Modified magnetic core-shell mesoporous silica nano-formulations with encapsulated quercetin exhibit anti-amyloid and antioxidant activity

Targeted tissue drug delivery is a challenge in contemporary nanotechnologically driven therapeutic approaches, with the interplay interactions between nanohost and encapsulated drug shaping the ultimate properties of transport, release and efficacy of the drug at its destination. Prompted by the need to pursue the synthesis of such hybrid systems, a family of modified magnetic core-shell mesoporous silica nano-formulations was synthesized with encapsulated quercetin, a natural flavonoid with proven bioactivity. The new nanocarriers were produced via the sol-gel process, using tetraethoxysilane as a precursor and bearing a magnetic core of surface-modified monodispersed magnetite colloidal superparamagnetic nanoparticles, subsequently surface-modified with polyethylene glycol 3000 (PEG3k). The arising nano-formulations were evaluated for their textural and structural properties, exhibiting enhanced solubility and stability in physiological media, as evidenced by the loading capacity, entrapment efficiency results and in vitro release studies of their load. Guided by the increased bioavailability of quercetin in its encapsulated form, further evaluation of the biological activity of the magnetic as well as non-magnetic core-shell nanoparticles, pertaining to their anti-amyloid and antioxidant potential, revealed interference with the aggregation of β-amyloid peptide (Aβ) in Alzheimer’s disease, reduction of Aβ cellular toxicity and minimization of Aβ-induced Reactive Oxygen Species (ROS) generation. The data indicate that the biological properties of released quercetin are maintained in the presence of the host nanocarriers. Collectively, the findings suggest that the emerging hybrid nano-formulations can function as efficient nanocarriers of hydrophobic natural flavonoids in the development of multifunctional nanomaterials toward therapeutic applications

Structural characterization of 3d metal complexes containing an unconventional schiff base ligand

The design of appropriated organic ligands capable of binding metal ions provides a targeted entry to new materials with distinct structural and physicochemical properties. A representative family of such ligands includes Schiff bases. Here, we report new mono, diand polynuclear materials [Co(L)]3(ClO4)3·4H2O (1), [Zn2(L)(CH3COO)2] (2) and [Cu3(L)2(µ3 -ClO4)0.66](ClO4)1.33·1.33CHCl3 (3) containing N,N’-bis[(2- hydroxybenzilideneamino)-propyl]-piperazine (H2L) Schiff base as hexadentate ligand (Figure 1). The X-ray crystallography of the complexes reveal a retaining of the original chair piperazine conformation from the free ligand in the complex 2 and a changing into a boat conformation in the complexes 1 and 3. Moreover, in the respective complexes a different coordination number as 6 (1), 5 (2) and 4 and 5 (3) was observed upon coordination of the free ligand to Co(III), Zn(II) and Cu(II) ions. The modulatory property of H2L is reflected upon the molecular assembly and coordination mode of the isolable species

Role of Vanadium in Cellular and Molecular Immunology: Association with Immune-Related Inflammation and Pharmacotoxicology Mechanisms

Over the last decade, a diverse spectrum of vanadium compounds has arisen as anti-inflammatory therapeutic metallodrugs targeting various diseases. Recent studies have demonstrated that select well-defined vanadium species are involved in many immune-driven molecular mechanisms that regulate and influence immune responses. In addition, advances in cell immunotherapy have relied on the use of metallodrugs to create a “safe,” highly regulated, environment for optimal control of immune response. Emerging findings include optimal regulation of B/T cell signaling and expression of immune suppressive or anti-inflammatory cytokines, critical for immune cell effector functions. Furthermore, in-depth perusals have explored NF-κB and Toll-like receptor signaling mechanisms in order to enhance adaptive immune responses and promote recruitment or conversion of inflammatory cells to immunodeficient tissues. Consequently, well-defined vanadium metallodrugs, poised to access and resensitize the immune microenvironment, interact with various biomolecular targets, such as B cells, T cells, interleukin markers, and transcription factors, thereby influencing and affecting immune signaling. A synthetically formulated and structure-based (bio)chemical reactivity account of vanadoforms emerges as a plausible strategy for designing drugs characterized by selectivity and specificity, with respect to the cellular molecular targets intimately linked to immune responses, thereby giving rise to a challenging field linked to the development of immune system vanadodrugs

In-depth synthetic, physicochemical and in vitro biological investigation of a new ternary V(IV) antioxidant material based on curcumin.

Curcumin is a natural product with a broad spectrum of beneficial properties relating to pharmaceutical applications, extending from traditional remedies to modern cosmetics. The biological activity of such pigments, however, is limited by their solubility and bioavailability, thereby necessitating new ways of achieving optimal tissue cellular response and efficacy as drugs. Metal ion complexation provides a significant route toward improvement of curcumin stability and biological activity, with vanadium being a representative such metal ion, amply encountered in biological systems and exhibiting exogenous bioactivity through potential pharmaceuticals. Driven by the need to optimally increase curcumin bioavailability and bioactivity through complexation, synthetic efforts were launched to seek out stable species, ultimately leading to the synthesis and isolation of a new ternary V(IV)-curcumin-(2,2’-bipyridine) complex. Physicochemical characterization (elemental analysis, FT-IR, Thermogravimetry (TGA), UV-Visible, NMR, ESI-MS, Fluorescence, X-rays) portrayed the solid-state and solution properties of the ternary complex. Pulsed-EPR spectroscopy, in frozen solutions, suggested the presence of two species, cis- and trans-conformers. Density Functional Theory (DFT) calculations revealed the salient features and energetics of the two conformers, thereby complementing EPR spectroscopy. The well-described profile of the vanadium species led to its in vitro biological investigation involving toxicity, cell metabolism inhibition in S. cerevisiae cultures, Reactive Oxygen Species (ROS)-suppressing capacity, lipid peroxidation, and plasmid DNA degradation. A multitude of bio-assays and methodologies, in comparison to free curcumin, showed that it exhibits its antioxidant potential in a concentration-dependent fashion, thereby formulating a bioreactivity profile supporting development of new efficient vanado-pharmaceuticals, targeting (extra)intra-cellular processes under (patho)physiological conditions

Assessment of Durability Indicators for Service Life Prediction of Portland Limestone Cementitious Systems Produced with Permeability-Reducing Admixtures

Supplementary cementing materials (SCMs) and the challenges associated with admixture compatibility and durability performance are continuous challenges for the construction industry. Utilizing SCMs has apparent benefits in reducing the carbon footprint and improving the durability performance of concrete structures. This work investigates the performance of mortars composed of Portland limestone cement, calcium carbonate, butyl stearate, and oleic acid. The effort focuses on transport properties using electrical resistivity, chloride migration, porosity, and water permeability measurements. Then, various methods based on the last parameters are compared to assess the changes in the effective chloride diffusion coefficient and the intrinsic liquid water permeability. Measurements for drying shrinkage, thermal expansion, and compressive strength are conducted to verify durability and mechanical performance. The effect of the admixture addition on the service life of a structure fully submerged in marine exposure conditions is then evaluated using Fick’s second law of diffusion and the approach described by FIB model code 34. The results indicate that incorporating calcium carbonate, butyl stearate, and oleic acid in mortar mixtures provides enhanced durability compared to plain Portland limestone cement mortars

Synthesis And Characterization Of New Iron/sulfur And Iron/metal/sulfur Clusters Containing The (2 Iron - 2 Sulfur)(ii), (6 Iron - 6 Sulfur) (iii,iv) And (6 Iron - 2 Metal - 6 Sulfur)(ii,iii) (m = Molybdenum,tungsten) Cores. (volumes I And Ii).

The synthesis, spectroscopic and structural characterization of novel (2Fe-2S) complexes containing sulfur as well as non-sulfur (oxygen, nitrogen) terminal ligands are reported. The dimeric clusters (Cat) \sb2Fe\sb2S\sb2L\sb4 (L\sb2 = o,o\sp\prime-C\sb{12}H\sb8O\sb2\sp{2-}; L = \sp{-}O-C\sb6H\sb4-p-CH\sb3, C\sb4H\sb4N\sp{-}; L\sb2 = \sp{-}O-o-C\sb6H\sb4-CH(n-Bu)-NH-C\sb6H\sb4-o\sp\prime-S\sp{-}; Cat = (C\sb2H\sb5)\sb4N\sp{+}, (C\sb6H\sb5)\sb4P\sp{+}) were prepared by metathetical reactions and fully characterized. Possible relevance of the newly discovered complexes to the (2Fe-2S) cluster of the iron-sulfur Rieske proteins is discussed. The synthesis, spectroscopic and structural characterization of the prismane clusters ((C\sb2H\sb5)\sb4N) \sb3(Fe\sb6S\sb6L\sb6) (L = Br\sp{-},CH\sb3-p-C\sb6H\sb4-O\sp{-}, C\sb2H\sb5-p-C\sb6H\sb4-O\sp{-}, CH\sb3-p-C\sb6H\sb4-S\sp{-}, CH\sb3-m-C\sb6H\sb4-S\sp{-}) are described. Structural data for two of those clusters, ((C\sb2H\sb5)\sb4N) \sb3Fe\sb6S\sb6L\sb6 (L = CH\sb3-p-C\sb6H\sb4-O\sp{-}, Br\sp{-}) reveal the presence of the prismatic (Fe\sb6S\sb6) \sp{3+} core which was first reported to exist in ((C\sb2H\sb5)\sb4N) \sb3Fe\sb6S\sb6Cl\sb6. The oxidized prismanes ((C\sb6H\sb5)\sb4P) \sb2Fe\sb6S\sb6L\sb6 (L = Cl\sp{-},Br\sp{-}) were prepared by oxidation of the respective cubanes with Cp\sb2FePF\sb6 in a ratio of 3:2. Mossbauer spectroscopic data are discussed in connection with X-ray data obtained at 298\sp\circK, 144\sp\circK and 20\sp\circK. In an approach to synthesize low molecular weight Fe/M/S clusters with the stoichiometry proposed for the polynuclear center of nitrogenase (Fe:Mo:S = 6-7:1:6-8), the new clusters (Cat) \sb{\rm n} (Fe\sb6S\sb6X\sb6\{M(Co)\sb3\}\sb2) (n = 3,4; M = Mo,W; X = Cl\sp{-},Br\sp{-},I\sp{-}, CH\sb3-p-C\sb6H\sb4-O\sp{-}, C\sb2H\sb5-p-C\sb6H\sb4-O\sp{-}; Cat = (C\sb2H\sb5)\sb4N\sp{+}, (C\sb6H\sb5)\sb4P\sp{+}) were prepared and studied. The properties of those (Fe\sb6S\sb6M\sb2\rbrack\sp{2+,3+} core containing clusters are reported and possible relevance to the active site of the nitrogenase enzyme is discussed.Ph.D.Inorganic chemistryPure SciencesUniversity of Michigan, Horace H. Rackham School of Graduate Studieshttp://deepblue.lib.umich.edu/bitstream/2027.42/128126/2/8801410.pd

Chromium Flavonoid Complexation in an Antioxidant Capacity Role

The plethora of flavonoid antioxidants in plant organisms, widespread in nature, and the appropriate metal ions known for their influence on biological processes constitute the crux of investigations toward the development of preventive metallodrugs and therapeutics in several human pathophysiologies. To that end, driven by the need to enhance the structural and (bio)chemical attributes of the flavonoid chrysin, as a metal ion complexation agent, thereby rendering it bioavailable toward oxidative stress, synthetic efforts in our lab targeted ternary Cr(III)-chrysin species in the presence of auxiliary aromatic N,N′-chelators. The crystalline metal-organic Cr(III)-chrysin-L (L = bipyridine (1) and phenanthroline (2)) compounds that arose were physicochemically characterized by elemental analysis, FT-IR, UV-Visible, ESI-MS, luminescence, and X-ray crystallography. The properties of these compounds in a solid state and in solution formulate a well-defined profile for the two species, thereby justifying their further use in biological experiments, intimately related to cellular processes on oxidative stress. Experiments in C2C12 myoblasts at the cellular level (a) focus on the antioxidant capacity of the Cr(III)-complexed flavonoids, emphasizing their distinct antiradical activity under oxidative stress conditions, and (b) exemplify the importance of structural speciation in Cr(III)-flavonoid interactions, thereby formulating correlations with the antioxidant activity of a bioavailable flavonoid toward cellular pathophysiologies, collectively supporting flavonoid introduction in new metallo-therapeutics

Machine Learning and Data Mining Methods in Diabetes Research

The remarkable advances in biotechnology and health sciences have led to a significant production of data, such as high throughput genetic data and clinical information, generated from large Electronic Health Records (EHRs). To this end, application of machine learning and data mining methods in biosciences is presently, more than ever before, vital and indispensable in efforts to transform intelligently all available information into valuable knowledge. Diabetes mellitus (DM) is defined as a group of metabolic disorders exerting significant pressure on human health worldwide. Extensive research in all aspects of diabetes (diagnosis, etiopathophysiology, therapy, etc.) has led to the generation of huge amounts of data. The aim of the present study is to conduct a systematic review of the applications of machine learning, data mining techniques and tools in the field of diabetes research with respect to a) Prediction and Diagnosis, b) Diabetic Complications, c) Genetic Background and Environment, and e) Health Care and Management with the first category appearing to be the most popular. A wide range of machine learning algorithms were employed. In general, 85% of those used were characterized by supervised learning approaches and 15% by unsupervised ones, and more specifically, association rules. Support vector machines (SVM) arise as the most successful and widely used algorithm. Concerning the type of data, clinical datasets were mainly used. The title applications in the selected articles project the usefulness of extracting valuable knowledge leading to new hypotheses targeting deeper understanding and further investigation in DM. Keywords: Machine learning, Data mining, Diabetes mellitus, Diabetic complications, Disease prediction models, Biomarker(s) identificatio

Structural speciation in chemical reactivity profiling of binary-ternary systems of Ni(II) with iminodialcohol and aromatic chelators

The importance of structural speciation in the control of chemical reactivity in Ni(II) binary-ternary systems, involving (O,O,N)-containing substrates (1,1’-iminodi-2-propanol), and aromatic chelators (2,2’-bipyridine, 1,10-phenanthroline), prompted the systematic synthesis of new crystalline materials characterized by elemental analysis, FT-IR, UV-Visible, Luminescence, TGA, magnetic susceptibility, and X-ray crystallography. The structures contain mononuclear octahedral assemblies, the lattice architecture of which exemplifies reaction conditions under which conformational variants and solvent-associated lattice-imposed complexes are assembled. Transformations between complex species denote their association with reactivity pathways, suggesting alternate synthetic methodologies for their isolation. Theoretical work (Hirshfeld, Electrostatic Potential, DFT) signifies the impact of crystal structure on energy profiles of the generated species. The arisen physicochemical profiles of all compounds portray a well-configured interwoven network of pathways, projecting strong connection between structural speciation and Ni(II) reactivity patterns in organic-solvent media. The collective results provide well-defined parameterized profiles, poised to influence the synthesis of new Ni(II)-iminodialcohol materials with specified structural-magneto-optical properties