Stem Cell Research & Therapy•2024•DOI: 10.1186/s13287-024-03945-4
Background Lung injury and pulmonary fibrosis (PF), frequently arising as sequelae of severe and acute lung disease, currently face a dearth of effective therapeutic potions. Mesenchymal stem cells (MSCs) with immunomodulatory and tissue repair functions have immense potential to treat lung injury and PF. However, the optimal route of administration, timing, and frequency of dosing remain elusive. Human embryonic stem cell-derived immunity-and-matrix-regulatory cells (IMRCs) have shown therapeutic potential for lung injury and PF. Methods To ascertain the optimal therapeutic regimen for IMRCs in PF, we conducted an experimental study. Utilizing a mouse model of PF induced by bleomycin (BLM), IMRCs were administered via either a single or double intravenous (IV) or intratracheal (IT) injection on the first and seventh days post-BLM induction. Results Our findings revealed that IV infusion of IMRCs surpassed IT infusion in enhancing survival rates, facilitating body weight recovery, and optimizing Ashcroft and Szapiel scores among the model mice. Notably, IV administration exhibited a more profound ability to mitigate lung inflammation and fibrosis. Moreover, earlier and more frequent administrations of IMRCs were found to be advantageous in enhancing their therapeutic effects. Specifically, early administration with two IV infusions significantly improved body weight, lung organ coefficient, pulmonary ventilation and diffusion functions, and PF. This was accompanied by an increase in alveolar type I and II epithelial cells and a suppression of macrophage infiltration via CD24. Conclusion Collectively, these results suggested that IMRCs infusion ameliorated lung injury by promoting lung regeneration and inhibiting macrophage infiltration in a route, time, and frequency-dependent manner.
Acta Biochimica et Biophysica Sinica•2026•DOI: 10.3724/abbs.2025130
Tumor radioresistance and severe toxicity make reirradiation for recurrent nasopharyngeal carcinoma (NPC) a significant clinical challenge. This study aims to investigate the ability of the poly(ADP-ribose) polymerase (PARP) inhibitor olaparib to sensitize recurrent NPC cells irradiated with photon or carbon ion (C-ion), and to explore the underlying mechanism of the synergistic promotion of cell death by olaparib and ionizing radiation. The results show that olaparib has significant X-ray and C-ion radiosensitization effects on recurrent NPC cells and the associated HK-RR photon-resistant model. Radiation, particularly C-ion exposure, induces a homologous recombination (HR)-deficient gene signature in HR-proficient NPC cells, potentially increasing their sensitivity to PARP inhibition. C-ion and X-ray irradiation induces similar modes of cell death, and multiple cell death pathways [including apoptosis, necrosis, ferroptosis, senescence, and autophagic cell death (ACD)] contribute to the cytotoxic effects of radiation combined with olaparib, with ACD being the dominant pathway. Both the pharmacological and genetic inhibition of autophagy significantly attenuate the radiosensitization effect of olaparib. In conclusion, olaparib effectively sensitizes recurrent NPC cells to both X-ray irradiation and C-ion irradiation, with autophagy playing a central role in mediating this effect.
Acta Biochimica et Biophysica Sinica•2024•DOI: 10.3724/abbs.2024088
Cloning short DNA fragments, such as shRNA and sgRNA, is a routine but time-consuming task in molecular biology. Traditional methods require annealing of complementary oligos or PCR amplification, which are labor-intensive and time-consuming. Here, we report a novel PCR-independent, annealing-free cloning method that enables the insertion of short DNA fragments using a single oligo. The method relies on T4 DNA ligase for ligation and host cell DNA polymerase for complementary strand synthesis. We demonstrate that adding T4 DNA polymerase and dNTPs to the ligation mixture significantly improves cloning efficiency. This approach simplifies the cloning process, reduces time to less than 1 hour, and is compatible with standard laboratory reagents. Our method provides a rapid and efficient alternative for cloning short DNA fragments, with broad applications in gene knockdown and genome editing.
Chinese Traditional and Herbal Drugs•2026•DOI: 10.7501/j.issn.0253-2670.2026.16.20261605
Property prediction of traditional Chinese medicine (TCM) molecules remains constrained by their complex ring systems and conformational flexibility. Conventional graph neural networks (GNNs) treat molecules as topological graphs, discarding bond length and angle strain information critical for accurate property estimation. This study introduces the flexibility-ring enhanced graph neural network (FRGNN), which augments the graph isomorphism network (GIN) with edge descriptors encoding bond length strain and angle strain, and incorporates multiple favorable conformations to construct multi-graph data. The model was evaluated on two TCM databases comprising 37,822 molecules across seven key molecular properties, benchmarked against three state-of-the-art (SOTA) GNN models and two basic GNN models. FRGNN achieved an average root mean square error (RMSE) reduction of 8.63% relative to the second-best model across all seven tasks. For molecules containing polycyclic and macrocyclic structures, the RMSE reduction reached 10.04%. These results demonstrate that FRGNN outperforms existing SOTA small-molecule property prediction models on TCM compounds, offering a robust computational approach for complex natural product characterization. The incorporation of flexibility and ring-specific descriptors addresses a critical gap in molecular representation learning, enabling more accurate predictions for structurally diverse TCM constituents.
Chinese Journal of Tissue Engineering Research•2026•DOI: 10.12307/2026.21545
BACKGROUND: Osteonecrosis of the femoral head is a refractory disorder characterized by osteocyte apoptosis and structural collapse of the femoral head. Its pathogenesis is closely associated with vascular injury, dysregulated bone metabolism, and aberrant mechanical stress. In recent years, animal models have served as indispensable tools for simulating pathological processes, playing an irreplaceable role in elucidating molecular mechanisms of osteonecrosis of the femoral head and evaluating novel interventions. Nevertheless, the standardization of model development and their clinical translational value require systematic investigation. OBJECTIVE: To analyze the research landscape in the field of osteonecrosis of the femoral head using bibliometric approaches, with an emphasis on evaluating the application characteristics, limitations, and future optimization directions of animal models in study design, providing a reference for advancing mechanistic understanding and therapeutic development. METHODS: Literature published between January 2015 and March 2025 was retrieved from the Web of Science Core Collection (SCI-Expanded), China National Knowledge Infrastructure (CNKI), and Wanfang databases. The search strategy for English literature was TS=(osteonecrosis of the femoral head) AND TS=(mouse OR mice OR rat OR rabbit OR dog OR swine OR pig OR sheep OR monkey OR "laboratory animal" OR "experiment animal"). For Chinese literature, the search was SU=股骨头坏死 AND SU=鼠+兔+犬+猪+羊+猴+实验动物+动物实验. CiteSpace 6.3.R1 software was used to perform visualization analysis of countries, institutions, authors, keywords, and co-cited references. Trends were summarized based on animal model classification and application characteristics. RESULTS AND CONCLUSION: (1) In English literature, China contributed over 80% of the research (458 articles). Hot topics focused on steroid-induced necrosis mechanisms (e.g., oxidative stress-autophagy axis), stem cell/tissue engineering therapies, and traditional Chinese medicine interventions. The research on animal models of osteonecrosis of the femoral head exhibited a "high output-low collaboration" characteristic. (2) In Chinese literature, the publishing institutions were mainly traditional Chinese medicine-related institutions, and traditional Chinese medicine and steroid-induced osteonecrosis of the femoral head were important research hotspots. (3) Future efforts should deepen cross-species validation platforms, multi-omics integration, and collaborative strategies for the development of Chinese and Western medicine to accelerate clinical translation.