[Mechanism of Potentilla discolor in treating UC by regulating mitochondrial autophagy].

To evaluate the therapeutic effect of Potentilla discolor on 2,4,6-trinitrobenzensulfonic acid(TNBS)-induced experimental ulcerative colitis(UC) in rats and to determine its therapeutic mechanism through mitochondrial autophagy, immune cells, and cytokines. A rat model of UC was established by TNBS-ethanol enema. Rats were divided into six groups: control, UC model, sulfasalazine(positive drug), and high-dose, moderate-dose, and low-dose ethanol extract groups. After 14-day continuous administration of the corresponding drugs, the disease activity index(DAI) and hematoxylin and eosin(HE) were evaluated. The morphological structure of mitochondria was observed by using transmission electron microscope(TEM), mitophagy-related mRNA expression was detected by using Real-time quantitative polymerase chain reaction(qRT-PCR), immune cell differentiation in rat serum was detected by using flow cytometry(FCM), and cytokine expression in colon tissues of rats was detected by protein microarray. The results showed that compared with the model group, each dose group of P. discolor could significantly reduce the DAI of UC model rats, and decrease the degree of inflammatory cells infiltration in the colon tissue of UC model rats. Meanwhile the expressions of T cells and Th cells in the serum increased significantly, the expression of Tc cells in the serum decreased significantly. Transmission electron microscope found that there was fusion of mitochondria and lysosomes in the colon tissue of the administration group. The expressions of mitochondrial autophagy related genes NF-κB, p62 and parkin were significantly increased in colon tissues. The results of protein chip showed that compared with the model group, the high dose group of P. discolor could significantly regulate the expression of cytokines. In conclusion, these results suggested that P. discolor improved TNBS-induced acute ulcerative colitis in rats by regulating the mitochondrial autophagy and the inflammatory factor expression.

Role of colonic microbiota in the pathogenesis of ulcerative colitis.

BACKGROUND: Recent studies have found gut microbiota to be closely associated with onset and perpetuation of UC. Currently, studies about gut microbiota have mainly covered samples collected from the intestinal lumen. However, the luminal flora is only part of the gut microbiota. Studies of the changes in mucosal flora under pathological conditions have been lacking. In this study, we investigated the correlation between the onset of UC and flora changes in different intestinal layers. METHODS: The dextran sulfate sodium(DSS)-induced UC model was established by exposing mice to cycles of DSS. The luminal contents, an inner mucus layer, and outer mucus layer were harvested under sterile conditions. The samples were then analyzed using high-throughput sequencing of 16S rRNA V3 + V4 amplicons. The colonic microbiota composition and diversity were analyzed and compared using MetaStat, LefSe, multivariate analysis of variance, and spatial statistics. RESULTS: The DSS-induced UC mouse model was successfully established. The diversity of the microbiota from luminal content, the outer mucus layer, and inner mucus layer were significantly different in both control and UC model groups. The statistically different OTUs belonged to Lachnospiraceae and Ruminococcaceae families within the order Clostridiales were mainly localized to the outer mucus layer. CONCLUSIONS: The alterations in flora composition and diversity mainly occurred in the colonic outer mucus layer. The change of flora in the colonic mucus layers is of great significance in the understanding of common features of gut flora in IBD and the understanding of the relationship between gut flora and disease progression.

Regulatory effect of Garidisan on dysbiosis of the gut microbiota in the mouse model of ulcerative colitis induced by dextran sulfate sodium.

BACKGROUND: Ulcerative colitis (UC) is a modern refractory disease, and its etiology has been difficult to discern. Studies have shown that UC is closely associated with the gut microbiota. Garidisan is composed of wild poppy and Artemisia frigida Willd and is commonly used for the treatment of UC in Inner Mongolia, China. In clinical settings, Garidisan has been found to treat UC effectively, with low recurrence. Previous studies have shown that Garidisan has a good therapeutic effect on mice with UC, but the therapeutic mechanism is still unclear. In this study, we investigated the regulatory effect of Garidisan on dysbiosis of the gut microbiota in a UC mouse model and explored the possible mechanism of the therapeutic effect of Garidisan on UC. METHODS: The UC mouse model was established by the dextran sulfate sodium (DSS) circulating free water drinking method, and the luminal contents were sampled under sterile conditions. High-throughput sequencing of the 16S rRNA gene V3 + V4 region of the luminal contents of the control group, model group, and Garidisan group was conducted, and clustering of operational taxonomic units (OTUs) and species annotation were performed. The differences in species composition and microbial community structure between individual groups of samples were analyzed using MetaStat, LefSe, rank sum test, and Bayesian causal network analysis. RESULTS: The UC mouse model was successfully established and the sequencing results were of adequate quality. There were significant differences in the diversity of luminal contents between the control group, model group, and Garidisan group, and the differences between groups were greater than those within any group. The therapeutic effect of Garidisan on UC is attributed to the direct effect on the Lachnospiraceae family of bacteria. CONCLUSION: Garidisan has a good regulatory effect on the gut microbiota, and Lachnospiraceae could be an important direct target of Garidisan for the treatment of UC.

The role of early cerebral edema and hematoma assessment in aneurysmal subarachnoid hemorrhage (a-SAH) in predicting early brain injury (EBI) and cognitive impairment: a case controlled study.

BACKGROUND: Early assessment and management of cerebral edema and hematoma following aneurysmal subarachnoid hemorrhage (a-SAH) can significantly impact clinical cognitive outcomes. However, current clinical practices lack predictive models to identify early structural brain abnormalities affecting cognition. To address this gap, the authors propose the development of a predictive model termed the a-SAH Early Brain Edema/Hematoma Compression Neural (Structural Brain) Networks Score System (SEBE-HCNNSS). METHODS: In this study, 202 consecutive patients with spontaneous a-SAH underwent initial computed tomography (CT) or MRI scans within 24 h of ictus with follow-up 2 months after discharge. Using logistic regression analysis (univariate and multivariate), the authors evaluated the association of clinically relevant factors and various traditional scale ratings with cognitive impairment (CI). Risk factors with the highest area under the curve (AUC) values were included in the multivariate analysis and least absolute shrinkage and selection operator (LASSO) analysis or Cox regression analysis. RESULTS: A total of 177 patients were enrolled in the study, and 43 patients were classified with a high SEBE-HCNNSS grade (3-5). After a mean follow-up of 2 months, 121 individuals (68.36%) with a-SAH and three control subjects developed incident CI. The CT interobserver reliability of the SEBE-HCNNSS scale was high, with a Kappa value of 1. Furthermore, ROC analysis identified the SEBE-HCNNSS scale (OR 3.322, 95% CI: 2.312-7.237, P =0.00025) as an independent predictor of edema, CI, and unfavorable prognosis. These results were also replicated in a validation cohort. CONCLUSION: Overall, the SEBE-HCNNSS scale represents a simple assessment tool with promising predictive value for CI and clinical outcomes post-a-SAH. Our findings indicate its practical utility as a prognostic instrument for risk evaluation after a-SAH, potentially facilitating early intervention and treatment.

Novel Subgroups in Subarachnoid Hemorrhage and Their Association With Outcomes-A Systematic Review and Meta-Regression.

Background and Purpose: Subarachnoid hemorrhage (SAH) has long been classified into two main forms, aneurysmal SAH (aSAH) and non-aneurysmal SAH (naSAH), but the related risk factors for aSAH and naSAH are heterogeneous. Our objective was to determine the risk factors for SAH of known or unknown origin with respect to diagnostic evaluation in a large patient cohort. We sought to determine whether our classification system can further predict middle long-term stroke and death. Methods: We performed a systematic review and meta-analysis to identify risk factors for each SAH subtype. The discovery phase analyzed 11 risk factors from case studies in the literature. Kruskal-Wallis, Cox regression, logistic regression, and Kaplan-Meier analyses were used to compare the two groups. Results: A total of 14,904 (34.53%) male and 22,801 (52.84%) female patients were eligible for this study. At a median follow-up of 45.6 months, the 5-years overall survival was 97.768% (95% CI: 0.259-0.292) for aSAH patients and 87.904% (95% CI: 1.459-1.643) for naSAH patients. The 10-years survival rate was 93.870% (95% CI: 2.075-3.086) and 78.115% (95% CI: 2.810-3.156), respectively. Multi-risk factor subgroups showed significant intergroup differences. We identified eight risk factors (drugs, trauma, neoplastic, vessels lesion, inflammatory lesion, blood disease, aneurysm, peri-mesencephalic hemorrhage) using logistic regression, which were optimally differentiated among the aSAH [aSAH-S (AUC: 1), a-d-SAH (AUC: 0.9998), aSAH-T (AUC: 0.9199), aSAH-N (AUC: 0.9433), aSAH-V (AUC: 1), aSAH-I (AUC: 0.9954), a-bd-SAH (AUC: 0.9955)] and naSAH [na-pmSAH (AUC: 0.9979), na-ni-ivl-SAH (AUC: 1), na-t-SAH (AUC: 0.9997), na-ne-SAH (AUC: 0.9475), na-d-SAH (AUC: 0.7676)] subgroups. These models were applied in a parallel cohort, showing eight risk factors plus survival rates to predict the prognosis of SAH. Conclusions: The classification of risk factors related to aSAH and naSAH is helpful in the diagnosis and prediction of the prognosis of aSAH and naSAH patients. Further validation is needed in future clinical applications.