Min Chen

Intracerebral hemorrhage (ICH) is a severe neurological condition characterized by high mortality and long‐term disability. The pathophysiology of ICH involves not only primary hematoma formation but also secondary injury mechanisms such as blood–brain barrier disruption, oxidative stress, excitotoxicity, and neuroinflammation. Hematoma‐derived factors like hemoglobin, iron, and thrombin, together with pro‐inflammatory cytokines from activated glial and immune cells, exacerbate neurovascular dysfunction. Emerging research highlights the role of the bone‐brain axis, where bone marrow‐derived cells and osteokines influence systemic inflammation, angiogenesis, and tissue repair. Hydrogel‐based drug delivery systems (HDDS) have gained attention for their potential to address these challenges, offering controlled release, biocompatibility, and targeted delivery. This review summarizes recent advancements in hydrogel‐based therapeutic strategies for ICH treatment, focusing on structure‐activity relationships and the integration of bone‐brain axis modulation for enhanced neuroregeneration. We discuss key translational barriers, including biosafety, manufacturing scalability, and inter‐patient heterogeneity. Future advances are expected to rely on the development of dynamic, microenvironment‐responsive hydrogels that can synchronize drug release with stage‐specific pathological cues, improving therapeutic precision. Moreover, combining HDDS with multimodal therapies and minimally invasive neurosurgical techniques may further enhance clinical outcomes. The potential for HDDS to target both local brain injury and systemic inter‐organ crosstalk represents a promising direction for advancing clinical applications in ICH.

Myocardial infarction (MI) triggers a systemic immune response involving bidirectional crosstalk between the injured heart and remote immune organs. However, the dynamic, multi-organ nature of this “heart-immune axis” remains poorly defined. By targeting specific aspects of the immune response, particularly the modulation of macrophage polarization and the attenuation of excessive inflammation, this strategy holds therapeutic potential for preserving cardiac function and enhancing long-term patient outcomes, thereby opening a new frontier in cardiovascular therapeutics. In this review, we propose a novel framework that divides post-MI immune response into three interconnected phases: inflammation, resolution, and remodeling. Within each phase, we delineate the bidirectional crosstalk mechanisms between the injured heart and immune organs via cytokine networks and hematopoietic progenitor mobilization. We then critically evaluate emerging immunomodulatory strategies, ranging from targeting CCR2/CCL2 axis, promoting regulatory T cells, with emphasis on their mechanistic rationale, clinical trial progress, and major translational gaps. Unlike conventional anti-inflammatory approaches that suppress broad immune activity, axis-targeted immunomodulation aims to preserve or restore protective cardiac repair. This review provides a phase-specific, multi-organ, and therapeutically actionable roadmap of the heart-immune axis, offering new perspectives for next-generation MI therapies.

Background: Colorectal cancer (CRC) remains a leading cause of cancer-related death worldwide, with distant organ metastasis accounting for the majority of fatal outcomes. Epithelial-mesenchymal transition (EMT) plays a central role in enabling tumor cells to acquire migratory and tissue-invasive competence. Within this context, the IκB kinase β (IKKβ)/nuclear factor-kappa B (NF-κB)/Snail signaling cascade has emerged as a key regulatory hub orchestrating EMT-associated gene programs. Curcumin, a plant-derived polyphenolic compound, displays pleiotropic antitumor properties; however, the molecular basis of its capacity to restrain CRC cell motility requires further clarification. Methods: This investigation evaluated the migration-suppressive capacity of curcumin using HCT116 and SW620 CRC cell lines. Half maximal inhibitory concentration (IC₅₀) values were derived from MTT-based cytotoxicity measurements after 48 hours of drug exposure. Cell cycle progression was characterized by flow cytometry, long-term proliferative potential was gauged through clonogenic assays, and motility was quantified using scratch wound and Transwell chamber approaches. Protein-level alterations in EMT-associated molecules [E-cadherin, N-cadherin, matrix metalloproteinase-2 (MMP-2), vascular endothelial growth factor (VEGF)] and constituents of the IKKβ/NF-κB/Snail signaling network were examined by immunoblotting. Results: Following 48-h curcumin exposure, IC₅₀ values of 11.8 µM (HCT116) and 19.5 µM (SW620) were obtained. Uniform working concentrations (0, 6, 12 µM for HCT116; 0, 10, 20 µM for SW620) were applied throughout all downstream assays. Curcumin provoked cell cycle arrest and concentration-dependently reduced proliferative capacity, clonogenic survival, and migratory potential. At the protein level, E-cadherin abundance increased while N-cadherin, MMP-2, and VEGF levels declined in a dose-responsive fashion. Mechanistically, curcumin lowered IKKβ expression, attenuated NF-κB p65 phosphorylation, and down-regulated Snail protein. Conclusions: Collectively, these results indicate that curcumin curtails CRC cell migration, at least in part, through suppression of the IKKβ/NF-κB/Snail-driven EMT program, thereby providing a mechanistic rationale for its further preclinical and clinical evaluation as an adjunctive anti-metastatic approach in CRC.

This review highlights an innovative co-delivery system using hydrogel microneedles (MNs) to encapsulate exosomes and drugs, presenting a transformative strategy for treating interconnected bone and brain disorders. By offering potential strategies to address the blood-brain barrier, MNs enable minimally invasive delivery of exosomes, natural vesicles rich in microRNAs and cytokines, facilitating spatiotemporal control over therapeutic release. This system enhances regenerative outcomes in diabetic wounds, myocardial infarction, osteochondral defects, and neurological conditions via multi-mechanistic actions including immunomodulation, angiogenesis, and tissue repair. However, clinical translation remains challenging due to issues in exosome standardization, microneedle mechanical properties, and long-term biosafety.

Background: Asthma affects approximately 334 million people worldwide. Accumulating evidence indicates that gut dysbiosis exacerbates airway inflammation through the gut–lung axis. In the present study, using an OVA-induced murine model of asthma, we investigated whether Huanglong Zhixiao Formula (HLZXF) restores gut lung homeostasis by reshaping the gut microbiota and enhancing intestinal barrier function, thereby attenuating pulmonary pathological changes. Methods: Female BALB/c mice were randomly assigned to three groups ( n = 15 per group): Control (C), Asthma Model (MX), and HLZXF-treated (ZG) groups. Asthma was induced by OVA sensitization and challenge over a 6-week period. The ZG group received daily oral gavage of HLZXF, 1 h prior to each OVA challenge. Fecal samples were collected for metagenomic sequencing. Lung and intestinal tissues were excised for HE and IHC staining of tight junction proteins, including Claudin, Occludin, and ZO-1. Alpha and beta diversity analyses were conducted to evaluate the composition and structure of the gut microbiota. Results: We analyzed the structure of the gut microbiota, detected the expression levels of intestinal barrier-related proteins, and assessed inflammatory injury in the lungs and intestines. Results demonstrated that HLZXF significantly ameliorated gut microbiota dysbiosis in asthmatic mice, as evidenced by the significant enrichment of Heminiphilus faecis and Paramuribaculum intestinale . Additionally, certain fungal taxa, such as Piromyces finnis and Rhizopus arrhizus , were significantly enriched in the ZG group. HLZXF also significantly upregulated the expression levels of the tight junction proteins Claudin, Occludin, and ZO-1 in intestinal tissues, thereby promoting the repair of the intestinal mucosal barrier. Furthermore, HLZXF significantly attenuated inflammatory cell infiltration and tissue injury in the lungs and intestines, alleviated alveolar septal thickening, and enhanced the integrity of the intestinal mucosal barrier. Conclusion: This study elucidates the potential therapeutic mechanisms of HLZXF in the treatment of asthma from the perspective of gut microbiota and intestinal barrier function. It highlights that HLZXF can attenuate pulmonary inflammation by regulating the balance of gut microbiota and enhancing intestinal barrier function.

This study investigated the mechanism by which curcumin induces apoptosis through glycolytic regulation in osteosarcoma cells (U2OS, MG63) via the MAPK axis. Network pharmacology, protein-protein interaction analysis, and molecular docking were integrated to identify core targets and validate the central role of the MAPK pathway. In vitro , curcumin dose-dependently inhibited cell proliferation (IC50: 32.6 μmol/L in MG63, 37.3 μmol/L in U2OS) and migration, while promoting apoptosis as confirmed by CCK-8, wound healing, flow cytometry, and TUNEL assays. Western blot analysis demonstrated that curcumin significantly upregulated the expression of pro-apoptotic proteins Bax and Cleaved-PARP, as well as phosphorylated P38 and JNK (P-P38, P-JNK), while downregulating the glycolytic enzymes HK2 and PKM2 and the anti-apoptotic protein Bcl-2 (all P < 0.05). Total JNK and P38 levels remained unchanged. The TUNEL assay further confirmed concentration-dependent enhancement of apoptosis, with a marked increase in TUNEL-positive cells at 40 μmol/L. Combined bioinformatic and experimental evidence indicates that curcumin inhibits glycolysis and promotes osteosarcoma cell apoptosis primarily through activation of the JNK/P38 MAPK signaling branch.

Accumulating evidence indicates that fermitin family member 1 (FERMT1) is closely related to various disease processes. However, its association with cancer prognosis, tumor microenvironment (TME), and metastatic progression remains unclear, particularly in lung adenocarcinoma (LUAD). We conducted a comprehensive pan-cancer analysis to evaluate the clinical relevance of FERMT1 expression in LUAD and its functional role in metastasis. We conducted a multi-omics and functional analysis to evaluate FERMT1 expression across multiple cancer types using 11,069 patient datasets from 33 cancers via The Cancer Genome Atlas (TCGA) database and the University of California, Santa Cruz (UCSC) Xena platform. We assessed FERMT1 expression heterogeneity, prognostic significance, genomic alterations, immune infiltration, and drug sensitivity in pan-cancer and LUAD-specific contexts. Additionally, functional experiments were performed to investigate its role in LUAD cell lines (NCI-H441 and Calu-3). FERMT1 was significantly overexpressed in 13 tumors and downregulated in 3 compared to normal tissues. Its high expression correlated with poor prognosis in multiple cancers and influenced immune cell infiltration. Genomic alterations in FERMT1 were prevalent across cancers. Pan-cancer analysis revealed significant correlations between FERMT1 expression, TME, and stemness scores. In LUAD, FERMT1 expression was significantly associated with tumor T classification (P=0.001) and higher levels in tumor tissues than in normal tissues. Functional assays demonstrated that FERMT1 deletion reduced LUAD cell migration and invasion. FERMT1 serves as a potential biomarker for LUAD prognosis and cancer immunotherapy, highlighting its role in tumor progression and therapeutic response.