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.     

DNA Methylation Signatures of Bone Metabolism in Osteoporosis and Osteoarthritis Aging-Related Diseases: An Updated Review

DNA methylation is one of the most studied epigenetic mechanisms that play a pivotal role in regulating gene expression. The epigenetic component is strongly involved in aging-bone diseases, such as osteoporosis and osteoarthritis. Both are complex multi-factorial late-onset disorders that represent a globally widespread health problem, highlighting a crucial point of investigations in many scientific studies. In recent years, new findings on the role of DNA methylation in the pathogenesis of aging-bone diseases have emerged. The aim of this systematic review is to update knowledge in the field of DNA methylation associated with osteoporosis and osteoarthritis, focusing on the specific tissues involved in both pathological conditions.     

Diphenyl-Methane Based Thyromimetic Inhibitors for Transthyretin Amyloidosis

Thyromimetics, whose physicochemical characteristics are analog to thyroid hormones (THs) and their derivatives, are promising candidates as novel therapeutics for neurodegenerative and metabolic pathologies. In particular, sobetirome (GC-1), one of the initial halogen-free thyromimetics, and newly synthesized IS25 and TG68, with optimized ADME-Tox profile, have recently attracted attention owing to their superior therapeutic benefits, selectivity, and enhanced permeability. Here, we further explored the functional capabilities of these thyromimetics to inhibit transthyretin (TTR) amyloidosis. TTR is a homotetrameric transporter protein for THs, yet it is also responsible for severe amyloid fibril formation, which is facilitated by tetramer dissociation into non-native monomers. By combining nuclear magnetic resonance (NMR) spectroscopy, computational simulation, and biochemical assays, we found that GC-1 and newly designed diphenyl-methane-based thyromimetics, namely IS25 and TG68, are TTR stabilizers and efficient suppressors of TTR aggregation. Based on these observations, we propose the novel potential of thyromimetics as a multi-functional therapeutic molecule for TTR-related pathologies, including neurodegenerative diseases.     

Study of the effect of noble metal promotion in Ni-based catalyst for the Sabatier reaction

This paper reports the preparation and the evaluation of the performance of Ni-based powder catalysts with low nickel loading on the CO2 methanation reaction, that is an integral part of the power-to-gas (PtG) technology. CeO₂, CeZrO₄ and CeO₂/SiO₂ were selected as possible supports, and the results of this first screening pointed out that 10%Ni/CeO₂ catalyst could offer the best reaction performances because of ceria's peculiar characteristics. Moreover, the promotion of this promising formulation with the addition of a small amount of noble metals (Pt, Ru, Rh) was investigated, showing that platinum in particular can enhance the catalyst performances. A further study related to the noble metal loading pointed out that platinum and ruthenium have a different optimum loading condition: this result, together with the activity tests performed on monometallic formulations with only the noble metal, suggested that the two metals are able to catalyse two different reactions, thus promoting two different reaction mechanisms.     

To treat or not to treat: comparison of different criteria used to determine whether weight loss is to be recommended

Background  

Excess body fat is a major risk factor for disease primarily due to its endocrine activity. In recent years several criteria have been introduced to evaluate this factor. Nevertheless, treatment need is currently assessed only on the basis of an individual's Body Mass Index (BMI), calculated as body weight (in kg) divided by height in m². The aim of our study was to determine whether application of the BMI, compared to adiposity-based criteria, results in underestimation of the number of subjects needing lifestyle intervention.     

Comparison between the LLC-MK2 and MDCK cell lines in the isolation of parainfluenza virus from nasopharyngeal aspirates

BACKGROUND: We report a prospective comparative study of the efficacy of three commercial cell lines in the isolation of the parainfluenza (PI) virus from nasopharyngeal samples. MATERIAL AND METHODS: In a 16 months period we studied all nasopharyngeal samples from patients with the suspension of a viral respiratory infection. The compared cell lines were LLC-MK2 and MDCK. All samples were processed by the shell-vial assay, incubated 3 days at 36 degrees C. The monolayers were stained by an indirect immunofluorescence assay with a monoclonal antibody against the nucleoprotein of the PI virus. RESULTS: In the study period 746 samples were analyzed, 46 PI virus were isolated, all belonged to the serotype 3. The LLC-MK2 cell line isolated 44 viruses (95.6%) and the MDCK cell line 41 (89.1%), no statistically significant differences were detected (p = 0.14) (qualitative sensitivity). In 84.8% of positive samples, the PI virus was isolated simultaneously in the two cell lines. Neither cell line isolated all PI virus. No statistical differences were detected in the quantitative sensitivity, although the LLC-MK2 cell line detected a slightly more samples with a low viral load (70.4 vs 68.2%). CONCLUSIONS: In view of the results obtained in this study, we believe that anyone of the two cell lines would be used in the isolation of the PI virus from respiratory samples.     

Presence of epithelial cells in the medullary canal after spinal anesthesia

BACKGROUND AND AIM: Several authors have focused on a causal link between the onset of neurological complications after lumbar injections and the fact that epithelial cells may be drawn into the vertebral canal during these procedures. Complications may arise both early (cephalea, septic and aseptic meningitis) and late (epidermoid tumours). The authors aimed to evaluate whether skin fragments which are carried down by the needle during subarachnoid anesthesia may even be present in the epidural or subarachnoid space three days later and may therefore justify the onset of the above neurological syndromes. METHODS: Five adult cats under narcosis underwent subarachnoid anesthesia using disposable 22G Quincke type needles. Between 0.7 and 1 ml isobaric bupivacaine at 0.50% was injected. The presence of the motor block of the lower limbs was ascertained once the effects of general anesthesia wore off. On the third day, again under general anesthesia, cardio-respiratory arrest was provoked by intravenous injection. Samples of meninges were collected in the injection area. After fixation in a phosphate glutaraldehyde buffer, dehydration in acetone, dehydration by critical point and gold metalisation, the samples were examined using SEM. RESULTS: No epidermal cells were found on the surface of the meninges. On the other hand, a squamous epithelial cell was observed which drained inside a sectioned epidural vessel towards the systemic circulation. CONCLUSIONS: This study confirms the possibility that, after subarachnoid anesthesia using 22G Quincke needles, skin fragments may enter the spinal canal. The permanence or otherwise of the epithelial fragments on the third day depends on the size of the fragment drawn down and the efficacy of the drainage system which removes isolated epithelial cells. This phenomenon may justify the self-limiting character of cephalea and meningisms which, even if not treated, regress in a few days, as well as the scarce development of epidermoid tumours.     

Chronically Elevated Exogenous Glucose Elicits Antipodal Effects on the Proteome Signature of Differentiating Human iPSC-Derived Pancreatic Progenitors

The past decade revealed that cell identity changes, such as dedifferentiation or transdifferentiation, accompany the insulin-producing β-cell decay in most diabetes conditions. Mapping and controlling the mechanisms governing these processes is, thus, extremely valuable for managing the disease progression. Extracellular glucose is known to influence cell identity by impacting the redox balance. Here, we use global proteomics and pathway analysis to map the response of differentiating human pancreatic progenitors to chronically increased in vitro glucose levels. We show that exogenous high glucose levels impact different protein subsets in a concentration-dependent manner. In contrast, regardless of concentration, glucose elicits an antipodal effect on the proteome landscape, inducing both beneficial and detrimental changes in regard to achieving the desired islet cell fingerprint. Furthermore, we identified that only a subgroup of these effects and pathways are regulated by changes in redox balance. Our study highlights a complex effect of exogenous glucose on differentiating pancreas progenitors characterized by a distinct proteome signature.