Psoriasis is a chronic inflammatory skin disease characterized by keratinocyte hyperproliferation and excessive immune activation, for which curative therapies remain limited. This study aimed to investigate the role of small proline-rich protein 2B (SPRR2B) in psoriasis pathogenesis. In this study, gene Expression Omnibus (GEO) dataset GSE13355 was analyzed using R Language. Cell proliferation, gene and protein expression were measured with CCK8, RT-qPCR and immunofluorescence staining, respectively. Bioinformatics analysis of the GSE13355 dataset revealed that SPRR2B was significantly overexpressed in psoriatic lesions and was positively correlated with immune cell infiltration and multiple inflammatory pathways. In an M5-induced HaCaT keratinocyte psoriatic model, SPRR2B knockdown markedly suppressed cell proliferation and promoted apoptosis via regulation of the MDM2/p53/CDKN1A axis. Furthermore, SPRR2B knockdown reduced the secretion of IL-6, IFN-γ, TNF-α, and IL-1β, and inhibited JAK1 phosphorylation. These findings demonstrated that SPRR2B promotes keratinocyte proliferation and inflammatory response in psoriasis, suggesting it may serve as a promising diagnostic biomarker and therapeutic target for the disease.
Prostate cancer (PCa) is a common malignancy in men with limited therapeutic options at advanced stages. Statins, widely prescribed lipid-lowering agents, have demonstrated antitumor activity in PCa, but underlying mechanisms are not fully understood. Studies suggested that tumor progression is facilitated upon activation of mevalonate (MVA) pathway, while it is reduced via MVA pathway inhibition–induced ferroptosis. Therefore, this study aimed to determine whether lovastatin suppresses prostate cancer progression by inducing ferroptosis through inhibition of the MVA pathway. Five clinically used statins were screened in prostate cancer cell lines to identify the most effective compound. Cell proliferation, migration, and invasion were assessed. Ferroptosis was evaluated by measuring intracellular Fe2+ and reactive oxygen species (ROS) levels, mitochondrial membrane potential, ferroptosis-related protein expression, and ultrastructural mitochondrial alterations. Rescue experiments were performed using the ferroptosis inhibitor deferoxamine and MVA supplementation. Lovastatin exhibited the strongest inhibitory effect, significantly reducing proliferation, migration, and invasion. Lovastatin significantly suppressing PCa cell aggressiveness and inducing ferroptosis, as evidenced by typical biochemical and morphological markers, all of which were reversed by deferoxamine. MVA supplementation restored cell viability, normalized oxidative stress and iron levels, and reversed alterations in MVA pathway enzymes and ferroptosis-associated proteins. Lovastatin suppresses prostate cancer cell growth and invasiveness by inhibiting the MVA pathway and inducing ferroptosis, highlighting the MVA-ferroptosis axis as a potential therapeutic target for PCa.
Colorectal cancer (CRC) is a prevalent malignancy with a complex genetic basis. Recent genome-wide association studies (GWAS) have identified a susceptibility locus at 3p21.31, however, the functional SNP(s) underlying the association between the 3p21.31 region and CRC remain to be elucidated. In this study, we identified rs2101247 as the potential functional SNP and further demonstrated that rs2101247 is significantly associated with the expression of the nearby long non-coding RNA (lncRNA) RP11-708J19.2 (ENSG00000271161.1). Functional experiments showed that RP11-708J19.2 is upregulated in CRC tumor tissues, and its knockdown reduces cell viability while promoting apoptosis in SW1116 and HCT116 cell lines. Mechanistically, RP11-708J19.2 interacts directly with the deacetylase SIRT7, modulating histone H3K18 acetylation (H3K18ac). Specifically, RP11-708J19.2 knockdown leads to a significant upregulation of H3K18ac levels, implicating a SIRT7-mediated epigenetic pathway in CRC progression. Our findings elucidate a novel functional SNP-lncRNA axis that contributes to CRC pathogenesis, providing potential biomarkers for early detection and therapeutic targets for intervention.
The effect of thyroid hormones (TH) on metabolism and energy balance relies on their impact on lipid storage in adipose tissue (AT). Since peroxisomes play a key role in lipid metabolism in white AT, hypothyroidism may critically influence peroxisome population/dynamics. This study aimed to determine depot- and time-dependent effects of methimazole-induced hypothyroidism on peroxisome biogenesis and remodeling in rat white AT. Hypothyroidism was induced using 0.04% methimazole over 7, 15, or 21 days. We show that hypothyroidism affects peroxisome biogenesis in subcutaneous AT (SAT) and visceral AT (VAT) (mesenteric-mVAT, retroperitoneal-rVAT and gonadal-gVAT) in a depot-specific manner. Firstly, although a gradual increase in peroxisomal number is present in all of the AT depots examined, the time course differs. Secondly, according to ultrastructural and protein expression analyses of Pex11β, Pex19, and PPARα, biogenesis pathways are switching from canonical to de novo pathway in hypothyroidism, again distinctively across particular depots. Furthermore, this is accompanied by the emergence of unusual peroxisomal structures (pexopodium) infiltrating lipid bodies in VAT. The absence of acyl-coenzyme A oxidase 1 (ACOX1) suggests that such structures may develop as a consequence of uncoordinated oxidation of accumulated fatty acids in VAT. The presence of pexopodium was increased from day 15 of hypothyroidism in mVAT. However, this increase was transient in rVAT and gVAT, indicating different peroxisomal dynamics between VAT depots during the monitored period of induction. Pexopodium-like structures were not observed in SAT. Our results identify peroxisomal remodeling as a previously underappreciated component of adipose tissue plasticity in hypothyroidism. Discrete temporal and depot-specific responses, including the formation of pexopodia in VAT, underscore the functional heterogeneity of white AT depots and suggest that peroxisomal dynamics may contribute to regional metabolic vulnerability under thyroid hormone deficiency over the time.
Alexander’s disease (AxD) is a rare neurodegenerative disorder of astrocytes caused by mutations in the GFAP gene, leading to the formation of protein aggregates (Rosenthal fibers) and severe neurological dysfunction, including myelin disruption. This study focuses on the R239C mutation, using zebrafish as a model organism in which the human mutation was genetically introduced [1,2]. The aim was to investigate glutamate and GABA release and uptake using isolated synaptosomal and gliosomal preparations. The results show an alteration in glutamate and GABA neurotransmission, suggesting a potential role of this mechanism in the pathogenesis of the disease.To better understand disease progression, we studied neurodegeneration by using isotropic fractionator combined with NeuN and DAPI staining to quantify neuronal and glial cell populations. These analyses aimed to determine whether zebrafish carrying the mutation exhibit alterations in the number of neurons and glial cells compared to controls. Furthermore, using a transgenic line for mpeg, neuroinflammation was assessed by comparing microglial cell numbers between control and R239C mutant lines. Our analyses show that the mutation leads to a progressive increase in neuroinflammation during development, followed by neuronal cell death and impaired neurotransmission, with the most pronounced effects observed in adulthood. These cellular alterations are also reflected at the metabolic level, as evidenced by changes in the production of specific lipids involved in myelin formation and in the sulfur metabolism. Our study clearly demonstrates the usefulness of the zebrafish model for better understanding the pathogenesis of AxD and highlights its potential for future drug screening studies. Acknowledgements: We gratefully acknowledge the Italian Alexander Syndrome Association “Più Unici che Rari”.
2D cultures poorly model tissue complexity. This study aims to develop a patient-iPSC-derived 3D model of the central nervous system - integrating neuronal and immune components - to study neurodegenerative diseases, specifically amyotrophic lateral sclerosis (ALS). ALS patients and healthy control fibroblasts were reprogrammed into iPSCs to generate liquid-cultured brain organoids (BOs), maintained for 50, 70, 80 and 100 days. To improve model complexity, BOs were stimulated with specific growth factors to induce oligodendrocytes differentiation. Microglial cells (generated from matched patient-derived iPSCs) were integrated. Morphometric analysis showed regular growth of both CTRL and ALS BOs over time, suggesting morphological stability. Immunofluorescence and gene expression analyses confirmed correct neuronal differentiation and spatial organization in both groups. Motor neurons and oligodendrocytes were detected. Microglia were effectively integrated into both CTRL and ALS BOs, displaying an amoeboid morphology in the latter group, suggesting a more activated state compared with CTRL BOs. This study establishes an optimized protocol for modeling a 3D platform suitable for investigating ALS. Acknowledgements: Funded by the European Union – Next Generation EU – PNRR M6C2 – Investment 2.1 Enhancement and strengthening of biomedical research in the National Health Service – project PNRR-MCNT2-2023-12377338 – [PI: Ornella Parolini; Co-PI: Mario Sabatelli] – CUP: C53C23001090007.
Echinoderms have always been an important resource for fisheries and aquaculture. More recently, growing interest in the study of natural products and their potential pharmacological applications led researchers to consider them a valuable source of bioactive compounds. Many echinoderm species have been shown to possess endogenous compounds exerting a wide range of biological activities. Of particular interest are recent findings regarding the ability of certain sea urchin pigments to exert significant bioactivity. Echinochrome A, a polyhydroxylated naphthoquinone pigment, has gained interest due to its promising antioxidant properties and potential therapeutic applications. The present study aimed to evaluate the toxicological and antioxidant activity of echinochrome extracted from the sea urchin Arbacia lixula using zebrafish as experimental model. Zebrafish embryos were exposed to different concentrations of A. lixula echinochrome and monitored throughout larval development until the 5 days post-fertilization. For the toxicological evaluation mortality and hatching rate, morphometric parameters, heart rate frequency, and behavioural alterations in larvae were analyzed. The antioxidant potential of echinochrome was investigated by experimentally inducing oxidative stress and evaluating the response by analysing the expression variations of SOD-1 through qRT-PCR, providing insights into the compound’s role in modulating cellular defence mechanisms. A. lixula echinochrome act on zebrafish early development in a concentration-dependent effect, with higher doses showing increased mortality rates and occurrence of sub-lethal malformations. On the other hand, A. lixula echinochrome-treated embryos exhibited a modulation of SOD-1 expression under oxidative stress conditions, coherent with a protective antioxidant effect. Given the emerging importance of echinochrome’s potential ecotoxicological and pharmacological applications, our basic characterization in the zebrafish model represents a crucial step to move forward.
Glioblastoma multiforme (GBM) is the most aggressive primary brain tumor in adults, characterized by marked molecular heterogeneity and rapid progression. Therefore, the identification of predictive biomarkers and novel therapeutic targets remains a major challenge. Among emerging regulatory mechanisms, microRNAs (miRNAs) and the ubiquitin–proteasome system have been increasingly implicated in glioma biology, playing key roles in tumor progression and therapy resistance. Based on these premises, this study aimed to identify novel prognostic biomarkers in GBM, focusing on miRNAs expression and activity. By small RNAseq analysis on paired primary and relapsed GBM tissues, we identified a subset of differentially expressed miRNAs associated to recurrence. Among these, miR-129-5p emerged as a candidate of interest, being predicted to regulate both MEX3A and RNF182, two E3 ubiquitin ligases which have been found to be deregulated in gliomas. We confirm that miR-129-5p overexpression is able to reduce MEX3A and RNF182 expression in U87MG cells. We also observed that miR-129-5p overexpression induced an impairment of cell proliferation, and the acquisition of a differentiated phenotype. Taken together, these data suggest miRNA–E3 ligase crosstalk as a previously underexplored regulatory network in GBM progression, nominating miR-129-5p as a putative prognostic biomarker and potential therapeutic target. Ongoing studies in advanced preclinical systems, including patient-derived cell models, will further refine the functional relevance of such miRNA/E3 ligase axis and its translational potential for GBM management. Acknowledgements: This work was supported by National Recovery and Resilience Plan (NRRP), Mission 6/C2 CALL 2023 Section: Tumori Rari. code: PNRR-TR1-2023-12377378
The coordinated interplay between mitophagy and the epithelial–mesenchymal transition (EMT) is essential for tumor adaptation, survival, and metastasis, enabling dynamic shifts between stationary and migratory states, evasion of therapeutic stress, and the acquisition of stem-like traits through mitochondrial quality control and energy regulation. Medulloblastoma is the most common malignant pediatric brain tumor and is classified into four molecular and clinical subgroups, among which Group 3 represents the most aggressive subtype, characterized by a high metastatic propensity and poor prognosis. Metastatic dissemination in MB is tightly associated with EMT; however, the role of mitophagy and the molecular mechanisms linking EMT and mitophagy remain poorly understood. Here, we identify an E3 ubiquitin ligase as a negative regulator of both mitophagy and EMT in MB. Its depletion enhances these processes and is accompanied by modulation of EMT markers, including ZEB1, as well as key mitophagy drivers, suggesting that this protein coordinates mitochondrial quality control with EMT-associated transcriptional programs. Collectively, our findings identify this protein as a previously unrecognized tumor suppressor that functionally links EMT and mitophagy, providing novel insight into the mechanisms underlying tumor cell plasticity and highlighting this crosstalk as a clinically relevant and potentially targetable vulnerability in aggressive disease.
The contamination of freshwater ecosystems by nanoplastics (NPs) is a growing concern, yet the eco-immunological responses of freshwater invertebrates remain largely unexplored. We characterized the short-term fate and immunological impact of fluorescently labelled Polyethylene terephthalate (PET)-NPs (Nile Red, mean diameter 82 nm) in the eco-immunological model Pomacea canaliculata, a freshwater snail with remarkable physiological resilience and a well-characterised innate immune system. Animals were injected in foot with 5 or 10 mg/L PET-NPs and sacrificed at 24 or 72 hours post-injection (hpi). Fluorescence microscopy on cryosections revealed rapid PET-NPs accumulation in both kidneys, persisting up to 72 hpi independently of dose. Despite clear particle accumulation, histological examination showed no signs of tissue damage. Transcriptional analysis of stress (Pc-HSP70, Pc-HSP90) and immune (Pc-AIF1) markers revealed no organ-specific modulations, with downregulation at 72 hpi in the lower dose group. Circulating hemocytes from injected animals showed internalized PET-NPs in both adherent cells displaying pseudopodia and smaller, round hemocytes. Intercellular particle transfer via cytoplasmic protrusions was also observed, as reported in other mollusks. Ex vivo phagocytosis experiments confirmed a positive correlation between PET-NP concentration and phagocytic activity, significantly reduced by anticoagulant treatment, supporting active NPs internalization. These findings indicate that P. canaliculata rapidly sequesters PET-NPs in immune-associated tissues through hemocyte-mediated mechanisms, with limited short-term physiological impact. This study promotes P. canaliculata as a resilient model for eco-immunological research on NPs and lays the groundwork for future investigations into chronic exposure and immune modulation. Acknowledgements: This work was supported by the PRIN (PNRR) project NANOPIN, Mission 4 cod. 2022SAHTRX – CUP E53D23007600006.
The invasive alien seaweed Caulerpa racemosa, which belongs to the Chlorophyta group, poses a serious threat to Mediterranean Sea ecosystems by disrupting native algal biodiversity and having toxic effects on aquatic organisms. This study analysed the effects of this species on the Mediterranean mussel Mytilus galloprovincialis, a sessile, filter-feeding organism, with the aim of understanding the biological and structural responses induced by exposure to the seaweed. Histological techniques were employed to evaluate the mussel’s tissue response to increasing concentrations of C. racemosa. The results revealed a state of multisystemic distress, particularly affecting the gills, digestive gland, and mantle. Significant structural alterations were observed in the gills, including changes in epithelial thickness and the presence of lipofuscin granules, indicative of degenerative processes and cellular stress. Similarly, the digestive gland exhibited marked cellular disorganisation, while cell hypertrophy was detected in the mantle. These morphological changes are most likely attributable to oxidative stress induced by the compounds produced by C. racemosa. This mechanism also appears to underlie the more severe alterations observed in the exposed specimens, particularly in the reproductive system. Processes of oocyte degeneration and abnormalities in sperm differentiation were indeed observed, accompanied by profound disorganisation of the gonads. In the long term, these effects could significantly compromise the reproductive fitness of adult individuals, posing a real risk to the survival of the species. Therefore, the observed alterations suggest that the spread of C. racemosa could have significant consequences for Mediterranean marine ecosystems, affecting their stability at both the individual and population levels.
Bisphenol A (BPA) is a widely used plastic additive with recognized endocrine-disrupting activity and was classified in 2017 by the European Chemicals Agency (ECHA) as a substance of very high concern. Increasing evidence has associated environmental exposure to BPA with developmental and congenital abnormalities in both humans and experimental animal models, including the amphibian Xenopus laevis. In addition to BPA, ethanol (Eth) is one of the most common environmental and dietary xenobiotics, known to interfere with embryonic development and neurobehavioral processes. Previous studies conducted by our group using the R-FETAX assay demonstrated for both BPA and Eth teratogenic and neuro-developmental effects. Despite the widespread co-occurrence of BPA and ethanol exposure, limited information is available regarding their combined effects during embryogenesis. In the present study, embryos obtained by natural mating were exposed to a binary mixture of BPA (0-12.5-25-30 µM) and ethanol (0.1%, dose described as not-effective for X. laevis development) during specific developmental windows: i) gastrulation and organogenetic periods, particularly sensitive to morphological abnormalities; ii) neurodevelopmental stages associated with behavioral alterations. Embryos were monitored throughout the six-day R-FETAX test for lethal effects, while external morphology and developmental progression were evaluated at the end of the exposure period. Neurobehavioral alterations were assessed using the neurobehavioral swimming test. Effects were modelled using PROAST software package (www.proastweb.rivm.nl): dose-relationship curves were obtained and benchmark dose level derived, setting response at levels used as point of departure for risk assessment. Results suggest that a non-effective concentration of Eth, when combined with BPA, enhanced the observed responses, affecting both teratogenic endpoints (head abnormalities) and neurobehavioral parameters (abnormal swimming pattern).
Microplastic particles, smaller than 5 mm, have been detected in humans and in marine and freshwater environments [1]. Due to their ability to bioaccumulate and biomagnify across trophic levels, they may seriously harm both humans and aquatic organisms [2]. In freshwater ecosystems, microplastics frequently co-occur with heavy metals (HMs), raising important environmental concerns [3]. However, the effects of combined exposure, often more toxic than single contaminants, remain poorly understood. In this study, we investigated the developmental toxicity induced by single and combined exposure to cadmium, copper, and lead together with 5 μm aged polystyrene microbeads (PSMBs), used to better mimic environmental conditions, in embryos of the model organism Xenopus laevis. This species is widely considered an excellent model for studying embryonic development in higher vertebrates. A multi-endpoint approach was employed, including a FETAX assay to evaluate mortality, growth, and malformations, together with histological and molecular analyses. Although mortality rates remained around 20%, except in cadmium-exposed groups, a high incidence of malformations was observed. Embryos exhibited craniofacial abnormalities involving the first and second branchial arches, intestinal malrotation, mucosal damage, altered pigmentation, and diffuse edema. Furthermore, exposure to these contaminants induced oxidative stress and increased apoptosis, particularly in embryos exposed to mixtures of metals and HM+PSMB combinations. Significant dysregulation of key developmental genes (otx2, pax6, sox3, sox9, egr2, bmp4, fgf8) was also detected and correlated with the observed malformations. In addition, genes associated with apoptosis (p53 and p65) and cellular detoxification (abcb1) showed marked alterations in expression, especially after combined exposures. Overall, our findings demonstrate that microplastics induce physiological stress during early development and exacerbate the bioaccumulation and toxicity of coexisting contaminants in aquatic organisms⁴. These results highlight the importance of evaluating microplastics within complex environmental contaminant mixtures.
The developmental origin of immune cells is an open field of research in animal biology. The snail Pomacea canaliculata (Pc) is a suitable model for studying developmental hematopoiesis and niche maintenance, as it has direct development, long lifespan and both circulating and tissue-resident hemocytes. However, it has never been investigated if Pc hemocytes are present in tissues at hatching or progressively colonize organs during post-hatching development. Here, we performed histological and histochemical analysis of whole snails at specific post-hatching timepoints (PHT) (3dph to 3mph) to characterize hemocyte distribution in the context of organ morphology. By 3dph, fully organized ganglia and sensory organs indicated their crucial early role in hatchlings, while hemocytes occurred in the mantle, gill leaflets, and pericardial cavity. Distinct hemocyte morphotypes were observed in the gills, including small blast-like cells (SCs) and larger alcian-PAS-negative granular cells (GCs). Interestingly, GCs were observed within and leaving the leaflets’ epithelium, suggesting a transition from circulation to organs and between organs. The posterior kidney, which presents epithelial crypts and hemocyte aggregates (HAs) in adults, exhibited mesenchymal-like organization until 2mph. At 3mph a structured parenchyma with HAs became evident, comprising mostly SCs and few GCs. These observations suggest that different sites contribute to hemocyte storage, with relevant involvement of the gills during early PHT. Overall, this study provides the first anatomical characterization of hatchlings Pc, enabling histological identification of post-hatching stages and opening new temporal windows to investigate hemocyte tissue seeding and organ-specific immune roles during growth. Acknowledgements: This work was supported by National Recovery and Resilience Plan (NRRP), Mission 4, CUP E93C22001090001, Project title “National Biodiversity Future Center - NBFC”.
The Mediterranean Sea, being a semi-enclosed basin, is severely affected by persistent pollution and the current climate change. Particularly vulnerable areas are those cross-border, characterized by strong human pressure that undermines the balance between the biota and its ecosystem, resulting in worrying repercussions on biodiversity. Therefore, in line with the European Union directives, the aim of the project COSTA "Cartography and solutions for the restoration of pollution effects in cross-border zones: a transversal approach" (INTERREG VI-A NEXT Italia-Tunisia 2021-2027; CUP J43C25000430003) is to restore the deteriorated state of the Mediterranean Sea by promoting shared, multidisciplinary actions between Italy and Tunisia. The five partners will collaborate to achieve common cross-border objectives: (i) to perform biomonitoring assessments of four pilot sites in both countries through chemical analyses of water, sediments and biota, besides a multi-biomarker approach including proton nuclear magnetic resonance (1H NMR) metabolomics (GT1); (ii) to collect macroalgae from field to obtain biocarbons through carbonization, to produce novel green biofilters able to remove pollutants from the environment (GT2); (iii) to develop innovative biosensors for monitoring aquatic pollution, besides to create a Living Lab as a collaborative platform for technological experimentation and knowledge sharing. Overall, these multidisciplinary activities, performed in synergy between the two countries, are intended to transfer expertise and effective green tools to alert and draw the attention of authorities and stakeholders in transfrontier countries, enabling them to implement active and shared actions to protect biodiversity and human health on both coasts of the Mediterranean Sea. Acknowledgements: This work was supported by the INTERREG VI-A NEXT Italia-Tunisia 2021-2027 - CUP J43C25000430003 (Cod. A1-2.7.164): “Cartographie et solutions pour la restauration des effets de la pollution dans la zone transfrontalière: une approche transversale - COSTA”.
Autism spectrum disorder (ASD) is a multifactorial neurodevelopmental disorder characterized by deficits in communication skills, social interaction and stereotyped behaviors, along with immune dysregulation, neuroinflammation and oxidative stress1. Recently, a Citrus bergamia extract (BPE), featured by high concentrations of flavonoids, has been shown to possess antioxidant and neuroprotective properties2,3. On this basis, PBE was used to evaluate its efficacy in some neurobiological activities of a murine model of ASD, the BTBR T+ Itpr3tf/J (BTBR) as compared with the control C57BL6J mice. Both strains were fed a standard chow diet (CD, 2019 Teklad Global Diet, 9% fat, 19% protein, 44.9% carbohydrate; Envigo RMS, Udine, Italy) ± BPE (100 mg/kg4; Quasiora Laboratory, University of Calabria) for four weeks. As expected, BPE significantly improved ASD-related symptoms in BTBR mice by reducing repetitive behavior (p
The inadequate treatment of municipal wastewater leads to the constant release into the environment of pharmaceutically active compounds (PhACs). The PhACs can induce multiple biological effects on various aquatic species compromising their welfare. Among these, dexamethasone (DEX), a synthetic glucocorticoid commonly detected in the environment, showed adverse effects on non-target organisms. Consequently, it is imperative to enhance strategies to mitigate its detrimental impact on aquatic biota. In this context, ulvans (U), polysaccharides extracted from green macroalgae (Ulva spp.), appear to exert various biological properties, mostly antioxidant and anti-inflammatory. This study aim to evaluate the action of U on mussels Mytilus galloprovincialis treated with DEX by exposure for 12 days (T12) at four experimental conditions: negative control (CTRL), 100 mg/L of U extracted by Ulva ohnoi (U100), 400 ng/L of DEX (DEX), mixture of U100 and DEX (UDEX). The effects on the antioxidant system (superoxide dismutase, SOD; catalase, CAT; lipid peroxidation, LPO; glutathione S-transferases, GST), immune response (acid phosphatase, ACP; alkaline phosphatase, ALP; phenoloxidase, PO), and energy metabolism (lactate dehydrogenase, LDH; electron transport system, ETS), were evaluated on mussel digestive gland, chosen for its role in xenobiotic detoxification. The results revealed a lack of impairments in the energy metabolism in mussels exposed to UDEX. Also, the antioxidant system results enforced by the U treatments, as confirmed by the reduction of LPO and the increase of CAT in samples from UDEX. Moreover, an improvement in the immune parameters, coupled to a lack of changes in the energy metabolism, was also observed in mussels from the same condition. Overall, the results confirm the beneficial biological properties of ulvans, thus supporting their use as eco-friendly solution against the impact of emerging contaminants, as well as their potential use as non-impactful food additives in mussel farms.
Telocytes have long, thin extensions called telopods, which present a beaded structure composed of thicker (podomes) and thinner (podomers) segments [1]. Telocytes are distributed throughout the myocardium [2] and are essential for intercellular communication, immune surveillance, and regenerative processes. Lipopolysaccharide (LPS) plays a key role in triggering a systemic inflammatory response, which can cause cardiac damage [3]. Cannabis sativa L. is an aromatic annual plant in the Cannabaceae family. Research has demonstrated that hemp possesses a wide range of pharmacological properties, including anti-inflammatory effects [4]. This study aims to characterize the involvement of telocytes in mice’s cardiac inflammation caused by LPS and the potential anti-inflammatory role of Cannabis sativa L. Cardiac telocytes were characterized using CD34 and vimentin antibodies, whereas CD86 and IL-6 were used to identify macrophages [5]. In inflamed tissues, telocyte numbers appear to increase, likely as a response to inflammation, playing a key role in tissue repair and protective responses. Macrophages were significantly more abundant in inflamed tissues compared to both control samples and those treated with LPS and hemp aqueous extracts. Some telocytes showed co-expression of CD34 and CD86, suggesting their active involvement in immunomodulation. In conclusion, this study confirms the involvement of telocytes in cardiac inflammation and offers potential avenues for the development of therapeutic strategies based on natural compounds.
The striped red mullet (Mullus surmuletus L., 1758) is a key target species with high commercial value for small-scale fisheries in the Mediterranean Sea. The species is widely distributed along the Mediterranean coasts as well as the northeastern Atlantic Ocean, from Scandinavia to Senegal. As ectotherms, aquatic species depend on heat exchange with their surrounding environment to regulate metabolism and adaptation. Consequently, climatic variation across their range can result in differing bioenergetic requirements. Mitochondrial OXPHOS (mtOXPHOS) genes are critically involved in these processes and have been extensively studied in the last decades as a system that is subject to selection under determined environmental constraints. Based on the above, the aim of this study was to analyze the nucleotide sequence of two mitochondrial OXPHOS genes, Cytochrome Oxidase I (COI) and NADH dehydrogenase subunit 1 (ND1), in five Mediterranean populations of the target species to detect the presence of positive selection based on different models of evolution. Various selection tests were conducted. In particular, the CodeML test identified the presence of one site under positive selection in the COI gene; the FUBAR test detected one site under positive selection and three under negative selection in the COI gene, as well as two sites under positive selection and twelve under negative selection in the ND1 gene. Finally, the MEME test indicated the presence of a single site under positive selection in the ND1 gene. Overall, these findings provide preliminary evidence of localized positive selection in mitochondrial OXPHOS genes of M. surmuletus, likely reflecting adaptive responses to spatial environmental variability across the Mediterranean Sea.
The use of metal compounds as therapeutic agents has attracted growing interest, as they tend to interact with biological macromolecules. Several studies have highlighted the therapeutic potential of various metals in the treatment of various pathologies, and currently, metallodrugs based on platinum, copper, gold, ruthenium, yttrium, silver, and lithium exist. Furthermore, some metallodrugs are used in clinical diagnosis: iodine, barium, and gadolinium. Vanadium (V) complexes have also attracted considerable interest in the biomedical field. From the middle of the last century to the present, the study of V compounds as potential therapeutic agents has experienced exponential growth. Cytotoxicological approaches carried out on whole marine embryos represent a valid research tool since they grow directly in contact with the pollutants and are equipped with highly responsive cells to stressors. Here, we discuss the impact on Paracentrotus lividus sea urchin embryos resulting from two V-based coordination compound UP3 and UP4, metal complexes of Schiff base ligands. The results demonstrate the remodeling of embryonic architecture at the morphometric level, revealing developmental delays and anomalies. Furthermore, both a modulation in total tissue remodeling enzymatic activities and a variation in the amount of two MMP-like gelatinases (MMP-2, and -14) were observed. Embryos activated a cytoprotective mechanism mediated by HSPs (-60, -70 and -90) and they eliminated cells with fragmented DNA, in order to safeguard the developmental program This research demonstrates that V-based metallodrugs activates different biological pathway (stress, cytoprotection and cell death) emphasizing the necessity for comprehensive toxicity assessments in in vivo evaluations.
