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BACKGROUND: The impact of tobacco smoking on global health persists and it is essential to understand the progression of addiction and the involvement of neurotransmitters. METHODS: This study assessed 47 participants with tobacco use disorder (TUD) categorized based on changes in Fagerström Test for Nicotine Dependence (FTND) scores over 6 years: progressive TUD (pTUD), regressive TUD (rTUD), and stable TUD (sTUD). Additionally, 35 healthy controls were included. Resting-state functional magnetic resonance imaging was used to evaluate brain regional homogeneity (ReHo) and correlations with neurotransmitter distributions using JuSpace. RESULTS: Significant differences in ReHo were observed among pTUD, rTUD, sTUD, and controls. After strict Bonferroni correction, rTUD exhibited increased ReHo in the dorsolateral superior frontal gyrus compared to sTUD (p < 0.001) and controls (p < 0.001). Both pTUD (p < 0.001) and rTUD (p < 0.001) showed decreased ReHo in the superior temporal gyrus compared to sTUD. sTUD had increased ReHo in the supramarginal gyrus compared to all other groups (p < 0.001, p < 0.001, p = 0.002, separately). The strongest association, which survived rigorous Bonferroni correction, was between the ReHo changes in rTUD compared to sTUD and neurotransmitter distribution. This includes 5-hydroxytryptamine receptor 2A (p = 0.001), gamma-aminobutyric acid type A receptor (p < 0.001), norepinephrine transporter (p < 0.001), and N-Methyl-D-Aspartate (p = 0.002). CONCLUSIONS: This study provides insights into how smoking behaviors correlate with alterations in brain activity and neurotransmitter function. By elucidating these neural links to tobacco use disorder progression, our findings contribute to a deeper understanding of smoking's neurological impact and potentially inform more targeted therapeutic strategies.
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Smoking puts patients at high risk for cognitive and psychiatric disorders. The aim of this study was to explore the effects of nicotine use on primary visual network (PVN) and its association with neurotransmitters. A total of 59 tobacco use disorder (TUD) patients and 51 healthy controls (HC) participated in this study and underwent resting state functional magnetic resonance imaging scans. Functional connectivity (FC) within the network was explored using independent component analysis. In addition, the spatial correlations of PVN changes with neurotransmitters and their correlations with clinical characteristics of patients were evaluated using the JuSpace toolbox and SPSS. We found reduced FC within the PVN in patients with TUD compared with HC. In terms of relevant analysis, there is a spatial correlation between FC changes in the patient's PVN and a higher distribution of dopamine receptor and gamma-aminobutyric acid receptor. This study revealed changes in the FC and neurotransmitters of the PVN in patients with TUD, expanding the potential neural mechanisms underlying sensory perception and psychiatric disorders.
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BACKGROUND: Currently, numerous studies have indicated that individuals with internet gaming disorder (IGDs) have aberrant functional connection patterns between multiple brain regions and networks. However, temporal variability in the intra- and interhemispheric dynamic functional connectivity in IGDs remains unknown. METHODS: This study investigated resting-state functional magnetic resonance data from 55 IGDs and 50 demographically matched healthy controls (HCs). Functional connectivity density (FCD) combined with sliding window analysis is employed to calculate the temporal variability of global functional connectivity. The temporal variability of dynamic functional connectivity further quantified utilizing the standard deviations of global, intra-, and interhemispheric FCD. Finally, correlation analyses were performed between dynamic FCD varience (dFCD) in differential brain regions and clinical behaviors. RESULT: IGDs showed decreased intra- and interhemispheric dFCD variance in the visual attention network (precuneus and calcarine) and also demonstrated hemispheric-level dFCD variance abnormalities in the posterior cingulate cortex (PCC) compared to HCs. Moreover, abnormal global dFCD variability of the calcarine and ipsilateral dFCD variability of the PCC were negatively correlated with the severity of IGDs in the IGD group. CONCLUSION: Our results demonstrate abberant intra- and interhemispheric dynamic functional connectivity in the visual attention network, which emphasizes the neurobiological basis for impaired concentration in IGDs.
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BACKGROUND: Internet gaming disorder (IGD) is mainly characterized by its core dysfunction in higher-order brain cortices involved in inhibitory control, whose neurobiological basis remains unclear. Then, we will investigate local intrinsic neural activity (INA) alterations in IGD, ascertain whether these potential alterations are related to clinical characteristics, and further explore the underlying molecular architecture. METHOD: In this study, we performed the fractional amplitude of low-frequency fluctuation (fALFF) and regional homogeneity (ReHo) derived from resting-state functional magnetic resonance imaging (rs-fMRI) to explore the impact of IGD on local INA. Correlation analysis revealed the relationship between ReHo and fALFF in terms of group differences and clinical characteristics. Moreover, correlations between fALFF, ReHo, and PET- and SPECT-driven maps were investigated to elucidate the specific molecular architecture alternations in IGD. Finally, receiver operating characteristic curve (ROC) analysis was used to show the potential abilities of fALFF and ReHo in distinguishing individuals with IGD (IGDs) from healthy controls (HCs). RESULT: Compared with HCs, IGDs revealed increased ReHo and fALFF in the prefrontal cortex. Significantly decreased ReHo was observed in the temporal lobe, occipital lobe, and cerebellum. In addition, the ReHo values in the cerebellum_7b_R were positively correlated with internet addiction severity. ROC curve analysis showed that ReHo and fALFF-altered brain regions could effectively distinguish IGDs from HCs. More importantly, cross-modal correlations revealed local INA changes in brain regions associated with the monoamine neurotransmitter system and the less studied cholinergic/GABAergic system. CONCLUSION: These results suggest that local functional impairments are shown in the audiovisual and inhibitory control circuits in IGDs. This may be associated with underlying neurotransmitter system alterations. Therefore, this study provides the possibility of GABAergic receptor agonists and cholinergic receptor inhibitors for the treatment of IGD.
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Encéfalo , Trastorno de Adicción a Internet , Imagen por Resonancia Magnética , Humanos , Masculino , Imagen por Resonancia Magnética/métodos , Trastorno de Adicción a Internet/metabolismo , Trastorno de Adicción a Internet/fisiopatología , Adulto Joven , Adulto , Encéfalo/metabolismo , Encéfalo/diagnóstico por imagen , Encéfalo/fisiopatología , Femenino , Mapeo Encefálico/métodosRESUMEN
BACKGROUND: Obsessive-compulsive disorder (OCD) is a disabling disorder in which the temporal variability of regional brain connectivity is not well understood. The aim of this study was to investigate alterations in static and dynamic intrinsic neural activity (INA) in first-episode OCD and whether these changes have the potential to reflect neurotransmitters. METHODS: A total of 95 first-episode OCD patients and 106 matched healthy controls (HCs) were included in this study. Based on resting-state functional magnetic resonance imaging (rs-fMRI), the static and dynamic local connectivity coherence (calculated by static and dynamic regional homogeneity, sReHo and dReHo) were compared between the two groups. Furthermore, correlations between abnormal INA and PET- and SPECT-derived maps were performed to examine specific neurotransmitter system changes underlying INA abnormalities in OCD. RESULTS: Compared with HCs, OCD showed decreased sReHo and dReHo values in left superior, middle temporal gyrus (STG/MTG), left Heschl gyrus (HES), left putamen, left insula, bilateral paracentral lobular (PCL), right postcentral gyrus (PoCG), right precentral gyrus (PreCG), left precuneus and right supplementary motor area (SMA). Decreased dReHo values were also found in left PoCG, left PreCG, left SMA and left middle cingulate cortex (MCC). Meanwhile, alterations in INA present in brain regions were correlated with dopamine system (D2, FDOPA), norepinephrine transporter (NAT) and the vesicular acetylcholine transporter (VAChT) maps. CONCLUSION: Static and dynamic INA abnormalities exist in first-episode OCD, having the potential to reveal the molecular characteristics. The results help to further understand the pathophysiological mechanism and provide alternative therapeutic targets of OCD.
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Imagen por Resonancia Magnética , Neurotransmisores , Trastorno Obsesivo Compulsivo , Humanos , Masculino , Femenino , Trastorno Obsesivo Compulsivo/fisiopatología , Trastorno Obsesivo Compulsivo/diagnóstico por imagen , Adulto , Adulto Joven , Neurotransmisores/metabolismo , Tomografía de Emisión de Positrones , Encéfalo/fisiopatología , Encéfalo/diagnóstico por imagen , Tomografía Computarizada de Emisión de Fotón Único , Estudios de Casos y Controles , Mapeo Encefálico , Corteza Cerebral/fisiopatología , Corteza Cerebral/diagnóstico por imagen , Corteza Cerebral/metabolismoRESUMEN
OBJECTIVES: To investigate potential of enhancing image quality, maintaining interobserver consensus, and elevating disease diagnostic efficacy through the implementation of deep learning-based reconstruction (DLR) processing in 3.0 T cervical spine fast magnetic resonance imaging (MRI) images, compared with conventional images. METHODS: The 3.0 T cervical spine MRI images of 71 volunteers were categorized into two groups: sagittal T2-weighted short T1 inversion recovery without DLR (Sag T2w-STIR) and with DLR (Sag T2w-STIR-DLR). The assessment covered artifacts, perceptual signal-to-noise ratio, clearness of tissue interfaces, fat suppression, overall image quality, and the delineation of spinal cord, vertebrae, discs, dopamine, and joints. Spanning canal stenosis, neural foraminal stenosis, herniated discs, annular fissures, hypertrophy of the ligamentum flavum or vertebral facet joints, and intervertebral disc degeneration were evaluated by three impartial readers. RESULTS: Sag T2w-STIR-DLR images exhibited markedly superior performance across quality indicators (median = 4 or 5) compared to Sag T2w-STIR sequences (median = 3 or 4) (p < 0.001). No statistically significant differences were observed between the two sequences in terms of diagnosis and grading (p > 0.05). The interobserver agreement for Sag T2w-STIR-DLR images (0.604-0.931) was higher than the other (0.545-0.853), Sag T2w-STIR-DLR (0.747-1.000) demonstrated increased concordance between reader 1 and reader 3 in comparison to Sag T2w-STIR (0.508-1.000). Acquisition time diminished from 364 to 197 s through the DLR scheme. CONCLUSIONS: Our investigation establishes that 3.0 T fast MRI images subjected to DLR processing present heightened image quality, bolstered diagnostic performance, and reduced scanning durations for cervical spine MRI compared with conventional sequences.
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Vértebras Cervicales , Aprendizaje Profundo , Imagen por Resonancia Magnética , Espondilosis , Humanos , Espondilosis/diagnóstico por imagen , Imagen por Resonancia Magnética/métodos , Masculino , Adulto , Femenino , Vértebras Cervicales/diagnóstico por imagen , Persona de Mediana Edad , Anciano , Procesamiento de Imagen Asistido por Computador/métodosRESUMEN
BACKGROUND: The incidence of behavioral addictions (BAs) associated with scientific and technological advances has been increasing steadily. Unfortunately, a large number of studies on the structural and functional abnormalities have shown poor reproducibility, and it remains unclear whether different addictive behaviors share common underlying abnormalities. Therefore, our objective was to conduct a quantitative meta-analysis of different behavioral addictions to provide evidence-based evidence of common structural and functional changes. METHODS: We conducted systematic searches in PubMed, Web of Science and Scopus from January 2010 to December 2023, supplementing reference lists of high-quality relevant meta-analyses and reviews, to identify eligible voxel-based morphometry (VBM) and functional magnetic resonance imaging (fMRI) studies. Using anisotropic seed-based D-Mapping (AES-SDM) meta-analysis methods, we compared brain abnormalities between BAs and healthy controls (HCs). RESULTS: There were 11 GMV studies (287 BAs and 292 HCs) and 26 fMRI studies (577 BAs and 545 HCs) that met inclusion criteria. Compared with HCs, BAs demonstrated significant reductions in gray matter volume (GMV) in (1) right anterior cingulate gyri extending into the adjacent superior frontal gyrus, as well as in the left inferior frontal gyrus and right striatum. (2) the bilateral precuneus, right supramarginal gyrus, and right fusiform gyrus were hyperfunction; (3) the left medial cingulate gyrus extended to the superior frontal gyrus, the left inferior frontal gyrus, and right middle temporal gyrus had hypofunction. CONCLUSIONS: Our study identified structural and functional impairments in brain regions involved in executive control, cognitive function, visual memory, and reward-driven behavior in BAs. Notably, fronto-cingulate regions may serve as common biomarkers of BAs.
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Conducta Adictiva , Sustancia Gris , Imagen por Resonancia Magnética , Humanos , Conducta Adictiva/diagnóstico por imagen , Conducta Adictiva/fisiopatología , Encéfalo/diagnóstico por imagen , Encéfalo/patología , Encéfalo/fisiopatología , Sustancia Gris/diagnóstico por imagen , Sustancia Gris/patología , Giro del Cíngulo/diagnóstico por imagen , Giro del Cíngulo/fisiopatologíaRESUMEN
Previous researches of tobacco use disorder (TUD) has overlooked the hierarchy of cortical functions and single modality design separated the relationship between macroscopic neuroimaging aberrance and microscopic molecular basis. At present, intrinsic timescale gradient of TUD and its molecular features are not fully understood. Our study recruited 146 male subjects, including 44 heavy smokers, 50 light smokers and 52 non-smokers, then obtained their rs-fMRI data and clinical scales related to smoking. Intrinsic neural timescale (INT) method was performed to describe how long neural information was stored in a brain region by calculating the autocorrelation function (ACF) of each voxel to examine the difference in the ability of information integration among the three groups. Then, correlation analyses were conducted to explore the relationship between INT abnormalities and clinical scales of smokers. Finally, cross-modal JuSpace toolbox was used to investigate the association between INT aberrance and the expression of specific receptor/transporters. Compared to healthy controls, TUD subjects displayed decreased INT in control network (CN), default mode network (DMN), sensorimotor areas and visual cortex, and such trend of decreasing INT was more pronounced in heavy smokers. Moreover, various neurotransmitters (including dopaminergic, acetylcholine and µ-opioid receptors) were involved in the molecular mechanism of timescale decreasing and differed in heavy and light smokers. These findings supplied novel insights into the brain functional aberrance in TUD from an intrinsic neural dynamic perspective and confirm INT was a potential neurobiological marker. And also established the connection between macroscopic imaging aberrance and microscopic molecular changes in TUD.
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Imagen por Resonancia Magnética , Tabaquismo , Humanos , Masculino , Adulto , Tabaquismo/diagnóstico por imagen , Tabaquismo/fisiopatología , Red en Modo Predeterminado/diagnóstico por imagen , Red en Modo Predeterminado/fisiopatología , Persona de Mediana Edad , Red Nerviosa/diagnóstico por imagen , Red Nerviosa/fisiopatología , Adulto Joven , Neurotransmisores/metabolismo , Conectoma , Encéfalo/diagnóstico por imagen , Encéfalo/patología , Encéfalo/metabolismo , Encéfalo/fisiopatologíaRESUMEN
This study aims to explore the changes of the aspartate (Asp) level in the medial-prefrontal cortex (mPFC) of subjects with nicotine addiction (nicotine addicts [NAs]) using the J-edited 1 H MR spectroscopy (MRS), which may provide a positive imaging evidence for intervention of NA. From March to August 2022, 45 males aged 40-60 years old were recruited from Henan Province, including 21 in NA and 24 in nonsmoker groups. All subjects underwent routine magnetic resonance imaging (MRI) and J-edited MRS scans on a 3.0 T MRI scanner. The Asp level in mPFC was quantified with reference to the total creatine (Asp/Cr) and water (Aspwater-corr , with correction of the brain tissue composition) signals, respectively. Two-tailed independent samples t-test was used to analyze the differences in levels of Asp and other coquantified metabolites (including total N-acetylaspartate [tNAA], total cholinine [tCho], total creatine [tCr], and myo-Inositol [mI]) between the two groups. Finally, the correlations of the Asp level with clinical characteristic assessment scales were performed using the Spearman criteria. Compared with the control group (n = 22), NAs (n = 18) had higher levels of Asp (Asp/Cr: p = .005; Aspwater-corr : p = .004) in the mPFC, and the level of Asp was positively correlated with the daily smoking amount (Asp/Cr: p < .001; Aspwater-corr : p = .004). No significant correlation was found between the level of Asp and the years of nicotine use, Fagerstrom Nicotine Dependence (FTND), Russell Reason for Smoking Questionnaire (RRSQ), or Barratt Impulsivity Scale (BIS-11) score. The elevated Asp level was observed in mPFC of NAs in contrast to nonsmokers, and the Asp level was positively correlated with the amount of daily smoking, which suggests that nicotine addiction may result in elevated Asp metabolism in the human brain.
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Nicotina , Tabaquismo , Masculino , Humanos , Adulto , Persona de Mediana Edad , Nicotina/metabolismo , Ácido Aspártico/metabolismo , Tabaquismo/diagnóstico por imagen , Creatina/metabolismo , Espectroscopía de Resonancia Magnética/métodos , Imagen por Resonancia Magnética , Inositol/metabolismo , Corteza Prefrontal/metabolismo , Agua/metabolismoRESUMEN
BACKGROUND: Studies have revealed that intrinsic neural activity varies over time. However, the temporal variability of brain local connectivity in internet gaming disorder (IGD) remains unknown. The purpose of this study was to explore the alterations of static and dynamic intrinsic brain local connectivity in IGD and whether the changes were associated with clinical characteristics of IGD. METHODS: Resting-state functional magnetic resonance imaging (rs-fMRI) scans were performed on 36 individuals with IGD (IGDs) and 44 healthy controls (HCs) matched for age, gender and years of education. The static regional homogeneity (sReHo) and dynamic ReHo (dReHo) were calculated and compared between two groups to detect the alterations of intrinsic brain local connectivity in IGD. The Internet Addiction Test (IAT) and the Pittsburgh Sleep Quality Index (PSQI) were used to evaluate the severity of online gaming addiction and sleep quality, respectively. Pearson correlation analysis was used to evaluate the relationship between brain regions with altered sReHo and dReHo and IAT and PSQI scores. Receiver operating characteristic (ROC) curve analysis was used to reveal the potential capacity of the sReHo and dReHo metrics to distinguish IGDs from HCs. RESULTS: Compared with HCs, IGDs showed both increased static and dynamic intrinsic local connectivity in bilateral medial superior frontal gyrus (mSFG), superior frontal gyrus (SFG), and supplementary motor area (SMA). Increased dReHo in the left putamen, pallidum, caudate nucleus and bilateral thalamus were also observed. ROC curve analysis showed that the brain regions with altered sReHo and dReHo could distinguish individuals with IGD from HCs. Moreover, the sReHo values in the left mSFG and SMA as well as dReHo values in the left SMA were positively correlated with IAT scores. The dReHo values in the left caudate nucleus were negatively correlated with PSQI scores. CONCLUSIONS: These results showed impaired intrinsic local connectivity in frontostriatothalamic circuitry in individuals with IGD, which may provide new insights into the underlying neuropathological mechanisms of IGD. Besides, dynamic changes of intrinsic local connectivity in caudate nucleus may be a potential neurobiological marker linking IGD and sleep quality.
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Conducta Adictiva , Juegos de Video , Humanos , Trastorno de Adicción a Internet/diagnóstico por imagen , Imagen por Resonancia Magnética , Encéfalo/diagnóstico por imagen , Corteza Prefrontal , Mapeo Encefálico/métodos , Conducta Adictiva/diagnóstico por imagen , InternetRESUMEN
Background: Chronic smokers have abnormal spontaneous regional activity and disrupted functional connectivity as revealed by previous neuroimaging studies. Combining different dimensions of resting-state functional indicators may help us learn more about the neuropathological mechanisms of smoking. Methods: The amplitude of low frequency fluctuations (ALFF) of 86 male smokers and 56 male non-smokers were first calculated. Brain regions that displayed significant differences in ALFF between two groups were selected as seeds for further functional connectivity analysis. Besides, we examined correlations between brain areas with abnormal activity and smoking measurements. Results: Increased ALFF in left superior frontal gyrus (SFG), left medial superior frontal gyrus (mSFG) and middle frontal gyrus (MFG) as well as decreased ALFF in right calcarine sulcus were observed in smokers compared with non-smokers. In the seed-based functional connectivity analysis, smokers showed attenuated functional connectivity with left SFG in left precuneus, left fusiform gyrus, left lingual gyrus, left cerebellum 4 5 and cerebellum 6 as well as lower functional connectivity with left mSGF in left fusiform gyrus, left lingual gyrus, left parahippocampal gyrus (PHG), left calcarine sulcus, left cerebellum 4 5, cerebellum 6 and cerebellum 8 (GRF corrected, Pvoxel < 0.005, Pcluster<0.05). Furthermore, attenuated functional connectivity with left mSGF in left lingual gyrus and PHG displayed a negative correlation with FTND scores (r = -0.308, p = 0.004; r = -0.326, p = 0.002 Bonferroni corrected). Conclusion: Our findings of increased ALFF in SFG with reduced functional connectivity to visual attention areas and cerebellum subregions may shed new light on the pathophysiology of smoking.
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OBJECTIVE: A comprehensive meta-analysis using correlated coordinate data to explore abnormalities in white matter (WM) microarchitecture and changes in gray matter volume (GMV) in patients with obsessive-compulsive disorder (OCD). METHODS: We reviewed 23 reported studies of diffusion tensor imaging (DTI) in OCD patients. The differences in WM fractional anisotropy (FA) between OCD patients and healthy controls (HCs) were investigated using tract-based spatial statistics (TBSS) and voxel-based analysis (VBA), respectively, and the results of the two methods were compared. In addition, we will explore changes in OCD GMV by analyzing studies (n = 21) using the voxel-based morphometry (VBM) approach and comparing the difference between adults and adolescents. RESULTS: In the pooled meta-analysis, WM study results presented that compared with HCs, OCD patients had higher FA in right lenticular nucleus (putamen), and lower FA in corpus callosum (CC), left insula, right cerebellum (hemispheric lobule), right gyrus rectal and left inferior parietal gyri. However, in subgroup analysis, there was a significant difference in FA changes between TBSS and VBA in OCD patients compared with HCs. In addition, we found that the GMV of OCD patients was significantly increased in left striatum and left precentral gyrus, and significantly decreased in right inferior frontal gyrus triangular part, right superior temporal gyrus and right hippocampus. Compared with adolescents, adult patients have increased GMV in left lenticular nucleus putamen. CONCLUSION: The meta-analysis showed that OCD patients had abnormal WM microarchitecture and altered GMV. These changes may be closely related to the pathophysiological mechanism of the disease.
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Trastorno Obsesivo Compulsivo , Sustancia Blanca , Humanos , Adulto , Adolescente , Imagen de Difusión Tensora/métodos , Sustancia Blanca/diagnóstico por imagen , Sustancia Gris/diagnóstico por imagen , Encéfalo/diagnóstico por imagen , Trastorno Obsesivo Compulsivo/diagnóstico por imagen , Imagen por Resonancia MagnéticaRESUMEN
Background: Previous voxel-based morphometric (VBM) and functional magnetic resonance imaging (fMRI) studies have shown changes in brain structure and function in cocaine addiction (CD) patients compared to healthy controls (HC). However, the results of these studies are poorly reproducible, and it is unclear whether there are common and specific neuroimaging changes. This meta-analysis study aimed to identify structural, functional, and multimodal abnormalities in CD patients. Methods: The PubMed database was searched for VBM and task-state fMRI studies performed in CD patients between January 1, 2010, and December 31, 2021, using the SEED-BASE d MAP software package to perform two independent meta-groups of functional neural activation and gray matter volume, respectively. Analysis, followed by multimodal analysis to uncover structural, functional, and multimodal abnormalities between CD and HC. Results: The meta-analysis included 14 CD fMRI studies (400 CD patients and 387 HCs) and 11 CD VBM studies (368 CD patients and 387 controls). Structurally, VBM analysis revealed significantly lower gray matter volumes in the right superior temporal gyrus, right insula, and right retrocentral gyrus than in the HC. On the other hand, the right inferior parietal gyrus increased in gray matter (GM) volume in CD patients. Functionally, fMRI analysis revealed activation in the right temporal pole, right insula, and right parahippocampal gyrus. In the right inferior parietal gyrus, the left inferior parietal gyrus, the left middle occipital gyrus, and the right middle frontal gyrus, the degree of activation was lower. Conclusion: This meta-analysis showed that CD patients had significant brain GM and neural changes compared with normal controls. Furthermore, multi-domain assessments capture different aspects of neuronal alterations in CD, which may help develop effective interventions for specific functions.
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Increasing evidence has demonstrated that long noncoding RNAs serve pivotal roles in tumor development, progression, metastasis and metabolism. However, to the best of our knowledge, the roles and molecular mechanisms of long intergenic nonproteincoding RNA 00514 (LINC00514) in esophageal squamous cell carcinoma (ESCC) remain unknown. The present study found that LINC00514 and sphingosine kinase 1 (SPHK1) were both upregulated in ESCC tissues and cells, and their high expression levels were closely associated with TumorNodeMetastasis stage, lymph node metastasis and poor prognosis of patients with ESCC. Functionally, knockdown of LINC00514 inhibited cell proliferation and invasion, and led to the downregulation of lipogenesisrelated proteins, including SPHK1, fatty acid synthase, acetylcoenzyme (Co)A carboxylase α and stearoylCoA desaturase 1, whereas LINC00514 overexpression promoted cell proliferation and invasion in ESCC KYSE150 and KYSE30 cells, and upregulated expression of lipogenesisrelated proteins. Mechanistically, LINC00514 functioned as a competing endogenous RNA by sponging microRNA (miR)378a5p, resulting in the upregulation of SPHK1, which was accompanied by the activation of lipogenesisrelated pathways, to promote ESCC cell proliferation and invasion. Taken together, these findings suggest that LINC00514 may participate in ESCC lipogenesis, and targeting the LINC00514/miR378a5p/SPHK1 signaling axis may be a novel and promising therapeutic strategy for management of patients with ESCC.
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Neoplasias Esofágicas/etiología , Carcinoma de Células Escamosas de Esófago/etiología , Lipogénesis/fisiología , MicroARNs/fisiología , Fosfotransferasas (Aceptor de Grupo Alcohol)/fisiología , ARN Largo no Codificante/fisiología , Adulto , Anciano , Anciano de 80 o más Años , Línea Celular Tumoral , Neoplasias Esofágicas/genética , Neoplasias Esofágicas/patología , Carcinoma de Células Escamosas de Esófago/genética , Carcinoma de Células Escamosas de Esófago/patología , Femenino , Humanos , Masculino , Persona de Mediana Edad , Invasividad Neoplásica , Fosfotransferasas (Aceptor de Grupo Alcohol)/genéticaRESUMEN
BACKGROUND: Emerging evidence demonstrates that lncRNAs play pivotal roles in tumor energy metabolism; however, the detailed mechanisms of lncRNAs in the regulation of tumor glycolysis remain largely unknown. METHODS: The expression of SLC2A1-AS1 was investigated by TCGA, GEO dataset and qRT-PCR. The binding of GLI3 to SLC2A1-AS1 promoter was detected by Luciferase Reporter Assay System and Ago2-RIP assay. FISH was performed to determine the localization of SLC2A1-AS1 in ESCC cells. Double Luciferase Report assay was used to investigate the interaction of miR-378a-3p with SLC2A1-AS1 and Glut1. Gain-of-function and Loss-of-function assay were performed to dissect the function of SLC2A1-AS1/miR-378a-3p/Glut1 axis in ESCC progression in vitro and in vivo. RESULTS: We identified a novel lncRNA SLC2A1-AS1 in ESCC. SLC2A1-AS1 was frequently overexpressed in ESCC tissues and cells, and its overexpression was associated with TNM stage, lymph node metastasis and poor prognosis of ESCC patients. Importantly, GLI3 and SLC2A1-AS1 formed a regulatory feedback loop in ESCC cells. SLC2A1-AS1 promoted cell growth in vitro and in vivo, migration and invasion, and suppressed apoptosis, leading to EMT progression and increased glycolysis in ESCC cells. SLC2A1-AS1 functioned as ceRNA for sponging miR-378a-3p, resulting in Glut1 overexpression in ESCC cells. MiR-378a-3p inhibited cell proliferation and invasion as well as induced apoptosis, resulting in reduced glycolysis, which was partly reversed by SLC2A1-AS1 or Glut1 overexpression in ESCC cells. CONCLUSION: SLC2A1-AS1 plays important roles in ESCC development and progression by regulating glycolysis, and SLC2A1-AS1/miR-378a-3p/Glut1 regulatory axis may be a novel therapeutic target in terms of metabolic remodeling of ESCC patients.