Steering the multipotent mesenchymal cells towards an anti-inflammatory and osteogenic bias via photobiomodulation therapy: How to kill two birds with one stone

The bone marrow-derived multipotent mesenchymal cells (MSCs) have captured scientific interest due to their multi-purpose features and clinical applications. The operational dimension of MSCs is not limited to the bone marrow reservoir, which exerts bone-building and niche anabolic tasks; they also meet the needs of quenching inflammation and restoring inflamed tissues. Thus, the range of MSC activities extends to conditions such as neurodegenerative diseases, immune disorders and various forms of osteopenia. Steering these cells towards becoming an effective therapeutic tool has become mandatory. Many laboratories have employed distinct strategies to improve the plasticity and secretome of MSCs. We aimed to present how photobiomodulation therapy (PBM-t) can manipulate MSCs to render them an extraordinary anti-inflammatory and osteogenic instrument. Moreover, we discuss the outcomes of different PBM-t protocols on MSCs, concluding with some perplexities and complexities of PBM-t in vivo but encouraging and feasible in vitro solutions

Novel Potent Muscarinic Receptor Antagonists: Investigation on the Nature of Lipophilic Substituents in the 5- and/or 6-Positions of the 1,4-Dioxane Nucleus

A series of novel 1,4-dioxane analogues of the muscarinic acetylcholine receptor (mAChR) antagonist 2 was synthesized and studied for their affinity at M1-M5 mAChRs. The 6-cyclohexyl-6-phenyl derivative 3b, with a cis configuration between the CH2N+(CH3)3 chain in the 2-position and the cyclohexyl moiety in the 6-position, showed pKi values for mAChRs higher than those of 2 and a selectivity profile analogous to that of the clinically approved drug oxybutynin. The study of the enantiomers of 3b and the corresponding tertiary amine 33b revealed that the eutomers are (2S,6S)-(-)-3b and (2S,6S)-(-)-33b, respectively. Docking simulations on the M3 mAChR-resolved structure rationalized the experimental observations. The quaternary ammonium function, which should prevent the crossing of the blood-brain barrier, and the high M3/M2 selectivity, which might limit cardiovascular side effects, make 3b a valuable starting point for the design of novel antagonists potentially useful in peripheral diseases in which M3 receptors are involved

Removal of the endocrine disrupter butyl benzyl phthalate from the environment

Butyl benzyl phthalate (BBP), an aryl alkyl ester of 1,2-benzene dicarboxylic acid, is extensively used in vinyl tiles and as a plasticizer in PVC in many commonly used products. BBP, which readily leaches from these products, is one of the most important environmental contaminants, and the increased awareness of its adverse effects on human health has led to a dramatic increase in research aimed at removing BBP from the environment via bioremediation. This review highlights recent progress in the degradation of BBP by pure and mixed bacterial cultures, fungi, and in sludge, sediment, and wastewater. Sonochemical degradation, a unique abiotic remediation technique, and photocatalytic degradation are also discussed. The degradation pathways for BBP are described, and future research directions are considered

Phthalate esters: Bioaccumulation and intracellular signal modifications in in vivo and in vitro models

Phthalates, a class of chemicals used in a whole range of industrial applications, are considered to be ubiquitous global contaminants and endocrine disruptors (EDs). These hormone-mimicking compounds bioaccumulate within organ tissues in several animals, including fishes, amphibians and mammals with different and selective patterns of distribution. The endocrine disrupting effects are probably related to the absorption of these chemicals via the alimentary canal. In particular, phthalates have been seen to be stored in the oxyntic cells of the gastric tubular glands in fishes and amphibians. A relation between bioconcentration and organ functions was also observed. Moreover, in vitro studies on rat osteoblastic cultures demonstrated that benzyl butyl phthalate and di-n-butyl phthalate bioaccumulate, modify actin cytoarchitecture and exert mitogenic effects involving microfilament disruption and nuclear actin/lamin A regulation. On the other hand, primary mouse calvarial osteoblasts, treated with the above chemicals showed DNA base lesions with an increase of apoptotic markers induced by the p53-related pathway. These data strongly suggest that chronic exposure to phthalates could probably affect new bone formation and matrix deposition with clinical implications on bone homeostasis and mineral density. Understanding the way of action of phthalates through the study of autochthon or laboratory animals could reveal the mechanism by which these compounds, as EDs, regulate the fate of the organism

Runx/Smads interaction is impaired in osteoblasts from Fgf2-/- mice

Bone morphogenetic protein 2 (BMP2) is one of the most potent regulator of osteoblast differentiation and bone formation. R-Smads (Smads 1/5/8) are the major transducers for BMPs receptors and, once activated, they translocated in the nucleus regulating transcription target genes by interacting with various transcription factors (1). Runx2 proteins have been shown to interact through their C-terminal segment with Smads and this interaction is required for in vivo osteogenesis (2). In particular, recruitment of Smads to intranuclear sites is Runx2 dependent, and Runx2 factor may accommodate the dynamic targeting of signal transducer to active transcription sites (3). Previously, we have shown, by in vitro and in vivo experiments, that BMP2 up-regulated FGF-2 which is important for the maximal responses of BMP-2 in bone (4). Now, by biochemical, immunofluorescence and immunoelectron microscopy approaches, we found that BPM2 was also able to induce nuclear accumulation and colocalization of Runx2 and Smads1/5/8 in presence of endogenous FGF-2, while Runx/Smads nuclear interaction was markedly reduced in Fgf2-/- osteoblasts. Based on these preliminary data, we hypothesize that the impaired nuclear accumulation of Runx2 in Fgf2-/- osteoblasts could reduce R-Smads sub-nuclear targeting with a consequent decreased expression of differentiating markers and impaired bone formation in Fgf2 null mice

Materiali elettroattivi per applicazioni Biomediche

Materiali elettroattivi per applicazioni Biomedich