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Background: Over recent decades, autism spectrum disorder (ASD) has been of increasing epidemiological importance, given the substantial increase in its prevalence; at present, clinical diagnosis is possible only after 2 years of age. In this study, we sought to develop a potential predictive model for ASD screening. Methods: We conducted a longitudinal follow-up study of newborns over 3 years. We measured transcript levels of 4 genes (superoxide dismutase-2 [ SOD2 ], retinoic acid–related orphan receptor-α [ RORA ], G protein–coupled estrogen receptor-1 [ GPER ], progesterone receptor [ PGR ]), 2 oxidative stress markers and epigenetic marks at the RORA promoter in case–control umbilical cord blood mononuclear cell (UCBMC) samples. Results: We followed 2623 newborns; we identified 41 children with ASD, 63 with delayed development and 2519 typically developing children. We matched the 41 children with ASD to 41 typically developing children for UCBMC measurements. Our results showed that children with ASD had significantly higher levels of H3K9me3 histone modifications at the RORA promoter and oxidative stress in UCBMC than typically developing children; children with delayed development showed no significant differences. Children with ASD had significantly lower expression of SOD2 , RORA and GPER , but higher PGR expression than typically developing children. We established a model based on these 4 candidate genes, and achieved an area under the curve of 87.0% (standard deviation 3.9%) with a sensitivity of 1.000 and specificity of 0.854 to predict ASD in UCBMC. Limitations: Although the gene combinations produced a good pass/fail cut-off value for ASD evaluation, relatively few children in our study sample had ASD. Conclusion: The altered gene expression in UCBMC can predict later autism development, possibly providing a predictive model for ASD screening immediately after birth. [ABSTRACT FROM AUTHOR]

Despite the importance of early diagnosis and intervention, the diagnosis of autism spectrum disorders (ASDs) remains delayed as it is mostly based on clinical symptoms and abnormal behaviours appearing after 2 years of age. Identification of autistic markers remains a top priority in achieving an early and effective ASD diagnosis. We have previously reported that prenatal exposure of hormones or diabetes triggers epigenetic changes and oxidative stress, resulting in gene suppression with autism‐like behaviours in offspring. Here, a potential biomarker for ASD diagnosis was established through gene analysis in peripheral blood mononuclear cells (PBMCs). The study from in vivo mouse showed that prenatal hormone exposure or maternal diabetes suppresses mRNA expression of estrogen‐related receptor α (ERRα), superoxide dismutase 2 (SOD2), G protein‐coupled estrogen receptor (GPER) and retinoic acid‐related orphan receptor α (RORA) in the brain as well as oxidative stress and mitochondrial dysfunction, subsequently triggering autism‐like behaviour in mouse offspring. Also, similar gene suppression was found in hematopoietic stem cells (HSCs) and PBMC, with inherited epigenetic changes being identified on the related promoters. The human case–control study found that mRNA levels of ERRα, SOD2, GPER and RORA were significantly reduced in PBMC from ASD subjects (n = 132) compared with typically developing (n = 135) group. The receiver operating characteristic curve showed a.869 ±.021 of area under the curve for ASD subjects with 95% confidence interval of.829–.909, together with 1.000 of sensitivity and.856 of specificity. In conclusion, the combined mRNA expression in PBMC based on prenatal factor exposure‐mediated gene suppression could be a potential biomarker for ASD diagnosis. [ABSTRACT FROM AUTHOR]

Background. Diabetic nephropathy (DN) is a common and serious complication of diabetes, but without a satisfactory treatment strategy till now. Liuwei Dihuang pills (LDP), an effective Chinese medicinal formula, has been used to treat DN for more than 1000 years. However, its underlying mechanism of action is still vague. Methods. Active compounds and corresponding targets of LDP were predicted from the TCMSP database. DN disease targets were extracted from the OMIM, GeneCards, TTD, DisGeNET, and DrugBank databases. Subsequently, the "herbal-compound-target" network and protein-protein interaction (PPI) network were constructed and analyzed via the STRING web platform and Cytoscape software. GO functional and KEGG pathway enrichment analyses were carried out on the Metascape web platform. Molecular docking utilized AutoDock Vina and PyMOL software. Results. 41 active components and 186 corresponding targets of LDP were screened out. 131 common targets of LDP and DN were acquired. Quercetin, kaempferol, beta-sitosterol, diosgenin, and stigmasterol could be defined as five crucial compounds. JUN, MAPK8, AKT1, EGF, TP53, VEGFA, MMP9, MAPK1, and TNF might be the nine key targets. The enrichment analysis showed that common targets were mainly associated with inflammation reaction, oxidative stress, immune regulation, and cell apoptosis. AGE-RAGE and IL-17 were the suggested two significant signal pathways. Molecular docking revealed that the nine key targets could closely bind to their corresponding active compounds. Conclusion. The present study fully reveals the multicompound's and multitarget's characteristics of LDP in DN treatment. Furthermore, this study provides valuable evidence for further scientific research of the pharmacological mechanisms and broader clinical application. [ABSTRACT FROM AUTHOR]

Seed germination is tightly regulated by multiple endogenous signaling molecules and metabolites, such as abscisic acid (ABA), the products of fatty acid β-oxidation for energy production and reactive oxygen species (ROS). In Arabidopsis the expression of pyruvate decarboxylase 1 (PDC1), which is involved in fermentation metabolism, was strongly induced by ABA during seed germination, suggesting that PDC1 might regulate seed germination in response to ABA. To prove this hypothesis, we characterized the role of PDC1 in ABA-mediated inhibition of seed germination. The percentages of seed germination and cotyledon greening of PDC1-deficiency pdc1 mutants were higher, whereas those of PDC1 -overexpression lines were lower, than those of wild-type (WT) plants in the presence of ABA. Chromatin immunoprecipitation and electrophoretic mobility shift assays indicated that the ABA-responsive element BINDING FACTOR 4 (ABF4) transcription factor could bind to the PDC1 promoter and activate gene expression. ABA-induction of PDC1 expression was impaired in abf4–1 mutants, and overexpression of ABF4 in pdc1–1 plants can partially rescue their ABA-insensitive phenotypes. In addition, ABA-induced ROS accumulation was impaired in pdc1–1 seedlings, whereas it was enhanced in PDC1 -overexpression lines, as compared with WT plants. Furthermore, the levels of free fatty acids were lower in pdc1–1 mutants, but higher in the PDC1 -overexpression lines, than WT plants. This is consistent with the altered expression of fatty acid β-oxidation-related genes in these plants. Taken together, our results indicated that ABF4 activates PDC1 expression, thereby promoting fatty acid β-oxidation and enhancing ROS accumulation, leading to inhibition of seed germination in Arabidopsis. • ABF4 binds to the PDC1 promoter and enhances its expression. • ABF4 acts upstream of PDC1 in the ABA-mediated inhibition of seed germination. • PDC1 participates in ABA-induce d ROS accumulation during the seed germination process. • Fatty acid metabolism is involved in PDC1-mediated ROS accumulation. [ABSTRACT FROM AUTHOR]