Anhui University of Chinese Medicine

This study aimed to investigate noncoding RNA (ncRNA) expression changes in renal fibrosis (RF) models induced by three distinct etiologies using whole-transcriptome RNA sequencing, identify overlapping differentially expressed (DE) ncRNAs, construct core competing endogenous RNA (ceRNA) networks, and explore their role in RF.

Three RF rat models, 5/6 nephrectomy, adenine, and unilateral ureteral obstruction, were established. DE RNAs were identified through sequencing and validated by real-time quantitative polymerase chain reaction. ceRNA and RNA-binding protein (RBP) networks were visualized using Cytoscape. Core ceRNA axes were validated with dual-luciferase assay, RNA fluorescence in situ hybridization, western blot, immunofluorescence, and immunohistochemistry. Enrichment analysis was performed to explore potential functions.

Sequencing analysis revealed significant dysregulation of ncRNAs in all models compared to the normal group. Intersection analysis identified 215 mRNAs, 19 lncRNAs, and 247 circRNAs as overlapping DE RNAs. lncRNA-based ceRNA networks comprising 7 lncRNAs, 8 miRNAs, and 21 mRNAs, and circRNA-based networks comprising 13 circRNAs, 29 miRNAs, and 41 mRNAs were constructed. The TCONS_00008870/circRNA_3140-miR-466b-3p-Adamts2 axis was identified as a key regulatory pathway. Enrichment analysis showed significant pathways including Rap1 signaling, extracellular matrix-receptor interaction, and PI3K-Akt signaling, with RBPs enriched in RNA binding and ferroptosis.

By integrating data from three distinct models, we identified conserved ceRNA axis-TCONS_00008870/circRNA_3140-miR-466b-3p-Adamts2-potentially modulating fibrotic progression in renal tissue.

Ulcerative colitis (UC) is a chronic and easy-to-relapse intestinal disease characterized by colon inflammation and microbial dysbiosis. Candida albicans is the most common fungal resident in the human gut. Overgrowth of C. albicans has been linked to the aggravation of UC. Previously, we demonstrated that miR-32-5p was the most differentially expressed microRNA in DSS-induced colitis model supplemented with C. albicans and might be a potential target in the treatment of Candida colitis. However, the underlying pathogenic and therapeutic mechanisms remain unclear. Here, we firstly used the ITS technique to analyse intestinal mycobiota. The miR-32-5p adenovirus in company with extracted Candida cell wall β-glucan were then employed to monitor the impacts of miR-32-5p and fungal β-glucan on the severity of Candida colitis. Subsequently, gene silencing together with inhibitors of reactive oxygen species (ROS) and apoptosis was used to survey the modulation of miR-32-5p on macrophage polarization. According to these results, C. albicans became the dominant intestinal fungal species in Candida colitis model. Candida β-glucan could instruct miR-32-5p expression to affect the severity of Candida colitis in a concentration-dependent manner. Interestingly, high fungal β-glucan with pro-inflammatory effects hindered further increases in gut inflammation. Further analysis showed that overexpression of miR-32-5p could effectively inhibit inflammation and apoptosis and enhance phagocytosis and ROS production through Dectin-1 signalling in macrophages. A panel of representative gene expressions verified the polarization of the M2-like phenotype induced by miR-32-5p. Mechanistically, our results reveal the therapeutic potential of miR-32-5p in the amelioration of Candida colitis.

Acute lung injury (ALI) is a lung disease characterized by pulmonary edema caused by an excessive inflammatory response within the lungs and disruption of the alveolar capillary barrier, with a high morbidity and mortality rate in critically ill patients. Dry powder inhalers (DPI) are an effective way of administering medication to improve efficacy, and inhalation administration not only improves efficacy but also increases the bioavailability of the drug. Synephrine, a natural ingredient derived from the fruit of the citrus plant in the Brassicaceae family, has anti-inflammatory and antioxidant properties. In the present study, we prepared a synephrine dry powder inhaler (SYN-DPI) by anti-solvent precipitation method and evaluated it in vivo and in vitro. The in vitro results show that SYN-DPI has low hygroscopicity and good aerodynamic properties. The in vitro and in vivo efficacy results showed that SYN-DPI not only had low toxicity but also possessed good anti-inflammatory and antioxidant capacity, which could significantly reduce inflammation, oxidative stress, and lung injury. Pharmacokinetic results showed that inhalation administration significantly increased SYN bioavailability. In conclusion, this study provides inhalation administration of synephrine as an inhalable formulation that can be used to improve ALI.