Extracellular vesicles (EVs) are stably present in body fluids and carry diverse molecular cargos, including proteins and nucleic acids, making them an ideal information carrier for liquid biopsy. However, most existing EV assays focus on a single class of markers, and combining multiple markers within the same class often introduces informational redundancy, thereby limiting diagnostic performance. To address this challenge, we developed a one-pot dual-biomarker detection platform driven by an AND logic gate, inspired by the enrichment of the endonuclease APE1 and tumor-associated miRNAs in cancer-related EVs. In our platform, low-abundance target miRNA was first efficiently converted into abundant product probes (Pp) via strand displacement amplification (SDA). The resulting Pp then hybridized with an AP-site containing signal probe to form a cleavage-competent substrate, which was catalytically cleaved by APE1 to restore fluorescence. Meanwhile, the released Pp can repeatedly initiate additional cleavage cycles, enabling cascading signal amplification. The platform achieved a limit of detection of 8 fM for miRNA and 0.008 U/mL for APE1. In plasma EVs from gastric cancer patients and healthy donors, the AND-gated dual-marker readout yields an area under the ROC curve (AUC) of 0.957, significantly outperforming single-marker RT-qPCR miRNA analysis (AUC=0.823), indicating improved discrimination in clinical samples. Overall, our work provided a simple synergistic logic-gated framework for integrating multi-class EV biomarkers, with potential applications in early cancer screening and dynamic disease monitoring.

Circular RNAs (circRNAs) are a type of non-coding RNA molecule whose functional processes in carcinogenesis and progression are not fully known. Recent studies suggest that circRNAs can act as functional RNAs involved in the progression of various tumors. This study aims to investigate the role of hsa_circ_0085465 in the proliferation, migration, and invasion processes of gastric cancer cells. By establishing models of Helicobacter pylori (H. pylori)-infected normal gastric epithelial cells and gastric cancer cells, we conducted whole transcriptome sequencing and bioinformatics analysis, which led to the identification of a significantly upregulated circular RNA molecule, hsa_circ_0085465. Subsequently, we investigated the function of hsa_circ_0085465 in gastric cancer through in vitro functional experiments, including scratch wound healing assays and transwell assays, as well as in vivo animal experiments. Then, the downstream target miRNA of hsa_circ_0085465 were identified using sequencing and bioinformatics analysis, and the binding between hsa_circ_0085465 and the target gene miR-33b-3p was validated using dual-luciferase reporter gene assays and fluorescence in situ hybridization (FISH). Finally, we explored the interaction between hsa_circ_0085465 and miR-33b-3p through in vitro functional analyses. In a gastric cell model infected with H. pylori, the expression level of hsa_circ_0085465 was significantly upregulated. In vitro experiments demonstrated that hsa_circ_0085465 promotes the proliferation, migration, and invasion of gastric cancer cells, while in vivo subcutaneous tumor model further confirmed that hsa_circ_0085465 markedly accelerates tumor growth. Subsequent analyses identified miR-33b-3p as a downstream target of hsa_circ_0085465, and miR-33b-3p was found to suppress the proliferation, migration, and invasion of gastric cancer cells. Rescue experiments further demonstrated that miR-33b-3p can partially reverse the oncogenic effects of hsa_circ_0085465 in gastric cancer. H. pylori induced the upregulation of hsa_circ_0085465 in gastric cells, and hsa_circ_0085465 functions as a molecular sponge for miR-33b-3p, thereby promoting the proliferation, migration, and invasion of gastric cancer cells.

Human pseudouridine synthase 7 (PUS7) catalyzes the isomerization of uridine to pseudouridine in RNA substrates. Although its catalytic region has been characterized, further studies are needed to clarify the mechanisms underlying its substrate recognition and specificity. PUS7 promotes tumor progression in glioblastoma, pancreatic adenocarcinoma, neuroblastoma, hepatocellular carcinoma, and colorectal cancer by altering RNA stability, translational fidelity, and splicing, ultimately regulating key oncogenic processes such as cell proliferation, self-renewal, metabolic reprogramming, and stress responses. Additionally, PUS7 can promote tumor progression through noncatalytic mechanisms, as observed in colorectal cancer, where it forms protein-protein complexes that activate oncogenic signaling pathways. Conversely, PUS7 exhibits tumor-suppressive functions in gastric carcinoma and papillary thyroid carcinoma by targeting mRNAs and miRNAs that regulate gene expression linked to reduced tumor aggressiveness. These findings indicate that PUS7 may represent a context-dependent therapeutic target and underscore the need for further research to clarify the molecular basis of its effects in cancer. Such knowledge may guide the development of new therapeutic strategies for PUS7-driven tumors. SIGNIFICANCE STATEMENT: Recent studies reveal that dysregulated pseudouridine synthase activity contributes to the progression of malignancies such as glioblastoma, pancreatic adenocarcinoma, neuroblastoma, colorectal cancer, and hepatocellular carcinoma. Here, we review the pseudouridine synthase's structure-function relationships and context-specific activities. The evidence discussed will help the development of selective therapeutic strategies targeting RNA modification pathways.

Gastric cancer remains a leading contributor to cancer-related mortality worldwide despite its declining incidence, with poor survival rates. Standard treatments, such as surgical resection, radiotherapy, chemotherapy, and immunotherapy, often achieve limited success, underscoring an urgent need for the development of novel and effective treatment strategies. Plant-derived diterpenoids demonstrate a wide range of bioactivities including antitumor activity. The aim of this review is to compile, integrate, and discuss the latest information concerning plant-derived diterpenoids with anti-gastric-cancer activities.

Astrocyte elevated gene-1 (AEG-1) is oncogenic in gastric cancer; however, its underlying mechanism has not been fully elucidated. In this study, we identified serine 308 (Ser308) as a phosphorylation site of AEG-1 in gastric cancer cells. By constructing AEG-1 point mutants to overexpress phospho-mimetic AEG-1 (S308D, serine-to-aspartate) and dephospho-mimetic AEG-1 (S308A, serine-to-alanine), we found that phosphorylation of AEG-1 at Ser308 significantly suppressed cell growth and migration, accompanied by downregulation of p65 NF-κB-mediated transcription of the downstream target genes FOS and IL-8. Mechanistically, TNF-α-induced dephosphorylation of AEG-1 at Ser308 promoted p65 NF-κB nuclear accumulation and activation through protein-protein interaction. This study reveals a novel phosphorylation-dependent switch that regulates AEG-1-mediated NF-κB signaling in gastric cancer.

Background/Objectives: The triglyceride-glucose (TyG) index, a reliable marker for insulin resistance, is strongly associated with T2DM, hypertension, and cardiovascular disease. Less well known is its relationship with cancer risk. The aim of this study was to quantify the association between the TyG index and risk of different types of cancer. Methods: Publications were searched in the PubMed, Web of Science, and Scopus databases using appropriate keywords. The PICOS framework was used to select the studies, and their quality was evaluated according to the "Newcastle-Ottawa Scale" (NOS). Meta-analysis was performed through a random-effects model using cancer risk parameters (RR: relative risk, OR: odds ratio and HR: hazard ratio) extracted from 26 selected studies associated with TyG index values. The weighted mean difference (WMD) was used to compare the mean of the TyG index in cancer patients to that of the control group. Heterogeneity was assessed by Cochran's Q and I2 statistics, while publication bias was evidenced using the Egger test and the Begg test, and funnel plot asymmetry. Results: A higher TyG index value was observed in cancer subjects (9483) compared to healthy controls (978,675) (WMD: 0.23, 95% CI: 0.16-0.31, p < 0.0001, n = 15). A statistically significant increase in cancer risk was associated with the TyG index level, expressed as both a categorical (OR 1.33, 95% CI 1.22-1.45, p < 0.0001, n = 29) and continuous (OR 1.14, 95% CI 1.10-1.19, p < 0.0001, n = 27) variable. The effect was more evident in case-control/cross-sectional studies compared to cohort studies (OR 1.78, 95% CI 1.51-2.09 vs. OR 1.19, 95% CI 1.10-1.29 TyG categorical; OR 1.46, 95% CI 1.21-1.76 vs. OR 1.09, 95% CI 1.05-1.12 TyG continuous). Stratified analysis showed an increased risk of cancer occurrence for gastrointestinal, gynecological, colorectal, breast, and gastric sites, while no association was observed for endometrial, ovarian, prostate, lung or esophageal cancers. Conclusions: Our results evidence an increase in cancer risk associated with higher TyG index values. However, due to the low number of studies, the effect on specific tumor sites was not statistically significant. Additional epidemiological studies with a cohort design are necessary to confirm these associations.

Leptomeningeal carcinomatosis (LMC) is extremely rare in gastric cancer, as is recurrence >10 years after gastrectomy. Herein, we report an autopsy case of LMC that developed 29 years after gastrectomy for gastric signet ring cell carcinoma. A 74-year-old man presented with multiple progressive cranial neuropathies involving cranial nerves III, V, VI, VII, IX, X, and XII. CSF analysis revealed pleocytosis and markedly elevated protein levels; however, cytological examination of five consecutive samples was negative for malignant cells. Multiplex PCR analysis excluded infectious etiologies. MRI demonstrated contrast enhancement of cranial nerves III, V, VII, and XII. Despite antiviral, antituberculous, and corticosteroid therapy, the patient's condition deteriorated, and he ultimately died three months after symptom onset. Autopsy revealed extensive infiltration of signet ring cell carcinoma in the leptomeninges and cranial nerves. Immunohistochemical analysis of this tissue revealed cytokeratin 7 positivity and cytokeratin 20 negativity, identical to the gastric carcinoma resected 29 years earlier. No recurrence was observed in the remnant stomach or other organs. This case suggests reactivation of microscopic leptomeningeal metastases following an exceptionally prolonged period of tumor dormancy. Signet ring cell carcinoma is thought to be prone to dormancy owing to its weak intercellular adhesion, leading to reduced proliferative signaling and activation of stress response pathways. This experience suggests that LMC should be considered when meningitis-like neurological symptoms develop, even in patients who remain recurrence-free for decades postoperatively.