In pursuit of effective agents for hepatocellular carcinoma derived from the Artemisia species, this study built upon initial findings that an ethanol (EtOH) extract and ethyl acetate (EtOAc) fraction of the aerial parts of Artemisia dubia Wall. ex Bess. exhibited cytotoxicity against HepG2 cells with inhibitory rates of 57.1% and 84.2% (100 μg·mL^-1), respectively. Guided by bioactivity, fourteen previously unidentified sesquiterpenes, artemdubinoids A-N (1-14), were isolated from the EtOAc fraction. Their structural elucidation was achieved through comprehensive spectroscopic analyses and corroborated by the comparison between the experimental and calculated ECD spectra. Single crystal X-ray diffraction provided definitive structure confirmation for artemdubinoids A, D, F, and H. Artemdubinoids A and B (1-2) represented unique sesquiterpenes featuring a 6/5-fused bicyclic carbon scaffold, and their putative biosynthetic pathways were discussed; artemdubinoid C (3) was a novel guaianolide derivative that might be formed by the [4 + 2] Diels-Alder reaction; artemdubinoids D and E (4-5) were rare 1,10-seco-guaianolides; artemdubinoids F-K (6-11) were chlorine-containing guaianolides. Eleven compounds exhibited cytotoxicity against three human hepatoma cell lines (HepG2, Huh7, and SK-Hep-1) with half-maximal inhibitory concentration (IC₅₀) values spanning 7.5-82.5 μmol·L^-1. Artemdubinoid M (13) exhibited the most active cytotoxicity with IC₅₀ values of 14.5, 7.5 and 8.9 μmol·L^-1 against the HepG2, Huh7, and SK-Hep-1 cell lines, respectively, which were equivalent to the positive control, sorafenib.
Humans ; Artemisia/chemistry* ; Sesquiterpenes/chemistry* ; Cell Line ; Hep G2 Cells ; Crystallography, X-Ray ; Molecular Structure

The present study explored the effect of co-amorphous technology in improving the dissolution rate and stability of silybin based on the puerarin-silybin co-amorphous system prepared by the spray-drying method. Solid-state characterization was carried out by powder X-ray diffraction(PXRD), polarizing microscopy(PLM), Fourier transform infrared spectroscopy(FT-IR), differential scanning calorimetry(DSC), etc. Saturated powder dissolution, intrinsic dissolution rate, moisture absorption, and stability were further investigated. The results showed that puerarin and silybin formed a co-amorphous system at a single glass transition temperature which was higher than that of any crude drug. The intrinsic dissolution rate and supersaturated powder dissolution of silybin in the co-amorphous system were higher than those of the crude drug and amorphous system. The co-amorphous system kept stable for as long as three months under the condition of 40 ℃, 75% relative humidity, which was longer than that of the single amorphous silybin. Therefore, the co-amorphous technology could significantly improve the dissolution and stability of silybin.
Calorimetry, Differential Scanning ; Desiccation ; Drug Compounding/methods* ; Drug Stability ; Silybin ; Solubility ; Spectroscopy, Fourier Transform Infrared ; Technology ; X-Ray Diffraction

A new coronavirus (SARS-CoV-2) has been identified as the etiologic agent for the COVID-19 outbreak. Currently, effective treatment options remain very limited for this disease; therefore, there is an urgent need to identify new anti-COVID-19 agents. In this study, we screened over 6,000 compounds that included approved drugs, drug candidates in clinical trials, and pharmacologically active compounds to identify leads that target the SARS-CoV-2 papain-like protease (PLpro). Together with main protease (M
Antiviral Agents/therapeutic use* ; Binding Sites ; COVID-19/virology* ; Coronavirus Papain-Like Proteases/metabolism* ; Crystallography, X-Ray ; Drug Evaluation, Preclinical ; Drug Repositioning ; High-Throughput Screening Assays/methods* ; Humans ; Imidazoles/therapeutic use* ; Inhibitory Concentration 50 ; Molecular Dynamics Simulation ; Mutagenesis, Site-Directed ; Naphthoquinones/therapeutic use* ; Protease Inhibitors/therapeutic use* ; Protein Structure, Tertiary ; Recombinant Proteins/isolation & purification* ; SARS-CoV-2/isolation & purification*

Nine new compounds, including five natural rarely-occurring 2, 3-dihydro-1H-indene derivatives named diaporindenes E-I (1-5), and four new benzophenone analogues named tenellones J-M (6-9) were isolated from the deep-sea sediment-derived fungus Phomopsis lithocarpus FS508. All the structures for these new compounds were fully characterized on the basis of spectroscopic data, NMR spectra, and ECD calculation and single-crystal X-ray diffraction analysis. The potential anti-tumor activities of compounds 1-9 against four tumor cell lines SF-268, MCF-7, HepG-2, and A549 were evaluated using the SRB method. Compound 7 exhibited cytotoxic activity against the SF-268 cell line with an IC
Antineoplastic Agents/pharmacology* ; Cell Line, Tumor ; Crystallography, X-Ray ; Fungi ; Molecular Structure ; Phomopsis

PURPOSE: The aim of this study was to investigate the effect of different numbers of heat treatments applied to superstructure porcelain on optical, thermal, and phase formation properties of zirconia.MATERIALS AND METHODS: Forty zirconia specimens were prepared in the form of rectangular prism. Specimens were divided into four groups (n = 10) according to the number of firing at heating values of porcelain. Color differences and translucency parameter were measured, and X-ray diffraction (XRD) analysis and differential scanning calorimetry (DSC) were performed. Data were analyzed with analysis of variance (ANOVA).RESULTS: There were no statistically significant differences in ΔE, TP, L, a, and b value changes of the zirconia specimens as a result of repetitive firing processes (P>.05).CONCLUSION: Although additional firing processes up to 4 increase peak density in thermal analysis, additional firing processes up to 4 times can be applied safely as they do not result in a change in color and phase character of zircon frameworks.
Calorimetry, Differential Scanning ; Dental Porcelain ; Fires ; Heating ; Hot Temperature ; X-Ray Diffraction

The calcium phosphate coating on various pretreated metals was prepared by soaking in modified simulated body fluid (m-SBF) solution. The coating structure and its surface morphologies were determined by x-ray diffraction, Fourier transform infrared spectroscopy, and scanning electron microscopy. The results revealed significant differences in morphology and composition of the calcium phosphate coatings with and without chitosan and NaOH-pretreated commercially pure titanium (cp-Ti) substrate. The calcium phosphates formed on chitosan coated-Ti pretreated with NaOH were ~ 350 nm-sized resulting in strong bonding of the apatite layer with the substrates and a uniform gradient of stress transfer from coating materials to the Ti-substrate. After NaOH pretreatment, the hydroxyl groups bind to Ca²⁺ to attract PO₄³⁻ anions, eventually resulting in a continuous layer of calcium phosphate on chitosan coated-Ti substrate during immersion in m-SBF solution. The chitosan coated-Ti showed hydrophobic surface while NaOH pretreatment resulted in maximum hydrophilicity to the Ti substrate. Due to improved wettability of Ti by NaOH pretreatment before chitosan coating, aggregation of calcium phosphate was prevented and size-controlled composite materials were obtained.
Anions ; Body Fluids ; Calcium Phosphates ; Calcium ; Chitosan ; Clothing ; Hydrophobic and Hydrophilic Interactions ; Immersion ; Metals ; Microscopy, Electron, Scanning ; Spectroscopy, Fourier Transform Infrared ; Titanium ; Wettability ; X-Ray Diffraction

PURPOSE: The purpose of this study was to evaluate the effects of various protocols and systems for finishing and polishing monolithic zirconia on surface topography, phase transformation, and bacterial adhesion. MATERIALS AND METHODS: Three hundred monolithic zirconia specimens were fabricated and then treated with three finishing and polishing systems (Jota [JO], Meisinger [ME], and Edenta [ED]) using four surface treatment protocols: coarse finishing alone (C); coarse finishing and medium polishing (CM); coarse finishing and fine polishing (CF); and coarse finishing, medium polishing, and fine polishing (CMF). Surface roughness, crystal phase transformation, and bacterial adhesion were evaluated using atomic force microscopy, X-ray diffraction, and streptococcal biofilm formation assay, respectively. One-way and two-way analysis of variance with Tukey post hoc tests were used to analyze the results (α=.05). RESULTS: In this study, the surface treatment protocols and systems had significant effects on the resulting roughness. The CMF protocol produced the lowest roughness values, followed by CM and CF. Use of the JO system produced the lowest roughness values and the smallest biofilm mass, while the ME system produced the smallest partial transformation ratio. The ED group exhibited the highest roughness values, biofilm mass, and partial transformation ratio. CONCLUSION: Stepwise surface treatment of monolithic zirconia, combined with careful polishing system selection, is essential to obtaining optimal microstructural and biological surface results.
Bacterial Adhesion ; Biofilms ; Clinical Protocols ; Dental Polishing ; Microscopy, Atomic Force ; X-Ray Diffraction

In the present study, rutile phase titanium dioxide nanoparticles (R-TiO₂ NPs) were prepared by hydrolysis of titanium tetrachloride in an aqueous solution followed by calcination at 900℃. The composition of R-TiO₂ NPs was determined by the analysis of X-ray diffraction data, and the characteristic features of R-TiO₂ NPs such as the surface functional group, particle size, shape, surface topography, and morphological behavior were analyzed by Fourier-transform infrared spectroscopy, scanning electron microscopy and energy dispersive X-ray spectroscopy, transmission electron microscopy, dynamic light scattering, and zeta potential measurements. The average size of the prepared R-TiO₂ NPs was 76 nm, the surface area was 19 m²/g, zeta potential was −20.8 mV, and average hydrodynamic diameter in dimethyl sulfoxide (DMSO)–H₂O solution was 550 nm. The 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay and morphological observations revealed that R-TiO₂ NPs were cytocompatible with oral cancer cells, with no inhibition of cell growth and proliferation. This suggests the efficacy of R-TiO₂ NPs for the aesthetic white pigmentation of teeth.
Dimethyl Sulfoxide ; Dynamic Light Scattering ; Hydrodynamics ; Hydrolysis ; Microscopy, Electron, Scanning ; Microscopy, Electron, Transmission ; Mouth Neoplasms ; Nanoparticles ; Particle Size ; Pigmentation ; Spectrometry, X-Ray Emission ; Spectrum Analysis ; Titanium ; Tooth ; X-Ray Diffraction

BACKGROUND: Alendronate (AL), a drug for inhibiting osteoclast-mediated bone-resorption, was intercalated into an inorganic drug delivery nanovehicle, layered double hydroxide (LDH), to form a new nanohybrid, AL-LDH, with 1:1 heterostructure along the crystallographic C-axis. Based on the intercalation reaction strategy, the present AL-LDH drug delivery system (DDS) was realized with an enhanced drug efficacy of AL, which was confirmed by the improved proliferation and osteogenic differentiation of osteoblast-like cells (MG63). METHODS: The AL-LDH nanohybrid was synthesized by conventional ion-exchange reaction and characterized by powder X-ray diffraction (PXRD), high-resolution transmission electron microscopy (HR-TEM), and Fourier transform infrared (FT-IR) spectroscopy. Additionally, in vitro efficacy tests, such as cell proliferation and alkaline phosphatase (ALP) activity, were analyzed. RESULTS: The AL was successfully intercalated into LDH via ion-exchange reaction, and thus prepared AL-LDH DDS was X-ray single phasic and chemically well defined. The accumulated AL content in MG63 cells treated with the AL-LDH DDS nanoparticles was determined to be 10.6-fold higher than that within those treated with the intact AL after incubation for 1 hour, suggesting that intercellular permeation of AL was facilitated thanks to the hybridization with drug delivery vehicle, LDH. Furthermore, both in vitro proliferation level and ALP activity of MG63 treated with the present hybrid drug, AL-LDH, were found to be much more enhanced than those treated with the intact AL. This is surely due to the fact that LDH could deliver AL drug very efficiently, although LDH itself does not show any effect on proliferation and osteogenic differentiation of MG63 cells. CONCLUSION: The present AL-LDH could be considered as a promising DDS for improving efficacy of AL.
Alendronate ; Alkaline Phosphatase ; Cell Proliferation ; Drug Delivery Systems ; Fourier Analysis ; In Vitro Techniques ; Microscopy, Electron, Transmission ; Nanoparticles ; Spectrum Analysis ; X-Ray Diffraction

Anoctamin1 (ANO1) also known as TMEM16A is a transmembrane protein that functions as a Ca²⁺ activated chloride channel. Recently, the structure determination of a fungal Nectria haematococca TMEM16 (nhTMEM16) scramblase by X-ray crystallography and a mouse ANO1 by cryo-electron microscopy has provided the insight in molecular architecture underlying phospholipid scrambling and Ca²⁺ binding. Because the Ca²⁺ binding motif is embedded inside channel protein according to defined structure, it is still unclear how intracellular Ca²⁺ moves to its deep binding pocket effectively. Here we show that EF-hand like region containing multiple acidic amino acids at the N-terminus of ANO1 is a putative site regulating the activity of ANO1 by Ca²⁺ and voltage. The EF-hand like region of ANO1 is highly homologous to the canonical EF hand loop in calmodulin that contains acidic residues in key Ca²⁺-coordinating positions in the canonical EF hand. Indeed, deletion and Ala-substituted mutation of this region resulted in a significant reduction in the response to Ca²⁺ and changes in its key biophysical properties evoked by voltage pulses. Furthermore, only ANO1 and ANO2, and not the other TMEM16 isoforms, contain the EF-hand like region and are activated by Ca²⁺. Moreover, the molecular modeling analysis supports that EF-hand like region could play a key role during Ca²⁺ transfer. Therefore, these findings suggest that EF-hand like region in ANO1 coordinates with Ca²⁺ and modulate the activation by Ca²⁺ and voltage.
Amino Acids, Acidic ; Animals ; Calcium ; Calmodulin ; Chloride Channels ; Cryoelectron Microscopy ; Crystallography, X-Ray ; EF Hand Motifs ; Mice ; Models, Molecular ; Mutagenesis ; Nectria ; Protein Isoforms