Objective To investigate the expression of neutrophil gelatinase-associated lipocalin (NGAL) signaling pathways in the early stage of porcine vein graft restenosis, and to explore the possible role and mechanism in the early vein graftrestenosis after coronary artery bypass surgery. Methods We selected 18 ordinary healthy pigs weighing 25-30 kg and collected samples of the vein graft of pigs at the preoperation and postoperative days 7, 14 and 30. Hematoxylin-eosin (HE) staining and Masson staining, immunohistochemical method were used to observe the neointimal hyperplasia, the migration of smooth muscle cells and and vascular remodeling of the vein bypass graft. The expression changes of NGAL, matrix metalloprotenase (MMP)9, MMP2 and tissue inhibitor of metalloproteinase (TIMP)1 in different periods of the vein bypass graft was tested. Results By HE and Masson staining, with the passing of modeling time, degradation of collagen matrix in the vein graft, gradually thickening of muscle fibers and the migration to the inner membrance and vascular remodeling caused the vascular stenosis. By immunohistochemistry, NGAL, MMP9 and MMP2 of normal vein in the model were seldom expressed and even did not express. At 14 days after the modeling, NGAL expression in the membrane layer of blood vessels began to appear, peaked at postoperative 30 days, and began to appear in the inner membrance. MMP9, MMP2 expression began to appear at postoperative 7 days, peaked at postoperative 14 days, and tended to decline at postoperative 30 days. TIMP1 expression was less in normal vascular walls and at the 14 days after the modeling, expression peaked in the vein graft. Conclusion NGAL, MMP9, MMP2 and TIMP1 may be involved in the formation of early vascular graft restenosis. NGAL as initiator, results in the expression of MMP9 and MMP2, and participates in the degradation of collagen matrix and the migration of smooth muscle cells in vein grafts. TIMP1 as a negative factor, may play an important role in maintaining their own balance.
The pathogenesis of Vogt-Koyanagi Harada disease (VKH) has not yet been fully defined. Current studies mainly suggest that VKH is actually an autoimmune disease, especially related to the immune response mediated by various signal transduction pathways involved in the function of T cells. In recent years, the influence of the balance imbalance of various T cell subsets in cellular immunity on the pathogenesis of VKH has been a hot research direction. Currently, T helper cell 17/T regulatory cells, balance is the focus of clinical research, meanwhile, new discoveries and potential clinical treatment schemes have been made for related cellular pathways, particularly the Janus kinase/signal transducers and activators of transcription pathway and NF-kappa B pathway. The exploration of B cells in the pathogenesis of VKH has also achieved initial results through the successful application of various targeted drugs. In the future, further screening and localization of genes or proteins that are abnormally regulated or expressed in VKH, for which early comprehensive and in-depth exploration will be helpful, thus improve the efficacy of clinical treatment programs and develop new therapeutic targets.
Objective To analyze the characteristics and changing trends of lung cancer-related projects funded by National Natural Science Foundation of China (NSFC) during 2019–2023, providing a reference for researchers in topic selection and for optimizing scientific research management and resource allocation. Methods Relevant databases, including the NSFC Big Data Knowledge Management Service Platform, were systematically searched to collect information on lung cancer-related funded projects from 2019 to 2023. Quantitative methods were applied to evaluate project categories, funding amounts, and the distribution of host institutions. Project themes were classified according to their titles, keywords, and abstracts, and were subsequently compared with those of projects funded during 2014–2018. Results A total of 1 327 lung cancer-related projects were funded from 2019 to 2023, with total funding of 554.92 million yuan. The Young Scientists Fund and the General Program accounted for 90.3% (1 199/1 327) of the projects and 84.1% (46 675/55 492) of the total funding; the top 10 host institutions comprised approximately 32.0% of all funded projects. Thematic analysis revealed that the core funding directions in the lung cancer field during 2019–2023 focused on molecular mechanisms and signaling pathways. Major research themes included metastasis and recurrence, tumor microenvironment and immunity, and targeted therapy resistance and drug development. Compared with 2014–2018, the proportion of projects focused on tumor microenvironment and immunity, as well as artificial intelligence and medical engineering, increased substantially. Overall, the themes of funded lung cancer projects were dominated by mechanistic studies and demonstrated cross-cutting features intersecting with disease progression, therapeutic resistance, immune regulation, and clinical translation. Conclusion The number of NSFC-funded lung cancer-related projects has continued to grow. Research themes have evolved from pure mechanistic exploration toward immune regulation and translational research, exhibiting characteristics of interdisciplinary integration with emerging technologies and multi-theme cross-fertilization. Researchers are encouraged to align with policy orientations and to emphasize the innovation and translational value of their proposed topics.
ObjectiveTo summarize the key roles of M2-tumor-associated macrophages (M2-TAMs) in the progression of colorectal cancer (CRC) through the regulation of signaling pathways, and to discuss corresponding potential intervention strategies. MethodBased on a systematic review of published literature, this article comprehensively analyzes the key roles of M2-TAMs in the signaling pathways governing CRC progression and summarizes the upstream pathways regulating M2-TAMs recruitment and polarization, as well as the core downstream effector networks driving their pro-tumorigenic functions. ResultsAmong the upstream pathways of M2-TAMs, cytokine/chemokine pathways (CCL2/CCR2, CSF-1R, IL-6/JAK/STAT3, and CXCL12-CXCR4) mediate chemotactic recruitment and pro-tumor polarization, whereas metabolic sensing pathways (lactate and succinate) shape the pro-tumor phenotype of TAMs through metabolic reprogramming. The downstream effector pathways exhibit a clear functional division: the EGF/EGFR/PI3K/Akt/mTOR axis primarily mediates proliferation and survival, whereas the TGF-β/Smad/non-Smad, Wnt/β-catenin, and Notch/Jagged1 pathways synergistically drive invasion and metastasis. These pathways coordinately facilitate the pro-tumorigenic effects of M2-TAMs. Based on the above mechanisms, intervention strategies targeting key nodes such as CSF-1R, CCR2, and CXCR4 provide promising therapeutic options for CRC. ConclusionsThis review elucidates the key regulatory roles of M2-TAMs in CRC signaling networks. Based on these findings, multi-pathway combinatorial blockade and precise modulation of TAMs subpopulations deserve further investigation. However, TAMs plasticity, signal context-dependency, and microenvironment heterogeneity remain core bottlenecks limiting clinical translation. Future efforts should focus on the development of novel therapeutic modalities and the design and validation of combination regimens to promote the clinical translation of TAMs-targeted therapeutic strategies.