Search Results (169)

Schwann cells (SCs) play a crucial role in peripheral nerve repair by supporting axonal regeneration and remyelination. While extensive research has been conducted using rodent SCs, increasing attention is being directed toward human SCs due to species-specific differences in phenotypical and functional properties, and accessibility of human SCs derived from diverse sources. A major challenge in translating SC-based therapies for nerve repair lies in the inability to replicate human SC myelination in vitro, posing a significant obstacle to drug discovery and preclinical research. In this study, we compared the myelination capacity of human, rodent, and porcine SCs in various co-culture conditions, including species-matched and cross-species neuronal environments in a serum-free medium. Our results confirmed that rodent and porcine SCs readily myelinate neurites under standard culture conditions after treatment with ascorbic acid for two weeks, whereas human SCs, at least within the four-week observation period, failed to show myelin staining in all co-cultures. Furthermore, we investigated whether cell culture manipulation impairs human SC myelination by transplanting freshly harvested and predegenerated human nerve segments into NOD-SCID mice for four weeks. Despite supporting host axonal regeneration into the grafts, human SCs exhibited very limited myelination, suggesting an intrinsic species-specific restriction rather than a cell culture-induced defect. These observations suggest fundamental differences between human and rodent SCs and highlight the need for human-specific models and protocols to advance our understanding of SC myelination. Full article

Characteristic manifestations of skin aging, due to either intrinsic or extrinsic factors, such as ultraviolet (UV) radiation and oxidative stress, include cell senescence, alterations in collagen and elastin networks, and melanogenesis disorders. Natural products are considered a rich source of anti-aging molecules. Accordingly, the screening of a plant extract library from the Greek flora for a panel of biological activities related to skin aging is presented herein. In particular, 52 plant materials extracted using Accelerated Solvent Extraction (ASE) and Supercritical Fluid Extraction (SFE) were assessed for their effects on (1) human skin cell viability, (2) antioxidant activity—using both cell-free and cell-based methods—(3) photoprotective capacity, and (4) interference with collagenase, elastase, and tyrosinase, as well as with proteasomal and lysosomal activities of human skin cells. In vivo phenotypic screens on Danio rerio (zebrafish) embryos were also used for assessing melanogenesis. Many active extracts were identified, some of them for the first time, and others in agreement with previous reports. In general, ASE extracts exhibited higher activities than SFE ones. Seven extracts showed multiple activities, being highly effective in at least four different assays. These data support the potential use of these extracts against skin aging in medicinal and cosmetic applications. Full article

The recent COVID-19 pandemic has prompted the scientific community to prioritize the discovery of preventive methods and new therapeutics, including the investigation of natural compounds with antiviral potential. Fungal secondary metabolites (SMs) represent a promising source of antiviral drugs due to their structural diversity and intrinsic biocompatibility. Herein, the antiviral activity of 6-pentyl-α-pyrone (6PP) against bovine coronavirus (BCoV) has been evaluated in vitro. Considering that BCoV and SARS-CoV-2 are both members of the Betacoronavirus genus and share several key features, BCoV represents a valuable reference model for human coronavirus research. A non-cytotoxic dose of 6PP was used on MDBK cells to evaluate its antiviral activity against BCoV. Different experimental conditions were employed to examine cell monolayer protection both pre- and post-infection, as well as the potential inhibition of viral internalization. Overall, post-infection 6PP treatment reduced viral load and decreased viral internalization. Results were analyzed using viral titration and quantitative PCR, while data interpretation was performed by statistical software tools. This study presents a novel fluorescence quantification approach with high confidence demonstrated by its significant concordance with RT-qPCR results. These data suggest that 6PP could be an effective antiviral agent for BCoV, warranting further investigation of its role in coronavirus inhibition. Full article

Due to the complementary operational features, photovoltaic (PV) and fuel cell (FC) systems are increasingly being integrated into hybrid microgrids. PV systems provide clean energy during the day, while FCs provide continuous power supply throughout the day and night; thus, FCs can address PV’s incapacity during the night. However, voltage instability, frequency deviation, and enhanced harmonic distortion can result from the intrinsic intermittency of solar energy, switching errors in power electronic equipment, and varying load demands. Thus, a fuzzy logic-based current-controlled voltage source inverter (CC-VSI) is proposed in this paper to overcome these issues and enhance power quality in PV-FC hybrid microgrids. As per IEEE 1547 regulations, the fuzzy controller dynamically modifies the inverter current to maintain steady voltage and frequency profiles. MATLAB/Simulink (R2022a) is used to model and simulate the system, and its performance is evaluated under various reactive load scenarios. To test the efficacy of the proposed control technique, various power quality metrics, viz., voltage profiles (sag and swell), frequency profile, and total harmonic distortions, are plotted when subjected to large reactive load variations. The simulation results that are obtained with the proposed fuzzy-based current control technique are compared with the conventional artificial neural networks-based controller to verify the effectiveness. From the comparison study, it is found that the proposed technique shows superior power quality performance over the conventional technique. This encourages the development of renewable energy-based sustainable hybrid microgrids worldwide. Full article

Background: Carbazoles represent one of the most important classes of nitrogen-based tricyclic aromatic heterocycles and are present in natural sources and chemically obtained drugs. Recently, several research groups disclosed their large biological and chemical applications in different fields, leading to an increased interest towards this class of molecules. Some of the obtained derivatives have been successfully employed in the clinical treatment of different tumor types, but the onset of heavy side effects impaired their efficacy and discouraged their use. Pursuing the aim of obtaining carbazoles with less negative features, a lot of chemically modified compounds have been produced and evaluated. Objectives/Methods: In this paper, we describe the in vitro and in vivo evaluation of a bis-carbazole derivative with strong anticancer properties against two breast cancer cell lines. Results: This compound has been found to impact the cell cytoskeleton dynamics, triggering the activation of some key proteins playing a role in the intrinsic and extrinsic apoptotic pathways. Equally important, this derivative has been found to be selective for cancer cells and has shown a safe profile in Balb/c-treated mice. Conclusions: Overall, the disclosed outcomes represent an important landmark for encouraging further studies directed toward the potentiation of this lead to be potentially exploited in both preclinical and clinical applications. Full article

Polysaccharide-based hydrogels have emerged as indispensable materials in tissue engineering and wound healing, offering a unique combination of biocompatibility, biodegradability, and structural versatility. Indeed, their three-dimensional polymeric network and high water content closely resemble the natural extracellular matrix, creating a microenvironment for cell growth, differentiation, and tissue regeneration. Moreover, their intrinsic biodegradability, tunable chemical structure, non-toxicity, and minimal immunogenicity make them optimal candidates for prolonged drug delivery systems. Notwithstanding numerous advantages, these polysaccharide-based hydrogels are confronted with setbacks such as variability in material qualities depending on their source, susceptibility to microbial contamination, unregulated water absorption, inadequate mechanical strength, and unpredictable degradation patterns which limit their efficacy in real-world applications. This review summarizes recent advancements in the application of polysaccharide-based hydrogels, including cellulose, starch, pectin, zein, dextran, pullulan and hyaluronic acid as innovative solutions in wound healing, drug delivery, tissue engineering, and regenerative medicine. Future research should concentrate on optimizing hydrogel formulations to enhance their effectiveness in regenerative medicine and antimicrobial therapy. Full article

Hydrogen peroxide (H₂O₂) plays a crucial role in cell signaling in response to physiological and environmental perturbations. H₂O₂ can oxidize typical 2-Cys peroxiredoxin (PRX) first into a sulfenic acid, which resolves into a disulfide that can be reduced by thioredoxin (TRX)/TRX reductase (TR). At high levels, H₂O₂ can also hyperoxidize sulfenylated PRX into a sulfinic acid that can be reduced by sulfiredoxin (SRX). Therefore, PRX, TRX, TR, and SRX (abbreviated as PTRS system here) constitute the coupled sulfenylation and sulfinylation cycle (CSSC), where certain oxidized PRX and TRX forms also function as redox signaling intermediates. Earlier studies have revealed that the PTRS system is capable of rich signaling dynamics, including linearity, ultrasensitivity/switch-like response, nonmonotonicity, circadian oscillation, and possibly, bistability. However, the origins of ultrasensitivity, which is fundamentally required for redox signal amplification, have not been adequately characterized, and their roles in enabling complex nonlinear dynamics of the PTRS system remain to be determined. Through in-depth mathematical modeling analyses, here we revealed multiple sources of ultrasensitivity that are intrinsic to the CSSC, including zero-order kinetic cycles, multistep H₂O₂ signaling, and a mechanism arising from diminished H₂O₂ removal at high PRX hyperoxidation state. The CSSC, structurally a positive feedback loop, is capable of bistability under certain parameter conditions, which requires embedding multiple sources of ultrasensitivity identified. Forming a negative feedback loop with cytosolic SRX as previously observed in energetically active cells, the mitochondrial PTRS system (where PRX3 is expressed) can produce sustained circadian oscillations through supercritical Hopf bifurcations. In conclusion, our study provided novel quantitative insights into the dynamical complexity of the PTRS system and improved appreciation of intracellular redox signaling. Full article

When fabricating Si-based devices, many process steps require the use of expensive, high-power consumption, environmentally unfriendly, operator-unsafe machines, and processes. Among the many involved process steps, the ones needed to fabricate the metallurgical junction make use of conventional doping methods, which do not always represent optimal solutions. The high costs of the processing equipment and the use of hazardous materials, not to count the structural damage produced, intrinsically limit future developments towards nm-scaled and low cost approaches. Recently a chemistry-based method has been proposed to form the junction on Si, the so-called molecular doping. In this approach, the samples to be doped are subjected to a silylation process, during which a layer of dopant-containing molecules is deposited in a liquid bath kept at boiling temperature. After the coating, the samples are annealed to decompose the molecule and release the dopants inside the target. The peculiarity of using a liquid source allows for avoiding the structural damage. The entire doping procedure is simple and cost-effective, and it is based on the use of ester molecules, which are less harmful than the standard materials. In this work, we present experimental results on this chemistry-based technique, demonstrating its efficiency in creating the junction and demonstrate its feasibility in the fabrication of solar cells prototypes. Moreover, with respect to the literature, we show for the first time the effects of the protective layer presence over the dopant source molecules in the final solar cells electrical properties. As a proof of concept, we have numerically investigated the Si-based solar cell using the SCPAS-1D simulator. The finding claims that, the proposed samples have a good match in terms of the performance of the devices compared to the conventional Si-solar cells. Henceforth, the proposed work can provide a guideline to achieve less expensive, more environmentally friendly techniques for molecular doping in Si without affecting its performance in the metallurgical junction. Full article

Cancer cells must reprogram their metabolism to sustain rapid growth. This is accomplished in part by switching to aerobic glycolysis, uncoupling glucose from mitochondrial metabolism, and performing anaplerosis via alternative carbon sources to replenish intermediates of the tricarboxylic acid (TCA) cycle and sustain oxidative phosphorylation (OXPHOS). While this metabolic program produces adequate biosynthetic intermediates, reducing agents, ATP, and epigenetic remodeling cofactors necessary to sustain growth, it also produces large amounts of byproducts that can generate a hostile tumor microenvironment (TME) characterized by low pH, redox stress, and poor oxygenation. In recent years, the focus of cancer metabolic research has shifted from the regulation and utilization of cancer cell-intrinsic pathways to studying how the metabolic landscape of the tumor affects the anti-tumor immune response. Recent discoveries point to the role that secreted metabolites within the TME play in crosstalk between tumor cell types to promote tumorigenesis and hinder the anti-tumor immune response. In this review, we will explore how crosstalk between metabolites of cancer cells, immune cells, and stromal cells drives tumorigenesis and what effects the competition for resources and metabolic crosstalk has on immune cell function. Full article

Background/Objectives: Skin wrinkles result from a myriad of multifaceted processes involving intrinsic and extrinsic aging. To combat this effect, plant stem cells offer a renewable and eco-friendly source for various industries, including cosmeceuticals. Salvia miltiorrhiza (SM), which contains the bioactive compound Rosmarinic acid (RA) and has been proposed for its anti-wrinkle effect. Methods: In the present study, calli from SM were cultured and Quality by Design (QbD) was implemented to investigate the effect of different types and concentrations of elicitors; jasmonic acid (JA) and salicylic acid (SA). Both raised RA levels yet, jasmonic acid (50 µM) has resulted in the highest yield for RA, at 16 mg/g. A nanofiber patch was prepared and characterized in-vitro by the release percentage, drug content, swelling degree, scanning electron microscope, and surface roughness. Then, the anti-wrinkle effect of the patch was tested in a UV wrinkle-induced mouse model. Results: Interestingly, after treatment, there were visibly fewer wrinkles, and the skin was softer than in the untreated control group. This study suggests that the treatment exerted its effect through the Nrf2/Keap1 pathway, which plays a crucial role in cellular antioxidant protective processes. By activating this pathway through boosting Nrf2 and diminishing Keap1 cellular content, the nanofiber patch enhances the production of antioxidant enzymes, such as superoxide dismutase and glutathione peroxidase, enhancesglutathione, and reduces the skin lipid peroxidation, collectively indicating enhanced skin quality. Conclusions: In conclusion, this study highlights the importance of this formula as an anti-wrinkle treatment, and future clinical studies are recommended to further unveil the potential of this formula. Full article

Constructing artificial tertiary lymphoid structures (TLSs) opens new avenues for advancing cancer immunotherapy and personalized medicine by creating controllable immune niches. Mesenchymal stromal cells (MSCs) offer an ideal stromal source for such constructs, given their potent immunomodulatory abilities and accessibility. In this study, we explored the potential of adipose-derived MSCs to adopt TLS-supportive phenotypes and facilitate lymphocyte organization. Single-cell RNA sequencing revealed a distinct subpopulation of MSCs expressing key fibroblastic reticular cell (FRC)-associated markers, including IL-7, PDPN, and IL-15, though lacking follicular dendritic cell (FDC) markers. TNF-α stimulation, but not LTα2β1, further enhanced FRC marker expression (IL-7, PDPN, and ICAM1). Notably, in 3D spheroid co-culture with lymphocytes, MSCs upregulated additional FRC markers, specifically CCL21. Upon implantation into adipose tissue, MSC-lymphocyte organoids maintained structural integrity and showed extensive T-cell infiltration and partial vascularization after 15 days in vivo, although organized B-cell follicles and FDC markers were still lacking. These findings highlight MSCs’ intrinsic ability to adopt an FRC-like phenotype that supports T-cell and HEV organization, suggesting that further optimization, including genetic modification, may be needed to achieve an FDC phenotype and replicate the full architectural and functional complexity of TLSs. Full article

Aging is synonymous with the skin becoming increasingly thin and fragile, which is associated with a decrease in epidermal cell layers. Beyond this intrinsic aging process, the skin is continually exposed to environmental stressors such as UV radiation that accelerate aging. To fight the signs of aging, a comprehensive program was implemented in this study to evaluate the efficacy of an innovative ingredient, Willaertia lysate, through a multi-scale approach encompassing cellular and advanced 3D skin models. The results show that Willaertia lysate, initially sourced from French Alps thermal spring waters, is able to (i) promote cell migration; (ii) improve the quality and abundance of the extracellular matrix in aged skins and in young skins exposed to UV radiation to a similar level to that in unexposed young skins; (iii) decrease tyrosinase activity and melanin content; and (iv) reduce oxidative stress after UV exposure by decreasing exposome markers such as protein carbonylation and lipid peroxidation expression. This complete set of coherent results demonstrates the global protective efficacy of Willaertia lysate against the effects of photoaging. This study is the first to report the use of a protozoan lysate as a natural and biosourced postbiotic active ingredient in the fields of cosmetics and dermocosmetics. Full article

Mesenchymal stromal cells (MSCs) and their secretome show intrinsic antitumor properties, however, the anti-cancer effects of MSCs remain debated and depend on the cancer type or model. MSCs derived from discarded samples, such as human amniotic fluid (hAFSC), have been introduced as an attractive and potent stem cell source for clinical applications due to their collection procedures, which minimize ethical issues. Until now, various studies have obtained controversial results and poor understanding of the mechanisms behind the effects of perinatal cells on cancer cells. To better clarify this aspect, protein and miRNA expression profiling isolated from Extracellular vesicles (EVs) secreted by hAFSCs, obtained in the II or III trimester, were evaluated. Bioinformatic analysis was performed aiming at evaluating differential expression, pathway enrichment, and miRNA-mRNA networks. We highlighted that most of the highest expressed proteins and miRNAs are mainly involved in antioxidant and anti-cancer effects. Indeed, in the presence of hAFSC-EVs, a reduction of the G2/M phase was observed on melanoma cell lines, an activation of the apoptotic pathway occurred and the migration and invasion ability reduced. Our data demonstrated that II or III trimester hAFSCs can release bioactive factors into EVs, causing an efficient anti-cancer effect inhibiting melanoma progression. Full article

Gliomas are the most common primary brain tumors, representing approximately 28% of all central nervous system tumors. These tumors are characterized by rapid progression and show a median survival of approximately 18 months. The therapeutic options consist of surgical resection followed by radiotherapy and chemotherapy. Despite the multidisciplinary approach and the biomolecular role of targeted therapies, the median progression-free survival is approximately 6–8 months. The incomplete tumor compliance with treatment is due to several factors such as the presence of the blood–brain barrier, the numerous pathways involved in tumor transformation, and the presence of intra-tumoral mutations. Among these, the interaction between the mutations of genes involved in tumor bio-energetic metabolism and the functional response of the tumor has become the protagonist of numerous studies. In this scenario, the main role is played by mitochondria, cellular organelles delimited by a double membrane and containing their own DNA (mtDNA), which participates in numerous cellular processes such as the regulation of cellular metabolism, cellular proliferation, and apoptosis and is also the main source of cellular energy production. Therefore, it is understood that the mitochondrion, specifically its functional alteration, is a leading figure in tumor transformation, including brain tumors. The acquisition of mutations in the mitochondrial DNA of tumor cells and the subsequent identification of the so-called mitochondria-related genes (MRGs), both functional (mutation of Complex I) and structural (mutations of Complex III/IV), have been seen to play an important role in metabolic reprogramming with increased proliferation, resistance to apoptosis, and the progression of tumorigenesis. This demonstrates that these mitochondrial alterations could have a role not only in the intrinsic tumor biology but also in the extrinsic one associated with the therapeutic response. We aim to summarize the main mitochondrial dysfunction interactions present in gliomas and how they might impact prognosis. Full article

T cell receptor beta (TRB) sequences were recovered from the Cancer Genome Atlas Uveal Melanoma blood exome files. Intrinsic disorder scores for amino acid (AA) sequences of the entire TRB variable region were obtained and evaluated as potentially representative of overall survival (OS) distinctions, i.e., for cases representing the upper and lower 50th percentiles for intrinsic disorder scores. Analyses using four intrinsic disorder assessment tools indicated that a lower intrinsic disorder of the blood-sourced TRB variable regions, including continuous AA sequences of the V-gene segment, the complementarity-determining region-3, and the J-gene segment, was associated with a better OS probability (with log-rank p-values ranging from 0.002 to 0.014). We further determined that intrinsic disorder assessments could be used for OS stratification for a second, immunologically cold cancer: MYCN amplified neuroblastoma. Thus, intrinsic disorder assessments of blood-sourced, full TRB variable regions may provide a novel patient stratification approach for patients with immunologically cold cancers. Full article