Acta Biochimica et Biophysica Sinica•2025•DOI: 10.3724/abbs.2025042
This study elucidates the mechanisms by which cancer-associated fibroblast (CAF)-derived platelet-derived growth factor C (PDGFC) promotes the progression of lung adenocarcinoma (LUAD) and explores the impact of PDGFC on immune regulation within the tumor microenvironment (TME). Our results show that there is higher expression of PDGFC in CAFs than in nontumor tissue fibroblasts (NFs) and that higher expression of PDGFC is correlated with poor prognosis in LUAD patients. Furthermore, CAF-derived PDGFC promotes epithelial-mesenchymal transition (EMT) in cancer cells as well as matrix metalloproteinase 2 (MMP2) expression through the PDGF receptor A (PDGFRA)-mitogen-activated protein kinase/extracellular signal-regulated kinase (MAPK/ERK) pathway. Moreover, our study demonstrates that CAF-derived PDGFC is essential for the activation and infiltration of fibroblasts in the TME, as well as the inflammatory infiltration of different immune cell types and the immunosuppressive conditions within the TME. In particular, PDGFC induces increased PDGFRA expression in both tumor cells and fibroblasts, which can lead to reciprocally positive feedback to accelerate malignant tumor progression. This discovery provides a novel TME-targeted strategy for LUAD treatment.
Acta Biochimica et Biophysica Sinica•2026•DOI: 10.3724/abbs.2025146
Actin-bundling protein Fascin1 (FSCN1) is encoded by the Fscn1 gene and is crucial for cytoskeletal remodeling and cellular migration. Although a previous study linked Fscn1 deficiency to neonatal lethality in mice, the underlying metabolic mechanism remains unclear. In this study, we report that systemic knockout (KO) of Fscn1 leads to 52.2% mortality within 24 h post-birth, accompanied by severe hypoglycemia in KO pups compared with their littermates. Remarkably, this lethality is fully rescued by oral glucose administration, indicating a glucose supply-dependent survival mechanism. Surviving Fscn1-KO neonates display persistent developmental deficits, including growth retardation and depleted lipid stores, despite intact canonical insulin-regulated hepatic gluconeogenic pathways. Transcriptomic profiling of P0 livers reveals that Fscn1 loss predominantly disrupts metabolic pathways, with the glycerol phosphate shuttle being the most significantly downregulated module. Mechanistically, Fscn1-KO livers exhibit markedly reduced protein levels of glycerol-3-phosphate dehydrogenase isoforms (GPD1/GPD2), key enzymes bridging glycolysis and gluconeogenesis. Consistently, glycerol tolerance tests demonstrate impaired glycerol-to-glucose conversion in Fscn1-KO mice, confirming defective glycerol-driven gluconeogenesis. Our findings establish FSCN1 as a novel cytoskeletal-metabolic integrator essential for neonatal survival by sustaining hepatic glucose production from glycerol, thus revealing an unexpected role of actin dynamics in coordinating metabolic adaptation during early postnatal development.
Acta Biochimica et Biophysica Sinica•2026•DOI: 10.3724/abbs.2025086
Liver regeneration is a critical adaptive response to hepatic injury, requiring precise metabolic reprogramming to meet the energetic and biosynthetic demands of proliferating hepatocytes. While the oncoprotein Gankyrin is well-established as a promoter of liver fibrosis and hepatocarcinogenesis, its role in metabolic adaptations underlying liver regeneration remains unclear. In this study, we demonstrate that Gankyrin deficiency in the liver (Gank△Hep/Y) induces hepatic hypertrophy and aberrant glycogen accumulation. Gankyrin expression is significantly upregulated after partial hepatectomy (PHx), whereas Gank△Hep/Y -PHx mice exhibit impaired liver regeneration. This impairment is marked by a delayed restoration of the liver-to-body weight ratio, blunted glycogenolysis, and reduced fatty acid uptake. Mechanistically, Gankyrin activates Pygl and Cd36, key regulators of glycogenolysis and lipid uptake, respectively. Pharmacological inhibition of PYGL activity retards liver regeneration. Furthermore, we identify a novel interaction between Gankyrin and FOXO1, wherein Gankyrin promotes FOXO1 ubiquitination and subsequent proteasomal degradation. This Gankyrin-dependent suppression of FOXO1 leads to the transcriptional upregulation of Pygl and Cd36, thereby fueling hepatocyte proliferation. Collectively, our findings reveal Gankyrin as a master regulator of liver regeneration, integrating metabolic reprogramming with proliferative signaling through the FOXO1-PYGL/CD36 axis. These insights not only elucidate the mechanistic underpinnings of liver regeneration but also unveil the therapeutic potential of targeting the Gankyrin/FOXO1 pathway to mitigate hepatic insufficiency and enhance regenerative capacity in clinical settings.
Acta Biochimica et Biophysica Sinica•2026•DOI: 10.3724/abbs.2026065
The degree of oxidative stress decreases osteoblast function with age, which leads to a decline in bone compressive capacity. Ginsenoside Rh2 is a known clinical or adjuvant therapy for various tissues. In this study, we investigate the pharmacological effects of Rh2 against oxidative stress-induced osteoblasts. Osteoblasts are pretreated with Rh2 for 48 h and then exposed to hydrogen peroxide (H2O2), which results in significantly decreased ROS levels, increased antioxidant enzyme activity, and enhanced mitochondrial function. Functionally, Rh2 increases alkaline phosphatase (ALP) expression, together with enhanced mineralization and expression of osteogenesis-associated genes. Rh2 also promotes the nuclear translocation of FoxO1 and β-catenin, whereas it does not reverse reduced mineralization caused by decreased FoxO1 or β-catenin activity, indicating that its effect is mediated through the functional interaction between FoxO1 and β-catenin. In a mouse model of lipopolysaccharide (LPS)-induced bone loss, Rh2 administration improves trabecular microstructure, increases osteoblast numbers, and upregulates serum metabolites associated with bone formation. Immunofluorescence analysis further reveals that Rh2 promotes the nuclear co-localization of FoxO1 and β-catenin in femurs, indicating their coordinated action within this signaling axis. These findings indicate that Rh2 mitigates oxidative stress-induced osteoblast dysfunction via the FoxO1/β-catenin pathway, highlighting the pivotal role of redox balance in bone remodeling and suggesting a promising therapeutic strategy for osteoporosis.
Acta Biochimica et Biophysica Sinica•2025•DOI: 10.3724/abbs.2025017
Studies of cell-to-cell activities in the tumor microenvironment (TME) have identified multiple potential targets for oncotherapy. The interplay between tumor cells and neighboring cancer-associated fibroblasts (CAFs) persists in all stages of tumor progression. In this study, we reveal that exosomes from breast cancer cells can be endocytosed into fibroblasts and transform normal fibroblasts (NFs) into CAFs and that the ability of exosomes from highly metastatic breast cancer cells is greater than that of those from poorly metastatic breast cancer cells. Further investigation reveals that exosomes from highly metastatic breast cancer cells contain much more miR-105-5p than those from poorly metastatic breast cells do and that exosomal miR-105-5p facilitates the transformation of NFs to CAFs. A detailed study reveals that RBMY1A1-dependent sorting of miR-105-5p into fibroblasts and subsequent internalization of miR-105-5p promote the transformation of NFs to CAFs by downregulating LATS2 expression and activating NF-κB signaling, which concurrently facilitates the EMT of breast cancer cells. Thus, our results indicate that exosomal miR-105-5p may be a potential target for novel therapeutic strategies to prevent the coevolution of breast cancer cells and CAFs.
Acta Biochimica et Biophysica Sinica•2025•DOI: 10.3724/abbs.2024103
Aberrant gene expression in cardiomyocyte has been revealed to be the fundamental essence of pathological cardiac hypertrophy. However, the detailed mechanisms are not fully understood. The underlying regulators of gene expression involved in cardiac hypertrophy remain to be further identified. Here, we report that the RNA-binding protein RNA-binding motif protein 4 (RBM4) functions as an endogenic protector that is able to fight against cardiomyocyte hypertrophy in vitro. Under pro-hypertrophic stimulation of angiotensin II (Ang II), the protein level of RBM4 in cardiomyocyte and myocardium is elevated. Knockdown of RBM4 can further aggravate cardiomyocyte hypertrophy, while over-expression of RBM4 represses cardiomyocyte hypertrophy. Mechanistically, RBM4 is localized in the nucleus and down-regulates the expression of polypyrimidine tract-binding protein 1 (PTBP1), which has been shown to aggravate cardiomyocyte hypertrophy. In addition, we suggest that the up-regulation of RBM4 in cardiomyocyte hypertrophy is caused by N6-methyladenosine (m6A). Ang II induces m6A methylation of RBM4 mRNA, which further enhances the YTH domain-containing family protein 1 (YTHDF1)-mediated translation of RBM4. Thus, our results reveal a novel pathway consisting of m6A, RBM4 and PTBP1, which is involved in cardiomyocyte hypertrophy.
Acta Biochimica et Biophysica Sinica•2026•DOI: 10.3724/abbs.2026065
The degree of oxidative stress decreases osteoblast function with age, which leads to a decline in bone compressive capacity. Ginsenoside Rh2 is a known clinical or adjuvant therapy for various tissues. In this study, we investigate the pharmacological effects of Rh2 against oxidative stress-induced osteoblasts. Osteoblasts are pretreated with Rh2 for 48 h and then exposed to hydrogen peroxide (H2O2), which results in significantly decreased ROS levels, increased antioxidant enzyme activity, and enhanced mitochondrial function. Functionally, Rh2 increases alkaline phosphatase (ALP) expression, together with enhanced mineralization and expression of osteogenesis-associated genes. Rh2 also promotes the nuclear translocation of FoxO1 and β-catenin, whereas it does not reverse reduced mineralization caused by decreased FoxO1 or β-catenin activity, indicating that its effect is mediated through the functional interaction between FoxO1 and β-catenin. In a mouse model of lipopolysaccharide (LPS)-induced bone loss, Rh2 administration improves trabecular microstructure, increases osteoblast numbers, and upregulates serum metabolites associated with bone formation. Immunofluorescence analysis further reveals that Rh2 promotes the nuclear co-localization of FoxO1 and β-catenin in femurs, indicating their coordinated action within this signaling axis. These findings indicate that Rh2 mitigates oxidative stress-induced osteoblast dysfunction via the FoxO1/β-catenin pathway, highlighting the pivotal role of redox balance in bone remodeling and suggesting a promising therapeutic strategy for osteoporosis.
Chinese Journal of Tissue Engineering Research•2026•DOI: 10.12307/2026.21394
BACKGROUND: Systemic fatigue increases injury risk in individuals with functional ankle instability, while stop-jump cutting is a high risk for ankle injuries. The biomechanical mechanisms underlying non-anticipated stop-jump cutting during systemic exercise fatigue in this population remain unclear. OBJECTIVE: To quantify differences in kinematic and kinetic characteristics during non-anticipated stop-jump cutting before and after exercise fatigue between individuals with functional ankle instability and healthy controls, revealing the impact of exercise fatigue on stop-jump cutting in individuals with functional ankle instability. METHODS: Fifteen male participants with unilateral functional ankle instability and 15 healthy male controls were recruited. Kinematic (peak angles of ankle dorsiflexion, plantarflexion, inversion, knee flexion, knee varus, knee valgus, hip flexion, and hip abduction) and kinetic (joint stiffness of hip, knee, and ankle) parameters were collected during non-anticipated stop-jump cutting before and after exercise fatigue. Two-way repeated measures ANOVA was used to analyze peak joint angles and joint stiffness. Statistical parametric mapping (SPM) was further used to analyze the effects of fatigue on time-series data of ankle angle and ground reaction forces. RESULTS AND CONCLUSION: Kinematic results: Two-way ANOVA revealed significant main effects of fatigue and group-by-fatigue interactions for peak ankle inversion, knee flexion, knee valgus, and hip flexion angles (P < 0.05). Compared with pre-fatigue, peak ankle inversion increased in the functional ankle instability group after fatigue (P < 0.05), peak knee flexion increased in both groups (P < 0.05), and peak hip flexion increased in the healthy control group (P < 0.05). After fatigue, the functional ankle instability group showed smaller peak ankle inversion and hip flexion angles but larger peak knee valgus and knee flexion angles than the healthy control group (P < 0.05). SPM analysis revealed that ankle inversion/eversion angle was greater during 4%-18% of the cutting movement after fatigue in the functional ankle instability group (P < 0.05). Kinetic results: Two-way ANOVA revealed significant main effects of fatigue and group-by-fatigue interactions for hip, knee, and ankle joint stiffness (P < 0.05). Compared with pre-fatigue, hip and ankle stiffness decreased in the healthy control group (P < 0.05), while knee and ankle stiffness decreased in the functional ankle instability group (P < 0.05). SPM analysis showed that vertical ground reaction force was greater during 5%-16% of the cutting movement, and mediolateral ground reaction force was greater during 35%-49% of the movement after fatigue in the functional ankle instability group (P < 0.05). CONCLUSION: Exercise fatigue alters kinematic and kinetic characteristics during non-anticipated stop-jump cutting in individuals with functional ankle instability, particularly affecting knee and ankle stability and shock absorption. Fatigue reduces joint stiffness and control, increasing injury risk, especially during the initial and transitional phases of the cutting movement.
Chinese Journal of Tissue Engineering Research•2026•DOI: 10.12307/2026.21465
BACKGROUND: Neural catheterization repair of peripheral nerve defects is a research hotspot in the field of biomedical engineering, but the autologous nerve graft repair method as the gold standard has limitations, so there is an urgent need for a method that can replace autologous nerve grafting to repair peripheral nerve defects. OBJECTIVE: To observe the degradation characteristics and biological toxicity of the new domestic polyglycolic acid neural catheters. METHODS: (1) Degradation performance: PBS was added to the test tubes of the blank control group. PBS and new domestic polyglycolic acid neural catheter were added to the test tubes of the fluid exchange group, with PBS changed every 3 days. PBS and the new domestic polyglycolic acid neural catheter were added to the test tubes of the non-fluid exchange group, without changing the fluid. All three groups of test tubes were placed in a 37℃ incubator, and the pH value of the liquid in each test tube was measured weekly. (2) Cell experiment: Human fibroblasts were divided into two groups: the control group was added with pure medium, and the experimental group was added with medium containing the extract of the new domestic polyglycolic acid neural catheter. The cytocompatibility of the neural catheter was evaluated by cell morphology, CCK-8 assay, scratch test, and Transwell assay. (3) In vivo histocompatibility: The new domestic polyglycolic acid neural catheter and an imported neural catheter were implanted between the biceps femoris and gluteus maximus muscles of SD rats to evaluate the degradation characteristics and biotoxicity of the neural catheters. RESULTS AND CONCLUSION: (1) In vitro degradation experiments showed that under fluid exchange conditions, the degradation of the new domestic polyglycolic acid neural catheter had little effect on the pH value of the surrounding fluid; under non-fluid exchange conditions, the degradation of the new domestic polyglycolic acid neural catheter could reduce the pH value of the surrounding fluid. (2) The growth state of cells in both groups was good, and the cell morphology and volume were normal. CCK-8 assay showed that the new domestic polyglycolic acid neural catheter did not affect the proliferation of human fibroblasts. Scratch test and Transwell assay showed that the new domestic polyglycolic acid neural catheter did not affect the migration of human fibroblasts. (3) The degradation of the new domestic polyglycolic acid neural catheter was similar to that of the imported neural catheter. Hematoxylin-eosin staining showed that the new domestic polyglycolic acid neural catheter had no obvious effect on the main organs of rats. Masson staining showed that the tissue around the neural catheter in both groups was normal, and no inflammatory cell infiltration was observed. (4) The results indicate that the new domestic polyglycolic acid neural catheter has good degradability and no biotoxicity.
Acta Biochimica et Biophysica Sinica•2025•DOI: 10.3724/abbs.2025042
Lung adenocarcinoma (LUAD) remains a leading cause of cancer-related mortality, with late-stage 5-year survival rates below 50%. Cancer-associated fibroblasts (CAFs) within the tumor microenvironment (TME) drive progression, yet the molecular mediators of CAF-tumor crosstalk are incompletely defined. This study identifies platelet-derived growth factor C (PDGFC) as a critical CAF-secreted factor that promotes epithelial-mesenchymal transition (EMT) and immunosuppression in LUAD. Analysis of patient specimens revealed elevated PDGFC expression in CAFs relative to nontumor tissue fibroblasts (NFs), and high PDGFC levels correlated with poor prognosis. Mechanistically, CAF-derived PDGFC activates the PDGF receptor A (PDGFRA)-mitogen-activated protein kinase/extracellular signal-regulated kinase (MAPK/ERK) pathway in cancer cells, inducing EMT and matrix metalloproteinase 2 (MMP2) expression. PDGFC also stimulates PDGFRA expression in both tumor cells and fibroblasts, establishing a reciprocal positive feedback loop that accelerates fibrotic TME remodeling and malignant progression. Immunologically, PDGFC promotes infiltration and polarization of immunosuppressive cell populations, including CD4+ Treg cells, M2 macrophages, and N2 neutrophils, while restraining immunocompetent NK cells. Immunoinhibitors TGFB1, CSF1R, PD-L1, PD-L2, KDR, IL10RB, and HAVCR2 may synergize with PDGFC in modulating immunosuppression. These findings position PDGFC as a diagnostic indicator and potential immunotherapy target for LUAD, offering a novel TME-targeted therapeutic strategy.