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Immune checkpoint inhibitors (ICIs) offer promise in breaking through the treatment and survival dilemma of triple-negative breast cancer (TNBC), yet only immunomodulatory subtype and ≈5% TNBC patients respond as monotherapy due to lack of effector immune cells (internal problem) and physical barrier (external limitation) formed by cancer-associated fibroblasts (CAFs). A hydrogel drug-delivery platform, ALG@TBP-2/Pt(0)/nintedanib (ALG@TPN), is designed to induce strong immune functions and the dual elimination of the internal and external tumor microenvironment (TME). Activated by white light, through type I and II photodynamic therapy (PDT), TBP-2 generates large amounts of reactive oxygen species (ROS) intracellularly, oxidizing mitochondrial DNA (mtDNA). The unique catalase activity of Pt(0) converts endogenous H2O2 to O2, reducing the anoxia-limiting PDT and enhancing ROS generation efficacy. Abundant ROS can oxidize Pt(0) to cytotoxic Pt(II), damaging the nuclear DNA (nDNA). Dual damage to mtDNA and nDNA might bi-directionally activate the cGAS/STING pathway and enhance the immune cell response. Besides, nintedanib demonstrates a significant inhibitory effect on CAFs, weakening the immune barrier and deepening immune cell infiltration. Overall, the study provides a self-oxygenating hydrogel with the "PDT/chemotherapy/anti-CAFs" effect, triggering the cGAS/STING pathway to reshape the TME. Both internal and external interventions increase anti-TNBC immune responses.
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Introduction: Cancer represents a significant global public health concern. In recent years, the incidence of cancer has been on the rise worldwide due to various factors, including diet, environment, and an aging population. Simultaneously, advancements in tumor molecular biology and genomics have led to a shift from systemic chemotherapy focused on disease sites and morphopathology towards precise targeted therapy for driver gene mutations. Therefore, we propose a comprehensive review aimed at exploring the research hotspots and directions in the field of Kirsten rat sarcoma viral oncogene homolog (KRAS)-mutant cancers over the past decade, providing valuable insights for cancer treatment strategies. Specifically, we aim to present an intellectual landscape using data obtained from the Web of Science (WoS) regarding KRAS mutation. Methods: Bibliometrix, VOSviewer, CiteSpace, and HistCite were employed to conduct scientometric analyses on national publications, influential authors, highly cited articles, frequent keywords, etc. Results: A total of 16,609 publications met the screening criteria and exhibited a consistent annual growth trend overall. Among 102 countries/regions, the United States occupied the vast majority share of the published volume. The journal Oncotarget had the highest circulation among all scientific publications. Moreover, the most seminal articles in this field primarily focus on biology and targeted therapies, with overcoming drug resistance being identified as a future research direction. Conclusion: The findings of the thematic analysis indicate that KRAS mutation in lung cancer, the prognosis following B-Raf proto-oncogene, serine/threonine kinase (BRAF) or rat sarcoma (RAS) mutations, and anti-epidermal growth factor receptor (EGFR)-related lung cancer are the significant hotspots in the given field. Considering the significant advancements made in direct targeting drugs like sotorasib, it is anticipated that interest in cancers associated with KRAS mutations will remain steadfast.
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Pumpkin seed oil (PSO), a rich source of nutrients, is extracted from the seeds of different pumpkin varieties for food and medicines. This article aims to provide an evidence-based review of the literature and to explore the extraction technologies, nutritional properties, and biological activity of PSO. From previous literature, PSO contains a large proportion of unsaturated fatty acids, with linoleic acid as the main component, and an amount of tocopherol, phytosterol, and phenolic acids. Some differences in the yield, composition, and physicochemical properties of PSO can be associated with the pumpkin's cultivars and the extraction methods. Some novel technologies involved in supercritical fluid extraction, enzyme-assisted aqueous extraction, and ultrasound-assisted extraction have been replacing the conventional technologies gradually as promising methods for the safe, non-polluting, and effective recovery of PSO. This healthy vegetable oil was reported by several in vitro and in vivo studies to have potential protective roles in oxidative stress, inflammation, cancer, and cardiovascular diseases. © 2023 Society of Chemical Industry.
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Cucurbita , Cucurbita/química , Ácidos Grasos/química , Tocoferoles/análisis , Antioxidantes/química , Semillas/química , Aceites de Plantas/químicaRESUMEN
In order to study the effects and mechanism of Monascus on the quality of hairtail surimi, high-throughput sequencing technology, headspace solid-phase microextraction-gas chromatography-mass spectrometry (HS-SPME-GC/MS), and electronic nose techniques were used to investigate the changes in the quality, microbial diversity, and volatile flavor compounds of Monascus-fermented hairtail surimi (MFHS) during fermentation. The results showed that the total volatile basic nitrogen (TVB-N) index of hairtail surimi fermented by Monascus for 0-5 h met the requirements of the national standard. Among them, the 1 h group showed the best gel quality, which detected a total of 138 volatile substances, including 20 alcohols, 7 aldehydes, 12 olefins, 4 phenols, 12 alkanes, 8 ketones, 15 esters, 6 acids, 16 benzenes, 4 ethers, and 8 amines, as well as 26 other compounds. In addition, the dominant fungal microorganisms in the fermentation process of MFHS were identified, and a Spearman correlation analysis showed that 16 fungal microorganisms were significantly correlated with the decrease in fishy odor substances in the fermented fish and that 8 fungal microorganisms were significantly correlated with the increase in aromatic substances after fermentation. In short, Monascus fermentation can eliminate and reduce the fishy odor substances in hairtail fish, increase and improve the aromatic flavor, and improve the quality of hairtail surimi gel. These findings are helpful for revealing the mechanism of the quality formation of fermented surimi and provide guidance for the screening of starter culture in the future.