ABSTRACT
It is a hot problem in epilepsy research to detect and predict seizures by EEG signals. Clinically, it is generally observed that there are only sudden abnormal signals during the ictal stage, but there is no significant difference in the EEG signal between the interictal and preictal stages. To solve the problem that preictal signals are difficult to recognize clinically, and then effectively improve the recognition efficiency of epileptic seizures, so, in this paper, some nonlinear methods are comprehensively used to extract the hidden information in the EEG signals in different stages, namely, phase space reconstruction (PSR), Poincaré section (PS), synchroextracting transform (SET), and machine learning for EEG signal analysis. First, PSR based on C-C method is used, and the results show that there are different diffuse attractor trajectories of the signals in different stages. Second, the confidence ellipse (CE) is constructed by using the scatter diagram of the corresponding trajectory on PS, and the aspect ratio and area of the ellipse are calculated. The results show that there is an interesting transitional phenomenon in preictal stage. To recognize ictal and preictal signals, time-frequency (TF) spectrums, which are processed by SET, are fed into the convolutional neural network (CNN) classifier. The accuracy of recognizing ictal and preictal signals reaches 99.7% and 93.7%, respectively. To summarize, our results based on nonlinear method provide new research ideas for seizure detection and prediction.NEW & NOTEWORTHY Our results based on nonlinear method have better practical significance and clinical application value and improved the prediction efficiency of epileptic EEG signals effectively. This work provides direct insight into the application of these biomarkers for seizure detection and prediction.
Subject(s)
Electroencephalography , Epilepsy , Nonlinear Dynamics , Signal Processing, Computer-Assisted , Humans , Electroencephalography/methods , Epilepsy/physiopathology , Epilepsy/diagnosis , Machine Learning , Neural Networks, Computer , Seizures/physiopathology , Seizures/diagnosisABSTRACT
BACKGROUND: Ginsenoside Rg3 is a component of ginseng that protects against myocardial ischemia/reperfusion (MI/R) injury. Ferroptosis is a new form of cell death characterized by oxidative damage to phospholipids. The purpose of this study was to examine the role and of ginsenoside Rg3 in MI/R and the mechanism. METHODS: A mouse model of left anterior descending (LAD) ligation-induced myocardial ischemia/reperfusion (MI/R) injury and oxygen-glucose deprivation/reperfusion (OGD/R) were used as in vitro and in vivo models, respectively. Echocardiographic analysis, 2,3,5-triphenyltetrazolium chloride (TTC) staining and hematoxylin-eosin (H&E) staining were used to assess the cardioprotective effects of ginsenoside Rg3. Western blotting, biochemical analysis, small interfering RNA analysis and molecular docking were performed to examine the underlying mechanism. RESULTS: Ginsenoside Rg3 improved cardiac function and infarct size in mice with MI/R injury. Moreover, ginsenoside Rg3 increased the expression of the ferroptosis-related protein GPX4 and inhibited iron deposition in mice with MI/R injury. Ginsenoside Rg3 also activated the Nrf2 signaling pathway. Ginsenoside Rg3 attenuated myocardial ischemia/reperfusion-induced ferroptosis via the Nrf2 signaling pathway. Notably, ginsenoside Rg3 regulated the keap1/Nrf2 signaling pathway to attenuate OGD/R-induced ferroptosis in H9C2 cells. Taken together, ginsenoside Rg3 attenuated myocardial ischemia/reperfusion-induced ferroptosis via the keap1/Nrf2/GPX4 signaling pathway. CONCLUSIONS: Our findings demonstrated that ginsenoside Rg3 ameliorate MI/R-induced ferroptosis via the keap1/Nrf2/GPX4 signaling pathway.
Subject(s)
Ferroptosis , Ginsenosides , Kelch-Like ECH-Associated Protein 1 , Mice, Inbred C57BL , Myocardial Reperfusion Injury , NF-E2-Related Factor 2 , Phospholipid Hydroperoxide Glutathione Peroxidase , Signal Transduction , Ginsenosides/pharmacology , Animals , Ferroptosis/drug effects , Mice , Myocardial Reperfusion Injury/drug therapy , NF-E2-Related Factor 2/metabolism , Kelch-Like ECH-Associated Protein 1/metabolism , Signal Transduction/drug effects , Male , Phospholipid Hydroperoxide Glutathione Peroxidase/metabolism , Disease Models, AnimalABSTRACT
[This corrects the article DOI: 10.3389/fnins.2023.1117340.].
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Background: Low back pain or sciatic pain because of lumbar intervertebral disc herniation (LDH) is caused by mechanical compression and/or an inflammatory component on the nerve root. However, it is difficult to define to what extent each component contributes to the pain. This study attempted to explore the effects of macrophage polarization on clinical symptoms in patients experiencing LDH after surgery, and investigated the association between macrophage cell percentages and clinical efficacy. Methods: This study retrospectively harvested nucleus pulposus (NP) tissue samples from 117 patients. Clinical symptoms and efficacy using the visual analog scale (VAS) and Oswestry Disability Index (ODI) were evaluated at different time points preoperatively and postoperatively. CD68, CCR7, CD163, and CD206 were selected as macrophage phenotypic markers. Results: Seventy-six samples showed positive expression of macrophage markers in NP samples of patients with LDH, whereas 41 patients displayed negative results. No significant differences were detected between the two groups, involvement of several demographic data, and preoperative clinical findings. With respect to the macrophage-positive group, no significant correlation was detected between the positive rate of the four markers and the VAS score or ODI after surgery. However, patients with NP samples positive for CD68 and CCR7 expression showed significantly lower VAS scores 1 week after surgery compared with those in the negative group. Moreover, the improvement in VAS score showed a strong positive correlation with CD68- and CCR7-positive cell percentages. Conclusions: Our results indicated that pro-inflammatory M1 macrophages may be associated with the reduction of chronic pain after surgery. Therefore, these findings contribute to better personalized pharmacological interventions for patients with LDH, considering the heterogeneity of pain.
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Lots of studies have been carried out on characteristic of epileptic Electroencephalograph (EEG). However, traditional EEG characteristic research methods lack exploration of spatial information. To study the characteristics of epileptic EEG signals from the perspective of the whole brainï¼this paper proposed combination methods of multi-channel characteristics from time-frequency and spatial domains. This paper was from two aspects: Firstly, signals were converted into 2D Hilbert Spectrum (HS) images which reflected the time-frequency characteristics by Hilbert-Huang Transform (HHT). These images were identified by Convolutional Neural Network (CNN) model whose sensitivity was 99.8%, accuracy was 98.7%, specificity was 97.4%, F1-score was 98.7%, and AUC-ROC was 99.9%. Secondly, the multi-channel signals were converted into brain networks which reflected the spatial characteristics by Symbolic Transfer Entropy (STE) among different channels EEG. And the results show that there are different network properties between ictal and interictal phase and the signals during the ictal enter the synchronization state more quickly, which was verified by Kuramoto model. To summarize, our results show that there was different characteristics among channels for the ictal and interictal phase, which can provide effective physical non-invasive indicators for the identification and prediction of epileptic seizures.
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Background and Objective: Esophageal cancer is one of the common malignant tumors in China. Previous studies have shown that surgery alone is less effective. Neoadjuvant therapy refers to preoperative chemoradiotherapy, which is the standard treatment for locally advanced and operable esophageal cancer. Selection of appropriate surgical methods and timing after neoadjuvant therapy is of great significance for improving the prognosis of patients and reducing postoperative complications. Methods: An online electronic search of all eligible literature through PubMed, Google Scholar, and the Cochrane Library database was conducted using a combination of the following keywords: esophageal cancer, neoadjuvant therapy, neoadjuvant chemotherapy, chemoradiotherapy, immunotherapy, targeting, surgery, complications. With a focus on the use of surgery after neoadjuvant therapy, Eligible articles were identified by one or both authors. Key Content and Findings: Neoadjuvant chemoradiotherapy combined with radical surgical resection remains the current standard of care for resectable esophageal cancer, significantly improving survival and pathologic complete response (PCR) compared with preoperative chemotherapy Recently, studies have also found that immunotherapy combined with chemotherapy has a more advantageous pathological response in patients with locally advanced disease. Although the emergence of targeted drugs has led to a change in treatment mode from traditional chemoradiotherapy to precision therapy, the postoperative progression-free survival (PFS) and overall survival (OS) need to be explored as well as how surgery-related risks caused by treatment can be reduced. Traditionally, surgery is performed 4-6 weeks after neoadjuvant therapy, and optimal timing for surgery after treatment is still being explored as research progresses, the surgical method also should be determined according to the specific situation of the patient. Postoperative complications should be dealt with in a timely manner, and of course, active preoperative intervention is equally important. Conclusions: Neoadjuvant therapy combined with surgery is the gold standard for resectable esophageal cancer. However, optimal timing of surgery after preoperative treatment remains unclear. Minimally invasive thoracoscopic surgery (including robotic surgery) has gradually replaced traditional open surgery. Active prevention before operation, accurate and meticulous operation during operation, and timely treatment after operation can minimize the incidence of adverse events.
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Protein glycation can result in the formation of advanced glycation end products (AGEs), which pose a potential health risk due to their association with diabetic complications. Natural products are a source of drugs discovery and the search for potential natural inhibitors of AGEs is of great significance. Glucosinolates (GSLs) mainly from cruciferous plants have potential antioxidant, anti-inflammatory, and anti-glycation activities. In this study, the inhibitory activity of GSLs on bovine serum albumin (BSA) along with its mechanism was investigated by virtual screening and various computational simulation techniques. Virtual screening revealed that 174 GSLs were screened using Maestro based on the glide score and 89% of the compounds were found to have potential anti-glycation ability with the docking scores less than -5 kcal/mol. Molecular docking showed that the top 10 GSLs were bound to the IIA structural domain of BSA. Among them, glucohesperin (1) and 2-hydroxyethyl glucosinolate (2) had the lowest docking scores of -9.428 and -9.333 kcal/mol, respectively, reflecting their good binding affinity. Molecular dynamics simulations of 1 (ΔG = -43.46 kcal/mol) and 2 (ΔG = -43.71 kcal/mol) revealed that the complexes of these two compounds with proteins had good stability. Further binding site analysis suggested that the mechanism of inhibition of protein glycation by these two active ingredients might be through competitive hydrogen bonding to maintain the structural integrity of the protein, thus inhibiting glycation reaction. Moreover, the ADMET values and CYP450 metabolism prediction data were within the recommended values. Therefore, it can be concluded that 1 and 2 may act as potential anti-glycation agents.
Subject(s)
Glucosinolates , Molecular Dynamics Simulation , Molecular Docking Simulation , Antiglycation Agents , Glycation End Products, AdvancedABSTRACT
Since the successful clinical trial of AuroShell for photothermal therapy, there is currently intense interest in developing gold-based core-shell structures with near-infrared (NIR) absorption ranging from NIR-I (650-900 nm) to NIR-II (900-1700 nm). Here, we propose a seed-mediated successive growth approach to produce gold nanoshells on the surface of the nanoscale metal-organic framework (NMOF) of UiO-66-NH2 (UiO = the University of Oslo) in one pot. The key to this strategy is to modulate the proportion of the formaldehyde (reductant) and its regulator / oxidative product of formic acid to harness the particle nucleation and growth rate within the same system. The gold nanoshells propagate through a well-oriented and controllable diffusion growth pattern (points â facets â octahedron), which has not been identified. Most strikingly, the gold nanoshells prepared hereby exhibit an exceedingly broad and strong absorption in NIR-II with a peak beyond 1300 nm and outstanding photothermal conversion efficiency of 74.0%. Owing to such superior performance, these gold nanoshells show promising outcomes in photoacoustic (PA), computed tomography (CT), and photothermal imaging-guided photothermal therapy (PTT) for breast cancer, as demonstrated both in vitro and in vivo.
Subject(s)
Nanoshells , Nanoshells/chemistry , Photothermal Therapy , Gold/chemistry , Multimodal Imaging , PhototherapyABSTRACT
Exceptional points (EPs) of non-Hermitian systems are gaining more and more attention due to their important applications in unidirectional transmitters, sensors, etc. However, theoretical studies on EPs of reflection, transmission, and absorption spectra are less available. In this paper, in the dark-bright mode-coupled plasmonic systems, the variations of EPs of reflection, transmission, and absorption spectra are numerically investigated using temporal coupled-mode theory, and an assumption is given using the representation transformation theory. The intermediate representation (IR) is firstly proposed and related to the reflection spectrum, while the normal representation (NR) is associated with the absorption spectrum. In the region far from EPs, the IR (or NR) describes the reflection (or absorption) spectrum well. Near EPs, modified formulas similar to the representation transformation theory are given. In order to verify the correctness of the assumption, two metasurfaces are designed. And the simulation results are in good agreement with the assumption and it is found in the near-infrared and visible-light band that the absorption loss of the dark mode is linearly related to the EPs of reflection, transmission, and absorption spectra, while the radiation loss of the bright mode is only linearly related to the EPs of the absorption spectrum. These laws can help to manipulate the splitting of spectral lines for reflection, transmission, and absorption by adjusting the radiation loss and absorption loss of bright mode, the absorption loss of dark mode, and the coupling coefficients between two resonant modes. This research provides a guiding scheme for the design of micro and nano photonics devices.
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Macrophage infiltration and polarization during lumbar intervertebral disc herniation (LDH) have attracted increased attention but their role remains unclear. To explore macrophage polarization in herniated nucleus pulposus (NP) tissue of patients with LDH and investigate the association between cell frequency and different clinical characteristics or symptoms, we conducted a retrospective study by analyzing NP tissue samples from 79 patients. Clinical features and symptoms, using the visual analog scale (VAS) and Oswestry disability index (ODI), were collected. The macrophage markers CD68, CCR7, CD163, and CD206; pro-inflammatory cytokine TNF-α; and anti-inflammatory factor IL-4 were analyzed by immunohistochemistry. The frequency of polarized macrophages and positivity rate of pro- and anti-inflammatory cytokines showed significant differences in some of clinical characteristics. Specifically, higher CCR7+ and TNF-α + proportions were identified in the high-intensity zone (HIZ) and the type of extrusion and sequestration NP tissue than in non-HIZ and protrude NP tissue. Higher CD206+ and IL-4+ proportion were detected in Modic changes. However, no differences in gender, age, smoking status, Pfirrmann grade, analgesic use, leg pain duration, and segments were found between groups. CD68+ , CCR7+ , and CD206+ cell proportions, and TNF-α and IL-4 showed positive associations with VAS scores preoperation. Associations between ODI and the macrophages markers were weak/insignificant. Our results indicated that macrophage polarization or macrophage-like cells contribute to LDH pathological features. Macrophage populations displaying significant associations with VAS score reflected continuous M1/M2 transition contributing to pain during LDH. These findings may contribute to enhanced/personalized pharmacological interventions for patients with LDH considering pain heterogeneity.
Subject(s)
Intervertebral Disc Degeneration , Intervertebral Disc Displacement , Intervertebral Disc , Nucleus Pulposus , Humans , Intervertebral Disc Displacement/pathology , Retrospective Studies , Nucleus Pulposus/pathology , Interleukin-4/metabolism , Receptors, CCR7/metabolism , Tumor Necrosis Factor-alpha/metabolism , Pain , Lumbar Vertebrae/surgery , Macrophages/metabolism , Intervertebral Disc Degeneration/pathology , Intervertebral Disc/pathologyABSTRACT
Introduction: Aged kidney is characterized by mitochondrial dysfunction, cellular senescence, and fibrogenesis. The activation of Wnt/ß-catenin signaling plays an important role in the initiation of kidney aging. However, the inhibiting strategies have not been discovered in detail. Here, we compared the therapeutic effects of two ß-catenin inhibitors, KYA1797K and ICG-001, to assess their superiority. Methods: Two-month-old male C57BL/6 mice which had undergone unilateral nephrectomy and received D-galactose (D-gal) injection were co-treated with KYA1797K or ICG-001 at 10 mg/kg/day for 4 weeks. Human proximal renal tubular cells were treated with D-gal and KYA1797K/ICG-001 to compare their effects. Results: Compared with ICG-001, which inhibits ß-catenin pathway through blocking the binding of ß-catenin and cAMP response element-binding protein (CREB)-binding protein (CBP), KYA1797K, a novel small molecule destabilizing ß-catenin through activating Axin-GSK3ß complex, possesses the superior effects on protecting against kidney aging. In D-gal-treated accelerated aging mice, KYA1797K could greatly inhibit ß-catenin pathway, preserve mitochondrial homeostasis, repress cellular senescence, and retard age-related kidney fibrosis. In cultured proximal tubular cells, KYA1797K shows a better effect on inhibiting cellular senescence and could better suppress mitochondrial dysfunction and ameliorate the fibrotic changes, at the same dose as that in ICG-001. Conclusion: These results show that effectively eliminating ß-catenin is a necessity to target against age-related kidney injury, suggesting the multiple transcriptional regulation of ß-catenin in kidney aging besides T-cell factor/lymphoid enhancer-binding factor family of transcription factors (TCF/LEF-1).
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Macrophage infiltration and polarization have been increasingly observed in intervertebral disc (IVD) degeneration (IDD). However, their biological roles in IDD are still unrevealed. We harvested conditioned media (CM) derived from a spectrum of macrophages induced from THP-1 cells, and examined how they affect nucleus pulposus cells (NPCs) in vitro, by studying cell proliferation, extracellular matrix (ECM) synthesis, and pro-inflammation expression; and in vivo by injection CM in a rat IDD model. Then, high-throughput sequencing was used to detect differentially expressed genes (DEGs). Gene Ontology (GO), the Kyoto Encyclopedia of Genes and Genomes (KEGG), and protein-protein interaction (PPI) networks were used to further analysis. Higher CCR7+ (M1 marker) and CD206+ (M2 marker) cell counts were found in the degenerated human IVD tissues as compared with the control. Furthermore, the cell co-culture model showed M1CM attenuated NPC proliferation, downregulated the expression of ECM anabolic genes encoding aggrecan and collagen IIα1, upregulated the expression of ECM catabolic genes encoding MMP-13, and inflammation-related genes encoding IL-1ß, IL-6, and IL-12, while M2CM showed contrasting trends. In IDD model, higher histological scores and lower disc height index were found following M1CM treatment, while M2CM exhibited opposite results. M1CM injection decreased ECM anabolic and increased ECM catabolic, as well as the upregulation of inflammation-related genes after 8 weeks treatment, while M2CM slowed down these trends. Finally, a total of 637 upregulated and 655 downregulated genes were detected in M1CM treated NPCs, and 975 upregulated genes and 930 downregulated genes in the M2CM groups. The top 30 GO terms were shown and the most significant KEGG pathway was cell cycle in both groups. Based on the PPI analysis, the five most significant hub genes were PLK1, KIF20A, RRM2, CDC20, and UBE2C in the M1CM groups and RRM2, CCNB1, CDC20, PLK1, and UBE2C in the M2CM groups. In conclusion, macrophage polarization exhibited diverse roles in IDD progression, with M1CM exacerbating cell proliferation suppression and IVD degeneration, while M2CM attenuated IDD development. These findings may facilitate the further elucidation of the role of macrophage polarization in IDD, and provide novel insights into the therapeutic potential of macrophages.
Subject(s)
Intervertebral Disc Degeneration , Animals , Cell Proliferation , Extracellular Matrix/metabolism , Humans , Inflammation/metabolism , Inflammation Mediators/metabolism , Intervertebral Disc Degeneration/genetics , Intervertebral Disc Degeneration/metabolism , Macrophages/metabolism , RatsABSTRACT
The main challenges in clinical applications of mesenchymal stem cells (MSCs) are attributed to their heterogeneity. It is believed that preconditioning of MSCs with active compounds may enhance the expression of potentially therapeutic molecules and thus achieve stable and effective therapeutic outcomes. In the present study, we investigated the mechanism by which pyrogallol increased the therapeutic efficacy of human umbilical cord mesenchymal stem cells (hUCMSCs) against LPS-induced acute lung injury (ALI). hUCMSCs with pyrogallol treatment increased expression of HO-1 at both mRNA and protein levels, accompanied by Kelch-Like ECH-Associated Protein 1 (Keap1) degradation, and upregulation of the Nrf2 protein levels as well as nuclear translocation of Nrf2. Moreover, the modulation of Keap1 and Nrf2 as well as HO-1 upregulation by pyrogallol was reversed by pretreatment with N-acetylcysteine (NAC) and a P38 kinase inhibitor (SB203580). Whereas, NAC pretreatment abrogated pyrogallol-mediated activation of P38 kinase, indicating that pyrogallol-derived ROS led to P38 kinase activation, thus promoting Nrf2/HO-1 signaling. Additionally, we found that the induction of p62 by the pyrogallol-mediated ROS/P38/Nrf2 axis interacted with Keap1 and resulted in autophagic degradation of Keap1, which created a positive feedback loop to further release of Nrf2. Furthermore, the increased expression of HO-1 in pyrogallol-pretreated hUCMSCs led to enhanced inhibitory effects on LPS-mediated TLR4/P-P65 signaling in BEAS-2B cells, resulting in increasing suppression of LPS-indued expression of a series of pro-inflammatory mediators. Compared to untreated hUCMSCs, Sprague-Dawley (SD) rats with pyrogallol-primed hUCMSCs transplantation showed enhanced improvements in LPS-mediated lung pathological alterations, the increased lung index (lung/body ratio), apoptosis of epithelial cells, the activation of TLR4/NF-κB signaling as well as the release of pro-inflammatory mediators. Together, these results suggested that hUCMSCs with pyrogallol pretreatment enhanced the therapeutic efficacy of hUCMSCs, which may provide a promising therapeutic strategy to maximize the therapeutic efficacy of hUCMSC-based therapy for treating LPS-associated ALI.
Subject(s)
Acute Lung Injury , Mesenchymal Stem Cell Transplantation , Pyrogallol , Acetylcysteine/metabolism , Acute Lung Injury/drug therapy , Acute Lung Injury/therapy , Animals , Heme Oxygenase-1/genetics , Heme Oxygenase-1/metabolism , Humans , Inflammation/drug therapy , Inflammation/therapy , Inflammation Mediators/metabolism , Kelch-Like ECH-Associated Protein 1/genetics , Kelch-Like ECH-Associated Protein 1/metabolism , Lipopolysaccharides , Mesenchymal Stem Cells/cytology , NF-E2-Related Factor 2/genetics , NF-E2-Related Factor 2/metabolism , NF-kappa B/metabolism , Pyrogallol/pharmacology , RNA, Messenger/metabolism , Rats , Rats, Sprague-Dawley , Reactive Oxygen Species/metabolism , Toll-Like Receptor 4/genetics , Toll-Like Receptor 4/metabolism , Umbilical Cord/cytologyABSTRACT
BACKGROUND: Inhibitory control, comprising cognitive inhibition and response inhibition, showed consistent deficits among several major psychiatric disorders. We aim to identify the trans-diagnostic convergence of neuroimaging abnormalities underlying inhibitory control across psychiatric disorders. METHODS: Inhibitory control tasks neuroimaging, including functional magnetic resonance imaging, single-photon emission computed tomography, and positron emission tomography articles published in PubMed and Web of Science before April 2020 comparing healthy controls with patients with several psychiatric disorders were searched. RESULTS: 146 experiments on 2653 patients with different disorders and 2764 control participants were included. Coordinates of case-control differences coded by diagnosis and inhibitory control components were analyzed using activation likelihood estimation. A robust trans-diagnostic pattern of aberrant brain activation in the bilateral cingulate gyri extending to medial frontal gyri, right insula, bilateral lentiform nuclei, right inferior frontal gyrus, right precuneus extending to inferior parietal lobule, and right supplementary motor area were detected. Frontostriatal pathways are the commonly disrupted neural circuits in the inhibitory control across psychiatric disorders. Furthermore, Patients showed aberrant activation in the dorsal frontal inhibitory system in cognitive inhibition, while in the frontostriatal system in response inhibition across disorders. CONCLUSION: Consistent with the Research Domain Criteria initiative, current findings show that psychiatric disorders may be productively formulated as a phenotype of trans-diagnostic neurocircuit disruption. Our results provide new insights for future research into mental disorders with inhibition-related dysfunctions.
Subject(s)
Mental Disorders , Neuroimaging , Brain/pathology , Brain Mapping , Humans , Magnetic Resonance Imaging , Positron-Emission TomographyABSTRACT
Aging is an important risk factor for kidney injury. Energy homeostasis plays a key role in retarding aging, and mitochondria are responsible for energy production. In the kidney, renal tubular cells possess high abundance of mitochondria to meet the high energy consumption. AMPK is an evolutionarily conserved serine/threonine kinase which plays a central role in maintaining energy homeostasis and mitochondrial homeostasis. Besides that, AMPK also commands autophagy, a clearing and recycling process to maintain cellular homeostasis. However, the effect of AMPK activators on kidney aging has not been fully elucidated. To this end, we testified the effects of O304, a novel direct AMPK activator, in naturally aging mice model and D-Galactose (D-Gal)-treated renal tubular cell culture. We identified that O304 beneficially protects against cellular senescence and aged-related fibrosis in kidneys. Also, O304 restored energy metabolism, promoted autophagy and preserved mitochondrial homeostasis. Transcriptomic sequencing also proved that O304 induced fatty acid metabolism, mitochondrial biogenesis and ATP process, and downregulated cell aging, DNA damage response and collagen organization. All these results suggest that O304 has a strong potential to retard aged kidney injury through regulating AMPK-induced multiple pathways. Our results provide an important therapeutic approach to delay kidney aging.
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Inflammation is the primary pathological phenomenon associated with disc degeneration; the inflammatory cytokine tumor necrosis factor (TNF-α) plays a crucial role in this pathology. The anti-inflammatory and regenerative effects of M2 macrophages on nucleus pulposus cells (NPCs) in intervertebral disc degeneration (IDD) progression remain unknown. Here, M2 conditioned medium (M2CM) was harvested and purified from human acute monocytic leukaemia cell line (THP-1) cells and mouse peritoneal macrophages, respectively; it was used for culturing human NPCs and a mouse intervertebral disc (IVD) organ culture model. NPCs and IVD organ models were divided into three groups: group 1 treated with 10% fetal bovine serum (control); group 2 treated with 10 ng/ml TNF-α; and group 3 treated with 10 ng/ml TNF-α and M2CM (coculture group). After 2-14 days, cell proliferation, extracellular matrix synthesis, apoptosis, and NPC senescence were assessed. Cell proliferation was reduced in TNF-α-treated NPCs and inhibited in the M2CM co-culture treatment. Moreover, TNF-α treatment enhanced apoptosis, senescence, and expression of inflammatory factor-related genes, including interleukin-6, MMP-13, ADAMTS-4, and ADAMTS-5, whereas M2CM coculture significantly reversed these effects. In addition, co-culture with M2CM promoted aggrecan and collagen II synthesis, but reduced collagen Iα1 levels in TNF-α treatment groups. Using our established three-dimensional murine IVD organ culture model, we show that M2CM suppressed the inhibitory effect of TNF-α-rich environment. Therefore, co-culture with M2CM promotes cell proliferation and extracellular matrix synthesis and inhibits inflammation, apoptosis, and NPC senescence. This study highlights the therapeutic potential of M2CM for IDD.
Subject(s)
Intervertebral Disc Degeneration , Intervertebral Disc , Nucleus Pulposus , Aggrecans/metabolism , Animals , Child , Collagen/metabolism , Culture Media, Conditioned/metabolism , Culture Media, Conditioned/pharmacology , Cytokines/metabolism , Humans , Inflammation/metabolism , Interleukin-6/metabolism , Intervertebral Disc/pathology , Intervertebral Disc Degeneration/pathology , Macrophages/metabolism , Matrix Metalloproteinase 13/metabolism , Mice , Nucleus Pulposus/metabolism , Serum Albumin, Bovine/metabolism , Serum Albumin, Bovine/pharmacology , Serum Albumin, Bovine/therapeutic use , Tumor Necrosis Factor-alpha/metabolismABSTRACT
Plant-plant interactions is one of the key field in ecology, which is important for the efficient nutrient utilization, productivity improvement, and plant community assembly. Arbuscular mycorrhizal fungi are important plant mutualistic microorganisms that connect plant roots to form common mycelial networks (CMNs), which play major roles in transferring nutrients and water and regu-lating plant community dynamics. Recent studies demonstrated that these CMNs could act as conduits for transmitting disease and aphid-induced signals among plants, and activating chemical defence in uninfested neighboring plants. In this review, we introduced recent research advances on the contribution of CMNs on plant interaction, the main factors that influences the functions of CMNs, and the role of CMNs transfer and redistribute nutrients and water among plant. In addition, the mechanism underlying underground chemical signal communication, seedling establishment and plants community assembly were summarized. Finally, we proposed challenges facing CMNs in plant-plant interactions and the practical problems. It would provide reference for further understanding the ecological functions of CMNs in plant-plant interactions.
Subject(s)
Mycorrhizae , Plant Roots , Plants , Seedlings , SymbiosisABSTRACT
This review highlights vital details that can be easily overlooked and discuss how to identify and fix failed cannulation from another novel insight. Appropriate arterial cannulation strategy during cardiopulmonary bypass (CPB) in Stanford type A aortic dissection (AAD) is highly necessary to reach satisfactory perfusion effects and appreciable clinical outcomes. Despite several previously published reviews on cannulation strategies in AAD, most focus on the advantages and disadvantages by comparing various cannulation strategies. In fact, most of evidence came from retrospective studies. More importantly, however, some important details and novel approaches maybe overlooked due to variety reasons. These overlooked details also make sense in clinical practice. Papers related to cannulation refer to type AAD were retrieved and analyzed from the PubMed and Medline database. The key words such as "aortic dissection", "cannula", "cannulation", "cannulation strategy", "cerebral perfusion", "type I aortic dissection" were conducted and analyzed. In addition, we looked at some new and very significant specific perfusion techniques such as anterograde cerebral perfusion combined with retrograde inferior vena caval perfusion (RIVP) and reperfusion via the right carotid artery before surgery. The arterial cannulation site and strategy should be determined individually. Monitoring measures are very necessary in the whole procedure.
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BACKGROUND: The aim of the present study was to use a numerical simulation based on computational fluid dynamics (CFD) to analyze the difference of different cannulation methods on hemodynamics characteristic in a type A aortic dissection (TAAD) model. METHODS: A finite-element analysis based on the CFD model of a TAAD patient was used, and axillary artery cannulation (AAC), innominate artery cannulation (IAC), and femoral artery cannulation (FAC) were analyzed under different situations, including a cardiac output (CO) of 2.5 L/min and cardiopulmonary bypass (CPB) of 2.5 L/min (partial CPB before cross-clamping aorta, defined as condition A), and a CO of 0 L/min and CPB of 5 L/min (aortic cross-clamping phase, defined as condition B). The insertion of an 8-mm cannula into the different models was simulated. Hemodynamic characteristics, including wall shear stress, wall stress, blood flow, and velocity were analyzed. RESULTS: In condition A, the total flow of branches of the aortic arch was 2,009.5 mL/min (AAC), 1,855.47 mL/min (IAC), and 1,648.03 mL/min (FAC). All cannulation methods improved left renal blood perfusion. However, in relation to blood flow in the right renal artery, FAC showed the highest blood flow (105 mL/min). The results in condition B were similar to those of condition A. The velocity, shear stress, and stress of entry tear via AAC and IAC decreased in condition B compared with condition A. The velocity, shear stress, stress of tear via AAC was lower than that of IAC. CONCLUSIONS: Different cannulation modes have an effect on the hemodynamic characteristic of the tear, but this effect is related to different states of CPB. AAC was found to superior to IAC, especially in reducing velocity, stress, and shear stress of site of tear. However, IAC and AAC are more conductive to blood supply than FAC in branch vessels of the aortic arch without being affected by the CPB state.
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BACKGROUND: To evaluate the short-term efficacy of azygos arch-sparing McKeown minimally invasive esophagectomy (McKeown-MIE). METHODS: We retrospectively analyzed the clinical data of 221 patients with thoracic esophageal squamous cell carcinoma who underwent McKeown-MIE at the Department of Thoracic Surgery of Gaozhou People's Hospital from August 1, 2017 to September 30, 2019. According to whether the azygos arch was preserved or not, the patients were assigned to one of two groups: the preservation group (40 cases) and the ligation group (181 cases). Within 3 months of the operation, the perioperative outcomes and the postoperative short-term efficacy of the two groups were compared. RESULTS: After propensity score (PS) matching, 40 pairs of patients were matched successfully. Between the two groups, there were no statistical difference in intraoperative blood loss, the number of lymph nodes dissected, thoracic drainage duration, fasting time, postoperative hospital stay time, and major postoperative complications (P>0.05). Compared with the ligation group, patients in the preservation group had a shorter intensive care unit (ICU) stay time, a shorter operative time, a lower volume of postoperative thoracic drainage (both the first 3 days and overall) following surgery, a tubular stomach that had a smaller caliber, and a lower incidence of tubular gastric malpositioning (P<0.05). CONCLUSIONS: Preserving the azygos arch during a McKeown-MIE is safe and feasible. Doing so, not only effectively restricts the expansion of the gastric conduit, leading to a lower incidence of malpositioning, but also dramatically reduces postoperative thoracic drainage, and ICU stay time.