Jidong Zhang

Plant-derived extracellular vesicle-like nanovesicles (PELNs) are being investigated as plant-derived preparations with intrinsic bioactivity and potential utility as nanocarriers. Microneedles (MNs) can create transient skin microchannels and may support localized intradermal delivery of vesicle-containing formulations. The intersection of these approaches is promising, but the available evidence remains heterogeneous and includes direct PELN–MN studies, PELN studies without MNs, and related mammalian extracellular vesicle platforms. Here we provide a comprehensive review of PELN identity, isolation, characterization, cargo, and proposed dermatological activities, followed by an assessment of MN designs relevant to vesicle delivery. We searched PubMed, Web of Science, Scopus, and Embase, screened records in duplicate, and classified each included study by the directness of evidence into studies providing direct PELN-MN skin evidence, PELN evidence without MNs, mammalian extracellular vesicle MN analogue evidence, and non-dermatological or conceptual evidence. Current limitations include uncertain vesicle identity, co-isolated plant constituents, variable preparation and dosing methods, limited controls for the mechanical effects of microneedling, and incomplete clinical follow-up. Progress toward translation will require source-specific quality attributes, orthogonal potency assays, transparent comparators, and adequately controlled clinical studies.

Objective: To evaluate whether human adipose-derived mesenchymal stem cells (ADSCs) protect against ᴅ-galactose (ᴅ-gal)-induced aging-like testicular injury and to investigate the involvement of the Keap1/Nrf2 pathway and NLRP3-associated pyroptosis. Methods: A mouse model of aging-like testicular injury was established by subcutaneous administration of ᴅ-gal for 8 weeks, followed by tail vein injection of ADSCs. Testicular morphology, blood–testis barrier (BTB) integrity, and senescence-associated markers (p16, p21) were assessed. In vitro, TM4 Sertoli cells were used to establish a senescence model and Tranwell co-cultured with ADSCs. Oxidative stress, inflammatory responses, and pyroptosis-related markers were evaluated using biochemical assays, immunofluorescence, Western blotting, and RT-qPCR. The involvement of the Keap1/Nrf2-NLRP3 axis was further examined using pharmacological inhibitors. Results: ADSC treatment significantly alleviated ᴅ-gal-induced testicular atrophy and histopathological injury, accompanied by reduced expression of the senescence markers p16 and p21 and partial restoration of BTB-related structures. ADSCs also attenuated oxidative stress, as evidenced by decreased ROS and MDA levels, increased SOD activity, and enhanced expression of Nrf2 and its downstream antioxidant targets, including HO-1 and NQO1. In parallel, ADSC administration suppressed NLRP3 activation, reduced caspase-1 cleavage, and lowered the expression of pro-inflammatory cytokines. In TM4 cells, inhibition of Nrf2 weakened the protective effects of ADSCs and was accompanied by reactivation of NLRP3-associated signaling, whereas inhibition of NLRP3 attenuated senescence- and inflammation-related changes without restoring Nrf2 activity. Conclusions: ADSCs alleviate ᴅ-gal-induced aging-like testicular injury, at least in part, by restoring redox balance, preserving BTB-associated structure, and suppressing NLRP3-associated pyroptosis through the Keap1/Nrf2 pathway. These findings suggest that ADSC-based therapy may represent a promising strategy for age-related male reproductive dysfunction, while further studies using genetic models and functional fertility endpoints are needed to confirm causality and translational relevance.

Liver fibrosis is a chronic pathological process driven by the activation of hepatic stellate cell (HSC) and characterized by the excessive deposition of extracellular matrix (ECM) components in response to persistent liver injury. This condition can lead to progressive hepatic dysfunction, cirrhosis, and ultimately liver failure. Growth differentiation factor 15 (GDF15) has emerged as a pivotal regulator in the initiation and progression of liver fibrosis, exhibiting context-dependent profibrotic and antifibrotic effects. GDF15 modulates multiple cellular processes, including HSC activation and macrophage polarization, as well as the functions of T cells, natural killer cells, B cells and mesenchymal stem cells. This review provides a comprehensive overview of the role of GDF15 in regulating HSC activation and immune cell responses and elaborates on its immunomodulatory functions in attenuating liver fibrosis. Furthermore, we discuss the therapeutic potential of targeting GDF15 for the treatment of liver fibrosis. Ultimately, this review aims to provide a theoretical foundation and propose novel intervention strategies for the early diagnosis and targeted therapy of liver fibrosis.

Background: Tectoridin is a prominent isoflavone glycoside found in herbs such as Belamcanda chinensis (L.) DC and Iris tectorum Maxim. It has drawn increasing research interest due to its promising pharmacological activities. However, no critical review to date has determined whether its broad pharmacological activity stems from binding to specific targets or from the non-specific, broad-spectrum activity commonly associated with flavonoids. This paper provides a comprehensive review of tectoridin, covering its plant sources, pharmacological effects, pharmacokinetics, and toxicity, alongside an in-depth analysis of the mechanisms underlying its pharmacological effects and strategic recommendations for advancing its clinical translation. Methods: A systematic literature search was conducted in PubMed, Web of Science, Google Scholar, SciFinder, and CNKI for publications from 1968 to 2025 using keywords including tectoridin, tectorigenin 7-O-glucoside, traditional uses, ethnopharmacology, pharmacology, bioactive compounds, biological activity, pharmacokinetics and toxicity. Results: Tectoridin exhibits a broad spectrum of pharmacological activities, including anticancer, anti-inflammatory, hepatoprotective, antidiabetic, antioxidant, cardiovascular, and estrogenic effects. Pharmacokinetic studies have shown rapid tissue distribution and slow elimination; the aglycone metabolite tectorigenin often displays enhanced bioactivity, and chemical modifications may further improve efficacy. Toxicity data suggest relative safety in medicinal food contexts, but comprehensive in vivo studies remain limited. Tectoridin shows promise for treating cancer and inflammatory diseases; however, further research is needed to elucidate its molecular mechanisms, clarify toxicity, and optimize bioactivity. Conclusions: This review bridges natural products and modern therapeutics by focusing on tectoridin, highlighting its therapeutic potential, addressing challenges, and offering new perspectives for treating various diseases.

Plant-derived exosome-like nanovesicles (PELNs) are naturally derived lipid-bilayer nanocarriers, which possess intrinsic activity to modulate oxidative stress through their diverse cargos of proteins, lipids, nucleic acids, and phytochemicals. Unlike conventional oxidative-stress interventions, PELNs achieve multifactorial, cargo-based redox regulation within a protective membrane that enhances bioavailability, preserves labile components, and improves cellular uptake while reducing off-target toxicity. Their low immunogenicity and inherent stability, together with the potential for surface modification and therapeutic co-loading, enable tissue-selective and sustained control of redox balance, including integration with biomaterial platforms such as hydrogels and scaffolds. This review synthesizes advances in PELN biogenesis, compositional characteristics, and isolation methods, and compares their biological and functional traits with mammalian exosomes. We propose an antioxidant/pro-oxidant dichotomy as a unifying mechanistic framework and highlight therapeutic prospects in oxidative stress–related disorders such as wound healing, atherosclerosis, neurodegeneration, and cancer. Translational considerations—including manufacturing scale-up, stability, biodistribution and biosafety—are critically discussed, alongside practical strategies to address these challenges. By linking mechanistic understanding with material-based engineering and application-oriented perspectives, this review establishes a materials-to-clinic roadmap for PELNs and positions them as promising next-generation nano-tools for precision oxidative-stress therapy.

Copper is an important trace element in the human body and plays an essential role in cells, where it is involved in synthesizing copper‑dependent enzymes, including superoxide dismutase, cytochrome c oxidase, tyrosinase, lysyl oxidase, dopamine‑β‑hydroxylase and other related copper‑containing enzymes. Copper overload or deficiency affects cell activity, leading to the development of neurodegenerative diseases or cancer. Neurodegenerative diseases, including Alzheimer's, Parkinson's and Huntington's disease, as well as cancer, represent significant chronic health burdens. The complexity of their pathophysiological mechanisms, coupled with the limitations of current targeted therapies, complicates the development of effective treatments. This review provides a comprehensive overview of the current understanding of copper's regulatory mechanisms in health and disease, with particular emphasis on its roles in neurodegenerative disorders and cancer. Recent advances in copper‑targeted therapeutic strategies, including copper chelators, ionophores and copper‑based nanoparticles, were highlighted. Furthermore, the clinical potential, key challenges and future prospects of these interventions were assessed. By synthesizing recent preclinical and clinical evidence, this review aims to contribute novel perspectives for improving the treatment of copper‑associated diseases.

Exosomes are lipid bilayer vesicles approximately 30–150 nm in diameter that serve as key mediators of intercellular communication. By transporting diverse bioactive molecules, including proteins and nucleic acids, they play a crucial role in tumor initiation and progression. Among their functional cargo, exosomal microRNAs (miRNAs) are central to epigenetic regulation and intercellular signaling, significantly influencing tumor biology. This review provides a comprehensive overview of the multifaceted roles of exosomal miRNAs in remodeling the tumor microenvironment (TME) and regulating cancer stem cells (CSCs). Specifically, exosomal miRNAs modulate various immune cells (such as macrophages, T cells, and NK cells) as well as cancer-associated fibroblasts (CAFs), thereby promoting immune evasion, angiogenesis, epithelial–mesenchymal transition (EMT), and metastatic progression. At the same time, they enhance CSC stemness, self-renewal, and therapeutic resistance, ultimately driving tumor recurrence and dissemination. Furthermore, exosome-mediated miRNA signaling acts as a critical force in malignant progression. Finally, we discuss the clinical potential of exosomal miRNAs as diagnostic and prognostic biomarkers, therapeutic targets, and vehicles for targeted drug delivery, highlighting their translational value and future directions in cancer research.

The spontaneous phenomena known as liquid–liquid phase separation (LLPS) is caused by weak interactions between substances. Under specific circumstances, macromolecules like proteins and nucleic acids can dynamically aggregate to form biomolecular condensates. This phenomenon offers a novel perspective on the intricate spatiotemporal coordination within living cells. Recent research has shown that LLPS is crucial for the initiation and progression of cancer, mainly by influencing multiple cellular activities such as metabolism, autophagy, stress responses, immune reactions, transcriptional regulation and intracellular signaling pathways, etc. Dysregulation of LLPS significantly affects the proliferation, metastasis, and therapeutic resistance of hepatocellular carcinoma (HCC) cells. Here, we introduce recent advances in understanding how LLPS regulates HCC-associated signaling pathways. Furthermore, we discuss the molecular mechanisms underlying the LLPS of oncogenic signaling molecules and its potential implication. Finally, we summarize several feasible approaches for treating HCC by targeting LLPS. These findings have the potential to establish a novel theoretical framework and therapeutic hypothesis for cancer treatment, thus providing more precise and individualized clinical strategies and significantly enhance patient prognosis and overall survival rates.

Exosomes are lipid bilayer vesicles measuring 30–150 nm in diameter that serve as crucial mediators of intercellular communication. By transporting bioactive molecules such as proteins and nucleic acids, they play a pivotal role in cancer progression. Among their cargo, exosomal microRNAs (miRNAs) are central to epigenetic regulation and signal transduction. Cancer stem cells (CSCs), a distinct subpopulation with self-renewal and multi-lineage differentiation capabilities, drive tumor initiation, metastasis, and recurrence, making them critical therapeutic targets. This review systematically summarizes the regulatory mechanisms of exosomal miRNAs in tumorigenesis, metastasis, and drug resistance, with a particular focus on their roles in maintaining CSC properties and promoting therapy resistance. We further discuss their clinical potential as liquid biopsy biomarkers and therapeutic targets. Finally, we outline current research limitations and future directions to advance precision oncology.

Icariin (ICA), a principal pharmacologically active constituent of the Chinese herbal medicine Epimedium, exhibits numerous therapeutic advantages. Current research has explored ICA's anti-tumor capabilities, including its inhibition of cell proliferation and promotion of cell death, as well as its potential therapeutic effects in repairing reproductive damage by promoting cell proliferation. However, the precise molecular mechanisms underlying ICA's ability to switch between promoting cell growth and inducing cell death remain inadequately understood. This review aims to elucidate the dual mechanisms of ICA in inhibiting cell proliferation and promoting cell proliferation.