Cell-extracellular matrix (ECM) interactions play a central role in tissue architecture and turnover. Particularly, integrin-mediated cell adhesion participates in biochemical and physical signals. The aim of this study is to investigate the importance of ECM organization for alveolar bone osteoblasts adhesion and to determine the effects on cell functions such as collagen and fibronectin production. By applying new concepts from the nanotechnology to biological systems, we have developed materials decorated with nano-patterns of peptides of the ECM arranged at a distance of 58 or 73 nm. On these surfaces, human osteoblasts from alveolar bone were cultured for 1-96 hr and examined by video and fluorescence microscopy. Protein quantification by western blotting and gene expression by RT-PCR were also performed. Good cell adhesion and spreading was observed on the 58 nm pattern after 30 min, while weak adhesion and increased motility was evident in osteoblasts on the 73 nm pattern, leading to alteration of cell shape and reduction of cell area after 24 hr. Moreover, cells on the 73 nm did not form focal adhesions and failed to organize the cytoskeleton. After 96 hr in culture, osteoblasts on the 73 nm retained intracellular collagen and produced a disorganized fibronectin network. Osteoblast adhesion and intra-and extra-cellular molecules reorganization are regulated not only by the composition but also by the structure of the extracellular environment. Our novel in vitro system makes it possible to elucidate some of the mechanisms necessary for the maintenance of tissue architecture and mechanical strength, as well as for the design of artificial materials for future clinical applications.
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Nat Commun
December 2024
State Key Laboratory of Protein and Plant Gene Research, School of Life Sciences, Biomedical Pioneering Innovative Center (BIOPIC) and Beijing Advanced Innovation Center for Genomics (ICG), Center for Bioinformatics (CBI), Peking University, 100871, Beijing, China.
Deciphering how noncoding DNA determines gene expression is critical for decoding the functional genome. Understanding the transcription effects of noncoding genetic variants are still major unsolved problems, which is critical for downstream applications in human genetics and precision medicine. Here, we integrate regulatory-specific neural networks and tissue-specific gradient-boosting trees to build SVEN: a hybrid sequence-oriented architecture that can accurately predict tissue-specific gene expression level and quantify the tissue-specific transcriptomic impacts of structural variants across more than 350 tissues and cell lines.
View Article and Find Full Text PDFArch Pharm (Weinheim)
January 2025
School of Chemistry and Pharmaceutical Engineering, Huanghuai University, Zhumadian, Henan, China.
Cancer, characterized by uncontrolled growth and spread of abnormal cells potentially influencing almost all tissues in the body, is one of the most devastating and lethal diseases throughout the world. Chemotherapy is one of the principal approaches for cancer treatment, but multidrug resistance and severe side effects represent the main barriers to the success of therapy, creating a vital need to develop novel chemotherapeutic agents. The 1,2,3-triazole moiety can be conveniently constructed by "click chemistry" and could exert diverse noncovalent interactions with various enzymes in cancer cells.
View Article and Find Full Text PDFJ Physiol Anthropol
December 2024
Faculty of Sport Management, Department of Sport Management, Shobi University, 1-1-1, Toyoda-cho, Kawagoe, Saitama, 350-1110, Japan.
Background: Muscle architecture is closely related to muscle function. Increased knowledge of growth changes in muscle architecture will provide insights into the development of human movements and sports performance during the growth period. However, it is unclear how the muscle architecture of the medial gastrocnemius (MG) grows.
View Article and Find Full Text PDFHum Genomics
December 2024
Department of Clinical Neurosciences, 'Carol Davila' University of Medicine and Pharmacy, Bucharest, Romania.
Neurodegenerative diseases present complex genetic architectures, reflecting a continuum from monogenic to oligogenic and polygenic models. Recent advances in multi-omics data, coupled with systems genetics, have significantly refined our understanding of how these data impact neurodegenerative disease mechanisms. To contextualize these genetic discoveries, we provide a comprehensive critical overview of genetic architecture concepts, from Mendelian inheritance to the latest insights from oligogenic and omnigenic models.
View Article and Find Full Text PDFMicrob Pathog
December 2024
Eastern Regional Station, ICAR-Indian Veterinary Research Institute, Kolkata-700037,West Bengal, India.
The cure rate of Staphylococcus aureus mastitis by conventional antibiotic therapy is very poor. Diflunisal (DIF), a difluorophenol derivative of salicylic acid, is reported to have strong anti-bacterial and anti-inflammatory effects against S. aureus infection.
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