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Adaptive immunity relies on the efficient recruitment of T cells from the blood into peripheral tissues. However, the current understanding of factor(s) coordinating these events is incomplete. Previous studies on galectin-9 (Gal-9), have proposed a functionally significant role for this lectin in mediating leukocyte adhesion and transmigration. However, very little is known about its function in T cell migration. Here, we have investigated the role of the Gal-9 on the migration behaviour of both human primary CD4 + and CD8 + T cells. Our data indicate that Gal-9 supports both CD4 + and CD8 + T cell adhesion and transmigration in a glycan dependent manner, inducing L-selectin shedding and upregulation of LFA-1 and CXCR4 expression. Additionally, when immobilized, Gal-9 promoted capture and firm adhesion of T cells under flow, in a glycan and integrin-dependent manner. Using an in vivo model, dorsal air pouch, we found that Gal-9 deficient mice display impaired leukocyte trafficking, with a reduction in pro-inflammatory cytokines/chemokines generated locally. Furthermore, we also demonstrate that Gal-9 inhibits the chemotactic function of CXCL12 through direct binding. In conclusion, our study characterises, for the first time, the capture, adhesion, and migration behaviour of CD4 + and CD8 + T cells to immobilised /endothelial presented Gal-9, under static and physiological flow conditions. We also demonstrate the differential binding characteristics of Gal-9 to T cell subtypes, which could be of potential therapeutic significance, particularly in the treatment of inflammatory-based diseases, given Gal-9 ability to promote apoptosis in pathogenic T cell subsets., (Copyright © 2022 The Authors. Published by Elsevier Masson SAS.. All rights reserved.)

One of the hallmarks of COVID-19 is the cytokine storm that provokes primarily pneumonia followed by systemic inflammation. Emerging evidence has identified a potential link between elevated interleukin-17A (IL-17A) levels and disease severity and progression. Considering that per se, IL-17A can activate several inflammatory pathways, it is plausible to hypothesize an involvement of this cytokine in COVID-19 clinical outcomes. Thus, IL-17A could represent a marker of disease progression and/or a target to develop therapeutic strategies. This hypothesis paper aims to propose this "unique" cytokine as a silent amplifier of the COVID-19 immune response and (potentially) related therapy., (Copyright © 2021 The Authors. Published by Elsevier Masson SAS.. All rights reserved.)

Alzheimer's disease (AD) is the most common type of dementia worldwide, characterized by the deposition of neurofibrillary tangles and amyloid-β (Aβ) peptides in the brain. Additionally, increasing evidence demonstrates that a neuroinflammatory state and oxidative stress, iron-dependent, play a crucial role in the onset and disease progression. Besides conventional therapies, the use of natural-based products represents a future medical option for AD treatment and/or prevention. We, therefore, evaluated the effects of a ribonucleotides-based ingredient (Ribodiet®) in a non-genetic mouse model of AD. To this aim, mice were injected intracerebroventricularly (i.c.v.) with Aβ 1-42 peptide (3 µg/3 μl) and after with Ribodiet® (0.1-10 mg/mouse) orally (p.o.) 3 times weekly for 21 days following the induction of experimental AD. The mnemonic and cognitive decline was then evaluated, and, successively, we have assessed ex vivo the modulation of different cyto-chemokines on mice brain homogenates. Finally, the level of GFAP, S100β, and iron-related metabolic proteins were monitored as markers of reactive gliosis, neuro-inflammation, and oxidative stress. Results indicate that Ribodiet® lessens oxidative stress, brain inflammation, and amyloid pathology via modulation of iron-related metabolic proteins paving the way for its rationale use for the treatment of AD and other age-related diseases., (Copyright © 2021 The Authors. Published by Elsevier Masson SAS.. All rights reserved.)

Medicinal plants from traditional chinese medicine are used increasingly worldwide for their benefits to health and quality of life for the relevant clinical symptoms related to pain. Among them, Salvia miltiorrhiza Bunge is traditionally used in asian countries as antioxidant, anticancer, anti-inflammatory and analgesic agent. In this context, several evidences support the hypothesis that some tanshinones, in particular cryptotanshinone (CRY), extracted from the roots (Danshen) of this plant exhibit analgesic actions. However, it is surprisingly noted that no pharmacological studies have been carried out to explore the possible analgesic action of this compound in terms of modulation of peripheral and/or central pain. Therefore, in the present study, by using peripheral and central pain models of nociception, such as tail flick and hot plate test, the analgesic effect of CRY in mice was evaluated. Successively, by the aim of a computational approach, we have evaluated the interaction mode of this diterpenoid on opioid and cannabinoid system. Finally, CRY was dosed in mice serum by an HPLC method validated according to European Medicines Agency guidelines validation rules. Here, we report that CRY displayed anti-nociceptive activity on both hot plate and tail flick test, with a prominent long-lasting peripheral analgesic effect. These evidences were indirectly confirmed after the daily administration of the tanshinone for 7 and 14 days. In addition, the analgesic effect of CRY was reverted by naloxone and cannabinoid antagonists and amplified by arginine administration. These findings were finally supported by HPLC and docking studies, that revealed a noteworthy presence of CRY on mice serum 1 h after its intraperitoneal administration and a possible interaction of tested compound on μ and k receptors. Taken together, these results provide a new line of evidences showing that CRY can produce analgesia against various phenotypes of nociception with a mechanism that seems to be related to an agonistic activity on opioid system., Competing Interests: Declaration of Competing Interest The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2020 The Author(s). Published by Elsevier Masson SAS.. All rights reserved.)

Antimicrobial peptides (AMPs) are an ancient group of defense molecules distributed in nature being found in mammals, birds, amphibians, insects, plants, and microorganisms. They display antimicrobial as well as immunomodulatory properties. The aim of this study was to investigate, for the first time, the anti-inflammatory activities of two synthetic temporin-L analogues (here named peptide 1 and 2) by an in vivo model of inflammation caused by intraperitoneal sub-lethal dose of zymosan. Our results show that peptide 1 and 2 exert anti-inflammatory activity in vivo in response to zymosan-induce peritonitis. Simultaneous administration of 10 mg/kg of both temporins, with a sub-lethal dose of zymosan (500 mg/kg), significantly rescued mice from the classical hallmarks of inflammation, including leukocyte infiltration and synthesis of inflammatory mediators including IL-6, TNF-α and MCP-1. More importantly, flow cytometry analysis highlighted a selective modulation of infiltrating inflammatory monocytes (defined as B220 - /GR1 hi -F480 hi /CD115 + ) after peptide 2 treatment. Our results and presented models offer the possibility to test, in a preclinical setting, the potential of temporin analogues as anti-inflammatory agents., Competing Interests: Declaration of Competing Interest The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2019 The Author(s). Published by Elsevier Masson SAS.. All rights reserved.)