RESUMO
Current treatments for schizophrenia (SCZ) remain largely ineffective in one-third of patients. Recent studies using stem cell therapy show a close relationship between stem cell immunomodulatory function and neuroinflammation in SCZ. To better investigate the efficacy of stem cell therapy for SCZ, human umbilical cord blood mesenchymal stem cells (hUC-MSC) with powerful immunomodulatory effects were administered to rats via the tail vein (once a week for 5 consecutive weeks starting from the weaning period) using a maternal immune activation (MIA) rodent model. Open field, PPI, Western blotting, Q-PCR, and immunofluorescence were used to assess the biological effects of repeated tail vein injections of hUC-MSC in offspring rats following the MIA model of SCZ. The results indicated that offspring of MIA rats exhibited schizophrenia-like (SCZ-like) anxiety behavior, with observed microglial activation triggering neuroinflammation. Furthermore, levels of IBA1, HMGB1, and PSD95 were significantly up-regulated, while SYP was significantly down-regulated. It is suggested that hUCB-MSCs may act through HMGB1, Iba1, PSD95, and related pathway molecules to alleviate neuroinflammation and repair synaptic damage by regulating the activity state of microglia. Consequently, this could improve the abnormal behavior observed in MIA offspring rats.
Assuntos
Ansiedade , Modelos Animais de Doenças , Proteína HMGB1 , Transplante de Células-Tronco Mesenquimais , Células-Tronco Mesenquimais , Microglia , Ratos Sprague-Dawley , Esquizofrenia , Animais , Ratos , Esquizofrenia/terapia , Esquizofrenia/induzido quimicamente , Transplante de Células-Tronco Mesenquimais/métodos , Humanos , Feminino , Ansiedade/terapia , Proteína HMGB1/metabolismo , Gravidez , Proteína 4 Homóloga a Disks-Large/metabolismo , Proteínas de Ligação ao Cálcio/metabolismo , Proteínas dos Microfilamentos/metabolismo , Masculino , Sangue Fetal/citologia , Doenças Neuroinflamatórias , Sinaptofisina/metabolismo , Transplante de Células-Tronco de Sangue do Cordão Umbilical/métodos , Efeitos Tardios da Exposição Pré-NatalRESUMO
OBJECTIVES: Genetic factors play an important role in the etiology of schizophrenia (SZ). Catenin Delta 2 (CTNND2) is one of the genes regulating neuronal development in the brain. It is unclear whether CTNND2 is involved in SZ. With the hypothesis that CTNND2 may be a risk gene for SZ, we performed a case-control association analysis to investigate if CTNND2 gene single nucleotide polymorphisms (SNPs) are implicated in SZ in a Han Chinese population. MATERIALS AND METHODS: We recruited subjects from 2010 to 2022 from the Han population of northern Henan and divided them into two case-control samples, including a discovery sample (SZ = 528 and controls = 528) and replication sample (SZ = 2458 and controls = 6914). Twenty-one SNPs were genotyped on the Illumina BeadStation 500G platform using GoldenGate technology and analyzed by PLINK. The Positive and Negative Syndrome Scale (PANSS) was used to assess clinical symptoms. RESULTS: Rs16901943, rs7733427, and rs2168878 SNPs were associated with SZ (Chi2 = 7.484, 11.576, and 5.391, respectively, df = 1; p = 0.006, 0.00067, and 0.02, respectively) in the two samples. Rs10058868 was associated with SZ in male patients in the discovery sample (Chi2 = 6.264, df = 1, p = .044). Only the relationship with rs7733427 survived Bonferroni correction. Linkage disequilibrium block three haplotypes were associated with SZ in the discovery and total sample. PANSS analysis of the four SNPs implicated rs10058868 and rs2168878 in symptoms of depression and excitement, respectively, in the patients with SZ. CONCLUSION: Four SNPs of the CTNND2 gene were identified as being correlated with SZ. This gene may be involved in susceptibility to SZ.
Assuntos
Predisposição Genética para Doença , Esquizofrenia , Humanos , Masculino , Estudos de Casos e Controles , delta Catenina , Estudos de Associação Genética , Esquizofrenia/genética , População do Leste Asiático , Genótipo , Polimorfismo de Nucleotídeo Único , Frequência do GeneRESUMO
Heterogeneous agglomeration (HA) is a very potential technology for coal-fired flue gas treatment. In this paper, the distribution and migration mechanisms of trace elements (TEs) such as Se, As and Pb in CFPPs were studied on a 30,000 m3/hr pilot-scale experimental platform. The influences of HA on the removal efficiency of gaseous and particulate TEs were well analyzed. The results showed that Se, As and Pb were enriched in fly ash, and their sensitivity to particle size is quite different. The content of Se was the highest in PM1, reaching 193.04 mg/kg at the electrostatic precipitator (ESP) outlet. The average particle size of the total dust before ESP increased significantly from 21.686 to 62.612 µm after injecting the heterogeneous agglomeration adsorbent, conducive to its further removal by ESP. In addition, the concentrations of gaseous Se, As and Pb in the flue gas decreased after adsorbent spray, and accordingly, their contents in the hierarchical particles increased, indicating that the adsorbent could effectively promote the adsorption of gaseous trace elements in fly ash and reduce the possibility of their escape to the atmosphere. Total concentrations of Se, As and Pb emitted by wet flue gas desulfurization (WFGD) are 0.223, 0.668 and 0.076 µg/m3, which decreased by 59.98%, 47.69% and 90.71%, respectively. Finally, a possible HA mechanism model was proposed, where chemical adsorption, physical condensation and collision agglomeration of gaseous TEs and fine particles with adsorbent droplets occurred to form larger agglomerates.