Yan Tao

Background: Transforming growth factor beta regulator 4 (TBRG4), regulates mitochondrial RNA processing. TBRG4 has been implicated in the progression of several malignancies, but its biological function and clinical relevance in prostate cancer remain unclear. Methods: Publicly available data from The Cancer Genome Atlas prostate adenocarcinoma cohort and three Gene Expression Omnibus cohorts were analyzed. Differential expression was assessed independently in TCGA-PRAD, GSE88808, GSE46602, and GSE70768. Progression-free survival (PFS) was evaluated in TCGA-PRAD. External PFS analyses were conducted in GSE70768 and GSE46602 using the publicly available biochemical-recurrence status and corresponding follow-up time. Gain- and loss-of-function experiments were performed in PC3 and DU145 cells, which showed the highest baseline TBRG4 expression among the tested prostate cancer cell lines. A PC3 subcutaneous xenograft was used for in vivo validation. Results: TBRG4 was upregulated in the analyzed PCa cohorts and cell lines and was associated with higher Gleason score, prostate-specific antigen level, and pathologic T category. High TBRG4 expression was associated with shorter PFS in TCGA-PRAD in univariable analysis [hazard ratio (HR), 2.138; 95% confidence interval (CI), 1.180–3.872; P = 0.012], but not after multivariable adjustment (HR, 1.411; 95% CI, 0.771–2.582; P = 0.264). TBRG4 overexpression increased colony formation, migration, invasion, and wound closure and was accompanied by decreased E-cadherin and increased N-cadherin and vimentin expression. TBRG4 knockdown produced the opposite effects. High TBRG4 expression was associated with phosphatidylinositol 3-kinase/protein kinase B/mechanistic target of rapamycin pathway enrichment, and TBRG4 manipulation was accompanied by changes in pathway-protein phosphorylation. TBRG4 knockdown also reduced PC3 xenograft growth. Conclusions: TBRG4 is upregulated across the evaluated prostate cancer cohorts and is associated with adverse clinicopathological features in TCGA-PRAD. Functionally, TBRG4 supports tumor growth and invasive phenotypes, accompanied by changes in PI3K/AKT/mTOR signaling. Associations between TBRG4 expression and progression-free survival were observed in selected cohorts, suggesting that TBRG4 may represent a prognostic factor in prostate cancer.

Objective: Endometrial cancer (EC) remains a significant clinical challenge, particularly for patients with advanced or recurrent disease. This study aims to investigate the effects of Sanguinarine Chloride (S.C), a natural benzophenanthridine alkaloid with broad anti-tumor properties, on EC cell growth and invasion, and to elucidate its underlying molecular mechanisms. Methods: S.C’s effects on EC cell viability, proliferation, invasion, and apoptosis were evaluated using CCK-8, EdU, colony formation, 3D matrigel drop assay, FACS and Western blotting (WB). To evaluate its effects on ferroptosis, malondialdehyde (MDA) assay kits, DCFH-DA and the C11 BODIPY581/591 probe, were employed. The molecular mechanisms through which S.C regulates FTO-ACSL4 axis were investigated using plasmid transfection and WB. Additionally, a mouse xenograft model derived from EC cells was established to evaluate the in vivo effects of S.C and its molecular mechanisms, utilizing hematoxylin and eosin (H&E) staining, immunohistochemistry (IHC) and WB. Results: S.C significantly inhibited EC cell growth and invasion. It induced cell death primarily through ferroptosis, as inhibitors (Ferrostatin-1, Deferoxamine) reversed this effect. S.C downregulated the RNA demethylase FTO, leading to increased ACSL4 expression, enhanced lipid peroxidation, suppression of the NRF2-GPX4 axis, and activated NCOA4-mediated ferritinophagy. Knocking down or pharmacologically inhibiting ACSL4 reduced S.C-induced ferroptosis. Furthermore, in a murine xenograft model, S.C significantly suppressed tumor growth, which was associated with consistent alterations in these ferroptosis-related markers in vivo. Conclusions: Our findings reveal that S.C triggers ferroptosis in EC via the novel FTO-ACSL4 axis, highlighting its potential as a therapeutic agent and identifying the FTO-ACSL4 pathway as a promising target for endometrial cancer treatment.

The relative benefits of single-port (SP) versus multi-port (MP) robot-assisted radical prostatectomy (RARP) for prostate cancer remain uncertain, with conflicting evidence reported in the literature. This systematic review aimed to compare perioperative outcome metrics, oncologic efficacy, and functional recovery outcomes between SP-RARP and MP-RARP. A thorough literature search was conducted using PubMed, Embase, Web of Science, and the Cochrane Library to locate English-language research published until June 2025. All statistical analyses, encompassing meta-analyses, were performed utilizing R software (version 4.3.1). Weighted mean differences (WMDs) and 95% CIs were used to summarize continuous outcomes, while odds ratios (ORs) with 95% CIs were computed for dichotomous variables. Statistical significance was established at P < 0.05. The review protocol was registered prospectively in PROSPERO (CRD420251114408). A total of 15 studies involving 3,116 patients (SP-RARP: 1,525; MP-RARP: 1,591) were included. Patients undergoing SP-RARP experienced significantly lower estimated blood loss (WMD –41.36 (–68.79, –13.94); P = 0.003), shorter hospital stays (SMD –0.95 (–1.77, –0.13); P = 0.02), and earlier urinary catheter removal (WMD –1.77 (–2.88, –0.66); P = 0.002) compared with those receiving MP-RARP. SP-RARP was also associated with lower pain scores on the day of surgery (WMD –0.88 (–1.29, –0.48); P < 0.001) and reduced opioid use during hospitalization (OR 0.35 (0.22, 0.54); P < 0.001) and at discharge (OR 0.03 (0.01, 0.10); P < 0.001). Nonetheless, for functional outcomes related to potency and continence, along with perioperative complications, positive surgical margins, biochemical recurrence, and duration of surgery, no statistically significant differences were seen between the groups. SP-RARP offers advantages in reducing intraoperative blood loss, accelerating recovery, and improving postoperative pain control compared to MP-RARP. Although operative time is longer, both approaches provide comparable oncological and functional outcomes.

Acute kidney injury (AKI) is a common side effect of the chemotherapy agent cisplatin, and ferroptosis serves as the primary mechanism underlying cell death in renal tubular epithelium in such cases. Salvianolic acid B (SAB), a compound derived from Salvia miltiorrhiza , has demonstrated promising anti‐inflammatory and antioxidant properties. However, its impact on ferroptosis in the context of AKI remains to be fully explored. In this study, we utilized cisplatin‐induced and folic acid‐induced AKI models to investigate the protective mechanisms of SAB on renal tissue and tubular epithelial cell injury. The impact of SAB on renal cell ferroptosis was thoroughly examined and confirmed in both AKI models. To predict the potential mechanism through which SAB regulates ferroptosis, we employed an online target prediction database and subsequently verified the specific target proteins involved. Furthermore, we used drug affinity responsive target stability (DARTS), cellular thermal shift assay (CETSA) and molecular docking techniques to assess the binding capacity of SAB to the target protein. Our results reveal that SAB alleviated cisplatin‐ and folic acid‐induced renal dysfunction in vivo and improved cisplatin‐induced HK‐2 cell injury. Mechanistically, SAB targeted and bound to PRDX5, enhancing its redox activity, which in turn potentiated the inhibitory effect of SLC7A11 and GPX4 on cisplatin‐induced ferroptosis. Silencing PRDX5 in HK‐2 cells could partially abrogate the protective effect of SAB. These results provide strong evidence for the potential of SAB in the treatment of AKI.

Background: Prostate cancer is a major global health challenge, characterized by high morbidity and mortality rates. Traditional treatment options, including androgen deprivation therapy and chemotherapy, often lead to drug resistance. In recent years, natural compounds have garnered attention for their potential therapeutic effects. Evodiamine, a bioactive alkaloid from Evodia rutaecarpa, has demonstrated promising anti-cancer properties in various malignancies, including oral squamous cell carcinoma, breast, colorectal, and ovarian cancers. This study explores the efficacy of evodiamine in prostate cancer cells and investigates the mechanisms underlying evodiamine-induced cell death. Methods: To investigate the effects of evodiamine on prostate cancer cells, various cell lines, including both castration-sensitive and castration-resistant variants, were treated with different concentrations of evodiamine for various durations. Cell viability, proliferation, invasion ability, and colony formation were assessed using the CCK8 assay, EdU assay, 3D matrigel drop invasion assay, and colony formation assay, respectively. The effects of evodiamine on apoptosis were analyzed using FACS, Hoechst staining, and Western blot. To evaluate its effects on ferroptosis, malondialdehyde (MDA) and glutathione (GSH) assay kits, as well as DCFH-DA and the lipid peroxidation sensor BODIPY^™ 581/501 C11 fluorescent probes, were employed. The molecular mechanisms through which evodiamine regulates GPX4 protein instability were investigated using Western blot and TRIM26 ectopic expression. Additionally, a mouse xenograft model derived from DU145 cells was established to evaluate the in vivo effects of evodiamine and its molecular mechanisms, utilizing hematoxylin and eosin (H&E) staining, immunohistochemistry (IHC), and Western blot analysis. Results: Evodiamine significantly suppressed cell viability, proliferation, invasion, and colony formation in prostate cancer cells. Importantly, evodiamine-induced cell death in the PC3 and DU145 cell lines was independent of apoptosis pathway. Instead, evodiamine increased reactive oxygen species (ROS) production, lipid ROS levels and MDA levels, while decreasing GSH levels, indicating the induction of ferroptosis. The key role of ROS in evodiamine-induced ferroptosis was further confirmed by the partial reversal of cell death upon treatment with the ROS scavenger N-acetylcysteine (NAC). Mechanistically, evodiamine induced ferroptosis by destabilizing GPX4 protein in a TRIM26-dependent manner. Moreover, in vivo studies demonstrated that evodiamine significantly inhibited tumor growth and induced ferroptosis in tumor cells, highlighting its therapeutic potential. Conclusion: This study demonstrates that evodiamine exerts potent antitumor effects against prostate cancer through inhibiting TRIM26-mediated stabilization of GPX4 protein and triggering ferroptosis. These findings suggest that evodiamine, a natural product derived from traditional Chinese medicine, could be a promising therapeutic agent for prostate cancer. Graphical