Macrophages play pivotal roles in tissue repair through remarkable functional plasticity, orchestrated by their developmental origins and local microenvironmental cues. Embryonically derived resident macrophages primarily maintain tissue homeostasis, while monocyte-derived macrophages respond predominantly to inflammation and extracellular matrix remodeling. Effective tissue repair requires precise temporal regulation of macrophage polarization, balancing inflammation resolution, angiogenesis, and scar formation. Metabolic reprogramming further enhances macrophage plasticity, enabling adaptation to fluctuating energy demands at injury sites. Emerging evidence also highlights that macrophages integrate biomechanical forces—such as matrix stiffness and shear stress—with biochemical signals to fine-tune their inflammatory and reparative programs. Recognizing this mechanoregulation broadens therapeutic avenues for precisely modulating macrophage behavior in regenerative medicine. Targeting macrophage subsets, polarization states, or metabolic pathways has emerged as a promising therapeutic strategy to optimize healing outcomes. However, the inherent complexity of macrophage heterogeneity presents considerable challenges to therapeutic precision. This review systematically summarizes the multifaceted roles of macrophages in tissue repair, emphasizing how developmental origins dictate functional specificity, dynamic phenotypic transitions, and metabolic adaptability, aiming to advance macrophage-based precision therapeutics for regenerative medicine.

Background: There is growing evidence that the gene named tumor necrosis factor α–induced protein 6 (TNFAIP6) has an important role in various tumors. However, a systematic pan-cancer analysis of TNFAIP6 is lacking. Here we aimed to analyze the expression of TNFAIP6 across multiple cancers and verify its expression during the progression of colon cancer. Methods: We performed a comprehensive bioinformatics analysis to examine the expression of TNFAIP6 across 27 tumor types. GEPIA2 was used to evaluate the effect of TNFAIP6 on clinical cancer prognosis. cBioportal was used to assess TNFAIP6 mutations. The correlation between TNFAIP6 and cancer immune infiltrates was explored using TIMER2.0. The CancerSEA database was used to perform functional analysis of TNFAIP6. Metascape was used to identify TNFAIP6-related gene enrichment pathways. Immunohistochemistry was performed to detect TNFAIP6 protein expression in the colon cancer. In addition, the Comparative Toxicogenomics Database was searched for known and possible antitumor drugs that may be associated with TNFAIP6. Results: We found that, in most of the cancers included in this analysis, TNFAIP6 was highly expressed, and there is a distinct relationship between TNFAIP6 expression and cancer prognosis. TNFAIP6 expression is associated with cancer-associated fibroblasts, neutrophils, and endothelial cells. TNFAIP6 and similar genes may also be involved in the PID_VEGF_VEGFR_ pathway. Immunohistochemistry revealed an increasing trend of TNFAIP6 protein expression in normal, adenoma, and colon cancer tissues. Several known and possible antitumor drugs that may be associated with TNFAIP6 were identified in the Comparative Toxicogenomics Database. These results suggest that a number of drugs may target TNFAIP6 during cancer treatment, including cisplatin, irinotecan, resveratrol, U 0126, NSC689534, genistein, NSC668394, oxaliplatin, plerixafor, topotecan, vincristine, flutamide, doxorubicin, MRK 003, folic acid, demecolcine, tunicamycin, zoledronic acid, and schizandrin B. Conclusions: TNFAIP6 may function as an oncogene in certain cancers. Furthermore, this study provides evidence that TNFAIP6 is an important factor in colon cancer progression.

Forkhead box J3 (FOXJ3) is a member of the forkhead box (Fox) family. Recently, increasing evidence has revealed the relationship between Fox family members and cancer.FOXJ3is involved in various types of cancer, including lung cancer, tongue squamous carcinoma, and prostate cancer; however, a comprehensive pan-cancer analysis ofFOXJ3remains lacking. Here, we explored the function ofFOXJ3across cancers using online websites and databases including TIMER2.0, SangerBox, UALCAN, GEPIA2.0, cBioPortal, CancerSEA,STRING, BioGRID and Metascape to analyze the role ofFOXJ3in cancers. Abnormal expression ofFOXJ3was found in various tumors. The genetic alteration percentage in tumors was determined, and elevatedFOXJ3expression was found to be associated with worse overall survival in brain lower grade glioma(LGG), liver hepatocellular carcinoma (LIHC), sarcoma (SARC) and thyroid carcinoma. ElevatedFOXJ3expression was related to worse prognosis with disease-free survival in adrenocortical carcinoma, LGG and LIHC.FOXJ3expression was related to immune infiltration in several cancers. Enrichment analysis showed that histone modification, the TGF-β signaling pathway, and chromatin organization were the top three enriched ontology clusters of the top 100 similar genes ofFOXJ3. Our pan-cancer analysis provides comprehensive insights intoFOXJ3from the perspective of bioinformatics in different cancers, where it serves as a potential biomarker for prognosis, especially in LGG and LIHC.FOXJ3is also correlated with immune infiltrates in certain human tumors.