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been used as 3D tissue structures in newly discovered drugs and personalized medicines and are more relevant to in vivo microenvironmental conditions than 2D substrates. [2] Recently, a variety of micro/nanoscale biofabrication methods have been used to build complex 3D biomedical structures. Unlike conventional processes, which can incur unpredictable properties, such as non-homogeneous physicochemical and mechanical properties, within the structure, 3D bioprinting provides precise control of various biophysical and biochemical properties. It can also be used to print different cell types that are appropriate to the region of tissue restoration.However, despite advances in 3D bioprinting of scaffolds for various tissue engineering applications, developing functional bioprinting of cell-laden structures remains challenging due to several limitations. A common shortcoming of bioprinted structures is the low degree of cell-cell interaction in matrix hydrogels, which are critical for tissue restoration. Additionally, relatively high cell densities in bioink can cause significant cell damage during the printing process. Even fabricated structures with high cell densities cannot sustain printed 3D structures due to their relatively low physical strength.However, although the appropriate cell density for a given application is highly dependent on the cell type and hydrogel physicochemical properties, high cell density induces efficient cell-to-cell signaling and regulates stem cell differentiation. [3][4][5] According to Maia et al., high densities of human mesenchymal stem cells cultured in Arg-Gly-Asp (RGD)-alginate 3D matrixes allow the development of multicellular structures and effectively stimulates osteogenic differentiation of the implanted cells. [6] Thus, cell spheroids, high density 3D cell aggregations, can be considered microtissues that mimic natural microenvironmental conditions by providing sufficient cell-to-cell or cell-to-ECM interactions to increase various cellular activities, including cell differentiation. [7] In general, spheroids are used to treat or regenerate damaged tissues through an injection process. However, to obtain the intricately designed configurations necessary for some applications, spheroids must be mixed with hydrogels and spheroid-laden bioink printed into 3D mesh structures.Cell-laden structures are widely applied for a variety of tissue engineering applications, including tissue restoration. Cell-to-cell interactions in bioprinted structures are important for successful tissue restoration, because cell-cell signaling pathways can regulate tissue development and stem cell fate. However, the low degree of cell-cell interaction in conventional cellladen bioprinted structures is challenging for the therapeutic application of this modality. Herein, a microfluidic device with cell-laden methacrylated gelatin (GelMa) bioink and alginate as a matrix hydrogel is used to fabricate a functional hybrid structure laden with cell-aggregated microbeads. This approach effectively increases t...
Nicotinamide adenine dinucleotide (NAD +) is an essential metabolite in energy metabolism as well as a co-substrate in biochemical reactions such as protein deacylation, protein ADP-ribosylation and cyclic ADP-ribose synthesis mediated by sirtuins, poly (ADP-ribose) polymerases (PARPs) and CD38. In eukaryotic cells, NAD + is synthesized through three distinct pathways, which offer different strategies to modulate the bioavailability of NAD +. The therapeutic potential of dietarily available NAD + boosters preserving the NAD + pool has been attracting attention after the discovery of declining NAD + levels in ageing model organisms as well as in several age-related diseases, including cardiometabolic and neurodegenerative diseases. Here, we review the recent advances in the biology of NAD + , including the salubrious effects of NAD + boosters and discuss their future translational strategies. K E Y W O R D S ageing, NAD + booster, nicotinamide adenine dinucleotide (NAD +), nicotinamide riboside (NR) 2 of 13 | KANG et Al.
Protein lysine acetylation is a post-translational modification that regulates protein structure and function. It is targeted to proteins by lysine acetyltransferases (KATs) or removed by lysine deacetylases. This work identifies a role for the KAT enzyme general control of amino acid synthesis protein 5 (GCN5; KAT2A) in regulating muscle integrity by inhibiting DNA binding of the transcription factor/repressor Yin Yang 1 (YY1). Here we report that a muscle-specific mouse knockout of GCN5 (Gcn5skm−/−) reduces the expression of key structural muscle proteins, including dystrophin, resulting in myopathy. GCN5 was found to acetylate YY1 at two residues (K392 and K393), disrupting the interaction between the YY1 zinc finger region and DNA. These findings were supported by human data, including an observed negative correlation between YY1 gene expression and muscle fiber diameter. Collectively, GCN5 positively regulates muscle integrity through maintenance of structural protein expression via acetylation-dependent inhibition of YY1. This work implicates the role of protein acetylation in the regulation of muscle health and for consideration in the design of novel therapeutic strategies to support healthy muscle during myopathy or aging.
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