Alzheimer’s disease (AD) is a progressive neurodegenerative disease in which the formation of extracellular aggregates of amyloid beta (Aβ) peptide, fibrillary tangles of intraneuronal tau and ...microglial activation are major pathological hallmarks. One of the key molecules involved in microglial activation is galectin-3 (gal3), and we demonstrate here for the first time a key role of gal3 in AD pathology. Gal3 was highly upregulated in the brains of AD patients and 5xFAD (familial Alzheimer’s disease) mice and found specifically expressed in microglia associated with Aβ plaques. Single-nucleotide polymorphisms in the
LGALS3
gene, which encodes gal3, were associated with an increased risk of AD. Gal3 deletion in 5xFAD mice attenuated microglia-associated immune responses, particularly those associated with TLR and TREM2/DAP12 signaling. In vitro data revealed that gal3 was required to fully activate microglia in response to fibrillar Aβ. Gal3 deletion decreased the Aβ burden in 5xFAD mice and improved cognitive behavior. Interestingly, a single intrahippocampal injection of gal3 along with Aβ monomers in WT mice was sufficient to induce the formation of long-lasting (2 months) insoluble Aβ aggregates, which were absent when gal3 was lacking. High-resolution microscopy (stochastic optical reconstruction microscopy) demonstrated close colocalization of gal3 and TREM2 in microglial processes, and a direct interaction was shown by a fluorescence anisotropy assay involving the gal3 carbohydrate recognition domain. Furthermore, gal3 was shown to stimulate TREM2–DAP12 signaling in a reporter cell line. Overall, our data support the view that gal3 inhibition may be a potential pharmacological approach to counteract AD.
Oestrus ovis is an obligate parasite that causes myiasis in domestic ruminants, being commonly found in the Mediterranean area. From 2009 to 2019 a total of 3476 heads of culling sheep and goats from ...the Mediterranean coast of Spain were examined for the presence of O. ovis. The total prevalence was 56.3%, significantly higher in sheep than in goats (61.2% and 43%, respectively). Differences were found in the mean annual prevalence, with the highest value being registered in 2018 (61.7%) and the lowest in 2012 (50.3%). Autumn, for sheep, and winter, for goats, were the seasons with the highest number of infested specimens. Temperature, but not rainfall, was found to be associated with prevalence (p < 0.05). Most L1 were found in the anatomic region I (septum, meatus, and ventral conchae), while L2 and L3 were mainly located in regions II (nasopharynx, ethmoid labyrinth, and dorsal conchae), and III (sinuses). The overall intensity was 12.8 larvae per head, significantly higher in sheep (13.3) than in goats (3.5). Our results confirm the high prevalence of O. ovis in sheep and goats in this geographic area over the last decade, with the trend increasing in recent years in association with higher mean temperatures.
There is an increasing trend of oestrosis in association with higher temperatures in the last decade.
Both the prevalence and the intensity of Oestrus ovis are higher in sheep than in goats.
Autumn for sheep, and winter for goats, are the seasons with the highest risk of larvae presence.
The advent of high-throughput single-cell transcriptomic analysis of microglia has revealed different phenotypes that are inherently associated with disease conditions. A common feature of some of ...these activated phenotypes is the upregulation of galectin-3. Representative examples of these phenotypes include disease-associated microglia (DAM) and white-associated microglia (WAM), whose role(s) in neuroprotection/neurotoxicity is a matter of high interest in the microglia community. In this review, we summarise the main findings that demonstrate the ability of galectin-3 to interact with key pattern recognition receptors, including, among others, TLR4 and TREM2 and the importance of galectin-3 in the regulation of microglia activation. Finally, we discuss increasing evidence supporting the involvement of this lectin in the main neurodegenerative diseases, including Alzheimer's disease, Parkinson's disease, Huntington's disease, amyotrophic lateral sclerosis, multiple sclerosis, traumatic brain injury, and stroke.
In 2022, the United Kingdom reported an increase in drug resistance in Shigella sonnei isolates. We report 33 cases in Spain genetically related to the UK cases and 4 cases with similar antimicrobial ...resistance profiles infected with genetically distant strains. Our results suggest circulation of multiple genetic clusters of multidrug-resistant S. sonnei in Spain.
The present study therefore aims to examine trait and state anxiety, sleep habits and executive functioning during 1 year and a half of the COVID-19 pandemic in children and adolescents through the ...lens of parents. Assessments were conducted at three different times: April 2020 (T1), October 2020 (T2) and October 2021 (T3). The main sample included 953 children and adolescents aged 6 to 18 years, and scales were used to assess anxiety (STAIC), sleep habits (BEARS) and executive functioning (BRIEF-2). The results showed that 6 months after the outbreak of the pandemic, state and trait anxiety, sleep disturbances and executive dysfunctions increased significantly. One and a half year later, trait anxiety and sleep disturbances have been maintained, while state anxiety and executive dysfunction have decreased their scores obtaining scores similar to those of April 2020. In conclusion, there has been a further decrease in children and adolescents’ mental health since the beginning of the pandemic, and it seems to remain at the present time, such as trait anxiety as a part of the personality.
Abstract
Context
Human obesity is associated with increased circulating TNF-α, a proinflammatory cytokine that induces hepatocyte cell death.
Objective
The potential beneficial effects of acylated ...and desacyl ghrelin in the progression of nonalcoholic fatty liver disease (NAFLD) to nonalcoholic steatohepatitis in obesity via the inhibition of TNF-α–induced hepatocyte apoptosis, autophagic cell death, and pyroptosis were investigated.
Design, Settings, and Participants
Plasma ghrelin isoforms and TNF-α were measured in 158 participants, and hepatocyte cell death was evaluated in liver biopsies from 76 patients with morbid obesity undergoing bariatric surgery with available liver echography and pathology analysis. The effect of acylated and desacyl ghrelin on basal and TNF-α–induced cell death was determined in vitro in human HepG2 hepatocytes.
Results
Circulating TNF-α and the acylated/desacyl ghrelin ratio were increased, whereas desacyl ghrelin levels were decreased in patients with obesity and NAFLD. Six months after bariatric surgery, decreased acylated/desacyl ghrelin levels, and improved hepatic function were found. Patients with obesity and type 2 diabetes showed increased hepatic ghrelin O-acyltransferase transcripts as well as an increased hepatic apoptosis, pyroptosis, and compromised autophagy. In HepG2 hepatocytes, acylated and desacyl ghrelin treatment reduced TNF-α–induced apoptosis, evidenced by lower caspase-8 and caspase-3 cleavage, as well as TUNEL-positive cells and pyroptosis, revealed by decreased caspase-1 activation and lower high-mobility group box 1 expression. Moreover, acylated ghrelin suppressed TNF-α–activated hepatocyte autophagy, as evidenced by a decreased LC3B-II/I ratio and increased p62 accumulation via AMPK/mTOR.
Conclusions
Ghrelin constitutes a protective factor against hepatocyte cell death. The increased acylated/desacyl ghrelin ratio in patients with obesity and NAFLD might constitute a compensatory mechanism to overcome TNF-α–induced hepatocyte apoptosis, autophagy, and pyroptosis.
Ghrelin acts as a survival factor by reducing TNF-α–induced apoptosis, autophagy, and pyroptosis mediated by HMGB1 in human hepatocytes, and thus prevents the progression of NAFLD to NASH.
Background: Ungulates from zoological institutions are frequently used as founders in reintroduction programmes. These animals are subject to specific parasite management as parasitic infections have ...previously been associated with failed Bovidae reintroductions.
Methods: Questionnaires to obtain data on how these institutions screen for seasonal parasite presence and the clinical signs they induced in threatened ungulates were sent to 65 institutions involved in European Ex situ Programmes (58.5% response rate). Temperature and relative humidity data were also obtained to categorize each zoological centre.
Results: Strongyloides spp. (52.6%), Trichuris spp. (42.1%), Trichostrongylidae family (39.4%) and Eimeria spp. (36.8%) were the most frequently reported parasites in the received questionnaires. Climatic variables did not influence parasite presence.
Conclusion: Our results suggest that artificial microenvironments created by husbandry practices and enclosure design in zoos could create hotspots for gastrointestinal parasites. To maximise the success of reintroduction projects, we recommend that the influence of microclimates on parasite burdens be evaluated.
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