Cancer-associated fibroblasts (CAFs) are key players in cancer development and therapy, and they exhibit multifaceted roles in the tumor microenvironment (TME). From their diverse cellular origins, CAFs undergo phenotypic and functional transformation upon interacting with tumor cells and their presence can adversely influence treatment outcomes and the severity of the cancer. Emerging evidence from single-cell RNA sequencing (scRNA-seq) studies have highlighted the heterogeneity and plasticity of CAFs, with subtypes identifiable through distinct gene expression profiles and functional properties. CAFs influence cancer development through multiple mechanisms, including regulation of extracellular matrix (ECM) remodeling, direct promotion of tumor growth through provision of metabolic support, promoting epithelial-mesenchymal transition (EMT) to enhance cancer invasiveness and growth, as well as stimulating cancer stem cell properties within the tumor. Moreover, CAFs can induce an immunosuppressive TME and contribute to therapeutic resistance. In this review, we summarize the fundamental knowledge and recent advances regarding CAFs, focusing on their sophisticated roles in cancer development and potential as therapeutic targets. We discuss various strategies to target CAFs, including ECM modulation, direct elimination, interruption of CAF-TME crosstalk, and CAF normalization, as approaches to developing more effective treatments. An improved understanding of the complex interplay between CAFs and TME is crucial for developing new and effective targeted therapies for cancer.

Macrophages are a major inflammatory cell type involved in the development and progression of many important chronic inflammatory diseases. We previously found that apolipoprotein E-deficient (Apoe(-/-)) mice with the C57BL/6 (B6) background develop type 2 diabetes mellitus (T2DM) and accelerated atherosclerosis when fed a Western diet and that there are increased macrophage infiltrations in pancreatic islets and aorta. The formyl peptide receptor 1 (FPR1) is abundantly expressed on the surface of macrophages. The purpose of this study was to evaluate the applicability of cinnamoyl-F-(D)L-F-(D)L-F (cFLFLF), a natural FPR1 antagonist, to detection of macrophages in the pancreatic islets and aorta. (64)Cu labeled cFLFLF and (18)F-fluorodeoxyglucose (FDG) were administered to mice with or without T2DM. Diabetic mice showed an increased (18)FDG uptake in the subcutaneous fat compared with control mice, but pancreatic uptake was minimal for either group. In contrast, diabetic mice exhibited visually noticeable more cFLFLF-(64)Cu retention in pancreas and liver than control mice. The heart and pancreas isolated from diabetic mice contained more macrophages and showed stronger PET signals than those of control mice. Flow cytometry analysis revealed the presence of macrophages but not neutrophils in pancreatic islets. Real-time PCR analysis revealed much higher FPR1 expression in pancreatic islets of diabetic over control mice. Autoradiography and immunohistochemical analysis confirmed abundant FPR1 expression in atherosclerotic lesions. Thus, (64)Cu-labeled cFLFLF peptide is a more effective PET agent for detecting macrophages compared to FDG.

An increasing number of studies indicate that the gut, cervical, and vaginal microbiota may play crucial roles in the development of cervical cancer (CC). However, the interactions between the microbiota and the host are yet unknown. To address this gap, a systematic review and meta-analysis were conducted to assess the microbiota alterations in a variety of body locations, including the gut and genital tract. Electronic searches of PubMed, Embase, Web of Science, and the Cochrane Library were conducted to retrieve eligible papers published from January 1, 2014, to January 1, 2024 (PROSPERO: CRD42024554433). This study was restricted to English-language studies reporting on alpha diversity, beta diversity, and relative abundance, as well as on patients with CC whose microbiota had been analyzed via next-generation sequencing technologies. To assess the risk of bias (RoB), we utilized the Newcastle‒Ottawa Quality Assessment Scale (NOS) and the ROBINS-I tool. For the meta-analysis, we employed Review Manager 5.4. Thirty-six eligible studies were included in this review. The Chao1 index (SMD = 0.96, [95% CI: 0.71, 1.21], I² = 0%) and the Shannon index (SMD = 1.02, [95% CI: 0.53, 1.50], I² = 85%) values from vaginal samples were significantly greater in patients than in the controls. In the cervical samples, the Shannon index value (SMD = 1.29, [95% CI: 0.61, 1.97], I² = 93%) significantly increased, whereas the Chao1 index value did not significantly differ (SMD = 0.50, [95% CI: -0.46, 1.46], I² = 89%). The Shannon index value (SMD = 0.25, [95% CI: -0.22, 0.72], I² = 38%) did not significantly differ across the gut samples. The majority of studies (19/25) indicated that the patients and noncancer controls differed significantly in terms of beta diversity. Cancer-associated changes were observed, with a dramatic decrease in the Lactobacillus genus and significant increases in pathogenic bacteria, including the Anaerococcus, Peptostreptococcus, Porphyromonas, Prevotella, and Sneathia genera. Additionally, the impact of antineoplastic therapies on microbial diversity was inconsistently reported across several studies. This systematic review elucidates the microbiota alterations associated with the prevalence of CC and its response to anti-tumor therapies, aiming to provide insights for future research directions and precision medicine strategies to enhance women’s quality of life. CRD42024554433. The online version contains supplementary material available at 10.1186/s12905-025-03599-1.

The effective and targeted treatment of resistant cancer cells presents a significant challenge. Targeting cell ferroptosis has shown remarkable efficacy against apoptosis‐resistant tumors due to their elevated iron metabolism and oxidative stress levels. However, various obstacles have limited its effectiveness. To overcome these challenges and enhance ferroptosis in cancer cells, we have developed a self‐powered photodynamic therapeutic tablet that integrates a ferroptosis inducer (FIN), imidazole ketone erastin (IKE). FINs augment the sensitivity of photodynamic therapy (PDT) by increasing oxidative stress and lipid peroxidation. Furthermore, they utilize the Fenton reaction to supplement oxygen, generating a greater amount of reactive oxygen species (ROS) during PDT. Additionally, PDT facilitates the release of iron ions from the labile iron pool (LIP), accelerating lipid peroxidation and inducing ferroptosis. In vitro and in vivo experiments have demonstrated a more than 85% tumor inhibition rate. This synergistic treatment approach not only addresses the limitations of inadequate penetration and tumor hypoxia associated with PDT but also reduces the required medication dosage. Its high efficiency and specificity towards targeted cells minimize adverse effects, presenting a novel approach to combat clinical resistance in cancer treatment.

Atopic dermatitis is a chronic inflammatory skin condition that typically manifests in infancy and is characterized by dry, irritated skin. Here, we propose a self-powered hydration-monitoring and drug-delivery skin patch for closed-loop treatment of atopic dermatitis. The patch is composed of piezoelectric generator, hydration sensing unit, microneedle treatment module and flexible circuit. The piezoelectric PZT generator can achieve self-powering by harvesting mechanical energy from patient activities, allowing for long-term work of the system without external power sources. The hydration sensing unit can rapidly and accurately detect changes in skin hydration by estimating the thermal conductivity. Upon detecting abnormal skin hydration levels for 65 s, the treatment module is automatically activated, heating hyaluronic acid-based microneedles (~42 °C) to release dexamethasone sodium phosphate (DEX), thereby providing timely targeted therapy and moisturization to the affected area within minutes. Therapeutic results in mice model of atopic dermatitis demonstrate that our patch can effectively treat this skin disease, improving the epidermal thickness, IL-4, spleen size and mass. The system achieves closed-loop detection and treatment of atopic dermatitis without external intervention, offering a novel approach to managing skin disease and expanding the scope of self-powered biomedical engineering systems. A self-powered hydration-monitoring and drug-delivery skin patch is designed for closed-loop treatment of atopic dermatitis. The patch composes of piezoelectric generator, hydration sensing unit, microneedle treatment module, and flexible circuit. This integrated system achieves closed-loop detection and treatment of atopic dermatitis without external intervention, offering a novel approach to managing skin disease and expanding the scope of self-powered biomedical engineering systems

Photodynamic therapy (PDT) represents a targeted approach for cancer treatment that employs light and photosensitizers (PSs) to induce the generation of reactive oxygen species (ROS). However, PDT faces obstacles including insufficient PS localization, limited light penetration, and treatment resistance. A potential solution lies in nanogenerators (NGs), which function as self-powered systems capable of generating electrical energy. Recent progress in piezoelectric and triboelectric NGs showcases promising applications in cancer research and drug delivery. Integration of NGs with PDT holds the promise of enhancing treatment efficacy by ensuring sustained PS illumination, enabling direct electrical control of cancer cells, and facilitating improved drug administration. This comprehensive review aims to augment our comprehension of PDT principles, explore associated challenges, and underscore the transformative capacity of NGs in conjunction with PDT. By harnessing NG technology alongside PDT, significant advancement in cancer treatment can be realized. Herein, we present the principal findings and conclusions of this study, offering valuable insights into the integration of NGs to overcome barriers in PDT.