Piezoelectric enhanced sulfur doped graphdiyne nanozymes for synergistic ferroptosis-apoptosis anticancer therapy.

Graphdiyne has excellent potential due to its enzymatic properties. Metal-free sulfur-doped Graphdiyne (S-GDY) has piezoelectric characteristics, and ultrasonic excitation of S-GDY enhances peroxidase activity. It can turn hydrogen peroxide into toxic hydroxyl radicals and induce apoptosis in 4T1 cells. More importantly, the ultrasound (US) enhanced nanozyme induced 4T1 cell ferroptosis by promoting an imbalanced redox reaction due to glutathione depletion and glutathione peroxidase 4 inactivation. S-GDY exhibited enhanced nanozyme activity in vitro and in vivo that may directly trigger apoptosis-ferroptosis for effective tumor therapy. Altogether, this study was expected to provide new insights into the design of piezoelectric catalytic nanozyme and expand their application in the catalytic therapy of tumors.

Analysis of the Diagnostic Value of Transrectal Ultrasonography for Rectal Submucosal Lesions.

Objective: This study aims to investigate the diagnostic value of transrectal ultrasonography for rectal submucosal lesions. Methods: A retrospective analysis was conducted on 132 patients with rectal submucosal lesions admitted to our hospital from June 2018 to May 2022. All patients underwent colonoscopy, miniprobe endoscopic ultrasonography, and transrectal ultrasonography before surgery, obtaining definitive pathological results. The lesions displayed smooth morphological eminence of the mucosa under a colonoscope. Among the patients, there were 76 males and 56 females, with an average age of 50.6 years. Using pathology as the gold standard, the diagnostic accuracy of transrectal ultrasonography and miniprobe endoscopic ultrasonography for rectal submucosal lesions was calculated, and the difference between the two was compared using the chi-square (χ2) test. Results: The overall diagnostic accuracy of transrectal ultrasonography and miniprobe endoscopic ultrasonography for all rectal submucosal lesions was 95.5% and 74.2%, respectively. It was observed that transrectal ultrasonography was superior to miniprobe endoscopic ultrasonography, and the difference was statistically significant (χ2 = 25.48, P < .05). Conclusions: Transrectal ultrasonography demonstrates high diagnostic value for rectal submucosal lesions and may serve as the preferred choice for their examination.

Phosphatidylserine-exposing tumor-derived microparticles exacerbate coagulation and cancer cell transendothelial migration in triple-negative breast cancer.

Background: Neoadjuvant chemotherapy is relevant to the formation of thromboembolism and secondary neoplasms in triple-negative breast cancer (TNBC). Chemotherapy-induced breast cancer cell-derived microparticles (BCMPs) may have important thrombogenic and pro-metastatic effects on platelets and endothelium, which may be related to the expression and distribution of phosphatidylserine (PS). However, investigating these interactions is challenging due to technical limitations. Methods: A study was conducted in 20 healthy individuals and 18 patients who had been recently diagnosed with TNBC and were undergoing neoadjuvant chemotherapy with doxorubicin and cyclophosphamide. BCMPs were isolated from patient blood samples and doxorubicin-treated breast cancer cell lines. Their structure and morphology were studied by electron microscopy and antigen levels were measured by fluorescence-activated cell sorting. In an inhibition assay, isolated BCMPs were pretreated with lactadherin or tissue factor antibodies. Platelets isolated from healthy subjects were treated with BCMPs and coagulation time, fibrin formation, and expression of intrinsic/extrinsic factor Xase (FXa) and thrombin were evaluated. The effects of BCMPs on endothelial thrombogenicity and integrity were assessed by confocal microscopy, electron microscopy, measurement of intrinsic/extrinsic FXa, prothrombinase assay, and transwell permeability assay. Results: Neoadjuvant chemotherapy significantly increased the expression of PS+ BCMPs in patient plasma. Its expression was associated with a rapid increase in procoagulant activity. Treatment with lactadherin, a PS-binding scavenging molecule, markedly reduced the adhesion of BCMPs and abolished their procoagulant activity, but this was not observed with tissue factor antibody treatment. Intravenous injection of BCMPs in mice induced a significant hypercoagulable state, reducing the extent of plasma fibrinogen and promoting the appearance of new thrombus. Cancer cells incubated with doxorubicin released large numbers of PS+ BCMPs, which stimulated and transformed endothelial cells into a procoagulant phenotype and increased the aggregation and activation of platelets. Moreover, cancer cells exploited this BCMP-induced endothelial leakiness and showed promoted metastasis. Pretreatment with lactadherin increased uptake of both PS+ BCMPs and cancer cells by endothelial cells and limited the transendothelial migration of cancer cells. Conclusion: Lactadherin, a biosensor that we developed, was used to study the extracellular vesicle distribution of PS, which revealed a novel PS+ BCMPs administrative axis that initiated a local coagulation cascade and facilitated metastatic colonization of circulating cancer cells.

CD52 Is a Prognostic Biomarker and Associated With Tumor Microenvironment in Breast Cancer.

Tumor microenvironment (TME) plays an essential role in the development and metastasis of breast cancer (BC). More studies are needed on the differences and functions of immune components and matrix components. In this study, we calculated the proportion of tumor-infiltrating immune cells (TICs) and the proportion of immune and matrix components of BC patients from The Cancer Genome Atlas (TCGA). We performed Cox regression analysis and constructed protein-protein interaction (PPI) network based on the differentially expressed genes (DEGs) and obtained the most crucial gene CD52. CD52 significantly upregulated and affected the prognosis of BC patients. Gene set enrichment analysis (GSEA) suggested that the genes in the CD52 high-expression group were mainly enriched in immune-related pathways, while those in the CD52 low-expression group were mainly enriched in metabolic pathways. TICs analyses showed that there should be a positive correlation between CD52 expression and CD8+ T cells, activated memory CD4+ T cells, macrophage M1, and Gamma Delta T cells. It indicated that CD52 might be an essential factor in maintaining the immune-dominant position of TME. These results suggest that CD52 might be a potential biomarker for prognosis and provide a new therapeutic target for BC patients.

Fiber-modified adenovirus can mediate human adipose tissue-derived mesenchymal stem cell-based anti-angiogenic gene therapy.

A fiber-modified adenovirus (rAd5F11B), loaded with the Kringle1-5 gene (rAd-K1-5) was used to infect human adipose tissue-derived mesenchymal stem cells (HAMSCs). At a multiplicity of infection of 20, the transfection efficiency in HAMSCs was 90% and the cell expansion and differentiation of infected HAMSCs were not significantly suppressed. HAMSCs infected with rAd-K1-5 expressed the exogenous Kringle1-5 protein, an angiogenic inhibitor, and conditioned media from HAMSCs expressing the Kringle1-5 protein blocked VEGF-induced neovascularization both in vitro and in vivo. rAd5F11B may therefore be a promising gene transfer vector in HAMSCs-based anti-angiogenic gene therapy because of its low toxicity and high transfection efficiency.