Shandong University of Traditional Chinese Medicene

To investigate the mechanism by which cinnamaldehyde (CA) alleviates pulmonary arterial hypertension (PAH) through the TLR4/NF-kB/HIF-1a pathway.

PAH was induced in rats via SU5416 injection and hypoxia. Hemodynamics (RVMP, RVSP, mPAP) were measured. Histological changes were assessed by HE staining, and protein expressions of α-SMA, Col I, TLR4, p-p65, p65, and HIF-1a were detected by western blot. In vitro, hypoxia-induced HPAECs were treated with CA and TLR4 activator RS09TFA. Cell function was assessed by CCK-8, colony formation, and scratch assays, with VE-Cadherin and α-SMA expression analyzed by western blot.

PAH rats showed increased RVMP, RVSP, mPAP, and pulmonary artery thickening. CA significantly alleviated lung damage and reduced α-SMA and Col I expression. TLR4/NF-kB/HIF-1a activation with RS09TFA inhibited CA's effects. In vitro, CA mitigated hypoxia-induced HPAEC dysfunction, restoring VE-Cadherin and α-SMA expression, while RS09TFA blocked these effects.

CA alleviates PAH by inhibiting the TLR4/NF-kB/HIF-1a pathway and suppressing vascular remodeling, suggesting its potential as a therapeutic agent for PAH.

Macrophages play a vital role in the inflammation and repair processes of ischemia/reperfusion-induced acute kidney injury (IR-AKI). The mechanosensitive ion channel Piezo1 is significant in these inflammatory processes. However, the exact role of macrophage Piezo1 in IR-AKI is unknown. The main purpose of this study was to determine the role of macrophage Piezo1 in the injury and repair process in IR-AKI. Genetically modified mice with targeted knockout of Piezo1 in myeloid cells were established, and acute kidney injury was induced by bilateral renal vascular clamping surgery. Additionally, hypoxia treatment was performed on bone marrow-derived macrophages in vitro. Our data indicate that Piezo1 is upregulated in renal macrophages in mice with IR-AKI. Myeloid Piezo1 knockout provided protective effects in mice with IR-AKI. Mechanistically, the regulatory effects of Piezo1 on macrophages are at least partially linked to calpain signaling. Piezo1 activates Ca²⁺-dependent calpain signaling, which critically upregulates HIF-1α signaling. This key pathway subsequently influences the Notch and CCL2/CCR2 pathways, driving the polarization of M1 macrophages. In conclusion, our findings elucidate the biological functions of Piezo1 in renal macrophages, underscoring its role as a crucial mediator of acute kidney injury. Consequently, the genetic or pharmacological inhibition of Piezo1 presents a promising strategy for treating IR-AKI.

Systemic lupus erythematosus (SLE) is an autoimmune disease with complex clinical manifestations and no current cure. Alternative splicing (AS) plays a key role in SLE by regulating immune-related genes, but its genome-wide regulatory mechanisms remain unclear. To investigate the involvement of abnormal splicing regulators and AS events in the immune regulation of SLE. Transcriptome data from the SLE dataset GSE162828 were analyzed for differential gene expression and AS events using bioinformatics tools. Immune infiltration analysis was conducted with CIBERSORT, and co-expression of key splicing factors (SFs) and AS events was assessed using SUVA software. A total of 5144 differentially expressed genes and 73 SFs were identified. Significant immune cell differences were observed between SLE and controls, highlighting SFs such as HNRNPDL, RBM47, TIA1, SSB, and DHX15. Eighty-three AS events were identified, with IRF9 and PTPRC emerging as key regulatory events linked to SLE. Dysregulated SFs influence AS in immune-related genes, affecting immune cell composition and SLE progression. These findings offer potential new therapeutic targets for modulating the immune microenvironment in SLE.