Semaglutide Attenuates Anxious and Depressive-Like Behaviors and Reverses the Cognitive Impairment in a Type 2 Diabetes Mellitus Mouse Model Via the Microbiota-Gut-Brain Axis.

Newly conducted research suggests that metabolic disorders, like diabetes and obesity, play a significant role as risk factors for psychiatric disorders. This connection presents a potential avenue for creating novel antidepressant medications by repurposing drugs originally developed to address antidiabetic conditions. Earlier investigations have shown that GLP-1 (Glucagon-like Peptide-1) analogs exhibit neuroprotective qualities in various models of neurological diseases, encompassing conditions such as Alzheimer's disease, Parkinson's disease, and stroke. Moreover, GLP-1 analogs have demonstrated the capability to enhance neurogenesis, a process recognized for its significance in memory formation and the cognitive and emotional aspects of information processing. Nonetheless, whether semaglutide holds efficacy as both an antidepressant and anxiolytic agent remains uncertain. To address this, our study focused on a mouse model of depression linked to type 2 diabetes induced by a High Fat Diet (HFD). In this model, we administered semaglutide (0.05 mg/Kg intraperitoneally) on a weekly basis to evaluate its potential as a therapeutic option for depression and anxiety. Diabetic mice had higher blood glucose, lipidic profile, and insulin resistance. Moreover, mice fed HFD showed higher serum interleukin (IL)-1ß and lipopolysaccharide (LPS) associated with impaired humor and cognition. The analysis of behavioral responses revealed that the administration of semaglutide effectively mitigated depressive- and anxiety-like behaviors, concurrently demonstrating an enhancement in cognitive function. Additionally, semaglutide treatment protected synaptic plasticity and reversed the hippocampal neuroinflammation induced by HFD fed, improving activation of the insulin pathway, demonstrating the protective effects of semaglutide. We also found that semaglutide treatment decreased astrogliosis and microgliosis in the dentate gyrus region of the hippocampus. In addition, semaglutide prevented the DM2-induced impairments of pro-opiomelanocortin (POMC), and G-protein-coupled receptor 43 (GPR43) and simultaneously increased the NeuN + and Glucagon-like Peptide-1 receptor (GLP-1R+) neurons in the hippocampus. Our data also showed that semaglutide increased the serotonin (5-HT) and serotonin transporter (5-HTT) and glutamatergic receptors in the hippocampus. At last, semaglutide changed the gut microbiota profile (increasing Bacterioidetes, Bacteroides acidifaciens, and Blautia coccoides) and decreased leaky gut, improving the gut-brain axis. Taken together, semaglutide has the potential to act as a therapeutic tool for depression and anxiety.

Effects of PAHs on meiofauna from three estuaries with different levels of urbanization in the South Atlantic.

Estuarine environments are suggested to be the final receivers of human pollution and are impacted by surrounding urbanization and compounds carried by the river waters that flow from the continent. Polycyclic aromatic hydrocarbons (PAHs) are among the contaminants that can reach estuaries and can directly affect marine conservation, being considered highly deleterious to organisms living in these environments. This research investigated the meiofauna of three estuaries exposed to different levels of urbanization and consequently different levels of PAH concentrations, in order to assess how these compounds and environmental factors affect the distribution, structure and diversity of these interstitial invertebrates. A total of 15 major meiofauna groups were identified, with Nematoda being the dominant taxon (74.64%), followed by Copepoda (9.55%) and Polychaeta (8.56%). It was possible to observe significant differences in all diversity indices studied in the estuaries. With the exception of average density, the diversity indices (richness, Shannon index and evenness) were higher in the reference estuary, Goiana estuarine system (GES). On the other hand, the Timbó estuarine system (TES) had the lowest Shannon index value and richness, while the Capibaribe estuarine system (CES) had the lowest evenness value. The latter two estuaries (TES and CES) presented intermediate and high levels of urbanization, respectively. The ecological quality assessment (EcoQ) in the studied estuaries was classified from Poor to Moderate and the estuary with the lowest demographic density in its surroundings, GES, showed a better ecological quality (Moderate EcoQ). A significant distance-based multivariate linear modelling regression (DistLM) was observed between the environmental variables and the density of the meiobenthic community, where PAHs and pH were the main contributors to organism variation. The sediments were characterized by predominance of very fine sand and silt-clay in the most polluted environments, while the control site environment (GES) was dominated by medium grains. The highest concentrations of PAHs were found in the most urbanized estuaries, and directly affected the structure of the interstitial benthic community. The metrics used in the present study proved to be adequate for assessing the environmental quality of the investigated estuaries.

Effect of maternal diet rich in omega-6 and omega-9 fatty acids on the liver of LDL receptor-deficient mouse offspring.

BACKGROUND: Omega-6 fatty acids are important to fetal development. However, during gestation/lactation, these fatty acids may contribute toward the development of fat tissue. Omega-9 fatty acids are associated with a reduction in serum lipids and protection from liver disease. OBJECTIVES: The present study investigated the effect of the maternal intake of omega-6 and omega-9 in hypercholesterolemic mothers on the liver of the offspring. METHODS: LDL receptor-deficient mice were fed a diet rich in either omega-6 (E6D) or omega-9 (E9D) for 45 days prior to mating and until the birth of the offspring, evaluating the effect on the offspring liver in comparison to a standard diet (STD). RESULTS: Mothers fed with the E6D experienced an increase in total cholesterol (TC) and the offspring exhibited an increase in TC, hepatic triglycerides (TG), and CC-chemokine ligand (CCL)2/monocyte chemoattractant protein (MCP)-1 as well as a reduction in HDL. Histological analysis on this group revealed steatosis, leukocyte infiltrate, and increased CCL2/MCP-1 expression. The ultrastructural analysis revealed hepatocytes with lipid droplets and myofibroblasts. The offspring of mothers fed the standard diet exhibited low serum TC, but microvesicular steatosis was observed. The offspring of mothers fed the E9D exhibited lower serum and hepatic TG as well as higher LDL in comparison to the other diets. The histological analyses revealed lower steatosis and leukocyte infiltrate. CONCLUSIONS: The findings suggest that hypercholesterolemic mothers with a diet rich in omega-6 fatty acids predispose their offspring to steatohepatitis, whereas a diet rich in omega-9 has a protective effect.

Folic acid retention evaluation in preparations with wheat flour and corn submitted to different cooking methods by HPLC/DAD.

Folic acid content was evaluated in food preparations containing wheat and corn flour submitted to baking, deep-frying, and steaming. Commercially fortified flours showed the absence of folic acid. Flours with laboratory folic acid fortification showed 487 and 474 µg of folic acid in 100 g of wheat and corn flours, respectively. In the corn flour preparations, the cake had the highest retention (99%) when compared to couscous (97%). Besides, the cake showed higher retention when compared to the wheat flour preparations due to the interactions of the folic acid with the hydrophobic amino acids of the Zein, a protein found in corn. In wheat flour preparations, vitamin retention was 87%, 80% and 57% in bread, cake, and White sauce respectively. These findings relate to the change of the physicochemical properties of food components that occurs during mixing and cooking of the ingredients.

Chronic treatment with sildenafil stimulates Leydig cell and testosterone secretion.

The phosphodiesterase type 5 (PDE5) inhibitor, Sildenafil, is a novel, oral treatment approach for pulmonary hypertension. As Leydig cells present PDE5, this study was conducted to investigate the effects of the chronic treatment with Sildenafil (25 mg/kg) on male Swiss Webster mice steroidogenesis. After a 4-week long experimental design, Leydig cells were analysed by morphological and immunocytochemical procedures. Serum testosterone was assayed by radioimmunoassay. Leydig cells presented noteworthy ultrastructural alterations, such as a vesicular smooth endoplasmic reticulum, large vacuoles scattered through the cytoplasm, enlarged mitochondria with discontinue cristaes and whorle membranes with vesicles at the periphery, which are typical characteristics of an activated steroid-secreting cell. Important immunocytochemical labelling for steroidogenic acute regulatory protein, cytochrome P450 side-chain cleavage enzyme and testosterone were detected in isolated Leydig cells. In addition, Sildenafil-treated mice showed significant increased levels of total testosterone. The results obtained in the present study are consistent with the hypothesis that the accumulation of cyclic guanosine monophosphate by PDE5 inhibition could be involved in the androgen biosynthesis stimulation. Important clinical implications of hormonal disorders should be taken into account for patients with pulmonary hypertension.

Assessment of organotins and imposex in two estuaries of the northeastern Brazilian coast.

Butyltin compounds (BTs) were used worldwide, especially because of their properties as biocides. Due to its high toxicity, the use of tributyltin (TBT) in antifouling paints has been prohibited in most countries. The occurrence and impact of BTs were assessed in surface sediments and in Stramonita rustica populations of two tropical estuaries that host major ports in northeastern Brazil. ΣBT concentrations ranged from

Hydrocarbons in sediments along a tropical estuary-shelf transition area: Sources and spatial distribution.

Estuaries generally act as sediment traps and may retain a range of contaminants associated to this matrix. Aliphatic hydrocarbons (AHs) were investigated in Capibaribe Estuarine System and adjacent shelf, Northeast of Brazil, to evaluate the contamination and to better understand its functionality related to the coast. Fourteen sediment samples were analyzed, using gas chromatography with flame ionization detection. Total AHs concentrations ranged from 7.5 to 190.3µgg-1 and n-alkanes ranged from below detection limit (

A catalogue of the scaleworm genus Lepidonotus (Polynoidae, Polychaeta) from South America, with two new records for Brazilian waters.

The genus Lepidonotus is the largest in number of species within the Polynoidae, with more than 70 described species and subspecies. A catalogue of 18 nominal species and subspecies of Lepidonotus from South America is provided, with valid names, synonyms and original citations. Redescriptions and illustrations of two species based on new specimens collected along the littoral of the State of Paraíba, northeastern Brazil are included. Lepidonotus carinulatus and Lepidonotus natalensis are reported for the first time for Brazilian waters. A comparative table of characters for all reported species and subspecies of Lepidonotus from South America is provided.

Sources and distribution of polycyclic aromatic hydrocarbons in a an urbanized tropical estuary and adjacent shelf, Northeast of Brazil.

Located in Northeastern Brazil, the Capibaribe Estuarine System is an important ecosystem that supplies food and protection for nursery of several species with ecological and economic importance. It is located inside an urbanized area, receives untreated domestic and industrial effluents, and houses some marinas and the Harbor of Recife, which are very important to national and international communities. The distribution and sources of PAHs were investigated in sediments from CES and adjacent shelf. Total PAH concentrations ranged from non-detectable to 497.6 µg g(-1). Pyrolytic sources predominated in most of sites, but petrogenic PAHs were also recorded. The concentration decrease of PAHs toward adjacent shelf suggests that the main source of these compounds is in the upper portion of estuary, where there is an intense discharge of sewage, but atmospheric input also seems to be relevant to the area. The results reinforce the important role of an estuary in contaminant retention.

Effect of new thiazolidine derivatives LPSF/GQ-02 and LPSF/GQ-16 on atherosclerotic lesions in LDL receptor-deficient mice (LDLR(-/-)).

BACKGROUND: Atherosclerotic cardiovascular disease is a chronic inflammatory condition. Thiazolidinediones (TZDs) are used to enhance sensitivity to insulin and have demonstrated a protective effect over a variety of cardiovascular markers and risk factors. Controversially, the TZDs are associated with the development of heart failure. Thus, lines of research have invested in the search for new molecules in order to obtain more selective and less harmful treatment alternatives for the pathogenesis of atherosclerosis and its risk factors. METHODS: Animals were fed a diet rich in fat for 10 weeks. In the last 2 weeks, animals received either pioglitazone, LPSF/GQ-02, or LPSF/GQ-16 daily through gavage. At the end of the treatment, blood was collected for biochemical analysis and the aortas were dissected for subsequent analyses. RESULTS: No changes in the blood lipid profile were found following the use of the drugs in comparison to the control. However, the new thiazolidine derivatives were more efficient in improving insulin resistance in comparison to pioglitazone and the control group. Morphometric analyses revealed that neither pioglitazone nor LPSF/GQ16 led to satisfactory effects over atherosclerosis. However, LPSF/GQ-02 led to a reduction in area of the atherosclerotic lesions. Ultrastructural analyses revealed extensive degeneration of the endothelium and an increase in apoptotic cells in the subendothelial space following the use of pioglitazone and LPSF/GQ-16. However, LPSF/GQ-02 caused minimal cell alterations in the aortic endothelium. Regarding markers, endothelial nitric oxide synthase (eNOS) and matrix metalloproteinase 9 (MMP-9), LPSF/GQ-16, and pioglitazone exerted similar effects, increasing the expression of MMP-9, and had no effect on the expression of eNOS compared with the control group. On the other hand, LPSF/GQ-02 was effective in reducing the expression of MMP-9 and increased eNOS significantly. CONCLUSIONS: The results suggest that the new thiazolidine derivative LPSF/GQ-02 is a promising candidate for the treatment of atherosclerosis.