Stem Cell Research & Therapy•2026•DOI: 10.1186/s13287-026-05061-x
Background Osteoporosis (OP) is a systemic bone disease characterized by damage to bone strength, leading to increased bone fragility and fracture risk. Cadherin 19 (CDH19) is located on chromosomes 18q22-q23, and 18q deletion is associated with terminal deletion diseases, including foot/hand deformities. However, the role of CDH19 in bone remains undefined. Methods A conditional knockout mouse model of the CDH19 gene was constructed using the Cre-loxP system, and the bone mass and bone morphology in mice were investigated using microCT and histological staining. Osteoblasts were isolated and cultured from wild-type and CDH19 knockout mice. Cell proliferation and differentiation were explored through EdU labeling, qPCR, alkaline phosphatase (ALP)/ alizarin red S (ARS) staining, and Western blot assays. The expression of genes altered in CDH19 gene knockout osteoblast was checked by RNA sequencing (RNA-seq), and subsequently confirmed by immunofluorescence and Western blot. Results We found that CDH19 could maintain the normal proliferation and differentiation in osteoblasts. After knocking out the CDH19 gene, the abilities of proliferation and osteogenesis were significantly inhibited in osteoblasts. Moreover, the bone mass of CDH19 knockout mice was significantly reduced, characterized by decreases in bone density, trabecular number, and bone volume fraction. The RNAseq analysis and western blot showed the PI3K/AKT signaling pathway was significantly inhibited in osteoblasts with CDH19 deletion. Furthermore, we demonstrated that administration of PI3K/AKT signaling pathway agonist 740Y-P partially alleviated the inhibition of osteogenic differentiation caused by CDH19 deletion in vitro and in vivo. Conclusion This study demonstrated that CDH19 regulated osteogenic differentiation by modulating the PI3K/AKT signaling pathway in osteoblasts. CDH19 may become a novel target for the treatment of bone diseases.
Stem Cell Research & Therapy•2026•DOI: 10.1186/s13287-026-04962-1
The Editor-in-Chief is issuing an Editorial Expression of Concern to alert readers about concerns regarding the reporting of animal ethics approval in this article [1]. The article cites approval number SYXK 2008 0050, which was noted to appear in multiple publications describing different experiments. The authors have explained that this number refers to an Experimental Animal Use License for the animal facility rather than a study specific ethics approval and have provided documentation indicating that separate ethical approval was obtained for this study. Despite this, the reporting of animal use approval in the article and the use of a general approval instead of a specific one is inadequate. Readers are therefore advised to interpret the information regarding animal ethics approval with caution.
Stem Cell Research & Therapy•2025•DOI: 10.1186/s13287-025-04267-9
Background: In premature newborn infants, preterm white matter injury (PWMI) causes motor and cognitive disabilities. Accumulating evidence suggests that PWMI may result from defected differentiation of oligodendrocyte precursor cells (OPCs) and impaired maturation of oligodendrocytes. However, the underlying mechanisms remain unclear. Methods: Using RNAscope, we analyzed the expression level of RNA-binding protein LIN28A in individual OPCs. Knockout of one or both alleles of Lin28a in OPCs was achieved by administrating tamoxifen to NG2CreER::Ai14::Lin28aflox/+ or NG2CreER::Ai14::Lin28aflox/flox mice. Lentivirus expressing FLEX-Lin28a was used in NG2CreER mice to overexpress LIN28A in OPCs. A series of behavioral tests were performed to assess the cognitive functions of mice. Two-tailed unpaired t-tests was carried out for statistical analysis between groups. Results: We found that the expression of Lin28a was decreased in OPCs in a PWMI mouse model. Knockout of one or both alleles of Lin28a in OPCs postnatally resulted in reduced OPC differentiation, decreased myelinogenesis and impaired cognitive functions. Supplementing LIN28A in OPCs postnatally was able to promote OPC differentiation and enhance myelinogenesis, thus rescuing the cognitive functions in PWMI mice. Conclusion: Our study reveals that LIN28A is critical in regulating postnatal myelinogenesis. Overexpression of LIN28A in OPCs rescues cognitive deficits in PWMI mice by promoting myelinogenesis, thus providing a potential strategy for the treatment of PWMI.
Acta Biochimica et Biophysica Sinica•2025•DOI: 10.3724/abbs.2025070
Schisandrin A (SchA), a bioactive lignan that was isolated from the dried fruit of Schisandra chinensis, has attracted much attention because of its diverse spectrum of pharmacological effects. The aim of this study is to clarify the function of SchA in diabetes-related fear memory impairment and its molecular mechanisms. Rats are randomly assigned to 4 groups: the control group (Con group), the DM group, the DM + SchA group, and the Con + SchA group. The results demonstrate that SchA treatment improves insulin sensitivity, reduces blood glucose, and significantly reduces memory impairment. SchA treatment also prevents histological damage, enhances synaptic protein production, and significantly decreases Aβ42 formation in the diabetic prefrontal cortex. Further research reveals that SchA therapy decreases microglial activation and the expression levels of variables linked to inflammation while increasing the phosphorylation of proteins implicated in the insulin resistance signaling pathway. Furthermore, in the prefrontal cortex of diabetic rats, SchA decreases ferroptosis by increasing the protein expressions of GPX4, SLC7A11, Nrf2, HO-1, and SIRT1. Overall, our findings suggest that SchA may lessen diabetes-associated fear memory impairment symptoms by, most likely, lowering ferroptosis and inflammatory responses in the prefrontal brain of diabetic rats. SchA may be a useful therapy for diabetes, including memory impairment.
Acta Biochimica et Biophysica Sinica•2025•DOI: 10.3724/abbs.2025076
EGFR-tyrosine kinase inhibitor (TKI) therapy is the most effective targeted therapy for non-small cell lung cancer (NSCLC). However, drug resistance remains a significant factor in the failure of lung cancer therapy. In the present study, we utilize network pharmacology, molecular docking, in vitro and in vivo experiments to explore the targets and biological mechanisms of CP, a novel curcumin-piperlongumine hybrid molecule, in EGFR-TKI-resistant NSCLC cells. The results reveal that CP exhibits enhanced biological activity compared to its parent compounds. CP can effectively inhibit cell proliferation by arresting cell cycle in the G2/M phase and inducing apoptosis. Mechanistically, CP-induced apoptosis is partially mediated by PI3K/AKT signaling pathway. These findings highlight the potential of CP as a promising therapeutic agent for EGFR-TKI-resistant lung cancer therapy.
Acta Biochimica et Biophysica Sinica•2026•DOI: 10.3724/abbs.2025101
Abnormal proliferation and migration of endothelial cells are key contributors to tumor angiogenesis. Recent studies have shown that the crucial role of E3 ubiquitin ligase neuronal precursor cell expression developmentally downregulated 4-like (NEDD4L) in tumorigenesis. However, the precise mechanisms by which NEDD4L functions in endothelial cells remain unclear. In this study, we investigate the mechanisms by which NEDD4L influences the function of human umbilical vein endothelial cells (HUVECs) and its effect on tumor angiogenesis. Our results show that NEDD4L overexpression in HUVECs suppresses both cell proliferation and migration. Additionally, we find that the autophagic activity in NEDD4L-overexpressing cells is increased. Proteomic profiling and ubiquitination assays reveal that NEDD4L interacts with eEF1A1, promoting K48-linked ubiquitination-mediated degradation of eEF1A1. This post-translational modification is a key step in the NEDD4L-mediated regulation of autophagy and cellular function. Moreover, we find that loss of endothelial NEDD4L significantly enhances tumor growth and promotes angiogenesis in vivo. Overall, NEDD4L plays a crucial role in inhibiting tumor angiogenesis by regulating eEF1A1 ubiquitination and degradation, providing new insights into the NEDD4L-eEF1A1 axis and its potential as a therapeutic target.
Acta Biochimica et Biophysica Sinica•2024•DOI: 10.3724/abbs.2024009
Dysregulation of microRNA (miRNA) expression in cancer is a significant factor contributing to the progression of chemoresistance. The objective of this study is to explore the underlying mechanisms by which miR-34b-3p regulates chemoresistance in cervical cancer (CC). Previous findings have demonstrated low expression levels of miR-34b-3p in both CC chemoresistant cells and tissues. In this study, we initially characterize the behavior of SiHa/DDP cells which are CC cells resistant to the chemotherapeutic drug cisplatin (DDP). Subsequently, miR-34b-3p mimics are transfected into SiHa/DDP cells. It is observed that overexpression of miR-34b-3p substantially inhibits the proliferation, migration, and invasion abilities of SiHa/DDP cells and also enhances their sensitivity to DDP-induced cell death. Quantitative RT-PCR and western blot analysis further reveal elevated expression levels of STC2 and FN1 in SiHa/DDP cells, contrary to the expression pattern of miR-34b-3p. Moreover, STC2 and FN1 contribute to DDP resistance, proliferation, migration, invasion, and decreased apoptosis in CC cells. Through dual-luciferase assay analysis, we confirm that STC2 and FN1 are direct targets of miR-34b-3p in CC. Finally, rescue experiments demonstrate that overexpression of either STC2 or FN1 can partially reverse the inhibitory effects of miR-34b-3p overexpression on chemoresistance, proliferation, migration and invasion in CC cells. In conclusion, our findings support the role of miR-34b-3p as a tumor suppressor in CC. This study indicates that targeting the miR-34b-3p/STC2 or FN1 axis has potential therapeutic implications for overcoming chemoresistance in CC patients.
Stem Cell Research & Therapy•2026•DOI: 10.1186/s13287-026-05061-x
Osteoporosis is characterized by impaired bone formation relative to resorption, yet the molecular drivers of osteoblast dysfunction remain incompletely defined. Cadherin 19 (CDH19), located at chromosome 18q22-q23, has been linked to 18q deletion syndromes presenting with skeletal deformities, but its role in bone homeostasis was previously unknown. Using a Cre-loxP conditional knockout model, we demonstrate that CDH19 deletion in mice significantly reduces bone mass, with decreases in bone density, trabecular number, and bone volume fraction. Osteoblasts isolated from CDH19 knockout mice exhibit suppressed proliferation and osteogenic differentiation, as evidenced by EdU labeling, qPCR, alkaline phosphatase and alizarin red S staining, and Western blot. RNA sequencing and subsequent immunofluorescence and Western blot analyses reveal that the PI3K/AKT signaling pathway is markedly inhibited in CDH19-deficient osteoblasts. Administration of the PI3K/AKT agonist 740Y-P partially rescues the osteogenic differentiation deficit both in vitro and in vivo. These findings establish CDH19 as a critical regulator of osteoblast function through PI3K/AKT signaling and identify it as a potential therapeutic target for bone diseases such as osteoporosis.
Stem Cell Research & Therapy•2026•DOI: 10.1186/s13287-026-04962-1
This Editorial Expression of Concern addresses ethical reporting discrepancies in the original study by Kong et al. (Stem Cell Research & Therapy, 2020;11:449), which claimed that co-encapsulation of HNF4α-overexpressing human umbilical cord mesenchymal stem cells (UMSCs) with human primary hepatocytes ameliorates mouse acute liver failure. The original article cited animal ethics approval number SYXK 2008 0050, an Experimental Animal Use License for the facility rather than a study-specific protocol. This license appeared in multiple publications describing distinct experiments, raising concerns about the specificity and validity of ethical oversight. The authors have provided documentation indicating separate ethical approval was obtained, but the reporting remains ambiguous. The Editor-in-Chief issues this expression of concern to alert readers that the animal ethics approval information is unreliable and should be interpreted with caution. The original findings on the therapeutic potential of HNF4α-overexpressing UMSCs and hepatocyte co-encapsulation for acute liver failure remain unverified pending resolution of these ethical reporting issues. This notice does not retract the article but highlights the need for rigorous ethical transparency in preclinical stem cell research. The DOI for the original article is 10.1186/s13287-020-01962-7.
Chinese Journal of Tissue Engineering Research•2026•DOI: 10.12307/2026.21287
BACKGROUND: The onset of cervical instability in middle-aged and young adults often begins with neck muscle injuries. A deeper understanding of changes in neck muscles during cervical instability and their correlation can provide valuable data to support the prevention and treatment of cervical instability in this population. OBJECTIVE: To explore the correlation between cervical instability and neck muscle changes in middle-aged and young adults. METHODS: A total of 98 patients with cervical C4/5 instability and 88 healthy subjects, aged 18-45 years, were enrolled through recruitment advertisements and the Department of Spine, Wangjing Hospital, China Academy of Traditional Chinese Medicine. Cervical X-rays were collected to measure cervical curvature and C4/5 vertebral angular displacement. Cervical magnetic resonance imaging was taken to obtain data on C4/5 intervertebral disc signal intensity, as well as the relative cross-sectional area and fat ratio of neck muscles, including prevertebral muscles, deep posterior cervical muscles, and superficial muscles. A univariate intergroup comparison of X-ray and magnetic resonance imaging data was conducted between cervical instability subjects and healthy controls, along with Spearman correlation analysis between C4/5 angular displacement and disc signal intensity, relative cross-sectional area of neck muscles and fat percentage at the C4/5 level in cervical instability patients. RESULTS AND CONCLUSION: The cervical instability group had significantly greater age, C4/5 horizontal displacement, C4/5 angular displacement, and fat ratio of deep posterior cervical muscles than the healthy group (P < 0.05), while cervical curvature and relative cross-sectional area of deep posterior cervical muscles were significantly smaller (P < 0.05). Spearman correlation analysis showed a negative correlation between C4/5 angular displacement and relative cross-sectional area of deep posterior cervical muscles (P < 0.05). These findings suggest that changes in deep posterior cervical muscles may be closely related to the occurrence of cervical instability in middle-aged and young adults.
Chinese Journal of Tissue Engineering Research•2026•DOI: 10.12307/2026.21382
BACKGROUND: Early prediction of cervical instability is crucial for the prevention and treatment of cervical spondylosis, and deep learning technology can provide robust support for intelligent prediction of cervical instability. OBJECTIVE: To develop a deep learning model of cervical instability based on cervical magnetic resonance imaging for early intelligent prediction of cervical instability. METHODS: This study recruited young and middle-aged participants (18-45 years), including both cervical instability patients and healthy controls, through the Spine Department Outpatient Clinic of Wangjing Hospital, China Academy of Chinese Medical Sciences, as well as community-based recruitment. All participants underwent cervical magnetic resonance imaging examinations. On the axial magnetic resonance imaging images, five key anatomical structures were manually annotated: intervertebral disc, facet, prevertebral muscle, deep muscle group in the back of the neck, and superficial muscle group in the back of the neck. A deep learning algorithm was then employed to develop a predictive model for cervical instability, utilizing both the original images and the delineated regions of interest. Finally, the model's predictive performance was systematically evaluated and validated. RESULTS AND CONCLUSION: (1) The study included a total of 308 young and middle-aged participants, comprising 196 individuals with cervical instability and 112 healthy controls. Based on enrollment time, the subjects' data were allocated to either the model training set or the test set. (2) The model demonstrated high predictive performance, with an area under the curve values of 0.97, an F1-score of 0.98, a precision of 0.98, and a recall of 0.97 in the training set. In the test set, these values were 0.97, 0.95, 1.00, and 0.90, respectively. (3) The results indicate that the deep learning model based on cervical magnetic resonance images can achieve early intelligent prediction of cervical instability with high predictive performance.
Chinese Journal of Tissue Engineering Research•2026•DOI: 10.12307/2026.21527
BACKGROUND: Prolonged forward head posture induces neck muscle fatigue, a significant contributing factor to cervical spondylosis. Current unimodal monitoring approaches are inadequate to capture the dynamic coupling among muscle activation, metabolic activity, and motor control. OBJECTIVE: To systematically evaluate the temporal characteristics of neck muscle fatigue using multimodal monitoring technology, thereby providing a theoretical foundation for early detection and intervention of cervical fatigue. METHODS: Twenty healthy participants were recruited. Surface electromyography, near-infrared spectroscopy, and three-dimensional motion capture technology were synchronized to record electrophysiological signals, oxygenated hemoglobin concentration, and cervical kinematics during a sustained 45° static forward flexion task until subjective fatigue was reached (Borg CR-10 score ≥ 4). Temporal changes in root mean square amplitude, mean power frequency, muscle oxygen saturation, and normalized forward head angle were analyzed across fatigue stages segmented into 10% intervals of total endurance time. RESULTS AND CONCLUSION: (1) The root mean square amplitude increased significantly (P < 0.001), while mean power frequency and muscle oxygen saturation decreased significantly (P < 0.001) throughout the task, with the reduction in muscle oxygen saturation commencing from the 40% fatigue stage. (2) Linear regression analysis between mean power frequency and muscle oxygen saturation showed high explanatory power (upper trapezius R²=0.58, middle trapezius R²=0.61), and metabolic compensation preceded significant electrophysiological changes. (3) The upper trapezius entered fatigue earlier than the middle trapezius (P < 0.05). These results indicate that combined monitoring of mean power frequency and muscle oxygen saturation provides highly sensitive indicators for early warning of neck muscle fatigue.
Chinese Journal of Tissue Engineering Research•2026•DOI: 10.12307/2026.21586
BACKGROUND: In recent years, hydrogels have become an important research direction in the treatment of rheumatoid arthritis due to their excellent biocompatibility, controllable drug release performance, and advantages in multiple drug delivery routes. OBJECTIVE: To systematically review the application of hydrogel-based materials as drug delivery carriers in the treatment of rheumatoid arthritis, and explore the impact of different administration routes on the therapeutic effect. METHODS: Using “hydrogel, rheumatoid arthritis, smart hydrogel system, injectable hydrogel, intra-articular injection, transdermal drug delivery” as Chinese and English search terms, we searched PubMed, Web of Science, CNKI, WanFang Data, and VIP. Based on the inclusion criteria, 62 articles were finally included for review. RESULTS AND CONCLUSION: Hydrogels, leveraging their three-dimensional network structures and tunable physicochemical properties, not only allows drugs to accurately reach the lesion area but also significantly prolongs the retention time of drugs in the joint cavity, making them an ideal carrier in the field of drug delivery. The drug release mechanisms of hydrogels mainly include diffusion, chemical regulation, and swelling-mediated release; in addition, stimulus-responsive hydrogels can dynamically regulate drug release behavior based on environmental conditions (such as pH, temperature, enzyme concentration, etc.). In the treatment of rheumatoid arthritis, common administration routes for hydrogel drug delivery systems include parenteral administration, oral administration, transdermal administration, and intra-articular injection, which significantly reduce systemic adverse reactions, improve drug absorption efficiency, and enhance patient compliance. Although hydrogels as drug delivery carriers have shown significant application potential in the treatment of rheumatoid arthritis, long-term safety, biodegradability, and large-scale production still need breakthroughs to promote the clinical translation of hydrogel drug delivery carriers.
Acta Biochimica et Biophysica Sinica•2026•DOI: 10.3724/abbs.2026035
Pulmonary fibrosis (PF) is a life-threatening interstitial lung disease characterized by scarring and inflammation in lung tissues. Aberrant activation of the JAK/STAT and NF-κB signaling pathways is critical in initiating and sustaining the inflammatory processes that drive fibrotic progression. In this study, we identify a novel small-molecule compound, T4015, a 4-indolyl-2-phenylaminopyrimidine derivative, as a dual-pathway inhibitor targeting both JAK/STAT and NF-κB signaling. Dual-luciferase reporter assays demonstrate the potent inhibitory activity of T4015 against these pathways. T4015 effectively suppresses the phosphorylation of STAT3, JAK1, and TYK2 induced by IL-6 and IFN-β, while suppressing LPS-induced NF-κB activation in macrophages. Transcriptome sequencing and pathway enrichment analyses further confirm that T4015 downregulates multiple inflammation-related signaling cascades, including the JAK/STAT, NF-κB, TNF, IL-17, and Toll-like receptor pathways. In a mouse model of bleomycin-induced PF, T4015 treatment significantly improves survival, attenuates collagen deposition, and reduces the expression of pro-inflammatory and profibrotic markers such as IL-6, CCL2, and COL1. Molecular docking and target prediction analyses suggest that T4015 exhibits strong binding affinity for multiple kinases within the JAK/STAT and NF-κB networks, including JAK1, TYK2, JAK2, JAK3, RIPK1, IRAK1/4, TAB1, and ZAP70. Collectively, these results highlight T4015 as a promising therapeutic candidate for PF through its simultaneous inhibition of the JAK/STAT and NF-κB signaling pathways.
Chinese Journal of Pathophysiology•2026•DOI: 10.3969/j.issn.1000-4718.2026.05.014
AIM: Psoriasis is a chronic inflammatory skin disease characterized by keratinocyte hyperproliferation and immune dysregulation, yet the spatial epigenetic and neuroimmune features within the skin remain poorly understood. This study aims to construct a spatial atlas of the neuroimmune and epigenetic microenvironment in psoriasis. METHODS: Formalin-fixed, paraffin-embedded skin tissue samples from five psoriasis patients and four healthy controls were stained with a 33-metal antibody panel targeting immune and epigenetic markers. Imaging data were processed to analyze immune cell composition, spatial relationships, and epigenetic marker distribution in psoriatic lesions. RESULTS: Analysis of over 163,000 cells from five psoriasis patients and four healthy controls revealed that psoriatic lesions have a more complex cellular composition than normal skin, including diverse immune subsets, endothelial cells, keratinocytes, and nerve fibers. Neighborhood analysis showed enrichment of multiple immune cells, such as CD14+ monocytes, CD4+/CD8+ T-lymphocytes (T cells), CD68+ macrophages, CD69+ tissue-resident memory T cells and CD20+ B-lymphocytes (B cells), and nerve fibers around keratinocytes. Notably, positive interactions were observed between cutaneous nerve fibers and specific immune cells (CD8+ T cells and CD68+ macrophages) as well as blood vessels. Additionally, histone H3 lysine 27 trimethylation (H3K27me3) modification was mapped across cell types and found in immune cells adjacent to keratinocytes. CONCLUSION: Imaging mass cytometry delineated the psoriatic microenvironment's multicellular structure integrating epigenetic and neuroimmune components, offering new insights into psoriasis pathogenesis.
Acta Biochimica et Biophysica Sinica•2025•DOI: 10.3724/abbs.2025076
Acquired resistance to third-generation EGFR tyrosine kinase inhibitors (TKIs) such as osimertinib (AZD9291) remains an unresolved clinical bottleneck in non-small cell lung cancer (NSCLC), with median progression-free survival plateauing at 18.9 months. This study evaluates CP, a novel curcumin-piperlongumine hybrid molecule, against AZD9291-resistant NSCLC using network pharmacology, molecular docking, and in vitro/in vivo validation. PPI network analysis of intersecting targets identified EGFR, SRC, PIK3R, PIK3CA, KDR, MET, GRB2, PIK3CB, HSP90AA1, and ITGB1 as core nodes, with KEGG enrichment converging on the PI3K/AKT signaling axis. Molecular docking confirmed hydrogen-bond-mediated binding between CP and these targets. Western blot analysis demonstrated that CP markedly suppressed phosphorylation of EGFR, PI3K, AKT, and GSK-3β. Functionally, CP arrested the cell cycle at G2/M and induced apoptosis in drug-resistant NSCLC cells, with enhanced potency relative to parent compounds curcumin and piperlongumine. In vivo xenograft experiments corroborated growth inhibition. The data position CP as a dual-pathway inhibitor targeting both EGFR and PI3K/AKT cascades, providing a mechanistic rationale for its development as a therapeutic candidate in EGFR-TKI-resistant advanced NSCLC. The unresolved question of whether GSK-3β inhibition operates independently of EGFR-AKT signaling warrants further investigation.