Hepatotoxicity assessment of innovative nutritional supplements based on olive-oil formulations enriched with natural antioxidants.

Introduction: This study focuses on the assessment of extra virgin olive-oil and olive fruit-based formulations enriched with natural antioxidants as potential nutritional supplements for alleviating symptoms and long-term consequences of illnesses whose molecular pathophysiology is affected by oxidative stress and inflammation, such as Alzheimer's disease (AD).

Methods: Besides evaluating cell viability and proliferation capacity of human hepatocellular carcinoma HepG2 cells exposed to formulations in culture, hepatotoxicity was also considered as an additional safety measure using quantitative real-time PCR on RNA samples isolated from the cell cultures and applying approaches of targeted molecular analysis to uncover potential pathway effects through gene expression profiling. Furthermore, the formulations investigated in this work contrast the addition of natural extract with chemical forms and evaluate the antioxidant delivery mode on cell toxicity.

In vitro and in silico evaluation of the serrapeptase effect on biofilm and amyloids of Pseudomonas aeruginosa.

Pseudomonas aeruginosa is an emerging threat for hospitalized and cystic fibrosis patients. Biofilm, a microbial community embedded in extracellular polymeric substance, fortifies bacteria against the immune system. In biofilms, the expression of functional amyloids is linked with highly aggregative, multi-resistant strains, and chronic infections.

Therapeutic and Diagnostic Potential of Exosomes as Drug Delivery Systems in Brain Cancer.

Cancer is designated as one of the principal causes of mortality universally. Among different types of cancer, brain cancer remains the most challenging one due to its aggressiveness, the ineffective permeation ability of drugs through the blood-brain barrier (BBB), and drug resistance. To overcome the aforementioned issues in fighting brain cancer, there is an imperative need for designing novel therapeutic approaches.

Serrapeptase impairs biofilm, wall, and phospho-homeostasis of resistant and susceptible Staphylococcus aureus.

Staphylococcus aureus biofilms are implicated in hospital infections due to elevated antibiotic and host immune system resistance. Molecular components of cell wall including amyloid proteins, peptidoglycans (PGs), and lipoteichoic acid (LTA) are crucial for biofilm formation and tolerance of methicillin-resistant S. aureus (MRSA).

RASSF1A disrupts the NOTCH signaling axis via SNURF/RNF4-mediated ubiquitination of HES1.

RASSF1A promoter methylation has been correlated with tumor dedifferentiation and aggressive oncogenic behavior. Nevertheless, the underlying mechanism of RASSF1A-dependent tumor dedifferentiation remains elusive. Here, we show that RASSF1A directly uncouples the NOTCH-HES1 axis, a key suppressor of differentiation.

Salivary GFAP as a potential biomarker for diagnosis of mild cognitive impairment and Alzheimer's disease and its correlation with neuroinflammation and apoptosis.

Glial fibrillary acidic protein (GFAP) is the main constituent of the astrocytic cytoskeleton, overexpressed during reactive astrogliosis-a hallmark of Alzheimer's Disease (AD). GFAP and established biomarkers of neurodegeneration, inflammation, and apoptosis have been determined in the saliva of amnestic-single-domain Mild Cognitive Impairment (MCI) (Ν = 20), AD (Ν = 20) patients, and cognitively healthy Controls (Ν = 20). Salivary GFAP levels were found significantly decreased in MCI and AD patients and were proven an excellent biomarker for discriminating Controls from MCI or AD patients.

Involvement and relationship of bacterial lipopolysaccharides and cyclooxygenases levels in Alzheimer's Disease and Mild Cognitive Impairment patients.

This study reports elevated levels of bacterial lipopolysaccharides (LPSs) and cyclooxygenases (COX-1/2) in blood serum and cerebrospinal fluid (CSF) of Alzheimer's Disease (AD) and Mild Cognitive Impairment (MCI) patients compared to cognitively healthy individuals, indicating LPSs as promising biomarkers, especially in serum. LPSs, in both fluids, positively correlate with COX-1/2, Αβ and tau and negatively with mental state. Furthermore, COX-2 is the main determinant of LPSs presence in serum, whereas COX-1 in CSF.

Unraveling the binding mechanism of an Oxovanadium(IV) - Curcumin complex on albumin, DNA and DNA gyrase by in vitro and in silico studies and evaluation of its hemocompatibility.

An oxovanadium(IV) - curcumin based complex, viz. [VO(cur)(2,2´-bipy)(HO)] where cur is curcumin and bipy is bipyridine, previously synthesized, has been studied for interaction with albumin and DNA. Fluorescence emission spectroscopy was used to evaluate the interaction of the complex with bovine serum albumin (BSA) and the BSA-binding constant (K) was calculated to be 2.

Synthesis, physicochemical characterization and biological properties of two novel Cu(II) complexes based on natural products curcumin and quercetin.

Curcumin and quercetin are two of the most prominent natural polyphenols with a diverse spectrum of beneficial properties, including antioxidant, anti-inflammatory, chemopreventive and chemotherapeutic activity. The complexation of these natural products with bioactive transition metal ions can lead to the generation of novel metallodrugs with enhanced biochemical and pharmacological activities. Within this framework, the synthesis and detailed structural and physicochemical characterization of two novel complex assemblies of Cu(II) with curcumin and quercetin and the ancillary aromatic chelator 2,2'-bipyridine is presented.

Modeling and Targeting Alzheimer's Disease With Organoids.

Human neurodegenerative diseases, such as Alzheimer's disease (AD), are not easily modeled due to the inaccessibility of brain tissue and the level of complexity required by existing cell culture systems. Three-dimensional (3D) brain organoid systems generated from human pluripotent stem cells (hPSCs) have demonstrated considerable potential in recapitulating key features of AD pathophysiology, such as amyloid plaque- and neurofibrillary tangle-like structures. A number of AD brain organoid models have also been used as platforms to assess the efficacy of pharmacological agents in disease progression.

Structurally characterized gallium-chrysin complexes with anticancer potential.

Chemotherapeutic metal-based compounds are effective anticancer agents; however, their cytotoxic profile and significant side effects limit their wide application. Natural products, especially flavonoids, are a prominent alternative source of anticancer agents that can be used as ligands for the generation of new bioactive complexes with metal ions of known biochemical and pharmacological activities. Herein, we present the synthesis and detailed structural and physicochemical characterizations of three novel complex assemblies of Ga(iii) with the flavonoid chrysin and the ancillary aromatic chelators 1,10-phenanthroline, 2,2'-bipyridine and imidazole.

Magnetic cationic liposomal nanocarriers for the efficient drug delivery of a curcumin-based vanadium complex with anticancer potential.

In this work novel magnetic cationic liposomal nanoformulations were synthesized for the encapsulation of a crystallographically defined ternary V(IV)-curcumin-bipyridine (VCur) complex with proven bioactivity, as potential anticancer agents. The liposomal vesicles were produced via the thin film hydration method employing N-[1-(2,3-dioleoyloxy)propyl]-N,N,N-trimethylammonium (DOTAP) and egg phosphatidylcholine lipids and were magnetized through the addition of citric acid surface-modified monodispersed magnetite colloidal magnetic nanoparticles. The obtained nanoformulations were evaluated for their structural and textural properties and shown to have exceptional stability and enhanced solubility in physiological media, demonstrated by the entrapment efficiency and loading capacity results and the in vitro release studies of their cargo.

A palladium(II) complex with the Schiff base 4-chloro-2-(N-ethyliminomethyl)-phenol: Synthesis, structural characterization, and in vitro and in silico biological activity studies.

The synthesis and characterization of the Pd(II) complex of the formula [Pd(L)] 1 with the Schiff base 4-chloro-2-(N-ethyliminomethyl)-phenol (HL) as derived in situ via the condensation reaction of 5-chloro-salicylaldehyde and ethylamine was undertaken. The structure of 1 was verified by single-crystal X-ray crystallography. The ability of 1 to interact with calf-thymus (CT) DNA was studied by UV-vis and viscosity experiments, and its ability to displace ethidium bromide (EB) from the DNA-EB conjugate was revealed by fluorescence spectroscopy.

Homoleptic and heteroleptic silver(I) complexes bearing diphosphane and thioamide ligands: Synthesis, structures, DNA interactions and antibacterial activity studies.

Three silver(I) complexes bearing different combinations of diphosphanes and N-heterocyclic thioamides or thioamidates as ligands have been synthesized and structurally characterized: the ionic, homoleptic compound [Ag(xantphos)][BF] (1), where xantphos = 4,5-bis(diphenylphosphano)-9,9-dimethyl-xanthene, and the neutral, heteroleptic compounds [Ag(xantphos)(κ-S-pymt)] (2), where pymt = pyrimidine-2-thiolate, and [AgCl(dppbz)(κ-S-mtdztH)] (3), where dppbz = bis(diphenylphosphano)benzene and mtdztH = 5-methyl-1,3,4-thiadiazole-2-thione. X-ray crystallography studies reveal tetrahedral coordination environments around the silver(I) ions in compounds 1 and 3, while a trigonal planar arrangement of the PS donor set has been found around the metal center in compound 2. The interaction of the three compounds with calf-thymus DNA was monitored by UV-vis spectroscopy, DNA-viscosity measurements and indirectly by testing their ability to compete with ethidium bromide for DNA intercalation sites studied by fluorescence emission spectroscopy.

In vitro and in silico study of the biological activity of manganese(III) inverse-[9-MC-3]-metallacrowns and manganese(II) complexes with the anti-inflammatory drugs diclofenac or indomethacin.

In the present contribution, the biological properties of four manganese complexes with the non-steroidal anti-inflammatory drugs sodium diclofenac (Nadicl) or indomethacin (Hindo) in the presence or absence of salicylaldoxime (Ηsao), i.e. [Μn(O)(dicl)(sao)(CHOH)] 1, [Μn(O)(indo)(sao)(HO)], 2, [Μn(dicl)(CHOH)], 3, and [Μn(indo)(CHOH)], 4 are presented.

Nanobrass CuZn Nanoparticles as Foliar Spray Nonphytotoxic Fungicides.

Inorganic nanoparticles (NPs) have been proposed as alternative fertilizers to suppress plant disease and increase crop yield. However, phytotoxicity of NPs remains a key factor for their massive employment in agricultural applications. In order to investigate new effective, nonphytotoxic, and inexpensive fungicides, in the present study CuZn bimetallic nanoparticles (BNPs) have been synthesized as antifungals, while assessment of photosystem II (PSII) efficiency by chlorophyll fluorescence imaging analysis is utilized as an effective and noninvasive phytotoxicity evaluation method.

Rhamnolipids, Microbial Virulence Factors, in Alzheimer's Disease.

Alzheimer's disease (AD) has been attributed to chronic bacterial infections. The recognition of human microbiota as a substantial contributor to health and disease is relatively recent and growing. During evolution, mammals live in a symbiotic state with myriads of microorganisms that survive at a diversity of tissue micro-surroundings.

Cobalt(II) complexes with the antimicrobial drug enrofloxacin: structure, antimicrobial activity, DNA- and albumin-binding.

The cobalt(II) complexes with the quinolone antimicrobial agent enrofloxacin (Herx) in the presence of the nitrogen-donor heterocyclic ligands pyridine (py), 2,2'-bipyridylamine (bipyam), 1,10-phenanthroline (phen), 2,2'-bipyridine (bipy) or the oxygen-donor ligand N,N-dimethylformamide (DMF) were synthesized and characterized. The crystal structures of complexes [Co(erx)2(py)2]·MeOH·6H2O and [Co(erx)2(bipyam)]·4.5MeOH·1.

Evidence for lytic transglycosylase and β-N-acetylglucosaminidase activities located at the polyhydroxyalkanoates (PHAs) granules of Thermus thermophilus HB8.

The thermophilic bacterium Thermus thermophilus HB8 accumulates polyhydroxyalkanoates (PHAs) as intracellular granules used by cells as carbon and energy storage compounds. PHAs granules were isolated from cells grown in sodium gluconate (1.5 % w/v) as carbon source.

Structure, antimicrobial activity, DNA- and albumin-binding of manganese(II) complexes with the quinolone antimicrobial agents oxolinic acid and enrofloxacin.

The reaction of MnCl2 with the quinolone antibacterial drug oxolinic acid (Hoxo) results to the formation of [KMn(oxo)3(MeOH)3]. Interaction of MnCl2 with the quinolone Hoxo or enrofloxacin (Herx) and the N,N'-donor heterocyclic ligand 1,10-phenanthroline (phen) results in the formation of metal complexes with the general formula [Mn(quinolonato)2(phen)]. The crystal structures of [KMn(oxo)3(MeOH)3] and [Mn(erx)2(phen)], exhibiting a 1D polymeric and a mononuclear structure, respectively, have been determined by X-ray crystallography.

Flagellin gene (fliC) of Thermus thermophilus HB8: characterization of its product and involvement to flagella assembly and microbial motility.

Thermus thermophilus HB8 flagellin protein (FliC) is encoded by the TTHC004 (fliC) gene, which is located in the pTT8 plasmid of the bacterium. Flagellin monomer and flagella fibres were isolated from a culture of T. thermophilus grown in rich medium, or in mineral salt medium with sodium gluconate as the carbon source.

Simultaneous polyhydroxyalkanoates and rhamnolipids production by Thermus thermophilus HB8.

The ability of Thermus thermophilus HB8 to produce simultaneously two environmentally-friendly biodegradable products, polyhydroxyalkanoates (PHAs) and rhamnolipids (RLs), using either sodium gluconate or glucose as sole carbon source, was demonstrated. The utilization of sodium gluconate resulted in higher levels of PHAs and RLs production than when glucose was used as sole carbon source. The initial phosphate concentration (as PO43-) influences both PHAs and RLs productions that were increased during cultivation time.

Sunflower seed oil and oleic acid utilization for the production of rhamnolipids by Thermus thermophilus HB8.

The potential production of rhamnolipids was demonstrated using the thermophilic eubacterium Thermus thermophilus HB8 and sunflower seed oil or oleic acid as carbon sources. Sunflower seed oil was directly hydrolyzed by secretion of lipase and became a favorable carbon source for rhamnolipids production. Rhamnolipids levels were attainted high values, comparable to those produced by Pseudomonas strains from similar sources.