Epidemiologic data suggest a link betweenatherosclerosis and chronic infections and inflammatory conditions. During infection andinflammation, a wide range of alterations in metabolism occur. These are part of the body´s reaction known as the acute phase response (APR). Infection and inflammation can also perturb lipoprotein metabolism and produce a widevariety of changes in the plasma concentrations of lipids and lipoproteins.Eicosanoids are a group of oxygenated fattyacids with diverse and potent biological activity, produced from the fatty acids. The varietyof eicosanoids products and their correspondingly diverse physiological effects have been well characterized, and probably represent the best-understood relationship between lipids and biological function. Consequently, attempts tomodulate the production of eicosanoids musttarget either the enzyme activities responsible for synthesizing eicosanoids or the concentration of fatty acids substrate entering biological system through the diet.

VEXAS (vacuoles, E1 enzyme, X-linked, autoinflammatory, somatic) syndrome was identified in 2020 by Beck et al, when analyzing the genome of 2560 patients with differenttypes of autoinflammatory manifestations. A literature review was carried out with the aim of disseminating existing scientific evidence and increasing the degree of clinical suspicion of the medical community. Currently, many mutations associated with this syndromehave been identified, causing defects in the ubiquitylationand activation of the innate immune system. From thephenotypic analyses of the mutation carriers, some common features were found: male, over 50 years old, cytopenias, fever and constitutional symptoms, and all organs and systems with variable manifestations and proportions may be involved. The inflammatory and multi-systemic nature of this disease leads to a diagnostic and treatment challenge, adding to the already existing high morbimortality. Presently, the treatments with greater efficiency are corticosteroid therapy, azacytidine, JAK-1/2 inhibitors and interleukin-6 inhibitors. There are also benefits in autologous stem cell transplants. Given its recent identification and low number of diagnosedpatients, most available studies have limitations related to the methodology and short duration of follow-up, prevailing the need for prospective clinical trials in order todefine the best therapeutic strategies and to improve thesepatients’ prognosis.

Psoriasis and depression are very prevalent diseases that often coexist. In fact, the prevalence of depression in patients with psoriasis is higher than that observed in the general population and increases with disease severity. At the same time, it is now known that inflammation plays a central role in both diseases, with high levels of pro-inflammatory cytokines corroborating these assumptions. Assuming that dysregulation of the immune system may be a possible precipitating event for both conditions, therapeutic strategies have been highlighted for various inflammatory pathways, with promising effects on both diseases, including anti-TNF-α and anti-IL-17A therapies, which further corroborate the association between them. Thus, with this perspective article, the authors intent to review not only the pathophysiological mechanisms behind these entities, focusing on the role of inflammation, but to understand the immune-mediated interaction that appears to be shared by them. The aim, therefore, is not only to provide greater clarification regarding existing knowledge, but also to highlight gaps that still exist, aspiring the development of large-scale studies that can fill them. Furthermore, we propose to expose the pathophysiological similarities of both diseases, aiming to transfer transversal knowledge between both, with an impact on the approach, therapy and prognosis.

Prostate cancer (PCa) is a hormone-dependent cancer whose development and progression are strongly influenced by the tumour microenvironment and exogenous factors, such as environmental influences. The periprostatic adipose tissue (PPAT), by its anatomical proximity and functional crosstalk with prostate cells, emerged as a key driver of tumour growth, particularly in obesity, with the secretome of “obese” PPAT being associated with enhanced tumour aggressiveness. On the other hand, epidemiological and experimental studies have implicated endocrine-disrupting chemicals (EDCs) as environmental risk factors for PCa. Given the hormone dependency of PCa, it is predictable that it is a cancer highly susceptible to the influence of environmental exposures, namely EDCs and specifically those with obesogenic properties (i.e. obesogens), which are capable of disrupting both endocrine and metabolic pathways. Notably, based on their mechanisms of action and the cellular and molecular alterations they induce, obesogens may promote tumorigenesis either directly by acting on prostate cells or indirectly by inducing adipose tissue dysfunction. However, the extent to which obesogenic compounds drive these alterations and the consequent impact on prostate tumorigenesis remain largely unknown. Moreover, despite the well-established effects of obesogens on adipose tissue, no study has characterised their actions on PPAT. Addressing these gaps is critical to understanding how environmental factors intersect with adipose tissue biology, influencing interorgan communication between the prostate and adipose tissue and PCa development. Based on this scientific rationale, this doctoral thesis hypothesises that obesogen-induced PPAT dysfunction represents a driving force in the initiation and progression of PCa. Tributyltin (TBT) is a well-characterised obesogenic EDC and a potent regulator of adipogenesis, widely used in experimental settings to investigate the effects of obesogens. Therefore, using the obesogen model TBT this thesis aimed to: (i) characterise the morphological and secretory alterations of PPAT following TBT exposure; (ii) assess the impact of TBT-induced PPAT dysregulation on prostate cell fate, metabolism, oxidative and inflammatory status, and response to chemotherapeutic drugs; and (iii) identify the molecular targets and signalling pathways mediating the crosstalk between dysregulated PPAT and prostate cells. First, it was demonstrated that in vivo exposure to TBT (50 μg/kg) besides increasing rat body weight, enhanced PPAT somatic index and altered its functional phenotype. TBT treatment promoted a shift in rat prostate cells toward a glycolytic and lipogenic metabolic profile and stimulated oncogenic signalling pathways, including increased phosphorylated/total protein kinase B (pAKT/AKT) ratio and androgen receptor expression. Moreover, macrophage infiltration and a shift in macrophage polarisation towards a pro-inflammatory phenotype were observed both in the prostate and PPAT of TBT-exposed animals, suggesting that TBT can perturb the local prostate-PPAT immune status, contributing to an environment permissive to prostate carcinogenesis. These findings confirmed the effects of TBT on prostate cells, supporting the hypothesis and the investigation into the contribution of PPAT-mediated effects in altering prostate cell behaviour. Culture of the PPAT from rats exposed to TBT clearly demonstrated that TBT induced a dysregulation of the PPAT secretome. TBT-treated PPAT (TBT-PPAT) displayed increased leptin/adiponectin ratio and C-C motif chemokine ligand 7 (CCL7) levels. This adipokine/chemokine profile induced by TBT mimics that observed in obesity and is concurrent with a metabolic reprogramming associated with enhanced glucose, free fatty acids, and lipid peroxidation. Importantly, ex vivo exposure of rat PPAT to TBT (100 nM) recapitulated the findings obtained in vivo concerning the features of its secretome, which are capable of having an impact on prostate cell fate. The results obtained in the subsequent preclinical approaches using co-cultures and conditioned media (CM) assays confirmed the ability of TBT-PPAT enhance the viability, proliferation and migration, as well as apoptosis resistance, in all the studied prostate cell line models, namely non-neoplastic prostate epithelial cells (PNT1A), and androgen-sensitive (22Rv1) and androgen-insensitive (DU145 and PC3) PCa cells. Notably, the TBT-PPAT secretome increased the expression of CCL7 receptor, the C-C motif receptor 3 (CCR3), in prostate cells, which, together with the enhanced CCL7 secretion observed in our experimental setting, raised curiosity about the role of the CCL7-CCR3 axis underlying the pro-tumorigenic effects of TBT-PPAT. The use of a CCR3 antagonist significantly reduced TBT-PPAT induced migration across all cell lines, allowing to implicate the CCL7 and CCR3 in the observed responses of prostate cells. Other molecular targets beyond the CCL7-CCR3 axis were also highlighted. It is the case of tribbles homolog 1 (TRIB1), a pseudokinase involved in tumorigenesis and lipid homeostasis that was overexpressed across all studied cell models exposed to TBT-PPAT-CM. Cell fate alterations observed upon TBT treatment were accompanied by metabolic changes with distinct outcomes in non-neoplastic and neoplastic cell lines: in PNT1A, enhanced fatty acid β-oxidation and synthesis indicate a plausible shift toward a cancer-like metabolic profile; in 22Rv1, the unaltered metabolic and oxidative status suggests the activation of alternative signalling pathways sustaining TBT-PPAT effects; in DU145 and PC3, the distinct metabolic responses observed underscore the differential responsiveness of androgen-insensitive PCa cell subtypes to adipose-derived cues. The investigation in the present thesis was extended to a clinically relevant setting. Human PPAT obtained from patients submitted to radical prostatectomy or prostatic adenomectomy (Millin’s procedure) was treated ex vivo with TBT (100 nM) to confirm if the human tissues resemble the pro-tumorigenic cues identified in controlled experimental models. This approach demonstrated that human PPAT is a target of obesogenic dysregulation and showed that the secretome of obesogen-dysregulated PPAT can significantly enhance the viability of prostate cells. Moreover, the presence of human TBT-PPAT reduced the sensitivity of PCa cells to docetaxel and cabazitaxel, suggesting that obesogenic dysregulation contributes to PCa resistance to taxane-based chemotherapy. Overall, the scientific evidence gathered in this thesis identifies PPAT as a key target of obesogenic EDCs, which disrupt PPAT function and its crosstalk with prostate cells, thereby contributing to the initiation and progression of PCa. These findings open new avenues for developing interventions aimed at modulating PPAT activity to counteract its tumour-promoting effects and emphasise obesity as a critical modulator of PCa aggressiveness.

Diabetes Mellitus (DM) and Alzheimer's disease (AD) are two prevalent diseases in modern societies, which are caused mainly by current lifestyle, aging and genetic alterations. It has already been demonstrated that these two diseases are associated, since individuals suffering from DM are prone to develop AD. Conversely, it is also known that individuals with AD are more susceptible to DM, namely type 2 diabetes (T2DM). Therefore, these two pathologies, although completely different in terms of symptomatology, end up sharing several mechanisms at the molecular level, with the most obvious being the increase of oxidative stress and inflammation. Polyphenols are natural compounds widely spread in fruits and vegetables whose dietary intake has been considered inversely proportional to the incidence of DM and AD. So, it is believed that this group of phytochemicals may have preventive and therapeutic potential, not only by reducing the risk and delaying the development of these pathologies, but also by improving brain's metabolic profile and cognitive function. The aim of this review is to understand the extent to which DM and AD are related pathologies, the degree of similarity and the relationship between them, to detail the molecular mechanisms by which polyphenols may exert a protective effect, such as antioxidant and anti-inflammatory effects, and highlight possible advantages of their use as common preventive and therapeutic alternatives.

Sweet cherries (Prunus avium L.) are among the most appreciated fruits worldwide because of their organoleptic properties and nutritional value. The accurate phytochemical composition and nutritional value of sweet cherries depends on the climatic region, cultivar, and bioaccessibility and bioavailability of specific compounds. Nevertheless, sweet cherry extracts are highly enriched in several phenolic compounds with relevant bioactivity. Over the years, technological advances in chemical analysis and fields as varied as proteomics, genomics and bioinformatics, have allowed the detailed characterization of the sweet cherry bioactive phytonutrients and their biological function. In this context, the effect of sweet cherries on suppressing important events in the carcinogenic process, such as oxidative stress and inflammation, was widely documented. Interestingly, results from our research group and others have widened the action of sweet cherries to many hallmarks of cancer, namely metabolic reprogramming. The present review discusses the anticarcinogenic potential of sweet cherries by addressing their phytochemical composition, the bioaccessibility and bioavailability of specific bioactive compounds, and the existing knowledge concerning the effects against oxidative stress, chronic inflammation, deregulated cell proliferation and apoptosis, invasion and metastization, and metabolic alterations. Globally, this review highlights the prospective use of sweet cherries as a dietary supplement or in cancer treatment.

Background: Exercise leads to a robust inflammatory response mainly characterized by the mobilization of leukocytes and an increase in circulating inflammatory mediators produced by immune cells and directly from the active muscle tissue. Both positive and negative effects on immune function and susceptibility to minor illness have been observed following different training protocols. While engaging in moderate activity may enhance immune function above sedentary levels, excessive amounts of prolonged, high-intensity exercise may impair immune function. Thus, the aim of the present review was to clarify the inflammatory effects in response to different exercise intensities. Methods: Search was performed on PubMed and was completed on July 31st, 2017. The studies were eligible if they met the predefined inclusion criteria: a) observational or interventional studies, b) conducted in healthy adults (18-65 years), c) written in Portuguese, English or Spanish, d) including moderate and/or intense exercise. Eighteen articles were included. The specific components that were examined included circulating blood levels of cytokines, leukocytes, creatine kinase (CK) and C-reactive protein (CRP). The methodological quality of the included studies was assessed. Results: Most of the intervention studies showed changes in the assessed biomarkers, although these changes were not consistent. White blood cells (WBC) had an increase immediately after intensive exercise (> 64% VO2max), without alteration after moderate exercise (46-64% VO2max). The results suggested an elevation of the pro-inflammatory cytokines, namely IL-6, followed by an elevation of IL-10 that were more evident after intense exercise bouts. CRP increased both after intense and moderate exercise, with peak increases up to 28 h. CK increased only after intensive and long exercising. Conclusion: In summary, intense long exercise can lead, in general, to higher levels of inflammatory mediators, and thus might increase the risk of injury and chronic inflammation. In contrast, moderate exercise or vigorous exercise with appropriate resting periods can achieve maximum benefit.

Even though Arcobacter butzleri has been implicated in some human disease as diarrhoea and bacteraemia, much of its pathogenesis and virulence factors remain unclear. In this work we have compared pathogenic and genotypic properties of six A. butzleri isolates from human and non-human sources. The tested isolates showed to be susceptible to tetracyclines and aminoglycosides, however non-human isolates were all resistant to quinolones. The ability to form biofilms was variable among the tested strains, and all of them showed a weak haemolytic activity. The presence of nine putative virulence genes was determined, with cadF, ciaB, cj1349, mviN, pldA, tlyA being detected in all strains, while irgA (3/6), hecA (5/6), hecB (4/6) were detected only in some strains. High levels of adhesion were observed for A. butzleri on Caco-2 cells, with pre-existing inflammation showing no significant effect on the adherence ability; yet variable levels of invasion were observed. A. butzleri isolates were able to survive intracellularly in Caco-2 cells and to induce a significant up-regulation of interleukin-8 secretion and structural cell rearrangements. These data brings new insights on A. butzleri virulence and highlights its pathogenic potential.

Aging is associated with physiological, inflammatory, and cognitive changes that increase the risk of neurodegenerative diseases and compromise quality of life. Despite the known benefits of physical exercise, adherence to exercise programs among older adults remains limited, posing a challenge for health promotion in this population. This study aimed to investigate the effects of an 8-week low-volume resistance training program on aging-related markers in a predominantly older population with cognitive impairment. Twenty-eight participants (86 ± 10 years) took part in the study, which was part of the Trainb4Brain program, based on single-set of low-volume resistance training. The choice of a single-set protocol was based on the premise that even low volumes of exercise can provide meaningful benefits while supporting long-term engagement in older adults. Physiological and biochemical parameters, including lipid profile, inflammatory markers, oxidative stress indicators, a cognitive marker and muscle-related measures, were assessed before and after the intervention. The results showed improvements in some lipid parameters and changes at the muscular level without indications of tissue damage, suggesting that short-duration resistance training can induce beneficial adaptations while remaining safe for this population. These findings support the feasibility of low-volume resistance training as a strategy to promote health in older adults. They also show that training programs can be adapted to individual needs, optimizing benefits while maintaining adherence and safety. Given these promising results, further research is warranted to better understand the long-term effects and potential mechanisms of the resistance training in older populations.

Introduction: Post-implantation syndrome (PIS) is characterized by fever, flu-like symptoms, leukocytosis and elevation of reactive C protein in the postoperative period of EVAR. The authors aim to estimate the incidence of PIS after EVAR in their institution, identify risk factors and determine the association with clinical events. Materials and Methods: A retrospective study was designed at a tertiary center. All patients undergoing EVAR between July 2014 and December 2016 were included. Data were collected through electronic clinical records, as leukogram, reactive C protein and body temperature. The primary endpoint evaluated was the incidence of PIS, defined as fever> 38 ° and reactive C protein > 75mg / L. The association with demographic and procedural characteristics, length of hospitalization and perioperative clinical events (death or major complications) was assessed. Results: 205 patients were identified in this period. After analysis of the clinical records, 25 patients were excluded due to the use of branched or fenestrated endografts; 11 patients were excluded due to EVAS; in 17 patients, the indication wasn’t a primary aneurysm or it was a mycotic aneurysm and; in 46 patients the time of surgery wasn’t elective. In the remaining 106 patients, the incidence of PIS was 19% (n = 20). A statistically significant association was found between PIS and smoking (p = 0.005), COPD (p = 0.005) and statin therapy (p = 0.031). The multivariate logistic regression analysis, correcting for smoking and statin therapy, revealed that smoking is an important risk factor (OR 7.26, p = 0.03) and statin therapy a protective factor (OR = 0.341, p = 0.049). Regarding for the characteristics of the procedure, percutaneous approach, amount of contrast, intraoperative complications and need for complementary procedures, no differences were observed. A significant difference was found between groups in hospitalization length, with a median of 5 days in the group without PIS and 7 days in the PIS group (p = 0.034). No significant differences were found in cardiovascular events, complications or death within 30 days postoperatively between the groups. Conclusion: The incidence of PIS was 19%, which is concordant with literature. The results suggest that smoking is a risk factor. There was also an increase in hospitalization length in 2 days in PIS group. Statin therapy at the time of surgery is a modifiable factor that has been shown to be protective with respect to PIS, reinforcing the benefit of this therapy in the perioperative period of AAA patients.