Tabersonine enhances cisplatin sensitivity by modulating Aurora kinase A and suppressing epithelial-mesenchymal transition in triple-negative breast cancer.

CONTEXT: Tabersonine has been investigated for its role in modulating inflammation-associated pathways in various diseases. However, its regulatory effects on triple-negative breast cancer (TNBC) have not yet been fully elucidated. OBJECTIVE: This study uncovers the anticancer properties of tabersonine in TNBC cells, elucidating its role in enhancing chemosensitivity to cisplatin (CDDP). MATERIALS AND METHODS: After tabersonine (10 µM) and/or CDDP (10 µM) treatment for 48 h in BT549 and MDA-MB-231 cells, cell proliferation was evaluated using the cell counting kit-8 and colony formation assays. Quantitative proteomics, online prediction tools and molecular docking analyses were used to identify potential downstream targets of tabersonine. Transwell and wound-healing assays and Western blot analysis were used to assess epithelial-mesenchymal transition (EMT) phenotypes. RESULTS: Tabersonine demonstrated inhibitory effects on TNBC cells, with IC50 values at 48 h being 18.1 µM for BT549 and 27.0 µM for MDA-MB-231. The combined treatment of CDDP and tabersonine synergistically suppressed cell proliferation in BT549 and MDA-MB-231 cells. Enrichment analysis revealed that the proteins differentially regulated by tabersonine were involved in EMT-related signalling pathways. This combination treatment also effectively restricted EMT-related phenotypes. Through the integration of online target prediction and proteomic analysis, Aurora kinase A (AURKA) was identified as a potential downstream target of tabersonine. AURKA expression was reduced in TNBC cells post-treatment with tabersonine. DISCUSSION AND CONCLUSIONS: Tabersonine significantly enhances the chemosensitivity of CDDP in TNBC cells, underscoring its potential as a promising therapeutic agent for TNBC treatment.

Distinct roles of CD244 expression in cancer diagnosis and prognosis: A pan-cancer analysis.

The abnormal expression of tumor associated genes in pan-cancer is closely related to the clinicopathological features of distinct cancer types. Thus, identifying the role of specific genes in pan-cancer is needed for developing effective anti-cancer strategies. However, the function of CD244 in pan-cancer has not been fully understood. In this study, we explored the CD244 expression profile across 33 tumor types based on The Cancer Genome Atlas project, the Gene Expression Omnibus database, and other bioinformatics tools. We found down-regulated expression levels in seven tumor types and up-regulated expression levels in two tumor types. We subsequently explored the relationship between survival rate and CD244 expression, and found the positive relationship in patients with adrenocortical carcinoma (ACC), head and neck squamous cell carcinoma (HNSC), skin cutaneous melanoma (SKCM), and uterine corpus endometrial carcinoma (UCEC). We further investigated the association between CD244 expression and tumor-infiltrating immune cells, and discovered their positive correlation in different tumors. We found that CD244 expression level was higher in normal samples than in UCEC samples, and was positively associated with CD8+ T cells infiltrating. The mutation status, promoter methylation, CD244-related molecules and signaling pathways were also employed to study the potential function of CD244 in tumor initiation and progression. Our study offers a comprehensive overview of CD244 in human tumors, revealing CD244 as a potential prognostic biomarker and immunotherapeutic target in cancers.

Suppression of ITPKB degradation by Trim25 confers TMZ resistance in glioblastoma through ROS homeostasis.

Temozolomide (TMZ) represents a standard-of-care chemotherapeutic agent in glioblastoma (GBM). However, the development of drug resistance constitutes a significant hurdle in the treatment of malignant glioma. Although specific innovative approaches, such as immunotherapy, have shown favorable clinical outcomes, the inherent invasiveness of most gliomas continues to make them challenging to treat. Consequently, there is an urgent need to identify effective therapeutic targets for gliomas to overcome chemoresistance and facilitate drug development. This investigation used mass spectrometry to examine the proteomic profiles of six pairs of GBM patients who underwent standard-of-care treatment and surgery for both primary and recurrent tumors. A total of 648 proteins exhibiting significant differential expression were identified. Gene Set Enrichment Analysis (GSEA) unveiled notable alterations in pathways related to METABOLISM_OF_LIPIDS and BIOLOGICAL_OXIDATIONS between the primary and recurrent groups. Validation through glioma tissue arrays and the Xiangya cohort confirmed substantial upregulation of inositol 1,4,5-triphosphate (IP3) kinase B (ITPKB) in the recurrence group, correlating with poor survival in glioma patients. In TMZ-resistant cells, the depletion of ITPKB led to an increase in reactive oxygen species (ROS) related to NADPH oxidase (NOX) activity and restored cell sensitivity to TMZ. Mechanistically, the decreased phosphorylation of the E3 ligase Trim25 at the S100 position in recurrent GBM samples accounted for the weakened ITPKB ubiquitination. This, in turn, elevated ITPKB stability and impaired ROS production. Furthermore, ITPKB depletion or the ITPKB inhibitor GNF362 effectively overcome TMZ chemoresistance in a glioma xenograft mouse model. These findings reveal a novel mechanism underlying TMZ resistance and propose ITPKB as a promising therapeutic target for TMZ-resistant GBM.

CRABP2 reduces the sensitivity of Olaparib in ovarian cancer by downregulating Caspase-8 and decreasing the production of reactive oxygen species.

Poly (adenosine diphosphate-ribose) polymerase (PARP) inhibitors, such as Olaparib, have been pivotal in treating BRCA-deficient ovarian cancer. However, their efficacy is limited in over 40% of BRCA-deficient patients, with acquired resistance posing new clinical challenges. To address this, we employed bioinformatics methods to identify key genes impacting Olaparib sensitivity in ovarian cancer. Through comprehensive analysis of public databases including GEO, CPTAC, Kaplan Meier Plotter, and CCLE, we identified CRABP2 as significantly upregulated at both mRNA and protein levels in ovarian cancer, correlating with poor prognosis and decreased Olaparib sensitivity. Using colony formation and CCK-8 assays, we confirmed that CRABP2 knockdown in OVCAR3 and TOV112D cells enhanced sensitivity to Olaparib. Additionally, 4D label-free quantitative proteomics analysis, GSEA, and GO/KEGG analysis revealed CRABP2's involvement in regulating oxidation signals. Flow cytometry, colony formation assays, and western blotting demonstrated that CRABP2 knockdown promoted ROS production by activating Caspase-8, thereby augmenting Olaparib sensitivity and inhibiting ovarian cancer cell proliferation. Moreover, in xenograft models, CRABP2 knockdown significantly suppressed tumorigenesis and enhanced Olaparib sensitivity, with the effect being reversed upon Caspase-8 knockdown. These findings suggest that CRABP2 may modulate Olaparib sensitivity in ovarian cancer through the Caspase-8/ROS axis, highlighting its potential as a target for Olaparib sensitization.

Tabersonine Enhances Olaparib Sensitivity through FHL1-Mediated Epithelial-Mesenchymal Transition in an Ovarian Tumor.

Ovarian cancer (OVC) is one of the most aggressive gynecological malignancies worldwide. Although olaparib treatment has shown favorable outcomes against the treatment of OVC, its effectiveness remains limited in some OVC patients. Investigating new strategies to improve the therapeutic efficacy of olaparib against OVC is imperative. Our study identified tabersonine, a natural indole alkaloid, for its potential to increase the chemosensitivity of olaparib in OVC. The combined treatment of olaparib and tabersonine synergistically inhibited cell proliferation in OVC cells and suppressed tumor growth in A2780 xenografts. The combined treatment effectively suppressed epithelial-mesenchymal transition (EMT) by altering the expression of E-cadherin, N-cadherin, and vimentin and induced DNA damage responses. Integrating quantitative proteomics, FHL1 was identified as a potential regulator to modulate EMT after tabersonine treatment. Increased expression of FHL1 was induced by tabersonine treatment, while downregulation of FHL1 reversed the inhibitory effects of tabersonine on OVC cells by mediating EMT. In vivo findings further reflected that the combined treatment of tabersonine and olaparib significantly inhibited tumor growth and OVC metastasis through upregulation of FHL1. Our findings reveal the role of tabersonine in improving the sensitivity of olaparib in OVC through FHL1-mediated EMT, suggesting that tabersonine holds promise for future application in OVC treatment.

Nanomaterial-encapsulated STING agonists for immune modulation in cancer therapy.

The cGAS-STING signaling pathway has emerged as a critical mediator of innate immune responses, playing a crucial role in improving antitumor immunity through immune effector responses. Targeting the cGAS-STING pathway holds promise for overcoming immunosuppressive tumor microenvironments (TME) and promoting effective tumor elimination. However, systemic administration of current STING agonists faces challenges related to low bioavailability and potential adverse effects, thus limiting their clinical applicability. Recently, nanotechnology-based strategies have been developed to modulate TMEs for robust immunotherapeutic responses. The encapsulation and delivery of STING agonists within nanoparticles (STING-NPs) present an attractive avenue for antitumor immunotherapy. This review explores a range of nanoparticles designed to encapsulate STING agonists, highlighting their benefits, including favorable biocompatibility, improved tumor penetration, and efficient intracellular delivery of STING agonists. The review also summarizes the immunomodulatory impacts of STING-NPs on the TME, including enhanced secretion of pro-inflammatory cytokines and chemokines, dendritic cell activation, cytotoxic T cell priming, macrophage re-education, and vasculature normalization. Furthermore, the review offers insights into co-delivered nanoplatforms involving STING agonists alongside antitumor agents such as chemotherapeutic compounds, immune checkpoint inhibitors, antigen peptides, and other immune adjuvants. These platforms demonstrate remarkable versatility in inducing immunogenic responses within the TME, ultimately amplifying the potential for antitumor immunotherapy.

Nickel-Catalyzed Ligand-Controlled Regioselective Allylic Alkenylation of Allylic Alcohols with Easily Accessible Alkenyl Boronates: Synthesis of 1,4-Dienes.

A nickel-catalyzed direct reaction of allylic alcohols with easily accessible alkenyl boronates has been developed, which provides valuable 1,4-dienes with high regio- and stereoselectivity in good to excellent yields, wide substrate scope, and functional group compatibility. The catalytic system simply consists of Ni(cod)2 as the catalyst and a ligand, without a need for a base and alcohol activator in most cases. The proper choice of ancillary ligands is highly important for this reaction. Depending on the substitution pattern of allylic alcohols and/or alkenyl boronates, different ligands were used for improving the reaction efficiency.

Drug metabolism-related gene ABCA1 augments temozolomide chemoresistance and immune infiltration abundance of M2 macrophages in glioma.

Gliomas are the most prevalent primary tumor in the central nervous system, with an abysmal 5-year survival rate and alarming mortality. The current standard management of glioma is maximum resection of tumors followed by postoperative chemotherapy with temozolomide (TMZ) or radiotherapy. Low chemosensitivity of TMZ in glioma treatment eventuates limited therapeutic efficacy or treatment failure. Hence, overcoming the resistance of glioma to TMZ is a pressing question. Our research centered on identifying the drug metabolism-related genes potentially involved in TMZ-treated resistance of glioma through several bioinformatics datasets and cell experiments. One efflux transporter, ATP-binding cassette transporter subfamily A1 (ABCA1), was discovered with an upregulated expression level and signaled poor clinical outcomes for glioma patients. The transcript level of ABCA1 significantly elevated across the TMZ-resistant glioma cells in contrast with non-resistant cells. Over-expressed ABCA1 restrained the drug activity of TMZ, and ABCA1 knockdown improved the treatment efficacy. Meanwhile, the results of molecular docking between ABCA1 protein and TMZ showed a high binding affinity. Additionally, co-expression and immunological analysis revealed that ABCA1 facilitates the immune infiltration of M2 macrophages in glioma, thereby stimulating tumor growth and aggravating the poor survival of patients. Altogether, we discovered that the ABCA1 transporter was involved in TMZ chemoresistance and the immune infiltration of M2 macrophages in glioma. Treatment with TMZ after ABCA1 knockdown enhances the chemosensitivity, suggesting that inhibition of ABCA1 may be a potential strategy for improving the therapeutic efficacy of gliomas.

Functional roles of magnetic nanoparticles for the identification of metastatic lymph nodes in cancer patients.

Staging lymph nodes (LN) is crucial in diagnosing and treating cancer metastasis. Biotechnologies for the specific localization of metastatic lymph nodes (MLNs) have attracted significant attention to efficiently define tumor metastases. Bioimaging modalities, particularly magnetic nanoparticles (MNPs) such as iron oxide nanoparticles, have emerged as promising tools in cancer bioimaging, with great potential for use in the preoperative and intraoperative tracking of MLNs. As radiation-free magnetic resonance imaging (MRI) probes, MNPs can serve as alternative MRI contrast agents, offering improved accuracy and biological safety for nodal staging in cancer patients. Although MNPs' application is still in its initial stages, exploring their underlying mechanisms can enhance the sensitivity and multifunctionality of lymph node mapping. This review focuses on the feasibility and current application status of MNPs for imaging metastatic nodules in preclinical and clinical development. Furthermore, exploring novel and promising MNP-based strategies with controllable characteristics could lead to a more precise treatment of metastatic cancer patients.

Ozonated triglyceride protects against septic lethality via preventing the activation of NLRP3 inflammasome. / é ¸åŒ–è„‚è‚ªé ¸é ¯é€šè¿‡æŠ‘åˆ¶NLRP3炎症小体活化减少脓毒症致死（英文）.

OBJECTIVES: Sepsis is a critical dysregulated host response with high mortality and current treatment is difficult to achieve optimal efficacy. Ozone therapy has been revealed to protect infection and inflammation-related diseases due to its role in antibiotic and immunoregulatory effect. Ozonated triglyceride is a key component of ozonated oil that is one of ozone therapy dosage form. However, the potential role of ozonated triglyceride in sepsis remains unclear. This study aims to explore the effect of ozonated triglyceride on septic mouse model and the molecular mechanism. METHODS: Intraperitoneal injection of lipopolysaccharide (LPS), cecal ligation and puncture (CLP) were applied to construct septic mouse model. The mouse serum was obtained for detection of cytokines, and lung tissues were collected for hematoxylin and eosin (HE) staining to evaluate the extent of lung injury in septic mouse with ozonated triglyceride treatment at different time and doses. The survival of septic mice was observed for 96 h and Kaplan-Meier analysis was used to analyze the survival rates. In addition, primary peritoneal macrophages and human acute monocytic-leukemia cell line (THP-1) were treated with inflammasome activators with or without ozonated triglyceride. The level of cytokines was detected by enzyme-linked immunosorbent assay (ELISA). The cleavage of caspase-1 and gasdermin-D (GSDMD) was detected by Western blotting. RESULTS: Ozonated triglyceride at different time and doses reduced the release of inflammasome-related cytokines [interleukin (IL)-1ß and IL-18] (all P<0.05) but not pro-inflammatory cytokines such as IL-6 and tumor necrosis factor-α (TNF-α) in septic mice (all P>0.05). Ozonated triglyceride significantly improved the survival rate of septic mice and reduced sepsis-induced lung injury (all P<0.05). Ozonated triglyceride significantly suppressed the canonical and non-canonical activation of NOD-like receptor family pyrin domain containing 3 (NLRP3) inflammasome (all P<0.05) but not affected absent in melanoma 2 (AIM2) and NLR family CARD domain-containing protein 4 (NLRC4) inflammasomes in vitro (all P>0.05). Ozonated triglyceride reduced the cleavage of caspase-1 and the downstream GSDMD. CONCLUSIONS: Ozonated triglyceride presents a protect effect on sepsis lethality via reducing cytokines release and sepsis-related organ injury. The mechanism is that ozonated triglyceride specifically suppresses the activation of NLRP3 inflammasome. Ozonated triglyceride is a promising candidate for sepsis treatment.

ICD-related risk model predicts the prognosis and immunotherapy response of patients with liver cancer.

Immunogenic cell death (ICD) is a novel cell death mechanism that activates and regulates the immune system against cancer. However, its prognostic value in liver cancer remains unclear. Here, several algorithms such as correlation analysis, Cox regression analysis, and Lasso regression analysis were carried out to evaluate the prognostic value of ICD-related genes in patients with liver cancer. Three ICD-related prognostic genes, the prion protein gene (PRNP), dynamin 1-like gene (DNM1L), and caspase-8 (CASP8), were identified and used to construct a risk signature. Patients with liver cancer were categorized into high- and low-risk groups using the ICD-related signature. Subsequently, a multivariate regression analysis revealed that the signature was an independent risk factor in liver cancer [hazard ratio (HR) = 6.839; 95% confidence interval (CI) = 1.625-78.785]. Patient survival was also predicted using the risk model, with area under the curve values of 0.75, 0.70, and 0.69 for 1-, 3-, and 5-year survival, respectively. Finally, a prognostic nomogram containing the clinical characteristics and risk scores of patients was constructed. The constructed ICD-related signature could serve as a prognostic and immunotherapeutic biomarker in liver cancer.

Metal-organic framework-encapsulated dihydroartemisinin nanoparticles induces apoptotic cell death in ovarian cancer by blocking ROMO1-mediated ROS production.

Dihydroartemisinin (DHA), a natural product derived from the herbal medicine Artemisia annua, is recently used as a novel anti-cancer agent. However, some intrinsic disadvantages limit its potential for clinical management of cancer patients, such as poor water solubility and low bioavailability. Nowadays, the nanoscale drug delivery system emerges as a hopeful platform for improve the anti-cancer treatment. Accordingly, a metal-organic framework (MOF) based on zeolitic imidazolate framework-8 was designed and synthesized to carry DHA in the core (ZIF-DHA). Contrast with free DHA, these prepared ZIF-DHA nanoparticles (NPs) displayed preferable anti-tumor therapeutic activity in several ovarian cancer cells accompanied with suppressed production of cellular reactive oxygen species (ROS) and induced apoptotic cell death. 4D-FastDIA-based mass spectrometry technology indicated that down-regulated reactive oxygen species modulator 1 (ROMO1) might be regarded as potential therapeutic targets for ZIF-DHA NPs. Overexpression of ROMO1 in ovarian cancer cells significantly reversed the cellular ROS-generation induced by ZIF-DHA, as well as the pro-apoptosis effects. Taken together, our study elucidated and highlighted the potential of zeolitic imidazolate framework-8-based MOF to improve the activity of DHA to treat ovarian cancer. Our findings suggested that these prepared ZIF-DHA NPs could be an attractive therapeutic strategy for ovarian cancer.

FHOD1 is upregulated in glioma cells and attenuates ferroptosis of glioma cells by targeting HSPB1 signaling.

BACKGROUND: As a new type of regulatory cell death, ferroptosis has been proven to be involved in cancer pathogenesis and therapeutic response. However, the detailed roles of ferroptosis or ferroptosis-associated genes in glioma remain to be clarified. METHODS: Here, we performed the TMT/iTRAQ-Based Quantitative Proteomic Approach to identify the differentially expressed proteins between glioma specimens and adjacent tissues. Kaplan-Meier survival was used to estimate the survival values. We also explored the regulatory roles of abnormally expressed formin homology 2 domain-containing protein 1 (FHOD1) in glioma ferroptosis sensitivity. RESULTS: In our study, FHOD1 was identified to be the most significantly upregulated protein in glioma tissues. Multiple glioma datasets revealed that the glioma patients with low FHOD1 expression displayed favorable survival time. Functional analysis proved that the knockdown of FHOD1 inhibited cell growth and improved the cellular sensitivity to ferroptosis in glioma cells T98G and U251. Mechanically, we found the up-regulation and hypomethylation of HSPB1, a negative regulator of ferroptosis, in glioma tissues. FHOD1 knockdown could enhance the ferroptosis sensitivity of glioma cells via up-regulating the methylated heat-shock protein B (HSPB1). Overexpression of HSPB1 significantly reversed FHOD1 knockdown-mediated ferroptosis. CONCLUSIONS: In summary, this study demonstrated that the FHOD1-HSPB1 axis exerts marked regulatory effects on ferroptosis, and might affect the prognosis and therapeutic response in glioma.

Non-coding RNAs: The recently accentuated molecules in the regulation of cell autophagy for ovarian cancer pathogenesis and therapeutic response.

Autophagy is a self-recycling and conserved process, in which the senescent cytoplasmic components are degraded in cells and then recycled to maintain homeostatic balance. Emerging evidence has suggested the involvement of autophagy in oncogenesis and progression of various cancers, such as ovarian cancer (OC). Meanwhile, the non-coding RNAs (ncRNAs) frequently regulate the mRNA transcription and other functional signaling pathways in cell autophagy, displaying promising roles in human cancer pathogenesis and therapeutic response. This article mainly reviews the cutting-edge research advances about the interactions between ncRNAs and autophagy in OC. This review not only summarizes the underlying mechanisms of dynamic ncRNA-autophagy association in OC, but also discusses their prognostic implications and therapeutic biomarkers. The aim of this review was to provide a more in-depth knowledge framework exploring the ncRNA-autophagy crosstalk and highlight the promising treatment strategies for OC patients.

Photoredox/Nickel Dual-Catalyzed Regioselective Allylic Arylations of Allyl Trifluoroborates with Aryl Halides.

An efficient photoredox/nickel dual-catalyzed coupling of allyl trifluoroborates with aryl halides has been developed, which provides an attractive route to diverse-substituted allylic benzenes. The method offers several advantages, such as high efficiency and regioselectivity, mild reaction conditions, wide substrate scope, and functional group compatibility. Mechanistic studies suggest that a π-allyl nickel(III) intermediate generated via the addition of an allyl radical to nickel species is possibly formed as a key reaction intermediate.

Unraveling the significance of exosomal circRNAs in cancer therapeutic resistance.

Exosomes are nanoscale extracellular vesicles secreted by a variety of cells, affecting the physiological and pathological homeostasis. They carry various cargoes including proteins, lipids, DNA, and RNA and have emerged as critical mediators of intercellular communication. During cell-cell communication, they can internalize either by autologous or heterologous recipient cells, which activate different signaling pathways, facilitating malignant progression of cancer. Among different types of cargoes in exosomes, the endogenous non-coding RNAs, such as circular RNAs (or circRNAs), have gained tremendous attention for their high stability and concentration, playing promising functional roles in cancer chemotherapeutic response by regulating the targeted gene expression. In this review, we primarily described the emerging evidence demonstrating the important roles of circular RNAs derived from exosomes in the regulation of cancer-associated signaling pathways that were involved in cancer research and therapeutic interventions. Additionally, the relevant profiles of exosomal circRNAs and their biological implications have been discussed, which is under investigation for their potential effect on the control of cancer therapeutic resistance.

COL12A1 as a prognostic biomarker links immunotherapy response in breast cancer.

Immunotherapy has shown promising efficacy for breast cancer (BC) patients. Yet the predictive biomarkers for immunotherapy response remain lacking. Based on two GEO datasets, 53 differentially expressed genes associated with durvalumab treatment response were identified. Using least absolute shrinkage and selection operator (LASSO) and univariate Cox regression, four genes (COL12A1, TNN, SCUBE2, and FDCSP) revealed prognostic value in the TCGA BC cohort. COL12A1 outperformed the others, without overlap in its survival curve. Survival analysis by Kaplan-Meier plotter demonstrated that COL12A1 was negatively associated with BC patients' prognosis. A COL12A1-based nomogram was further developed to predict the overall survival in BC patients. The calibration plot revealed an optimal agreement between nomogram prediction and actual observation. Moreover, COL12A1 expression was significantly up-regulated in BC tissues and COL12A1 knockdown impaired the proliferation of MDA-MB-231 and BT549 cells. Gene Ontology, Kyoto Encyclopedia of Genes and Genomes, and Gene Set Enrichment analysis pathway indicated that the function of COL12A1 was related to immunity-related pathways. Immunological analyses illustrated that COL12A1 was correlated with M2 macrophage infiltration and M2 macrophage markers (transforming growth factor beta 1 (TGFB1), interleukin-10, colony stimulating factor 1 receptor (CSF1R) and CD163) in BC. Immunohistochemistry staining further revealed a highly positive relationship of COL12A1 with TGF-ß1. The co-incubated models of BC cells and M2 macrophges showed COL12A1 knockdown suppressed M2 macrophage infiltration. Additionally, silencing COL12A1 suppressed TGF-B1 protein expression, and treating with TGFB1 could reverse the inhibitory effects on M2 macrophage infiltration by COL12A1 knockdown. Using immunotherapy datasets, we also found elevated expression of COL12A1 predicted poor response to anti-PD-1/PD-L1 therapy. These results reinforce the current understanding of COL12A1's roles in tumorigenesis and immunotherapy response in BC.

Plant-derived extracellular vesicles (PDEVs) in nanomedicine for human disease and therapeutic modalities.

BACKGROUND: The past few years have witnessed a significant increase in research related to plant-derived extracellular vesicles (PDEVs) in biological and medical applications. Using biochemical technologies, multiple independent groups have demonstrated the important roles of PDEVs as potential mediators involved in cell-cell communication and the exchange of bio-information between species. Recently, several contents have been well identified in PDEVs, including nucleic acids, proteins, lipids, and other active substances. These cargoes carried by PDEVs could be transferred into recipient cells and remarkably influence their biological behaviors associated with human diseases, such as cancers and inflammatory diseases. This review summarizes the latest updates regarding PDEVs and focuses on its important role in nanomedicine applications, as well as the potential of PDEVs as drug delivery strategies to develop diagnostic and therapeutic agents for the clinical management of diseases, especially like cancers. CONCLUSION: Considering its unique advantages, especially high stability, intrinsic bioactivity and easy absorption, further elaboration on molecular mechanisms and biological factors driving the function of PDEVs will provide new horizons for the treatment of human disease.

Current understanding of plant-derived exosome-like nanoparticles in regulating the inflammatory response and immune system microenvironment.

Natural compounds are widely used to prevent and treat various diseases due to their antioxidant and anti-inflammatory effects. As a kind of promising natural compound, plant-derived exosome-like nanoparticles (PELNs) are extracted from multivesicular bodies of various edible plants, including vegetables, foods, and fruits, and mainly regulate the cellular immune response to pathogen attacks. Moreover, PELNs could remarkably interfere with the dynamic imbalance between pro-inflammatory and anti-inflammatory effects, facilitating to maintain the homeostasis of cellular immune microenvironment. PELNs may serve as a better alternative to animal-derived exosomes (ADEs) owing to their widespread sources, cost-effectiveness, and easy accessibility. PELNs can mediate interspecies communication by transferring various cargoes such as proteins, lipids, and nucleic acids from plant cells to mammalian cells. This review summarizes the biogenesis, composition, and classification of exosomes; the common separation, purification, and characterization methods of PELNs, the potential advantages of PELNs over ADEs; and the anti-inflammatory and immunomodulatory functions of PELNs in various diseases including colitis, cancer, and inflammation-associated metabolic diseases. Additionally, the future perspectives of PELNs and the challenges associated with their clinical application are discussed.