Abstract Schizophrenia (SCZ) and bipolar disorder (BPD) are associated with abnormal expression of immune-related factors (IRFs), which have been proposed as biomarkers of either disease diagnosis (trait markers) or treatment (state markers). However, the state markers have been found to be less reproducible than the trait markers in previous studies. In the current study, we focused on the changes of IRFs in blood of SCZ and BPD patients receiving monotherapy. SCZ ( N = 49) and BPD ( N = 49) Chinese patients were recruited at acute episode and followed for 9 to 51 days until remission. Blood samples were collected at two state-points, acute state before treatment and remission state after treatment. A total of 41 IRFs in plasma were quantified by the Luminex assay. After adjusting covariates, we found four cytokines or cytokine receptors were significantly increased at remission when compared to acute episode in all the patients, including CD30, BAFF, CCL20, and CXCL10 (Bonferroni corrected p < 0.05). CD30 and BAFF were consistently increased in both SCZ and BPD while the increase of CCL20 was only observed in BPD but not SCZ when analyzing the two disorders separately. CXCL10 change was not significant in either SCZ or BPD alone. The changes of these four factors were correlated with each other, but not with clinical features. CD30 concentration in the BPD acute state was correlated with sleep quality (Spearman’s r s = 0.365, Bonferroni corrected p < 0.05). Overall, we found that four factors (CD30, BAFF, CCL20, and CXCL10) might be associated with treatment of psychosis.
Abstract Understanding the genetic architecture of gene expression and splicing in human brain is critical to unlocking the mechanisms of complex neuropsychiatric disorders like schizophrenia (SCZ). Large-scale brain transcriptomic studies are based primarily on populations of European (EUR) ancestry. The uniformity of mono-racial resources may limit important insights into the disease etiology. Here, we characterized brain transcriptional regulatory architecture of East Asians (EAS; n=151), identifying 3,278 expression quantitative trait loci (eQTL) and 4,726 spliceQTL (sQTL). Comparing these to PsychENCODE/BrainGVEX confirmed our hypothesis that the transcriptional regulatory architecture in EAS and EUR brains align. Furthermore, distinctive allelic frequency and linkage disequilibrium impede QTL translation and gene-expression prediction accuracy. Integration of eQTL/sQTL with genome-wide association studies reveals common and novel SCZ risk genes. Pathway-based analyses showing shared SCZ biology point to synaptic and GTPase dysfunction as a prospective pathogenesis. This study elucidates the transcriptional landscape of the EAS brain and emphasizes an essential convergence between EAS and EUR populations.
Abstract Asarone could decrease Aβ, APP, Beclin-1level and clearing Aβ accumulation, which makes it to be one potential therapeutic agent for AD treatment. This study investigated the endophytic fungus got from Asarum heterotropoides Fr.Schmidt var. mandshuricum (Maxim.) kitag. The phylogenetic tree based on single copy orthologues at protein level got from genome sequence analysis showed that the endophytic fungus we got was Aspergillus niger . The total length of nonredundant sequences was nearly 34.7 Mb, comprising approximately 61 contigs sequences. In total, 8,755 genes were predicted to encoding proteins, and 18,611,392 high-quality clean reads were generated using the Illumina NovaSeq platform with paired-end sequencing mode. In this study, the theoretical yield of cis-asarone was higher than the traditional ways extracted from essential oil, which was evaluated according to the reverse-phase high performance liquid chromatography (HPLC). The highest yield appeared from the slant cultivation instead of liquid fermentation, and the mature black spore were the final supporter of cis-asarone. This strain was capable of producing cis-asarone and could be a fascinating reservoir of cis-asarone for further industrial manufacture.
Abstract Research on brain expression quantitative trait loci (eQTLs) has illuminated the genetic underpinnings of schizophrenia (SCZ). Yet, the majority of these studies have been centered on European populations, leading to a constrained understanding of population diversities and disease risks. To address this gap, we examined genotype and RNA-seq data from African Americans (AA, n=158), Europeans (EUR, n=408), and East Asians (EAS, n=217). When comparing eQTLs between EUR and non-EUR populations, we observed concordant patterns of genetic regulatory effect, particularly in terms of the effect sizes of the eQTLs. However, 343,737 cis-eQTLs (representing ∼17% of all eQTLs pairs) linked to 1,276 genes (about 10% of all eGenes) and 198,769 SNPs (approximately 16% of all eSNPs) were identified only in the non-EUR populations. Over 90% of observed population differences in eQTLs could be traced back to differences in allele frequency. Furthermore, 35% of these eQTLs were notably rare (MAF < 0.05) in the EUR population. Integrating brain eQTLs with SCZ signals from diverse populations, we observed a higher disease heritability enrichment of brain eQTLs in matched populations compared to mismatched ones. Prioritization analysis identified seven new risk genes ( SFXN2 , RP11-282018.3 , CYP17A1 , VPS37B , DENR , FTCDNL1 , and NT5DC2 ), and three potential novel regulatory variants in known risk genes ( CNNM2 , C12orf65 , and MPHOSPH9 ) that were missed in the EUR dataset. Our findings underscore that increasing genetic ancestral diversity is more efficient for power improvement than merely increasing the sample size within single-ancestry eQTLs datasets. Such a strategy will not only improve our understanding of the biological underpinnings of population structures but also pave the way for the identification of novel risk genes in SCZ.
Gene expression changes over the lifespan and varies among different tissues or cell types. Gene co-expression also changes by sex, age, different tissues or cell types. However, gene expression under the normal state and gene co-expression in the human brain has not been fully defined and quantified. Here we present a database named Brain EXPression Database (BrainEXP) which provides spatiotemporal expression of individual genes and co-expression in normal human brains. BrainEXP consists of 4567 samples from 2863 healthy individuals gathered from existing public databases and our own data, in either microarray or RNA-Seq library types. We mainly provide two analysis results based on the large dataset: (i) basic gene expression across specific brain regions, age ranges and sexes; (ii) co-expression analysis from different platforms.http://www.brainexp.org/.Supplementary data are available at Bioinformatics online.
Alzheimer's disease (AD) is a complex and multifactorial neurodegenerative disorder, and it is unlikely that any single drug or intervention will be very successful. The pathophysiology of Alzheimer's disease involves a range of complicated biological processes, including the accumulation of beta-amyloid protein and tau protein. Given the complexity of AD and amyloid accumulation, a combination of interventions remains to be further explored. Here, we investigated the potential of combining β-asarone and cannabidiol (CBD) as a treatment for AD. The study analyzed the combined effects of these two phytochemicals on beta-amyloid (Aβ) protein aggregation and toxicity in bulk solution, in cells as well as in C.elegans. We detailed the morphological and size changes of Aβ40 aggregates in the presence of β-asarone and cannabidiol. More importantly, the presence of both compounds synergistically inhibited apoptosis and downregulated relative gene expression in cells, and that it may also slow aging, decrease the rate of paralysis, enhance learning capacity, and boost autophagy activity in C.elegans. Our studies suggest that multiple drugs, like β-asarone and CBD, may be potentially developed as a medicinal adjunct in the treatment of AD, although further clinical trials are needed to determine the efficacy and safety of this combination treatment in humans.
Depression is a common mental disorder, the effective treatment of which remains a challenging issue worldwide. The clinical pathogenesis of depression has been deeply explored, leading to the formulation of various pathogenic hypotheses. Among these, the monoamine neurotransmitter hypothesis holds a prominent position, yet it has significant limitations as more than one-third of patients do not respond to conventional treatments targeting monoamine transmission disturbances. Over the past few decades, a growing body of research has highlighted the link between inflammation and depression as a potential key factor in the pathophysiology of depression. In this review, we first summarize the relationship between inflammation and depression, with a focus on the pathophysiological changes mediated by inflammation in depression. The mechanisms linking inflammation to depression as well as multiple anti-inflammatory strategies are also discussed, and their efficacy and safety are assessed. This review broadens the perspective on specific aspects of using anti-inflammatory strategies for treating depression, laying the groundwork for advancing precision medicine for individuals suffering from "inflamed" depression.
'/%3e%3cuse xlink:href='%23a' transform='rotate(23.036 .093 25.536)'/%3e%3cuse xlink:href='%23a' transform='rotate(45.87 1.273 16.18)'/%3e%3cuse xlink:href='%23a' transform='rotate(69.945 .996 12.078)'/%3e%3cuse xlink:href='%23a' transform='rotate(20.66 -19.689 31.932)'/%3e%3c/svg%3e)