Cancer-associated fibroblasts (CAFs), as a central component of the tumor microenvironment in primary and metastatic tumors, profoundly influence the behavior of cancer cells and are involved in cancer progression through extensive interactions with cancer cells and other stromal cells. Furthermore, the innate versatility and plasticity of CAFs allow their education by cancer cells, resulting in dynamic alterations in stromal fibroblast populations in a context-dependent manner, which highlights the importance of precise assessment of CAF phenotypical and functional heterogeneity. In this review, we summarize the proposed origins and heterogeneity of CAFs as well as the molecular mechanisms regulating the diversity of CAF subpopulations. We also discuss current strategies to selectively target tumor-promoting CAFs, providing insights and perspectives for future research and clinical studies involving stromal targeting.

Neutrophil Extracellular Traps (NETs) are neutrophil-derived extracellular scaffolds, which typically consist of fibrous decondensed chromatins decorated with histones and granule proteins. Initially discovered as a host defence mechanism of neutrophil against pathogens, they have also been implicated in the progression of sterile inflammation-associated diseases such as autoimmune disease, diabetes, and cancer. In this review, we highlight and discuss the more recent studies on the roles of NETs in cancer development, with a special focus on cancer metastasis. Moreover, we present the strategies for targeting NETs in pre-clinical models, but also the challenging questions that need to be answered in the field.

Nonalcoholic fatty liver disease (NAFLD) is the most prevalent chronic disease in modern society. It is characterized by an accumulation of lipids in the liver and an excessive inflammatory response. Clinical trials have provided evidence that probiotics may prevent the onset and relapse of NAFLD. The aim of this study was to explore the effect of Lactiplantibacillus plantarum NKK20 strain (NKK20) on high-fat-diet-induced NAFLD in an ICR murine model and propose the underlying mechanism whereby NKK20 protects against NAFLD. The results showed that the administration of NKK20 ameliorated hepatocyte fatty degeneration, reduced total cholesterol and triglyceride concentrations, and alleviated inflammatory reactions in NAFLD mice. In addition, the 16S rRNA sequencing results indicated that NKK20 could decrease the abundance of Pseudomonas and Turicibacter and increase the abundance of Akkermansia in NAFLD mice. LC-MS/MS analysis showed that NKK20 could significantly increase the concentration of short-chain fatty acids (SCFAs) in the colon contents of mice. The obtained non-targeted metabolomics results revealed a significant difference between the metabolites in the colon contents of the NKK20 administration group and those in the high-fat diet group, in which a total of 11 different metabolites that were significantly affected by NKK20 were observed, and these metabolites were mainly involved in bile acid anabolism. UPLC-MS technical analysis revealed that NKK20 could change the concentrations of six conjugated and free bile acids in mouse liver. After being treated with NKK20, the concentrations of cholic acid, glycinocholic acid, and glycinodeoxycholic acid in livers of the NAFLD mice were significantly decreased, while the concentration of aminodeoxycholic acid was significantly increased. Thus, our findings indicate that NKK20 can regulate bile acid anabolism and promote the production of SCFA, which can inhibit inflammation and liver damage and thus prevent the development of NAFLD.

Hepatic stellate cells (HSCs), specialized liver‑resident pericytes, play pivotal roles in both liver fibrogenesis and regeneration. Following hepatic injury, quiescent HSCs undergo activation and transdifferentiation into myofibroblasts, which drive tissue remodeling and scar formation. Recent advances have uncovered notable phenotypic and functional heterogeneity within HSC populations, with distinct subsets displaying context‑dependent activation states and specialized functions across diverse liver pathologies. The present review synthesizes current insights into the dynamic spectrum of HSC phenotypes and the molecular mechanisms governing their plasticity, emphasizing the mechanisms through which niche‑specific signaling, epigenetic regulation and metabolic reprogramming coordinate their functional diversity. The present review further discuss emerging therapeutic strategies that leverage this heterogeneity to selectively target pathogenic HSC subsets, while preserving their homeostatic roles, thereby opening new avenues for precision anti‑fibrotic therapies and liver regeneration.