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Transient receptor potential vanilloid 1 (TRPV1) is a polymodal cation channel gated by a large array of chemical and physical stimuli and distributed across different brain regions on neuronal and glial cells. Preclinical studies indicate that TRPV1 might be a target for the treatment of anxiety, depression and addictive disorders. The aim of this narrative review is to focus on studies examining the effects of TRPV1 antagonism on neuroinflammation, neuroprotection and epigenetic regulation. Results suggest that TRPV1 modulation leads to pro- or anti-inflammatory effects depending on the cytokine environment and that the TRPV1 antagonism can switch the microglia towards an anti-inflammatory phenotype. Moreover, TRPV1 inhibitors have neuroprotective properties through the regulation of calcium levels. Finally, TRPV1 antagonism exerts regulatory effects on genes involved in synaptic and cognitive functions through histone deacetylase 2 inhibition. These findings highlight different mechanisms that may underlie the efficacy of TRPV1 antagonists in animal models of severe psychiatric disorders.

Purpose The purpose of this paper is to identify the main criteria for selecting actors to compose these business platforms and addressing the co-creation of value and improve the performance of startups. Design/methodology/approach The methodology is based on the search for key factors for the selection of actors and the understanding of co-creation of value and the concept of startups. The content of this paper is substantiated on an extensive review of the literature related to the subjects’ value-cocreation and new startups, and the review is based on the articles found in the databases of Ebsco, Emerald, Science Direct, Scopus, Village and Web of Science. Findings This paper identifies the main key-factors found in the literature for selecting actors to co-create value in startups and organizes the findings in five categories: value creation, interaction, actor behavior, client and partnership. It also presents the possibility of future research that will be able to put the study in practice. Research limitations/implications The results of this research have not been tested empirically, which opens the door for future studies that can prove the effectiveness of the findings. It is also important to mention that there are few articles in the literature that directly address this topic, and some definitions of actor/co-creation of value/business model may also change. Practical implications The selection criteria of the actors listed are useful for service entrepreneurs and managers to assist in decision-making at the stage of choosing their partners for value co-creation in startups. Furthermore, it involves mitigating waste in startups and maximizing the economic gains of partners through value co-creation in startups. Originality/value This study is one of the first attempts to recognize the key factors for selecting actors to co-create value in startups, aiming at their success in the market.

Pseudomonas aeruginosa is an opportunistic bacterium in patients with cystic fibrosis and hospital acquired infections. It presents a plethora of virulence factors and antioxidant enzymes that help to subvert the immune system. In this study, we identified the 2-Cys peroxiredoxin, alkyl-hydroperoxide reductase C1 (AhpC1), as a relevant scavenger of oxidants generated during inflammatory oxidative burst and a mechanism of P. aeruginosa (PA14) escaping from killing. Deletion of AhpC1 led to a higher sensitivity to hypochlorous acid (HOCl, IC 50 3.2 ± 0.3 versus 19.1 ± 0.2 μM), hydrogen peroxide (IC 50 91.2 ± 0.3 versus 496.5 ± 6.4 μM) and the organic peroxide urate hydroperoxide. ΔahpC1 strain was more sensitive to the killing by isolated neutrophils and less virulent in a mice model of infection. All mice intranasally instilled with ΔahpC1 survived as long as they were monitored (15 days), whereas 100% wild-type and ΔahpC1 complemented with ahpC1 gene (Δ ahpC 1 attB : ahpC1 ) died within 3 days. A significantly lower number of colonies was detected in the lung and spleen of ΔahpC1 -infected mice. Total leucocytes, neutrophils, myeloperoxidase activity, pro-inflammatory cytokines, nitrite production and lipid peroxidation were much lower in lungs or bronchoalveolar liquid of mice infected with ΔahpC1 . Purified AhpC neutralized the inflammatory organic peroxide, urate hydroperoxide, at a rate constant of 2.3 ± 0.1 × 10 6 M −1 s −1 , and only the ΔahpC1 strain was sensitive to this oxidant. Incubation of neutrophils with uric acid, the urate hydroperoxide precursor, impaired neutrophil killing of wild-type but improved the killing of ΔahpC1 . Hyperuricemic mice presented higher levels of serum cytokines and succumbed much faster to PA14 infection when compared to normouricemic mice. In summary, ΔahpC1 PA14 presented a lower virulence, which was attributed to a poorer ability to neutralize the oxidants generated by inflammatory oxidative burst, leading to a more efficient killing by the host. The enzyme is particularly relevant in detoxifying the newly reported inflammatory organic peroxide, urate hydroperoxide.