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IntroductionColorectal cancer (CRC) is a serious threat to human health. Screening new biomarkers can provide basis for improving the prognosis and individualized treatment of CRC. Although some members of the defensin family were found increased in pancreatic cancer and CRC, their exact function and clinical significance remain unclear.MethodsIn this study, the expression, correlation, mutation, and functional enrichment of several defensin family members in pancreatic cancer and CRC were analyzed using tumor public databases and verified in several patients.ResultsResults showed no significant correlation between the expression levels of DEFA1-4 and CRC. The expression levels of DEFA5 and DEFA6 significantly increased in CRC tissues compared with those in normal tissues. DEFA5 may be associated with better prognosis of CRC, while DEFA6 may be associated with poor prognosis. Immunohistochemistry (IHC) experiments showed that the expression of DEFA6 was significantly higher in adenoma than in normal mucosa and slightly higher in carcinoma than in normal mucosa. The Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis found that DEFAs were closely related to hsa05202: transcriptional misregulation in cancer and Hsa04015: Rap1 signaling pathway. DEFA5 may be a stable and good prognostic marker, and DEFA6 may be a poor prognostic marker in CRC of metastasis.ConclusionOverall, DEFA5 and DEFA6 have a certain degree of sensitivity and specificity in predicting CRC.

ObjectivesDrug treatment of metabolic associated fatty liver disease (MAFLD) remains lacking. This study analyzes the efficacy and mechanism underlying intermittent fasting combined with lipidomics.MethodsThirty-two male rats were randomly divided into three groups: Normal group, administered a standard diet; MAFLD group, administered a 60% high-fat diet; time-restricted feeding (TRF) group, administered a 60% high-fat diet. Eating was allowed for 6 h per day (16:00–22:00). After 15 weeks, liver lipidomics and other indicators were compared.ResultsA total of 1,062 metabolites were detected. Compared with the Normal group, the weight, body fat ratio, aspartate aminotransferase, total cholesterol, low-density cholesterol, fasting blood glucose, uric acid, and levels of 317 lipids including triglycerides (TG) (17:0−18:1−20:4) were upregulated, whereas the levels of 265 lipids including phosphatidyl ethanolamine (PE) (17:0−20:5) were downregulated in the MAFLD group (P < 0.05). Compared with the MAFLD group, the weight, body fat ratio, daily food intake, and levels of 253 lipids including TG (17:0−18:1−22:5) were lower in the TRF group. Furthermore, the levels of 82 lipids including phosphatidylcholine (PC) (20:4−22:6) were upregulated in the TRF group (P < 0.05), while serum TG level was increased; however, the increase was not significant (P > 0.05). Enrichment analysis of differential metabolites showed that the pathways associated with the observed changes mainly included metabolic pathways, regulation of lipolysis in adipocytes, and fat digestion and absorption, while reverse-transcription polymerase chain reaction showed that TRF improved the abnormal expression of FAS and PPARα genes in the MAFLD group (P < 0.05).ConclusionOur results suggest that 6 h of TRF can improve MAFLD via reducing food intake by 13% and improving the expression of genes in the PPARα/FAS pathway, thereby providing insights into the prevention and treatment of MAFLD.

Celiac disease (CeD) is one of the most common intestinal inflammatory diseases, and its incidence and prevalence have increased over time. CeD affects multiple organs and systems in the body, and environmental factors play a key role in its complex pathogenesis. Although gluten exposure is known to be the causative agent, many unknown environmental factors can trigger or exacerbate CeD. In this study, we investigated the influence of genetic and environmental factors on CeD. Data from a CeD genome-wide association study that included 12,041 CeD cases and 12,228 controls were used to conduct a transcriptome-wide association study (TWAS) using FUSION software. Gene expression reference data were obtained for the small intestine, whole blood, peripheral blood, and lymphocytes. We performed Gene Ontology and Kyoto Encyclopedia of Genes and Genomes enrichment analyses using the significant genes identified by the TWAS and conducted a protein–protein interaction network analysis based on the STRING database to detect the function of TWAS-identified genes for CeD. We also performed a chemical-related gene set enrichment analysis (CGSEA) using the TWAS-identified genes to test the relationships between chemicals and CeD. The TWAS identified 8,692 genes, including 101 significant genes (padjusted < 0.05). The CGSEA identified 2,559 chemicals, including 178 chemicals that were significantly correlated with CeD. This study performed a TWAS (for genetic factors) and CGSEA (for environmental factors) and identified several CeD-associated genes and chemicals. The findings expand our understanding of the genetic and environmental factors related to immune-mediated diseases.

This study aimed to identify susceptibility genes and pathways associated with ankylosing spondylitis (AS) by integrating whole transcriptome-wide association study (TWAS) analysis and mRNA expression profiling data. AS genome-wide association study (GWAS) summary data from the large GWAS database were used. This included data of 1265 AS patients and 452264 controls. A TWAS of AS was conducted using these data. The analysis software used was FUSION, and Epstein-Barr virus–transformed lymphocytes, transformed fibroblasts, peripheral blood, and whole blood were used as gene expression references. Gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses were performed for the important genes identified via TWAS. Protein-protein interaction (PPI) network analysis based on the STRING database was also performed to detect genes shared by TWAS and mRNA expression profiles in AS. TWAS identified 920 genes (P Via PPI network analysis, we obtained the protein interaction network and performed MCODE analysis to acquire the HUB genes. Similarly, we performed GO and KEGG analyses on the genes identified by TWAS, obtained 98 pathways after screening, and analyzed protein interactions via the PPI network. Through the integration of TWAS and mRNA expression analysis, genes related to AS and GO and KEGG terms were determined, providing new evidence and revealing the pathogenesis of AS. Our AS TWAS work identified novel genes associated with AS, as well as suggested potential tissues and pathways of action for these TWAS AS genes, providing a new direction for research into the pathogenesis of AS.

Menarche is the first occurrence of menstrual bleeding and one of the most important events of female puberty. Alarmingly, over the last several decades, the mean age at menarche (AAM) has decreased. Environmental endocrine disruptors (EEDs) are chemicals that may interfere with the endocrine system, resulting in adverse developmental, immunological, neurological, and reproductive effects in humans. Thus, the effects of EEDs on fertility and reproduction are growing concerns in modern societies. In this study, we aimed to determine the influence of genetic and environmental factors on AAM. We used data from an AAM genome-wide association study of 329,345 women to conduct a transcriptome-wide association study (TWAS) with FUSION software. As references, we determined the gene-expression levels in the hypothalamus, pituitary gland, ovaries, uterus, and whole blood. We performed Gene Ontology and Kyoto Encyclopedia of Genes and Genomes enrichment analyses using the significantly dysregulated genes identified by the TWAS. Using the STRING database, we also generated a protein–protein-interaction network to analyze common AAM-specific genes identified by the TWAS with different tissues. We performed chemical-related gene set enrichment analysis (CGSEA) and identified significant TWAS genes to uncover relationships between different chemicals and AAM. The TWAS identified 9,848 genes; among these, 1580 genes were significant (P < 0.05), and 11 genes were significant among the hypothalamus, pituitary, ovary, uterus, and whole blood. CGSEA identified 1,634 chemicals, including 120 chemicals significantly correlated with AAM. In summary, we performed a TWAS (for genetic factors) and CGSEA (for environmental factors) focusing on AAM and identified several AAM-associated genes and EEDs. The results of this study expand our understanding of genetic and environmental factors related to the onset of female puberty.