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OBJECTIVES: Whether paraspinal muscle degeneration is related to poor clinical outcomes after lumbar surgery is still indistinct, which limits its clinical application. This study aimed to evaluate the predictive value of paraspinal muscle morphology on functional status and re-operation after lumbar spinal surgery. METHODS: A review of the literature was conducted using a total of 6917 articles identified from a search of PubMed, EMBASE, and Web of Science databases through September 2022. A full-text review of 140 studies was conducted based on criteria including an objective assessment of preoperative paraspinal muscle morphology including multifidus (MF), erector spinae (ES), and psoas major (PS) in addition to measuring its relationship to clinical outcomes including Oswestry disability index (ODI), pain and revision surgery. Meta-analysis was performed when required metrics could be calculated in ≥ three studies, otherwise vote counting model was a good alternative to show the effect direction of evidence. The standardized mean difference (SMD) and 95% confidence interval (CI) were calculated. RESULTS: A total of 10 studies were included in this review. Of them, five studies with required metrics were included in the meta-analysis. The meta-analysis suggested that higher preoperative fat infiltration (FI) of MF could predict higher postoperative ODI scores (SMD = 0.33, 95% CI 0.16-0.50, p = 0.0001). For postoperative pain, MF FI could also be an effective predictor for persistent low back pain after surgery (SMD = 0.17, 95% CI 0.02-0.31, p = 0.03). However, in the vote count model, limited evidence was presented for the prognostic effects of ES and PS on postoperative functional status and symptoms. In terms of revision surgery, there was conflicting evidence that FI of MF and ES could predict the incidence of revision surgery in the vote count model. CONCLUSION: The assessment of MF FI could be a viable method to stratify patients with lumbar surgery by the risk of severe functional disability and low back pain. KEY POINTS: ⢠The fat infiltration of multifidus can predict postoperative functional status and low back pain after lumbar spinal surgery. ⢠The preoperative evaluation of paraspinal muscle morphology is conducive for surgeons.
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Dor Lombar , Humanos , Dor Lombar/cirurgia , Músculos Paraespinais/diagnóstico por imagem , Vértebras Lombares/cirurgia , Reoperação , Estado Funcional , Imageamento por Ressonância MagnéticaRESUMO
This work combined the stability of the porous structure of metal-organic frameworks with the strong reducibility of nano zero-valent iron, for the controllable integration of NZVI into MOFs to utilize the advantages of each component with enhancing the rapid decontamination and scavenging of Cr(VI) from wastewater. Hence, four kinds of MOFs/NZVI composites namely ZIF67/NZVI, MOF74/NZVI, MIL101(Fe)/NZVI, CuBTC/NZVI, were prepared for Cr(VI) capture. The results indicated that the stable structure of ZIF67, MOF74, MIL101(Fe), CuBTC, was beneficial for the dispersion of NZVI that could help more close contact between MOFs/NZVI reactive sites and Cr(VI), subsequently, MOFs/NZVI was proved to be better scavengers for Cr(VI) scavenging than NZVI alone. The Cr(VI) capture achieved the maximum adsorption capacity at pH ~ 4.0, which might be due to the participation of more H+ in the reaction and better corrosion of NZVI at lower pH. Mechanism investigation demonstrated synergy of adsorption, reduction and surface precipitation resulted in enhanced Cr(VI) scavenging, and Fe(0), dissolved and surface-bound Fe(II) were the primary reducing species. The findings of this investigation indicated that the as-prepared composites of ZIF67/NZVI, MOF74/NZVI, MIL101(Fe)/NZVI, CuBTC/NZVI, with high oxidation resistance and excellent reactivity, could provide reference for the decontamination and purification of actual Cr(VI)-containing wastewater.
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BACKGROUND CONTEXT: Although the relationships between paraspinal muscles and lumbar degenerative disorders have been acknowledged, paraspinal muscle evaluation has not been incorporated into clinical therapies. PURPOSE: We aimed to establish a novel paraspinal muscle endurance and morphology (PMEM) score to better predict mechanical complications after lumbar fusion. STUDY DESIGN: Prospective cohort study. PATIENT SAMPLE: A total of 212 patients undergoing posterior lumbar interbody fusion with at least 1 year of follow-up were finally included. OUTCOME MEASURES: Mechanical complications including screw loosening, pseudarthrosis and other complications like cage subsidence, and patient-reported outcomes were evaluated at last follow-up. METHODS: The PMEM score comprised 1 functional muscular parameter (the performance time of the endurance test) and 2 imaging muscular parameters (relative functional cross-sectional area [rFCSA] of paraspinal extensor muscles [PEM] and psoas major [PS] on magnetic resonance imaging). The score was established based on a weighted scoring system created by rounding ß regression coefficients to the nearest integer in univariate logistic regression. The diagnostic performance of the PMEM score was determined by binary logistic regression model and receiver operating characteristic (ROC) curve with the area under the curve (AUC). Additionally, pairwise comparisons of ROC curves were conducted to compare the diagnostic performance of the PMEM score with conventional methods based on a single muscular parameter. Moreover, differences of mechanical complications and patient-reported outcomes among the PMEM categories were analyzed using Chi-square test with Bonferroni correction. RESULTS: The PMEM score, calculated by adding the scores for each parameter, ranges from 0 to 5 points. Patients with higher PMEM scores exhibited higher rates of mechanical complications (p<.001). Binary logistic regression revealed that the PMEM score was an independent factor of mechanical complications (p<.001, OR=2.002). Moreover, the AUC of the PMEM score (AUC=0.756) was significantly greater than those of the conventional methods including the endurance test (AUC=0.691, Z=2.036, p<.05), PEM rFCSA (AUC=.690, Z=2.016, p<.05) and PS rFCSA (AUC=0.640, Z=2.771, p<.01). In terms of the PMEM categories, a score of 0-1 was categorized as low-risk muscular state of mechanical complications; 2-3, as moderate; and 4-5, as high-risk state. Moving from the low-risk state to the high-risk state, there was a progressive increase in the rates of mechanical complications (13.8% vs. 32.1% vs. 72.7%; p<.001), and a decrease in the rates of clinically significant improvement of patient-reported outcomes (all p<.05). CONCLUSIONS: The PMEM score might comprehensively evaluate paraspinal muscle degeneration and exhibit greater ability in predicting mechanical complications than the conventional evaluations after lumbar fusion. Surgeons might develop individualized treatment strategy tailored to different muscle degeneration statuses reflected by the PMEM score for decreasing the risk of mechanical complications.
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Alzheimer's disease (AD), the most common form of dementia, has gotten considerable attention. Previous studies have demonstrated that clioquinol (CQ) as a metal chelator is a potential drug for the treatment of AD. However, the mode of action of CQ in AD is still unclear. In our study, the antioxidant effects of CQ on yeast cells expressing Aß42 were investigated. We found that CQ could reduce Aß42 toxicity by alleviating reactive oxygen species (ROS) generation and lipid peroxidation level in yeast cells. These alterations were mainly attributable to the increased reduced glutathione (GSH) content and independent of activities of superoxide dismutase (SOD) and/or catalase (CAT). CQ could affect antioxidant enzyme activity by altering the transcription level of related genes. Interestingly, it was noted for the first time that CQ could combine with antioxidant enzymes to reduce their enzymatic activities by molecular docking and circular dichroism spectroscopy. In addition, CQ restored Aß42-mediated disruption of GSH homeostasis via regulating YAP1 expression to protect cells against oxidative stress. Our findings not only improve the current understanding of the mechanism of CQ as a potential drug for AD treatment but also provide ideas for subsequent drug research and development.
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Peptídeos beta-Amiloides , Antioxidantes , Clioquinol , Glutationa , Estresse Oxidativo , Espécies Reativas de Oxigênio , Saccharomyces cerevisiae , Estresse Oxidativo/efeitos dos fármacos , Peptídeos beta-Amiloides/metabolismo , Peptídeos beta-Amiloides/toxicidade , Saccharomyces cerevisiae/efeitos dos fármacos , Saccharomyces cerevisiae/metabolismo , Clioquinol/farmacologia , Espécies Reativas de Oxigênio/metabolismo , Glutationa/metabolismo , Antioxidantes/farmacologia , Peroxidação de Lipídeos/efeitos dos fármacos , Proteínas de Saccharomyces cerevisiae/metabolismo , Proteínas de Saccharomyces cerevisiae/genética , Superóxido Dismutase/metabolismo , Superóxido Dismutase/genética , Fragmentos de Peptídeos/metabolismo , Simulação de Acoplamento Molecular , Catalase/metabolismo , Fatores de Transcrição/metabolismo , Fatores de Transcrição/genética , Doença de Alzheimer/tratamento farmacológico , Doença de Alzheimer/metabolismoRESUMO
OBJECTIVE: Pathological cardiac remodelling, including cardiac hypertrophy and fibrosis, is a key pathological process in the development of heart failure. However, effective therapeutic approaches are limited. The ß-adrenergic receptors are pivotal signalling molecules in regulating cardiac function. G-alpha interacting protein (GAIP)-interacting protein, C-terminus 1 (GIPC1) is a multifunctional scaffold protein that directly binds to the C-terminus of ß1-adrenergic receptor (ß1-adrenergic receptor). However, little is known about its roles in heart function. Therefore, we investigated the role of GIPC1 in cardiac remodelling and its underlying molecular mechanisms. METHODS: Pathological cardiac remodelling in mice was established via intraperitoneal injection of isoprenaline for 14 d or transverse aortic constriction surgery for 8 weeks. Myh6-driving cardiomyocyte-specific GIPC1 conditional knockout (GIPC1 cKO) mice and adeno-associated virus 9 (AAV9)-mediated GIPC1 overexpression mice were used. The effect of GIPC1 on cardiac remodelling was assessed using echocardiographic, histological, and biochemical analyses. RESULTS: GIPC1 expression was consistently reduced in the cardiac remodelling model. GIPC1 cKO mice exhibited spontaneous abnormalities, including cardiac hypertrophy, fibrosis, and systolic dysfunction. In contrast, AAV9-mediated GIPC1 overexpression in the heart attenuated isoproterenol-induced pathological cardiac remodelling in mice. Mechanistically, GIPC1 interacted with the ß1-adrenergic receptor and stabilised its expression by preventing its ubiquitination and degradation, maintaining the balance of ß1-adrenergic receptor/ß2-adrenergic receptor, and inhibiting hyperactivation of the mitogen-activated protein kinase signalling pathway. CONCLUSIONS: These results suggested that GIPC1 plays a cardioprotective role and is a promising therapeutic target for the treatment of cardiac remodelling and heart failure.
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Insuficiência Cardíaca , Remodelação Ventricular , Animais , Camundongos , Cardiomegalia/patologia , Fibrose , Insuficiência Cardíaca/patologia , Isoproterenol/efeitos adversos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Miócitos Cardíacos , Receptores Adrenérgicos beta/metabolismoRESUMO
Clioquinol (CQ) is considered as a promising drug of neurodegenerative diseases. However, the underlying mechanism is unclear. Our previous study has proved that CQ induces S-phase cell cycle arrest through the elevation of intracellular calcium concentration ([Ca2+]i) with high levels of SERCA2. Furthermore, it could induce autophagy in an intracellular calcium independent manner in human neurotypic SH-SY5Y cells. In this study, the involvement of calreticulin (CRT) in autophagy induced by CQ was investigated. Our results illustrated the endoplasmic reticulum (ER) stress induced by CQ and DTT led to the cell death in different manners. DTT, an ER stress positive control, induced UPR accompanied with up-regulation of CRT and apoptosis, while CQ inhibited UPR accompanied with down-regulation of CRTï¼resulting in autophagy. Then, overexpression of CRT was shown to cause UPR and decrease [Ca2+]i, leading to cell apoptosis and inhibition of S-phase arrest induced by CQ. While the UPR was alleviated and autophagy was further enhanced in CRT deficient cells by using targeted siRNA. Meanwhile, down-regulation of CRT resulted in [Ca2+]i overload and induction of S-phase arrest. Finally, we found that the effect of CQ on the HT22 cells was similar to that on the SH-SY5Y cells. Our data showed for the first time that CQ decreased expression of CRT, leading to autophagy, an increase of [Ca2+]i, and cell S-phase arrest in the neurotypic cells. The present study describes the cellular signal pathways regulating autophagy by CQ and highlights the potential therapeutic application of CQ in neurodegenerative disorders.
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Clioquinol , Neuroblastoma , Humanos , Regulação para Baixo , Cálcio/metabolismo , Clioquinol/farmacologia , Calreticulina/metabolismo , Calreticulina/farmacologia , Estresse do Retículo Endoplasmático , Apoptose , Autofagia , Linhagem Celular TumoralRESUMO
STUDY DESIGN: Finite element analysis (FEA). OBJECTIVE: This study aimed to explore the effects of cage elastic modulus (Cage-E) on the endplate stress in different bone conditions: osteoporosis (OP) and non-osteoporosis (non-OP). We also explored the correlation between endplate thickness and endplate stress. METHOD: The FEA models of L4-L5 with lumbar interbody fusion were designed to access the effects of Cage-E on the endplate stress in different bone conditions. Two groups of the Young's moduli of bony structure were assigned to simulate the conditions of OP and non-OP, and the bony endplates were analyzed in 2 kinds of thicknesses: .5 mm and 1.0 mm, with the insertion of cages with different Young's moduli including .5, 1.5, 3, 5, 10, and 20 GPa. After model validation, an axial compressive load of 400 N and a flexion/extension moment of 7.5Nm was performed on the superior surface of L4 vertebral body in order to analyze the distribution of stress. RESULT: The maximum Von Mises stress in the endplates increased by up to 100% in the OP model compared with non-OP model under the same condition of cage-E and endplate thickness. In both OP and non-OP models, the maximum endplate stress decreased as the cage-E decreased, but the maximum stress in the lumbar posterior fixation increased as the cage-E decreased. Thinner endplate thickness was associated with increased endplate stress. CONCLUSION: The endplate stress is higher in osteoporotic bone than non-osteoporotic bone, which explains part of the mechanism of OP-related cage subsidence. It is reasonable to reduce the endplate stress by reducing the cage-E, but we should balance the risk of fixation failure. Endplate thickness is also important when evaluating the cage subsidence risk.
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Atrial fibrillation (AF), one of the most common types of arrhythmias, is associated with high morbidity and mortality, seriously endangering human health. Inflammation is closely associated with AF development. Activation of the nucleotide-binding domain-like receptor protein 3 (NLRP3) inflammasome in cardiomyocytes has been shown to promote AF progression. Here, we demonstrate the effect of miR-135 on NLRP3 inflammasome and study the cardioprotective role of miR-135 in AF. We observed that overexpression of miR-135 in mice reduced the AF incidence and duration, and inhibited both excessive activation of NLRP3 inflammasome and the increased intracellular calcium release during AF. However, the inhibitory effect of miR-135 on AF was partly abolished in the presence of a specific agonist of the calcium-sensing receptor (CaSR). We showed in the present study that miR-135 has a protective effect against AF by suppressing intracellular calcium-mediated NLRP3 inflammasome activation, suggesting the potential of miR-135 as a therapeutic agent in the treatment of AF.
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BACKGROUND: The role of paraspinal muscle degeneration in the cascade of sagittal imbalance is still unclear. This study aimed to compare paraspinal muscle degeneration in the 4 stages of sagittal imbalance: sagittal balance (SB), compensated sagittal balance (CSB), decompensated sagittal imbalance (DSI), and sagittal imbalance with failure of pelvic compensation (SI-FPC). In addition, it aimed to compare the effects paraspinal muscle endurance and morphology on sagittal spinopelvic alignment in patients with lumbar spinal stenosis. METHODS: A cross-sectional study of 219 patients hospitalized with lumbar spinal stenosis was performed. The isometric paraspinal extensor endurance test and evaluation of atrophy and fat infiltration of the paraspinal extensor muscles and psoas major on magnetic resonance imaging were performed at baseline. Spinopelvic parameters including lumbar lordosis, pelvic tilt, sacral slope, pelvic incidence, and the sagittal vertical axis were measured. RESULTS: The patients with lumbar spinal stenosis were divided into 67 with SB, 85 with CSB, 49 with DSI, and 17 with SI-FPC. There were significant differences in paraspinal muscle endurance and morphology among the 4 groups. Furthermore, the SI-FPC group had poorer paraspinal muscle endurance than either the SB or the CSB group. In multiple linear regression analysis, paraspinal muscle endurance and the relative functional cross-sectional area of the paraspinal extensor muscles were the independent predictors of the sagittal vertical axis, and the relative functional cross-sectional area of the psoas major was the independent predictor of relative pelvic version. CONCLUSIONS: This study indicated that paraspinal muscle degeneration is not only an initiating factor in pelvic retroversion but also a risk factor for progression from a compensated to a decompensated stage. Specifically, the impairment of muscle endurance in the CSB stage may be the reason why patients experience failure of pelvic compensation. In addition, paraspinal muscle endurance and muscle morphology (relative functional cross-sectional area of the paraspinal extensor muscles and psoas major) had different clinical consequences. LEVEL OF EVIDENCE: Prognostic Level II . See Instructions for Authors for a complete description of levels of evidence.
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Lordose , Estenose Espinal , Humanos , Estudos Retrospectivos , Estenose Espinal/diagnóstico por imagem , Músculos Paraespinais/diagnóstico por imagem , Estudos Transversais , Imageamento por Ressonância Magnética , Vértebras Lombares/diagnóstico por imagemRESUMO
[This corrects the article DOI: 10.3389/fbioe.2021.694908.].
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Aspirin is a commonly used anti-inflammatory, analgesic and antithrombotic drug. It has attracted attention due to its potential antifungal therapeutic effect; however, the molecular mechanism is poorly understood. Here, the effects of aspirin on the cell wall of Saccharomyces cerevisiae were explored. We observed by scanning electron microscopy that aspirin could damage the cell wall ultrastructure. Meanwhile, a cellular surface hydrophobicity (CSH) assay showed that aspirin increased the hydrophobicity of the yeast cell surface. A drug sensitivity assay indicated that the overexpression of dolichol phosphate mannose synthase 1 (DPM1) reversed the cell wall damage and decreased the CSH induced by aspirin. Importantly, aspirin decreased the expression and enzyme activity of DPM1 in S. cerevisiae. Molecular docking results demonstrated that aspirin could directly bind to the Ser141 site of DPM1. Similarly, we found that aspirin damaged the cell wall and inhibited the expression of DPM1 in Candida albicans. These findings improve the current understanding of the action mode of aspirin and provide new strategies for antifungal drug design.
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Saccharomyces cerevisiaeRESUMO
BACKGROUND: Hydrogen sulfide (H2S), an endogenous gas, can also be generated from organics putrefaction. It is difficult for suspected cases of H2S poisoning to determine whether H2S in specimens is ingested by antemortem poisoning or generated from organics putrefaction. The aim of this study was to find the biomarkers of acute H2S poisoning via comparing the concentrations of H2S and its metabolites over time in specimens. METHODS: The H2S-spiked blood and blank blood group were established. The decomposition kinetics and the postmortem production of H2S were studied due to organics putrefaction. The specimens were placed under 4 conditions of 37, 20, 4 and - 20 â. The content of H2S in specimens was quantified by gas chromatography-mass spectrometry, and the contents of its metabolites (thiosulfate and trimethylsulfonium) were measured by liquid chromatography-mass spectrometry, and the variation of its concentration was evaluated. RESULTS: In H2S-spiked blood, H2S decreased sharply in the initial stage at 37, 20 and 4 °C, and increased first and then decreased later; but it was relatively stable at - 20 °C. In spiked blood, thiosulfate was 9-fold higher than endogenous concentrations, which increased at first and then decreased during storage. Except for thiosulfate at 37 °C, H2S and thiosulfate in blank blood both increased at first and then decreased in storage; but trimethylsulfonium (TMS) gradually decreased over time in both groups. CONCLUSIONS: Thiosulfate is a reliable biomarker of acute H2S poisoning at - 20â within 7 days. But H2S, because of instability and volatility, is not an ideal poisoning marker. TMS is not an appropriate biomarker due to extremely low concentration in blood.
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Antígenos de Grupos Sanguíneos , Sulfeto de Hidrogênio , Compostos de Sulfônio , Humanos , Mudanças Depois da Morte , TiossulfatosRESUMO
Adipose derived mesenchymal stem cells (AD-MSCs) have shown therapeutic potential in treatments of inflammatory bowel disease (IBD). Due to the harsh host environment and poor survival of the cells, controversy concerning the homing, proliferation and differentiation of MSCs in lesion tissue still remains. It has been reported that conditioned media from MSCs could improve the colitis, whereas the therapeutic efficiency could be significantly elevated by the stimulation of pro-cytokines. In this study, we pre-treated the adipose derived MSCs with the serum from colitis rats and then the activated conditioned media (CM-AcMSC) were collected. To compare the therapeutic effects of CM-MSC and CM-AcMSC on IBD, we constructed dextran sodium sulphate (DSS)-induced colitis rat models. The colitis was induced in rats by administrating 5% DSS in drinking water for 10 days, and the disease symptoms were recorded daily. The colon histopathological changes were observed by different staining methods (H&E and PAS). The expression levels of MUC2 and tight junctions (TJs) were determined by RT-qPCR. The levels of inflammatory cytokines were analyzed by ELISA and western blot analysis. Our findings suggested that CM-AcMSC was more effective in ameliorating the clinical features and histological damage scores. Treatment with CM-AcMSC significantly increased the expression of MUC2 and TJs and suppressed the production of pro-inflammatory cytokines in colonic tissues of colitis rats. The inhibitory effects of CM-AcMSC on inflammatory responses of colitis rats were mediated by NF-κB signaling pathway. These results suggested that pre-activation of MSCs with serum from colitis rats could promote the production of paracrine factors and improve the therapeutic effects of conditioned medium on colitis rats.