Background: Pterostilbene (PTE) is a natural polyphenol compound that has been proven to improve intestinal inflammation, but its laxative effect on slow transit constipation (STC) has never been studied. This study aims to investigate the laxative effect of PTE on loperamide (LOP)-induced STC mice and its influence on intestinal microbes through a combination of network pharmacological analysis and experimental verification.Material and Methods: PTE was used to treat LOP-exposed mice, and the laxative effect of PTE was evaluated by the total intestinal transit time and stool parameters. The apoptosis of Cajal interstitial cells (ICCs) was detected by immunofluorescence. The mechanism of PTE’s laxative effect was predicted by network pharmacology analysis. We used western blot technology to verify the predicted hub genes and pathways. Malondialdehyde (MDA) and GSH-Px were tested to reflect oxidative stress levels and the changes of gut microbiota were detected by 16S rDNA high-throughput sequencing.Results: PTE treatment could significantly improve the intestinal motility disorder caused by LOP. Apoptosis of ICCs increased in the STC group, but decreased significantly in the PTE intervention group. Through network pharmacological analysis, PTE might reduce the apoptosis of ICCs by enhancing PI3K/AKT and Nrf2/HO-1 signaling, and improve constipation caused by LOP. In colon tissues, PTE improved the Nrf2/HO-1 pathway and upregulated the phosphorylation of AKT. The level of MDA increased and GSH-Px decreased in the STC group, while the level of oxidative stress was significantly reduced in the PTE treatment groups. PTE also promoted the secretion of intestinal hormone and restored the microbial diversity caused by LOP.Conclusion: Pterostilbene ameliorated the intestinal motility disorder induced by LOP, this effect might be achieved by inhibiting oxidative stress-induced apoptosis of ICCs through the PI3K/AKT/Nrf2 signaling pathway.

Background: Glioblastoma (GBM) is the most prevalent malignant brain tumor, significantly impacting the physical and mental wellbeing of patients. Several studies have demonstrated a close association between gut microbiota and the development of GBM. In this investigation, Mendelian randomization (MR) was employed to rigorously evaluate the potential causal relationship between gut microbiota and GBM.Methods: We utilized summary statistics derived from genome-wide association studies (GWAS) encompassing 211 gut microbiota and GBM. The causal association between gut microbiota and GBM was scrutinized using Inverse Variance Weighted (IVW), MR-Egger, and Weighted Median (WM) methods. Cochrane’s Q statistic was employed to conduct a heterogeneity test. MR-Pleiotropic Residuals and Outliers (MR-PRESSO) were applied to identify and eliminate SNPs with horizontal pleiotropic outliers. Additionally, Reverse MR was employed to assess the causal relationship between GBM and pertinent gut microbiota.Results: The MR study estimates suggest that the nine gut microbiota remain stable, considering heterogeneity and sensitivity methods. Among these, the family.Peptostreptococcaceae and genus.Eubacterium brachy group were associated with an increased risk of GBM, whereas family.Ruminococcaceae, genus.Anaerostipes, genus.Faecalibacterium, genus.LachnospiraceaeUCG004, genus.Phascolarctobacterium, genus.Prevotella7, and genus.Streptococcus were associated with a reduced risk of GBM. Following Benjamini and Hochberg (BH) correction, family.Ruminococcaceae (OR = 0.04, 95% CI: 0.01–0.19, FDR = 0.003) was identified as playing a protective role against GBM.Conclusion: This groundbreaking study is the first to demonstrate that family.Ruminococcaceae is significantly associated with a reduced risk of GBM. The modulation of family_Ruminococcaceae for the treatment of GBM holds considerable potential clinical significance.

A cavernous hemangioma, well-known as vascular malformation, is present at birth, grows proportionately with the child, and does not undergo regression. Although a cavernous hemangioma has well-defined histopathological characteristics, its origin remains controversial. In the present study, we characterized the cellular heterogeneity of a cavernous hemangioma using single-cell RNA sequencing (scRNA-seq). The main contribution of the present study is that we discovered a large number of embryonic mesenchymal stem cells (MSCs) in a cavernous hemangioma and proposed that cavernous hemangiomas may originate from embryonic MSCs. Further analysis of the embryonic MSCs revealed that: 1) proinflammatory cytokines and related genes TNF, TNFSF13B, TNFRSF12A, TNFAIP6, and C1QTNF6 are significantly involved in the MSC-induced immune responses in cavernous hemangiomas; 2) UCHL1 is up-regulated in the embryonic MSC apoptosis induced by proinflammatory cytokines; 3) the UCHL1-induced apoptosis of MSCs may play an important role in the MSC-induced immune responses in cavernous hemangiomas; and 4) UCHL1 can be used as a marker gene to detect embryonic MSCs at different apoptosis stages. In addition to MSCs, ECs, macrophages, T lymphocytes and NKCs were intensively investigated, revealing the genes and pathways featured in cavernous hemangiomas. The present study revealed the origin of cavernous hemangiomas and reported the marker genes, cell types and molecular mechanisms, which are associated with the origin, formation, progression, diagnosis and therapy of cavernous hemangiomas. The better understanding of the MSC-induced immune responses in benign tumours helps to guide future investigation and treatment of embryonic MSC-caused tumours. Our findings initiated future research for the rediscovery of MSCs, cancers/tumours and the UCHL1-induced apoptosis.