RESUMEN
Sensitivity to criticism, which can be defined as a negative evaluation that a person receives from someone else, is considered a risk factor for the development of psychiatric disorders in adolescents. They may be more vulnerable to social evaluation than adults and exhibit more inadequate emotion regulation strategies such as rumination. The neural network involved in dealing with criticism in adolescents may serve as a biomarker for vulnerability to depression. However, the directions of the functional interactions between the brain regions within this neural network in adolescents are still unclear. In this study, 64 healthy adolescents (aged 14 to 17 years) were asked to listen to a series of self-referential auditory segments, which included negative (critical), positive (praising), and neutral conditions, during fMRI scanning. Dynamic Causal Modeling (DCM) with Parametric Empirical Bayesian (PEB) analysis was performed to map the interactions within the neural network that was engaged during the processing of these segments. Three regions were identified to form the interaction network: the left pregenual anterior cingulate cortex (pgACC), the left dorsolateral prefrontal cortex (DLPFC), and the right precuneus (preCUN). We quantified the modulatory effects of exposure to criticism and praise on the effective connectivity between these brain regions. Being criticized was found to significantly inhibit the effective connectivity from the preCUN to the DLPFC. Adolescents who scored high on the Perceived Criticism Measure (PCM) showed less inhibition of the preCUN-to-DLPFC connectivity when being criticized, which may indicate that they required more engagement of the Central Executive Network (which includes the DLPFC) to sufficiently disengage from negative self-referential processing. Furthermore, the inhibitory connectivity from the DLPFC to the pgACC was strengthened by exposure to praise as well as criticism, suggesting a recruitment of cognitive control over emotional responses when dealing with positive and negative evaluative feedback. Our novel findings contribute to a more profound understanding of how criticism affects the adolescent brain and can help to identify potential biomarkers for vulnerability to develop mood disorders before or during adulthood.
Asunto(s)
Mapeo Encefálico , Encéfalo , Adulto , Adolescente , Humanos , Teorema de Bayes , Emociones/fisiología , Giro del Cíngulo , Imagen por Resonancia Magnética , Corteza Prefrontal/fisiologíaRESUMEN
Manganese (Mn) is an essential element for bacteria, but the overload of manganese is toxic. In a previous study, we showed that the cation diffusion facilitator protein MetA and the resistance-nodulation-division efflux pump MetB are responsible for Mn efflux in the bacterial pathogen Riemerella anatipestifer CH-1. However, whether this bacterium encodes additional manganese efflux proteins is unclear. In this study, we show that R. anatipestifer CH-1 encodes a tellurium resistance C (TerC) family protein with low similarity to other characterized TerC family proteins. Compared to the wild type (WT), the terC mutant of R. anatipestifer CH-1 (∆terC) is sensitive to Mn(II) intoxication. The ability of TerC to export manganese is higher than that of MetB but lower than that of MetA. Consistently, terC deletion (∆terC) led to intracellular accumulation of Mn2+ under excess manganese conditions. Further study showed that ∆terC was more sensitive than the WT to the oxidant hypoclorite but not to hydrogen peroxide. Mutagenesis studies showed that the mutant at amino acid sites of Glu116 (E116), Asp122 (D122), Glu245 (E245) Asp248 (D248), and Asp254 (D254) may be involved in the ability of TerC to export manganese. The transcription of terC was upregulated under excess manganese and downregulated under iron-limited conditions. However, this was not dependent on the manganese metabolism regulator MetR. In contrast to a strain lacking the manganese efflux pump MetA or MetB, the terC mutant is attenuated in virulence in a duckling model of infection due to increased sensitivity to duck serum. Finally, comparative analysis showed that homologs of TerC are distributed across the bacterial kingdom, suggesting that TerC exerts a conserved manganese efflux function.IMPORTANCERiemerella anatipestifer is a notorious bacterial pathogen of ducks and other birds. In R. anatipestifer, the genes involved in manganese efflux have not been completely identified, although MetA and MetB have been identified as two manganese exporters. Additionally, the function of TerC family proteins in manganese efflux is controversial. Here, we demonstrated that a TerC family protein helps prevent Mn(II) intoxication in R. anatipestifer and that the ability of TerC to export manganese is intermediate compared to that of MetA and MetB. Sequence analysis and mutagenesis studies showed that the conserved key amino sites of TerC are Glu116, Asp122, Glu245, Asp248, and Asp254. The transcription of terC was regulated by manganese excess and iron limitation. Finally, we show that TerC plays a role in the virulence of R. anatipestifer due to the increased sensitivity to duck serum, rather than the increased sensitivity to manganese. Taken together, these results expand our understanding of manganese efflux and the pathogenic mechanisms of R. anatipestifer.
Asunto(s)
Infecciones por Flavobacteriaceae , Enfermedades de las Aves de Corral , Riemerella , Animales , Virulencia/genética , Proteínas Bacterianas/genética , Manganeso/metabolismo , Telurio/metabolismo , Riemerella/genética , Patos/microbiología , Hierro/metabolismo , Enfermedades de las Aves de Corral/microbiología , Infecciones por Flavobacteriaceae/microbiologíaRESUMEN
The eyes are our windows to the brain. There are differences in brain activity between people who have their eyes closed (EC) and eyes open (EO). Previous studies focused on differences in brain functional properties between these eyes conditions based on an assumption that brain activity is a static phenomenon. However, the dynamic nature of the brain activity in different eyes conditions is still unclear. In this study, we collected resting-state fMRI data from 21 healthy subjects in the EC and EO conditions. Using a sliding time window approach and a k-means clustering algorithm, we calculated the temporal properties of dynamic functional connectivity (dFC) states in the eyes conditions. We also used graph theory to estimate the dynamic topological properties of functional networks in the two conditions. We detected two dFC states, a hyper-connected State 1 and a hypo-connected State 2. We showed the following results: (i) subjects in the EC condition stayed longer in the hyper-connected State 1 than those in the EO; (ii) subjects in the EO condition stayed longer in the hypo-connected State 2 than those in the EC; and (iii) the dFC state transformed into the other state more frequently during EC than during EO. We also found the variance of the characteristic path length was higher during EC than during EO in the hyper-connected State 1. These results indicate that brain activity may be more active and unstable during EC than during EO. Our findings may provide insights into the dynamic nature of the resting-state brain and could be a useful reference for future rs-fMRI studies.
Asunto(s)
Encéfalo/fisiología , Ojo , Red Nerviosa/fisiología , Descanso/fisiología , Adulto , Mapeo Encefálico/métodos , Análisis por Conglomerados , Femenino , Humanos , Procesamiento de Imagen Asistido por Computador/métodos , Imagen por Resonancia Magnética/métodos , Masculino , Adulto JovenRESUMEN
The pathogenesis of inflammation bowel disease (IBD) involves exaggerated effector T cell responses and impaired regulatory T cell functions. We previously found that sauchinone (SAU) ameliorated experimental colitis via facilitating Th17 cell production of IL-10, but how SAU regulated Th17 cell differentiation remains unknown. MicroRNAs (miR) have been recognized as a crucial regulator of T cell biology and play a considerable role in IBD. Here, we demonstrated that SAU significantly suppressed miR-340 expression in Th17 cells, and enforced miR-340 expression abrogated SAU inhibition of Th17 differentiation. miR-340 itself was found to facilitate Th17 differentiation, especially the pathogenic "Th1-like" subset. In human IBD, miR-340 was intimately correlated with the disease severity. SAU markedly decreased miR-340 in the inflamed mucosa tissues from IBD patients. Scaffold/matrix-associated region-binding protein 1 (SMAR1) was identified as a target gene of miR-340. We revealed that blockade of miR-340 significantly reduced mucosal damage and Th17 responses in the lamina propria in a mouse colitis model. Our findings suggest that miR-340 negatively affects SAU inhibition of Th17 differentiation and might play a crucial role in the regulation of pathogenic "Th1-like" Th17 cell generation, which might serve as a novel therapeutic target of IBD.
Asunto(s)
Benzopiranos/farmacología , Diferenciación Celular/efectos de los fármacos , Dioxoles/farmacología , Inflamación/inmunología , Enfermedades Inflamatorias del Intestino/genética , Enfermedades Inflamatorias del Intestino/inmunología , Intestinos/patología , MicroARNs/metabolismo , Células Th17/patología , Secuencia de Bases , Proteínas de Ciclo Celular/genética , Proteínas de Ciclo Celular/metabolismo , Colitis/inducido químicamente , Colitis/inmunología , Colitis/patología , Proteínas de Unión al ADN/genética , Proteínas de Unión al ADN/metabolismo , Susceptibilidad a Enfermedades , Regulación hacia Abajo/efectos de los fármacos , Factores de Transcripción Forkhead/metabolismo , Humanos , MicroARNs/genética , Proteínas Nucleares/genética , Proteínas Nucleares/metabolismo , Índice de Severidad de la Enfermedad , Linfocitos T Reguladores/efectos de los fármacos , Linfocitos T Reguladores/inmunología , Células TH1/efectos de los fármacos , Células TH1/patología , Células Th17/efectos de los fármacos , Células Th17/inmunología , Ácido Trinitrobencenosulfónico , Regulación hacia Arriba/efectos de los fármacosRESUMEN
Inflammatory bowel disease (IBD) is a complex inflammatory disorder of the digestive tract with dysregulated innate and adaptive immune responses. Dendritic cells (DC), the most important antigen presenting cells, act as bridges connecting the adaptive and innate immune systems, and play a crucial role in the regulation of local homeostasis in the gut and are also essential mediators in the initiation and development of intestinal inflammation. Our recent study found that sauchinone (SAU) was able to ameliorate experimental colitis in mice by restraining Th17 cell differentiation and their pathogenicity. Here, we found that SAU significantly inhibited LPS-induced DC activation. Moreover, SAU suppressed the ability of LPS-primed DC to induce Th1/Th17 cell differentiation, but SAU-treated DC up-regulated their ability to initiate Foxp3+ Treg cell generation. Of note, we found that genetical ablation of Blimp-1 in DC markedly abrogated the SAU suppression of pro-inflammatory cytokine or promote immunomodulatory molecule production by DC. Blimp-1 deficiency boosted the ability of DC to polarize naïve CD4+ T cells into Th1/Th17 cell lineages. SAU failed to alleviated DSS-induced colitis in mice with Blimp-1-deficient DC. Our results shed new lights on the mechanisms of how SAU regulates DC biology and intestinal inflammation.
Asunto(s)
Antiinflamatorios/uso terapéutico , Benzopiranos/uso terapéutico , Colitis/tratamiento farmacológico , Células Dendríticas/efectos de los fármacos , Dioxoles/uso terapéutico , Inflamación/tratamiento farmacológico , Factor 1 de Unión al Dominio 1 de Regulación Positiva/inmunología , Animales , Antiinflamatorios/farmacología , Benzopiranos/farmacología , Colitis/inducido químicamente , Colitis/inmunología , Células Dendríticas/inmunología , Sulfato de Dextran , Dioxoles/farmacología , Inflamación/inmunología , Masculino , Ratones Endogámicos C57BL , Células Th17/efectos de los fármacos , Células Th17/inmunologíaRESUMEN
Dendritic cells (DC) are the most important antigen-presenting cells, which guide T cell activation and function, and dysregulated DC function might be one of the crucial causes of inflammatory bowel disease (IBD). It has been well-known that microbiota and their metabolites play an essential role in regulating the biology and function of DC, thus contributing to the pathogenesis of IBD. However, the underlying mechanisms remain largely unknown. Amphiregulin (AREG), a molecule of the epidermal growth factor (EGF) family, is primarily described as an epithelial cell-derived cytokine and recognized as a critical regulator of cell proliferation and tissue repair. Here, we found that DC expression of AREG depended on butyrate (a microbiota-derived short chained fatty acid), which required the interaction between butyrate and G-protein-coupled receptor 43 (GPR43). Furthermore, we found that butyrate-GPR43 interaction failed to induce AREG expression in DC deficient in B lymphocyte induced maturation protein 1 (Blimp-1). Notably, DC-derived AREG was indispensable for the protection against experimental colitis in mice. Additionally, AREG expression was significantly decreased in DC from IBD patients. Our data provide novel evidences to interpret how AREG expression is regulated in DC, and shed new light on the mechanisms whereby microbiota regulate DC function.
Asunto(s)
Anfirregulina/genética , Butiratos/inmunología , Colitis Ulcerosa/genética , Enfermedad de Crohn/genética , Células Dendríticas/inmunología , Factor 1 de Unión al Dominio 1 de Regulación Positiva/genética , Receptores de Superficie Celular/genética , Anfirregulina/inmunología , Animales , Linfocitos B/inmunología , Linfocitos B/microbiología , Linfocitos B/patología , Butiratos/metabolismo , Butiratos/farmacología , Estudios de Casos y Controles , Colitis Ulcerosa/inducido químicamente , Colitis Ulcerosa/inmunología , Colitis Ulcerosa/microbiología , Enfermedad de Crohn/inmunología , Enfermedad de Crohn/microbiología , Enfermedad de Crohn/patología , Células Dendríticas/microbiología , Células Dendríticas/patología , Femenino , Microbioma Gastrointestinal/inmunología , Regulación de la Expresión Génica , Humanos , Masculino , Ratones , Ratones Endogámicos C57BL , Ratones Noqueados , Proteínas Asociadas a Pancreatitis/deficiencia , Proteínas Asociadas a Pancreatitis/genética , Proteínas Asociadas a Pancreatitis/inmunología , Factor 1 de Unión al Dominio 1 de Regulación Positiva/inmunología , Receptores de Superficie Celular/inmunología , Receptores Acoplados a Proteínas G/deficiencia , Receptores Acoplados a Proteínas G/genética , Receptores Acoplados a Proteínas G/inmunología , Transducción de Señal , Dodecil Sulfato de Sodio/administración & dosificación , Proteína de la Zonula Occludens-1/genética , Proteína de la Zonula Occludens-1/inmunologíaRESUMEN
OBJECTIVE: To evaluate the effect of endoscopy assisted pars plana vitrectomy for severe ocular trauma with no light perception. METHODS: A retrospective case-series study. Medical records of 6 eyes of 6 patients undergoing endoscopy assisted vitrectomy for severe ocular trauma with no light perception from December 2006 to August 2009 were studied. Four patients were male and 2 patients were female. Their age ranged from 6 to 67 years old with an mean age of 38 years. History of trauma, visual acuity prior to vitrectomy and at final follow-up, bacterial culture results and surgical approaches were recorded. RESULTS: Visual acuity prior to vitrectomy was no light perception in all the 6 patients with a mean intraocular pressure of 3 mmHg (1 mmHg=0.133 kPa) . All the patients had diffuse corneal edema along with opacities caused by corneal perforation from trauma in 3 patients, blood staining of cornea in 2 patients and endophthalmitis in 1 patient. B-scan ultrasound echography carried out before surgery showing that all the patients had retinal detachment. Three patients' vitreous samples were sent for bacterial culture. Bacillus cereus, S.epidermidis and Aeromonas Hydrophila were identified respectively. Patients were followed up for 18 to 36 months. Postoperatively, 5 of the patients' visual acuity was better than light perception, ranging from light perception to 0.04. The retina was reattached in 4 patients. CONCLUSION: Endoscopy assisted vitrectomy is a safe and effective option for the treatment of severe traumatic eye with no light perception.
Asunto(s)
Opacidad de la Córnea/cirugía , Endoscopía , Lesiones Oculares/cirugía , Vitrectomía/métodos , Adolescente , Adulto , Anciano , Niño , Opacidad de la Córnea/complicaciones , Lesiones Oculares/complicaciones , Femenino , Humanos , Masculino , Persona de Mediana Edad , Estudios Retrospectivos , Resultado del Tratamiento , Adulto JovenRESUMEN
UNLABELLED: To decrease evisceration of eyes, endoscopy-assisted pars plana vitrectomy is a choice for patients with severe endophthalmitis accompanied with retinal detachment and corneal edema. PURPOSE: To evaluate surgical outcomes using an intraocular videoendoscope for vitrectomy in patients with severe endophthalmitis with retinal detachment. METHODS: From December 2006 to August 2009, the medical records of 21 patients undergoing endoscopy-assisted vitrectomy for endophthalmitis with retinal detachment were studied. Only patients with ≥18 months follow-up were included. RESULTS: Intraocular infections were under control in 19 of the 21 patients. Postoperatively, the visual acuity of three of the patients ranged from 2/100 to 20/100 (14.3 %), two of the patients left with finger counting (9.5 %), eight had hand motion (38.1 %), six had light perception (28.6 %), and the other two had their eyes eviscerated (9.5 %) because of recurrent and uncontrollable infection. CONCLUSIONS: In patients with severe endophthalmitis accompanied with retinal detachment and marked corneal opacity, it is appropriate to conduct endoscopy-assisted pars plana vitrectomy to decrease evisceration of eyes.
Asunto(s)
Endoftalmitis/cirugía , Endoscopía/métodos , Desprendimiento de Retina/cirugía , Vitrectomía/métodos , Cuerpo Vítreo/cirugía , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Antibacterianos/administración & dosificación , Niño , Preescolar , Opacidad de la Córnea/microbiología , Endoftalmitis/microbiología , Endotaponamiento , Evisceración del Ojo , Femenino , Fluorocarburos/administración & dosificación , Estudios de Seguimiento , Humanos , Lactante , Masculino , Persona de Mediana Edad , Desprendimiento de Retina/microbiología , Estudios Retrospectivos , Aceites de Silicona/administración & dosificación , Resultado del Tratamiento , Grabación en Video , Agudeza Visual/fisiología , Cuerpo Vítreo/microbiologíaRESUMEN
Anxiety is a common disease within human psychiatric disorders and has also been described as a frequently neuropsychiatric problem in dogs. Human neuroimaging studies showed abnormal functional brain networks might be involved in anxiety. In this study, we expected similar changes in network topology are also present in dogs. We performed resting-state functional MRI on 25 healthy dogs and 13 patients. The generic Canine Behavioral Assessment & Research Questionnaire was used to evaluate anxiety symptoms. We constructed functional brain networks and used graph theory to compare the differences between two groups. No significant differences in global network topology were found. However, focusing on the anxiety circuit, global efficiency and local efficiency were significantly higher, and characteristic path length was significantly lower in the amygdala in patients. We detected higher connectivity between amygdala-hippocampus, amygdala-mesencephalon, amygdala-thalamus, frontal lobe-hippocampus, frontal lobe-thalamus, and hippocampus-thalamus, all part of the anxiety circuit. Moreover, correlations between network metrics and anxiety symptoms were significant. Altered network measures in the amygdala were correlated with stranger-directed fear and excitability; altered degree in the hippocampus was related to attachment/attention seeking, trainability, and touch sensitivity; abnormal frontal lobe function was related to chasing and familiar dog aggression; attachment/attention seeking was correlated with functional connectivity between amygdala-hippocampus and amygdala-thalamus; familiar dog aggression was related to global network topology change. These findings may shed light on the aberrant topological organization of functional brain networks underlying anxiety in dogs.
Asunto(s)
Encéfalo , Imagen por Resonancia Magnética , Humanos , Perros , Animales , Imagen por Resonancia Magnética/métodos , Encéfalo/diagnóstico por imagen , Ansiedad/diagnóstico por imagen , Amígdala del Cerebelo/diagnóstico por imagen , Miedo , Mapeo EncefálicoRESUMEN
Anxiety and fear are dysfunctional behaviors commonly observed in domesticated dogs. Although dogs and humans share psychopathological similarities, little is known about how dysfunctional fear behaviors are represented in brain networks in dogs diagnosed with anxiety disorders. A combination of diffusion tensor imaging (DTI) and graph theory was used to investigate the underlying structural connections of dysfunctional anxiety in anxious dogs and compared with healthy dogs with normal behavior. The degree of anxiety was assessed using the Canine Behavioral Assessment & Research Questionnaire (C-BARQ), a widely used, validated questionnaire for abnormal behaviors in dogs. Anxious dogs showed significantly decreased clustering coefficient ([Formula: see text]), decreased global efficiency ([Formula: see text]), and increased small-worldness (σ) when compared with healthy dogs. The nodal parameters that differed between the anxious dogs and healthy dogs were mainly located in the posterior part of the brain, including the occipital lobe, posterior cingulate gyrus, hippocampus, mesencephalon, and cerebellum. Furthermore, the nodal degree ([Formula: see text]) of the left cerebellum was significantly negatively correlated with "excitability" in the C-BARQ of anxious dogs. These findings could contribute to the understanding of a disrupted brain structural connectome underlying the pathological mechanisms of anxiety-related disorders in dogs.
Asunto(s)
Conectoma , Imagen de Difusión Tensora , Humanos , Perros , Animales , Imagen de Difusión Tensora/métodos , Conectoma/métodos , Encéfalo/diagnóstico por imagen , Encéfalo/patología , Ansiedad/diagnóstico por imagen , Lóbulo Occipital/patologíaRESUMEN
Glaucoma is the leading cause of irreversible blindness. Currently, most therapeutic strategies aim to reduce elevated intraocular pressure (EIOP), but this does not always halt disease progression. Evidence suggests a role for T cells in glaucoma pathogenesis, but the underlying mechanisms remain largely unknown. Here, we found that the percentage of circulating CD4+ T cells expressing a gut-homing integrin ß7 was increased in patients with glaucoma and was associated with disease stage. In an EIOP-triggered glaucoma mouse model, ß7+ CD4+ T cells infiltrated the retina in the progressive phase of glaucoma via eliciting retinal endothelial cell expression of mucosal vascular addressin cell adhesion molecule 1 (MAdCAM-1). MAdCAM-1 was minimally detected in retinas of healthy mice, and neutralization with an MAdCAM-1 antibody ameliorated retinal ganglion cell (RGC) loss and glial activity in mice with glaucoma. We furthermore found that EIOP-induced ß7+ CD4+ T cells homed to the gut during the acute phase of glaucoma, which was essential for progressive RGC damage in diseased mice. Gut-homing ß7+ CD4+ T cells underwent transcriptional reprogramming, showing up-regulated pathways enriched in autoimmune diseases, bacteria responses, mucosal immunity, and glial activity. Gut-homing ß7+ CD4+ T cells gained the competence to induce retinal MAdCAM-1 expression and to cross the blood-retina barrier. Together, our study reveals a role of gut-licensed ß7+ CD4+ T cells and MAdCAM-1 in RGC degeneration and emphasizes the importance of the "gut-retina" axis in glaucoma.
Asunto(s)
Glaucoma , Células Ganglionares de la Retina , Linfocitos T , Animales , Ratones , Linfocitos T CD4-Positivos , Progresión de la Enfermedad , Glaucoma/patologíaRESUMEN
Parkinson's disease (PD), a chronic neurodegenerative disease, is characterized by sensorimotor and cognitive deficits. Previous diffusion tensor imaging (DTI) studies found abnormal DTI metrics in white matter bundles, such as the corpus callosum, cingulate, and frontal-parietal bundles, in PD patients. These studies mainly focused on alterations in microstructural features of long-range bundles within the deep white matter (DWM) that connects pairs of distant cortical regions. However, less is known about the DTI metrics of the superficial white matter (SWM) that connects local cortical regions in PD patients. To determine whether the DTI metrics of the SWM were different between the PD patients and the healthy controls, we recruited DTI data from 34 PD patients and 29 gender- and age-matched healthy controls. Using a probabilistic tractographic approach, we first defined a population-based SWM mask across all the subjects. Using a tract-based spatial statistical (TBSS) analytic approach, we then identified the SWM bundles showing abnormal DTI metrics in the PD patients. We found that the PD patients showed significantly lower DTI metrics in the SWM bundles connecting the sensorimotor cortex, cingulate cortex, posterior parietal cortex (PPC), and parieto-occipital cortex than the healthy controls. We also found that the clinical measures in the PD patients was significantly negatively correlated with the fractional anisotropy in the SWM (FASWM) that connects core regions in the default mode network (DMN). The FASWM in the bundles that connected the PPC was significantly positively correlated with cognitive performance in the PD patients. Our findings suggest that SWM may serve as the brain structural basis underlying the sensorimotor deficits and cognitive degeneration in PD patients.
Asunto(s)
Enfermedades Neurodegenerativas , Enfermedad de Parkinson , Sustancia Blanca , Imagen de Difusión Tensora , Humanos , Imagen por Resonancia Magnética , Enfermedad de Parkinson/diagnóstico por imagen , Sustancia Blanca/diagnóstico por imagenRESUMEN
Aiming to reduce the difficulty of managing and motivating knowledge workers (k-workers), and promote the psychological well-being of them in Chinese hospitals, this study examines how k-workers' leader-member exchange (LMX) influences their task performance and the mediation effect of organizational citizenship behavior (OCB). Through a self-administered survey, valid questionnaires were collected from 384 k-workers in Chinese hospitals, and partial least squares structural equation modeling was employed for data analysis. The findings show that LMX is positively related to OCB and task performance, and that OCB mediates the relationship between LMX and task performance. This research has theoretical implications and also provides practical suggestions on how to manage, motivate, and inspire k-workers, and promote the psychological well-being of them, and finally enhance the organizational performance in Chinese hospitals.
RESUMEN
BACKGROUND: Irritable bowel syndrome (IBS) is characterized with abdominal pain, bloating, and changes in bowel habits, and dealing with IBS is still a clinical challenge. The pathogenesis of IBS has been reported to be linked to low-grade mucosal inflammation, and macrophages contribute to the pathological process of this disease. Kurarinone (KAR), a flavanoid derived from Sophora flavescens, has been found medically effective in many inflammatory conditions and cancers. KAR was previously reported to inhibit LPS-induced expression of inflammatory cytokines in macrophages, whether and how KAR regulates the functions of macrophage in IBS remains to be elusive. METHODS: We established a TNBS-induced IBS mouse model, in which KAR was administrated, and mucosal cytokine expression was measured by qRT-PCR. Additionally, mouse macrophages were generated in vitro and their responses to LPS were evaluated by flow cytometry and qRT-PCR. AhR+/+ or AhR-/- macrophages were transferred into DTx-treated CD11b-DTR transgenic mice to investigate the role of AhR in IBS. We collected colonic biopsies and peripheral blood samples from 64 patients with IBS, and analyzed AhR expression by qRT-PCR. RESULTS: We found KAR effectively alleviated visceral hypersensitivity and maintained intestinal barrier functions in mice with IBS. KAR inhibited LPS-induced macrophage activation and expression of pro-inflammatory genes, while increased anti-inflammatory gene expression including IL-10 in an AhR-dependent manner. Using macrophage-depleted mice, we found that chimera mice with AhR-/- macrophages were more susceptible to TNBS-induced IBS and the therapeutic effect of KAR on IBS was significantly impaired in mice with AhR-/- macrophages. Additionally, we found AhR expression in macrophages of IBS patients was associated with the disease severity. CONCLUSION: Our findings provide new evidences that KAR regulates IBS development via macrophage-intrinsic AhR. KAR might show promise as an immunomodulatory therapeutic agent in treating IBS.
RESUMEN
BACKGROUND: Glaucoma is a group of retinal neurodegenerative diseases causing irreversible visual impairment. The pathogenesis of this disease is complicated. Studies have shown that the immune system is involved in the neurodegenerative process of glaucoma. There are continuous evidences that autoantibodies play a crucial role in the pathogenesis of glaucoma. However, focuses on B cells, the antibody-producing cells in glaucoma are surprisingly limited. METHODS: Fresh peripheral blood samples were collected from 44 glaucoma patients (38 with primary angle-closure glaucoma (PACG) and 6 with (primary open-angle glaucoma POAG)) and 36 age-matched healthy donors (HD). Density gradient centrifugation was performed to obtain peripheral blood mononuclear cells (PBMC). Flow cytometry was performed to determine B cell phenotypes. The severity of glaucoma was determined based on the mean deviation (MD) of visual field. RESULTS: In this study, we demonstrated that total B cells was significantly increased in glaucoma patients compared to HD. Next, we checked changes of different B cell subsets in glaucoma. Glaucoma patients were found to have a significant increase in the frequencies of antibody-secreting cells (ASC)/plasmablasts, naïve, and CD19+ CD27- IgD- double negative (DN) subpopulations, but a decrease in the CD27+ IgD+ unswitched memory compartment. Notably, we found that the increment of CD27- IgD- DN B cells was significantly magnified according to the clinical severity. CONCLUSION: We demonstrate, for the first time, that peripheral B cell subsets are altered and unveil the correlation of a newly identified pro-inflammatory CD27- IgD- DN subset with clinical features of glaucoma, suggesting that these B cell subsets could serve as potential biomarkers to monitor the disease progression of glaucoma patients.
RESUMEN
Background: Frequent exposure to criticism is a known risk factor for various adult psychiatric disorders. Adolescents may be even more vulnerable to (parental) criticism, as their imbalanced brain maturation makes them prone to stronger mood changes and less effective emotional regulation. Identifying which adolescent subgroups are more vulnerable than others could be of great clinical relevance. Perceived criticism (PC) and self-criticism (SC), two related but distinct traits, could well be crucial vulnerability factors. Hypotheses: After exposure to criticism during fMRI scanning, rapid changes in amygdalar functional connectivity (FC) with other brain areas involved in emotion regulation and social cognitive processing will occur. These changes will depend on trait moderators, such as the adolescents' proneness to (a) perceive others as critical of them (PC) or (b) perceive themselves positively or negatively (SC). Methods: Sixty-four healthy 14-17-year-olds were exposed to a series of auditory comments. Changes in mood states were assessed based on the Profile of Mood States (POMS) prior to and after exposure to these segments. Pre- and post-experiment FC of the left and right amygdalae with other brain areas were also measured. Correlates between FC changes and psychometric measures-including the perceived criticism measure (PCM) and self-perception profile for adolescents (SPPA)-were assessed. Results: First, after being criticized, FC increases of the left amygdala seed region with brain areas related to sustained emotional processing were found, but no right amygdalar FC changes. Second, there was a significant positive partial correlation between individual PCM scores and FC changes between the left amygdala seed region and the left precuneus and left superior parietal cortex, both part of the default mode network. Conclusion: Exposure to criticism resulted in a rapid negative mood change accompanied by an increase in FC between the left amygdala and regions known to be involved in sustained emotional processing, but no right amygdalar FC changes. Furthermore, higher PC but not SC was correlated with stronger left amygdalar FC increases with these regions, suggesting an elevated vulnerability for disturbed emotional processing, as observed in mood disorders, in healthy adolescents with higher PCM scores.
RESUMEN
Extra-intestinal manifestations (EIMs) of the eyes are found in IBD patients, but the underlying pathogenesis remains unknown. To investigate the pathogenesis of IBD-associated retinal dysfunction, chronic colitis was induced in mice by oral administration of dextran sodium sulfate (DSS). Electroretinography (ERG) was performed to evaluate retinal function. Retinal neuron degeneration was analyzed by immunohistochemistry. Colitic mice displayed aberrant amplitudes of ERG a-, b-wave and oscillatory potentials (OP). Importantly, we observed severe degeneration of bipolar and ganglion cells. In contrast, outer retinal neurons (mainly photoreceptor cells) are mildly affected by colitis. Moreover, retinal inflammatory responses were significantly upregulated during colitis, including microglia activation, lymphocyte infiltration and cytokine/chemokine production. Notably, mucosal addressin cell adhesion molecule 1 (MAdCAM-1) was upregulated in retinal microvessels, especially the superficial and deep plexuses, and recruited gut-homing CD4+ T cells to be co-localized with bipolar and ganglion cells during colitis. Expectedly, in vivo depletion of CD4+ T cells or blockade of MAdCAM-1 greatly alleviated colitis-induced retinal inflammatory responses and neuron degeneration. Therefore, our data provide novel insight into the pathogenesis of IBD-associated retinal dysfunction, and targeted immune therapy directly against MAdCAM-1 might provide a novel approach in the management of eye EIM of IBD.
Asunto(s)
Linfocitos T CD4-Positivos/inmunología , Linfocitos T CD4-Positivos/metabolismo , Moléculas de Adhesión Celular/genética , Colitis/complicaciones , Colitis/inmunología , Mucoproteínas/genética , Degeneración Nerviosa/etiología , Neuronas Retinianas/metabolismo , Animales , Biomarcadores , Moléculas de Adhesión Celular/metabolismo , Colitis/etiología , Colitis/patología , Citocinas/metabolismo , Modelos Animales de Enfermedad , Susceptibilidad a Enfermedades , Mediadores de Inflamación/metabolismo , Mucosa Intestinal/inmunología , Mucosa Intestinal/metabolismo , Mucosa Intestinal/patología , Ratones , Mucoproteínas/metabolismo , Degeneración Nerviosa/diagnóstico , Degeneración Nerviosa/metabolismo , Neuronas Retinianas/patologíaRESUMEN
Cognitive and emotional impairments observed in mild traumatic brain injury (mTBI) patients may reflect variances of brain connectivity within specific networks. Although previous studies found altered functional connectivity (FC) in mTBI patients, the alterations of brain structural properties remain unclear. In the present study, we analyzed structural covariance (SC) for the acute stages of mTBI (amTBI) patients, the chronic stages of mTBI (cmTBI) patients, and healthy controls. We first extracted the mean gray matter volume (GMV) of seed regions that are located in the default-mode network (DMN), executive control network (ECN), salience network (SN), sensorimotor network (SMN), and the visual network (VN). Then we determined and compared the SC for each seed region among the amTBI, the cmTBI and the healthy controls. Compared with healthy controls, the amTBI patients showed lower SC for the ECN, and the cmTBI patients showed higher SC for the both DMN and SN but lower SC for the SMN. The results revealed disrupted ECN in the amTBI patients and disrupted DMN, SN and SMN in the cmTBI patients. These alterations suggest that early disruptions in SC between bilateral insula and the bilateral prefrontal cortices may appear in amTBI and persist into cmTBI, which might be potentially related to the cognitive and emotional impairments.
Asunto(s)
Conmoción Encefálica , Sustancia Gris , Encéfalo/diagnóstico por imagen , Conmoción Encefálica/diagnóstico por imagen , Mapeo Encefálico , Sustancia Gris/diagnóstico por imagen , Humanos , Imagen por Resonancia MagnéticaRESUMEN
Previous neuroimaging studies revealed radiation-induced brain injury in patients with nasopharyngeal carcinoma (NPC) in the years after radiotherapy (RT). These injuries may be associated with structural and functional alterations. However, differences in the brain structural connectivity of NPC patients at different times after RT, especially in the early-delayed period, remain unclear. We acquired diffusion tensor imaging (DTI) data from three groups of NPC patients, 25 in the pre-RT (before RT) group, 22 in the early-delayed (1-6 months) period (post-RT-ED) group, and 33 in the late-delayed (>6 months) period (post-RT-LD) group. Then, we constructed brain white matter (WM) structural networks and used graph theory to compare their between-group differences. The NPC patients in the post-RT-ED group showed decreased global properties when compared with the pre-RT group. We also detected the nodes with between-group differences in nodal parameters. The nodes that differed between the post-RT-ED and pre-RT groups were mainly located in the default mode (DMN) and central executive networks (CEN); those that differed between the post-RT-LD and pre-RT groups were located in the limbic system; and those that differed between the post-RT-LD and post-RT-ED groups were mainly in the DMN. These findings may indicate that radiation-induced brain injury begins in the early-delayed period and that a reorganization strategy begins in the late-delayed period. Our findings may provide new insight into the pathogenesis of radiation-induced brain injury in normal-appearing brain tissue from the network perspective.
Asunto(s)
Carcinoma Nasofaríngeo/radioterapia , Neoplasias Nasofaríngeas , Sustancia Blanca , Encéfalo/diagnóstico por imagen , Imagen de Difusión Tensora , Humanos , Imagen por Resonancia Magnética , Carcinoma Nasofaríngeo/diagnóstico por imagen , Neoplasias Nasofaríngeas/diagnóstico por imagen , Neoplasias Nasofaríngeas/radioterapia , Sustancia Blanca/diagnóstico por imagenRESUMEN
Resting-state functional magnetic resonance imaging (rs-fMRI) is widely used to research abnormal functional connectivity (FC) in patients with disorders of consciousness (DOC). However, most studies assumed steady spatial-temporal signal interactions between distinct brain regions during the scan period. The aim of this study was to explore abnormal dynamic functional connectivity (dFC) in DOC patients. After excluding 26 patients' data that failed to meet the requirements of imaging quality, we retained 19 DOC patients (12 with unresponsive wakefulness syndrome and 7 in a minimally conscious state, diagnosed with the Coma Recovery Scale-Revised [CRS-R]) for the dFC analysis. We used the sliding windows approach to construct dFC matrices. Then these matrices were clustered into distinct states using the k-means clustering algorithm. We found that the DOC patients showed decreased dFC in the sensory and somatomotor networks compared with the healthy controls. There were also significant differences in temporal properties, the mean dwell time (MDT) and the number of transitions (NT), between the DOC patients and the healthy controls. In addition, we also used a hidden Markov model (HMM) to test the robustness of the results. With the connectome-based predictive modeling (CPM) approach, we found that the properties of abnormal dynamic network can be used to predict the CRS-R scores of the patients after severe brain injury. These findings may contribute to a better understanding of the abnormal brain networks in DOC patients.