Algorithms for Liver Segmentation in Computed Tomography Scans: A Historical Perspective.

Oncology has emerged as a crucial field of study in the domain of medicine. Computed tomography has gained widespread adoption as a radiological modality for the identification and characterisation of pathologies, particularly in oncology, enabling precise identification of affected organs and tissues. However, achieving accurate liver segmentation in computed tomography scans remains a challenge due to the presence of artefacts and the varying densities of soft tissues and adjacent organs. This paper compares artificial intelligence algorithms and traditional medical image processing techniques to assist radiologists in liver segmentation in computed tomography scans and evaluates their accuracy and efficiency. Despite notable progress in the field, the limited availability of public datasets remains a significant barrier to broad participation in research studies and replication of methodologies. Future directions should focus on increasing the accessibility of public datasets, establishing standardised evaluation metrics, and advancing the development of three-dimensional segmentation techniques. In addition, maintaining a collaborative relationship between technological advances and medical expertise is essential to ensure that these innovations not only achieve technical accuracy, but also remain aligned with clinical needs and realities. This synergy ensures their applicability and effectiveness in real-world healthcare environments.

Longitudinal SARS-CoV-2 seroprevalence in Portugal and antibody maintenance 12 months after infection.

During the COVID-19 pandemic, Portugal has experienced three distinct SARS-CoV-2 infection waves. We previously documented the prevalence of SARS-CoV-2 immunity, measured by specific antibodies, in September 2020, 6 months after the initial moderate wave. Here, we show the seroprevalence changes 6 months later, up to the second week of March 2021, shortly following the third wave, which was one of the most severe in the world, and 2 months following the start of the vaccination campaign. A longitudinal epidemiological study was conducted, with a stratified quota sample of the Portuguese population. Serological testing was performed, including ELISA determination of antibody class and titers. The proportion of seropositives, which was 2.2% in September 2020, rose sharply to 17.3% (95% CI: 15.8-18.8%) in March 2021. Importantly, circulating IgG and IgA antibody levels were very stable 6 months after the initial determination and up to a year after initial infection, indicating long-lasting infection immunity against SARS-CoV-2. Moreover, vaccinated people had higher IgG levels from 3 weeks post-vaccination when compared with previously infected people at the same time post-infection.

Adaptation of Lipid Profiling in Depression Disease and Treatment: A Critical Review.

Major depressive disorder (MDD), also called depression, is a serious disease that impairs the quality of life of patients and has a high incidence, affecting approximately 3.8% of the world population. Its diagnosis is very subjective and is not supported by measurable biomarkers mainly due to the lack of biochemical markers. Recently, disturbance of lipid profiling has been recognized in MDD, in animal models of MDD or in depressed patients, which may contribute to unravel the etiology of the disease and find putative new biomarkers, for a diagnosis or for monitoring the disease and therapeutics outcomes. In this review, we provide an overview of current knowledge of lipidomics analysis, both in animal models of MDD (at the brain and plasma level) and in humans (in plasma and serum). Furthermore, studies of lipidomics analyses after antidepressant treatment in rodents (in brain, plasma, and serum), in primates (in the brain) and in humans (in plasma) were reviewed and give evidence that antidepressants seem to counteract the modification seen in lipids in MDD, giving some evidence that certain altered lipid profiles could be useful MDD biomarkers for future precision medicine.

Prevalence of SARS-CoV-2 Antibodies after First 6 Months of COVID-19 Pandemic, Portugal.

In September 2020, we tested 13,398 persons in Portugal for antibodies against severe acute respiratory syndrome coronavirus 2 by using a quota sample stratified by age and population density. We found a seroprevalence of 2.2%, 3-4 times larger than the official number of cases at the end of the first wave of the pandemic.

Exposure to tricyclic antidepressant nortriptyline affects early-life stages of zebrafish (Danio rerio).

Psychiatric drugs are among the leading medications prescribed for humans, with their presence in aquatic environments raising concerns relating to potentially harmful effects on non-target organisms. Nortriptyline (NTP) is a selective serotonin-norepinephrine reuptake inhibitor antidepressant, widely used in clinics and found in environmental water matrices. In this study, we evaluated the toxic effects of NTP on zebrafish (Danio rerio) embryos and early larval stages. Developmental and mortality analyses were performed on zebrafish exposed to NTP for 168 h at concentrations ranging from 500 to 46,900 µg/L. Locomotor behaviour and acetylcholinesterase (AChE) activity were evaluated by exposing embryos/larvae to lower NTP concentrations (0.006-500 µg/L). The median lethal NTP concentration after 168 h exposure was 2190 µg/L. Although we did not identify significant developmental changes in the treated groups, lack of equilibrium was already visible in surviving larvae exposed to ≥ 500 µg/L NTP. The behavioural analyses showed that NTP was capable of modifying zebrafish larvae swimming behaviour, even at extremely low (0.006 and 0.088 µg/L) environmentally relevant concentrations. We consistently observed a significant reduction in AChE activity in the animals exposed to 500 µg/L NTP. Our results highlight acute toxic effects of NTP on the early-life stages of zebrafish. Most importantly, exposure to environmentally relevant NTP concentrations may affect zebrafish larvae locomotor behaviour, which in turn could reduce the fitness of the species. More studies involving chronic exposure and sensitive endpoints are warranted to better understand the effect of NTP in a more realistic exposure scenario.

Neuromotor activity inhibition in zebrafish early-life stages after exposure to environmental relevant concentrations of caffeine.

Caffeine (CAF), a neuroactive compound, has been found in surface waters at concentrations ranging from few nanograms up to micrograms and may induce adverse effects in aquatic vertebrates. Thus, the aim of this study was to evaluate the potential of CAF in affecting fish early-life stages in a wide concentration range, including occurring levels in surface waters. Specimens of zebrafish in early-life stages were exposed to CAF for 168 h and survival, developmental alterations, locomotor activity and acetylcholinesterase activity were evaluated. CAF induced mortality in embryos unable to hatch or in larvae after hatching (LC50 - 168 h = 283.2 mg/L). Tail deformities were observed in organisms exposed to concentrations ≥ 40 mg/L, while edemas were found at concentrations of 100 mg/L. CAF also decreased the total swimming time and distance moved of exposed organisms (LOEC = 0.0006 mg/L). Locomotor inhibition may be associated with an acetylcholinesterase inhibition observed at concentration ≥ 0.0088 mg/L. Therefore, the hazard of CAF for fish populations deserves further attention since unexpected effects on neuro-behavioral parameters occurs at concentrations often detected in natural aquatic ecosystems.

Steroid androgen 17 alpha methyltestosterone used in fish farming induces biochemical alterations in zebrafish adults.

The 17 alpha methyltestosterone (MT) hormone is fed to Oreochromis niloticus larvae in fish farms with the purpose of inducing sex reversal. The aim of this study was to evaluate the toxicity and sub-lethality of MT (99.9% purity) and cMT (a commercial MT with 90% purity) in zebrafish (Danio rerio) adults, where the animals were exposed to concentrations of 0, 4, 23, 139, 833 and 5000 µg/L for 96 hours. Genotoxicity was evaluated by micronucleus test (MN), nuclear abnormalities (NA) and comet assay. A low genotoxic potential of MT was showed, inducing micronucleus, nuclear abnormalities and DNA damage in Danio rerio, depending on the use of MT or cMT, gender and tested concentrations. In the sub-lethality trials, there was a basal difference in the activity of the enzymatic biochemical markers for males and females, while the Glutatione S transferase (GST) activity decreased in all analyzed tissues, and for males the enzymatic activity decreased only in the intestine. Results suggest that MT has a toxic potential to fish because it alters enzymatic metabolic pathways and may pose a risk to the ecosystems.

The impact of antibiotic exposure in water and zebrafish gut microbiomes: A 16S rRNA gene-based metagenomic analysis.

In order to supply human demand for food, the aquaculture industry has been growing fast in the last years, being fish usually cultivated in overcrowded conditions. Hence, to prevent the rapidly disease spreading, antibiotics may be applied to both sick and healthy animals. Due to its broad spectrum, oxytetracycline (OTC) is one of the most used antibiotics in food-production. Yet, although useful to prevent infections, antibiotics may reshape aquatic animals' microbiome, disturbing hosts' welfare. However, the impact of this exposure to the organism microbiome and its surrounding environment is poorly understood. Then, the objective of this study was to analyze in detail the long-term effect of OTC in both zebrafish gut and water microbiomes. Zebrafish adults were exposed, via water, for two months to three concentrations of OTC (0, 10 and 10000 µg/L). Total DNA was extracted from gut and water samples and the V3-V4 region of the bacterial 16 S rRNA gene was sequenced using Illumina technology. Results of alpha and beta-diversity analyses revealed that long-term exposure to OTC impacted both zebrafish gut and water microbiomes. In water samples, effects were observed even at the lowest (10 µg/L) OTC concentration tested resulting in an increase in Deltaproteobacteria, namely the Myxococcales and Bdellovibrionales orders. On the other hand, effects on zebrafish gut were only observed at the highest concentration with the selection of Alphaproteobacteria and Actinobacteria classes. Although these classes are common in fish gut, the increase of Actinobacteria may represent a health problem since some genera like Gordonia are linked to some human infection disease. Nevertheless, in both gut and water, it was observed a decrease in Gamaproteobacteria, probably due to OTC mode of action. In silico functional metagenomic analysis revealed that OTC exposure selected general detoxification mechanisms. In addition, the abundance of functional genes involved in Quorum Sensing (QS) increased under OTC exposure suggesting that QS may help bacteria to survive OTC stress. Thus, future studies should consider post-exposure scenarios for a deeper analysis of the water and zebrafish gut resistome, since bacteria may react differently after exposure ceased.

Biochemical and behavioral responses of zebrafish embryos to magnetic graphene/nickel nanocomposites.

Graphene nanocomposites are emerging carbon-based materials with interesting electrical, mechanical, optical and magnetic properties, relevant for applications in different fields. Despite this increased use, the impact of graphene nanocomposites residues in the environment has not been properly studied. Thus, the goal of this work was to assess the toxicity of two nickel/graphene nanocomposites (G/Ni1 and G/Ni2) differing in size and shape to Danio rerio embryos. Their toxicity was evaluated using apical (mortality, development and hatching), biochemical [cholinesterase (ChE), glutathione-S-transferase (GST), and catalase (CAT) activities] and behavioral (locomotor activity) endpoints. At the tested concentrations, neither of the nanocomposites presented lethal or developmental effects. Nevertheless, both nanocomposites induced behavioral effects, reducing swimming distances. This effect was, however detected at lower concentrations in the G/Ni1 nanocomposite. At biochemical level, only G/Ni1 nanocomposite showed to interfere with the measured parameters, increasing the activities of ChE, CAT and GST. Differences in the effects induced by the two nanocomposites seem to be related not only with their size, but also with the shape and the ability to continuously release nickel ions to aqueous medium. This work highlights the importance of studying graphene nanocomposites effects to aquatic organisms even when acute toxicity is not expected. The relevance of the effects found in this work need to be further analyzed in light of the consequences to the long-term fitness of the organisms and in light of the environmental concentrations expected for this type of compounds.

Chronic effects of carbamazepine on zebrafish: Behavioral, reproductive and biochemical endpoints.

Carbamazepine (Cbz), one of the most prescribed pharmaceuticals in the world is often detected in surface waters and sediments. However, few studies addressed its chronic effects in fish. In the present study, Danio rerio adults were exposed for 63 days to Cbz (0 - control, 10 µg L-1 - concentration found in effluents, and 10,000 µg L-1 - 5% of LC50 at 72 h). Assessed endpoints were: feeding behavior, growth rate, number of eggs produced and their viability, histological alterations in female gonads, and biochemical biomarkers associated with antioxidant defenses (catalase - CAT, and glutathione S-transferase - GST activities), neurotransmission (acetylcholinesterase activity - AChE) and metabolism (lactate dehydrogenase - LDH). Cbz exposure increased the total time for food intake but did not affect D. rerio growth. Although the total number of eggs was not affected by Cbz exposure, the eggs viability was significantly impaired. Exposure to Cbz caused alterations in the female gonads follicular stages. In terms of biochemical endpoints, CAT activity in liver and gills, was sensitive to the pharmaceutical exposure presenting a decreased activity. AChE activity was induced in the head (both concentrations) and muscle (10,000 µg L-1). GST activity was increased in gills (both concentrations) but inhibited in the intestine. Concerning LDH, enzymatic activity was increased in the liver and decreased in muscle and gills. Several of the above-mentioned effects can be directly linked with effects at population level (e.g. feeding behavior) and occurred at environmental concentrations (the lowest concentration tested), thus serious concerns regarding risks posed by Cbz residues to fish populations arise with this study.

Endocrine disruption effects of p,p'-DDE on juvenile zebrafish.

The persistent organic pollutant p,p'-DDE, the major metabolite of the insecticide DDT, has displayed evidence of endocrine disruption through the inhibition of androgen binding to androgen receptors in different species. Although p,p'-DDE was continuously detected in wild fish with abnormal gonad development such as intersex, little is known about its mode of action during gonad development in fish. To elucidate the potential endocrine effects of this pollutant in zebrafish (Danio rerio), juveniles (30 days post hatch) were exposed to p,p'-DDE during the critical window of sexual differentiation. Fish were exposed to sublethal concentrations ranging from 0.01 to 20 µg l(-1) over 14 days and were maintained in control water for an additional 4 months. As core endpoints, the vitellogenin (vtg) concentration was measured at the end of exposure, and sex ratio and the gonadosomatic index were assessed 4 months after the end of exposure. An increase in vtg production in whole body homogenate was observed in fish exposed to 0.2 and 2.0 µg l(-1) p,p'-DDE. No significant differences were displayed in morphological parameters such as the gonadosomatic index of males and females or sex ratio. However, exposed females presented histopathological changes that include the reduction of the number of mature oocytes, which might impair their successful reproduction. These results demonstrate the ability of p,p'-DDE to cause endocrine disruption in zebrafish exposed during gonad differentiation of juvenile specimens. Furthermore, vtg induction by p,p'-DDE in juvenile zebrafish arises as a predictive marker for adverse effects of this DDT metabolite on the ovarian function of female zebrafish.

Is UV radiation changing the toxicity of compounds to zebrafish embryos?

At ecosystems level, environmental parameters such as temperature, pH, dissolved oxygen concentration and intensity of UV radiation (UVR) have an important role on the efficiency of organisms' physiological and behavioral performances and consequently on the capacity of response to contaminants. Insignificant alterations of these parameters may compromise this response. In addition, these parameters can additionally alter chemical compounds by inducing their degradation, producing thereafter other metabolites. Understanding the combined effects of chemicals and environmental parameters is absolutely necessary for an adequate prediction of risk in aquatic environments. According to this scenario, this work aims at studying the combined toxicity of UVR and three xenobiotics: the biocide triclosan (TCS), the metal chromium (as potassium dichromate, PD) and the fungicide prochloraz (PCZ). To achieve this goal zebrafish (Danio rerio) embryos (3h post fertilization (hpf)) were exposed to several concentrations of each chemical combined with different UV intensities; mortality and eggs were recorded every 24h for the all test duration (96 h). Results showed different response patterns depending on the toxicant, stress levels and duration of exposure. The combination of UVR and TCS indicated a dose ratio deviation where synergism was observed when UVR was the dominant stressor (day 2). The combination of UVR and PD presented a dose level dependency at day 3 indicating antagonism at low stress levels, changing with time where at day 4, a dose ratio deviation showed statistically that synergism occurred at higher PD concentrations. Finally, UVR combined with PCZ indicated a dose ratio at day 3 and dose level deviation at day 4 of exposure, suggesting a synergistic response when PCZ is the dominant stressor in the combination. The obtained results in this study highlighted the importance of taking into account the possible interaction of stressors and time of exposure to better predict environmental risk.

Suitability of enzymatic markers to assess the environmental condition of natural populations of Gambusia affinis and Daphnia magna--a case study.

In recent years, the use of biochemical markers, especially in the assessment of toxic effects and modes of action, under controlled laboratory conditions has increased. However, transposing their use to in situ monitoring or risk assessment evaluations has encountered barriers, mainly related to the difficulty in interpreting the meaning of biochemical variation. In this work, we aimed at understanding if biochemical marker activities (cholinesterase, glutathione S-transferase and lactate dehydrogenase) can be used to monitor the health status of natural populations of fish (Gambusia affinis) and daphnids (Daphnia magna). For that, two ponds with different water properties were chosen as study sites, and organisms collected at four sampling periods along the year. The pattern of biochemical marker responses was not the same in the two species, showing higher integrated biochemical marker response values in the winter for G. affinis and in the autumn for D. magna, suggesting specificities that must be taken into account in biomonitoring programmes by including representative species of several trophic levels. In the case of G. affinis, the differences in key physicochemical parameters between the two ponds (especially dissolved oxygen levels) did not seem to affect biochemical marker levels as if organisms were already perfectly adapted to their environment. In general, seasonal variation of water quality seems to have an important role on biochemical marker responses. Several parameters above Environmental Quality Standards were identified such as dissolved oxygen (DO), ammonia, nitrites, sulphides and metals, but eventual responses to these stressors could not be discriminated from natural variation except for particular cases.

Biological responses in Danio rerio by the disinfectant SDBS in SARS-CoV-2 pandemic.

The use of disinfectants, such as Sodium Dodecylbenzene Sulfonic acid salt (SDBS), has grown since the SARS-CoV-2 pandemic, with environmentally unknown consequences. The present study analyzed SDBS effects in the fish species Danio rerio, using a combination of biomarkers. Our data reported that larvae had their total locomotor activity increased when exposed to 1 mg/L of SDBS, but this parameter was decreased in fish exposed to 5 mg/L. A significant increment of erratic movements was reported in fish exposed to 1 and 5 mg/L of SDBS. These concentrations inhibited CYP1A1/CYP1A2, and of GSTs inhibition, suggesting SDBS is not preferentially biotransformed by these routes. Results concerning the antioxidant defense biomarkers (CAT and GPx) showed no straightforward pattern, suggesting SDBS exposure may have resulted in changes in redox balance. Finally, acetylcholinesterase activity increased. In summary, increased use of SDBS in a near future may result in deleterious effects in environmentally exposed fish.

Radiomic Pipelines for Prostate Cancer in External Beam Radiation Therapy: A Review of Methods and Future Directions.

Background: Prostate Cancer (PCa) is asymptomatic at an early stage and often painless, requiring only active surveillance. External Beam Radiotherapy (EBRT) is currently a curative option for localised and locally advanced diseases and a palliative option for metastatic low-volume disease. Although highly effective, especially in a hypofractionation scheme, 17.4% to 39.4% of all patients suffer from cancer recurrence after EBRT. But, radiographic findings also correlate with significant differences in protein expression patterns. In the PCa EBRT workflow, several imaging modalities are available for grading, staging and contouring. Using image data characterisation algorithms (radiomics), one can provide a quantitative analysis of prognostic and predictive treatment outcomes. Methods: This literature review searched for original studies in radiomics for PCa in the context of EBRT. Following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines, this review includes 73 new studies and analyses datasets, imaging modality, segmentation technique, feature extraction, selection and model building methods. Results: Magnetic Resonance Imaging (MRI) is the preferred imaging modality for radiomic studies in PCa but Computed Tomography (CT), Positron Emission Tomography (PET) and Ultrasound (US) may offer valuable insights on tumour characterisation and treatment response prediction. Conclusions: Most radiomic studies used small, homogeneous and private datasets lacking external validation and variability. Future research should focus on collaborative efforts to create large, multicentric datasets and develop standardised methodologies, ensuring the full potential of radiomics in clinical practice.

Changes in bryophyte functional composition during post-fire succession.

Climate and land-use changes are altering fire regimes in many regions around the world. To date, most studies have focused on the effects of altered fire regimes on woody and herbaceous communities, while the mechanisms driving post-fire bryophyte succession remain poorly understood, particularly in Mediterranean-type ecosystems. Here, we examined changes in bryophyte functional composition along a post-fire chronosequence (ranging from 1 to 20+ years) in Pyrenean oak woodlands (northeastern Portugal). To do so, we defined bryophyte functional groups based on seven morphological, reproductive, and life history traits. Then, we fitted linear and structural equation models to disentangle the direct and indirect effects of fire (time since fire and fire intensity), vegetation structure, climate, topography, and edaphic conditions on the abundance of each group. We identified two main functional groups: early colonizers (species with traits associated with strong colonization ability and desiccation tolerance) and perennial stayers (species with high competitive ability, i.e., large perennial mosses). Overall, the abundance of early colonizer species decreased with time since fire and increased with fire intensity, while the opposite was observed for perennial stayers. Thus, successional dynamics reflected a trade-off between species' competitive and colonization abilities, highlighting the role of biotic interactions later in succession. Patterns of functional composition were also consistent with changes in environmental conditions during succession, suggesting that species may experience stressful conditions (i.e., high radiation and low water availability) in early stages of post-fire succession. Our results also indicate that increased fire intensity may alter successional trajectories, leading to long-term changes in bryophyte communities. By understanding the response of bryophyte communities to fire, we were able to identify species with potential use as soil restoration materials.

Impact of chronic fluoxetine exposure on zebrafish: From fatty acid profile to behavior.

The consumption of antidepressants, such as fluoxetine, has increased over the years and, as a result, they are increasingly found in aquatic systems. Given the increasing use of zebrafish as an animal model in toxicological studies, this work proposed to evaluate the effects of chronic exposure, for 21 days, to fluoxetine at environmentally relevant concentrations (1, 10, 100, and 1000 ng/L). The behavioral tests performed did not reveal significant effects of fluoxetine. However, oxidative stress and changes in energy metabolism were detected after exposure to the highest concentrations of fluoxetine tested, namely a decrease in glutathione S-transferase (GST) activity (decrease of ca. 31%), increase in catalase (CAT) activity (increase of ca. 71%), and decrease in lactate dehydrogenase (LDH) activity (decrease of ca. 53%). Analysis of the fatty acid profile (FA) revealed a decrease in the omega-3 FA, docosahexaenoic acid (DHA), C22:6 (decrease in relative abundance between 6% and 8% for both the head and body), an increase in omega-6 FA, linoleic acid (LA), C18:2, (increased relative abundance between 8% and 11% in the head and between 5% and 9% in the body), which may suggest changes in the inflammatory state of these organisms. The integrated analysis adopted proved to be useful in detecting subindividual effects of fluoxetine and modes of action in fish.

"Green" synthesized versus chemically synthesized zinc oxide nanoparticles: In vivo antihyperglycemic activity and pharmacokinetics.

Zinc is one of the most studied trace elements, commonly used as supplement in diabetes treatment. By its involvement in the synthesis, secretion of insulin, promotion of insulin sensitivity and its multiple enzymatic functions it is known to contribute to reduce hyperglycemia. Researchers have shown that zinc administered under the form of zinc oxide nanoparticles (ZnONPs) is more effective than under its ionic form. Studies evaluating the antihyperglycemic activity of these nanocarriers include both ZnONPs synthesised using plants (i.e. green synthesized) or chemically synthesized. The present work aims to compare green synthesized ZnONPs with the marketed chemically synthesized ones. Green ZnONPs were synthesized using the aqueous extract of the stem bark of the medicinal plant Panda oleosa and zinc nitrate hexahydrate. Both nanocarriers were compared in terms of optical properties, morphology, composition, chemical functions, resistance to oxidation, in vivo antihyperglycemic activity via oral glucose tolerance test (OGTT) and pharmacokinetics in relation to zinc in C57BL/6J mice. A UV absorption peak was observed at 354 nm and 374 nm for the green and marketed ZnONPs, respectively. The shape and hydrodynamic diameters were anisotropic and of 228.8 ± 3.0 nm for the green ZnONPs and spherical and of 225.6 ± 0.9 nm for the marketed ZnONPs. Phenolic compounds accounted for 2.58 ± 0.04% of the green ZnONPs and allowed them to be more stable and unaffected by an oxidizing agent during the experiment, while the marketed chemically synthesized ZnONPs aggregated with or without contact with an oxidizing agent. No significant differences were observed on the amounts of zinc absorbed when comparing green ZnONPs, chemically synthesized ZnONPs and zinc sulfate in a pharmacokinetics study in normoglycemic mice. When evaluating the in vivo hypoglycemic activity of the nanocarriers in obese/diabetic mice, green synthesized ZnONPs displayed a significant hypoglycemic effect compared with the chemically synthesized nanoparticles following an OGTT. Altogether, these data indicate that phytocompounds, as catechin derivatives and polyphenols, attached to the green synthesized ZnONPs' surface, could contribute to their hypoglycemic activity. The comparison thus demonstrated that green synthesized ZnONPs are significantly more efficient than chemically ones at reducing hyperglycemia regardless of their absorption.

Effects of semaglutide-loaded lipid nanocapsules on metabolic dysfunction-associated steatotic liver disease.

Metabolic dysfunction-associated steatotic liver disease (MASLD) is a highly prevalent chronic liver disease that can progress to end-stage conditions with life-threatening complications, but no pharmacologic therapy has been approved. Drug delivery systems such as lipid nanocapsules (LNC) are very versatile platforms that are easy to produce and can induce the secretion of the native glucagon-like peptide 1 (GLP-1) when orally administered. GLP-1 analogs are currently being studied in clinical trials in the context of MASLD. Our nanosystem provides with increased levels of the native GLP-1 and increased plasmatic absorption of the encapsulated GLP-1 analog (semaglutide). Our goal was to use our strategy to demonstrate a better outcome and a greater impact on the metabolic syndrome associated with MASLD and on liver disease progression with our strategy compared with the oral marketed version of semaglutide, Rybelsus®. Therefore, we studied the effect of our nanocarriers on a dietary mouse model of MASLD, the Western diet model, during a daily chronic treatment of 4 weeks. Overall, the results showed a positive impact of semaglutide-loaded lipid nanocapsules towards the normalization of glucose homeostasis and insulin resistance. In the liver, there were no significant changes in lipid accumulation, but an improvement in markers related to inflammation was observed. Overall, our strategy had a positive trend on the metabolic syndrome and at reducing inflammation, mitigating the progression of the disease. Oral administration of the nanosystem was more efficient at preventing the progression of the disease to more severe states when compared to the administration of Rybelsus®, as a suspension.