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AIM: To identify the spectrum of autoimmune encephalitis antibody biomarkers (AE-Abs) in children with suspected autoimmune encephalitis and explore the clinical features indicating AE-Abs presence. METHOD: We included children with suspected autoimmune encephalitis who underwent AE-Abs tests at the Children's Hospital of Chongqing Medical University between June 2020 and June 2022. Clinical features suggestive of AE-Abs were analysed based on AE-Abs test results. RESULTS: A total of 392 children were tested for AE-Abs with suspected autoimmune encephalitis. Of these, 49.5% were male, with a median age of 7 years 11 months (6 months-17 years 11 months); 93.6% (367/392) of all patients had both serum and cerebrospinal fluid (CSF) tests performed. The antibody-positive rate in the cohort was 23.7% (93/392), the serum antibody-positive rate was 21.9% (84/384), and the CSF antibody-positive rate was 20.8% (78/375). Eleven different AE-Abs were detected. Serum analysis revealed that N-methyl-D-aspartate receptor immunoglobulin-G (NMDAR-IgG) (15.1%) was greater than myelin oligodendrocyte glycoprotein (MOG)-IgG (14.6%) and glial fibrillary acidic protein (GFAP)-IgG (3.3%). CSF analysis revealed that NMDAR-IgG (16.3%) was greater than MOG-IgG (13.8%) and GFAP-IgG (3.3%). Compared with antibody-negative patients, antibody-positive patients were more often female (odds ratio [OR] 1.86, p = 0.03), with memory impairment (OR 2.91, p = 0.01) and sleep disorders (OR 2.08, p = 0.02). INTERPRETATION: In children, the most frequent AE-Abs detected were NMDAR-IgG and MOG-IgG. Female sex, memory impairment, and sleep disorders predict a higher likelihood of AE-Abs.
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Encefalite Antirreceptor de N-Metil-D-Aspartato , Encefalite , Doença de Hashimoto , Transtornos do Sono-Vigília , Criança , Humanos , Masculino , Feminino , Encefalite Antirreceptor de N-Metil-D-Aspartato/diagnóstico , Glicoproteína Mielina-Oligodendrócito , Autoanticorpos , Imunoglobulina G , Receptores de N-Metil-D-AspartatoRESUMO
AIM: This study aimed to assess hard and soft tissue contour changes following micro crestal flap-alveolar ridge preservation (MCF-ARP) and natural healing (NH) in periodontally compromised molar extraction sites and to analyse the feasibility and need for bone augmentation during implant therapy. MATERIALS AND METHODS: Fifty-six patients with 70 sites were randomized into two groups at the site level (35 sites from 31 patients in the test group and 35 sites from 29 patients in the control group). Among whom, four patients contributed one tooth to the control group and one tooth to the test group. Hard tissue indicators were measured using cone beam computed tomography performed before tooth extraction and 6 months after surgery. Soft tissue contour changes were assessed using intraoral scanning performed before and immediately after surgery and also 2 weeks and 1, 3 and 6 months after surgery. RESULTS: Six months after surgery, the MCF-ARP group showed less resorption in buccal bone height (p = .032) and greater augmentation in central bone height (p = .001) and ridge width (p = .009). The mean, vertical and horizontal collapse of buccal soft tissue contour in the MCF-ARP group were 0.95 mm (p = .010), 0.61 mm (p = .019) and 0.56 mm (p = .013) less than that in the NH group, respectively. There were significantly (p = .007) fewer sites in the MCF-ARP group than in the NH group (0% vs. 26.7%) for staged bone augmentation and more sites that could be treated with simple implant procedure in the MCF-ARP group than in the NH group (71.9% vs. 56.6%). CONCLUSIONS: Compared with NH, MCF-ARP reduced bone resorption in periodontally compromised molar extraction sites and maintained the buccal soft tissue contour. MCF-ARP reduces the need for complex bone augmentation procedures in implant therapy. TRIAL REGISTRATION: Chinese Clinical Trial Register (ChiCTR) ChiCTR2200056335. Registered on 4 February 2022, Version 1.0.
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OBJECTIVE: This study aimed to compare hard- and soft-tissue changes after ridge preservation in periodontally compromised molar sockets with and without primary wound closure. MATERIALS AND METHODS: Forty molars with severe periodontitis requiring extraction were included and allocated to two treatment modalities. After tooth extraction, the sockets were filled with deproteinized bovine bone mineral and covered with a bioabsorbable porcine collagen membrane. Primary wound closure was achieved in the control group, whereas the test group underwent minimally invasive open healing. The dimensions of the bone and soft tissue were recorded at baseline and 6 months. RESULTS: Over 6 months, the control and test groups had similar mean ridge heights at the center of sockets of 8.59 ± 2.47 mm and 8.47 ± 2.51 mm, respectively. The total volume of the control group increased from 1070.17 to 1713.52 mm3 for a mean gain of 643.35 mm3 , whereas that of the test group increased from 992.51 to 1514.05 mm3 for a mean gain of 521.54 mm3 . Compared with the test group, the control group showed a statistically significant decrease in keratinized tissue width of 1.08 ± 1.63 mm. CONCLUSIONS: Bone dimensional changes following ridge preservation with and without primary wound closure were comparable. ARP without primary wound closure preserves more keratinized tissue than that with (Chinese Clinical Trial Registry: ChiCTR-ONN-16009433).
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Aumento do Rebordo Alveolar , Dente Molar , Aumento do Rebordo Alveolar/métodos , Colágeno/uso terapêutico , Dente Molar/cirurgia , Extração Dentária , Alvéolo Dental/cirurgia , HumanosRESUMO
BACKGROUND: The assessment of hard and soft tissue at edentulous sites is important for subsequent implant treatment design. The aim of the present study was to explore the associations between the keratinized mucosa width (KMW) and the underlying alveolar bone dimensions at partial edentulous molar sites. METHODS: In this retrospective study, a total of 110 patients with at least one missing molar were selected. The buccal KMW of the edentulous molar sites was evaluated. Cone-beam computed tomography scans were collected, and the height discrepancy between the alveolar crest and the buccal bone plate (HC-B) as well as the alveolar bone height (ABH) were measured. The KMW was compared among the HC-B and ABH groups at both maxillary and mandibular sites. Linear regression and generalized estimation equations (GEEs) were used to explore the associations between the KMW and alveolar bone dimensions at α = 0.05. RESULTS: Among the 110 patients, 158 edentulous molar sites were analyzed. The average HC-B and ABH were significantly lower at the maxillary sites (1.26 ± 1.62 mm, 11.62 ± 3.94 mm) than at the mandibular sites (3.67 ± 2.85 mm, 14.91 ± 3.01 mm, p < 0.001). The KMW was significantly lower at sites with HC-B > 2 mm than at sites with HC-B ≤ 2 mm both in the maxilla and mandible (p < 0.001). No significant differences were found between the KMW at sites with ABH < 10 mm and sites with ABH ≥ 10 mm (p > 0.05). Linear regression and GEEs analyses revealed that the HC-B was significantly associated with the KMW (B = -0.339, p < 0.001), while the association between the KMW and the ABH was not statistically significant (B = -0.046, p = 0.352). CONCLUSIONS: The buccal KMW at edentulous molar sites was significantly associated with the HC-B. Alveolar ridges presenting with a sloped configuration were more prone to possess a narrower band of keratinized mucosa. Both hard and soft tissue augmentation should be considered for implant treatment at these sites. The correlations of dynamic changes between the KMW and alveolar bone dimensions after tooth extraction should be further investigated.
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Processo Alveolar , Tomografia Computadorizada de Feixe Cônico , Dente Molar , Humanos , Estudos Retrospectivos , Feminino , Masculino , Processo Alveolar/diagnóstico por imagem , Processo Alveolar/patologia , Pessoa de Meia-Idade , Estudos Transversais , Dente Molar/diagnóstico por imagem , Arcada Parcialmente Edêntula/diagnóstico por imagem , Arcada Parcialmente Edêntula/patologia , Adulto , Idoso , Mucosa Bucal/diagnóstico por imagem , Mucosa Bucal/patologia , Mandíbula/diagnóstico por imagem , Mandíbula/patologia , Maxila/diagnóstico por imagem , Maxila/patologiaRESUMO
BACKGROUND: Migraine is a common neurological disorder with a strong genetic component. Despite the identification of over 100 loci associated with migraine susceptibility through genome-wide association studies (GWAS), the underlying causative genes and biological mechanisms remain predominantly elusive. METHODS: The FinnGen R10 dataset, consisting of 333,711 subjects (20,908 cases and 312,803 controls), was utilized in conjunction with the Genotype-Tissue Expression Project (GTEx) v8 EQTls files to conduct cross-tissue transcriptome association studies (TWAS). Functional Summary-based Imputation (FUSION) was employed to validate these findings in single tissues. Additionally, candidate susceptibility genes were screened using Gene Analysis combined with Multi-marker Analysis of Genomic Annotation (MAGMA). Subsequent Mendelian randomization (MR) and colocalization analyses were conducted. Furthermore, GeneMANIA analysis was employed to enhance our understanding of the functional implications of these susceptibility genes. RESULTS: We identified a total of 19 susceptibility genes associated with migraine in the cross-tissue TWAS analysis. Two novel susceptibility genes, REV1 and SREBF2, were validated through both single tissue TWAS and MAGMA analysis. Mendelian randomization and colocalization analyses further confirmed these findings. REV1 may reduce the migraine risk by regulating DNA damage repair, while SREBF2 may increase the risk of migraine by regulating cholesterol metabolism. CONCLUSION: Our study identified two novel genes whose predicted expression was associated with the risk of migraine, providing new insights into the genetic framework of migraine.
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Predisposição Genética para Doença , Estudo de Associação Genômica Ampla , Transtornos de Enxaqueca , Transcriptoma , Humanos , Transtornos de Enxaqueca/genética , Predisposição Genética para Doença/genética , Transcriptoma/genética , Análise da Randomização Mendeliana , Polimorfismo de Nucleotídeo Único/genéticaRESUMO
Epidemiological studies have demonstrated that exposure to air particulate matter (PM) increases the incidence of cardiovascular and respiratory diseases and exerts a significant neurotoxic effect on the nervous system, especially on the immature nervous system. Here, we selected PND28 rats to simulate the immature nervous system of young children and used neurobehavioral methods to examine how exposure to PM affected spatial learning and memory, as well as electrophysiology, molecular biology, and bioinformatics to study the morphology of hippocampus and the function of hippocampal synapses. We discovered that spatial learning and memory were impaired in rats exposed to PM. The morphology and structure of the hippocampus were altered in the PM group. In addition, after exposure to PM, the relative expression of synaptophysin (SYP) and postsynaptic density 95 (PSD95) proteins decreased dramatically in rats. Furthermore, PM exposure impaired long-term potentiation (LTP) in the hippocampal Schaffer-CA1 pathway. Interestingly, RNA sequencing and bioinformatics analysis revealed that the differentially expressed genes (DEGs) were rich in terms associated with synaptic function. Five hub genes (Agt, Camk2a, Grin2a, Snca, and Syngap1) that may play a significant role in the dysfunctionality of hippocampal synapses were identified. Our findings implied that exposure to PM impaired spatial learning and memory via exerting impacts on the dysfunctionality of hippocampal synapses in juvenile rats and that Agt, Camk2a, Grin2a, Snca, and Syngap1 may drive PM-caused synaptic dysfunction.
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Plasticidade Neuronal , Aprendizagem Espacial , Ratos , Animais , Plasticidade Neuronal/fisiologia , Material Particulado/metabolismo , Memória , Hipocampo/metabolismo , SinapsesRESUMO
BACKGROUND: Assessment of the keratinized mucosa width (KMW) at edentulous sites is important for the subsequent implant treatment design. This pilot study aimed to evaluate the characteristics of the KMW at edentulous molar sites and explore the associated factors. METHODS: A total of 150 patients with 222 edentulous molar sites were included. The buccal KMW of the edentulous molar sites was measured during implant treatment planning. Potentially associated factors, including age, sex, smoking status, location, reasons for tooth loss/extraction, gingival phenotype (GP) and keratinized gingival width (KGW) of the adjacent teeth, were collected and analyzed. The ShapiroâWilk test, Student's t test, one-way ANOVA, generalized estimation equations (GEEs) and linear regression analysis were used for data analysis at α = 0.05. RESULTS: The buccal KMW at edentulous molar sites was 3.97 ± 2.06 mm, and 41.9% of sites presented with KMW < 4 mm. The mean KMWs of the maxillary sites were significantly higher than that those of the mandibular sites (4.96 ± 2.05 mm vs. 3.41 ± 1.85 mm, respectively). In total, 54.7%, 46.5%, 29.8%, and 0.0% of mandibular first and second molar sites and maxillary first and second molar sites, respectively, displayed a KMW of < 4 mm. Statistically significant linear correlations were found between KMW and GP (r = 0.161, p = 0.025) and between KMW and KGW of the adjacent teeth (r = 0.161, p = 0.023), while other factors were found to have no significant association. CONCLUSION: Within the limitations of the present study, the KMW at edentulous molar site was related to the location of molar tooth loss/extraction. The GP and KGW of the adjacent teeth of edentulous molar sites were also associated with their KMW, which was probably attributed to the continuity of the adjacent soft tissue.
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Implantes Dentários , Boca Edêntula , Perda de Dente , Humanos , Projetos Piloto , Mucosa Bucal , Dente MolarRESUMO
BACKGROUND: Changes in alveolar bone dimension after tooth extraction may affect placement of the subsequent implant, resulting in ridge deficiency that can adversely impact long-term implant stability or aesthetics. Alveolar ridge preservation (ARP) was effective in reducing the amount of ridge resorption following tooth extraction. There is sparse evidence regarding the benefit of ARP at periodontally compromised molar extraction sockets. This study will be a randomized trial to assess the soft tissue contour, radiographical, and histological changes of ARP at molar extraction sites in order to compare severe periodontitis cases with natural healing results and determine the most beneficial and least traumatic clinical treatment for such patients. METHODS: This research is designed as a two-group parallel randomized controlled trial. The total number of tooth extraction sites will be 70 after calculation with power analysis. Teeth will be randomly assigned to two groups with the test group conducting ridge preservation and the control group healing naturally. Periodontal examination, cone beam-computed tomography (CBCT) data, and stereolithographic (STL) files obtained by intraoral scanning will be collected through the follow-up period, and bone biopsy samples would be obtained during implant surgery. The primary outcomes are the vertical and horizontal change of alveolar ridge measured on CBCT images, soft tissue contour changes evaluated by superimposing the digital impressions, alterations of mucosa thickness (as measured by superimposing the CBCT data and STL files), histological features of implant sites and periodontal parameter changes. The secondary outcomes are patient-reported post-operative reaction and conditions of simultaneous bone graft or sinus lifting procedures during implantation. DISCUSSION: This study will provide information about hard and soft tissue dimension changes and histomorphology evaluation following ARP and natural healing in periodontally compromised molar sites, which may contribute to complement the missing information of ARP at periodontally compromised molar extraction sockets. TRIAL REGISTRATION: Chinese Clinical Trial Register (ChiCTR) ChiCTR2200056335. Registered on February 4, 2022, Version 1.0.
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Perda do Osso Alveolar , Aumento do Rebordo Alveolar , Periodontite , Extração Dentária , Humanos , Perda do Osso Alveolar/diagnóstico por imagem , Perda do Osso Alveolar/prevenção & controle , Perda do Osso Alveolar/patologia , Aumento do Rebordo Alveolar/métodos , Dente Molar/cirurgia , Periodontite/cirurgia , Periodontite/patologia , Alvéolo Dental/diagnóstico por imagem , Alvéolo Dental/cirurgiaRESUMO
OBJECTIVES: To evaluate the dimensional changes of the keratinized tissue width (KTW) in molar regions after augmentation by free gingival grafts (FGG) before implant placement. MATERIAL AND METHODS: In seventeen patients, twenty implant sites in molar regions with KTW ≤3 mm at the buccal aspect received FGG 2 months before implant placement. KTW at the buccal aspect was measured before FGG (T0), immediately before implant placement (T1), at the time of impression taking for final prosthesis fabrication (T2), and at the end of the follow-up period after loading (T3, 12-48 months). Changes in KTW before and after FGG, as well as the alterations during the follow-up period after loading, were analyzed. Shapiro-Wilk test, paired Student's t test, and Wilcoxon signed-rank test were used for the data analysis at α = 0.05. RESULTS: KTW at the buccal aspect of the alveolar ridge was observed with a significant gain of 5.9 ± 1.3 mm at T1 (p < .001). The shrinkage of KTW from T2 to T3 was 8.5%, which was limited but statistically significant (p = .008). KTW at the buccal aspect of implant restorations was 5.0 ± 1.5 mm at T3. CONCLUSIONS: Within the limitations of the present study, our data suggest that using FGG to increase KTW in molar regions before implant placement had a predictable result. The buccal KTW had a limited reduction and was ≥3 mm with more than 12 months of follow-up after loading.
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Implantes Dentários , Processo Alveolar , Gengiva , Humanos , Dente Molar/cirurgia , Estudos Retrospectivos , Resultado do TratamentoRESUMO
PURPOSE: This study aimed to investigate whether minocycline could influence alterations of microglial subtypes, the morphology of dendrites and dendritic spines, the microstructures of synapses and synaptic proteins, or even cognition outcomes in immature male mice following status epilepticus (SE) induced by kainic acid. METHODS: Golgi staining was performed to visualize the dendrites and dendritic spines of neurons of the hippocampus. The microstructures of synapses and synaptic proteins were observed using transmission electron microscopy and western blotting analysis, respectively. Microglial reactivation and their markers were evaluated using flow cytometry. The Morris water maze (MWM) test was used to analyze spatial learning and memory ability. RESULTS: Significant partial spines increase (predominate in thin spines) was observed in the dendrites of neurons after acute SE and partial loss (mainly in thin spines) was presented by days 14 and 28 post-SE. The postsynaptic ultrastructure was impaired on the 7th and 14th days after SE. The proportion of M1 microglia increased significantly only after acute SE Similarly, the proportion of M2 microglia increased in the acute stage with high expression levels of all surface markers. In contrast, a decrease in M2 microglia and their markers was noted by day 14 post-SE. Minocycline could reverse the changes in dendrites and synaptic proteins caused by SE, and increase the levels of synaptic proteins. Meanwhile, minocycline could inhibit the reactivation of M1 microglia and the expression of their markers, except for promoting CD200R. In addition, treatment with minocycline could regulate the expression of M2 microglia and their surface markers, as well as ameliorating the impaired spatial learning and memory on the 28th day after SE. CONCLUSIONS: Dendritic spines and microglia are dynamically changed after SE. Minocycline could ameliorate the impaired cognition in the kainic acid-induced mouse model by decreasing the damage to dendrites and altering microglial reactivation.
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Ácido Caínico , Estado Epiléptico , Camundongos , Masculino , Animais , Ácido Caínico/toxicidade , Microglia , Minociclina/farmacologia , Minociclina/uso terapêutico , Espinhas Dendríticas/metabolismo , Hipocampo/metabolismo , Estado Epiléptico/induzido quimicamente , Estado Epiléptico/tratamento farmacológicoRESUMO
PM2.5 exposure is a challenging environmental issue that is closely related to cognitive development impairment; however, currently, relevant means for prevention and treatment remain lacking. Herein, we determined the preventive effect of docosahexaenoic acid (DHA) supplementation on the neurodevelopmental toxicity induced by PM2.5 exposure. Neonatal rats were divided randomly into three groups: control, PM2.5, and DHA + PM2.5 groups. DHA could ameliorate PM2.5-induced learning and memory dysfunction, as well as reverse the impairment of hippocampal synaptic plasticity, evidenced by enhanced long-term potentiation, recovered synaptic ultrastructure, and increased expression of synaptic proteins. Moreover, DHA increased CREB phosphorylation and BDNF levels and attenuated neuroinflammation and oxidative stress, reflected by lower levels of IBA-1, IL-1ß, and IL-6 and increased levels of SOD1 and Nrf2. In summary, our findings demonstrated that supplementation of DHA effectively mitigated the cognitive dysfunction and synaptic plasticity impairment induced by early postnatal exposure to PM2.5. These beneficial effects may be attributed to the upregulation of the CREB/BDNF signaling pathway, as well as the reduction of neuroinflammation and oxidative stress.
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Epidemiological studies have established a robust correlation between exposure to ambient particulate matter (PM) and various neurological disorders, with dysregulation of intracellular redox processes and cell death being key mechanisms involved. Ferroptosis, a cell death form characterized by iron-dependent lipid peroxidation and disruption of antioxidant defenses, may be involved in the neurotoxic effects of PM exposure. However, the relationship between PM-induced neurotoxicity and ferroptosis in nerve cells remains to be elucidated. In this study, we utilized a rat model (exposed to PM at a dose of 10 mg/kg body weight per day for 4 weeks) and an HT-22 cell model (exposed to PM at concentrations of 50, 100, and 200 µg/mL for 24 h) to investigate the potential induction of ferroptosis by PM exposure. Furthermore, RNA sequencing analysis was employed to identify hub genes that potentially contribute to the process of ferroptosis, which was subsequently validated through in vivo and in vitro experiments. The results revealed that PM exposure increased MDA content and Fe2+ levels, and decreased SOD activity and GSH/GSSG ratio in rat hippocampal and HT-22 cells. Through RNA sequencing analysis, bioinformatics analysis, and RT-qPCR experiments, we identified GSK3B as a possible hub gene involved in ferroptosis. Subsequent investigations demonstrated that PM exposure increased GSK3B levels and decreased Nrf2, and GPX4 levels in vivo and in vitro. Furthermore, treatment with LY2090314, a specific inhibitor of GSK3B, was found to mitigate the PM-induced elevation of MDA and ROS and restore SOD activity and GSH/GSSG ratio. The LY2090314 treatment promoted the upregulation of Nrf2 and GPX4 and facilitated the nuclear translocation of Nrf2 in HT-22 cells. Moreover, treatment with LY2090314 resulted in the upregulation of Nrf2 and GPX4, along with the facilitation of nuclear translocation of Nrf2. This study suggested that PM-induced ferroptosis in hippocampal cells may be via the GSK3B/Nrf2/GPX4 pathway.
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Ferroptose , Compostos Heterocíclicos com 3 Anéis , Maleimidas , Síndromes Neurotóxicas , Animais , Ratos , Ferroptose/genética , Dissulfeto de Glutationa , Fator 2 Relacionado a NF-E2/genética , Hipocampo , Superóxido DismutaseRESUMO
BACKGROUND: Sleep apnea is regarded as a significant global public health issue. The relationship between sleep apnea and nervous system diseases is intricate, yet the precise mechanism remains unclear. METHODS: In this study, we conducted a comprehensive analysis integrating the human brain proteome and transcriptome with sleep apnea genome-wide association study (GWAS), employing genome-wide association study (PWAS), transcriptome-wide association study (TWAS), Mendelian randomization (MR), and colocalization analysis to identify brain proteins associated with sleep apnea. RESULTS: The discovery PWAS identified six genes (CNNM2, XRCC6, C3orf18, CSDC2, SQRDL, and DGUOK) whose altered protein abundances in the brain were found to be associated with sleep apnea. The independent confirmatory PWAS successfully replicated four out of these six genes (CNNM2, C3orf18, CSDC2, and SQRDL). The transcriptome level TWAS analysis further confirmed two out of the four genes (C3orf18 and CSDC2). The subsequent two-sample Mendelian randomization provided compelling causal evidence supporting the association of C3orf18, CSDC2, CNNM2, and SQRDL with sleep apnea. The co-localization analysis further supported the association between CSDC2 and sleep apnea (posterior probability of hypothesis 4 = 0.75). CONCLUSIONS: In summary, the integration of brain proteomic and transcriptomic data provided multifaceted evidence supporting causal relationships between four specific brain proteins (CSDC2, C3orf18, CNNM2, and SQRDL) and sleep apnea. Our findings provide new insights into the molecular basis of sleep apnea in the brain, promising to advance understanding of its pathogenesis in future research.
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Proteoma , Síndromes da Apneia do Sono , Humanos , Proteoma/genética , Estudo de Associação Genômica Ampla , Proteômica , Encéfalo , Síndromes da Apneia do Sono/genética , Polimorfismo de Nucleotídeo Único/genéticaRESUMO
Background: The development of anti-N-methyl-d-aspartate receptor (NMDAR) encephalitis following viral encephalitis, such as Japanese encephalitis, has received increasing attention in recent years. However, the mechanism of anti-NMDAR antibody production following Japanese encephalitis has not been explored. Methods: A peptide from the Japanese encephalitis virus (JEV), which shares a similar amino acid sequence with GluN1, was identified by sequence comparison. We then explored whether active subcutaneous immunization with the JEV peptide could induce the production of anti-NMDAR antibodies and related pathophysiological and behavioral changes in mice. In addition, a published active immune model of anti-NMDAR encephalitis using a GluN1 peptide was used as the positive control. Results: A 6-amino-acid sequence with 83 % similarity between the envelope protein of the JEV (HGTVVI) and GluN1 (NGTHVI) was identified, and the sequence included the N368/G369 region. Active immunization with the JEV peptide induced a substantial and specific immune response in mice. However, anti-NMDAR antibodies were not detected in the serum of mice immunized with the JEV peptide by ELISA, CBA, and TBA. Moreover, mice immunized with the JEV peptide presented no abnormities related to anti-NMDAR antibodies according to western blotting, patch clamp, and a series of behavioral tests. In addition, active immunization with a recently reported GluN1 peptide failed to induce anti-NMDAR antibody production in mice. Conclusions: In this study, the attempt of active immunization with the JEV peptide to induce the production of anti-NMDAR antibodies via molecular mimicry failed. The pathogenesis of anti-NMDAR encephalitis following Japanese encephalitis remains to be elucidated.
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Ambient fine particulate matter (PM) is a global public and environmental problem. PM is closely associated with several neurological diseases, which typically involve neuroinflammation. We investigated the impact of PM exposure on neuroinflammation using both in vivo (in a juvenile rat model with PM exposure concentrations of 1, 2, and 10 mg/kg for 28 days) and in vitro (in BV-2 and HT-22 cell models with PM concentrations of 50-200 µg/ml for 24 h). We observed that PM exposure induced the activation of the NLRP3 inflammasome, leading to the production of IL-1ß and IL-18 in the rat hippocampus and BV-2 cells. Furthermore, inhibition of the NLRP3 inflammasome with MCC950 effectively reduced neuroinflammation and ameliorated hippocampal damage. In addition, autophagy activation was observed in the hippocampus of PM-exposed rats, and the promotion of autophagy by rapamycin (Rapa) effectively attenuated the NLRP3-mediated neuroinflammation induced by PM exposure. However, autophagic flow was blocked in BV-2 cells exposed to PM, and Rapa failed to ameliorate NLRP3 inflammasome activation. We found that autophagy was activated in HT-22 cells exposed to PM and that treatment with Rapa reduced the release of reactive oxygen species (ROS) and malondialdehyde (MDA), as well as cell apoptosis. In a subsequent coculture model of BV-2 and HT-22 cells, we observed the activation of the NLRP3 inflammasome in BV-2 cells when the HT-22 cells were exposed to PM, and this activation was alleviated when PM-exposed HT-22 cells were pretreated with Rapa. Overall, our study revealed that PM exposure triggered hippocampal neuroinflammation by activating the NLRP3 inflammasome. Notably, autophagy mitigated NLRP3 inflammasome activation, potentially by reducing neuronal ROS and apoptosis. This research emphasized the importance of reducing PM exposure and provided valuable insight into its neurotoxicity.
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Inflamassomos , Proteína 3 que Contém Domínio de Pirina da Família NLR , Ratos , Animais , Inflamassomos/metabolismo , Espécies Reativas de Oxigênio , Doenças Neuroinflamatórias , Material Particulado/toxicidade , Autofagia , Hipocampo/metabolismoRESUMO
BACKGROUND: Depression is a major public health problem, and epilepsy and a high-inflammatory diet are important causes of depression. We aimed to explore the level of dietary inflammation in epileptic patients and its relationship with moderate to severe depression (MSD). METHODS: This cross-sectional study included 12,788 participants aged 20-80 years from the NHANES database from 2013 to 2018. Depressive symptoms were evaluated using the nine-item Patient Health Questionnaire (PHQ-9), and epilepsy was diagnosed based on the use of antiepileptic drugs within the previous 30 days. Dietary inflammatory index (DII) scores and energy-adjusted DII (E-DII) scores were calculated based on dietary recalls of the past 24 h, and average DII (ADII) and energy-adjusted ADII (E-ADII) were calculated based on two 24-hour dietary recalls. RESULTS: The DII, E-DII, and ADII scores and prevalence of MSD were significantly increased in epileptic patients compared with non-epilepsy subjects. The E-ADII score (P = 0.078) was weakly associated with comorbid MSD in patients with epilepsy. Mediation models showed that dietary inflammation scores mediated 2.31 % to 12.25 % of epilepsy-related MSD. In stratified analysis, an increased prevalence of MSD was present in the Quartile 2 subgroup based on DII and E-ADII scores and in the Quartile 3 subgroup of epileptic patients based on DII, E-DII, and ADII scores. CONCLUSIONS: Epileptics consume more proinflammatory foods and nutrients than control subjects. MSD in patients with epilepsy is associated with their high inflammatory diet. Suggesting an urgent need for rational dietary management in the epileptic population.
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Depressão , Transtorno Depressivo Maior , Humanos , Inquéritos Nutricionais , Depressão/epidemiologia , Depressão/etiologia , Estudos Transversais , Transtorno Depressivo Maior/epidemiologia , Transtorno Depressivo Maior/complicações , Dieta , Inflamação/epidemiologia , Inflamação/etiologia , Fatores de RiscoRESUMO
Flavonoids possess the latent ability to protect against sleep disorders. We examined the correlation between daily flavonoid intake and sleep duration, and sleep disorders. We enrolled 8216 participants aged ≥ 20 from the National Health and Nutrition Examination Survey (NHANES, 2007-2010), carrying out a cross-sectional study. Flavonoid intake was collected by dietary intake interview recalls. Logistic regression was utilized to evaluate the association between flavonoid intake sleep duration, and sleep disorders. We used subgroup and interaction analysis to explore differences between subgroups. When adjusting covariates in model 2, anthocyanidins, flavan-3-ols, flavones, flavonols, and the sum of flavonoids were considerably related to insufficient sleep duration (odds ratio (OR) (95% confidence interval (CI)); 0.83 (0.72, 0.95); 0.91 (0.83, 0.98); 0.63 (0.41, 0.98); 0.78 (0.64, 0.94); 0.85 (0.76, 0.95), respectively); the converse association was observed between flavanones, and flavones and the risk of sleep disorders (OR (95% CI); 0.85 (0.77, 0.95); 0.61 (0.41, 0.90), respectively). In relation to insufficient sleep, there were statistically significant interactions between flavonoid consumption and race/ethnicity, and education level. In relation to insufficient sleep, there were statistically significant interactions between flavonoid consumption and working status. In this study, we found that certain flavonoids were linked to increased sleep duration and a lower risk of sleep problems. Our research indicated that flavonoids might be a preventive factor for sleep disorders.
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Few studies have examined the association between dietary quality and the risk of developmental disabilities (DDs). This study aimed to investigate the association between dietary quality and the risk of DDs in US children aged 5 to 15. We employed data from the National Health and Nutrition Examination Survey (NHANES) 2003-2018. Multivariable logistic regression was used to evaluate the association between HEI-2015 score, HEI component score, and the likelihood of DDs. Restricted cubic splines (RCS) were utilized to investigate nonlinear links between HEI-2015 score and the likelihood of DDs. Interaction analysis was utilized to explore differences between subgroups. HEI-2015 score was negatively linked with the risk of DDs after adjusting covariates [odds ratio (OR) = 0.99; 95% confidence interval (CI) = (0.98, 1.00)]. HEI-2015 score was separated by quartile into Q1, Q2, Q3, and Q4. Q1 represents the lowest HEI scores, while Q4 represents the highest HEI scores. Children in the fourth quartile of the HEI-2015 exhibited a decreased prevalence of DDs compared to those in the first quartile [(OR = 0.69; 95% CI = (0.53, 0.89)]. The association between HEI-2015 score and the risk of DDs was modified by race/ethnicity. The higher HEI-2015 score was associated with a lower risk of DDs, suggesting that better dietary quality may reduce the risk of DDs in children.
RESUMO
BACKGROUND: Few studies have investigated the associations between heavy metals and anxiety. The purpose of this study was to examine the associations between single and combined exposure to heavy metals and anxiety. METHODS: This study employed data from the National Health and Nutrition Examination Survey (NHANES) from 2007 to 2012. Anxiety was assessed by patients self-reporting the number of anxious days per month. First, we evaluated the associations between 10 heavy metals single exposure and anxiety by multivariable logistic regression. We then selected 5 heavy metals (cadmium, antimony, cobalt, tungsten, and uranium) for further analysis by elastic net regression. Subsequently, principal component analysis (PCA), weighted quantile regression (WQS), and Bayesian kernel machine regression (BKMR) were utilized to evaluate the associations between 5 heavy metals co-exposure and anxiety. RESULTS: This study included 4512 participants, among whom 1206 participants were in an anxiety state. Urinary cadmium and antimony were separately related to an increased risk of anxiety (p for trend <0.01 and < 0.01, respectively). In PCA analysis, PC1 was associated with an increased risk of anxiety (p for trend <0.001). In WQS analysis, the positive WQS index was substantially linked with the risk of anxiety (OR (95%CI): 1.23 (1.04,1.39)). In BKMR analysis, the overall effects of co-exposure to heavy metals were positively connected with anxiety. CONCLUSION: Our study identified a positive correlation between individual exposure to cadmium and antimony and the risk of anxiety. Additionally, the co-exposure to cadmium, antimony, cobalt, tungsten, and uranium was associated with an increased risk of anxiety.
Assuntos
Antimônio , Urânio , Humanos , Adulto , Inquéritos Nutricionais , Cádmio , Tungstênio , Teorema de Bayes , Ansiedade/epidemiologia , CobaltoRESUMO
Ambient particulate matter (PM) is a global public and environmental problem. PM is closely associated with several neurological disorders that typically involve neuroinflammation. There have been few studies on the effect of PM on neuroinflammation to date. In this study, we used a juvenile rat model (PM exposure was conducted at a dose of 10 mg/kg body weight per day for 4 weeks) and a BV-2 cell model (PM exposure was conducted at concentrations of 50, 100, 150, and 200 µg/ml for 24 h) to investigate PM-induced neuroinflammation mediated by NLRP3 inflammasome activation and the role of TREM2 in this process. Our findings revealed that PM exposure reduced TREM2 protein and mRNA levels in the rat hippocampus and BV-2 cells. TREM2 overexpression attenuated PM-induced spatial learning and memory deficits in rats. Moreover, we observed that TREM2 overexpression in vivo and in vitro effectively mitigated the increase in NLRP3 and pro-Caspase1 protein expression, as well as the secretion of IL-1ß and IL-18. Exposure to PM increased the expression of NF-κB and decreased the phosphorylation of PI3k/Akt in vivo and in vitro, and this process was effectively reversed by overexpressing TREM2. Our results indicated that PM exposure could reduce TREM2 expression and induce NLRP3 inflammasome-mediated neuroinflammation and that TREM2 could mitigate NLRP3 inflammasome-mediated neuroinflammation by regulating the NF-κB and PI3k/Akt signaling pathways. These findings shed light on PM-induced neuroinflammation mechanisms and potential intervention targets.