Disulfidptosis, a novel form of programmed cell death characterized by cystine accumulation and disulfide stress, primarily affects metabolically active tumors like bladder cancer, which is often considered to be a highly metabolic and energy-consuming tumor. However, translating disulfidptosis induction into clinical practice face substantial obstacles, including the limited solubility of key inducers, insufficient cystine buildup within cells, and cellular mechanisms regulating the NADP+/NADPH equilibrium. To fully unlock the therapeutic potential of disulfidptosis, a promising solution has emerged in the form of nanotechnology combined with sonodynamic therapy (SDT). This study reports a novel approach that enhances disulfidptosis through SDT, simultaneously promoting immunogenic cell death (ICD) and improving the immunosuppressive tumor microenvironment. The system, SPCP/CCP@Bay, comprises a degradable sonodynamic-pseudo-conjugate-polymer (SPCP) and a cystine-containing polymer (CCP), loaded with Bay-876. Following intravenous administration, SPCP/CCP@Bay effectively accumulates at tumor sites. Under ultrasound radiation, SPCP/CCP@Bay effectively releases Bay-876, disrupts the intracellular redox balance, releases cystine from CCP, and induces disulfidptosis. Moreover, SPCP/CCP@Bay induces ICD and synergizes with PD-1 monoclonal antibodies (α-PD-1) to suppress tumor growth. This integrated strategy holds significant promise in reshaping the tumor microenvironment, converting "cold tumors" to "hot tumors", and advancing the field of cancer immunotherapy.
Rationale: P21-activated kinase 6 (PAK6) is a member of the class II PAKs family, which is a conserved family of serine/threonine kinases. Although the effects of PAK6 on many malignancies, especially in prostate cancer, have been studied for a long time, the role of PAK6 in mitochondria remains unknown.
Two new β-bergamotane sesquiterpenoids, E-β-trans-5,8,11-trihydroxybergamot-9-ene (1) and β-trans-2β,5,15-trihydroxybergamot-10-ene (2), were isolated from the marine-derived fungus Aspergillusfumigatus YK-7, along with three known terpenoids 3–5. Their structures were determined by spectroscopic methods (1D and 2D NMR, HR-ESI-MS). Antiproliferative effects on human leukemic monocyte lymphoma U937 and human prostate cancer PC-3 cell lines were measured in vitro. Compound 4 exhibited potent activity against the U937 cell line with an IC50 value of 4.2 μM.
Thousands of papers on primary aldosteronism (PA) have been published in the last two decades. This study aimed to evaluate the research hotspots and future trends in PA research using bibliometric analysis. A total of 2,365 PA research papers between 2000 and 2020 were included. The dominant position of the United States in global PA research throughout this 20-year period was evident, and it was also the country most frequently involved in international cooperation. The University of Padua was the most productive institution and a leader in research collaboration. The Journal of Clinical Endocrinology & Metabolism was the most productive journal in terms of the number of publications on PA. Further, Mulatero P, Reincke M, Beuschlein F and Wu VC all made significant contributions to PA research. Five hotspots have been identified: (1) metabolic syndrome associated with PA; (2) molecular mechanisms of PA; (3) adrenal adenoma and adrenal cortex; (4) hypertension associated with PA; and (5) clinical monitoring parameters and diagnosis in patients with PA. Our results suggest that the molecular mechanisms of PA will remain research hotspots in the future. International collaboration is also expected to widen and deepen in the field of PA research.
Aim: We aim to demonstrate that a surface-enhanced Raman spectroscopy (SERS) probe can be effectively used for protein detection in adrenal tumors. Materials & methods: The SERS probe method, which...
Bladder cancer (BC) is one of the most common malignancies in terms of incidence and recurrence worldwide. The aim of this study was to identify novel prognostic biomarkers related to BC progression utilizing weighted gene co-expression network analysis (WGCNA) and further bioinformatic analysis. First, we constructed a co-expression network by using WGCNA among 274 TCGA-BLCA patients and preliminarily screened out four genes (CORO1C, TMPRSS4, PIK3C2B, and ZNF692) associated with advanced clinical traits. In support, GSE19915 and specimens from 124 patients were used to validate the genes selected by WGCNA; then, CORO1C and TMPRSS4 were confirmed as hub genes with strong prognostic values in BC. Moreover, the result of gene set enrichment analysis (GSEA) and gene set variation analysis (GSVA) indicated that CORO1C and TMPRSS4 might be involved in the process of epithelial to mesenchymal transition (EMT) reversely. In addition, high expression of CORO1C was found to be significantly correlated with tumor-infiltrating neutrophils (TINs), a negative regulatory component that facilitates tumor distant progression and induces poor clinical outcome. In conclusion, our study first identified CORO1C and TMPRSS4 as vital regulators in the process of tumor progression through influencing EMT and could be developed to effective prognostic and therapeutic targets in future BC treatment.