Cardiotoxicity has been well documented as a side effect of cisplatin (CDDP) treatment. The inflammatory response plays a crucial role in the pathological process of CDDP-induced cardiotoxicity. Wogonin is a natural flavonoid compound that possesses cardioprotective and anti-inflammatory qualities. Knowledge of the pharmacological effect and mechanism of wogonin could reveal an efficient way to identify therapeutic strategies. In this study, the potential of wogonin to antagonize CDDP-induced cardiotoxicity was evaluated in C57BL/6 mice in vivo and in H9c2 cells in vitro. The results showed that wogonin protected against CDDP-induced cardiac dysfunction, myocardial injury, and pyroptosis in vivo. Using a Gasdermin D expression plasmid, we revealed that wogonin dramatically reduced CDDP-induced pyroptosis by modulating the Gasdermin D protein in H9c2 cells. In conclusion, wogonin has great potential in attenuating CDDP-induced cardiotoxicity. In addition, greater emphasis should be placed on the antipyroptotic effects of wogonin for the treatment of other diseases.

Heart failure with preserved ejection fraction (HFpEF) is a clinically diverse disease characterized by intricate pathophysiological pathways, for which effective treatment options remain limited. Aberrant activation of the mineralocorticoid receptor (MR) significantly contributes to the development and progression of HFpEF. Finerenone, an innovative non-steroidal mineralocorticoid receptor antagonists (MRAs), has enhanced MR selectivity, more potent anti-fibrotic and anti-inflammatory effects, and improved safety relative to conventional steroidal MRAs like spironolactone and eplerenone. Therefore, future large-scale phase III head-to-head randomized controlled trials comparing finerenone and spironolactone in the HFpEF population, with cardiovascular outcomes as the primary endpoint, will be crucial. In preclinical models, finerenone has demonstrated improvement in multiple pathophysiological parameters of HFpEF. The FIDELIO-DKD and FIGARO-DKD trials in individuals with chronic kidney disease (CKD) and type 2 diabetes mellitus (T2DM) initially demonstrated finerenone’s cardiorenal advantages, including substantial decreases in cardiovascular events and the risk of renal function decline. The FINEARTS-HF trial has expanded this data to patients with HFmrEF/HFpEF, showing a significant decrease in the incidence of total worsening HF events and mortality from cardiovascular causes. Additionally, the potential for combining finerenone with sodium-glucose cotransporter-2 inhibitors (SGLT2is) or glucagon-like peptide-1 receptor agonists (GLP-1 RAs) is gaining attention. Current trials, including REDEFINE-HF, CONFIRMATION-HF, and FINALITY-HF, are examining its effectiveness across various HF phenotypes. These research will elucidate finerenone’s function in the management of cardiometabolic disorders. This review focuses on the clinical evidence of finerenone in patients with HFpEF and concomitant CKD, along with its potential cardiorenal protective mechanisms. It aims to provide new evidence-based medical evidence and theoretical support for the clinical management of HFpEF patients.

Introduction: Pancreatic ductal adenocarcinoma (PDAC) is one of the most lethal malignancies, characterized by dense desmoplastic stroma, metabolic reprogramming, and poor therapeutic response. Stromal desmoplasia limits drug penetration, while glycolytic adaptation supports tumor progression. Effective strategies that simultaneously target stromal barriers and tumor metabolism are urgently needed. Methods: To overcome these challenges, we developed a dual-targeted, pH-responsive nanoplatform (PLA–THF–PEG/AV3/KH3 nanoparticles, termed AKNPs) that co-delivers AV3, a peptide antagonist of integrin α5 (ITGA5), and KH3, an allosteric inhibitor of phosphoglycerate mutase 1 (PGAM1). AKNPs were prepared by self-assembly and characterized for morphology, colloidal stability, and pH-triggered disassembly under acidic conditions mimicking tumor and endo/lysosomal environments. In vitro and in vivo therapeutic evaluations were performed using PANC-1 models. Results: AKNPs exhibited uniform spherical morphology, excellent colloidal stability, and pH-sensitive disassembly. In vitro, AKNPs showed superior cytotoxicity in PANC-1 cells compared with free AV3 or AV3+KH3, accompanied by downregulation of fibrosis markers (α-SMA, COL1A1), metabolic regulator PGAM1, ITGA5, and immune checkpoint PD-L1, indicating combined stromal-remodeling and immunomodulatory effects. In vivo, in a PANC-1 xenograft model, AKNPs significantly inhibited tumor growth compared with PBS, AV3, or AV3+KH3. Tumor volumes and weights were reduced, and histological analyses revealed decreased fibrosis, lower tumor density, and enhanced necrosis. Western blot analysis of tumor tissues confirmed suppression of α-SMA, COL1A1, ITGA5, PGAM1, and PD-L1. Discussion: These findings demonstrate that pH-sensitive AKNPs integrate stromal remodeling and metabolic inhibition to synergistically suppress PDAC progression. This nanoplatform provides a promising therapeutic strategy for overcoming stromal and metabolic barriers in pancreatic cancer and may serve as a foundation for future combination regimens.

Pancreatic cancer (PC) is a highly aggressive cancer with poor clinical outcomes. F-box only protein 22 (FBXO22), as an integral part of the SCF E3 ubiquitin ligase complex, has been associated with various cancers, but its role in PC remains underexplored. FBXO22 expression in pancreatic cancer tissues and adjacent normal tissues was analyzed by bioinformatics and validated using quantitative real-time PCR (qPCR). Functional assays, including proliferation, invasion, and apoptosis analyses, were conducted in pancreatic cancer cell lines following FBXO22 overexpression or knockdown. Mass spectrometry-based proteomic profiling was performed to identify potential ubiquitination targets of FBXO22. The interaction between FBXO22 and candidate targets was confirmed by co-immunoprecipitation, western blotting, and ubiquitination assays. The in vivo role of FBXO22 in pancreatic tumor progression was further evaluated using a xenograft model in BALB/c nude mice. FBXO22 was significantly overexpressed in pancreatic cancer tissues compared to adjacent normal tissues. FBXO22 overexpression enhanced pancreatic cancer cell proliferation and invasion, whereas its knockdown suppressed these oncogenic properties. Mass spectrometry identified KLF10 as a potential substrate of FBXO22-mediated ubiquitination. Further experiments confirmed that FBXO22 promotes KLF10 degradation via the ubiquitin-proteasome pathway. Overexpression of KLF10 suppressed pancreatic cancer cell proliferation and induced apoptosis through the TGF-β signaling pathway. In vivo, FBXO22 knockdown significantly inhibited pancreatic tumor growth and increased KLF10 expression. FBXO22 promotes pancreatic cancer progression by mediating KLF10 ubiquitination and degradation, thereby impairing its tumor-suppressive functions. FBXO22 may serve as a potential oncogenic and therapeutic target associated with pancreatic cancer progression.

Background: Cancer of unknown primary (CUP) represents a heterogeneous group of metastatic malignancies in which the primary site remains unidentified despite comprehensive clinical, laboratory, radiological, and pathological evaluation. CUP is generally characterized by aggressive biological behavior, poor prognosis, and the absence of standardized treatment strategies. Tumor-associated blood eosinophilia (TABE) is relatively uncommon and typically occurs after tumor dissemination, often indicating an unfavorable prognosis. SMARCB1 (INI-1) is a core subunit of the switch/sucrose non-fermentable (SWI/SNF) chromatin remodeling complex, and its functional loss can drive tumorigenesis through epigenetic dysregulation. However, cases of SMARCB1-deficient carcinoma presenting as CUP with marked TABE are exceedingly rare, posing significant diagnostic and therapeutic challenges. Case report: A 71-year-old man presented with a painless mass in the left side of the neck accompanied by generalized pruritus. Laboratory evaluation revealed persistent peripheral blood eosinophilia, and imaging studies demonstrated multiple enlarged lymph nodes in the left supraclavicular region and abdominal cavity. Histopathological examination of a lymph node biopsy showed poorly differentiated carcinoma. Immunohistochemistry revealed loss of nuclear SMARCB1 expression. A final diagnosis of SMARCB1-deficient undifferentiated carcinoma was established, and comprehensive systemic evaluation failed to identify a primary tumor. The patient received paclitaxel combined with cisplatin and a programmed cell death protein 1 (PD-1) inhibitor. Immunotherapy was discontinued due to the development of immune-related cutaneous adverse events. Despite subsequent management, the disease progressed rapidly, with the development of brainstem metastasis, and the patient ultimately died. Conclusion: We report a case of SMARCB1-deficient undifferentiated carcinoma presenting as CUP, predominantly with cervical lymph node metastases, accompanied by marked TABE. The benefit of current empirical treatment strategies appears limited. Future prospective clinical studies targeting the epigenetic vulnerabilities of this entity are warranted to improve patient outcomes.