The utility of Hibiscus sabdariffa L. to prepare metal oxides NPs for clinical application on osteoporosis supported by theoretical study.

Green synthesis of metal oxides as a treatment for bone diseases is still exploring. Herein, MgO and Fe2O3 NPs were prepared from the extract of Hibiscus sabdariffa L. to study their effect on vit D3, Ca+2, and alkaline phosphatase enzyme ALP associated with osteoporosis. Computational chemistry was utilized to gain insight into the possible interactions. These oxides were characterized by X-ray diffraction, SEM, FTIR, and AFM. Results revealed that green synthesis of MgO and Fe2O3 NPs was successful with abundant. MgO NPs were in vitro applied on osteoporosis patients (n = 35) and showed a significant elevation of vit D3 and Ca+2 (0.0001 > p < 0.001) levels, compared to healthy volunteers (n = 25). Thus, Hibiscus sabdariffa L. is a good candidate to prepare MgO NPs, with a promising enhancing effect on vit D3 and Ca+2 in osteoporosis. In addition, interactions of Fe2O3 and MgO NPs with ALP were determined by molecular docking study.

Experimental and density functional theory studies on some metal oxides and the derived nanoclusters: a comparative effects on human ferritin.

A comprehensive investigation into the green synthesis of metal oxide nanoparticles (NPs) has garnered significant attention due to its commendable reliability, sustainability, and environmentally friendly attributes. Green synthesis methods play a crucial role in mitigating the adverse effects associated with conventional approaches employed for nanostructure preparation. This research endeavors to examine the impact of ginger plant extract-assisted green synthesis of metal oxides NPs on the serum ferritin levels of anemic diabetic patients in vitro, focusing specifically on α-Fe2O3 and ZnO NPs. Sixty diabetic volunteers with anemia (35-50 years) and thirty healthy volunteers were enrolled as controls. The assessment was conducted using the VIDAS Ferritin (FER) assay. Photoluminescence (PL) spectroscopy measurements were performed to elucidate the intrinsic and extrinsic transitions of these NPs, affirming the successful formation of α-structured iron oxide. Density functional theory (DFT) calculations were carried out at the B3LYP/6-311++G(d,2p) level of theory to investigate the geometry optimization and molecular electrostatic potential maps of the NPs. Furthermore, TD-DFT calculations were employed to explore their frontier molecular orbitals and various quantum chemical parameters. The binding affinity and interaction types of ZnO and α-Fe2O3 NPs to the active site of the human H-Chain Ferritin (PDB ID: 2FHA) target were determined with the help of molecular docking. Results unveiled the crystalline structure of ZnO and the α-structure of α-Fe2O3. Analysis of the frontier molecular orbitals and dipole moment values demonstrated that ZnO (total dipole moment (D) = 5.80 µ) exhibited superior chemical reactivity, biological activity, and stronger molecular interactions with diverse force fields compared to α-Fe2O3 (D = 2.65 µ). Molecular docking of the metal oxides NPs with human H-chain ferritin provided evidence of robust hydrogen bond interactions and metal-acceptor bonds between the metal oxides and the target protein. This finding could have a great impact on using metal oxides NPs-ferritin as a therapeutic protein, however, further studies on their toxicity are required.

Antiureolytic activity of new water-soluble thiadiazole derivatives: Spectroscopic, DFT, and molecular docking studies.

Two new water-soluble thiadiazole compounds are prepared and characterized with various techniques. These compounds, 5-amino-1,3,4-thiadiazole hydrochloride (1) and 5-amino-3-(N-propane-2-imine)-1,3,4-thiadiazole chloride salt (2) were synthesized via Mannich reaction, and characterized by microelemental analysis, and some spectroscopic means (FTIR, UV-Vis, 1H NMR, 13C NMR and mass), in addition to single-crystal X-ray diffraction for compound 2. DFT calculations were conducted to study their geometry optimization, vibrational spectra, MEP maps, and NBO analysis. In addition, TD-DFT calculations were performed to study their absorption spectra. The prepared compounds were tested against Jack beans urease enzyme (in vitro) to indicate their antiureolytic activity potency. The activity of the enzyme was measured under optimal conditions, before and after mixing with the prepared organic compounds. The results showed that both compounds have potentially inhibited the enzyme activity with respect to their IC50 values: 13.76 µM ± 0.15 for 1, and 18.81 µM ± 0.18 for 2. These values are even lower than that of thiourea (21.40 ± 0.21 µM) as a standard inhibitor. The inhibition activity of urease enzyme was confirmed by a Lineweaver-Burk plot. According to the kinetic parameters obtained from the Lineweaver-Burk plot, the inhibition of urease enzyme by compounds 1 and 2 seems to be non-competitive. Molecular docking studies of the prepared compounds 1 and 2 were performed in order to interpret the obtained biological results and to investigate their interactions with the urease enzyme active site. These studies reveal that compounds 1 and 2 are good candidates as inhibitors for urease enzyme. Moreover, compound 1 exhibits a higher promising inhibition activity.

Transition of Nano-Architectures Through Self-Assembly of Lipidated ß3-Tripeptide Foldamers.

ß3-peptides consisting exclusively of ß3-amino acids adopt a variety of non-natural helical structures and can self-assemble into well-defined hierarchical structures by axial head-to-tail self-assembly resulting in fibrous materials of varying sizes and shapes. To allow control of fiber morphology, a lipid moiety was introduced within a tri-ß3-peptide sequence at each of the three amino acid positions and the N-terminus to gain finer control over the lateral assembly of fibers. Depending on the position of the lipid, the self-assembled structures formed either twisted ribbon-like fibers or distinctive multilaminar nanobelts. The nanobelt structures were comprised of multiple layers of peptide fibrils as revealed by puncturing the surface of the nanobelts with an AFM probe. This stacking phenomenon was completely inhibited through changes in pH, indicating that the layer stacking was mediated by electrostatic interactions. Thus, the present study is the first to show controlled self-assembly of these fibrous structures, which is governed by the location of the acyl chain in combination with the 3-point H-bonding motif. Overall, the results demonstrate that the nanostructures formed by the ß3-tripeptide foldamers can be tuned via sequential lipidation of N-acetyl ß3-tripeptides which control the lateral interactions between peptide fibrils and provide defined structures with a greater homogeneous population.

The CDR1 and Other Regions of Immunoglobulin Light Chains are Hot Spots for Amyloid Aggregation.

Immunoglobulin light chain-derived (AL) amyloidosis is a debilitating disease without known cure. Almost nothing is known about the structural factors driving the amyloidogenesis of the light chains. This study aimed to identify the fibrillogenic hotspots of the model protein 6aJL2 and in pursuing this goal, two complementary approaches were applied. One of them was based on several web-based computational tools optimized to predict fibrillogenic/aggregation-prone sequences based on different structural and biophysical properties of the polypeptide chain. Then, the predictions were confirmed with an ad-hoc synthetic peptide library. In the second approach, 6aJL2 protein was proteolyzed with trypsin, and the products incubated in aggregation-promoting conditions. Then, the aggregation-prone fragments were identified by combining standard proteomic methods, and the results validated with a set of synthetic peptides with the sequence of the tryptic fragments. Both strategies coincided to identify a fibrillogenic hotspot located at the CDR1 and ß-strand C of the protein, which was confirmed by scanning proline mutagenesis analysis. However, only the proteolysis-based strategy revealed additional fibrillogenic hotspots in two other regions of the protein. It was shown that a fibrillogenic hotspot associated to the CDR1 is also encoded by several κ and λ germline variable domain gene segments. Some parts of this study have been included in the chapter "The Structural Determinants of the Immunoglobulin Light Chain Amyloid Aggregation", published in Physical Biology of Proteins and Peptides, Springer 2015 (ISBN 978-3-319-21687-4).

Evaluation of Some Trace Elements and Vitamins in Major Depressive Disorder Patients: a Case-Control Study.

Major depressive disorder (MDD) is a common mental disorder worldwide; however, little is known about its etiology. It is well known that levels of certain trace elements are associated with the pathogenesis of some diseases. Accordingly, this study aims to evaluate the effect of trace elements and vitamins in the etiology of MDD. In this case-control study, sixty men patients with MDD and sixty, age and gender matched, control subjects were examined. Serum levels of Cu, Zn, Ni, Cr, Mn, Mg, and Al were determined by atomic absorption spectrometry as well as serum levels of vitamins E and A were determined using high-performance liquid chromatography. The results revealed that there were significantly higher levels (p < 0.001) of Cu, Cr, and Al in patients sera compared with control. While there were significantly lower levels (p < 0.001) of Zn, Ni, Mn, Mg, vitamin E, and vitamin A in MDD patients as compared with control. In addition, high Cu/Zn ratio (p < 0.05) was observed with the depressive disorder patients. The present study highlights some main indications: a significant relationship between the disturbances of element levels and vitamins (E and A) with MDD. Cu and Zn seemed to have a crucial role in understanding the pathogenesis of depressive disorders, where Cu/Zn ratio could have an important role in the diagnosis and monitoring of MDD. Moreover, the results suggest that the reduction in the antioxidant vitamin E leads to increased risk of MDD. Finally, more studies on using trace element supplementation would be suggested to clarify their effect, in order to improve the therapy of MDD.

Identifying the Coiled-Coil Triple Helix Structure of ß-Peptide Nanofibers at Atomic Resolution.

Peptide self-assembly represents a powerful bottom-up approach to the fabrication of nanomaterials. ß3-Peptides are non-natural peptides composed entirely of ß-amino acids, which have an extra methylene in the backbone, and we reported fibers derived from the self-assembly of ß3-peptides that adopt 14-helical structures. ß3-Peptide assemblies represent a class of stable nanomaterials that can be used to generate bio- and magneto-responsive materials with proteolytic stability. However, the three-dimensional structure of many of these materials remains unknown. To develop structure-based criteria for the design of ß3-peptide-based biomaterials with tailored function, we investigated the structure of a tri-ß3-peptide nanoassembly by molecular dynamics simulations and X-ray fiber diffraction analysis. Diffraction data was collected from aligned fibrils formed by Ac-ß3[LIA] in water and used to inform and validate the model structure. Models with 3-fold radial symmetry resulted in stable fibers with a triple-helical coiled-coil motif and measurable helical pitch and periodicity. The fiber models revealed a hydrophobic core and twist along the fiber axis arising from a maximization of contacts between hydrophobic groups of adjacent tripeptides on the solvent-exposed fiber surface. These atomic structures of macroscale fibers derived from ß3-peptide-based materials provide valuable insight into the effects of the geometric placement of the side chains and the influence of solvent on the core fiber structure which is perpetuated in the superstructure morphology.

The diversity and utility of amyloid fibrils formed by short amyloidogenic peptides.

Amyloidogenic peptides are well known for their involvement in diseases such as type 2 diabetes and Alzheimer's disease. However, more recently, amyloid fibrils have been shown to provide scaffolding and protection as functional materials in a range of organisms from bacteria to humans. These roles highlight the incredible tensile strength of the cross-ß amyloid architecture. Many amino acid sequences are able to self-assemble to form amyloid with a cross-ß core. Here we describe our recent advances in understanding how sequence contributes to amyloidogenicity and structure. For example, we describe penta- and hexapeptides that assemble to form different morphologies; a 12mer peptide that forms fibrous crystals; and an eight-residue peptide originating from α-synuclein that has the ability to form nanotubes. This work provides a wide range of peptides that may be exploited as fibrous bionanomaterials. These fibrils provide a scaffold upon which functional groups may be added, or templated assembly may be performed.

Chemically and thermally stable silica nanowires with a ß-sheet peptide core for bionanotechnology.

BACKGROUND: A series of amyloidogenic peptides based on the sequence KFFEAAAKKFFE template the silica precursor, tetraethyl orthosilicate to form silica-nanowires containing a cross-ß peptide core. RESULTS: Investigation of the stability of these fibres reveals that the silica layers protect the silica-nanowires allowing them to maintain their shape and physical and chemical properties after incubation with organic solvents such as 2-propanol, ethanol, and acetonitrile, as well as in a strong acidic solution at pH 1.5. Furthermore, these nanowires were thermally stable in an aqueous solution when heated up to 70 °C, and upon autoclaving. They also preserved their conformation following incubation up to 4 weeks under these harsh conditions, and showed exceptionally high physical stability up to 1000 °C after ageing for 12 months. We show that they maintain their ß-sheet peptide core even after harsh treatment by confirming the ß-sheet content using Fourier transform infrared spectra. The silica nanowires show significantly higher chemical and thermal stability compared to the unsiliconised fibrils. CONCLUSIONS: The notable chemical and thermal stability of these silica nanowires points to their potential for use in microelectromechanics processes or fabrication for nanotechnological devices.

Silica Nanowires Templated by Amyloid-like Fibrils.

Many peptides self-assemble to form amyloid fibrils. We previously explored the sequence propensity to form amyloid using variants of a designed peptide with sequence KFFEAAAKKFFE. These variant peptides form highly stable amyloid fibrils with varied lateral assembly and are ideal to template further assembly of non-proteinaceous material. Herein, we show that the fibrils formed by peptide variants can be coated with a layer of silica to produce silica nanowires using tetraethyl-orthosilicate. The resulting nanowires were characterized using electron microscopy (TEM), X-ray fiber diffraction, FTIR and cross-section EM to reveal a nanostructure with peptidic core. Lysine residues play a role in templating the formation of silica on the fibril surface and, using this library of peptides, we have explored the contributions of lysine as well as arginine to silica templating, and find that sequence plays an important role in determining the physical nature and structure of the resulting nanowires.

Silica Nanowires Templated by Amyloid-like Fibrils.

Many peptides self-assemble to form amyloid fibrils. We previously explored the sequence propensity to form amyloid using variants of a designed peptide with sequence KFFEAAAKKFFE. These variant peptides form highly stable amyloid fibrils with varied lateral assembly and are ideal to template further assembly of non-proteinaceous material. Herein, we show that the fibrils formed by peptide variants can be coated with a layer of silica to produce silica nanowires using tetraethyl-orthosilicate. The resulting nanowires were characterized using electron microscopy (TEM), X-ray fiber diffraction, FTIR and cross-section EM to reveal a nanostructure with peptidic core. Lysine residues play a role in templating the formation of silica on the fibril surface and, using this library of peptides, we have explored the contributions of lysine as well as arginine to silica templating, and find that sequence plays an important role in determining the physical nature and structure of the resulting nanowires.