NLRP3 Inflammasome’s Activation in Acute and Chronic Brain Diseases—An Update on Pathogenetic Mechanisms and Therapeutic Perspectives with Respect to Other Inflammasomes

Increasingly prevalent acute and chronic human brain diseases are scourges for the elderly. Besides the lack of therapies, these ailments share a neuroinflammation that is triggered/sustained by different innate immunity-related protein oligomers called inflammasomes. Relevant neuroinflamma- tion players such as microglia/monocytes typically exhibit a strong NLRP3 inflammasome activation. Hence the idea that NLRP3 suppression might solve neurodegenerative ailments. Here we review the recent Literature about this topic. First, we update conditions and mechanisms, including RNAs, ex- tracellular vesicles/exosomes, endogenous compounds, and ethnic/pharmacological agents/extracts regulating NLRP3 function. Second, we pinpoint NLRP3-activating mechanisms and known NLRP3 inhibition effects in acute (ischemia, stroke, hemorrhage), chronic (Alzheimer’s disease, Parkinson’s disease, Huntington’s disease, MS, ALS), and virus-induced (Zika, SARS-CoV-2, and others) human brain diseases. The available data show that (i) disease-specific divergent mechanisms activate the (mainly animal) brains NLRP3; (ii) no evidence proves that NLRP3 inhibition modifies human brain diseases (yet ad hoc trials are ongoing); and (iii) no findings exclude that concurrently activated other-than-NLRP3 inflammasomes might functionally replace the inhibited NLRP3. Finally, we highlight that among the causes of the persistent lack of therapies are the species difference problem in disease models and a preference for symptomatic over etiologic therapeutic approaches. Therefore, we posit that human neural cell-based disease models could drive etiological, pathogenetic, and therapeutic advances, including NLRP3’s and other inflammasomes’ regulation, while minimizing failure risks in candidate drug trials

Effects of a Ceiling Fan Ventilation System and THI on Young Limousin Bulls’ Social Behaviour

The study investigated the relationship between the temperature humidity index (THI) and the behaviour of 24 young fattening Limousin bulls reared in two farms in Tuscany, Italy. In each farm, six animals were undergone to ceiling fans (switched on at THI values up to 72), and six animals represented the control group. The trial lasted three days for two consecutive weeks in August 2020. Behavioural observations were conducted using scan sampling technique and eating, ruminating, drinking, resting and other social activities were registered every 5 min, from 9.30 am to 4.00 pm. Two different microclimatic conditions were evaluated to assess the effect of the ventilation system: normal (THI < 78) and alert (THI ≥ 78) conditions. Results showed that the ventilation system had significant effects increasing inactivity and lying down compared to control groups and decreasing eating and drinking activities. THI alert condition caused a significant decrease in eating and an increase in lying down behaviours. Ventilation system did not influence the animals’ cleanliness. The ceiling fans’ efficiency in changing the behaviour of young fattening bulls was demonstrated but further studies are needed to assess the ventilation system effects, especially during longer heat stress periods

Influence of Wet Ageing on Beef Quality Traits

Fresh samples of Longissimus thoracis of Charolais (n = 12), Romagnola (n = 15), Limousine (n = 77), and crossbreed (n = 62) animals were evaluated with different storage periods (0, 4, 9, and 14 days). Proximate analysis (i.e., pH, humidity, color, free water content, and physical parameters) was performed for each sample. The data obtained were evaluated with a mixed model, setting 5 fixed effects (breed, storage time, animals age, EUROP conformation, number of animal transports) and the animal as random. The results demonstrated that meat quality was affected mainly by the wet ageing period and that the visual and tactile parameters were also found to be susceptible to the storage time. The conservation entailed a decrease in meat humidity and an increase in L* and b* traits; it also led to a decrease in the hardness of the sample, in turn affecting the other texture profile analysis parameters considered. Fixed effects affected in different ways the traits analyzed i.e., pH and humidity changed with breed, as well as with EUROP classification, animals’ age for some TPA parameters, and the number of animal transports for both visual and tactile parameters. Wet ageing influenced the meat quality, often improving it, confirming how important further research would be to identify precise storage times in relation to the parameters studied

Metabolic slowing vanished 5 years after sleeve gastrectomy in patients with obesity and prediabetes/diabetes

Resting energy expenditure (REE) decreases after weight loss more than expected according to body composition changes. Metabolic adaptation (MA) or metabolic slowing represents the difference between measured (m) and predicted (p) REE and it is not clear if it persists in the long-term. The aim of this study is to evaluate MA occurring 1 year (V1) and 5 years (V5) after laparoscopic sleeve gastrectomy (LSG) in patients with obesity and normal glucose tolerance, prediabetes (preDM) and type 2 diabetes (T2DM)

Characterization of subcutaneous and omental adipose tissue in patients with obesity and with different degrees of glucose impairment

Abstract Although obesity represents a risk factor for the development of type 2 diabetes mellitus (T2DM), the link between these pathological conditions is not so clear. The manner in which the different elements of adipose tissue (AT) interplay in order to grow has been suggested to have a role in the genesis of metabolic complications, but this has not yet been fully addressed in humans. Through IHC, transmission electron microscopy, cytometry, and in vitro cultures, we described the morphological and functional changes of subcutaneous and visceral AT (SAT and VAT) in normoglycemic, prediabetic and T2DM patients with obesity compared to lean subjects. In both SAT and VAT we measured a hypertrophic and hyperplastic expansion, causing similar vascular rarefaction in obese patients with different degrees of metabolic complications. Capillaries display dysfunctional basement membrane thickening only in T2DM patients evidencing VAT as a new target of T2DM microangiopathy. The largest increase in adipocyte size and decrease in adipose stem cell number and adipogenic potential occur both in T2DM and in prediabetes. We showed that SAT and VAT remodeling with stemness deficit is associated with early glucose metabolism impairment suggesting the benefit of an AT-target therapy controlling hypertrophy and hyperplasia already in prediabetic obese patients