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This Special Issue collects some scientific pieces of the multifaceted research on the mast cell (MC), and it intends to highlight the broad spectrum of activity that MCs have, both in physiological conditions and in pathological states, focusing attention on some of them [...].

Fear conditioning constitutes the best and most reproducible paradigm to study the neurobiological mechanisms underlying emotions. On the other hand, studies on the synaptic plasticity phenomena underlying fear conditioning present neural circuits enforcing this learning pattern related to post-traumatic stress disorder (PTSD). Notably, in both humans and the rodent model, fear conditioning and context rely on dependent neurocircuitry in the amygdala and prefrontal cortex, cingulate gyrus, and hippocampus. In this review, an overview of the role that classical neurotransmitters play in the contextual conditioning model of fear, and therefore in PTSD, was reported.

The intestinal epithelium constitutes a selectively permeable barrier between the internal and external environment that allows the absorption of nutrients, electrolytes, and water, as well as an effective defense against intraluminal bacteria, toxins, and potentially antigenic material. Experimental evidence suggest that intestinal inflammation is critically dependent on an imbalance of homeostasis between the gut microbiota and the mucosal immune system. In this context, mast cells play a crucial role. The intake of specific probiotic strains can prevent the development of gut inflammatory markers and activation of the immune system. Here, the effect of a probiotic formulation containing L. rhamnosus LR 32, B. lactis BL04, and B. longum BB 536 on intestinal epithelial cells and mast cells was investigated. To mimic the natural host compartmentalization, Transwell co-culture models were set up. Co-cultures of intestinal epithelial cells interfaced with the human mast cell line HMC-1.2 in the basolateral chamber were challenged with lipopolysaccharide (LPS), and then treated with probiotics. In the HT29/HMC-1.2 co-culture, the probiotic formulation was able to counteract the LPS-induced release of interleukin 6 from HMC-1.2, and was effective in preserving the epithelial barrier integrity in the HT29/Caco-2/ HMC-1.2 co-culture. The results suggest the potential therapeutic effect of the probiotic formulation.

The human coronavirus SARS-CoV-2 or COVID-19 that emerged in late 2019 causes a respiratory tract infection and has currently resulted in more than 627 million confirmed cases and over 6.58 million deaths worldwide up to October 2022. The highest death rate caused by COVID-19 is in older people, especially those with comorbidities. This evidence presents a challenge for biomedical research on aging and also identifies some key players in inflammation, including mast cells and platelets, which could represent important markers and, at the same time, unconventional therapeutic targets. Studies have shown a decrease in the diversity of gut microbiota composition in the elderly, particularly a reduced abundance of butyrate-producing species, and COVID-19 patients manifest faecal microbiome alterations, with an increase in opportunistic pathogens and a depletion of commensal beneficial microorganisms. The main purpose of this narrative review is to highlight how an altered condition of the gut microbiota, especially in the elderly, could be an important factor and have a strong impact in the lung homeostasis and COVID-19 phenomenon, jointly to the activation of mast cells and platelets, and also affect the outcomes of the pathology. Therefore, a targeted and careful control of the intestinal microbiota could represent a complementary intervention to be implemented for the management and the challenge against COVID-19.

In healthy individuals, tight junction proteins (TJPs) maintain the integrity of the intestinal barrier. Dysbiosis and increased intestinal permeability are observed in several diseases, such as inflammatory bowel disease. Many studies highlight the role of probiotics in preventing intestinal barrier dysfunction. The present study aims to investigate the effects of a commercially available probiotic formulation of L. rhamnosus LR 32, B. lactis BL 04, and B. longum BB 536 (Serobioma, Bromatech s.r.l., Milan, Italy) on TJPs and the integrity of the intestinal epithelial barrier, and the ability of this formulation to prevent lipopolysaccharide-induced, inflammation-associated damage. An in vitro model of the intestinal barrier was developed using a Caco-2 cell monolayer. The mRNA expression levels of the TJ genes were analyzed using real-time PCR. Changes in the amounts of proteins were assessed with Western blotting. The effect of Serobioma on the intestinal epithelial barrier function was assessed using transepithelial electrical resistance (TEER) measurements. The probiotic formulation tested in this study modulates the expression of TJPs and prevents inflammatory damage. Our findings provide new insights into the mechanisms by which probiotics are able to prevent damage to the gut epithelial barrier.

Multiple Sclerosis is a chronic neurological disease characterized by demyelination and axonal loss. This pathology, still largely of unknown etiology, carries within it a complex series of etiopathogenetic components of which it is difficult to trace the origin. An inflammatory state is likely to be the basis of the pathology. Crucial elements of the inflammatory process are the interactions between platelets and mast cells as well as the bacterial component of the intestinal microbiota. In addition, the involvement of mast cells in autoimmune demyelinating diseases has been shown. The present work tries to hang up on that Ariadne's thread which, in the molecular complexity of the interactions between mast cells, platelets, microbiota and inflammation, characterizes Multiple Sclerosis and attempts to bring the pathology back to the causal determinism of psychopathological phenomenology. Therefore, we consider the possibility that the original error of Multiple Sclerosis can be investigated in the genetic origin of the depressive pathology.

Neuroinflammation is a feature of many classic neurodegenerative diseases. In the healthy brain, microglia cells are distributed throughout the brain and are constantly surveilling the central nervous system (CNS). In response to CNS injury, microglia quickly react by secreting a wide array of apoptotic molecules. Virgin olive oil (VOO) is universally recognized as a symbol of the Mediterranean diet. In the current study, using lipopolysaccharide (LPS)-stimulated BV2 microglia, the anti-inflammatory effects of VOO phenolic extracts from Moraiolo cultivar (MVOO-PE) were investigated. The results showed that low concentration of MVOO-PE prevented microglia cell death and attenuated the LPS-induced activation of toll-like receptor 4 (TLR4)/NOD-like receptor pyrin domain-containing-3 (NLRP3) signaling cascade. The levels of TLR4 and NF-kB were diminished, as well as NLRP3 inflammasome and interleukin-1β (IL-1β) production. Cyclooxygenase-2 (COX-2) isoenzyme and ionized calcium binding adaptor molecule 1 (Iba-1) inflammatory mediator were also reduced. By modulating the TLR4/NLRP3 axis, MVOO-PE pretreatment was able to significantly down-regulate the mRNA expression of inflammatory mediators and suppress the cytokine secretion. Finally, we showed protective effect of MVOO-PE in a transwell neuron-microglia co-culture system. In conclusion, these results suggest that MVOO-PE could exerts anti-inflammatory activity on brain cells and become a promising candidate for preventing several neuroinflammatory diseases.

Studies on the relationship between reactive oxygen species (ROS)/manganese superoxide dismutase (MnSOD) and sphingomyelinase (SMase) are controversial. It has been demonstrated that SMase increases the intracellular ROS level and induces gene expression for MnSOD protein. On the other hand, some authors showed that ROS modulate the activation of SMase. The human recombinant manganese superoxide dismutase (rMnSOD) exerting a radioprotective effect on normal cells, qualifies as a possible pharmaceutical tool to prevent and/or cure damages derived from accidental exposure to ionizing radiation. This study aimed to identify neutral SMase (nSMase) as novel molecule connecting rMnSOD to its radiation protective effects. We used a new, and to this date, unique, experimental model to assess the effect of both radiation and rMnSOD in the brain of mice, within a collaborative project among Italian research groups and the Joint Institute for Nuclear Research, Dubna (Russia). Mice were exposed to a set of minor γ radiation and neutrons and a spectrum of neutrons, simulating the radiation levels to which cosmonauts will be exposed during deep-space, long-term missions. Groups of mice were treated or not-treated (controls) with daily subcutaneous injections of rMnSOD during a period of 10 days. An additional group of mice was also pretreated with rMnSOD for three days before irradiation, as a model for preventive measures. We demonstrate that rMnSOD significantly protects the midbrain cells from radiation-induced damage, inducing a strong upregulation of nSMase gene and protein expression. Pretreatment with rMnSOD before irradiation protects the brain with a value of very high nSMase activity, indicating that high levels of activity might be sufficient to exert the rMnSOD preventive role. In conclusion, the protective effect of rMnSOD from radiation-induced brain damage may require nSMase enzyme.