Bioinformatics Approach to Identify the Pathogenetic Link of Gut Microbiota-Derived Short-Chain Fatty Acids and Ischemic Stroke.

Stroke is a life-threatening condition that impairs the arteries and causes neurological impairment. The incidence of stroke is increasing year by year with the arrival of the aging population. Thus, there is an urgent need for early stroke diagnosis. Short-chain fatty acids (SCFAs) can modulate the central nervous system and directly and indirectly impact behavioral and cognitive functions. This study aimed to investigate the connection between SCFA metabolism and stroke development via bioinformatic analysis. Initially, the Gene Set Enrichment Analysis (GSEA) and immune cell infiltration analysis were performed based on RNA data from stroke patients to comprehend the mechanisms governing stroke pathogenesis. The functional analysis, including Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG), and Protein-Protein Interaction (PPI), was performed based on the Differentially Expressed Gene (DEG) selected by the limma package. 1220 SCFA metabolism-related genes screened from Genecards databases were intersected with 242 genes in main modules determined by Weighted Gene Co-Expression Network Analysis (WGCNA), and the final 10 SCFA key genes were obtained. GO analysis revealed that these genes were involved in immune response processes. Through lasso regression analyses, we established a stroke early diagnosis model and selected 6 genes with diagnostic value. The genes were validated by the area under curve (AUC) values and had a relatively good diagnostic performance. Finally, 4 potential therapeutic drugs targeting these genes were predicted using the Drug Signatures Database (DSigDB) via Enrichr. In conclusion, this paper analyzes the involvement of SCFAs in the complex gut-brain axis mechanism, which contributes to developing new targets for treating central nervous system diseases and provides new ideas for early ischemic stroke diagnosis.

Hispidulin exhibits neuroprotective activities against cerebral ischemia reperfusion injury through suppressing NLRP3-mediated pyroptosis.

AIM: Ischemia/reperfusion (I/R) injury is the major cause of neurological deficit following stroke. Our previous study showed neuroprotective effects of hispidulin against cerebral ischemia reperfusion injury (IRI). In this study, we further examined the involvement of pyroptosis in this neuroprotective function. MATERIALS AND METHODS: IRI was simulated in a rat model by middle cerebral artery occlusion (MCAO) surgery, and the animals were treated with different doses of hispidulin. The neurological function of the rats was evaluated by the neural function defect score (NFDS), balance beam test and limb placement test. The infarct volume and brain water content were measured 72 h following IRI. Neuronal cell survival and pyroptosis in the ischemic cortex were respectively detected by Nissl staining and TUNEL assay. The relative expression of pyroptosis markers was determined by qRT-PCR, Western blotting and ELISA as appropriate. IRI was simulated in vitro in primary cerebral astrocytes using the OGD/R procedure. AMPKα was blocked genetically or pharmacologically using siRNA and compound C respectively. CCK-8 and LDH release assays were performed using suitable kits. RESULTS: Hispidulin improved the neurological symptoms of the rats after IRI, in addition to decreasing the infarct size and brain edema. Mechanistically, hispidulin exerted its neuroprotective effects in vivo and in vitro by suppressing NLRP3-mediated pyroptosis by modulating the AMPK/GSK3ß signaling pathway. CONCLUSION: Hispidulin is a neuroprotective agent with clinical potential against IR-induced neurological injury.

Hispidulin Protects Against Focal Cerebral Ischemia Reperfusion Injury in Rats.

Focal cerebral ischemia is associated with ischemia/reperfusion (I/R) injury. Hispidulin is a flavonoid compound with a variety of pharmacological properties. The neuroprotective effects of hispidulin have not been fully elucidated. Herein, we demonstrated that pretreatment of animals with hispidulin improved the neurological outcomes and decreased the infarct size and brain edema in the cerebral focal I/R model. Mechanistically, we showed in vivo and in vitro that hispidulin exerted a protective effect against I/R injury by inducing the Nrf2 antioxidant pathway through modulation of AMPK/GSK3ß signaling. Taken together, our results suggest that hispidulin may be a useful neuroprotective agent against ischemia/reperfusion (I/R) injury.

Milk fatty acid profiles in Holstein dairy cows fed diets based on corn stover or mixed forage.

In this study the influence of modulated concentrate-to-roughage ratio on the fatty acid profile of milk fat was investigated in dairy cows. Therefore, corn stover was compared with better-quality roughages. Two groups of in total 24 Holstein dairy cows (136 ± 37 days in milk) received either a high-forage diet (Diet MF, forage-to-concentrate ratio [F:C] = 60:40) with alfalfa hay, corn silage and Chinese wild rye as forage sources, or a low-forage diet with corn stover as forage source (Diet CS, F: C = 40:60) for an experimental period of nine weeks. During the study, milk yield as well content and fatty acid profiles of milk fat were examined. Dietary treatments had no effect on milk yield and milk fat content, whereas dry matter intake (p < 0.01) and milk fat yield (p < 0.05) were higher for Diet MF than for Diet CS. Compared with Diet CS, feeding Diet MF increased the daily intake of total unsaturated fatty acids and the C18:0 and C18:3 contents (p < 0.01) in milk fat, whereas the total content of fatty acids <16C was decreased (p < 0.05). No influence on total saturated, monounsaturated and polyunsaturated fatty acids in milk was observed. The ratio of total unsaturated fatty acids in milk fat to its daily intake was substantially lower for Diet MF compared with Diet CS, suggesting that the high proportion of roughage resulted in a high rate of biohydrogenation in the rumen.