Small RNAs (sRNAs) in plant-derived exosome-like nanoparticles (PELNs) have attracted considerable attention as biologically active substances that play a crucial role in cross-kingdom regulatory processes. However, there is insufficient research dedicated to identifying sRNAs within PELNs. We aimed to analyze the expression profile of sRNAs in onion-derived exosomes-like nanoparticles (OELNs) and explore their potential role in cross-kingdom regulation. In this study, OELNs were extracted, possessing an optimal particle size of approximately 139 nm and a Zeta potential of roughly -20 mV. Subsequently, high-throughput small RNA sequencing was conducted to analyze sRNAs in onion tissues and OELNs. The expression profile of sRNAs in OELNs was elucidated, and it was predicted that highly expressed microRNAs (miRNAs) in OELNs may exert potential regulatory effects on the human genome. By comparing with the reference genome of onion (Allium cepa L.), 11 known miRNAs and 248 novel miRNAs were identified in both onion tissues and OELNs. Target gene prediction analysis of the human genome has revealed that 20 miRNAs highly expressed in OELNs potentially participate in the regulation of human tumor and cardiovascular-related signaling pathways. Furthermore, differential analysis was conducted on small/short interfering RNA (siRNA), small nucleolar RNA (snoRNA), and transfer ribonucleic acid (tRNA) in OELNs. This study laid a theoretical foundation for further exploring the cross-kingdom role of non-coding RNAs in OELNs, and provided new ideas for the development of plant-derived functional components.

Gastric cancer is a malignant tumor that severely threat to human health worldwide. Onions (Allium cepa L.), as a common dietary source, offer a promising candidate for exploring natural approaches to cancer chemoprevention and therapy through their bioactive components. Plant-derived exosome-like nanoparticles are attracting growing interest as a novel strategy in the plant-based chemoprevention and treatment of cancers. This study established a malignant transformation model using N-methyl-N '-nitro-N-nitrosoguallidine (MNNG)-treated human gastric mucosa epithelial cells (GES-1) and investigated the protective effects of onion-derived exosomelike nanoparticles (OELNs) in gastric carcinogenesis. Chronic MNNG exposure induced malignant transformation in GES-1 cells, characterized by EMT and increased proliferation. OELNs effectively suppressed oncogenic phenotypes, including proliferation and EMT. Small RNA sequencing identified novel-miR-75-5p as a key miRNA in OELNs, which directly targeted YPEL2 to inhibit gastric carcinogenesis. Functional studies demonstrated that YPEL2 knockdown mimicked the tumor-suppressive effects of OELNs, while YPEL2 overexpression promoted the progression of gastric cancer. RNA sequencing and co-immunoprecipitation revealed YPEL2's interaction with TEM1, further elucidating its role in gastric carcinogenesis. Additionally, engineered OELNs loaded with novelmiR-75-5p exhibited enhanced anti-tumor activity in cell models and mouse models. These findings highlight the therapeutic potential of OELNs and the OELNs/novel-miR-75-5p/YPEL2 axis in gastric cancer chemoprevention.

Gastric cancer remains a leading global malignancy, necessitating the development of novel therapeutic approaches. Plant-derived exosome-like nanoparticles have emerged as promising therapeutic vehicles due to their high biocompatibility and low immunogenicity; however, the potential anti-gastric cancer effects of Sarcandra glabra-derived exosome-like nanoparticles (SELNs) have not been previously investigated. Given the central role of Wnt/β-catenin signaling in driving gastric cancer progression, we investigated whether SELNs exert antitumor effects by modulating this axis. SELNs were isolated via differential ultracentrifugation, and their efficacy and underlying mechanisms were evaluated using a combination of in vitro functional assays and in vivo xenograft models. We found that SELNs significantly inhibited gastric cancer cell proliferation, migration, invasion, and epithelial-mesenchymal transition, while promoting apoptosis. In vivo administration of SELNs effectively suppressed tumor growth. Mechanistically, SELNs impaired the protein stability and nuclear translocation of β-catenin, which subsequently downregulated its downstream targets, c-Myc and Cyclin D1. Furthermore, SELNs sensitized gastric cancer cells to cisplatin, demonstrating a synergistic suppression of Wnt pathway activity. In conclusion, this study revealed that SELNs exert multifaceted anti-gastric cancer effects by targeting the Wnt/β-catenin pathway and can sensitize cancer cells to chemotherapy, providing a novel natural nanotherapeutic strategy for gastric cancer treatment.

Accumulating evidence indicates that environmental exposures, particularly to nitrites, play a critical role in the initiation and progression of gastric cancer (GC). During carcinogenesis, exosomes act as key mediators of intercellular communication. Exosomes derived from N‑methyl-N'‑nitro‑N‑nitrosoguanidine (MNNG)‑induced malignantly transformed GES‑1 cells (TGES‑1), as well as serum exosomes from gastric cancer patients with a history of high nitrite exposure, were found to influence normal cells and promote GC initiation. The present study established a malignant transformation model and applied bioinformatics analyses to screen and validate candidate circRNAs. A series of functional and mechanistic experiments were performed to elucidate the regulatory role of exosomes in GC progression. Circ0000549 was markedly upregulated in MNNG‑exposed GES‑1 cells, their derived exosomes and serum exosomes from patients with GC. Further investigations revealed that circ0000549 overexpression enhanced GES‑1 cell malignant features, while also modulating epithelial‑mesenchymal transition and stemness‑related properties. Nude mouse experiments demonstrated that circ0000549, carried by malignantly transformed exosomes, plays a crucial role in MNNG‑induced gastric carcinogenesis. Mechanistically, miR‑15b‑5p was identified as a potential target of circ0000549. Circ0000549 functioned as a sponge for miR‑15b‑5p, leading to increased KIF1B expression and subsequent activation of the PI3K/AKT signaling pathway. Collectively, these findings reveal that exosomal circ0000549 promotes malignant transformation of GES‑1 cells through the miR‑15b‑5p/KIF1B/PI3K/AKT axis. Exosomal circ0000549 may serve as a promising biomarker for GC diagnosis and prognosis, highlighting its potential as a target for future therapeutic investigation.

Plant-derived exosome-like nanoparticles (PELNs) have demonstrated substantial potential and promising prospects in the realms of disease prevention and therapy. Composed of a diverse array of bioactive constituents and secondary metabolites, they are poised to exert significant influence in anti-inflammatory, antitumor, and antioxidant activities. Furthermore, their inherent nanomaterial properties coupled with excellent biocompatibility render PELNs natural candidates for drug delivery systems, enhancing bioavailability. This paper mainly reviews the biogenesis, isolation, and characterization of PELNs, then endeavors to synthesize the current body of knowledge on them and emphasize their potential therapeutic applications. We focus on key findings regarding anti-inflammatory, antitumor, and antioxidant effects and discuss how these insights can guide the design of next-generation nanomedicines.

BACKGROUND:Hesperetin, a flavonoid predominantly present in citrus fruits, exhibits significant intervention effects on both the initiation and progression of gastric cancer. However, the specific mechanisms underlying this effect remain unclear. AIM:To investigate the interventional role of hesperetin on N-methyl-N'-nitro-N-nitrosoguanidine (MNNG)-induced exosomes in inducing gastric carcinogenesis. METHODS:Bioinformatics technology was used to identify the critical molecular components underlying hesperetin-mediated inhibition of MNNG induced gastric carcinogenesis through exosomal circular RNA. Biological experiments were conducted to validate these findings. RESULTS:Exosomes derived from TGES-1 cells (TGES-1-EX) significantly enhanced the proliferation, migration, invasion, epithelial-mesenchymal transition (EMT), and stemness of GES-1 cells. The oncogenic potential of TGES-1-EX was significantly diminished following hesperetin pretreatment. TGES-1-EX with overexpressed or knocked down circ0008274 was extracted and GES-1 cells were treated in combination with hesperetin or alone. Our investigation revealed that hesperetin exerted significant inhibitory effects on MNNG-induced gastric carcinogenesis by exosomal circ0008274. Bioinformatics prediction identified microRNA (miR)-526b-5p as a potential miRNA binding to circ0008274. Functional experiments demonstrated that hesperetin may mediate its intervention in MNNG-induced gastric cancer initiation by targeting miR-526b-5p through exosomal circ0008274. TGES-1-EX circ0008274 promoted the proliferation, EMT, and cancer stem cell-like characteristics in GES-1 cells through miR-526b-5p-mediated regulatory mechanisms. CONCLUSION:Hesperetin exerted an interventional effect on the gastric carcinogenesis process, particularly through the modulation of exosomal circ0008274 and its interaction with miR-526b-5p.

Gastric cancer has emerged as a major global public health threat due to its high incidence and mortality rates. Despite advances in diagnostic and therapeutic approaches, treatment outcomes remain unsatisfactory with frequent disease recurrence and poor prognosis. This underscores the urgent need to develop novel therapeutic strategies against gastric cancer. Cuproptosis, a novel form of cellular death, has garnered increasing attention from researchers regarding its relationship with the onset and progression of gastric cancer. This article aims to explore the molecular mechanisms of cuproptosis, its functions in gastric cancer, and its potential therapeutic applications. We analyze the driving factors and defense mechanisms of cuproptosis, as well as how it influences the growth, metastasis, and drug resistance of gastric cancer cells. Furthermore, we discuss the interplay between cuproptosis and the gastric cancer microenvironment, and consider the possibilities of this mechanism in future clinical treatments.

Gastric cancer is one of the common malignant tumors of digestive tract. Early diagnosis, process monitoring, and appropriate treatment strategies are crucial to reducing mortality and improving patient outcomes. However, the lack of specific early symptoms and reliable diagnostic markers often leads to delayed diagnosis and suboptimal treatment strategies. Exosomes, as small vesicular structures derived from endosomes, play crucial roles in cell-to-cell communication and have emerged as promising biomarkers and therapeutic targets in various cancers, including gastric cancer. This comprehensive review delves into the significance of exosomes and their cargo proteins, particularly focusing on their applications in the diagnosis, progress and treatment of gastric cancer. Based on this review, we believe that the real-time release characteristics of extracellular vesicle proteins make them an ideal tool for dynamically monitoring gastric cancer progression and treatment response. The potential of extracellular vesicles in “liquid biopsy” can be explored to replace traditional invasive examinations and achieve non-invasive and continuous disease monitoring. In the future, nanotechnology can be combined with artificial intelligence to develop an efficient extracellular vesicle protein capture and analysis platform, in order to enhance diagnostic sensitivity and specificity.

Cancer, including gastric cancer, has become a serious disease that jeopardizes public life. Currently, the main treatment methods are surgery, radiation therapy, and chemotherapy. One of the primary causes of death for patients with gastric cancer is drug resistance. Several mechanisms of anticancer drugs resistance have been reported, including changes in drugs transport and metabolism, mutations in drug targets, changes in DNA repair systems, inhibition of cell apoptosis and autophagy, gastric cancer stem cells, invasion and migration. It is becoming more widely known that non-coding RNAs, like circRNAs, play a critical role in the resistance of drugs used to treat gastric cancer. CircRNAs have a unique structure and function that is related to gastric cancer resistance, cell proliferation, apoptosis, autophagy, DNA repair systems, migration, and invasion. A clear understanding of the molecular mechanism of circRNAs mediated the resistance of gastric cancer drugs will open a new window for the treatment and management of gastric cancer. Therefore, in this review, we will summarize the current mechanism of drug resistance, and finally discuss the molecular mechanism of circRNAs in regulating the development of drug resistance in gastric cancer.

Cancer has become an important public health problem worldwide, and there is currently a lack of effective treatment and prevention strategies. Natural plant active ingredients have been proven to be a safe and highly promising method for preventing and treating cancer. It has been found that diallyl trisulfide have anticancer effects in multiple types of cancer via inhibiting cancer proliferation, enhancing chemotherapy sensitivity, inducing apoptosis/autophagy, suppressing invasion/migration, regulating microenvironment. With the deepening of research on new strategies for cancer prevention and treatment, the role of diallyl trisulfides in cancers occurrence, prognosis, and drug resistance is also receiving increasing attention. In order to better understand the relationship between diallyl trisulfides and various cancer, as well as the role and mechanism of diallyl trisulfides in cancer prevention and treatment, we briefly summarized the role and function of diallyl trisulfide in cancers.

The health of individuals is seriously threatened by intestinal cancer, which includes pancreatic, colorectal, esophageal, gastric and gallbladder cancer. Most gastrointestinal cancers do not have typical and specific early symptoms, and lack specific and effective diagnostic markers and treatment methods. It is critical to understand the etiology of gastrointestinal cancer and develop more efficient methods of diagnosis and treatment. The cyclic GMP‑AMP synthase (cGAS)/stimulator of interferon genes (STING) pathway serves a crucial role in the occurrence, progression and treatment of gastrointestinal cancer. The present review focuses on the latest progress regarding the role and mechanism of the cGAS/STING pathway in gastrointestinal cancer, and discusses treatment approaches and related applications based on the cGAS/STING signaling pathway. In order to improve the knowledge of the connection between the cGAS/STING pathway and gastrointestinal cancer, aid the diagnosis and treatment of gastrointestinal cancer, and lessen the burden on patients and society, the present review also discusses future research directions and existing challenges regarding cGAS/STING in the study of gastrointestinal cancer.

Gastric cancer (GC) is a malignant cancer with the highest global rates of morbidity and death. Dietary factors have a close relationship with the occurrence of GC. Circular RNAs (circRNAs) and N6-methyladenine (m6A) are important factors in the onset and progression of GC and other malignancies. However, little is known about the role of circRNA m6A modifications in the occurrence and development of GC. Initially, a transformed malignant cell model generated by the chemical carcinogen N-methyl-N'-nitro-N-nitrosoguanidine (MNNG) was established in this investigation. Furthermore, following exposure to MNNG, circ0049271 is substantially expressed in gastric epithelial cells (GES-1). Subsequent research revealed that the knockdown of circ0049271 prevented the epithelial-mesenchymal transition (EMT) as well as the migration, invasion, and proliferation of gastric epithelial cells induced by long-term exposure to MNNG. The opposite effects were observed when circ0049271 was overexpressed. Mechanistically, circ0049271 activates the TGFβ/SMAD signaling pathway and has m6A modifications mediated by WTAP. Our findings indicate that circ0049271 promotes the occurrence of GC by regulating the TGFβ/SMAD pathway, and WTAP may mediate the methylation of circ0049271 m6A. This study provides new insights into the regulation of circRNA-mediated m6A modifications and the discovery of early GC induced by dietary factors such as nitrite.

Gastric cancer (GC) is the fourth most common malignant cancer and is a life-threatening disease worldwide. Phytochemicals have been shown to be a rational, safe, non-toxic, and very promising approach to the prevention and treatment of cancer. It has been found that phytochemicals have protective effects against GC through inhibiting cell proliferation, inducing apoptosis and autophagy, suppressing cell invasion and migration, anti-angiogenesis, inhibit Helicobacter pylori infection, regulating the microenvironment. In recent years, the role of phytochemicals in the occurrence, development, drug resistance and prognosis of GC has attracted more and more attention. In order to better understand the relationship between phytochemicals and gastric cancer, we briefly summarize the roles and functions of phytochemicals in GC tumorigenesis, development and prognosis. This review will probably help guide the public to prevent the occurrence and development of GC through phytochemicals, and develop functional foods or drugs for the prevention and treatment of gastric cancer.

Gastric cancer is a common malignant tumor of the digestive tract, with a low early diagnosis rate. N-methyl-N-nitro-N-nitroguanidine (MNNG) is one of the main risk factors for gastric cancer. Phytochemicals are healthy active substances derived from vegetables, fruits, nuts, tea, herbal medicines and other plants. Taking phytochemicals is a very promising strategy for the prevention and treatment of gastric cancer. Many studies have proved that phytochemicals have protective effects on MNNG induced gastric cancer via inhibiting cell proliferation, enhancing immunity, suppressing cell invasion and migration, inducing apoptosis and autophagy, blocking angiogenesis, inhibiting Helicobacter pylori infection as well as regulating metabolism and microbiota. The intervention and therapeutic effects of phytochemicals in MNNG induced gastric cancer have attracted more and more attention. In order to better study and explore the role, advantages and challenges of phytochemicals in MNNG induced gastric cancer, we summarized the intervention and therapeutic effects of phytochemicals in MNNG induced gastric cancer. This review may help to further promote the research and clinical application of phytochemicals in MNNG induced gastric cancer, and provide some new insights.

Tobacco smoke (TS) is the major cause of lung cancer. The abnormal proliferation and epithelial-mesenchymal transition (EMT) of lung cells promote occurrence and development of lung cancer. The p38 pathway intervenes in this cancer development. Hesperidin also serves a role in human health and disease prevention. The roles of p38 in TS-mediated abnormal cell proliferation and EMT, and the hesperidin intervention thereof are not yet understood. In the present study, it was demonstrated that TS upregulated proliferating cell nuclear antigen, vimentin and N-cadherin expression, whereas it downregulated E-cadherin expression, as assessed using western blotting and reverse transcription-quantitative PCR. Furthermore, it was observed that inhibition of the p38 pathway inhibit TS-induced proliferation and EMT. Hesperidin treatment prevented the TS-induced activation of the p38 pathway, EMT and cell proliferation in mouse lungs. The findings of the present study may provide insights into the pathogenesis of TS-related lung cancer.

Background Exosome, a component of liquid biopsy, loaded protein, DNA, RNA and lipid gradually emerges as biomarker in tumors. However, exosomal circRNAs as biomarker and function mechanism in gastric cancer (GC) are not well understood. Methods Differentially expressed circRNAs in GC and healthy people were screened by database. The identification of hsa_circ_000200 was verified by RNase R and sequencing, and the expression of hsa_circ_000200 was evaluated using qRT-PCR. The biological function of hsa_circ_000200 in GC was verified in vitro. Western blot, RIP, RNA fluorescence in situ hybridization, and double luciferase assay were utilized to explore the potential mechanism of hsa_circ_000200. Results Hsa_circ_000200 up-regulated in GC tissue, serum and serum exosomes. Hsa_circ_000200 in serum exosomes showed better diagnostic ability than that of tissues and serum. Combined with clinicopathological parameters, its level was related to invasion depth, TNM staging, and distal metastasis. Functionally, knockdown of hsa_circ_000200 inhibited GC cells proliferation, migration and invasion in vitro, while its overexpression played the opposite role. Importantly, exosomes with up-regulated hsa_circ_000200 promoted the proliferation and migration of co-cultured GC cells. Mechanistically, hsa_circ_000200 acted as a “ceRNA” for miR-4659a/b-3p to increase HBEGF and TGF-β/Smad expression, then promoted the development of GC. Conclusions Our findings suggest that hsa_circ_000200 promotes the progression of GC through hsa_circ_000200/miR-4659a/b-3p/HBEGF axis and affecting the expression of TGF-β/Smad. Serum exosomal hsa_circ_000200 may serve as a potential biomarker for GC.

Cigarette smoke is a major risk factor for gastric cancer. Exosomes are an important part of intercellular and intra-organ communication systems and can carry circRNA and other components to play a regulatory role in the occurrence and development of gastric cancer. However, it is unclear whether cigarette smoke can affect exosomes and exosomal circRNA to promote the development of gastric cancer. Exosomes secreted by cancer cells promote cancer development by affecting surrounding normal cells. Herein, we aimed to clarify whether the exosomes secreted by cigarette smoke-induced gastric cancer cells can promote the development of gastric cancer by affecting the surrounding gastric mucosal epithelial cells (GES-1). In the present study, we treated gastric cancer cells with cigarette smoke extract for 4 days and demonstrated that cigarette smoke promotes the stemness and EMT of gastric cancer cells and cigarette smoke-induced exosomes promote stemness gene expression, EMT processes and the proliferation of GES-1 cells. We further found that circ0000670 was up-regulated in tissues of gastric cancer patients with smoking history, cigarette smoke-induced gastric cancer cells and their exosomes. Functional assays showed that circ0000670 knockdown inhibited the promoting effects of cigarette smoke-induced exosomes on the stemness and EMT characteristic of GES-1 cells, whereas its overexpression had the opposite effect. In addition, exosomal circ0000670 was found to promote the development of gastric cancer by regulating the Wnt/β-catenin pathway. Our findings indicated that exosomal circ0000670 promotes cigarette smoke-induced gastric cancer development, which might provide a new basis for the treatment of cigarette smoke-related gastric cancer.

While previous research on cancer biology has focused on genes that code for proteins, in recent years it has been discovered that non-coding RNAs (ncRNAs)play key regulatory roles in cell biological functions. NcRNAs account for more than 95% of human transcripts and are an important entry point for the study of the mechanism of cancer development. An increasing number of studies have demonstrated that ncRNAs can act as tumor suppressor genes or oncogenes to regulate tumor development at the epigenetic level, transcriptional level, as well as post-transcriptional level. Because of the importance of ncRNAs in cancer, most clinical trials have focused on ncRNAs to explore whether ncRNAs can be used as new biomarkers or therapies. In this review, we focus on recent studies of ncRNAs including microRNAs (miRNAs), long ncRNAs (lncRNAs), circle RNAs (circRNAs), PIWI interacting RNAs (piRNAs), and tRNA in different types of cancer and explore the application of these ncRNAs in the development of cancer and the identification of relevant therapeutic targets and tumor biomarkers. Graphical abstract drawn by Fidraw.

Gastrointestinal cancer is frequently detected at an advanced stage and has an undesirable prognosis due to the absence of efficient and precise biomarkers and therapeutic targets. Exosomes are small, living‑cell‑derived vesicles that serve a critical role in facilitating intercellular communication by transporting molecules from donor cells to receiver cells. circular RNAs (circRNAs) are mis‑expressed in a variety of diseases, including gastrointestinal cancer, and are promising as diagnostic biomarkers and tumor therapeutic targets for gastrointestinal cancer. The main features of exosomes and circRNAs are discussed in the present review, along with research on the biological function of exosomal circRNAs in the development and progression of gastrointestinal cancer. It also assesses the advantages and disadvantages of implementing these findings in clinical applications.

Gastric cancer (GC) is a malignant cancer of the digestive tract and is a life-threatening disease worldwide. Ferroptosis is a newly discovered form of regulated cell death, which involves the accumulation of iron-dependent lipid peroxides. It has been found that ferroptosis plays an important regulatory role in the occurrence, development, drug resistance, and prognosis of GC. Non-coding RNAs (ncRNAs) play a critical role in the occurrence and progression of a variety of diseases including GC. In recent years, the role of ferroptosis and ferroptosis-related ncRNAs (miRNA, lncRNA, and circRNA) in the occurrence, development, drug resistance, and prognosis of GC has attracted more and more attention. Herein, we briefly summarize the roles and functions of ferroptosis and ferroptosis-related ncRNAs in GC tumorigenesis, development, and prognosis. We also prospected the future research direction and challenges of ferroptosis and ferroptosis-related ncRNAs in GC.