MaiJiTong granule attenuates atherosclerosis by reducing ferroptosis via activating STAT6-mediated inhibition of DMT1 and SOCS1/p53 pathways in LDLR-/- mice.

BACKGROUND AND PURPOSE: Atherosclerosis is the primary pathological basis of cardiovascular disease. Ferroptosis is a regulated form of cell death, a process of lipid peroxidation driven by iron, which can initiate and promote atherosclerosis. STAT6 is a signal transducer that shows a potential role in regulating ferroptosis, but, the exact role in ferroptosis during atherogenesis remains unclear. The Traditional Chinese Medicine Maijitong granule (MJT) is used for treating cardiovascular disease and shows a potential inhibitory effect on ferroptosis. However, the antiatherogenic effect and the underlying mechanism remain unclear. In this study, we determined the role of STAT6 in ferroptosis during atherogenesis, investigated the antiatherogenic effect of MJT, and determined whether its antiatherogenic effect was dependent on the inhibition of ferroptosis. METHODS: 8-week-old male LDLR-/- mice were fed a high-fat diet (HFD) at 1st and 10th week, respectively, to assess the preventive and therapeutic effects of MJT on atherosclerosis and ferroptosis. Simultaneously, the anti-ferroptotic effects and mechanism of MJT were determined by evaluating the expression of genes responsible for lipid peroxidation and iron metabolism. Subsequently, we reanalyzed microarray data in the GSE28117 obtained from cells after STAT6 knockdown or overexpression and analyzed the correlation between STAT6 and ferroptosis. Finally, the STAT6-/- mice were fed HFD and injected with AAV-PCSK9 to validate the role of STAT6 in ferroptosis during atherogenesis and revealed the antiatherogenic and anti-ferroptotic effect of MJT. RESULTS: MJT attenuated atherosclerosis by reducing plaque lesion area and enhancing plaque stability in both preventive and therapeutic groups. MJT reduced inflammation via suppressing inflammatory cytokines and inhibited foam cell formation by lowering the LDL level and promoting ABCA1/G1-mediated lipid efflux. MJT ameliorated the ferroptosis by reducing lipid peroxidation and iron dysregulation during atherogenesis. Mechanistically, STAT6 negatively regulated ferroptosis by transcriptionally suppressing SOCS1/p53 and DMT1 pathways. MJT suppressed the DMT1 and SOCS1/p53 via stimulating STAT6 phosphorylation. In addition, STAT6 knockout exacerbated atherosclerosis and ferroptosis, which abolished the antiatherogenic and anti-ferroptotic effects of MJT. CONCLUSION: STAT6 acts as a negative regulator of ferroptosis and atherosclerosis via transcriptionally suppressing DMT1 and SOCS1 expression and MJT attenuates atherosclerosis and ferroptosis by activating the STAT6-mediated inhibition of DMT1 and SOCS1/p53 pathways, which indicated that STAT6 acts a novel promising therapeutic target to ameliorate atherosclerosis by inhibiting ferroptosis and MJT can serve as a new therapy for atherosclerosis treatment.

A systematic review and meta-analysis of efficacy and safety comparing greenlight laser vaporization with transurethral resection of the prostate for benign prostatic hyperplasia with prostate volume less than 80 ml.

We conducted a meta-analysis to evaluate the efficacy and safety of photo selective vaporisation of the prostate (PVP) with the GreenLight Laser versus transurethral resection of the prostate (TURP) for the treatment of small-volume benign prostatic hyperplasia (BPH). As of July 2022, relevant literature in online databases such as Cochrane Library, PubMed, and Embase was searched, including studies published on or before that date, and there were 9 studies in total, including 5 RCTs and 4 non-RCTs. In total 1525 patients were included to compare the efficacy of PVP and TURP in treating BPH. The Cochrane Collaboration criteria were used to evaluate the risk of bias. The software was used for random effect meta-analysis with RevMan 5.3. Data extraction included: clinical baseline characteristics, perioperative parameters, complication rates, International Prostate Symptom Score (IPSS), prostate specific antigen (PSA), post-void residual urine (PVR), maximum flow rate (Qmax), and quality of life (QoL). The pooled analysis showed that PVP was associated with reduced blood loss, blood transfusion, clot retention, catheterization time, definitive catheter removal, and hospital stay, but was associated with longer operative time and more severe dysuria (all p < 0.05). The results of this meta-analysis show that PVP as a technique for the treatment of benign prostatic hyperplasia with a volume of less than 80 cc has similar efficacy to standard TURP in IPSS, PSA, PVR, Qmax and QoL, and is an effective alternative. It outperformed TURP in terms of blood transfusion, catheterization time and hospital stay, while TURP is superior to PVP in terms of operation time.