, ischemic stroke, and transient ischemic attack), and major bleeding within 30 days. Results: There were 168 patients in the SAPT group (100 taking aspirin and 68 taking clopidogrel) and 300 in the DAPT group. A primary outcome occurred in 35 (24.11 per 100 patient-months) patients in the SAPT group and 39 (14.26 per 100 patient-months) patients in the DAPT group [adjusted hazard ratio (HR): 0.67; 95% confidence interval (CI): 0.40-1.10; p = 0.1145]. Kaplan-Meier curves showed favorable results in the DAPT group (log-rank p = 0.0243). Bleeding events occurred in 18 (10.71 per 100 patient-months) patients in the SAPT group and 18 (6.40 per 100 patient-months) patients in the DAPT group (adjusted HR: 0.66; 95% CI: 0.32-1.36; p = 0.2573). Conclusions: DAPT versus SAPT as discharge anti-thrombotic strategy in thrombocytopenic patients with medically treated AMI did not significantly improve NACEs at 30 days. However, there was a trend towards favorable outcomes in the DAPT group. These results should be interpreted carefully with respect to the relatively limited trial population and study design.
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Background: Heart rate complexity, derived from nonlinear heart rate variability (HRV), has been shown to help predict the outcomes of various diseases. Changes in heart rate complexity before and after paroxysmal atrial fibrillation (PAF) events are unclear. Objectives: To evaluate changes in heart rate complexity through nonlinear HRV before and after PAF events. Methods: We enrolled 65 patients (72 ± 12.34 years old, 31 females) with 99 PAF events who received 24-hour Holter recording, and analyzed nonlinear HRV variables including Poincaré plot analysis, sample entropy (SampEn), and multiscale entropy (MSE). HRV analyses were applied to a 20-minute window before the onset and after the termination of PAF events. HRV parameters were evaluated and compared based on eight different 5-minute time segments, as we divided each 20-minute window into four segments of 5 minutes each. Results: SampEn and MSE1~5 significantly decreased before the onset of PAF events, whereas SampEn, MSE1~5 and MSE6~20 significantly increased after the termination of PAF events. SD1 and SD2, which are nonlinear HRV parameters calculated via Poincaré plot analysis, did not significantly change before the PAF events, however they both decreased significantly after termination. Conclusions: Heart rate complexity significantly decreased before the initiation and increased after the termination of PAF events, which indicates the crucial role of nonlinear heart rate dynamics in the initiation and termination of PAF.
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Size-selected 3 nm gas-phase Au clusters dispersed by cluster beam deposition (CBD) on a conducting fluorine-doped tin oxide template show strong enhancement in mass activity for the methanol electro-oxidation (MEO) reaction compared to previously reported nanostructured gold electrodes. Density functional theory-based modeling on the corresponding Au clusters guided by experiments attributes this high MEO activity to the high density of exposed under-coordinated Au atoms at their faceted surface. In the description of the activity trends, vertices and edges are the most active sites due to their favorable CO and OH adsorption energies. The faceted structures occurring in this size range, partly preserved upon deposition, may also prevent destructive restructuring during the oxidation-reduction cycle. These results highlight the benefits of using CBD in fine-tuning material properties on the nanoscale and designing high-performance fuel cell electrodes with less material usage.
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BACKGROUND: The autonomic activity plays a critical role in generating paroxysmal atrial fibrillation (PAF). This study aimed to evaluate the changes in the autonomic nerve activity before and after PAF events in patients with and without ischemic heart disease (IHD). METHODS: The study included 49 patients (71.43 ± 12.24 years old, 26 males) with PAF events lasting more than 30 s during 24-hr ambulatory Holter monitoring. The 20-min intervals before and after PAF events were divided into eight segments of 5 min each. Heart rate variability (HRV) analyses of the time and frequency domains were applied to each time segment. RESULTS: Patients with IHD had significant increases in the root mean square successive differences (r-MSSD, p = .008) and HF component (p = .04), followed by a significant increase in the LF/HF ratio (p = .02) preceding the onset of PAF. Patients without IHD had only a significant increase in the r-MSSD (p = .045) preceding the onset of PAF. During the termination of PAF events, patients in both the IHD and control groups had a significantly decreased r-MSSD and HF, respectively. CONCLUSION: Ischemic heart disease causes a sympathovagal imbalance in the initiation of PAF. Decreased parasympathetic activity regulated the termination of PAF in both the IHD and control groups. The modification of the autonomic nervous system (ANS) activity should be individualized due to the autonomic complexity in AF arrhythmogenesis and termination.
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Fibrilación Atrial/complicaciones , Fibrilación Atrial/fisiopatología , Sistema Nervioso Autónomo/fisiopatología , Electrocardiografía Ambulatoria/métodos , Isquemia Miocárdica/complicaciones , Isquemia Miocárdica/fisiopatología , Anciano , Fibrilación Atrial/diagnóstico , Femenino , Humanos , MasculinoRESUMEN
Hydrogen is considered as sustainable and environmentally friendly energy for global energy demands in the future. Here a Co-FeS2 catalyst with surface phosphide doping (P/Co-FeS2 ) for hydrogen evolution reaction (HER) in acidic solutions is developed. The P/Co-FeS2 exhibits superior HER electrochemical performance with overpotential of -90 mV at 100 mA cm-2 and Tafel slope of 41 mV/decade and excellent durability.
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The Ta2O5-based micro-ring resonator with an unloaded quality factor of 182,000 has been demonstrated to realize efficient nonlinear wavelength generation. The propagation loss of the resonator is 0.5 cm-1, and the buildup factor of the ring resonator is estimated to be â¼50. With a high buildup factor of the ring structure, the four-wave-mixing (FWM) conversion efficiency of -30 dB is achieved in the resonator with a pump power of 6 mW. Based on power-dependent FWM results, the nonlinear refractive index of Ta2O5 is estimated to be 1.4×10-14 cm2/W at a wavelength of â¼1550 nm. The demonstration of an enhanced FWM process in the Ta2O5-based micro-ring cavity implies the possibility of realizing FWM-based optical parametric oscillation in a Ta2O5-based micro-ring resonator.
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Membranes and their size-selective filtering properties are universal in nature and their behavior is exploited to design artificial membranes suited for, e.g., molecule or nanoparticle filtering and separation. Exploring and understanding penetration and transmission mechanisms of nanoparticles in thin-film systems may provide new opportunities for size selective deposition or embedding of the nanoparticles. Here, we demonstrate an unexpected finding that the sieving of metal nanoparticles through atomically thin nonporous alkali halide films on a metal support is size dependent and that this sieving effect can be tuned via the film thickness. Specifically, relying on scanning tunneling microscopy and spectroscopy techniques, combined with density functional theory calculations, we find that defect-free NaCl films on a Au(111) support act as size-dependent membranes for deposited Au nanoclusters. The observed sieving ability is found to originate from a driving force toward the metal support and from the dynamics of both the nanoparticles and the alkali halide films.
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In this paper, a sandwich structure comprising a SiO2 capping layer, amorphous Germanium (a-Ge) nanodots (NDs), and a pit-patterned Silicon (Si) substrate is developed, which is then annealed by utilizing a pulsed ultraviolet excimer laser in order to fabricate an array of pure, single crystal Ge NDs at room temperature. A wide bandgap SiO2 capping layer is used as a transparent thermally isolated layer to prevent thermal loss and Si-Ge intermixing. The two-dimensional pit-patterned Si substrate is designed to confine the absorbed laser energy, reduce the melting point, and block the surface migration of the Ge. After optimizing the laser radiation parameters such that the laser energy density is 200 mJ cm(-2), the laser annealing period is 10 s, and the number of laser shots is 10, pure, single crystal Ge NDs that have both a regular arrangement and a uniform size distribution are obtained in the pits of the Si substrates. The Raman spectrum shows a highly symmetric Ge transversal optical peak with a full width at half maximum of 4.2 cm(-1) at 300.7 cm(-1), which is close to that of the original Ge wafer. In addition, the high-resolution transmission electron microscopy image for the Ge NDs and the corresponding selected area electron diffraction pattern shows a clear single crystalline structure without any impurities.
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INTRODUCTION: Computed tomography-digital subtraction angiography (CT-DSA) is a radiological method for assessing spinal metastatic tumor vascularity. The study aimed to investigate the association between CT-DSA results and perioperative outcomes in spinal metastatic surgery. MATERIAL AND METHODS: Patients who underwent spinal metastatic operations with preoperative CT-DSA examinations at any time between January 2018 to December 2022. CT-DSA was classified into five grades ranging from grade 0 to grade 4. Grades 3 and 4 were indicative of hypervascularity. We analyzed the perioperative outcomes of intraoperative blood loss amount, massive hemorrhage (≥2500 ml) occurrence, blood transfusion status, operation time, hospital stay duration, and 30-day and 60-day mortality rates. Logistic regression analyses were conducted to identify factors affecting the likelihood of massive hemorrhage in conjunction with CT-DSA. RESULTS: Data from 212 operations involving 209 patients were analyzed. In total, 30, 36, 66, 56, and 24 operations had CT-DSA grades from grade 0 to grade 4, respectively. Eighty (38 %) studies were indicative of hypervascularity. CT-DSA grade was positively correlated with the amount of operative blood loss, the occurrence of massive hemorrhage, and the amount of blood in blood transfusion (p < 0.05). However, CT-DSA grades was not significantly associated with operation duration or mortality rate. A multivariable analysis indicated that factors such as hemoglobulin, hypervascular pathology, and spinal instability neoplastic scores were positively correlated with CT-DSA grade. CT-DSA grade (odds ratio: 2.37, p = 0.02), spinal metastatic invasiveness index, and tumor size (≥50 mL) were found to be independent predictors in a multivariable logistic regression analysis where factors associated with massive hemorrhage were included. Hypervascular pathology type was not significantly associated with the likelihood of hemorrhage in the univariable and multivariable analyses. CONCLUSIONS: CT-DSA serves as an effective tool for assessing vascularity, and is associated with intra-operative blood loss and likelihood of experiencing massive hemorrhage. The predictive capability of CT-DSA surpasses that of traditional histopathology classifications, making it a useful method for preoperative planning in spinal metastatic surgeries.
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Angiografía de Substracción Digital , Neoplasias de la Columna Vertebral , Humanos , Femenino , Masculino , Neoplasias de la Columna Vertebral/diagnóstico por imagen , Neoplasias de la Columna Vertebral/cirugía , Neoplasias de la Columna Vertebral/secundario , Persona de Mediana Edad , Anciano , Adulto , Pérdida de Sangre Quirúrgica , Estudios Retrospectivos , Resultado del Tratamiento , Anciano de 80 o más Años , Angiografía por Tomografía Computarizada/métodosRESUMEN
OBJECTIVES: Obstructive sleep apnea (OSA) is known to increase the risk of cardiovascular disease and inflammation plays a significant role in this process. Renal denervation (RDN) is a novel approach aimed at reducing sympathetic nervous system activity. The role of RDN in the inflammatory response to chronic OSA (COSA) is currently unclear. The main objective was to study inflammatory mechanisms in the rabbit heart with COSA and the effects of RDN. METHODS: Eighteen rabbits were randomized into three groups: sham control, COSA, and COSA-RDN. COSA and COSA-RDN groups received liquid silicone injections, while the sham control group received normal saline. We performed combined surgical and chemical RDN through bilateral retroperitoneal flank incisions in the COSA-RDN group after silicone injections. The inflammatory mechanisms were assessed through immunoblotting, real-time PCR, and ELISA after the experiment. RESULTS: H&E staining showed immune cell infiltration in COSA, which decreased after RDN treatment. The level of α7nAChR was significantly reduced in COSA compared to the sham control but was restored to a similar level in the COSA-RDN group. Furthermore, the expressions of p-JAK2 and p-STAT3 were significantly reduced in COSA but showed an up-regulation following RDN treatment. Similarly, levels of the inflammatory markers IL-6, IL-1ß and TNF-α were markedly increased in COSA but decreased after RDN therapy. We observed NF-κB activation in the COSA rabbit model, which decreased after RDN treatment, as evidenced by decreased NF-κB expression. CONCLUSIONS: Our study suggests that RDN treatment may prevent COSA-associated heart inflammation via the JAK2-STAT3 signaling pathway.
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Quinasas Janus , Apnea Obstructiva del Sueño , Animales , Conejos , FN-kappa B , Transducción de Señal , Factores de Transcripción STAT , Simpatectomía , Modelos Animales de Enfermedad , Inflamación , Apnea Obstructiva del Sueño/cirugía , SiliconasRESUMEN
Animals rapidly acquire surrounding information to perform the appropriate behavior. Although social learning is more efficient and accessible than self-learning for animals, the detailed regulatory mechanism of social learning remains unknown, mainly because of the complicated information transfer between animals, especially for aversive conditioning information transmission. The current study revealed that, during social learning, the neural circuit in observer flies used to process acquired aversive conditioning information from demonstrator flies differs from the circuit used for self-learned classic aversive conditioning. This aversive information transfer is species dependent. Solitary flies cannot learn this information through social learning, suggesting that this ability is not an innate behavior. Neurons used to process and execute avoidance behavior to escape from electrically shocked flies are all in the same brain region, indicating that the fly brain has a common center for integrating external stimuli with internal states to generate flight behavior.