Colorectal cancer (CRC) is a leading cause of cancer-related morbidity and mortality globally. Exosomal microRNAs (miRNAs) are known to modulate tumor progression by influencing immune responses and vascular dynamics. However, the roles of specific exosomal miRNAs, such as miR-425-5p and miR-135b-3p, in CRC remain unclear.
To explore the specific roles and underlying mechanisms of exosomal miR-425-5p and miR-135b-3p in CRC progression.
Differentially expressed miRNAs were identified through microarray analysis of exosomes isolated from CRC tissues and adjacent normal mucosa. Functional roles of miR-425-5p and miR-135b-3p were evaluated in vitro using macrophage polarization, T cell differentiation, and vascular permeability assays, as well as in vivo tumor formation and metastasis experiments in nude mice. Validation experiments were performed using CRC cell lines (HCT116 and SW620).
Exosomal miR-425-5p and miR-135b-3p were significantly upregulated in CRC compared to normal tissues. Functional studies revealed that miR-425-5p promotes macrophage M2-like polarization and suppresses T cell proinflammatory responses, while miR-135b-3p enhances vascular permeability and angiogenesis. Inhibition of these miRNAs in CRC cell-derived exosomes significantly suppressed tumor growth and metastasis in nude mice, reprogramming the tumor microenvironment toward reduced angiogenesis and enhanced immune activation. Combined inhibition of both miRNAs resulted in the most pronounced effects.
Exosomal miR-425-5p and miR-135b-3p drive CRC progression by promoting immune suppression and vascular permeability. Their inhibition offers a promising strategy for modulating the tumor microenvironment and limiting CRC metastasis.
©The Author(s) 2025. Published by Baishideng Publishing Group Inc. All rights reserved.

Chronic prostatitis is a common urological disorder in young and middle-aged men, characterized by frequent relapses and an unknown etiology. We investigated the potential function of insulin-like growth factor 1 (IGF1) -related ligands in chronic prostatitis in the current study.
In this study, we established the chronic experimental autoimmune prostatitis mouse model H&E staining was used to assess immune cell infiltration in prostate tissue, while RT-qPCR and Western blot analyses were performed to validate gene and protein expression differences across groups, respectively. Immunofluorescence staining was utilized to determine the spatial distribution of key proteins. Flow cytometry was conducted to analyze the proportions of immune cell populations in different experimental groups. Adeno-associated virus (AAV) was employed to knock down Igflr, and ELISA was used to measure cytokine levels in the peripheral blood of mice. Statistical significance was defined as P < 0.05, and all tests were conducted as two-tailed. Data analysis was performed using R software (version 4.2.2).
We successful established the EAP model and discovered that the expression of IGF1R, content of IGF1-related ligands, was highest in prostate tissue and CD4+ T cell subset. Furthermore, protein expression levels of IGF1R were also validated that upregulated in mouse prostate tissue. Colocalization of immunofluorescence suggested that IGF1R protein is highly expressed on CD4+ T cells. Stimulation with desIGF1, a truncated analogue of IGF1, resulted in the significantly increased prostate inflammation and pain scores observed in the EAP+desIGF1 group mouse compared to other groups In vitro study further suggested that desIGF1 could increase the proportion of Th17 cells while decreasing the proportion of Treg cells. In the EAP+AAV-shIgf1r group, the knock down function of igf1r led to the alleviative prostate inflammation and response frequency of pain behavior test. We found that calcium ion associated pathways are active in EAP by bioinformatics, and further validated that PKC-β protein with significantly increased expression noted in the EAP+desIGF1 group, and decreased in the EAP+AAV-shIgf1r group. We also found that the proportion of Th17 cells increased after activation of PKC- β by flow cytometry.
These findings support that PKC-β associated pathways mediated by IGF1/IGF1R axis may impact Th17 cell differentiation and exacerbating prostate inflammation in EAP mouse, providing new molecular targets for the clinical therapeutic strategy.
© 2025 Guan et al.

Clinical approaches for cancer therapy face several interrelated challenges involving inefficient drug delivery, potential adverse side effects, and inconvenience. Here, we present an integrated wearable flexible ultrasound microneedle patch (wf-UMP) that serves as a portable platform for convenient, efficient, and minimally invasive cancer therapy. The wf-UMP adopts an all-in-one bioelectronic concept, which integrates a stretchable lead-free ultrasound transducer array for acoustic emission, a bioadhesive hydrogel elastomer for robust adhesion and acoustic coupling, and a dissolvable microneedle patch loaded with biocompatible piezoelectric nanoparticles for painless drug delivery and reactive oxygen species generation. With soft mechanical properties and enhanced electromechanical performance, wf-UMP can be robustly worn on curved and dynamic tissue surfaces for easy and effective manipulation. In preclinical studies involving mice, wf-UMP demonstrated notable anticancer effects by inducing tumor cell apoptosis, amplifying oxidative stress, and modulating immune cell proliferation. Furthermore, the synergistic immunotherapy induced by wf-UMP and Anti-PD1 further improved anticancer immunity by activating immunogenic cell death and regulating macrophages polarization, inhibiting distant tumor growth and tumor recurrence.
© 2025. The Author(s).

Immune checkpoint inhibitors (ICIs) have achieved great success; however, a subset of patients exhibits no response. Consequently, there is a critical need for reliable predictive biomarkers. Our focus is on CDC42, which stimulates multiple signaling pathways promoting tumor growth. We hypothesize that an impaired function of CDC42 may serve as an indicator of a patient's response to ICI therapy.
We consider CDC42 and its downstream binding and effector proteins as a gene set, as mutations in these components could lead to defective CDC42 function. To elucidate the biomarker function of mutations within the CDC42 gene set, we curated a comprehensive discovery dataset that included seven ICI treatment cohorts. And we curated two ICI treatment cohorts for validation. We explored the mechanism based on The Cancer Genome Atlas database. We also examined whether combining a CDC42 inhibitor with ICI could enhance ICI's efficacy.
Mutations in the CDC42 gene set were associated with improved overall survival and progression-free survival. Furthermore, our analysis of immune response landscapes among different statuses of the CDC42 gene set supports its role as a biomarker. Animal experiments also revealed that the combination of the CDC42 inhibitor (ML141) with anti-PD-1 blockade can additively reduce tumor growth.
Our study suggests that the CDC42 gene set mutations could potentially serve as a novel biomarker for the clinical response to ICI treatment. This finding also provides insights into the potential of combining ICI and CDC42 inhibitor use for more efficient patient treatment.
© 2025 The Author(s). Cancer Medicine published by John Wiley & Sons Ltd.

The hypoxic and immunosuppressive tumor microenvironment (TME) remains a major obstacle to impede cancer immunotherapy. Here, we found that sononeoperfusion-a new effect of tumor perfusion enhancement induced by low mechanical index ultrasound stimulated microbubble cavitation (USMC)-ameliorated tumor tissue oxygenation and induced tumor vascular normalization (TVN). This TVN might be associated with the down-regulation of hypoxia-inducible factor 1-alpha (HIF-1α) and vascular endothelial growth factor (VEGF) within tumors. Moreover, the sononeoperfusion effect reduced the accumulation of immunosuppressive cells, such as regulatory T cells (Tregs), myeloid-derived suppressor cells (MDSCs) and M2-like tumor-associated macrophages (M2-TAMs), and decreased the production of immune inhibitory factors like transforming growth factor-β1 (TGF-β1), interleukin 10 (IL-10), chemoattractant chemokines CC-chemokine ligand 22 (CCL22), CCL28, adenosine and lactate within tumors. Notably, flow cytometry analysis revealed that sononeoperfusion not only increased the percentage of tumor infiltrating-CD8+ T cells, but also promoted the generation of interferon-γ (IFN-γ) and tumor necrosis factor-α (TNF-α) by these cells. Furthermore, the improved immune TME by sononeoperfusion effect sensitized anti-PD-L1 treatment both in MC38 colon cancer and Lewis lung carcinoma mice, resulting in tumor regression and prolonged survival. Mechanically, the enhanced efficacy of combination therapy was mainly based on promoting the infiltration and function of CD8+ T cells within tumors. Together, sononeoperfusion could ameliorate hypoxia and immunosuppression in the TME, thereby potentiating anti-PD-L1 therapy for solid tumors. This novel method of USMC generating sononeoperfusion effect may provide a new therapeutic modality for facilitating cancer immunotherapy.
Copyright © 2024 The Author(s). Published by Elsevier B.V. All rights reserved.