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Volume 26 ， Issue 9 ， 2025
- Abstract：The dysfunction of the lysosome and autophagy-lysosome system serves as a driving force for neurodegenerative diseases, metabolic disorders, inflammatory conditions, and other related diseases, closely influencing their onset and progression. Therefore, restoring the function of the lysosome or autophagy-lysosome system has become an increasingly crucial therapeutic strategy in disease management. In this review, we will introduce the lysosomal biogenesis, structure, and function, as well as the biological process of the autophagy-lysosome system. Various diseases closely associated with lysosomal/autophagic dysfunction are also reviewed, emphasizing the significance of targeting the function of the lysosome or autophagy-lysosome system in disease treatment. Finally, we focus on engineered nanomaterials that have the capabilities to restore the function of the lysosome or autophagy-lysosome system, and summarize different strategies and methods for achieving this goal. This review aims to elucidate the latest progress in the field of nanomedicine for lysosomal/autophagic defect-related diseases and inspire the development of innovative and clinically valuable nanomedicines.Keywords：Lysosome;Autophagy;Lysosomal/autophagic disfunction;Acidic nanoparticle;Transcription factor EB (TFEB);Dementia;Alzheimer’s disease4|0|0Updated：2025-09-22
- Abstract：Megakaryocytes and hepatocytes are unique cells in mammals that undergo polyploidization through endomitosis in terminal differentiation. Many polyploidization regulators and underlying mechanisms have been reported, most of which are tightly coupled with development, organogenesis, and cell differentiation. However, the nature of endomitosis, which involves successful entry into and exit from mitosis without complete cytokinesis, has not yet been fully elucidated. We highlight that endomitosis is a new cell fate in the cell cycle, and tetraploidy is a critical stage at the bifurcation of cell fate decision. This review summarizes the recent research progress in this area and provides novel insights into how cells manipulate mitosis toward endomitosis. Endomitotic cells can evade the tetraploidy restrictions and proceed to multiple rounds of the cell cycle. This knowledge not only deepens our understanding of endomitosis as a fundamental biological process but also offers new perspectives on the physiological and pathophysiological implications of polyploidization.Keywords：Polyploidy;Endomitosis;Megakaryocyte;Hepatocyte;Cell cycle;Tetraploidy checkpoint;Whole-genome doubling4|0|0Updated：2025-09-22
Review
- Abstract：Bone repair remains an important target in tissue engineering, making the development of bioactive scaffolds for effective bone defect repair a critical objective. In this study, β-tricalcium phosphate (β-TCP) scaffolds incorporated with processed pyritum decoction (PPD) were fabricated using three-dimensional (3D) printing-assisted freeze-casting. The produced composite scaffolds were evaluated for their mechanical strength, physicochemical properties, biocompatibility, in vitro pro-angiogenic activity, and in vivo efficacy in repairing rabbit femoral defects. They not only demonstrated excellent physicochemical properties, enhanced mechanical strength, and good biosafety but also significantly promoted the proliferation, migration, and aggregation of pro-angiogenic human umbilical vein endothelial cells (HUVECs). In vivo studies revealed that all scaffold groups facilitated osteogenesis at the bone defect site, with the β-TCP scaffolds loaded with PPD markedly enhancing the expression of neurogenic locus Notch homolog protein 1 (Notch1), vascular endothelial growth factor (VEGF), bone morphogenetic protein-2 (BMP-2), and osteopontin (OPN). Overall, the scaffolds developed in this study exhibited strong angiogenic and osteogenic capabilities both in vitro and in vivo. The incorporation of PPD notably promoted the angiogenic-osteogenic coupling, thereby accelerating bone repair, which suggests that PPD is a promising material for bone repair and that the PPD/β-TCP scaffolds hold great potential as a bone graft alternative.Keywords：Bone defect;Processed pyritum;Three-dimensional (3D) printing-assisted freeze-casting;Angiogenesis;Bone regeneration;VEGF-Notch1-BMP-2-OPN coupling5|0|0Updated：2025-09-22
- Abstract：BackgroundPeriodontitis is characterized by alveolar bone resorption, aggravated by osteoblast dysfunction, and associated with intracellular oxidative stress linked to the nuclear factor erythroid 2-related factor 2 (NRF2) level. We evaluated the molecular mechanism of periodontitis onset and development and the role of NRF2 in osteogenic differentiation.MethodsPrimary murine mandibular osteoblasts were extracted and exposed to Porphyromonas gingivalis lipopolysaccharide (Pg-LPS) or other stimuli. Reactive oxygen species (ROS) and 5,5',6,6'-tetrachloro-1,1',3,3'-tetraethylbenzimidazolylcarbocyanine iodide (JC-1) staining were used to detect intracellular oxidative stress. Alkaline phosphatase staining and alizarin red S staining were used to detect the osteogenic differentiation of osteoblasts. Immunofluorescence and western blotting were used to determine the changes in the mitogen-activated protein kinase (MAPK) pathway and related molecule activities. Immunofluorescence colocalization and co-immunoprecipitation were performed to examine the nuclear translocation of NRF2 and its interaction with dual-specific phosphatase 1 (DUSP1) in cells.ResultsLigated tissue samples showed higher alveolar bone resorption rate and lower NRF2 level than healthy periodontal tissue samples. Pg-LPS increased intracellular oxidative stress levels and inhibited osteogenic differentiation, whereas changes in NRF2 expression were correlated with changes in the oxidative stress and osteogenesis rate. NRF2 promoted the dephosphorylation of the MAPK pathway by nuclear translocation and the upregulation of DUSP1 expression, thus enhancing the osteogenic differentiation capacity of mandibular osteoblasts. The interaction between NRF2 and DUSP1 was observed.ConclusionsNRF2 and its nuclear translocation can regulate the osteogenic differentiation of mandibular osteoblasts under Pg-LPS conditions by interacting with DUSP1 in a process linked to the MAPK pathway. These findings form the basis of periodontitis treatment.Keywords：Periodontitis;Nuclear factor erythroid 2-related factor 2 (Nrf2);Dual-specific phosphatase 1 (DUSP1);Mitogen-activated protein kinase (MAPK);Oxidative stress;Osteogenesis4|0|0Updated：2025-09-22
- Abstract：Mycophenolic acid (MPA), the active moiety of both mycophenolate mofetil (MMF) and enteric-coated mycophenolate sodium (EC-MPS), serves as a primary immunosuppressant for maintaining solid organ transplants. Therapeutic drug monitoring (TDM) enhances treatment outcomes through tailored approaches. This study aimed to develop an evidence-based guideline for MPA TDM, facilitating its rational application in clinical settings. The guideline plan was drawn from the Institute of Medicine and World Health Organization (WHO) guidelines. Using the Delphi method, clinical questions and outcome indicators were generated. Systematic reviews, Grading of Recommendations Assessment, Development, and Evaluation (GRADE) evidence quality evaluations, expert opinions, and patient values guided evidence-based suggestions for the guideline. External reviews further refined the recommendations. The guideline for the TDM of MPA (IPGRP-2020CN099) consists of four sections and 16 recommendations encompassing target populations, monitoring strategies, dosage regimens, and influencing factors. High-risk populations, timing of TDM, area under the curve (AUC) versus trough concentration (C0), target concentration ranges, monitoring frequency, and analytical methods are addressed. Formulation-specific recommendations, initial dosage regimens, populations with unique considerations, pharmacokinetic-informed dosing, body weight factors, pharmacogenetics, and drug–drug interactions are covered. The evidence-based guideline offers a comprehensive recommendation for solid organ transplant recipients undergoing MPA therapy, promoting standardization of MPA TDM, and enhancing treatment efficacy and safety.Keywords：Guideline;Mycophenolic acid (MPA);Therapeutic drug monitoring (TDM);Grading of Recommendations Assessment, Development, and Evaluation (GRADE);Solid organ transplant4|0|0Updated：2025-09-22
Research Article
- Abstract：皮肤鳞状细胞癌（cSCC）是非黑色素瘤皮肤癌中最常见的肿瘤之一，根据其临床表现可分为原位、侵袭性和特殊亚型（如角化棘皮瘤、疣状癌等）。原位cSCC好发于中老年人群，常见于头面部和四肢等暴露部位，典型皮损表现为单一的、边界清晰的红色斑块。由于皮肤鳞状细胞癌的发病率和死亡率呈不断升高的趋势，亟需采取新的防治措施。5-氨基酮戊酸光动力疗法（5-ALA PDT）在临床上广泛应用于尖锐湿疣、痤疮、光线性角化病和某些皮肤恶性肿瘤（如浅表型基底细胞癌和原位cSCC等）。然而，5-ALA PDT在原位cSCC治疗中的安全性仍有待阐明。本文报道了1例53岁的原位cSCC女性患者。患者主诉“左侧鼻根皮疹一年余”，皮疹局部伴有轻度疼痛，且逐渐增大。出于美容考虑，患者拒绝行扩大手术切除根治术，并要求保守治疗。因此，作为手术的替代治疗，患者每周接受1次5-ALA PDT，共治疗4周。4次治疗结束后患者皮损消退，疗效显著，未遗留明显瘢痕形成，随访2年未见肿瘤复发。Keywords：非黑色素瘤皮肤癌;皮肤鳞状细胞癌（cSCC）;5-氨基酮戊酸光动力疗法（5-ALA PDT）4|0|0Updated：2025-09-22
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