Search Results (38)

Epithelial–mesenchymal transition (EMT) is a key process in cancer progression and fibrogenesis. In this study, EMT was induced in Huh7 hepatocellular carcinoma cells via TGF-β1 treatment, and the resulting lipidomic and metabolomic alterations were characterized. Morphological changes and protein marker analyses confirmed the transition to a mesenchymal phenotype, with reduced E-cadherin and increased vimentin and N-cadherin expression. Lipidomic profiling revealed a dose-dependent reorganization of membrane lipids, with a pronounced increase in the levels of ceramides, cholesteryl esters, and lysophospholipids, consistent with alterations in membrane structure, potential cellular stress, and modulation of inflammatory pathways. Changes in the content of phospholipid classes, including phosphatidylethanolamines and phosphatidylserines, indicate possible variations in membrane dynamics and potentially point to modifications in mitochondrial function, cellular stress responses, and redox balance. Metabolomic analysis further indicates an alteration of choline and phosphatidylcholine metabolism, consistent with a shift from de novo membrane synthesis toward lipid turnover. Reduced glycolytic capacity and modified acylcarnitine levels indicated impaired metabolic flexibility and mitochondrial efficiency. The integration of phenotypic, lipidomic, and metabolomic data suggests that TGF-β1 induces EMT and drives a coordinated metabolic reprogramming. These findings highlight the involvement of lipid and energy metabolism in sustaining EMT and suggest that specific metabolic reprogramming events characterize the mesenchymal shift in hepatocellular carcinoma. By exploring this process in a tumor-specific context, we aim to deepen our understanding of EMT complexity and its implications for tumor progression and therapeutic vulnerability. Full article

Background: Perfectionism is a growing concern among university students, who face high expectations, demanding workloads, and complex academic tasks. These pressures often lead to stress, negatively impacting performance, well-being, and career trajectories. Existing measures of perfectionism and related stress lack focus on their causes and relevance to students. Methods: This study developed and psychometrically tested an inventory assessing the causes (ROOTS), manifestations (MPS-R), and stress (IPSS-R) related to perfectionism. A multicenter cross-sectional online survey was conducted across multiple Italian universities with 469 students. The ROOTS tool was developed, and the MPS and IPSS were adapted following established guidelines. Content validity was examined, and pilot testing was performed. Confirmatory factor analyses tested three-factor models with a second-order factor for each instrument. Construct validity and reliability were also assessed. Results: The ROOTS, MPS-R, and IPSS-R demonstrated strong structural and construct validity, with acceptable reliability. Significant correlations highlighted the interconnectedness of perfectionism’s causes, manifestations, and stress. Conclusions: The Perfectionism Inventory offers a comprehensive tool for identifying causes, manifestations, and consequences of perfectionism in university students. It can help educators and policymakers develop strategies to mitigate its impact on mental health and academic success. Future research should explore its applicability in other populations. Full article

Sphingomyelin is a crucial molecule in the sphingolipid metabolic pathway, and its action is closely related to that of vitamin D3. Both molecules are recognized for their involvement in brain pathophysiology. In this study, the effect of a sphingomyelin + vitamin D3-enriched diet was investigated in rabbits. The results showed a strong immunopositive GFAP staining in the brain’s white matter. Furthermore, a remodeling of the balance between glycero-phospholipids and ether-phospholipids was observed in the brain, along with an increase in ceramides and hexose ceramides, molecules relevant for the structure, function, and stability of myelin. Taken together, these findings provide clues as to how the combination sphingomyelin + vitamin D3 may play a vital role in normal brain physiology and could potentially be leveraged in the context of neurodegenerative diseases. Full article

Background: Oral and implant surgery represent highly specialized fields within dentistry that require a deep understanding of complex anatomical structures, together with practical hands-on experience. The present review examines common trends in oral and implant surgery training, focusing on how traditional methods like donated body dissection coexist with different and modern educational tools, and highlights the pros and cons of the different approaches in order to optimize training outcomes. Methods: A systematic literature search was carried out using the databases PubMed and Cochrane Library including the last 10 years of published articles about training in oral surgery and implantology. Starting from a total of 1319 studies, 47 were included to be carefully evaluated, and 20 studies were finally selected for this narrative review. The studies utilize methodologies such as randomized controlled trials (RCTs), cross-sectional surveys, case–control studies, and systematic reviews. The results were thematically organized, highlighting key quantitative outcomes and drawing connections between the different educational approaches. Results: From the narrative review, it emerged that oral and implant surgery training requires a careful balance between traditional methods, such as donated human body dissection, and modern technological advancements like virtual simulations and synthetic models. While animal and synthetic models have specific uses, their application remains limited in replicating the full complexity of human anatomy. These last technologies offer flexibility and expanded access to education but do not substitute for the hands-on experience gained through donated human body dissection. Conclusions: As educational institutions continue to evolve their training programs, ensuring access to human body dissection remains of paramount importance. Combining the strengths of both traditional and modern approaches may help optimize oral and implant surgery education, enhancing student preparedness without overlooking the critical value of direct anatomical experience. Full article

Background: Ustekinumab (UST) is an interleukin-12/interleukin-23 receptor antagonist approved for the treatment of Crohn’s disease (CD). Only limited real-life data on the long-term outcomes of CD patients treated with UST are available. This study assessed UST’s long-term effectiveness and safety in a large population-based cohort of moderate to severe CD patients. Methods: This was a multicenter, retrospective, observational cohort study that included both naïve and biologic-experienced patients treated with UST who achieved clinical remission or clinical response after at least one year of treatment. Clinical activity was scored according to the Harvey–Bradshaw Index (HBI). The primary endpoints were the maintenance or achievement of clinical remission after a further 12-month period of treatment, defined as an HBI of ≤5, and safety. Other endpoints included steroid-free remission, mucosal healing (MH), steroid discontinuation, and the need for treatment optimization during the follow-up. Results: Out of 562 CD patients, after an overall 24-month follow-up, clinical remission was present in 450 (80.0%) patients, and at 12 months, clinical remission was observed in 417/437 (95.4%) patients; 33/125 (26.4%) showed clinical response at 12 months (p = 0.000). A total of 38/103 (36.9%) patients achieved MH. Only 2.1% (12/562), 3% (17/562), and 1.1% (6/562) of patients required surgery, optimization, and re-induction, respectively. Adverse events occurred in eight patients (1.42%). According to a multivariate analysis, the only predictor of long-term remission was the presence of remission at the 12-month follow-up (p = 0.000). Conclusions: Long-term treatment with UST presents good efficacy and safety profiles in CD patients, especially for patients who achieve remission after one year. Full article

Background: The malar bone provides an anchorage point for zygomatic implants, avoiding invasive reconstructive surgeries in the fixed rehabilitation of fully edentulous and severely atrophic maxillae. The limited bone volume, however, requires precise implant placement to prevent complications related to nearby anatomical structures. This observational cross-sectional study aims to measure the malar and zygomatic arch bones and their distances from critical anatomical landmarks to guide surgeons in safe zygomatic implant placement. Methods: Dissections were performed bilaterally on 29 heads from human donated bodies in a cross-sectional observational study. Key landmarks evaluated include the infraorbital foramen (IF), pyriform nasal aperture (PNA), infraorbital margin (IM), zygomaticofacial foramen (ZFF), anterior end (A), and the most protruding point of the zygomatic arch (B). Measurements included IF-PNA, IF-IM, IF-ZFF, ZFF-IM, A-B, and orbital floor depth (OFD). Results: Significant findings showed IF-PNA was greater in males (18.66 ± 2.63 mm, p = 0.001), and IF-ZFF varied between sides (26.72 ± 8.7 mm, p = 0.002). ZFF-IM was larger in males (7.43 ± 2.09 mm, p < 0.001). Heights and thicknesses were also assessed, with significant side differences observed. Conclusions: These findings underscore the importance of understanding precise anatomical distances for successful implant placement. The study provides essential data to enhance surgical planning and training, ensuring safer procedures and minimizing the risk of complications. Full article

The growing interest in plant-origin active molecules with medicinal properties has led to a revaluation of plants in the pharmaceutical field. Plant-derived extracellular vesicles (PDEVs) have emerged as promising candidates for next-generation drug delivery systems due to their ability to concentrate and deliver a plethora of bioactive molecules. These bilayer membranous vesicles, whose diameter ranges from 30 to 1000 nm, are released by different cell types and play a crucial role in cross-kingdom communication between plants and humans. Notably, PDEVs have demonstrated efficacy in treating various diseases, including cancer, alcoholic liver disease, and inflammatory bowel disease. However, further research on plant vesicles is necessary to fully understand their traits and purposes. This study investigates the phototoxic effects of extracellular vesicles (EVs) from Aloe arborescens, Aloe barbadensis, and Aloe chinensis on the human melanoma cell line SK-MEL-5, focusing on their anthraquinone content, recognized as natural photosensitizers. The phototoxic impact of Aloe EVs is associated with ROS production, leading to significant oxidative stress in melanoma cells, as validated by a metabolome analysis. These findings suggest that EVs from Aloe arborescens, Aloe barbadensis, and Aloe chinensis hold promise as potential photosensitizers, thus highlighting their potential for future application in photodynamic cancer therapy and providing valuable insights into the possible utilization of PDEVs for therapeutic purposes. Full article

Clostridioides difficile (C. difficile) is responsible for a spectrum of nosocomial/antibiotic-associated gastrointestinal diseases that are increasing in global incidence and mortality rates. The C. difficile pathogenesis is due to toxin A and B (TcdA/TcdB), both causing cytopathic and cytotoxic effects and inflammation. Recently, we demonstrated that TcdB induces cytopathic and cytotoxic (apoptosis and necrosis) effects in enteric glial cells (EGCs) in a dose/time-dependent manner and described the underlying signaling. Despite the role played by lipids in host processes activated by pathogens, to counter infection and/or induce cell death, to date no studies have investigated lipid changes induced by TcdB/TcdA. Here, we evaluated the modification of lipid composition in our in vitro model of TcdB infection. Apoptosis, cell cycle, cell viability, and lipidomic profiles were evaluated in EGCs treated for 24 h with two concentrations of TcdB (0.1 ng/mL; 10 ng/mL). In EGCs treated with the highest concentration of TcdB, not only an increased content of total lipids was observed, but also lipidome changes, allowing the separation of TcdB-treated cells and controls into different clusters. The statistical analyses also allowed us to ascertain which lipid classes and lipid molecular species determine the clusterization. Changes in lipid species containing inositol as polar head and plasmalogen phosphatidylethanolamine emerged as key indicators of altered lipid metabolism in TcdB-treated EGCs. These results not only provide a picture of the phospholipid profile changes but also give information regarding the lipid metabolism pathways altered by TcdB, and this might represent an important step for developing strategies against C. difficile infection. Full article

Extracellular vesicles (EVs) can be isolated from biological fluids and cell culture medium. Their nanometric dimension, relative stability, and biocompatibility have raised considerable interest for their therapeutic use as delivery vehicles of macromolecules, namely nucleic acids and proteins. Deficiency in lysosomal enzymes and associated proteins is at the basis of a group of genetic diseases known as lysosomal storage disorders (LSDs), characterized by the accumulation of undigested substrates into lysosomes. Among them, GM2 gangliosidoses are due to a deficiency in the activity of lysosomal enzyme β-hexosaminidase, leading to the accumulation of the GM2 ganglioside and severe neurological symptoms. Current therapeutic approaches, including enzyme replacement therapy (ERT), have proven unable to significantly treat these conditions. Here, we provide evidence that the lysosomal β-hexosaminidase enzyme is associated with EVs released by HEK cells and that the EV-associated activity can be increased by overexpressing the α-subunit of β-hexosaminidase. The delivery of EVs to β-hexosaminidase-deficient fibroblasts results in a partial cross-correction of the enzymatic defect. Overall findings indicate that EVs could be a source of β-hexosaminidase that is potentially exploitable for developing therapeutic approaches for currently untreatable LSDs. Full article

T-cell acute lymphoblastic leukemia (T-ALL) is an aggressive tumor mainly affecting children and adolescents. It is driven by multiple genetic mutations that together define the leukemic phenotype. Interestingly, based on genetic alterations and/or deregulated expression, at least six genetic subgroups have been recognized. The TAL/LMO subgroup is one of the most represented genetic subgroups, characterizing 30–45% of pediatric T-ALL cases. The study of lipid and metabolic profiles is increasingly recognized as a valuable tool for comprehending the development and progression of tumors. In this study, metabolic and lipidomic analysis via LC/MS have been carried out on four T-ALL cell lines belonging to the TAL/LMO subgroup (Jurkat, Molt-4, Molt-16, and CCRF-CEM) to identify new potential metabolic biomarkers and to provide a subclassification of T-ALL cell lines belonging to the same subgroup. A total of 343 metabolites were annotated, including 126 polar metabolites and 217 lipid molecules. The statistical analysis, for both metabolic and lipid profiles, shows significant differences and similarities among the four cell lines. The Molt-4 cell line is the most distant cell line and CCRF-CEM shows a high activity in specific pathways when compared to the other cell lines, while Molt-16 and Jurkat show a similar metabolic profile. Additionally, this study highlighted the pathways that differ in each cell line and the possible enzymes involved using bioinformatic tools, capable of predicting the pathways involved by studying the differences in the metabolic profiles. This experiment offers an approach to differentiate T-ALL cell lines and could open the way to verify and confirm the obtained results directly in patients. Full article

Edible plant and fruit-derived nanovesicles (NVs) are membrane-enclosed particles with round-shape morphology and signaling functions, which resemble mammalian cell-derived extracellular vesicles. These NVs can transmit cross-kingdom signals as they contain bioactive molecules and exert biological effects on mammalian cells. Their properties and stability in the gastrointestinal tract suggest NVs as a promising nutraceutical tool. In this study, we have demonstrated for the first time the presence of NVs in olive vegetation water (OVW), a waste by-product generated during olive oil production. Biophysical characterization by scanning electron microscopy, cryo-transmission electron microscopy, and nanoparticle tracking analysis revealed the presence in OVW of NVs having size and morphology similar to that of vesicles isolated from edible plants. Integrated lipidomic, metabolomic, and proteomic analyses showed that OVW-NVs carry a set of lipids, metabolites and proteins which have recognized antioxidant and anti-inflammatory activities. The nature of biomolecules identified in OVW-NVs suggests that these vesicles could exert beneficial effects on mammalian cells and could be used in the nutraceutical and food industries. The successful isolation of OVW-NVs and the characterization of their features strengthen the idea that agricultural waste might represent a source of NVs having features similar to NVs isolated from edible plants/fruits. Full article

Background and Aims: The COVID-19 pandemic, caused by the novel coronavirus SARS-CoV-2, has fundamentally reshaped the landscape of global public health, with some people suffering more adverse clinical outcomes than others. The aim of this study is to deepen our understanding of the specific impact of acute kidney injury (AKI) on the in-hospital mortality in octogenarian patients with COVID-19. Methods: This is a prospective observational cohort study, which involved 23 COVID-19 hospital units in the Campania Region, Italy. Exposure variables were collected during hospital admission and at discharge. Only patients aged ≥80 years were deemed eligible for the study. Results: 197 patients were included in the study (median age 83.0 [82.0–87.0] years; 51.5% men), with a median duration of hospitalization of 15.0 [8.0–25.0] days. From the multivariable Cox regression analysis, after the application of Šidák correction, only the respiratory rate (HR 1.09, 95% CI: 1.04 to 1.14; p < 0.001) and AKI development (HR: 3.40, 95% CI: 1.80 to 6.40; p < 0.001) were independently associated with the primary outcome. Moreover, the Kaplan–Meier analysis showed a significantly different risk of in-hospital mortality between patients with and without AKI (log-rank: <0.0001). Conclusions: In our investigation, we identified a significant association between AKI and mortality rates among octogenarian patients admitted for COVID-19. These findings raise notable concerns and emphasize the imperative for vigilant monitoring of this demographic cohort. Full article

Krabbe disease is a rare neurodegenerative disease with an autosomal recessive character caused by a mutation in the GALC gene. The mutation leads to an accumulation of psychosine and a subsequent degeneration of oligodendrocytes and Schwann cells. Psychosine is the main biomarker of the disease. The Twitcher mouse is the most commonly used animal model to study Krabbe disease. Although there are many references to this model in the literature, the lipidomic study of nervous system tissues in the Twitcher model has received little attention. This study focuses on the comparison of the lipid profiles of four nervous system tissues (brain, cerebellum, spinal cord, and sciatic nerve) in the Twitcher mouse compared to the wild-type mouse. Altogether, approximately 230 molecular species belonging to 19 lipid classes were annotated and quantified. A comparison at the levels of class, molecular species, and lipid building blocks showed significant differences between the two groups, particularly in the sciatic nerve. The in-depth study of the lipid phenotype made it possible to hypothesize the genes and enzymes involved in the changes. The integration of metabolic data with genetic data may be useful from a systems biology perspective to gain a better understanding of the molecular basis of the disease. Full article

The beech mushroom (Hypsizygus marmoreus) is a highly nutritious, edible medicinal mushroom native to East Asia. The present research investigated the impact of different substrates on the metabolite compositions of H. marmoreus mycelia cultivated in vitro. The substrates tested included malt extract agar, malt extract agar enriched with barley malt, and malt extract agar enriched with grape pomace. The study also assessed antimicrobial and antiradical activities of the extracts against gram-positive bacteria (Bacillus subtilis and Staphylococcus aureus), gram-negative bacteria (Escherichia coli, Salmonella typhi, and Pseudomonas aeruginosa), yeasts (Candida albicans, C. tropicalis, and C. parapsilosis), and dermatophytes (Trichophyton mentagrophytes, T. tonsurans, T. rubrum, Arthroderma quadrifidum, A. gypseum, A. curreyi, and A. insingulare). The results revealed that the H. marmoreus mycelia extracts demonstrated antibacterial and antifungal activities against the tested microorganisms. Extracts obtained from the cultivation in substrates enriched with either barley malt or grape pomace exhibited the highest antibacterial activity among all the tested bacterial strains except for P. aeruginosa. The same extracts showed the highest inhibitory effect against C. albicans and C. parapsilosis. Noteworthy, the extract from the mushroom cultivated in the substrate enriched with grape pomace also exhibited remarkable efficacy against T. mentagrophytes and T. tonsurans. Terpenoid and carbapenem compounds could be related to the antimicrobial properties of the extracts from mushrooms cultivated in substrates enriched with grape pomace. In comparison, the higher antiradical properties could be related to the content of indole compounds. In conclusion, growth substrate selection affects the nutritional and medicinal properties of H. marmoreus, making it a valuable contribution to the understanding of the cultivation of this mushroom. Full article

The pet food market is constantly expanding, and more and more attention is paid to the feeding of pets. Dry foods stand out and are often preferred due to their long shelf life, ease of administration, and low cost. In this context, dry foods are formulated from fresh meats, meat meals, or a mix of the two. These raw materials are often meat not fit for human consumption; they might be subject to contamination and proliferation of microorganisms which, by degrading the organic component, can lead to the formation of undesirable by-products such as biogenic amines. These nitrogenous compounds obtained by decarboxylation of amino acids can therefore be found in high-protein foods, and their ingestion in large quantities can cause intoxication and be harmful. This study aims at analyzing the possible presence of biogenic amines in three different formulations of chicken-based kibbles for pets: one obtained from fresh meat, one from meat meal, and one from a mix of the two. This study is also focused on the presence of free amino acids as they represent the key substrate for decarboxylating enzymes. Mass spectrometry (Q-TOF LC/MS) was used to analyze the presence of biogenic amines and free amino acids. The results show that fresh-meat-based products have a lower content of biogenic amines, and at the same time a higher quantity of free amino acids; on the contrary, meat-meal- and mix-based products have a greater quantity of biogenic amines and a lower concentration of free amino acids, suggesting that there has been a higher microbial proliferation as proved by the total aerobic mesophilic bacteria counts. It is therefore clear that fresh-meat-based kibbles are to be preferred when they are used for preparing dry pet food due to the lowest concentration of biogenic amines. Full article