Therapeutic Effects of Salvianolic Acid B on Angiotensin II-Induced Atrial Fibrosis by Regulating Atrium Metabolism via Targeting AMPK/FoxO1/miR-148a-3p Axis.

The present study highlights the effects of salvianolic acid B (Sal B) on angiotensin II (Ang II)-activated atrial fibroblasts as well as the associated potential mechanism from the metabonomics perspective. Metabolic profile analysis performed an optimal separation of the Ang II and control group, indicating a recovery impact of Sal B on Ang II-activated fibroblasts (FBs). We found that metabolite levels in the Ang II + Sal B group were reversed to normal. Moreover, 23 significant metabolites were identified. Metabolic network analysis indicated that these metabolites participated in purine metabolism and FoxO signaling pathway. We found that Sal B activated AMP-activated protein kinase (AMPK) phosphorylation, which further promoted FoxO1 activation and increased miR-148a-3p level. We further verified that Sal B modulate the abnormal AMP, phosphocreatine, glutathione (GSH), and reactive oxygen species (ROS) production in Ang II-stimulated FBs. Collectively, Sal B can protect the Ang II-activated FBs from fibrosis and oxidative stress via AMPK/FoxO1/miRNA-148a-3p axis.

Mesenchymal Stem Cell-Derived Exosomes Ameliorate Delayed Neurocognitive Recovery in Aged Mice by Inhibiting Hippocampus Ferroptosis via Activating SIRT1/Nrf2/HO-1 Signaling Pathway.

Delayed neurocognitive recovery (dNCR) is a prevalent perioperative neurological complication in older patients and has common characteristics such as acute cognitive dysfunction, impaired memory, and inattention. Mesenchymal stem cell-derived exosomes (MSCs-Exo) are enclosed by a lipid bilayer contain proteins, DNA, miRNA, and other components, which are important mediators of intercellular communication. It has been reported that exosomes could play an important role in the treatment of neurodegenerative diseases, nerve injury, and other neurological diseases. In this study, we examined the effects of MSCs-Exo on dNCR aged mice after exploratory laparotomy and evaluated their potential regulatory mechanisms. We found that MSCs-Exo treatment ameliorated cognitive impairment in dNCR aged mice. MSCs-Exo inhibit hippocampus ferroptosis and increase the expression of silent information regulator 1 (SIRT1), factor nuclear factor-erythroid 2-related factor 2 (Nrf2), and heme oxygenase-1 (HO-1) in dNCR aged mice. Interestingly, the above effects of MSCs-Exo on dNCR aged mice were abolished by SIRT1 selective inhibitor EX-527. In conclusion, these findings indicated that MSCs-Exo can ameliorate cognitive impairment by inhibiting hippocampus ferroptosis in dNCR aged mice via activating SIRT1/Nrf2/HO-1 signaling pathway, providing a potential avenue for the treatment of dNCR.

Macrophages-targeting mannosylated nanoparticles based on inulin for the treatment of inflammatory bowel disease (IBD).

In the present experimental series, we have developed a novel nanocomposite to target activated macrophages in the colon with real time imaging and therapeutic capabilities. This binary nanocomposite was formed by the covalent conjugation of mannosylated NPs (Man-NPs) with carbon dots (CDs). Man-NPs were prepared using a self-assembly method based on mannosylated decamethylenediamine-grafted carboxymethyl inulin amphiphilic acid. While, the CDs were synthesized using a simple bottom-up process using citric acid monohydrate and diethylenetriamine, which were tightly bonded to the Man-NPs surface by carbodimide coupling. The resulting nanocomposite had a uniform size of 241.3 nm with a negative charge and a high drug casing density of 25.54 wt% and blue self-fluorescence were emitted. Whereas, in vitro observation of cellular uptake indicated the greater nanocomposite uptake in inflamed macrophage as compared to the untreated macrophage and mannose receptor-negative cell lines, 4T1 respectively. However, in vivo bio distribution exhibited a large number (60%) of CDs/Man-NPs nanocomposite accumulated in the inflamed colon of colitis mice. It should be noted that the novel nanocomposite, as macrophage-targeted drug delivery, could have promise for the treatment of inflammatory bowel disease (IBD).