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BACKGROUND: Intronic GAA repeat expansion ([GAA] ≥250) in FGF14 is associated with the late-onset neurodegenerative disorder, spinocerebellar ataxia 27B (SCA27B, GAA-FGF14 ataxia). We aim to determine the prevalence of the GAA repeat expansion in FGF14 in Chinese populations presenting late-onset cerebellar ataxia (LOCA) and evaluate the characteristics of tandem repeat inheritance, radiological features and sympathetic nerve involvement. METHODS: GAA-FGF14 repeat expansion was screened in an undiagnosed LOCA cohort (n = 664) and variations in repeat-length were analyzed in families of confirmed GAA-FGF14 ataxia patients. Brain magnetic resonance imaging (MRI) was used to evaluate the radiological feature in GAA-FGF14 ataxia patients. Clinical examinations and sympathetic skin response (SSR) recordings in GAA-FGF14 patients (n = 16) were used to quantify sympathetic nerve involvement. RESULTS: Two unrelated probands (2/664) were identified. Genetic screening for GAA-FGF14 repeat expansion was performed in 39 family members, 16 of whom were genetically diagnosed with GAA-FGF14 ataxia. Familial screening revealed expansion of GAA repeats in maternal transmissions, but contraction upon paternal transmission. Brain MRI showed slight to moderate cerebellar atrophy. SSR amplitude was lower in GAA-FGF14 patients in pre-symptomatic stage compared to healthy controls, and further decreased in the symptomatic stage. CONCLUSIONS: GAA-FGF14 ataxia was rare among Chinese LOCA cases. Parental gender appears to affect variability in GAA repeat number between generations. Reduced SSR amplitude is a prominent feature in GAA-FGF14 patients, even in the pre-symptomatic stage.
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CONTEXT AND OBJECTIVE: Cushing's disease (CD) provides a unique and naturalist model for studying the influence of hypercortisolism on the human brain and the reversibility of these effects after resolution of the condition. This cross-sectional study used resting-state fMRI (rs-fMRI) to investigate the altered spontaneous brain activity in CD patients and the trends for potential reversibility after the resolution of the hypercortisolism. We also aim to determine the relationship of these changes with clinical characteristics and cortisol levels. SUBJECTS AND METHODS: Active CD patients (n = 18), remitted CD patients (n = 14) and healthy control subjects (n = 22) were included in this study. Amplitude of low-frequency fluctuation (ALFF) and regional homogeneity (ReHo) values were calculated to represent spontaneous brain activity. RESULTS: Our study resulted in three major findings: (i) active CD patients showed significantly altered spontaneous brain activity in the posterior cingulate cortex (PCC)/precuneus (PCu), occipital lobe (OC)/cerebellum, thalamus, right postcentral gyrus (PoCG) and left prefrontal cortex (PFC); (ii) trends for partial restoration of altered spontaneous brain activity after the resolution hypercortisolism were found in several brain regions; and (iii) active CD patients showed a significant correlation between cortisol levels and ALFF/ReHo values in the PCC/PCu, a small cluster in the OC and the right IPL. CONCLUSIONS: This study provides a new approach to investigating brain function abnormalities in patients with CD and enhances our understanding of the effect of hypercortisolism on the human brain. Furthermore, our explorative potential reversibility study of patients with CD may facilitate the development of future longitudinal studies.
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Encéfalo/fisiopatologia , Hipersecreção Hipofisária de ACTH/fisiopatologia , Adulto , Encéfalo/diagnóstico por imagem , Estudos de Casos e Controles , Estudos Transversais , Síndrome de Cushing/fisiopatologia , Humanos , Imageamento por Ressonância Magnética/métodos , Pessoa de Meia-Idade , Hipersecreção Hipofisária de ACTH/diagnóstico por imagem , Adulto JovemRESUMO
OBJECTIVE: The data on patients with short-term remission of Cushing's disease (CD) might provide information that is not available from previous long-term remission studies. We aimed to investigate structural changes in the brain in these patients and to examine whether these changes were associated with clinical characteristics. DESIGN: A cross-sectional study was performed. METHODS: Thirty-four patients with CD (14 with CD in short-term remission and 20 with active CD) and 34 controls matched for age, sex and education underwent clinical evaluation and magnetic resonance imaging brain scans. Biometric measurements, disease duration and remission duration data were collected. Grey matter volumes in the whole brain were examined using voxel-based morphometry (VBM). RESULTS: No differences were observed in the grey matter volumes of the medial frontal gyrus (MFG) and cerebellum between the patients with remitted CD and healthy controls, whereas patients with active CD had smaller grey matter volumes in these two regions compared with controls and patients with remitted CD. Furthermore, significant correlations were found between remission time and grey matter values in these regions in short-term remission patients with CD. Additionally, greater grey matter volumes in the bilateral caudate of short-term remission patients with CD were observed. CONCLUSIONS: Trends for structural restoration were found in CD patients with short-term remission. This finding was associated with the number of days elapsed since curative surgery and the current age of the patients. This study enhances our understanding of potential reversibility after the resolution of hypercortisolism in CD patients.
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Imageamento por Ressonância Magnética/métodos , Hipersecreção Hipofisária de ACTH/diagnóstico por imagem , Hipersecreção Hipofisária de ACTH/patologia , Adulto , Estudos Transversais , Síndrome de Cushing/diagnóstico por imagem , Síndrome de Cushing/patologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Córtex Pré-Frontal/diagnóstico por imagem , Córtex Pré-Frontal/patologia , Adulto JovemRESUMO
AIM: Aquaporins (AQPs) are the water-channels that play important roles in brain water homeostasis and in cerebral edema induced by brain injury. In this study we investigated the relationship between AQPs and a neuroprotective agent curcumin that was effective in the treatment of brain edema in mice with intracerebral hemorrhage (ICH). METHODS: ICH was induced in mice by autologous blood infusion. The mice immediately received curcumin (75, 150, 300 mg/kg, ip). The Rotarod test scores, brain water content and brain expression of AQPs were measured post ICH. Cultured primary mouse astrocytes were used for in vitro experiments. The expression of AQP1, AQP4 and AQP9 and NF-κB p65 were detected using Western blotting or immunochemistry staining. RESULTS: Curcumin administration dose-dependently reduced the cerebral edema at d 3 post ICH, and significantly attenuated the neurological deficits at d 5 post ICH. Furthermore, curcumin dose-dependently decreased the gene and protein expression of AQP4 and AQP9, but not AQP1 post ICH. Treatment of the cultured astrocytes with Fe(2+) (10-100 µmol/L) dose-dependently increased the expression and nuclear translocation of NF-κB p65 and the expression of AQP4 and AQP9, which were partly blocked by co-treatment with curcumin (20 µmol/L) or the NF-κB inhibitor PDTC (10 µmol/L). CONCLUSION: Curcumin effectively attenuates brain edema in mice with ICH through inhibition of the NF-κB pathway and subsequently the expression of AQP4 and AQP9. Curcumin may serve as a potential therapeutic agent for ICH.
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Anti-Inflamatórios não Esteroides/uso terapêutico , Aquaporina 4/genética , Aquaporinas/genética , Edema Encefálico/tratamento farmacológico , Encéfalo/efeitos dos fármacos , Curcumina/uso terapêutico , Regulação para Baixo/efeitos dos fármacos , Animais , Aquaporina 4/análise , Aquaporinas/análise , Astrócitos/efeitos dos fármacos , Astrócitos/imunologia , Astrócitos/metabolismo , Astrócitos/patologia , Encéfalo/imunologia , Encéfalo/metabolismo , Encéfalo/patologia , Edema Encefálico/genética , Edema Encefálico/imunologia , Edema Encefálico/patologia , Células Cultivadas , Masculino , Camundongos , Camundongos Endogâmicos C57BL , NF-kappa B/imunologiaRESUMO
AIM: Carvacrol (2-methyl-5-isopropylphenol), a phenolic monoterpene in the essential oils of the genera Origanum and Thymus, has been shown to exert a variety of therapeutic effects. Here we examined whether carvacrol protected neuroblastoma SH-SY5Y cells against Fe(2+)-induced apoptosis and explored the underlying mechanisms. METHODS: Neuroblastoma SH-SY5Y cells were incubated with Fe(2+) for 24 h, and the cell viability was assessed with CCK-8 assay. TUNEL assay and flow cytometric analysis were performed to evaluate cell apoptosis. The mRNA levels of pro-inflammatory cytokines and NF-κB p65 were determined using qPCR. The expression of relevant proteins was determined using Western blot analysis or immunofluorescence staining. RESULTS: Treatment of SH-SY5Y cells with Fe(2+) (50-200 µmol/L) dose-dependently decreased the cell viability, which was significantly attenuated by pretreatment with carvacrol (164 and 333 µmol/L). Treatment with Fe(2+) increased the Bax level and caspase-3 activity, and decreased the Bcl-2 level, resulting in cell apoptosis. Furthermore, treatment with Fe(2+) significantly increased the gene expression of IL-1ß, IL-6 and TNF-α, and induced the nuclear translocation of NF-κB. Treatment with Fe(2+) also significantly increased the phosphorylation of p38, ERK, JNK and IKK in the cells. Pretreatment with carvacrol significantly inhibited Fe(2+)-induced activation of NF-κB, expression of the pro-inflammatory cytokines, and cell apoptosis. Moreover, pretreatment with carvacrol inhibited Fe(2+)-induced phosphorylation of JNK and IKK, but not p38 and ERK in the cells. CONCLUSION: Carvacrol protects neuroblastoma SH-SY5Y cells against Fe(2+)-induced apoptosis, which may result from suppressing the MAPK/JNK-NF-κB signaling pathways.
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Apoptose/efeitos dos fármacos , Ferro/toxicidade , MAP Quinase Quinase 4/imunologia , Proteínas Quinases Ativadas por Mitógeno/imunologia , Monoterpenos/uso terapêutico , NF-kappa B/imunologia , Fármacos Neuroprotetores/uso terapêutico , Cátions Bivalentes/toxicidade , Linhagem Celular Tumoral , Cimenos , Humanos , Transdução de Sinais/efeitos dos fármacosRESUMO
Facial features are important sources of information about perceived trustworthiness. Masks and protective clothing diminish the visibility of facial cues by either partially concealing the mouth and nose or covering the entire face. During the pandemic, the use of personal protective equipment affected and redefined who trusts whom in society. This study used the classical investment game of interpersonal trust with Chinese participants to explore the impact of occlusion on interpersonal trust. Faces with moderate initial trustworthiness were occluded by a mask or protective clothing in Experiment 1 and were digitally occluded by a square in Experiment 2, and faces with three levels of initial trustworthiness were occluded by a mask in Experiment 3. Results showed that both undergraduates (Experiment 1a) and non-student adults (Experiment 1b) perceived the faces with protective clothing as more trustworthy than faces wearing standard masks and faces not wearing masks. Faces with the top halves showing were perceived as trustworthy as full faces, while faces with the bottom halves showing were perceived as less trustworthy. The effect of masks is weak and complex. Masks reduced participants' trust in faces with high initial trustworthiness, had no effect on faces with low and moderate initial trustworthiness, and only slightly increased the trust of undergraduates in faces with moderate initial trustworthiness. Our findings indicate that the lack of information caused by occlusion and the social significance associated with occlusion collectively affect people's trust behavior in Chinese society. We believe the findings of this study will be useful in elucidating the effects of personal protective equipment usage on perceptions of trustworthiness.
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Reconhecimento Facial , Máscaras , Roupa de Proteção , Percepção Social , Confiança , Humanos , Masculino , Feminino , Adulto Jovem , Adulto , China , Reconhecimento Facial/fisiologia , Roupa de Proteção/normas , Adolescente , Jogos Experimentais , COVID-19/prevenção & controle , População do Leste AsiáticoRESUMO
Background: Cushing disease (CD) is a rare clinical neuroendocrine disease. CD is characterized by abnormal hypercortisolism induced by a pituitary adenoma with the secretion of adrenocorticotropic hormone. Individuals with CD usually exhibit atrophy of gray matter volume. However, little is known about the alterations in topographical organization of individuals with CD. This study aimed to investigate the structural covariance networks of individuals with CD based on the gray matter volume using graph theory analysis. Methods: High-resolution T1-weighted images of 61 individuals with CD and 53 healthy controls were obtained. Gray matter volume was estimated and the structural covariance network was analyzed using graph theory. Network properties such as hubs of all participants were calculated based on degree centrality. Results: No significant differences were observed between individuals with CD and healthy controls in terms of age, gender, and education level. The small-world features were conserved in individuals with CD but were higher than those in healthy controls. The individuals with CD showed higher global efficiency and modularity, suggesting higher integration and segregation as compared to healthy controls. The hub nodes of the individuals with CD were Short insular gyri (G_insular_short_L), Anterior part of the cingulate gyrus and sulcus (G_and_S_cingul-Ant_R), and Superior frontal gyrus (G_front_sup_R). Conclusions: Significant differences in the structural covariance network of patients with CD were found based on graph theory. These findings might help understanding the pathogenesis of individuals with CD and provide insight into the pathogenesis of this CD.
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Dominance is a major organizing principle of human societies that impacts a wide range of human behaviors, from gaze-following to voting choices. Here, we examined how dominance modulates a fundamental perceptual ability: the perception of proximity. We used the "Fat Face" illusion, a novel paradigm that measures perceived proximity implicitly. The illusion depicts a phenomenon that occurs when two identical faces are aligned vertically (one above the other) and the bottom face consistently appears larger. This illusion suggests that our visual system uses a vertical layout to infer the relative proximity of faces, so that the bottom face appears closer, and is thereby perceived as larger than the top one. We found that the illusion was larger for dominant than for submissive faces (Experiment 1). Moreover, when a dominant face was presented below a submissive one, participants reported a larger illusion than when a dominant face was above a submissive face (Experiments 2a and 2b). These findings suggest that dominant faces are perceived to be closer to observers than submissive faces. Furthermore, we found a stronger illusion for other-race faces as opposed to own-race faces, suggesting that we also misperceive other-race faces as closer than own-race faces. Together, these findings suggest that the visual system is highly sensitive to self-relevant, potentially threatening stimuli (e.g., dominant faces and other-race individuals) in the environment by misperceiving them as closer. In line with the recently proposed threat-signal hypothesis, this mechanism may allow for rapid and adaptive behaviors in our everyday social interactions. (PsycInfo Database Record (c) 2023 APA, all rights reserved).
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Reconhecimento Facial , Ilusões , Humanos , Face , Adaptação PsicológicaRESUMO
Previous studies suggested that upper and lower facial halves might be involved in the human holistic face processing differently. In this study, we replicated and extended the finding above. In Experiment 1, we used the standard composite-face task to measure holistic face processing when participants made judgements on the upper and lower facial halves separately. Results showed that the composite-face effect was stronger for the upper facial half compared to the lower half. In Experiment 2, we investigated how facial information was integrated when participants focused on different features, using the perceptual field paradigm. Results showed that: (1) more "peripheral faces" were chosen when participants fixated at the eyes than when they fixated at the mouth; (2) less "peripheral faces" were chosen for inverted faces regardless of the fixated features. Findings from both experiments together indicate that more peripheral facial information were integrated when participants focused on the upper facial half, highlighting the significance of focusing on the upper facial half in face processing.
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Reconhecimento Facial , Humanos , Orientação Espacial , Julgamento , Face , BocaRESUMO
People recognize familiar faces better than unfamiliar faces. However, it remains unknown whether familiarity affects part-based and/or holistic processing. Wang et al., Frontiers in Psychology, 6, 559 (2015), Vision Research, 157, 89-96 (2019) found both enhanced part-based and holistic processing in eye relative to mouth regions (i.e., in a region-selective manner) for own-race and own-species faces, i.e., faces with more experience. Here, we examined the role of face familiarity in eyes (part-based, region-selective) and holistic processing. Face familiarity was tested at three levels: high-familiar (faces of students from the same department and the same class who attended almost all courses together), low-familiar (faces of students from the same department but different classes who attended some courses together), and unfamiliar (faces of schoolmates from different departments who seldom attended the same courses). Using the old/new task in Experiment 1, we found that participants recognized eyes of high-familiar faces better than low-familiar and unfamiliar ones, while similar performance was observed for mouths, indicating a region-selective, eyes familiarity effect. Using the "Perceptual field" paradigm in Experiment 2, we observed a stronger inversion effect for high-familiar faces, a weaker inversion effect for low-familiar faces, but a non-significant inversion effect for unfamiliar faces, indicating that face familiarity plays a role in holistic processing. Taken together, our results suggest that familiarity, like other experience-based variables (e.g., race and species), can improve both eye processing and holistic processing.
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Reconhecimento Facial , Reconhecimento Psicológico , Humanos , Olho , Face , Boca , Reconhecimento Visual de ModelosRESUMO
Previous studies suggested that (1) facial attractiveness perception can be increased with facial skin homogeneity improving; and (2) human's facial change detection increases along with facial skin homogeneity increases. However, it's unknown whether a face can be perceived prettier than it did before while still being considered as physically the same. It is possible that these two kinds of cognitive-aesthetic processing may have separate mathematical functions in psychophysical studies. In other words, human's facial attractiveness differentiation may be more sensitive than facial change detection. In this current study, we explored the above questions. Using three types of psychophysical techniques to manipulate facial skin homogeneity, we measured how participants' sensitivity to facial skin homogeneity and attractiveness change. Results showed a linear function curve for facial physical change detection and a logarithmic function curve was drawn in the forced-choice technique, which was the most sensitive one, indicating that participants can judge a face prettier than before without being aware of it has physically changed. Besides, two linear function curves were shown in the same/different technique and a rating technique. Taken together, this current study revealed that facial attractiveness can be enhanced and discriminated by improving facial skin homogeneity, without being realized by people with conscious awareness that the face has been changed.
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Interleukin-3 (IL-3) is a hematopoietic growth factor and critical regulator of inflammatory response such as sepsis. IL-3 binds to IL-3 receptor α (IL-3Rα), which is then associated with IL-3Rß to initiate signaling. How IL-3-triggered physiological and pathological effects are regulated at the receptor level is unclear. Here, we show that the plasma membrane-associated E3 ubiquitin ligase MARCH3 negatively regulates IL-3-triggered signaling. MARCH3 is associated with IL-3Rα, mediates its K48-linked polyubiquitination at K377 and promotes its proteasomal degradation. MARCH3-deficiency promotes IL-3-triggered transcription of downstream effector genes and IL-3-induced expansion of myeloid cells. In the cecal ligation and puncture (CLP) model of sepsis, MARCH3-deficiency aggravates IL-3-ampified expression of inflammatory cytokines, organ damage and inflammatory death. Our findings suggest that regulation of IL-3Rα by MARCH3 plays an important role in IL-3-triggered physiological functions and inflammatory diseases.
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Subunidade alfa de Receptor de Interleucina-3/imunologia , Interleucina-3/imunologia , Peptídeos e Proteínas de Sinalização Intracelular/imunologia , Proteólise , Ubiquitinação/imunologia , Animais , Células HEK293 , Humanos , Inflamação/genética , Inflamação/imunologia , Interleucina-3/genética , Subunidade alfa de Receptor de Interleucina-3/genética , Peptídeos e Proteínas de Sinalização Intracelular/genética , Camundongos , Ubiquitinação/genéticaRESUMO
Converging evidence has demonstrated our remarkable capacities to process individual faces. However, in real-life contexts, we rarely see faces in isolation. It is largely unknown how our visual system processes a multitude of faces. The current study explored this question by using the "Fat Face" illusion: when two identical faces are vertically aligned, the bottom face appears bigger. In Experiment 1, we tested the robustness of this illusion by using faces varied by gender and race, by recruiting participants from different countries (Canadian, Chinese, and French), and by implementing different task requirements. We found that the illusion was stable and immune to variations in face gender or face race, perceptual familiarity, and task requirements. Experiment 2 further indicated that binocular vision was essential for this visual illusion. When participants performed the task with one eye covered, the previously robust illusion completely disappeared. Together, these findings revealed a visual adaptation for processing multiple faces in the environment: the face at the top is perceived as more distant from the viewer and appears smaller in size than the face at the bottom. More broadly, overestimating the size of the bottom face may represent a fundamental mechanism for social interactions, ensuring the deployment of attention to those closest to self.
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Ilusões Ópticas , Canadá , Face , Humanos , Reconhecimento Psicológico , Visão BinocularRESUMO
OBJECTIVE: Cushing disease (CD) is a rare clinical disease in which brain structural and function are impaired as the result of excessive cortisol. However, little is known whether rich-club organization changes in patients with CD, as visualized on resting-state magnetic resonance imaging (fMRI), can reverse to normal conditions after transsphenoidal surgery (TSS). In this study, we aimed to investigate whether the functional connectivity of rich-club organization is affected and whether any abnormal changes may reverse after TSS. METHODS: In this study, 38 patients with active CD, 33 with patients with CD in remission, and 41 age-, sex-, and education-matched healthy control participants underwent resting-state fMRI. Brain functional connectivity was constructed based on fMRI and rich club was calculated with graph theory approach. We constructed the functional brain networks for all participants and calculated rich-club connectivity based on fMRI. RESULTS: We identified left precuneus, right precuneus, left middle cingulum, right middle cingulum, right inferior temporal, right middle temporal, right lingual, right postcentral, right middle occipital, and right precentral regions as rich club nodes. Compared with healthy control participants, rich-club connectivity was significantly lower in patients with active CD (P < 0.001). Moreover, abnormal rich-club connectivity improved to normal after TSS. CONCLUSIONS: Our results show rich-club organization was disrupted in patients with active CD with excessive cortisol production. TSS can reverse abnormal rich-club connectivity. Rich club may be a new indicator to investigate the outcomes of TSS and to increase our understanding of the effect of excessive cortisol on brain functional connectivity in patients with CD.
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Adenoma Hipofisário Secretor de ACT/cirurgia , Conectoma , Substância Cinzenta/patologia , Hipersecreção Hipofisária de ACTH/fisiopatologia , Neoplasias Hipofisárias/cirurgia , Adenoma Hipofisário Secretor de ACT/complicações , Adolescente , Adulto , Mapeamento Encefálico , Feminino , Substância Cinzenta/diagnóstico por imagem , Humanos , Hidrocortisona/sangue , Hipofisectomia/métodos , Imageamento por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Modelos Teóricos , Neuroimagem , Hipersecreção Hipofisária de ACTH/diagnóstico por imagem , Hipersecreção Hipofisária de ACTH/patologia , Hipersecreção Hipofisária de ACTH/cirurgia , Neoplasias Hipofisárias/complicações , Indução de Remissão , Osso Esfenoide/cirurgia , Adulto JovemRESUMO
The IL-6-STAT3 axis is critically involved in inflammation-associated carcinogenesis (IAC). How this axis is regulated to modulate IAC remains unknown. Here, we show that the plasma membrane-associated E3 ubiquitin ligase MARCH3 negatively regulates STAT3 activation triggered by IL-6, as well as another IL-6 subfamily member, Oncostatin M (OSM). MARCH3 is associated with the IL-6 receptor α-chain (IL-6Rα) and its coreceptor gp130. Biochemical experiments indicated that MARCH3 mediates the polyubiquitination of IL-6Rα at K401 and gp130 at K849 following IL-6 stimulation, leading to their translocation to and degradation in lysosomes. MARCH3 deficiency increases IL-6- and OSM-triggered activation of STAT3 and induction of downstream effector genes in various cell types. MARCH3 deficiency enhances dextran sulfate sodium (DSS)-induced STAT3 activation, increases the expression of inflammatory cytokines, and exacerbates colitis, as well as azoxymethane (AOM)/DSS-induced colitis-associated cancer in mice. In addition, MARCH3 is downregulated in human colorectal cancer tissues and associated with poor survival across different cancer types. Our findings suggest that MARCH3 is a pivotal negative regulator of IL-6-induced STAT3 activation, inflammation, and inflammation-associated carcinogenesis.
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Colite , Ubiquitina-Proteína Ligases , Animais , Carcinogênese/metabolismo , Colite/induzido quimicamente , Colite/complicações , Colite/metabolismo , Sulfato de Dextrana/efeitos adversos , Modelos Animais de Doenças , Interleucina-6/metabolismo , Camundongos , Camundongos Endogâmicos C57BL , Receptores de Interleucina-6 , Transdução de Sinais , Ubiquitina-Proteína Ligases/genética , Ubiquitina-Proteína Ligases/metabolismoRESUMO
To investigate the whole functional brain networks of active Cushing disease (CD) patients about topological parameters (small world and rich club et al.) and compared with healthy control (NC). Nineteen active CD patients and twenty-two healthy control subjects, matched in age, gender, and education, underwent resting-state fMRI. Graph theoretical analysis was used to calculate the functional brain network organizations for all participants, and those for active CD patients were compared for and NCs. Active CD patients revealed higher global efficiency, shortest path length and reduced cluster efficiency compared with healthy control. Additionally, small world organization was present in active CD patients but higher than healthy control. Moreover, rich club connections, feeder connections and local connections were significantly decreased in active CD patients. Functional network properties appeared to be disrupted in active CD patients compared with healthy control. Analyzing the changes that lead to abnormal network metrics will improve our understanding of the pathophysiological mechanisms underlying CD.
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Encéfalo/fisiopatologia , Rede Nervosa/fisiopatologia , Hipersecreção Hipofisária de ACTH/fisiopatologia , Adulto , Estudos de Casos e Controles , Feminino , Humanos , Imageamento por Ressonância Magnética , Masculino , Pessoa de Meia-IdadeRESUMO
PURPOSE: Glucocorticoid (GC) is probably related to biological aging, but the exact mechanism remains unknown. Cushing's disease (CD) could represent a unique human model for examining the effects of prolonged exposure to hypercortisolism and its relationship with aging. Thus, we studied the alterations of neurites in CD patients with Neurite orientation dispersion and density imaging (NODDI). METHODS: CD patients (n = 15) and healthy control subjects (n = 15) were included in this study. Orientation dispersion index (Odi), neurite density index (Ndi), partial fraction of free water (fiso), partial fraction of extracellular water (fec) were examined in a cross-sectional analysis. RESULTS: Significant altered NODDI parameters were found in CD patients. Some of these alterations were correlated with current age. Additionally, increased dendritic density was found in cerebellar of CD patients. CONCLUSION: Hypercortisolism relative reductions of the dendritic density were correlated with current age in several regions of CD patients. Our study enhances the understanding of the link between the aging and GC.
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Neuritos , Hipersecreção Hipofisária de ACTH , Envelhecimento , Encéfalo , Estudos Transversais , Imagem de Difusão por Ressonância Magnética , Imagem de Tensor de Difusão , Humanos , Hipersecreção Hipofisária de ACTH/diagnóstico por imagemRESUMO
Using a composite-face paradigm, we examined the holistic processing induced by Asian faces, Caucasian faces, and monkey faces with human Asian participants in two experiments. In Experiment 1, participants were asked to judge whether the upper halves of two faces successively presented were the same or different. A composite-face effect was found for Asian faces and Caucasian faces, but not for monkey faces. In Experiment 2, participants were asked to judge whether the lower halves of the two faces successively presented were the same or different. A composite-face effect was found for monkey faces as well as for Asian faces and Caucasian faces. Collectively, these results reveal that own-species (i.e., own-race and other-race) faces engage holistic processing in both upper and lower halves of the face, but other-species (i.e., monkey) faces engage holistic processing only when participants are asked to match the lower halves of the face. The findings are discussed in the context of a region-based holistic processing account for the species-specific effect in face recognition.
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Reconhecimento Facial , Reconhecimento Psicológico , Adolescente , Adulto , Análise de Variância , Animais , Povo Asiático , Feminino , Haplorrinos , Humanos , Masculino , População Branca , Adulto JovemRESUMO
The adverse effects of hypercortisolism on the human brain have been highlighted in previous studies of Cushing's disease (CD). However, the reversibility of brain damage after the resolution of hypercortisolism remains unclear. Thus, we studied the potential volumetric reversibility in biochemically remitted CD patients. Cross-sectional analysis demonstrated the active CD patients (nâ¯=â¯61) had the smallest gray matter (GM) volumes (553.33⯱â¯45.90â¯CM3) among four groups. While the GM volumes of short-term remitted CD patients (586.62⯱â¯46.89â¯CM3, nâ¯=â¯28) and long-term remitted CD patients (596.58⯱â¯45.95â¯CM3, nâ¯=â¯35) were between those of the active CD patients and healthy control subjects (628.14⯱â¯46.88â¯CM3, nâ¯=â¯74). Moreover, significant positive correlations between remitted time and GM volumes were only found in short-term remitted CD patients. On the contrary, the alterations of white matter (WM) in CD patients seem to be independent of concomitant hypercortisolism, persisting after remission. A preliminary longitude analysis also demonstrated similar results. Volumetric reversibility of GM, but not WM is highly prevalent in short-term after resolution of hypercortisolism in Cushing disease. Our study enhances our understanding of the reversible and the irreversible structural alterations in the human brain due to hypercortisolism.
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Encéfalo/patologia , Síndrome de Cushing/patologia , Adulto , Encéfalo/diagnóstico por imagem , Encéfalo/metabolismo , Estudos Transversais , Síndrome de Cushing/diagnóstico por imagem , Síndrome de Cushing/metabolismo , Feminino , Humanos , Imageamento por Ressonância Magnética , MasculinoRESUMO
AIM: To explore precise deleted regions and screen the candidate tumor suppressor genes related to sporadic colorectal carcinoma. METHODS: Six markers on 1q31.1-32.1 were chosen. These polymorphic microsatellite markers in 83 colorectal cancer patients tumor and normal DNA were analyzed via PCR. PCR products were electrophoresed on an ABI 377 DNA sequencer. Genescan 3.1 and Genotype 2.1 software were used for Loss of heterozygosity (LOH) scanning and analysis. Comparison between LOH frequency and clinicopathological factors was performed by c2 test. RESULTS: 1q31.1-32.1 exhibited higher LOH frequency in colorectal carcinoma. The average LOH frequency of 1q31.1-32.1 was 23.0%, with the highest frequency of 36.7% (18/49) at D1S2622, and the lowest of 16.4% (11/67) at D1S412, respectively. A minimal region of frequent deletion was located within a 2 cM genomic segment at D1S413-D1S2622 (1q31.3-32.1). There was no significant association between LOH of each marker on 1q31.1-32.1 and the clinicopathological data (patient sex, age, tumor size, growth pattern or Dukes stage), which indicated that on 1q31.1-32.1, LOH was a common phenomenon in all kinds of sporadic colorectal carcinoma. CONCLUSION: Through our refined deletion mapping, the critical and precise deleted region was located within 2 cM chromosomal segment encompassing 2 loci (D1S413, D1S2622). No significant association was found between LOH and clinicopathologic features in 1q31.1-32.1.