Preeclampsia (PE) is a serious pregnancy-related hypertensive disorder characterized by insufficient trophoblast invasion, yet the underlying molecular mechanisms remain incompletely understood. This study aims to investigate the role of transmembrane protein 165 (TMEM165) and its regulatory mechanism in trophoblast migration and invasion within the context of PE. We examined TMEM165 and insulin-like growth factor 2 mRNA-binding protein 1 (IGF2BP1) expression in eight normal and eight preeclamptic placental tissues using qPCR and western blotting. The CCK8 assay was performed for assessing cell viability, while cell migration and invasion capabilities were examined via wound-healing and Transwell assays. RNA immunoprecipitation (RIP), RNA pull-down, and actinomycin D assays were used to validate the IGF2BP1–TMEM165 interaction and mRNA stability. Our results showed that TMEM165 and IGF2BP1 were significantly downregulated in PE placentas and exhibited a strong positive correlation. Overexpression of TMEM165 enhanced trophoblast viability, migration, and invasion, accompanied by upregulation of MMP2, MMP3, N-cadherin, and vimentin, while TMEM165 knockdown produced the opposite effects. Mechanistically, IGF2BP1 directly bound to TMEM165 mRNA and prolonged its half-life, as demonstrated by RIP, RNA pull-down, and actinomycin D decay assays. Rescue experiments confirmed that IGF2BP1 promoted trophoblast migration and invasion through TMEM165 stabilization. Collectively, these findings identify the IGF2BP1–TMEM165 axis as a novel regulator of trophoblast motility, offering new mechanistic insights into PE pathogenesis and suggesting potential therapeutic targets for PE intervention.
This study investigated the expression patterns of Toll-like receptor 3 (TLR3) and TLR9 and their relationships with apoptosis and tumor growth during prostate cancer progression in an orthotopic xenograft model. Human androgen-dependent LNCaP cells were orthotopically implanted into 24 athymic nude mice and evaluated at weeks 3, 5, and 7. Histopathological, immunohistochemical, and double immunofluorescence analyses were performed to evaluate tumor morphology and the expression of Toll-like receptor 3 (TLR3), Toll-like receptor 9 (TLR9), Bax, Bcl-2, proliferating cell nuclear antigen (PCNA), vascular endothelial growth factor (VEGF), and fibroblast growth factor 2(FGF). Progressive tumor growth was characterized by increased mitotic activity, angiogenesis, necrosis, and lymph node metastasis. Immunohistochemical results demonstrated a progressive increase in TLR3, TLR9, Bcl-2, PCNA, VEGF, TGF-β, and FGF expression, whereas Bax expression significantly decreased. Correlation analysis revealed positive associations between TLR3/TLR9 and anti-apoptotic, proliferative, and angiogenic markers, while Bax correlated negatively with TLR3, TLR9, and Bcl-2. Double immunofluorescence confirmed the co-localization of TLR3 and TLR9 with Bax and Bcl-2 in tumor tissues. In conclusion, increased TLR3 and TLR9 expression accompanies prostate tumor progression and is associated with a shift toward an anti-apoptotic, proliferative, and angiogenic phenotype. Therefore, TLR3 and TLR9 represent potential biomarkers of prostate cancer progression and warrant further investigation as therapeutic targets.
Acute myeloid leukemia (AML) is a heterogeneous hematological malignancy driven by diverse genetic and cytogenetic alterations. Serine protease inhibitor Kazal-type 2 (SPINK2) has been reported to be overexpressed in AML and associated with adverse clinical outcomes; recent studies have implicated SPINK2 in the regulation of leukemic proliferation, differentiation, and ferroptosis-related pathways; however, its functional role in MLL–MLLT3-rearranged AML cells remains incompletely understood. This study aimed to investigate the effect of SPINK2 knockdown on cell viability and cell death in MLL–MLLT3-rearranged human monocytic leukemia (THP-1) cells. SPINK2 knockdown was achieved through lentiviral transduction using SPINK2 shRNA. Cell proliferation and apoptosis were assessed using the MTT assay and flow cytometry, respectively. Expression levels of SPINK2 and ferroptosis-related genes were analyzed by real-time quantitative polymerase chain reaction (RT-qPCR), protein expression levels were determined by western blot analysis, and subcellular morphological changes were evaluated by transmission electron microscopy (TEM). Suppression of SPINK2 expression resulted in a significant reduction in cell viability. However, western blot and RT-qPCR findings did not support caspase−3 activation or ferroptosis as the predominant mechanism of cell death. These findings indicate that SPINK2 knockdown reduces cell viability and is associated with increased cell death and autophagy-associated ultrastructural changes in MLL–MLLT3-rearranged THP-1 cells. Further studies using additional AML models and pathway-specific functional assays are required to determine the underlying cell-death mechanism and the broader relevance of these findings.
We read with great interest the recent article by Tao et al. describing the protective effects of amifostine against radiation-induced small intestinal dysmotility through preservation of the enteric nervous system (ENS). Their demonstration that amifostine selectively protects nitrergic neurons while reducing enteric glial activation provides an important mechanistic advance beyond the drug’s established antioxidant properties. We wish to highlight several recent publications that may further strengthen the mechanistic interpretation of these findings. These include the emerging role of enteric glia in neuroimmune regulation after intestinal injury, the contribution of endothelial injury to radiation-induced gastrointestinal damage, and growing evidence implicating ferroptosis as a mechanism of selective neuronal vulnerability. These complementary observations suggest several future research directions that may further clarify the cellular mechanisms underlying amifostine-mediated enteric neuroprotection.
Forkhead box protein N1 (FOXN1) is a pivotal transcription factor governing the development of the immune system and cutaneous tissues. This comprehensive review systematically elucidates the molecular structural features of FOXN1, with a particular focus on its essential biological functions within the thymic and cutaneous microenvironments. Specifically, it details the intricate regulation of thymic epithelial cell differentiation, cellular aging, and tissue regeneration, alongside its distinct impacts on skin homeostasis, local metabolism, and accelerated wound repair. Building upon this foundational biology, the article explores the broad clinical phenotype spectrum associated with FOXN1 deficiency, outlining its diagnostic and therapeutic value in conditions such as immunodeficiency, chronic skin disorders, and thymic neoplasms. Furthermore, it highlights cutting-edge translational strategies reshaping regenerative medicine, including FOXN1-based organoid construction and innovative targeted protein delivery systems. Ultimately, this review aims to provide a systematic, multi-disciplinary reference for understanding the pathophysiological significance of FOXN1, effectively bridging basic laboratory insights with advanced clinical applications.
