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Clinically, a multitude of factors can contribute to the development of bone defects. In the process of bone healing, the nervous system plays a vital role in bone regeneration. Small molecules from the nervous system, such as neurotrophic factors and neuropeptides, have been found to stimulate osteoblast proliferation and differentiation by activating signaling pathways associated with bone calcification and angiogenesis. These small molecules play a crucial regulatory role at various stages of bone healing. The systematic release mechanism of small molecules within the nervous system through diverse bone tissue engineering materials holds significant clinical implications for the controlled regulation of the bone healing process. This review provides an overview of the involvement of various nervous system small molecules at different stages of bone healing and discusses their regulatory mechanisms, aiming to establish a theoretical foundation for programmed regulation in bone regeneration and design of replacement materials in bone tissue engineering.
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http://dx.doi.org/10.2147/IJN.S505677 | DOI Listing |
Chem Biodivers
September 2025
Zhejiang Provincial Engineering Research Center of New Technologies and Applications for Targeted Therapy of Major Diseases, Laboratory of Anti-Allergy Functional Compounds, College of Life Sciences and Medicine, Zhejiang Sci-Tech University, Hangzhou, China.
Autoimmune diseases (AIDs), defined by irregularities in immune system function, pose a substantial health challenge worldwide, impacting millions with persistent and frequently debilitating conditions. Conventional treatments, such as glucocorticoid-based immunosuppressive therapies, are associated with notable drawbacks and limitations. In response to these difficulties, recent scientific efforts have increasingly focused on natural compounds as potential therapeutic agents.
View Article and Find Full Text PDFJ Am Chem Soc
September 2025
Department of Chemistry and Biochemistry, University of Delaware, Newark, Delaware 19716, United States.
Among the different types of HIV-1 maturation inhibitors, those that stabilize the junction between the capsid protein C-terminal domain (CA) and the spacer peptide 1 (SP1) within the immature Gag lattice are promising candidates for antiretroviral therapies. Here, we report the atomic-resolution structure of CA-SP1 assemblies with the small-molecule maturation inhibitor PF-46396 and the assembly cofactor inositol hexakisphosphate (IP6), determined by magic angle spinning (MAS) NMR spectroscopy. Our results reveal that although the two PF-46396 enantiomers exhibit distinct binding modes, they both possess similar anti-HIV potency.
View Article and Find Full Text PDFPharm Dev Technol
September 2025
School of Pharmaceutical Engineering, Shenyang Pharmaceutical University, wenhua Road 103, Shenyang 110016, PR China.
Nimodipine (NMP), a poorly water-soluble small-molecule agent, demonstrates notable therapeutic limitations in addressing cerebral vasospasm secondary to subarachnoid hemorrhage (SAH). Owing to its inherent physicochemical properties characterized by low oral bioavailability, rapid elimination half-life, and extensive first-pass metabolism, conventional formulations necessitate frequent dosing regimens to sustain therapeutic plasma concentrations. These pharmacological challenges collectively result in suboptimal patient adherence, marked plasma concentration fluctuations, and recurrent vascular irritation.
View Article and Find Full Text PDFProc Natl Acad Sci U S A
September 2025
State Key Laboratory of Bioactive Molecules and Druggability Assessment, Guangdong Province Key Laboratory of Pharmacodynamic Constituents of Traditional Chinese Medicine and New Drugs Research, International Cooperative Laboratory of Traditional Chinese Medicine Modernization and Innovative Drug De
Proliferative retinopathy is a leading cause of irreversible blindness in humans; however, the molecular mechanisms behind the immune cell-mediated retinal angiogenesis remain poorly elucidated. Here, using single-cell RNA sequencing in an oxygen-induced retinopathy (OIR) model, we identified an enrichment of sorting nexin (SNX)-related pathways, with SNX3, a member of the SNX family that is involved in endosomal sorting and trafficking, being significantly upregulated in the myeloid cell subpopulations of OIR retinas. Immunostaining showed that SNX3 expression is markedly increased in the retinal microglia/macrophages of mice with OIR, which is mainly located within and around the neovascular tufts.
View Article and Find Full Text PDFACS Synth Biol
September 2025
The Key Laboratory of Industrial Biotechnology, Ministry of Education, School of Biotechnology, Jiangnan University, Wuxi 214122, P. R. China.
Human Bone Morphogenetic Protein-2 (hBMP-2) serves as a critical regulator in bone and cartilage formation; however, its industrial application is hindered by its inherent tendency to form inclusion bodies in prokaryotic expression systems. To address this issue, we established a recombinant hBMP-2 (rhBMP-2) expression system using the pCold II plasmid and the SHuffle T7 strain. We explored several strategies to enhance the solubility of rhBMP-2, including coexpression with molecular chaperones, vesicle-mediated secretory expression, fusion expression with synthetic intrinsically disordered proteins (SynIDPs), and fusion expression with small-molecule peptide tags.
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