Full article ">Figure 1
<p>Overview of the screening process.</p> Full article ">Figure 2
<p><b>Validation of OATP2B1, BCRP, and P-gp transporter assays.</b> (<b>a</b>) Uptake of <sup>3</sup>H-ES by human OATP2B1: HEK-293 cells expressing OATP2B1 (<span class="html-italic">n</span> = 6), OATP2B1 in the presence of 20 μM erlotinib (an OATP2B1 inhibitor; <span class="html-italic">n</span> = 3), or an empty vector (<span class="html-italic">n</span> = 12) were incubated with <sup>3</sup>H-ES at 37 °C for 10 min. (<b>b</b>) Uptake of <sup>3</sup>H-CCK8 by human BCRP: BCRP membrane vesicles (25 μg/well) were incubated with <sup>3</sup>H-CCK8 with either 5 mM ATP (<span class="html-italic">n</span> = 6), 5 mM ATP with 200 μM BSP (<span class="html-italic">n</span> = 3), or 5 mM AMP (<span class="html-italic">n</span> = 3) at 37 °C for 20 min. (<b>c</b>) Uptake of <sup>3</sup>H-NMQ by human P-gp: P-gp membrane vesicles (25 μg/well) were incubated with <sup>3</sup>H-NMQ in the presence of 5 mM ATP (<span class="html-italic">n</span> = 6), 5 mM ATP with 200 μM verapamil (<span class="html-italic">n</span> = 3), or 5 mM AMP (<span class="html-italic">n</span> = 3) at 37 °C for 20 min. Transport in the absence of inhibitors is expressed as 100% and each value represents the mean ± SD; a two-tailed <span class="html-italic">t</span>-test was applied <span class="html-italic">p</span> < 0.0001: ****; <span class="html-italic">p</span> < 0.01: **.</p> Full article ">Figure 3
<p><b>Concentration–response relationships for inhibition of intestinal transporters by AP and BHA.</b> (<b>a</b>) AP and BHA inhibition of OATP2B1; (<b>b</b>) BHA inhibition of BCRP; (<b>c</b>) BHA inhibition of P-gp. Reported IC<sub>50</sub>s are the mean ± SD of three independent experiments. Plots show the mean ± SD from one representative experiment.</p> Full article ">Figure 4
<p>Concentration–response relationships for inhibition of OATP2B1-mediated valsartan transport by AP and BHA. Plots show mean ± SD from one representative experiment.</p> Full article ">Figure 5
<p><b>Effects of elacridar or BHA on the efflux of digoxin by MDCK-hMDR1-cMDR1-KO cells.</b> The MDCK-hMDR1-cMDR1-KO cell line is a CRISPR-Cas9 engineered MDCK line that expresses human MDR1 while lacking the endogenous canine MDR1 (cABCB1). Elacridar (2 μM) or BHA (62.5 or 178 μM) was applied to both the basal and apical sides of the cells. The control cell line was MDCK, in which the canine MDR1 (cABCB1) has been knocked out. The efflux of <sup>3</sup>H-digoxin (2.5 µM) from the basal to apical side was measured over a period of 4 h, both with and without the addition of the compounds to both sides. Data are presented as mean values ± SD from one representative experiment.</p> Full article ">
<p>Schematic classification of HDAC family.</p> Full article ">Figure 2
<p>A 3D structure available for human Class I HDAC. HDAC1 in complex with the dimeric ELM2-SANT domain of MTA1 from the NuRD complex (PDB code 4BKX) [<a href="#B44-pharmaceuticals-17-00620" class="html-bibr">44</a>]; HDAC2 in complex with SAHA (Vorinostat) (PDB code 4LXZ) [<a href="#B45-pharmaceuticals-17-00620" class="html-bibr">45</a>]; HDAC3 bound to corepressor and inositol tetraphosphate (PDB code 4A69) [<a href="#B43-pharmaceuticals-17-00620" class="html-bibr">43</a>]; HDAC8 complexed with Trichostatin A (PDB code 1T64) [<a href="#B43-pharmaceuticals-17-00620" class="html-bibr">43</a>].</p> Full article ">Figure 3
<p>Dynamics and catalytic mechanisms of zinc ion-dependent HDACs during the deacylation process. The hydrolyzing portion is highlighted in red.</p> Full article ">Figure 4
<p>A 3D structure available for human Class IIa and IIb HDAC. HDAC4 catalytic domain bound to a hydroxamic acid inhibitor (PDB code 2VQM) [<a href="#B59-pharmaceuticals-17-00620" class="html-bibr">59</a>]; HDAC6 with catalytic domain 2 in complex with Trichostatin A (PDB code 5EDU) [<a href="#B60-pharmaceuticals-17-00620" class="html-bibr">60</a>]; HDAC7 catalytic domain in complex with Trichostatin A (PDB code 3C10) [<a href="#B61-pharmaceuticals-17-00620" class="html-bibr">61</a>].</p> Full article ">Figure 5
<p>A 3D structure available for human Class III HDAC (SIRT-7). SIRT1 catalytic domain bound to NAD and an EX527 analog (PDB code 4I5I) [<a href="#B77-pharmaceuticals-17-00620" class="html-bibr">77</a>]; SIRT2 apoform (PDB code 3ZGO) [<a href="#B78-pharmaceuticals-17-00620" class="html-bibr">78</a>]; SIRT3 in complex with ADP-ribose (PDB code 4BN4) [<a href="#B79-pharmaceuticals-17-00620" class="html-bibr">79</a>]; SIRT5 in complex with diazirine inhibitor 9 [PDB code 7X3P] [<a href="#B80-pharmaceuticals-17-00620" class="html-bibr">80</a>]; SIRT6 in complex with ADP-ribose [<a href="#B81-pharmaceuticals-17-00620" class="html-bibr">81</a>].</p> Full article ">Figure 6
<p>A 2D structure of the four HDACis (Vorinostat, Panobinostat, Romidepsin and Belinostat) approved by FDA for the treatment of various cancers and of Tucidinostat, the only HDACi approved by CFDA.</p> Full article ">Figure 7
<p>A 2D structure of Vorinostat showing the HDACis shared pharmacophore model.</p> Full article ">Figure 8
<p>Schematic diagram of a PROTAC, as an innovative approach to improve selectivity for a specific HDAC isoform.</p> Full article ">Figure 9
<p>Schematic representation of some ligand-based (LB) approaches for the virtual screening of large databases to discover new HDACis. The features of the ligand-based pharmacophore based on Vorinostat are illustrated as follows: the aromatic ring is represented by an orange ring, the hydrophobic feature is depicted as green spheres, and H-bond acceptors and donors are shown as red and light-blue spheres associated with arrows, respectively. In the scaffold hopping analysis, blue and yellow spheres denote the H-bond donor/acceptor moiety of Vorinostat. Specifically, blue spheres are designated as optional matches.</p> Full article ">Figure 10
<p>Schematic representation of some structure-based (SB) approaches for the virtual screening of large databases to discover new HDACis. HDAC8 is represented as violet surface and ribbons, while the main residues of the catalytic site are shown as violet thin tube.</p> Full article ">Figure 11
<p>Schematic representation of ADME prediction, Molecular Dynamics and MM-PBSA/MM-GBSA binding energy calculations. HDAC8 structure is depicted as violet surface and ribbons situated within a water box.</p> Full article ">
<p>Classification of composites (based on matrix).</p> Full article ">Figure 2
<p>Classification of CMCs based on the nature of the matrix.</p> Full article ">Figure 3
<p>O-CMC material categories.</p> Full article ">Figure 4
<p>Non-oxide CMC material categories.</p> Full article ">Figure 5
<p>Synthesis of CMC using PIP.</p> Full article ">Figure 6
<p>Synthesis of CMC using CVI.</p> Full article ">Figure 7
<p>Synthesis of CMCs using direct melt oxidation.</p> Full article ">Figure 8
<p>Synthesis of CMCs using LSI.</p> Full article ">Figure 9
<p>Flowchart of synthesis of CMCs using sol–gel infiltration.</p> Full article ">Figure 10
<p>Flowchart of synthesis of CMCs using slurry infiltration.</p> Full article ">Figure 11
<p>EPD cell process.</p> Full article ">Figure 12
<p>Illustration of SPS process.</p> Full article ">Figure 13
<p>Directed energy deposition process.</p> Full article ">Figure 14
<p>Additive manufacturing of CMC using a laser-embedded system [<a href="#B72-ceramics-07-00043" class="html-bibr">72</a>].</p> Full article ">Figure 15
<p>Stress–strain behavior of CMCs, compared with monolithic ceramics [<a href="#B76-ceramics-07-00043" class="html-bibr">76</a>].</p> Full article ">Figure 16
<p>Comparing the bending strength of composites to the tensile strength of reinforcement fibers involves exploring three densification cycles, utilizing the matrix polymer wacker silres H62 C, and subjecting the material to calcination at a temperature of 750 °C [<a href="#B78-ceramics-07-00043" class="html-bibr">78</a>].</p> Full article ">Figure 17
<p>Application of CMCs in various fields [<a href="#B107-ceramics-07-00043" class="html-bibr">107</a>,<a href="#B108-ceramics-07-00043" class="html-bibr">108</a>,<a href="#B109-ceramics-07-00043" class="html-bibr">109</a>,<a href="#B110-ceramics-07-00043" class="html-bibr">110</a>,<a href="#B111-ceramics-07-00043" class="html-bibr">111</a>,<a href="#B112-ceramics-07-00043" class="html-bibr">112</a>,<a href="#B113-ceramics-07-00043" class="html-bibr">113</a>,<a href="#B114-ceramics-07-00043" class="html-bibr">114</a>,<a href="#B115-ceramics-07-00043" class="html-bibr">115</a>].</p> Full article ">Figure 18
<p>Application of CMCs in various fields [<a href="#B125-ceramics-07-00043" class="html-bibr">125</a>,<a href="#B126-ceramics-07-00043" class="html-bibr">126</a>,<a href="#B127-ceramics-07-00043" class="html-bibr">127</a>,<a href="#B128-ceramics-07-00043" class="html-bibr">128</a>,<a href="#B129-ceramics-07-00043" class="html-bibr">129</a>,<a href="#B130-ceramics-07-00043" class="html-bibr">130</a>,<a href="#B131-ceramics-07-00043" class="html-bibr">131</a>].</p> Full article ">Figure 19
<p>The global market of CMCs will increase from 2021–2030.</p> Full article ">
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