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Osteogenesis imperfecta (OI) is a rare genetic disorder of the connective tissue and 90% of cases are due to dominant mutations in COL1A1 and COL1A2 genes. To increase OI disease knowledge and contribute to patient follow-up management, a homogeneous Italian cohort of 364 subjects affected by OI types I–IV was evaluated. The study population was composed of 262 OI type I, 24 type II, 39 type III, and 39 type IV patients. Three hundred and nine subjects had a type I collagen affecting function mutations (230 in α1(I) and 79 in α2(I)); no disease-causing changes were noticed in 55 patients. Compared with previous genotype–phenotype OI correlation studies, additional observations arose: a new effect for α1- and α2-serine substitutions has been pointed out and heart defects, never considered before, resulted associated to quantitative mutations (P = 0.043). Moreover, some different findings emerged if compared with previous literature; especially, focusing the attention on the lethal form, no association with specific collagen regions was found and most of variants localized in the previously reported “lethal clusters” were causative of OI types I–IV. Some discrepancies have been highlighted also considering the “50–55 nucleotides rule,” as well as the relationship between specific collagen I mutated region and the presence of dentinogenesis imperfecta and/or blue sclera. Despite difficulties still present in defining clear rules to predict the clinical outcome in OI patients, this study provides new pieces for completing the puzzle, also thanks to the inclusion of clinical signs never considered before and to the large number of OI Italian patients.

Adipose tissue-derived stem cells (ADSCs) possess multipotent differentiation potential and significant immunomodulatory properties, making them valuable in regenerative medicine. However, their adipogenic differentiation can lead to triglyceride accumulation, chronic inflammation, and metabolic dysfunction. This study evaluated the effects of Radio Electric Asymmetric Conveyer (REAC) technology tissue optimization regenerative adipogenesis reprogramming (TO RGN-AR) on ADSC differentiation, focusing on its ability to preserve stemness, suppress adipogenesis, and promote beneficial phenotypes. REAC TO RGN-AR treatment significantly increased the expression of stemness-related genes (Oct-4, Sox2, and Nanog) while downregulating the expression of adipogenic markers (PPAR-γ, LPL, and ACOT2). Additionally, REAC TO RGN-AR treated cells presented a phenotypic shift toward beige adipocytes, characterized by increased TMEM26 expression and reduced ASC-1 expression. These findings underscore the novelty of using REAC TO RGN-AR to modulate cellular endogenous bioelectrical activity, presenting a noninvasive and operator-independent approach to enhance ADSC-based therapies. This work highlights the potential of this treatment to address metabolic disorders and chronic inflammation while advancing regenerative medicine.

Fibroblasts play a fundamental role in maintaining tissue architecture, regulating repair processes, and adapting to metabolic and inflammatory stress. Increasing evidence indicates that endogenous bioelectrical states contribute to gene expression regulation and cellular homeostasis. In this study, we investigated the effects of Radio Electric Asymmetric Conveyer (REAC) Metabolic Optimization–Inside Blue Zone (MO-IBZ) treatment on key regulators of stress response and metabolic control in human foreskin fibroblasts (HFF-1). Cells were exposed to nine standardized REAC MO-IBZ sessions, and changes in gene and protein expression were evaluated. Quantitative RT-PCR revealed a significant downregulation of SIRT1 and an upregulation of PPAR-γ expression in treated cells compared with untreated controls. These findings indicate molecular changes involving stress-responsive and metabolic regulatory pathways; however, they should be interpreted primarily as transcriptional signatures, as no direct functional stress-response or metabolic assays were performed. Immunofluorescence analysis showed visually increased expression of mTOR, IGF-1 receptor, and cytochrome c in REAC-treated fibroblasts, supporting a qualitative indication of activation of pathways associated with anabolic signaling, mitochondrial function, and metabolic efficiency. Taken together, these findings indicate that REAC MO-IBZ induces a coordinated molecular profile compatible with changes in cellular metabolic regulatory capacity. Within the framework of current bioelectrical literature, these changes may plausibly reflect broader regulatory adaptations; however, the present work does not provide direct measurements of bioelectrical parameters, functional metabolic activity, or epigenetic regulation, and therefore such interpretations remain speculative. These results provide descriptive mechanistic evidence supporting further investigation of REAC-based bioelectrical modulation as a potential strategy to influence cellular pathways involved in metabolic balance and tissue repair, encouraging future studies incorporating direct bioelectrical, epigenetic, and functional analyses.

Grape leaves influence several biological activities in the cardiovascular system, acting as antioxidants. In this study, we aimed at evaluating the effect of ethanolic and water extracts from grape leaves grown in Algeria, obtained by accelerator solvent extraction (ASE), on cell proliferation. The amount of total phenols was determined using the modified Folin-Ciocalteu method, antioxidant activities were evaluated by the 2,2-diphenyl-l-picrylhydrazyl free radical (DPPH*) method and ·OH radical scavenging using electron paramagnetic resonance (EPR) spectroscopy methods. Cell proliferation of HepG2 hepatocarcinoma, MCF-7 human breast cancer cells and vein human umbilical (HUVEC) cells, as control for normal cell growth, was assessed by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide reduction assay (MTT). Apoptosis- related genes were determined by measuring Bax and Bcl-2 mRNA expression levels. Accelerator solvent extractor yield did not show significant difference between the two solvents (ethanol and water) (p > 0.05). Total phenolic content of water and ethanolic extracts was 55.41 ± 0.11 and 155.73 ± 1.20 mg of gallic acid equivalents/g of dry weight, respectively. Ethanolic extracts showed larger amounts of total phenols as compared to water extracts and interesting antioxidant activity. HepG2 and MCF-7 cell proliferation decreased with increasing concentration of extracts (0.5, 1, and 2 mg/mL) added to the culture during a period of 1–72 h. In addition, the expression of the pro-apoptotic gene Bax was increased and that of the anti-apoptotic gene Bcl-2 was decreased in a dose-dependent manner, when both MCF-7 and HepG2 cells were cultured with one of the two extracts for 72 h. None of the extracts elicited toxic effects on vein umbilical HUVEC cells, highlighting the high specificity of the antiproliferative effect, targeting only cancer cells. Finally, our results suggested that ASE crude extract from grape leaves represents a source of bioactive compounds such as phenols, with potential antioxidants activity, disclosing a novel antiproliferative effect affecting only HepG2 and MCF-7 tumor cells.

Chronic low-grade inflammation, altered microvascular support, and progressive stress-related cellular dysfunction are major contributors to tissue aging and impaired repair. Dermal fibroblasts are central regulators of these processes because they integrate cytokine-related signaling, redox balance, and extracellular matrix homeostasis. Increasing evidence indicates that endogenous bioelectrical activity may influence these cellular functions by shaping upstream regulatory conditions linked to downstream molecular responses. In the present study, we investigated the molecular effects of the Radio Electric Asymmetric Conveyer Anti-Inflammatory Cellular Treatment delivered under Inside Blue Zone conditions (REAC ACT-IBZ) in human dermal fibroblasts (HFF1). Cells were exposed to nine standardized treatment sessions, and molecular changes were assessed by RT-qPCR, ELISA, and immunofluorescence analysis complemented by supportive semi-quantitative fluorescence intensity assessment. REAC ACT-IBZ exposure was associated with increased SIRT1 and VEGF expression and with transcriptional modulation of selected cytokine-related genes, including IL-1α, IL-1β, IL-2, and IL-8. Immunofluorescence analysis, complemented by supportive semi-quantitative fluorescence intensity assessment, showed a pattern consistent with increased FOXO1 and SIRT1 staining and reduced mTOR staining in treated cells. Overall, these findings identify a molecular profile associated with REAC ACT-IBZ exposure in human dermal fibroblasts, involving stress-response regulators, angiogenesis-related signaling, and selective cytokine-related transcriptional changes. Within the limits of the present in vitro model, the data support the view that endogenous bioelectrical modulation may interact with molecular networks relevant to tissue homeostasis and inflammaging.

Bipolar disorder (BD) is a severe, chronic, and disabling neuropsychiatric disorder characterized by recurrent mood disturbances (mania/hypomania and depression, with or without mixed features) and a constellation of cognitive, psychomotor, autonomic, and endocrine abnormalities. The etiology of BD is multifactorial, including both biological and epigenetic factors. Recently, microRNAs (miRNAs), a class of epigenetic regulators of gene expression playing a central role in brain development and plasticity, have been related to several neuropsychiatric disorders, including BD. Moreover, an alteration in the number/distribution and differentiation potential of neural stem cells has also been described, significantly affecting brain homeostasis and neuroplasticity. This review aimed to evaluate the most reliable scientific evidence on miRNAs as biomarkers for the diagnosis of BD and assess their implications in response to mood stabilizers, such as lithium. Neural stem cell distribution, regulation, and dysfunction in the etiology of BD are also dissected.

The hepatocellular carcinoma is one of the most common malignant tumour with high level of mortality rate due to its rapid progression and high resistance to conventional chemotherapies. Thus, the search for novel therapeutic leads is of global interest. Herein, a small set of derivatives of magnolol 1 and honokiol 2, the main components of Magnolia grandiflora and Magnolia obovata, were evaluated in in vitro assay using tumoral hepatocytes. The pro-drug approach was applied as versatile strategy to the improve bioactivity of the compounds by careful transformation of the hydroxyl groups of magnolol 1 and honokiol 2 in suitable ester derivatives. Compounds 10 and 11 resulted to be more potent than the parental honokiol 2 at concentration down to 1 μM with complete viability of treated fibroblast cells up to concentrations of 80 μM. The combination of a butyrate ester and a bare phenol-OH group in the honokiol structure seemed to play a significant role in the antiproliferative activity identifying an interesting pharmacological clue against hepatocellular carcinoma.

In this review, we described different factors that modulate pluripotency in stem cells, in particular we aimed at following the steps of two large families of miRNAs: the miR-200 family and the miR-302 family. We analyzed some factors tuning stem cells behavior as TGF-β, which plays a pivotal role in pluripotency inhibition together with specific miRNAs, reactive oxygen species (ROS), but also hypoxia, and physical stimuli, such as ad hoc conveyed electromagnetic fields. TGF-β plays a crucial role in the suppression of pluripotency thus influencing the achievement of a specific phenotype. ROS concentration can modulate TGF-β activation that in turns down regulates miR-200 and miR-302. These two miRNAs are usually requested to maintain pluripotency, while they are down-regulated during the acquirement of a specific cellular phenotype. Moreover, also physical stimuli, such as extremely-low frequency electromagnetic fields or high-frequency electromagnetic fields conveyed with a radioelectric asymmetric conveyer (REAC), and hypoxia can deeply influence stem cell behavior by inducing the appearance of specific phenotypes, as well as a direct reprogramming of somatic cells. Unraveling the molecular mechanisms underlying the complex interplay between externally applied stimuli and epigenetic events could disclose novel target molecules to commit stem cell fate.

Inflammatory response represents one of the main mechanisms of healing and tissue function restoration. On the other hand, chronic inflammation leads to excessive secretion of pro-inflammatory cytokines involved in the onset of several diseases. Oxidative stress condition may contribute in worsening inflammatory state fall, increasing reactive oxygen species (ROS) production and cytokines release. Polyphenols can counteract inflammation and oxidative stress, modulating the release of toxic molecules and interacting with physiological defenses, such as cytochromes p450 enzymes. In this paper, we aimed at evaluating the anti-inflammatory properties of different concentrations of Myrtus communis L. pulp and seeds extracts, derived from liquor industrial production, on human fibroblasts. We determined ROS production after oxidative stress induction by H2O2 treatment, and the gene expression of different proinflammatory cytokines. We also analyzed the expression of CYP3A4 and CYP27B1 genes, in order to evaluate the capability of Myrtus polyphenols to influence the metabolic regulation of other molecules, including drugs, ROS, and vitamin D. Our results showed that Myrtus extracts exert a synergic effect with vitamin D in reducing inflammation and ROS production, protecting cells from oxidative stress damages. Moreover, the extracts modulate CYPs expression, preventing chronic inflammation and suggesting their use in development of new therapeutic formulations.

Development of electrospun nanofibers with suitable properties to promote wound healing is an advantage in developing non-invasive skin treatments. We showed the potential application of Polyvinyl acetate (PVA) and Polyvinylpyrrolidone (PVP) combined with Helichrysum italicum oil ( HO ) in wound healing. During this process, Tight junctions (TJs) play a crucial role in maintaining skin integrity. TJs are intercellular junctions composed of a variety of transmembrane proteins, including Occludin (OCLN), observed also in migrating epithelial cells. Changes in OCLN expression affect epidermal permeability, indicating an active role in the healing process. Within this context, we studied the OCLN expression during healing after scratch assay on Keratinocytes (HaCaT), by a confocal microscopic analysis. In addition, we evaluated the effect of treatment after scratch on cell elasticity by Atomic Force Microscopy (AFM) analysis. All results show a positive trend in cell proliferation and viability on HaCaT treated with functionalized nanofibers. These results were confirmed by the expression of genes involved in the early stages of the regenerative process. Understanding the cell mechanisms involved in skin changes during repair process would allow future application of nanomaterials combined with HO in vivo.