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Eighteen nitrogen-containing compounds (1-18) were isolated from cultures of the lichen-associated Streptomyces flavidovirens collected from the Qinghai-Tibet Plateau, including seven phenazine derivatives with three new ones, named subphenazines A-C (2-4), two new furan pyrrolidones (8-9), and nine known alkaloids. The structures were elucidated by spectroscopic data analysis, and absolute configurations were determined by single-crystal X-ray diffraction and ECD calculations. The phenazine-type derivatives, in particular compound 3, exhibited significantly better antineuroinflammatory activity than other isolated compounds (8-18). Compound 3 inhibited the release of proinflammatory cytokines including IL-6, TNF-α, and PGE2, and the nuclear translocation of NF-κB; it also reduced the oxidative stress and activated the Nrf2 signaling pathway in LPS-induced BV2 microglia cells. In vivo anti-inflammatory activity in zebrafish indicated that 3 inhibited LPS-stimulated ROS generation. These findings suggested that compound 3 might be a potent antineuroinflammatory agent through the regulation of the NF-κB/Nrf2 signaling pathways.
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Charcoal is commonly preserved in both natural and artificial sediments, and is intensively used in paleontological, paleoenvironmental, and archaeological studies due to the abundant bio-information it contains. The biochemical properties of charcoal are also used for paleoclimatic reconstruction; however, the reliability of this approach has been challenged due to a lack of clarity on how physicochemical properties change during the charring process, as well as the temperatures required for charcoalification. To address this lack, in this study, Qinghai spruce and Chinese pine wood samples from the northeastern Tibetan Plateau were heated at different temperatures and for different lengths of time under restricted oxygen conditions. The reflectance; carbon, nitrogen, and oxygen content; and tracheid morphology were quantified before and after heating to assess changes related to the charring process. Archaeological charcoal remains were then evaluated to determine the charcoalification temperatures by comparing with the experimental results. The minimum temperature required for wood charcoalification was â¼300 °C, while temperatures recorded by archaeological charcoal were concentrated at 400-500 °C. During the charring experiments, the tracheid cell walls gradually homogenized, and tracheid cell wall thickness and lumen area decreased by â¼20%. On average, 50% mass losses were observed; the carbon and oxygen content (% wt.) approximately changed from 47% to 60% and 48% to 35% respectively, while the nitrogen content (% wt.) fluctuated around 0.2%. The reflectance increased slightly from 0% to 0.5%. We propose that the charcoalification of wood tissue refers to charring (in restricted air) and carbonization (in the almost absence of air) when the wood is exposed to a heat source, which then finally transforms into a black, inert solid. This quantitative study provided valuable data and a thorough assessment of the process of wood charcoalification, as well as accurately estimated the feasibility of using charcoal physicochemical properties in paleoclimatic research.
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A chemical investigation of the arils of Torreya grandis led to the isolation of seven abietane-type diterpenoids (compounds 1-7) including three previously undescribed compounds, one unreported natural product, and three known analogs. The structures of these compounds were determined by means of spectroscopy, single-crystal X-ray diffraction, and ECD spectra. An antibacterial activity assay showed that compounds 5 and 6 had significant inhibitory effects on methicillin-resistant Staphylococcus aureus, with MIC values of 100 µM. Moreover, compounds 1, 3, 4, and 7 exhibited anti-neuroinflammatory activity in LPS-stimulated BV-2 microglia cells, with the IC50 values ranging from 38.4 to 67.9 µM.
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Abietanos , Antibacterianos , Abietanos/química , Abietanos/farmacología , Antibacterianos/farmacología , Antibacterianos/química , Pruebas de Sensibilidad Microbiana , Microglía/efectos de los fármacos , Microglía/metabolismo , Ratones , Staphylococcus aureus Resistente a Meticilina/efectos de los fármacos , Animales , Estructura Molecular , Línea Celular , Antiinflamatorios/farmacología , Antiinflamatorios/química , Extractos Vegetales/química , Extractos Vegetales/farmacología , Diterpenos/farmacología , Diterpenos/química , Diterpenos/aislamiento & purificación , Lipopolisacáridos/farmacologíaRESUMEN
Asymptomatic Leucine-Rich Repeat Kinase 2 Gene (LRRK2) carriers are at risk for developing Parkinson's disease (PD). We studied presymptomatic substantia nigra pars compacta (SNc) regional neurodegeneration in asymptomatic LRRK2 carriers compared to idiopathic PD patients using neuromelanin-sensitive MRI technique (NM-MRI). Fifteen asymptomatic LRRK2 carriers, 22 idiopathic PD patients, and 30 healthy controls (HCs) were scanned using NM-MRI. We computed volume and contrast-to-noise ratio (CNR) derived from the whole SNc and the sensorimotor, associative, and limbic SNc regions. An analysis of covariance was performed to explore the differences of whole and regional NM-MRI values among the groups while controlling the effect of age and sex. In whole SNc, LRRK2 had significantly lower CNR than HCs but non-significantly higher volume and CNR than PD patients, and PD patients significantly lower volume and CNR compared to HCs. Inside SNc regions, there were significant group effects for CNR in all regions and for volumes in the associative region, with a trend in the sensorimotor region but no significant changes in the limbic region. PD had reduced volume and CNR in all regions compared to HCs. Asymptomatic LRRK2 carriers showed globally decreased SNc volume and CNR suggesting early nigral neurodegeneration in these subjects at risk of developing PD.
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Proteína 2 Quinasa Serina-Treonina Rica en Repeticiones de Leucina , Imagen por Resonancia Magnética , Melaninas , Enfermedad de Parkinson , Sustancia Negra , Humanos , Proteína 2 Quinasa Serina-Treonina Rica en Repeticiones de Leucina/genética , Proteína 2 Quinasa Serina-Treonina Rica en Repeticiones de Leucina/metabolismo , Masculino , Femenino , Persona de Mediana Edad , Melaninas/metabolismo , Imagen por Resonancia Magnética/métodos , Enfermedad de Parkinson/genética , Enfermedad de Parkinson/diagnóstico por imagen , Enfermedad de Parkinson/patología , Enfermedad de Parkinson/metabolismo , Sustancia Negra/diagnóstico por imagen , Sustancia Negra/patología , Sustancia Negra/metabolismo , Anciano , Heterocigoto , Adulto , Estudios de Casos y ControlesRESUMEN
Ochratoxin A (OTA) is a mycotoxin that globally contaminates fruits and their products. Since OTA have a huge negative impact on health hazards and economic losses, it is imperative to establish an effective and safe strategy for detoxification. Here, pancreatin was immobilized on the surface of polydopamine functionalized magnetic porous chitosan (MPCTS@ PDA) for the degradation of OTA. Compared with free pancreatin, MPCTS@ PDA@ pancreatin displayed excellent thermal stability, acid resistance, storage stability and OTA detoxification in wine (>58%). Moreover, the MPCTS@ PDA@ pancreatin retained 43% initial activity after 8 reuse cycles. There was no significant change in the quality of wine after MPCTS@ PDA@ pancreatin treatment. Moreover, it did not exhibit cytotoxicity which facilitated its application in wine. These results demonstrated that MPCTS@ PDA@ pancreatin can be used as a highly effective biocatalysate for OTA detoxification in wine.
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Quitosano , Contaminación de Alimentos , Indoles , Ocratoxinas , Pancreatina , Polímeros , Vino , Ocratoxinas/química , Ocratoxinas/análisis , Vino/análisis , Indoles/química , Polímeros/química , Quitosano/química , Porosidad , Pancreatina/química , Pancreatina/metabolismo , Contaminación de Alimentos/análisis , Enzimas Inmovilizadas/química , Enzimas Inmovilizadas/metabolismoRESUMEN
BACKGROUND: Long noncoding RNAs (lncRNAs) participate in diseases, especially tumorigenesis, including gastric cancer (GC). Although lncRNAs in GC tissues have been extensively studied in previous research, the possible significance of circulating lncRNAs in diagnosing GC is still unknown. OBJECTIVE: The present work investigated lncRNAs ZFPM2-AS1 and XIST with high expression in GC tissues proved as potential plasma biomarkers from 20 early GC cases, 100 GC cases, and 90 normal subjects. METHODS: The possible correlation between ZFPM2-AS1 and XIST expression levels was analyzed with general characteristics and clinicopathological features. The performance in diagnosis was assessed according to receiver operating characteristic (ROC) analysis. RESULTS: According to the results, XIST and ZFPM2-AS1 expression remarkably increased within GC plasma relative to normal subjects (P< 0.01); besides, lncRNA XIST expression after surgery had a tendency of downregulation compared with preoperative levels (P< 0.05). Moreover, the area under ROC curve (AUC) values were 0.62 for ZFPM2-AS1 and 0.68 for XIST, while the pooled AUC value of CA-724 and two lncRNAs was 0.751. CONCLUSION: Circulating lncRNAs ZFPM2-AS1 and XIST can serve as the candidate plasma biomarkers used to diagnose GC.
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Nanocellulose is a kind of renewable natural polymer material with high specific surface area, high crystallinity, and strong mechanical properties. RC nanofibers (RCNFs) have attracted an increasing attention in various applications due to their high aspect ratio and good flexibility. Herein, a novel and facile strategy for RCNFs preparation with high-speed shear induced in urea solution through "bottom-up" approach was proposed in this work. Results indicated that the average diameter and yield of RCNF was approach to 136.67 nm and 53.3 %, respectively. Meanwhile, due to the regular orientation RC chains and arrangement micro-morphology, RCNFs exhibited high crystallinity, strong mechanical properties, stable thermal degradation performance, and excellent UV resistance. In this study, a novel regeneration process with high-speed shear induced was developed to produce RCNFs with excellent properties. This study paved a strategy for future low-energy production of nanofibers and high value-added conversion applications of agricultural waste.
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Celulosa , Nanofibras , Urea , Zea mays , Nanofibras/química , Celulosa/química , Zea mays/química , Urea/química , SolucionesRESUMEN
BACKGROUND: Periodontitis is a common complication of diabetes, with advanced glycation end products (AGEs) playing a key role in its pathogenesis. Albiflorin, a monoterpene glycoside, has shown potential anti-inflammatory and antioxidant properties. This study aims to investigate the effects of albiflorin on AGEs-induced gingival fibroblasts and its underlying mechanisms. OBJECTIVE: This study aimed to evaluate the role of albiflorin in mitigating ROS production, inflammation, and MMP-1 expression in AGEs-induced gingival fibroblasts. METHODS: The viability of gingival fibroblasts treated with albiflorin and AGEs was assessed using CCK-8 assays. ROS levels were measured by DCF staining, and the expression of inflammatory markers and MMP-1 was evaluated by ELISA and qPCR. The involvement of the NF-κB and Nrf2 pathways was examined by immunoblotting. RESULTS: Albiflorin enhanced the viability of AGEs-induced gingival fibroblasts and reduced ROS production. It also decreased the expression of IL-6, IL-8, RAGE, and MMP-1, suggesting an anti- inflammatory effect. Mechanistically, albiflorin modulated the NF-κB and Nrf2 pathways in AGEs-induced gingival fibroblasts. CONCLUSION: Albiflorin exhibited protective effects against AGEs-induced oxidative stress and inflammation in gingival fibroblasts, highlighting its potential as a therapeutic agent for periodontitis in diabetic patients. The modulation of the NF-κB and Nrf2 pathways by albiflorin provides insight into its mechanism of action.
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Murepavadin is a peptidomimetic that specifically targets the lipopolysaccharide transport protein LptD of Pseudomonas aeruginosa. Here, we found that murepavadin enhances the bactericidal efficacies of tobramycin and amikacin. We further demonstrated that murepavadin enhances bacterial respiration activity and subsequent membrane potential, which promotes intracellular uptake of aminoglycoside antibiotics. In addition, the murepavadin-amikacin combination displayed a synergistic bactericidal effect in a murine pneumonia model.
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Amicacina , Péptidos Cíclicos , Infecciones por Pseudomonas , Animales , Ratones , Amicacina/farmacología , Pseudomonas aeruginosa , Potenciales de la Membrana , Antibacterianos/farmacología , Aminoglicósidos/farmacología , Tobramicina/farmacología , Infecciones por Pseudomonas/tratamiento farmacológico , Infecciones por Pseudomonas/microbiología , Pruebas de Sensibilidad MicrobianaRESUMEN
As a typical perovskite material, NaTaO3 has been regarded as a potential catalyst for photocatalytic hydrogen evolution (PHE) process, due to its excellent photoelectric property and superior chemical stability. However, the photocatalytic activity of pure NaTaO3 was largely restricted by its poor visible-light absorption ability and rapid recombination of photogenerated charge carriers. Therefore, a covalently bonded TpBpy covalent organic framework (COF)/NaTaO3 (TpBpy/NaTaO3) heterostructure was designed and synthesized by the post modification strategy with (3-aminopropyl) triethoxysilane (APTES) and the in situ solvothermal process. Benefiting from the enhanced built-in electric field by the interfacial covalent bonds and the formation of S-scheme heterostructure between TpBpy and NaTaO3, which were proved by the Ar+-cluster depth profile and X-ray photoelectron spectroscopy (XPS), as well as density functional theory (DFT) calculation results, both the charge transfer efficiency and the PHE performance of the TpBpy/NaTaO3 composites were significantly improved. Additionally, the composites exhibited an excellent absorption performance in the visible region, which was also beneficial for the photocatalytic process. As expected, the optimal TpBpy/20%NaTaO3 composite achieved a remarkable hydrogen evolution rate of 17.3 mmol·g-1·h-1 (10 mg of catalyst) under simulated sunlight irradiation, which was about 173 and 2.4 times higher than that of pure NaTaO3 and TpBpy, respectively. This work provided a novel strategy for constructing highly effective and stable semiconductor/COFs heterostructures with strong interfacial interaction for photocatalytic hydrogen evolution.
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PURPOSE: The goal of this study was to examine changes in testicular stiffness at various intervals after the induction of testicular torsion, as well as to assess the predictive value of testicular stiffness for testicular spermatogenesis after torsion. METHODS: Sixty healthy male rabbits were randomly assigned to one of three groups: complete testicular torsion, incomplete testicular torsion, or control. All rabbits underwent preoperative and postoperative scrotal ultrasonography, including shear wave elastography (SWE), at predetermined intervals. Changes in SWE values were analyzed and compared using repeatedmeasures analysis of variance. To assess the diagnostic performance of SWE in determining the degree of spermatogenic function impairment, the areas under the receiver operating characteristic curves (AUCs) were calculated. RESULTS: SWE measurements in both central and peripheral zones of the testicular parenchyma affected by torsion demonstrated significant negative correlations with spermatogenesis, with coefficients of r=-0.759 (P<0.001) and r=-0.696 (P<0.001), respectively. The AUCs of SWE measurements in the central or peripheral zones of the torsed testicular parenchyma were 0.886 (sensitivity, 83.3%; specificity, 100%) and 0.824 (sensitivity, 83.3%; specificity, 73.3%) for distinguishing between hypospermatogenesis and spermatogenic arrest, respectively (P=0.451, DeLong test). CONCLUSION: Variations in the stiffness of both central and peripheral regions of the testicular parenchyma correlate with the extent and duration of torsion, exhibiting a specific pattern. The "stiff ring sign" is the characteristic SWE finding associated with testicular torsion. SWE appears to aid in the non-invasive determination of the extent of spermatogenic damage in torsed testes.
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REM sleep behavior disorder (RBD) symptoms in Parkinson's disease (PD) suggest both a clinically and pathologically malignant subtype. However, whether RBD symptoms are associated with alterations in the organization of whole-brain intrinsic functional networks in PD, especially at early disease stages, remains unclear. Here we use resting-state functional MRI, coupled with graph-theoretical approaches and network-based statistics analyses, and validated with large-scale network analyses, to characterize functional brain networks and their relationship with clinical measures in early PD patients with probable RBD (PD+pRBD), early PD patients without probable RBD (PD-pRBD) and healthy controls. Thirty-six PD+pRBD, 57 PD-pRBD and 71 healthy controls were included in the final analyses. The PD+pRBD group demonstrated decreased global efficiency (t = -2.036, P = 0.0432) compared to PD-pRBD, and decreased network efficiency, as well as comprehensively disrupted nodal efficiency and whole-brain networks (all eight networks, but especially in the sensorimotor, default mode and visual networks) compared to healthy controls. The PD-pRBD group showed decreased nodal degree in right ventral frontal cortex and more affected edges in the frontoparietal and ventral attention networks compared to healthy controls. Furthermore, the assortativity coefficient was negatively correlated with Montreal cognitive assessment scores in the PD+pRBD group (r = -0.365, P = 0.026, d = 0.154). The observation of altered whole-brain functional networks and its correlation with cognitive function in PD+pRBD suggest reorganization of the intrinsic functional connectivity to maintain the brain function in the early stage of the disease. Future longitudinal studies following these alterations along disease progression are warranted.
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Cavernous angiomas (CAs) are benign vascular malformations predominantly seen in the brain parenchyma and therefore referred to as intra-axial. Extra-axial dural-based cavernous angiomas, on the other hand, are rare vascular lesions found outside of the brain parenchyma. They occur in the middle fossa and may be easily misdiagnosed as meningiomas due to their extra-axial location. In addition, CAs that are located outside the middle fossa, such as in the convexity, have a better prognosis since they are more surgically accessible. Surgical resection is the main treatment of choice in CAs. However, other options, such as embolization and radiotherapy, may also be considered therapeutic choices or additive treatment options. The pathogenesis of CA and the involvement of other factors (genetics or environmental factors) are still unknown and require further investigation. We are presenting a young man who presented for evaluation of seizure-like events without any family history of neurologic conditions. The physical examination was unremarkable except for a slightly antalgic gait. Imaging studies showed an extra-axial left tentorial mass suggestive of a meningioma, hemangiopericytoma, or other extra-axial lesions. The lesion was resected where its vascular nature was mentioned initially, and the histology proved the diagnosis of cavernous angioma. Here we give an overview of the known pathogenesis, causes, clinical features, and diagnostic and therapeutic options in CA. Better knowledge about CA, its causes, clinical features, and treatment options would help clinicians in early diagnosis and patient management.
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Deep neural networks (DNNs) have been effective in classifying structural magnetic resonance imaging (sMRI) images for Alzheimer's disease (AD) diagnosis. In this study, we propose a novel two-phase slice-to-volume feature representation (SVFR) framework for AD diagnosis. Specifically, we design a slice-level feature extractor to automatically select informative slice images and extract their slice-level features, by combining DNN and clustering models. Furthermore, we propose a joint volume-level feature generator and classifier to hierarchically aggregate the slice-level features into volume-level features and to classify images, by devising a spatial pyramid set pooling module and a fusion module. Experimental results demonstrate the superior performance of the proposed SVFR, surpassing the majority of the state-of-the-art methods and achieving comparable results to the best-performing approach. Experimental results also showcase the efficacy of the slice-level feature extractor in the selection of informative slice images, as well as the effectiveness of the volume-level feature generator and classifier in the integration of slice-level features for image classification. The source code for this study is publicly available at https://github.com/gll89/SVFR.
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BACKGROUND: Recent animal model studies have suggested that the parafascicular nucleus has the potential to be an effective deep brain stimulation target for Parkinson's disease. However, our knowledge on the role of the parafascicular nucleus in Parkinson's disease patients remains limited. OBJECTIVE: We aimed to investigate the functional alterations of the parafascicular nucleus projections in Parkinson's disease patients. METHODS: We enrolled 72 Parkinson's disease patients and 60 healthy controls, then utilized resting-state functional MRI and spectral dynamic causal modeling to explore the effective connectivity of the bilateral parafascicular nucleus to the dorsal putamen, nucleus accumbens, and subthalamic nucleus. The associations between the effective connectivity of the parafascicular nucleus projections and clinical features were measured with Pearson partial correlations. RESULTS: Compared with controls, the effective connectivity from the parafascicular nucleus to dorsal putamen was significantly increased, while the connectivity to the nucleus accumbens and subthalamic nucleus was significantly reduced in Parkinson's disease patients. There was a significantly positive correlation between the connectivity of parafascicular nucleus-dorsal putamen projection and motor deficits. The connectivity from the parafascicular nucleus to the subthalamic nucleus was negatively correlated with motor deficits and apathy, while the connectivity from the parafascicular nucleus to the nucleus accumbens was negatively associated with depression. CONCLUSION: The present study demonstrates that the parafascicular nucleus-related projections are damaged and associated with clinical symptoms of Parkinson's disease. Our findings provide new insights into the impaired basal ganglia-thalamocortical circuits and give support for the parafascicular nucleus as a potential effective neuromodulating target of the disease.
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Núcleos Talámicos Intralaminares , Enfermedad de Parkinson , Núcleo Subtalámico , Animales , Humanos , Enfermedad de Parkinson/diagnóstico por imagen , Putamen , Ganglios Basales , Núcleo Subtalámico/diagnóstico por imagenRESUMEN
Identifying progressive mild cognitive impairment (pMCI) and stable mild cognitive impairment (sMCI) plays a significant role in early Alzheimer's disease (AD) diagnosis, which can effectively boost the life quality of patients. Recently, convolutional neural network (CNN)- based methods using structural magnetic resonance imaging (sMRI) images have shown effective for AD identification. However, these CNN-based methods fail to effectively explore the feature extraction of disease-related multi-scale tissues, such as ventricles, hippocampi and cerebral cortex. To address this issue, we propose an end-to-end disease-related attentional UNet framework (DAUF) for identifying pMCI and sMCI, by embedding a devised dual disease-related attention module (D2AM) and a novel tree-structured feature fusion classifier (TFFC). Specifically, D2AM leverages the complementarity between feature maps and attention maps and the complementary features from the encoder and decoder, so as to highlight discriminative semantic and detailed features. Additionally, TFFC is a powerfully joint multi-scale feature fusion and classification head, by employing the homogeneity among multi-scale features, so that the discriminative features of the multi-scale tissues are adequately fused for enhancing classification performance. Finally, extensive experiments demonstrate the superior performance of DAUF, with the effectiveness of D2AM and TFFC on identifying pMCI and sMCI subjects.
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Enfermedad de Alzheimer , Disfunción Cognitiva , Humanos , Enfermedad de Alzheimer/diagnóstico por imagen , Corteza Cerebral , Disfunción Cognitiva/diagnóstico por imagen , Ventrículos Cardíacos , HipocampoRESUMEN
Locus coeruleus (LC) is severely affected in Parkinson's Disease (PD). However, alterations in LC-related resting-state networks (RSNs) in PD remain unclear. We used resting-state functional MRI to investigate the alterations in functional connectivity (FC) of LC-related RSNs and the associations between RSNs changes and clinical features in idiopathic rapid eye movement sleep behavior disorder (iRBD) and PD patients with (PDRBD+) and without RBD (PDRBD-). There was a similarly disrupted FC pattern of LC-related RSNs in iRBD and PDRBD+ patients, whereas LC-related RSNs were less damaged in PDRBD- patients than that in patients with iRBD and PDRBD+. The FC of LC-related RSNs correlated with cognition and duration in iRBD, depression in PDRBD-, and cognition and severity of RBD in patients with PDRBD+. Our findings demonstrate that LC-related RSNs are significantly disrupted in the prodromal stage of α-synucleinopathies and proposed body-first PD (PDRBD+), but are less affected in brain-first PD (PDRBD-).
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Background: /purpose: Periodontal disease is a chronic inflammatory disease that occurs in the tissues that support and attach teeth. There is considerable evidence of a relationship between diabetes and periodontal disease. Emerging studies have reported that myeloid-derived growth factor (MYDGF) can inhibit apoptosis and inflammation. The purpose of this study was to investigate whether MYDGF mediates the role of hyperglycemia in fibroblasts in periodontitis tissues. Materials and methods: Fibroblasts were isolated and cultured from normal gums. Gene expression levels were detected by RT-PCR. The protein level was detected by western blotting. Cell viability was determined by MTT assay. To investigate the role of MYDGF, the plasmid was transfected into fibroblasts. The expression levels of cytokines were determined by ELISA. Results: High glucose can down-regulate the expression of MYDGF in human gingival fibroblasts in a time-dependent manner, and decrease the fibroblast activity. SOD level was decreased and MDA level was increased in gingival fibroblasts by high glucose. High glucose up-regulates pro-apoptotic indicator Bax, down-regulates anti-apototic indicator Bcl-2, and increased endoplasmic reticulum stress related indicators Nox 2, GRP78, ATF6, and PERK. In addition, high glucose increased TNF-α, IL-1ß, IL-8 and CXCL1 protein levels in fibroblasts. Our study also found that high glucose inhibits the AKT signaling pathway and activates the nuclear factor κB (NF-κB) pathway. Interestingly, overexpression of MYDGF reversed these effects. Conclusion: MYDGF is down-regulated in gingival fibroblasts induced by high glucose. Overexpression of MYDGF inhibits apoptosis induced by high glucose, inhibits oxidative stress and cytokine secretion of gingival fibroblasts induced by high glucose, and induces AKT pathway activation and NF-κB pathway inhibition.