Pulsed Electromagnetic Field Stimulation in Osteogenesis and Chondrogenesis: Signaling Pathways and Therapeutic Implications

Mesenchymal stem cells (MSCs) are the main cell players in tissue repair and thanks to their self-renewal and multi-lineage differentiation capabilities, they gained significant attention as cell source for tissue engineering (TE) approaches aimed at restoring bone and cartilage defects. Despite significant progress, their therapeutic application remains debated: the TE construct often fails to completely restore the biomechanical properties of the native tissue, leading to poor clinical outcomes in the long term. Pulsed electromagnetic fields (PEMFs) are currently used as a safe and non-invasive treatment to enhance bone healing and to provide joint protection. PEMFs enhance both osteogenic and chondrogenic differentiation of MSCs. Here, we provide extensive review of the signaling pathways modulated by PEMFs during MSCs osteogenic and chondrogenic differentiation. Particular attention has been given to the PEMF-mediated activation of the adenosine signaling and their regulation of the inflammatory response as key player in TE approaches. Overall, the application of PEMFs in tissue repair is foreseen: (1) in vitro: to improve the functional and mechanical properties of the engineered construct; (2) in vivo: (i) to favor graft integration, (ii) to control the local inflammatory response, and (iii) to foster tissue repair from both implanted and resident MSCs cells.     

The Role of microRNAs in Development of Colitis-Associated Colorectal Cancer

Colorectal cancer (CRC) is the third most deadly cancer worldwide, and inflammatory bowel disease (IBD) is one of the critical factors in CRC carcinogenesis. IBD is responsible for an unphysiological and sustained chronic inflammation environment favoring the transformation. MicroRNAs (miRNAs) belong to a class of highly conserved short single-stranded segments (18–25 nucleotides) non-coding RNA and have been extensively discussed in both CRC and IBD. However, the role of miRNAs in the development of colitis-associated CRC (CAC) is less clear. The aim of this review is to summarize the major upregulated (miR-18a, miR-19a, miR-21, miR-31, miR-155 and miR-214) and downregulated (miR-124, miR-193a-3p and miR-139-5p) miRNAs in CAC, and their roles in genes’ expression modulation in chronic colonic-inflammation-induced carcinogenesis, including programmed cell-death pathways. These miRNAs dysregulation could be applied for early CAC diagnosis, to predict therapy efficacy and for precision treatment.     

The Antibacterial Drug Candidate SBC3 is a Potent Inhibitor of Bacterial Thioredoxin Reductase

Antibiotic resistance is a growing problem for public health and associated with increasing economic costs and mortality rates. Silver and silver-related compounds have been used for centuries due to their antimicrobial properties. In this work, we show that 1,3-dibenzyl-4,5-diphenyl-imidazol-2-ylidene silver(I) acetate/NHC*-Ag-OAc (SBC3) is a reversible, high affinity inhibitor of E. coli thioredoxin reductase (TrxR; K_i=10.8±1.2 nM). Minimal inhibition concentration (MIC) tests with different E. coli and P. aeruginosa strains demonstrated that SBC3 can efficiently inhibit bacterial cell growth, especially in combination with established antibiotics like gentamicin. Our results show that SBC3 is a promising antibiotic drug candidate targeting bacterial TrxR.     

Inverse identification of constitutive parameters from heat source fields: A local approach applied to hyperelasticity

In this paper, a new inverse identification method of constitutive parameters is developed from full kinematic and thermal field measurements. It consists in reconstructing the heat source field from two different approaches by using the heat diffusion equation. The first one requires the temperature field measurement and the value of the thermophysical parameters. The second one is based on the kinematic field measurement and the choice of a thermo-hyperelastic model that contains the parameters to be identified. The identification is carried out at the local scale, ie, at any point of the heat source field, without using the boundary conditions. In the present work, the method is applied to the challenging case of hyperelasticity from a heterogeneous test. Due to large deformations undergone by the rubber specimen tested, a motion compensation technique is developed to plot the kinematic and the thermal fields at the same points before reconstructing the heterogeneous heat source field. In the present case, the constitutive parameter of the Neo-Hookean model has been identified, and its distribution has been characterized with respect to the strain state at the surface of a cross-shaped specimen.     

Crystal violet dye sorption and transport in/through biobased PVA cryogel membranes

Cryogels based on poly(vinyl alcohol) [PVA] and three types of bioinsertions such as scleroglucan, cellulose microfibers, and zein, respectively, have been prepared using capacity of PVA to crosslink by repeated freezing–thawing cycles. The effect of the incorporation of biopolymers on the properties of PVA cryogel has been studied by using several techniques such as: scanning electron microscopy, differential scanning calorimetry, and Fourier transform infrared studies. The obtained biobased cryogel membranes were subjected to sorption and to diffusion experiments using Crystal Violet (CV), a dye commonly used in the textile industry and in medicine. Image analysis with CIELAB system was used both to monitor the cryogels loading with CV and to gain insight in the dye state into the gel, in correlation with the bioinsertion type and gels morphology. Dye diffusion but also sorption capacity of the cryogels was found to be closely related to the type of biopolymer. In this article the equilibrium (sorption isotherms) and transport properties (diffusion and permeability coefficients) of CV, in/through physical cross‐linked PVA hydrogel membranes with bioinsertions has been reported. The highest efficiency for the CV removal from aqueous solutions was obtained for the PVA/Scl cryogels. © 2015 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2015 , 132, 41838.     

Impact of the anode operating conditions on the liquid water distribution in the cathode gas diffusion layer

Previous experimental results indicate that the humidification conditions at the anode have an impact on the liquid water distribution in the cathode gas diffusion layer. Numerical simulations are developed to reproduce and analyze this effect. Results consistent with the experimental results are first obtained by playing with the partition coefficients of an advanced pore network model computing the liquid water formation and transfer in the cathode gas diffusion layer (GDL) for a large range of operating conditions. Then, a model for the full anode – cathode assembly is developed by combining the pore network model of the cathode GDL and a 1D model describing the heat and water transfer in the various components of the anode-cathode assembly. This enables one to generalize the dry – wet regime diagram introduced in a previous work by incorporating the effect of the humidity condition at the anode.     

Mitochondrial Bioenergetic,Photobiomodulation and Trigeminal Branches Nerve Damage,What’s the Connection? A Review

Background: Injury of the trigeminal nerve in oral and maxillofacial surgery can occur. Schwann cell mitochondria are regulators in the development, maintenance and regeneration of peripheral nerve axons. Evidence shows that after the nerve injury, mitochondrial bioenergetic dysfunction occurs and is associated with pain, neuropathy and nerve regeneration deficit. A challenge for research is to individuate new therapies able to normalise mitochondrial and energetic metabolism to aid nerve recovery after damage. Photobiomodulation therapy can be an interesting candidate, because it is a technique involving cell manipulation through the photonic energy of a non-ionising light source (visible and NIR light), which produces a nonthermal therapeutic effect on the stressed tissue. Methods: The review was based on the following questions: (1) Can photo-biomodulation by red and NIR light affect mitochondrial bioenergetics? (2) Can photobiomodulation support damage to the trigeminal nerve branches? (preclinical and clinical studies), and, if yes, (3) What is the best photobiomodulatory therapy for the recovery of the trigeminal nerve branches? The papers were searched using the PubMed, Scopus and Cochrane databases. This review followed the ARRIVE-2.0, PRISMA and Cochrane RoB-2 guidelines. Results and conclusions: The reliability of photobiomodulatory event strongly bases on biological and physical-chemical evidence. Its principal player is the mitochondrion, whether its cytochromes are directly involved as a photoacceptor or indirectly through a vibrational and energetic variation of bound water: water as the photoacceptor. The 808-nm and 100 J/cm² (0.07 W; 2.5 W/cm²; pulsed 50 Hz; 27 J per point; 80 s) on rats and 800-nm and 0.2 W/cm² (0.2 W; 12 J/cm²; 12 J per point; 60 s, CW) on humans resulted as trustworthy therapies, which could be supported by extensive studies.