Large-scale network abnormality in behavioral addiction.

BACKGROUND: Researchers have endeavored to ascertain the network dysfunction associated with behavioral addiction (BA) through the utilization of resting-state functional connectivity (rsFC). Nevertheless, the identification of aberrant patterns within large-scale networks pertaining to BA has proven to be challenging. METHODS: Whole-brain seed-based rsFC studies comparing subjects with BA and healthy controls (HC) were collected from multiple databases. Multilevel kernel density analysis was employed to ascertain brain networks in which BA was linked to hyper-connectivity or hypo-connectivity with each prior network. RESULTS: Fifty-six seed-based rsFC publications (1755 individuals with BA and 1828 HC) were included in the meta-analysis. The present study indicate that individuals with BAs exhibit (1) hypo-connectivity within the fronto-parietal network (FN) and hypo- and hyper-connectivity within the ventral attention network (VAN); (2) hypo-connectivity between the FN and regions of the VAN, hypo-connectivity between the VAN and regions of the FN and default mode network (DMN), hyper-connectivity between the DMN and regions of the FN; (3) hypo-connectivity between the reward system and regions of the sensorimotor network (SS), DMN and VAN; (4) hypo-connectivity between the FN and regions of the SS, hyper-connectivity between the VAN and regions of the SS. CONCLUSIONS: These findings provide impetus for a conceptual framework positing a model of BA characterized by disconnected functional coordination among large-scale networks.

Abnormal Cerebral Blood Flow and Volumetric Brain Morphometry in Patients With Obstructive Sleep Apnea.

Obstructive sleep apnea (OSA) is a serious breathing disorder, leading to myocardial infarction, high blood pressure, and stroke. Brain morphological changes have been widely reported in patients with OSA. The pathophysiological mechanisms of cerebral blood flow (CBF) changes associated with OSA are not clear. In this study, 20 patients with OSA and 36 healthy controls (HCs) were recruited, and then pseudo-continuous arterial spin labeling (pCASL) and voxel-based morphometry (VBM) methods were utilized to explore blood perfusion and morphological changes in the patients with OSA. Compared with the HC group, the OSA group showed increased CBF values in the right medial prefrontal cortex (mPFC), left precentral gyrus, and right insula and showed decreased CBF values in the right temporal pole (TP) and the right cerebellum_Crus2. Compared with the HC group, the patients with OSA showed decreased gray matter volume (GMV) in the right dorsal lateral prefrontal cortex (DLPFC), the right occipital pole, and the vermis. There were no significantly increased GMV brain regions found in patients with OSA. Pearson correlation analysis showed that the reduced GMV in the right DLPFC and the right occipital pole was both positively correlated with Mini-Mental State Examination (MMSE) (r = 0.755, p < 0.001; r = 0.686, p = 0.002) and Montreal Cognitive Assessment (MoCA) scores (r = 0.716, p = 0.001; r = 0.601, p = 0.008), and the reduced GMV in the right occipital pole was negatively correlated with duration of illness (r = -0.497, p = 0.036). Patients with OSA have abnormal blood perfusion metabolism and morphological changes in brain regions including the frontal lobe and the cerebellum and were closely related to abnormal behavior, psychology, and cognitive function, which play an important role in the pathophysiological mechanism of OSA.

Shared and specific characteristics of regional cerebral blood flow and functional connectivity in unmedicated bipolar and major depressive disorders.

BACKGROUND: Identifying brain similarities and differences between bipolar disorder (BD) and major depressive disorder (MDD) can help us better understand their pathophysiological mechanisms and develop more effective treatments. However, the features of whole-brain regional cerebral blood flow (CBF) and intrinsic functional connectivity (FC) underlying BD and MDD have not been directly compared. METHODS: Eighty-eight unmedicated BD II depression patients, 95 unmedicated MDD patients, and 96 healthy controls (HCs) underwent three-dimensional arterial spin labeling (3D ASL) and resting-state functional MRI (rs-fMRI). The functional properties of whole brain CBF and seed-based resting-state FC further performed based on those regions with changed CBF were analyzed between the three groups. RESULTS: The patients with BD and MDD showed commonly increased CBF in the left posterior lobe of the cerebellum and the left middle temporal gyrus (MTG) compared with HCs. The CBF of the left MTG was positively associated with 24-items Hamilton Depression Rating Scale scores in MDD patients. Decreased FC between the left posterior lobe of the cerebellum and the left inferior frontal gyrus (IFG) was observed only in patients with BD compared with HCs. CONCLUSION: Patients with BD and those with MDD shared common features of CBF in the posterior lobe of the cerebellum and the MTG. The altered posterior lobe of the cerebellum-IFG FC can be considered as a potential biomarker for the differentiation of patients with BD from those with MDD.

Association between resting-state functional connectivity of amygdala subregions and peripheral pro-inflammation cytokines levels in bipolar disorder.

The pathophysiological mechanisms of bipolar disorder (BD) are not completely known, and systemic inflammation and immune dysregulation are considered as risk factors. Previous neuroimaging studies have proved metabolic, structural and functional abnormalities of the amygdala in BD, suggesting the vital role of amygdala in BD patients. This study aimed to test the underlying neural mechanism of inflammation-induced functional connectivity (FC) in the amygdala subregions of BD patients. Resting-state functional MRI (rs-fMRI) was used to delineate the amygdala FC from two pairs of amygdala seed regions (the bilateral lateral and medial amygdala) in 51 unmedicated BD patients and 69 healthy controls (HCs). The levels of pro-inflammatory cytokines including interleukin (IL)-1ß, IL-6 and tumor necrosis factor (TNF)-α were measured in the serum. The correlation between abnormal levels of pro-inflammatory cytokines and FC values were calculated in BD patients. The BD group exhibited decreased FC between the right medial amygdala and bilateral medial frontal cortex (MFC), and decreased FC between the left medial amygdala and the left temporal pole (TP), right orbital inferior frontal gyrus compared with HCs. The BD patients had higher levels of TNF-α than HCs. Correlation analysis showed negative correlation between the TNF-α level and abnormal FC of the right medial amygdala-bilateral MFC; and negative correlation between TNF-α levels and abnormal FC of the left medial amygdala-left TP in BD group. These findings suggest that dysfunctional and immune dysregulation between the amygdala and the frontotemporal circuitry might play a critical role in the pathogenesis of BD.

Shared and specific patterns of dynamic functional connectivity variability of striato-cortical circuitry in unmedicated bipolar and major depressive disorders.

BACKGROUND: Accumulating studies have found structural and functional abnormalities of the striatum in bipolar disorder (BD) and major depressive disorder (MDD). However, changes in intrinsic brain functional connectivity dynamics of striato-cortical circuitry have not been investigated in BD and MDD. This study aimed to investigate the shared and specific patterns of dynamic functional connectivity (dFC) variability of striato-cortical circuitry in BD and MDD. METHODS: Brain resting-state functional magnetic resonance imaging data were acquired from 128 patients with unmedicated BD II (current episode depressed), 140 patients with unmedicated MDD, and 132 healthy controls (HCs). Six pairs of striatum seed regions were selected: the ventral striatum inferior (VSi) and the ventral striatum superior (VSs), the dorsal-caudal putamen (DCP), the dorsal-rostral putamen (DRP), and the dorsal caudate and the ventral-rostral putamen (VRP). The sliding-window analysis was used to evaluate dFC for each seed. RESULTS: Both BD II and MDD exhibited increased dFC variability between the left DRP and the left supplementary motor area, and between the right VRP and the right inferior parietal lobule. The BD II had specific increased dFC variability between the right DCP and the left precentral gyrus compared with MDD and HCs. The MDD had increased dFC variability between the left VSi and the left medial prefrontal cortex compared with BD II and HCs. CONCLUSIONS: The patients with BD and MDD shared common dFC alteration in the dorsal striatal-sensorimotor and ventral striatal-cognitive circuitries. The patients with MDD had specific dFC alteration in the ventral striatal-affective circuitry.

Psychological Effects of People Isolated in Hubei Due to COVID-19 Epidemic.

The Coronavirus Disease 2019 (COVID-19) epidemic broke out from Wuhan in Hubei province, China, spread nationwide and then gradually developed into other countries in the world. The implementation of unprecedented strict isolation measures has affected many aspects of people's lives and posed a challenge to psychological health. To explore whether people isolated for 14 days due to having contact with COVID-19 patients had more psychosocial problems. We conducted an online survey from February 29 to March 10, 2020. Depression, anxiety, post-traumatic stress disorder (PTSD) symptoms, and coping style were assessed by the Patient Health Questionnaire-9 (PHQ-9), 7-item Generalized Anxiety Disorder Scale (GAD-7), Impact of Event Scale-Revised (IES-R), and Simplified Coping Style Questionnaire-20-Chinese Version. This study included 1,315 isolated respondents in Hubei province (58.5% located in Wuhan). 69.3% respondents isolated at home, 30.7% respondents isolated at centralized quarantined spot. Of all respondents, 66.8% reported depressive symptoms, 49.7% reported anxiety symptoms, 89.0% reported PTSD symptoms. The Cronbach α of the IES-R, PHQ-9, GAD-7, and total SCSQ-20 were 0.935, 0.847, 0.843, and 0.888, respectively. Persons who isolated at home were associated with a lower risk of PTSD, depressive and anxiety symptoms (P < 0.01). People who knew someone to have COVID-19 were associated with severe symptoms of PTSD symptoms (P = 0.001). As for coping style, higher level of passive coping style was associated with severe symptoms of PTSD, depression and anxiety (P < 0.001). Our findings identify that person isolated during the COVID-19 epidemic was associated with high proportion of depression, anxiety, and PTSD symptoms. Public health officials should be aware of and prepared to take necessary measures.

LncRNA UCA1 promotes development of gastric cancer via the miR-145/MYO6 axis.

BACKGROUND: Long noncoding RNA (lncRNA), urothelial carcinoma-associated 1 (UCA1) is aberrantly expressed in multiple cancers and has been verified as an oncogene. However, the underlying mechanism of UCA1 in the development of gastric cancer is not fully understood. In the present study, we aimed to identify how UCA1 promotes gastric cancer development. METHODS: The Cancer Genome Atlas (TCGA) and Genotype-Tissue Expression (GTEx) data were used to analyze UCA1 and myosin VI (MYO6) expression in gastric cancer. Western blot and quantitative real-time PCR (QPCR) were performed to test the expression level of the UCA1/miR-145/MYO6 axis in gastric cancer cell lines and tissues. The roles of the UCA1/miR-145/MYO6 axis in gastric cancer in vitro and in vivo were investigated by CCK-8 assay, flow cytometry, siRNAs, immunohistochemistry, and a mouse xenograft model. The targeted relationship among UCA1, miR-145, and MYO6 was predicted using LncBase Predicted v.2 and TargetScan online software, and then verified by luciferase activity assay and RNA immunoprecipitation. RESULTS: UCA1 expression was higher but miR-145 expression was lower in gastric cancer cell lines or tissues, compared to the adjacent normal cell line or normal tissues. Function analysis verified that UCA1 promoted cell proliferation and inhibited cell apoptosis in the gastric cancer cells in vitro and in vivo. Mechanistically, UCA1 could bind directly to miR-145, and MYO6 was found to be a downstream target gene of miR-145. miR-145 mimics or MYO6 siRNAs could partly reverse the effect of UCA1 on gastric cancer cells. CONCLUSIONS: UCA1 accelerated cell proliferation and inhibited cell apoptosis through sponging miR-145 to upregulate MYO6 expression in gastric cancer, indicating that the UCA1/miR-145/MYO6 axis may serve as a potential therapeutic target for gastric cancer.

Large-scale network abnormality in bipolar disorder: A multimodal meta-analysis of resting-state functional and structural magnetic resonance imaging studies.

BACKGROUND: Bipolar disorder (BD) has been linked to abnormalities in the communication and gray matter volume (GMV) of large-scale brain networks, as reflected by impaired resting-state functional connectivity (rs-FC) and aberrant voxel-based morphometry (VBM). However, identifying patterns of large-scale network abnormality in BD has been elusive. METHODS: Whole-brain seed-based rs-FC and VBM studies comparing individuals with BD and healthy controls (HCs) were retrieved from multiple databases. Multilevel kernel density analysis was used to identify brain networks in which BD was linked to hyper-connectivity or hypo-connectivity with each prior network and the overlap between dysconnectivity and GMV changes. RESULTS: Thirty-six seed-based rs-FC publications (1526 individuals with BD and 1578 HCs) and 70 VBM publications (2715 BD and 3044 HCs) were included in the meta-analysis. Our results showed that BD was characterized by hypo-connectivity within the default network (DN), hyper-connectivity within the affective network (AN), and ventral attention network (VAN) and hypo- and hyper-connectivity within the frontoparietal network (FN). Hyper-connectivity between-network of AN-DN, AN-FN, AN-VAN, AN-thalamus network (TN), VAN-TN, VAN-DN, VAN-FN, and TN-sensorimotor network were found. Hypo-connectivity between-network of FN and DN was observed. Decreased GMV was found in the insula, inferior frontal gyrus, and anterior cingulate cortex. LIMITATIONS: Differential weights in the number of included studies and sample size of FC and VBM might have a disproportionate influence on the meta-analytic results. CONCLUSIONS: These results suggest that BD is characterized by both structural and functional abnormalities of large-scale neurocognitive networks, especially in the DN, AN, VAN, FN, and TN.

The Psychological Status of General Population in Hubei Province During the COVID-19 Outbreak: A Cross-Sectional Survey Study.

Introduction: The current outbreak of the novel coronavirus disease 2019 (COVID-19), originating from Wuhan (Hubei, China), has rapidly spread across China and several other countries. During the outbreak of COVID-19, mental health of the general population in Hubei province may be affected. This study aimed to assess the psychological status and associated risk factors of the general population in Hubei province during the COVID-19 outbreak. Methods: A cross-sectional online survey was used to evaluate the symptoms of posttraumatic stress disorder (PTSD), depression, and anxiety, which were assessed by the Chinese version of the Impact of Event Scale-Revised, the Patient Health Questionnaire 9, and the seven-item Generalized Anxiety Disorder Scale, respectively. Coping style was assessed by the Simplified Coping Style Questionnaire. Multivariate logistic regression analysis was carried out to detect factors associated with mental health outcomes. Results: Among 9,225 participants, 44.5% rated symptoms of PTSD, and 17.9 and 12.7% suffered from moderate and severe symptoms of depression and anxiety, respectively. Individuals who were geographically located in Wuhan and familiar with someone who has COVID-19 had more severe symptoms of PTSD, depression, and anxiety, as well as a higher score in passive coping style (P < 0.05). Multivariate logistic regression analysis showed that people who were geographically located in Wuhan [odds ratio (OR) = 1.25, 95% confidence interval (CI) = 1.14-1.36, P < 0.001] were associated with severe symptoms of PTSD. Besides, individuals who were familiar with someone who had COVID-19 (OR = 2.33, 95% CI = 2.07-2.63, P < 0.001; OR = 1.90, 95% CI = 1.66-2.17, P < 0.001; OR = 2.06, 95% CI = 1.78-2.39, P < 0.001) and had a higher score in passive coping style (OR = 1.16, 95% CI = 1.14-1.17, P < 0.001; OR = 1.17, 95% CI = 1.15-1.19, P < 0.001; OR = 1.17, 95% CI = 1.15-1.19, P < 0.001) were associated with severe symptoms of PTSD, depression, and anxiety. Moreover, a higher score in active coping style (OR = 0.96, 95% CI = 0.95-0.97, P < 0.001; OR = 0.94, 95% CI = 0.93-0.94, P < 0.001; OR = 0.95, 95% CI = 0.94-0.96, P < 0.001) was associated with a lower risk of symptoms of PTSD, depression, and anxiety. Conclusions: During the midphase of COVID-19 outbreak, quite a few people have mental health problems; nearly half of the respondents rated symptoms of PTSD, and approximately one-fifth reported moderate to severe symptoms of anxiety and depression. Our findings may lead to better comprehend the psychological status of the general public and alleviate the public mental health crisis during the COVID-19 outbreak.

Inflammation is correlated with abnormal functional connectivity in unmedicated bipolar depression: an independent component analysis study of resting-state fMRI.

BACKGROUND: Inflammation might play a role in bipolar disorder (BD), but it remains unclear the relationship between inflammation and brain structural and functional abnormalities in patients with BD. In this study, we focused on the alterations of functional connectivity (FC), peripheral pro-inflammatory cytokines and their correlations to investigate the role of inflammation in FC in BD depression. METHODS: In this study, 42 unmedicated patients with BD II depression and 62 healthy controls (HCs) were enrolled. Resting-state-functional magnetic resonance imaging was performed in all participants and independent component analysis was used. Serum levels of Interleukin-6 (IL-6) and Interleukin-8 (IL-8) were measured in all participants. Correlation between FC values and IL-6 and IL-8 levels in BD was calculated. RESULTS: Compared with the HCs, BD II patients showed decreased FC in the left orbitofrontal cortex (OFC) implicating the limbic network and the right precentral gyrus implicating the somatomotor network. BD II showed increased IL-6 (p = 0.039), IL-8 (p = 0.002) levels. Moreover, abnormal FC in the right precentral gyrus were inversely correlated with the IL-8 (r = -0.458, p = 0.004) levels in BD II. No significant correlation was found between FC in the left OFC and cytokines levels. CONCLUSIONS: Our findings that serum IL-8 levels are associated with impaired FC in the right precentral gyrus in BD II patients suggest that inflammation might play a crucial role in brain functional abnormalities in BD.

Shared and specific dynamics of brain segregation and integration in bipolar disorder and major depressive disorder: A resting-state functional magnetic resonance imaging study.

BACKGROUND: When bipolar disorder (BD) presents as the depressive state, it is often misdiagnosed as major depressive disorder (MDD). However, few studies have focused on dynamic differences in local brain activity and connectivity between BD and MDD. Therefore, the present study explored shared and specific patterns of abnormal dynamic brain segregation and integration in BD and MDD patients. METHODS: BD Patients (n = 106), MDD patients (n = 114), and 130 healthy controls (HCs) underwent resting state functional magnetic resonance imaging (fMRI). We first used a sliding window analysis to evaluate the dynamic amplitude of low-frequency fluctuations (dALFF) and, based on the altered dALFF, further analyzed the dynamic functional connectivity (dFC) using a seed-based approach. RESULTS: Both the BD and MDD groups showed decreased temporal variability of the dALFF (less dynamic segregation) in the bilateral posterior cingulate cortex (PCC)/precuneus compared with the HCs. The MDD group showed increased temporal variability of the dALFF (more dynamic segregation) in the left putamen compared with the controls, but there was no significant difference between the BD and HCs. The dFC analysis also showed that both the BD and MDD groups had reduced dFC (less dynamic integration) between the bilateral PCC/ precuneus and the left inferior parietal lobule compared with the HCs. LIMITATIONS: This study was cross-sectional and did not examine data from remitted BD and MDD patients. CONCLUSION: Our findings indicated disrupted dynamic balance between segregation and integration within the default mode network in both BD and MDD. Moreover, we found MDD-specific abnormal brain dynamics in the putamen.

Common and distinct patterns of intrinsic brain activity alterations in major depression and bipolar disorder: voxel-based meta-analysis.

Identification of intrinsic brain activity differences and similarities between major depression (MDD) and bipolar disorder (BD) is necessary. However, results have not yet yielded consistent conclusions. A meta-analysis of whole-brain resting-state functional MRI (rs-fMRI) studies that explored differences in the amplitude of low-frequency fluctuation (ALFF) between patients (including MDD and BD) and healthy controls (HCs) was conducted using seed-based d mapping software. Systematic literature search identified 50 studies comparing 1399 MDD patients and 1332 HCs, and 15 studies comparing 494 BD patients and 593 HCs. MDD patients displayed increased ALFF in the right superior frontal gyrus (SFG) (including the medial orbitofrontal cortex, medial prefrontal cortex [mPFC], anterior cingulate cortex [ACC]), bilateral insula extending into the striatum and left supramarginal gyrus and decreased ALFF in the bilateral cerebellum, bilateral precuneus, and left occipital cortex compared with HCs. BD showed increased ALFF in the bilateral inferior frontal gyrus, bilateral insula extending into the striatum, right SFG, and right superior temporal gyrus (STG) and decreased ALFF in the bilateral precuneus, left cerebellum (extending to the occipital cortex), left ACC, and left STG. In addition, MDD displayed increased ALFF in the left lingual gyrus, left ACC, bilateral precuneus/posterior cingulate gyrus, and left STG and decreased ALFF in the right insula, right mPFC, right fusiform gyrus, and bilateral striatum relative to BD patients. Conjunction analysis showed increased ALFF in the bilateral insula, mPFC, and decreased ALFF in the left cerebellum in both disorders. Our comprehensive meta-analysis suggests that MDD and BD show a common pattern of aberrant regional intrinsic brain activity which predominantly includes the insula, mPFC, and cerebellum, while the limbic system and occipital cortex may be associated with spatially distinct patterns of brain function, which provide useful insights for understanding the underlying pathophysiology of brain dysfunction in affective disorders, and developing more targeted and efficacious treatment and intervention strategies.

Characteristics of temporal dynamics of intrinsic brain activity in unmedicated bipolar disorder with suicidality.

BACKGROUND: Bipolar disorder is associated with a high risk of suicide. Routine neuroimaging examination exhibited that bipolar disorder with suicidality was associated with brain structural and functional changes. However, the alterations of brain dynamics have still remained elusive. PURPOSE: To investigate the alterations of brain dynamics in unmedicated bipolar disorder II depression with suicidality and predict the severity of suicidality. MATERIALS AND METHODS: This prospective study included 106 bipolar disorder II participants (20 with suicidal attempt, 35 with suicidal ideation, 51 without suicidal ideation) and 50 healthy controls who underwent resting-state functional magnetic resonance imaging between February 2016 and December 2017. We first used sliding window analysis to evaluate the dynamic amplitude of low-frequency fluctuations. Then, we predicted the severity of suicidality using a multivariate regression model. RESULTS: One-way analysis of covariance revealed that the dynamic amplitude of low-frequency fluctuations in the right temporal pole, inferior temporal gyrus, superior temporal gyrus and the bilateral precuneus/posterior cingulate cortex was significantly different among the four groups. Post hoc pairwise comparisons revealed that dynamic amplitude of low-frequency fluctuations was remarkably decreased in the bilateral precuneus/posterior cingulate cortex in the three bipolar disorder II groups compared with that in healthy controls group. Increased dynamic amplitude of low-frequency fluctuations was found in the right superior temporal gyrus and inferior temporal gyrus in the suicidal attempt group compared with that in the other groups, and in the right temporal pole in the suicidal attempt group compared with that in the suicidal ideation and healthy controls groups. Importantly, these temporal variabilities could be used to predict the severity of suicidality (r = 0.330, p = 0.036), whereas static amplitude of low-frequency fluctuations couldn't (r = -0.050, p = 0.532). CONCLUSION: Our findings indicated that alterations of temporal variability in the precuneus/posterior cingulate cortex are such a common feature of bipolar disorder patients. Besides, the severity of suicidality could be predicted by the dynamic amplitude of low-frequency fluctuations abnormalities rather than static amplitude of low-frequency fluctuations abnormalities, which is the first evidence of dynamic brain alterations in bipolar disorder patients with suicidality. The proposed predictive model may be advantageous for clinical applications.

Inflammation is associated with decreased functional connectivity of insula in unmedicated bipolar disorder.

BACKGROUND: Systemic inflammation and immune dysregulation have been considered as risk factors in the pathophysiology of mood disorders including bipolar disorder (BD). Previous neuroimaging studies have demonstrated metabolic, structural and functional abnormalities in the insula in BD, proposed that the insula played an important role in BD. We herein aimed to explore neural mechanisms underlying inflammation-induced in the insular subregions functional connectivity (FC) in patients with BD. METHODS: Brain resting-state functional magnetic resonance imaging (rs-fMRI) data were acquired from 41 patients with unmedicated BD II (current episode depressed), 68 healthy controls (HCs). Three pairs of insular seed regions were selected: the bilateral anterior insula (AI), the bilateral middle insula (MI) and the bilateral posterior insula (PI), and calculated the whole-brain FC for each subregion. Additionally, the serum levels of pro-inflammatory cytokines in patients and HCs, including IL-6 and TNF-α, were detected. Then the partial correlation coefficients between the abnormal insular subregions FC values and pro-inflammatory cytokines levels in patients with BD II depression were calculated. RESULTS: The BD II depression group exhibited decreased FC between the right PI and the left postcentral gyrus, and increased FC between the left AI and the bilateral insula (extended to the right putamen) when compared with the HC group. Moreover, the patients with BD II depression showed higher IL-6 and TNF-α levels than HCs, and IL-6 level was negatively correlated with FC of the right PI to the left postcentral gyrus. CONCLUSIONS: Our results demonstrated that abnormal FC between the bilateral insula, and between the insula and sensorimotor areas in BD. Moreover, disrupted FC between the insula and sensorimotor areas was associated with elevated pro-inflammatory cytokine levels of IL-6 in BD.

Mimic peptides bonding specifically with the first and second extracellular loops of the CC chemokine receptor 5 derived from a phage display peptide library are potent inhibitors of experimental autoimmune encephalomyelitis.

PURPOSE: To obtain mimic peptides that specifically bind with the first and second extracellular loops (ECL1, ECL2) of the CC chemokine receptor 5 (CCR5) and to study their treatment effects on experimental autoimmune encephalomyelitis (EAE) mice. METHODS: A phage display peptide library was applied to screen peptides that bond with ECL1 and ECL2. ELISA and DNA sequence analysis were used to identify positive clones. EAE mice were treated with synthesized peptides by intraperitoneal injection. RESULTS: Eighteen positive clones were obtained and four peptides with sequences STFTTTL, TPIPQLL, SLPLPKP and QTSSAAL were identified. These peptides could significantly protect against and reduce the severity of EAE. The infiltration of monocytes and lymphocytes into the spinal cord decreased significantly in treated mice, while abundant inflammatory cells and demyelination were observed in spinal cords of EAE mice. CONCLUSION: CCR5 mimic peptides provided a significant protective effect to EAE mice. These potent inhibitory mimic peptides could be useful in the clinical treatment of multiple sclerosis.