Xiaojia Chen

Periodontitis-induced destruction of periodontal tissues and tooth loss remain major clinical challenges. Although periodontal regenerative therapies aim to reconstruct damaged structures, particularly the repair of alveolar bone defects, current biomaterials have limited capacity to simultaneously promote cell adhesion and osteogenic differentiation. Amelogenin (Am) plays a key role in mineralized tissue development through its highly conserved N-terminal and C-terminal regions, but studies have shown that Am has certain limitations in promoting cell adhesion. In contrast, the arginine-glycine-aspartic acid (RGD) domain of fibronectin (FN) effectively mediates cell–matrix adhesion. Based on these properties, we developed a novel recombinant fusion protein (rtAmR) by combining the conserved regions of Am with the RGD domain of FN. In vitro, rtAmR significantly promoted the adhesion and spreading of human stem cells from the apical papilla (hSCAPs) compared with the control group. Quantitative analysis showed that the number of adherent cells and the cell spreading area in the rtAmR group were 1.9-fold and 2.1-fold higher than those in the rhAm group, respectively. In osteogenic differentiation assays, rtAmR exhibited activity comparable to that of rhAm and even outperformed rhAm in terms of alkaline phosphatase (ALP) activity, collagen type I (COL I) expression, and calcium nodule formation. In a Sprague–Dawley (SD) rat alveolar bone defect model, rtAmR treatment significantly promoted bone regeneration, achieving superior bone volume/total volume (BV/TV) values compared to the rhAm and rhFN groups. Immunohistochemistry revealed that rtAmR did not obviously increase neutrophils, mast cells, or M2 macrophages versus control, confirming its biosafety and suggesting M2-independent osteogenesis. These findings suggest that rtAmR is a promising bifunctional bioactive protein for periodontal bone regeneration.

Background: Hepatocellular carcinoma (HCC) is characterized by marked intratumoral heterogeneity and poor clinical outcomes. Dysregulated ribosome biogenesis has emerged as a fundamental hallmark of tumor initiation and progression; however, the specific molecular drivers linking this machinery to HCC pathogenesis remain largely undefined. Methods: By integrating multi-omics data from the TCGA and ICGC cohorts, FBLL1 was identified as a key prognostic candidate gene. Its cellular and spatial distribution was analyzed using single-cell RNA sequencing and spatial transcriptomics. Its biological functions in vitro and in vivo were validated through functional experiments, including lentivirus-mediated ectopic expression and siRNA-mediated gene knockdown. Finally, its molecular mechanism was elucidated through transcriptomic analysis and Western blotting. Results: FBLL1 was significantly upregulated in HCC and correlated with poor patient survival. Spatial and single-cell analyses showed that FBLL1 expression was preferentially enriched in malignant hepatocytes within the tumor region. Functionally, knockdown FBLL1 could inhibit the proliferation and clonogenic capacity of HCC cells, while overexpression FBLL1 in non-tumorigenic hepatocytes could promote the tumorigenic phenotype in xenograft models. Transcriptomic analysis indicated that FBLL1 overexpression was associated with the synergistic upregulation of c-Myc and multiple EGFR ligands, as well as decreased expression of hepatocyte functional markers. Consistently, modulation of FBLL1 expression affected the activity of the EGFR–MAPK signaling pathway. Conclusions: Our study identifies FBLL1 as a previously unrecognized regulator associated with malignant state transition in HCC. Rather than acting as a direct regulator of core signaling components, FBLL1 is associated with ligand-dependent activation of the EGFR–MAPK pathway in conjunction with c-Myc upregulation. These findings indicate that FBLL1 represents a promising therapeutic target for disrupting oncogenic signaling programs in liver cancer.

Periodontal ligament cells (PDLCs) are considered ideal seed cells for periodontal tissue engineering and regeneration, and optimizing their efficacy is a pressing challenge. Although basic fibroblast growth factor (bFGF) has been extensively studied for promoting periodontal regeneration, its instability limits its application. This study introduces a smaller, less degradable peptide, CH02, to address this issue. Therefore, this study aims to explore the promoting effect of the CH02 peptide on the osteogenic differentiation of PDLCs, providing new support for periodontal regeneration. Extracted PDLCs from human premolars; used bFGF as a positive control to analyze the effects of CH02 on the proliferation, toxicity, migration, osteogenic differentiation, and calcification ability of PDLCs; RT-qPCR analysis of osteogenesis-related gene expression; Construct a rat periodontal bone defect model, deliver PDLCs encapsulated in Matrigel to the defect site, and intervene with CH02 for 2 and 4 weeks. Subsequently, evaluate bone regeneration through Micro-CT, HE staining, Masson staining, and immunohistochemical analysis. PDLCs were successfully extracted. In vitro experiments showed that CH02 was comparable to bFGF in promoting PDLCs proliferation, but CH02 was more effective in promoting cell migration and osteogenic differentiation. CH02 enhanced the expression of osteogenic-related genes (such as RUNX2, OCN, and COL-1) in PDLCs. In vivo experiments demonstrated that CH02 could promote PDLCs to repair rat periodontal bone defects. CH02 promotes osteogenic differentiation of PDLCs in vitro more effectively than bFGF; in vivo, CH02 effectively promotes PDLCs to repair rat periodontal bone defects.

Aims: The precise pathogenic mechanism of long‐term detrimental effects on mothers and infants resulting from gestational diabetes (GDM) remains unclear. This study aimed to examine the long‐term detrimental consequences of GDM on mothers and newborns, particularly the impact of glucose concentration variations on vascular endothelial cells and its possible pathogenic mechanisms. Materials and Methods: An analysis was conducted on the clinical data of 68 healthy pregnant women and 67 pregnant women diagnosed with GDM. Human umbilical vein endothelial cells (HUVECs) were obtained from six pairs of pregnant women for transcriptomic sequencing and analysis, which were concurrently analysed with existing databases. The study examined the effects of varying glucose concentrations on HUVECs, incorporating relevant biological experimental verifications, and assessed oxidative stress, inflammation, and the TGF‐β signalling pathway. Results: Clinical data analysis indicated that in patients with gestational diabetes mellitus, early pregnancy hyperglycemia is significantly linked to adverse pregnancy outcomes, even when blood glucose levels are well‐controlled. Transcriptomic sequencing revealed significant alterations in the gene expression of HUVECs under GDM conditions, highlighting enrichment in genes associated with metabolism, inflammation, oxidative stress, and diabetes signalling pathways. Cellular experiments indicated that a transition in glucose concentration from elevated to reduced levels can result in damage and dysfunction in HUVECs, elevate ROS levels, and activate the TGF‐β signalling pathway. Additionally, injured HUVECs release CTGF through the TGF‐β signalling pathway, influencing the extracellular matrix and surrounding cells. Conclusions: The findings demonstrate that alterations in glucose concentration, particularly the shift from high to low levels, can lead to vascular endothelial cell dysfunction, increase ROS levels, and are associated with the TGF β/SMAD3 signalling pathway. Furthermore, compromised HUVECs can influence the microenvironment via their secretions, potentially jeopardising the health of both the mother and foetus.

Following the COVID-19 pandemic, the prevalence of pulmonary fibrosis has increased significantly, placing patients at higher risk and presenting new therapeutic challenges. Current anti-fibrotic drugs, such as Nintedanib, can slow the decline in lung function, but their severe side effects highlight the urgent need for safer and more targeted alternatives. This study explores the anti-fibrotic potential and underlying mechanisms of an endogenous peptide (P5) derived from fibroblast growth factor 2 (FGF2), developed by our research team. Using a bleomycin-induced pulmonary fibrosis mouse model, we observed that P5 alleviated fibrosis by inhibiting collagen deposition, as confirmed by CT scans and histological staining. In TGF-β-induced cell models, P5 effectively suppressed collagen deposition and epithelial–mesenchymal transition (EMT). Transcriptome analysis highlighted pathways related to receptor binding, extracellular matrix organization, and cell adhesion, with KEGG analysis confirming FGFR/MAPK signaling inhibition as the primary mechanism underlying its anti-fibrotic effects. In summary, our study demonstrates that P5 significantly attenuates pulmonary fibrosis through the inhibition of EMT, collagen deposition, and FGFR/MAPK signaling, providing a promising therapeutic approach for fibrosis.

Corneal neovascularization is a significant cause of vision loss, often resulting in corneal clouding and chronic inflammation. Shark cartilage is widely recognized as a significant natural source of anti-angiogenic compounds. Our previous studies have shown that a polypeptide from white-spotted catshark (Chiloscyllium plagiosum Bonnet) has the potential to inhibit the angiogenesis of breast tumors. This study applied this peptide (SAIF) to a corneal alkali injury model to assess its effect on corneal neovascularization. Results revealed that SAIF inhibits endothelial cell proliferation, migration, and tube formation. SAIF inhibited VEGF-induced angiogenesis in the matrigel plug. Using the corneal alkali injury model, SAIF significantly inhibited corneal vascular neovascularization in mice. We found that SAIF not only significantly inhibited the upregulation of pro-angiogenic factors such as VEGF, bFGF, and PDGF expression induced by alkali injury, but also promoted the expression of anti-angiogenesis factor PEDF. Moreover, we also analyzed the MMPs and TIMPs involved in extracellular matrix (ECM) remodeling, angiogenesis, and lymphangiogenesis. We found that SAIF treatment inhibited the expression of pro-angiogenic factors like MMP1, MMP2, MMP3, MMP9, MMP13, and MMP14, and promoted the expression of anti-angiogenesis factors such as MMP7, TIMP1, TIMP2, and TIMP3. In conclusion, SAIF acts as an anti-angiogenic factor to inhibit the proliferation, migration, and tube formation of endothelial cells, inhibit pro-angiogenic factors, promote anti-angiogenic factors, and regulate the expression of MMPs, ultimately inhibiting corneal neovascularization.