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Tumor-associated macrophages (TAMs) may be noticed in gastric carcinomas (GC), but their clinicopathological significance has not been yet explored. From a histological review of 400 cases of tubular/papillary adenocarcinomas, 24 cases of stage I–II gastric adenocarcinomas with intraglandular and stromal TAMs were identified. Their clinicopathological features were compared with 72 pT-matched as well as stage-matched control cases of adenocarcinomas without TAMs. TAMs present in GC cases were present either in glands or in neoplastic stroma, showing an immunoreactivity for CD68 and CD80; sometimes, they were organized in mature granulomas with occasional giant cells. Therefore, the stained TAMs were reminiscent of a specific polarized macrophage M1 phenotype; however, in any case of our cohort, no M2 phenotype macrophages were documented by CD 163 and CD 204 immunostainings. Statistically, no significant differences in age, gender, tumor location, size, and lymphovascular and perineural invasion between the case group with TAMs and pT- as well as stage-matched controls were reported; furthermore, the case group showed lower frequency of lymph node metastasis (p = 0.02). In addition, a significantly different clinical course and overall survival rate were also observed in gastric adenocarcinomas with M1 TAMs (p = 0.02) in comparison to controls. These results suggest that tumor-associated M1 macrophages are related to a quite indolent growth and a better prognosis of patients with this peculiar variant of gastric adenocarcinomas.

Introduction: The “migrant” term indicates a resident born in a country other than the host country. Resident foreigners made up 8.4% of the total Italian population in 2020. The Sicilian trend reflects the national one, with 190,974 resident foreigners as of 1th January 2020. The aim of this study was to identify the presence of tumors in foreign patients residing in the RTI’s provinces of interest in 2003–2017 and to analyze the clinical-biological variables. Materials and Methods: We analyzed 3541 foreign patients with tumors (out of a total of 160,912 patients) residing in the RTI’s provinces of interest in 2003–2017. Foreign patients were identified by tax code. Tumors are described ((number and percentage). Results: Of the 3541 foreign patients, 36% were male and 64% were female. They resided in the provinces of Catania (42.6%), Messina (29.9%), Siracusa (20.7%), and Enna (6.6%). They came from Europe (57%), Africa (22.4%), the Americas (12.03%), Asia (5.08%), and Oceania (1.80%); 0.3% were stateless. The average age was 58 for males and 54.4 for females. The number of tumors (excluding non-melanoma skin tumors) was 3715. Sixty-two males and 98 females had one or more multiple tumors. In foreign females, the three most common tumors were breast (28%), thyroid (9%), and cervical (6%) tumors. Most breast cancers were diagnosed as stage T1 (35%) or T2 (26%). In foreign males, the three most common tumors were lung (13%), bladder (12%), and prostate (11%) tumors. Conclusions: The growing presence of foreign citizens in the provinces studied calls for more attention on oncology-related problems and more careful surveillance of changes in incidence and mortality by the RTI.

Antarctica is the continent with the lowest local human impact; however, it is susceptible to pollution from external sources. Emerging pollutants such as perfluoroalkyl substances pose an increasing threat to this environment and therefore require more in-depth investigations to understand their environmental fate and biological impacts. The present study focuses on expression analysis at the transcriptional level of genes coding for four antioxidant enzymes (sod1, sod2, gpx1, and gpx4) in the liver and kidney of an Antarctic fish species, Trematomus newnesi (Boulenger, 1902). mRNA levels were also assessed in fish exposed to 1.5 μg/L of perfluoro-octanoic acid for 10 days. The kidney showed a higher level of expression than the liver in wildlife specimens. In the liver, the treatment induced an increase in gene expression for all the considered enzymes, whereas in the kidney, it induced a general decrease. The obtained results advance the scientific community’s understanding of how the potential future presence of anthropogenic contaminants in the Southern Ocean can affect the antioxidant system of Antarctic fishes. The presence of pollutants belonging to the perfluoroalkyl substances in the Southern Ocean needs to be continuously monitored in parallel with this type of research.

Metal bioaccumulation and metallothionein (MT) expression were investigated in the gills and liver of the red-blooded Antarctic teleost Trematomus hansoni to evaluate the possibility for this species to face, with adequate physiological responses, an increase of copper and cadmium concentrations in its tissues. Specimens of this Antarctic fish were collected from Terra Nova Bay (Ross Sea) and used for a metal exposure experiment in controlled laboratory conditions. The two treatments led to a significant accumulation of both metals and increased gene transcription only for the MT-1. The biosynthesis of MTs was verified especially in specimens exposed to Cd, but most of these proteins were soon oxidized, probably because they were involved in cell protection against oxidative stress risk by scavenging reactive oxygen species. The obtained data highlighted the phenotypic plasticity of T. hansoni, a species that evolved in an environment characterized by naturally high concentrations of Cu and Cd, and maybe the possibility for the Antarctic fish to face the challenges of a world that is becoming more toxic every day.

Metallothioneins (MTs) are low-molecular weight sulfur-rich proteins, widely distributed in nature. They play a homeostatic role in the control and detoxification of metal ions. Previous studies indicated that MTs also have the capacity to scavenge reactive oxygen species. This study aimed to investigate the evolution of the protein in the notothenioid fish, evolved under the selective pressure of relatively high oxygen partial pressures, characteristics of cold Antarctic seawaters, and relatively high concentrations of metal ions, Cd and Cu in particular. The cDNA sequences of MT isoforms were characterized in members of the Nototheniidae, Bathydraconidae, Artedidraconidae, and Channichthyidae families. The phylogenetic relationships of MTs from these families and other teleosts were inferred by using Maximum Likelihood and Bayesian methods. The analysis of coding region and untranslated (UTR) sequences indicated the presence of two MT clades, each containing one of the two MT isoforms, MT-1 and MT-2. Our results indicated, for the first time for these proteins, that the evolution of MT genes has been characterized by strong purifying selection, whereas it did not observe any evidence of positive selection. In addition, phylogenetic analysis of the UTRs suggested that functional changes, in particular related to the MT-1 gene expression, had accompanied the duplication event.

This work aimed to evaluate the effects of zinc (Zn) relating to cadmium (Cd)-induced toxicity and the role played by MTF-1. This transcription factor regulates the expression of genes encoding metallothioneins (MTs), some Zn transporters and the heavy chain of γ-glutamylcysteine synthetase. For this reason, two cell lines of mouse fibroblasts were used: a wild-type strain and a knockout strain to study the effects. Cells were exposed to complete medium containing: (1) 50 μM ZnSO4 (Zn), (2) 1 μM CdCl2 (Cd 1), (3) 2 μM CdCl2 (Cd 2), (4) 50 μM ZnSO4 + 1 μM CdCl2 (ZnCd 1) and (5) 50 μM ZnSO4 + 2 μM CdCl2 (ZnCd 2) for 4, 18 and 24 h. Following exposure, cell viability, the intracellular content of metals, glutathione (GSH) and MT and the gene expression of the two isoforms of MT was evaluated. The results obtained suggest that a lower Cd content in the co-treatments is responsible for the protection offered by Zn due to the probable competition for a common transporter. Furthermore, Zn determines an increase in GSH in co-treatments compared to treatments with Cd alone. Finally, the MTF-1 factor is essential for the expression of MT-1 but not of MT-2 nor probably for the heavy chain of γ-glutamylcysteine synthetase.

In recent decades, the interest in PFAS has grown exponentially around the world, due to the toxic effects induced by these chemical compounds in humans, as well as in other animals and plants. However, current knowledge related to the antistress responses that organisms can express when exposed to these substances is still insufficient and, therefore, requires further investigation. The present study focuses on antioxidant responses in Squalius cephalus and Padogobius bonelli, exposed to significant levels of PFAS in an area of the Veneto Region subjected to a recent relevant pollution case. These two ubiquitous freshwater species were sampled in three rivers characterised by different concentrations of PFAS. Several biomarkers of oxidative stress were evaluated, and the results suggest that PFAS chronic exposure induces some physiological responses in the target species, at both cellular and tissue scales. The risk of oxidative stress seems to be kept under control by the antioxidant system by means of gene activation at the mitochondrial level. Moreover, the histological analysis suggests an interesting protective mechanism against damage to the protein component based on lipid vacuolisation.

It is well known that the excessive production of reactive oxygen species (ROS) can lead to the peroxidation of membrane lipids, glycation/oxidation/nitration of proteins, inactivation of enzymes, DNA mutation and damage, and other alterations in the subcellular components [...]

Pleomorphic carcinoma is an aggressive neoplasm defined by the World Health Organization (WHO) as a poorly differentiated (squamous cell carcinoma or adenocarcinoma) or undifferentiated carcinoma in which at least 10% spindle and/or giant cells are identified, or as a carcinoma constituted purely of spindle and giant cells. Although this entity has initially been shown in the lung, it has been described also in extrapulmonary locations, with only one report for a colonic site. A 65-year-old woman developed a caecal tumour. Gross examination revealed an endophytic/ulcerative mass 7 cm in length. Microscopically, the tumour was a poorly differentiated adenocarcinoma with a pleomorphic component that occupied more than 10% of the specimen. The tumour shared these histopathological findings with pulmonary giant cell carcinoma but differed in other clinicopathological features such as a pushing growth pattern, stage pT3N1, and an uneventful outcome 24 months after operation. The pleomorphic component showed morphological and immunohistochemical features compatible with mitotic catastrophe, a non-apoptotic cell death occurring in cycling cells after aberrant mitosis. These features included multinucleation, micronucleation, atypical mitoses, foci of geographic necrosis, as well as immunohistochemical overexpression of p53 and Ki-67. The interpretation of the pleomorphic component as morphological expression of mitotic catastrophe may be useful in comprehending the pathogenesis of this rare neoplasm, and it may have practical implications as a potential cancer therapeutic target.

Glutathione peroxidases (GPxs) form a broad family of antioxidant proteins essential for maintaining redox homeostasis in eukaryotic cells. In this study, we used an integrative approach that combines bioinformatics, molecular biology, and biochemistry to investigate the role of GPxs in reactive oxygen species detoxification in the unicellular eukaryotic model organism Tetrahymena thermophila. Both phylogenetic and mechanistic empirical model analyses provided indications about the evolutionary relationships among the GPXs of Tetrahymena and the orthologous enzymes of phylogenetically related species. In-silico gene characterization and text mining were used to predict the functional relationships between GPxs and other physiologically-relevant processes. The GPx genes contain conserved transcriptional regulatory elements in the promoter region, which suggest that transcription is under tight control of specialized signaling pathways. The bioinformatic findings were next experimentally validated by studying the time course of gene transcription and enzymatic activity after copper (Cu) exposure. Results emphasize the role of GPxs in the detoxification pathways that, by complex regulation of GPx gene expression, enable Tethraymena to survive in high Cu concentrations and the associated redox environment.

In the present study, we describe the purification and molecular characterization of Cu,Zn superoxide dismutase (SOD) from Chionodraco hamatus, an Antarctic teleost widely distributed in many areas of the Ross Sea that plays a pivotal role in the Antarctic food chain. The primary sequence was obtained using biochemical and molecular biology approaches and compared with Cu,Zn SODs from other organisms. Multiple sequence alignment using the amino acid sequence revealed that Cu,Zn SOD showed considerable sequence similarity with its orthologues from various vertebrate species, but also some specific substitutions directly linked to cold adaptation. Phylogenetic analyses presented the monophyletic status of Antartic Teleostei among the Perciformes, confirming the erratic differentiation of these proteins and concurring with the theory of the “unclock-like” behavior of Cu,Zn SOD evolution. Expression of C. hamatus Cu,Zn SOD at both the mRNA and protein levels were analyzed in various tissues, highlighting the regulation of gene expression related to environmental stress conditions and also animal physiology. The data presented are the first on the antioxidant enzymes of a fish belonging to the Channichthyidae family and represent an important starting point in understanding the antioxidant systems of these organisms that are subject to constant risk of oxidative stress.

The aims of the work presented here were to determine the effect of long term treatment with zinc (Zn) on both total metallothionine (MT) and, in particular, oxidized MT (MTox) concentrations in Long-Evans Cinnamon (LEC) rat liver. We also evaluated semi-quantitatively the cell death index using TUNEL assay as it is a useful method to localize the nuclear fragmentation occurring in oxidative stress conditions. The results demonstrate there were no statistically different MT concentrations between Zn-treated and untreated rats, whereas the Zn treatment was very effective in reducing the percentage of oxidized MT (MTox). MTox is not able to bind metals, so it does not perform its “scavenger” action against copper (Cu) accumulation in LEC rats. The intensity and quantity of fluorescent staining observed in untreated rat sections decreased compared to the treated ones. These findings suggest that in LEC rats one of zinc's roles is to protect from oxidative stress, however, its mode of action remains partially unknown: a hypothesis is competition for Cu binding sites. A new insight is that Zn induced MT can protect efficiently against DNA damage by free radicals.

The aim of the present work was to determine the activities of selected antioxidant enzymes (SOD, Se-GPX, CAT) in two species of bivalves, Scapharca inaequivalvis and Tapes philippinarum, from two sites of the lagoon of Venice that are characterized by different pO2 (Marghera and Chioggia). The specimens were collected at four times during a 1-year period. In the two species studied, enzyme activities were found to be present in both digestive glands and gills, but with some species-specific differences that may also represent a different adaptation to seasonal variations. The presence of high SOD activities in the gills of both species may be related to their physiological role in respiration. Scapharca inaequivalvis is less sensitive than T. philippinarum to environmental changes, perhaps due to the presence of hemoglobins in this species. Moreover, in the digestive gland of T. philippinarum we found a significant negative correlation between the activities of SOD and GPX that may indicate the presence of oxidative stress. Some correlations between temperature/dissolved oxygen and antioxidant enzyme activity were present in specimens sampled in Marghera. Only GPX adequately responded to changes in dissolved oxygen and temperature, while the decrease in the activity of SOD and CAT in winter may be directly responsible for an enhanced susceptibility of mussels to oxidative stress during this period. We can conclude that the observed differences between Chioggia and Marghera are due to different concentrations of dissolved oxygen. Marghera is an appropriate location to study seasonal variations in water temperature. In fact, in this site, the differences between hot and cold months are quite evident. [Copyright &y& Elsevier]

Summary: The patterns of expression of two metallothionein (MT) genes, MT-1 and MT-2, previously identified as Cd-MT and Cu-MT, were analysed in Tetrahymena pigmentosa in response to metal inducers cadmium, copper and zinc and to a mixture of copper and cadmium at appropriate concentrations. Co-treatment induces synergistic accumulation of both metals and higher expression of MT-mRNAs in the first few hours. mRNA levels were observed not to completely correlate with MT-protein levels, suggesting that post-transcriptional regulation may be involved in MT induction. MT-1 is induced to higher levels than MT-2. Zinc does not induce any MT expression. The lowest level of mRNA was observed for MT-2, induced only by copper. Cadmium is a powerful inducer of the MT-1 gene, although a very low transcription rate by copper occurs in the first hour. [Copyright &y& Elsevier]

Stress granules (SGs) are cytoplasmic foci lacking membranes, comprising non-translating messenger ribonucleoproteins, translational initiation factors, and additional proteins. Their formation is crucial for rapidly modulating gene expression in response to adverse environmental conditions, such as pollution and infections. Limited research has focused on investigating the molecular components of SGs in fish, with minimal exploration in Antarctic fish. This study characterises for the first time the transcript sequences of one key protein component of SGs, TIA-1 (T-cell intracellular antigen 1), in two Antarctic endemic fish species, i.e. Trematomus bernacchii and Chionodraco hamatus. The mRNA-binding protein TIA-1 acts as a post-transcriptional regulator of gene expression and its aggregation leads to the formation of SGs in response to cellular damage. The in vitro and bioinformatic analyses of the TIA-1 gene sequences of these two species highlighted interesting peculiarities, which include the transcription of alternatively spliced isoforms unique to the notothenioid lineage, potentially unlocking further insights into their unique adaptations to extreme environmental conditions. This is the first study to analyze tia-1 expression levels in different tissues of Antarctic fish species. Our key findings indicate that the TIA-1 gene is expressed at particularly high levels in the liver and spleen of C. hamatus, as well as in the heart and skeletal muscle of T. bernacchii. This suggests that those tissues play a significant role in the stress response mechanisms of the studied species. This study provides novel insights into the molecular adaptations of Antarctic fish, highlighting the potential importance of TIA-1 in their response to environmental stressors. The unique features of TIA-1 identified in these species may offer broader implications for understanding how Antarctic fish regulate gene transcriptions in their extreme environments., (Copyright © 2024 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

In the context of increasing environmental contamination, our study employed fish as bioindicators, focusing on non-invasive cortisol measurements in scales and fins in response to severe PFAS pollution in the Veneto area of Italy. Our preliminary findings showed species-specific stress responses, as observed in Squalius cephalus and Padogobius bonelli, suggesting the need for broader biomonitoring to capture the complex impact of environmental stressors on aquatic organisms. Moreover, due to the unusual characteristics of the rivers selected for the biomonitoring activity, a possible link between PFAS exposure and cortisol levels in S. cephalus demonstrates the method's potential., Competing Interests: Declaration of competing interest There is no conflict of interest., (Copyright © 2024 Elsevier Ltd. All rights reserved.)