Neutrophil microvesicles resolve gout by inhibiting C5a-mediated priming of the inflammasome

Objectives Gout is a highly inflammatory but self-limiting joint disease induced by the precipitation of monosodium urate (MSU) crystals. While it is well established that inflammasome activation by MSU mediates acute inflammation, little is known about the mechanism controlling its spontaneous resolution. The aim of this study was to analyse the role of neutrophil-derived microvesicles (PMN-Ecto) in the resolution of acute gout. Methods PMN-Ecto were studied in a murine model of MSU-induced peritonitis using C57BL/6, MerTK(-/-) and C5aR(-/-) mice. The peritoneal compartment was assessed for the number of infiltrating neutrophils (PMN), neutrophil microvesicles (PMN-Ecto), cytokines (interleukin-1 beta, TGF beta) and complement factors (C5a). Human PMN-Ecto were isolated from exudates of patients undergoing an acute gouty attack and functionally tested in vitro. Results C5a generated after the injection of MSU primed the inflammasome for IL-1 beta release. Neutrophils infiltrating the peritoneum in response to C5a released phosphatidylserine (PS)-positive PMN-Ecto early on in the course of inflammation. These PMN-Ecto in turn suppressed C5a priming of the inflammasome and consequently inhibited IL-1 beta release and neutrophil influx. PMN-Ecto-mediated suppression required surface expression of the PS-receptor MerTK and could be reproduced using PS-expressing liposomes. In addition, ectosomes triggered the release of TGF beta independent of MerTK. TGF beta, however, was not sufficient to control acute MSU-driven inflammation in vivo. Finally, PMN-Ecto from joint aspirates of patients with gouty arthritis had similar anti-inflammatory properties. Conclusions PMN-Ecto-mediated control of inflammasome-driven inflammation is a compelling concept of autoregulation initiated early on during PMN activation in gout

Does the taste matter? Taste and medicinal perceptions associated with five selected herbal drugs among three ethnic groups in West Yorkshire, Northern England

In recent years, diverse scholars have addressed the issue of the chemosensory perceptions associated with traditional medicines, nevertheless there is still a distinct lack of studies grounded in the social sciences and conducted from a cross-cultural, comparative perspective. In this urban ethnobotanical field study, 254 informants belonging to the Gujarati, Kashmiri and English ethnic groups and living in Western Yorkshire in Northern England were interviewed about the relationship between taste and medicinal perceptions of five herbal drugs, which were selected during a preliminary study. The herbal drugs included cinnamon (the dried bark of Cinnamomum verum, Lauraceae), mint (the leaves of Mentha spp., Lamiaceae), garlic (the bulbs of Allium sativum, Alliaceae), ginger (the rhizome of Zingiber officinale, Zingiberaceae), and cloves (the dried flower buds of Syzygium aromaticum, Myrtaceae). The main cross-cultural differences in taste perceptions regarded the perception the perception of the spicy taste of ginger, garlic, and cinnamon, of the bitter taste of ginger, the sweet taste of mint, and of the sour taste of garlic. The part of the study of how the five selected herbal drugs are perceived medicinally showed that TK (Traditional Knowledge) is widespread among Kashmiris, but not so prevalent among the Gujarati and especially the English samples. Among Kashmiris, ginger was frequently considered to be helpful for healing infections and muscular-skeletal and digestive disorders, mint was chosen for healing digestive and respiratory troubles, garlic for blood system disorders, and cinnamon was perceived to be efficacious for infectious diseases. Among the Gujarati and Kashmiri groups there was evidence of a strong link between the bitter and spicy tastes of ginger, garlic, cloves, and cinnamon and their perceived medicinal properties, whereas there was a far less obvious link between the sweet taste of mint and cinnamon and their perceived medicinal properties, although the link did exist among some members of the Gujarati group. Data presented in this study show how that links between taste perceptions and medicinal uses of herbal drugs may be understood as bio-cultural phenomena rooted in human physiology, but also constructed through individual experiences and culture, and that these links can therefore be quite different across diverse cultures

Association of chronic pain with biomarkers of neurodegeneration, microglial activation and inflammation in the CSF and impaired cognitive function

ObjectivesDebate surrounds the role of chronic pain as a risk factor for cognitive decline and dementia. This study aimed at examining the association of chronic pain with biomarkers of neurodegeneration using data from the Alzheimer's Disease Neuroimaging Initiative (ADNI).MethodsParticipants were classified using the ATN classification. Chronic pain was defined as persistent or recurrent pain reported at baseline. For each ATN group, ANCOVA models identified differences in CSF levels of Aβ1‐42, ptau181, t‐tau, sTREM2 and cognitive function between chronic pain states. Differences in CSF levels of inflammatory markers between chronic pain states were further analysed. Linear mixed‐effect models examined longitudinal changes.ResultsThe study included 995 individuals with 605 (60.81%) reporting chronic pain at baseline. At baseline, individuals with suspected non‐Alzheimer's pathophysiology (SNAP) and chronic pain showed increased CSF levels of t‐tau and sTREM2. Chronic pain was associated with increased TNF‐α levels, irrespective of the ATN group. Longitudinally, an increase in ptau181 CSF levels was observed in chronic pain patients with negative amyloid and neurodegeneration markers. Amyloid positive and neurodegeneration negative chronic pain patients showed higher memory function cross‐sectionally. No significant longitudinal decline in cognitive function was observed for any ATN group.Interpretationour study suggests that chronic pain induces neuronal damage and microglial activation in particular subgroups of patients along the AD spectrum. Further studies are needed to confirm those findings.This article is protected by copyright. All rights reserved.</jats:sec

The use of phylogeny to interpret cross-cultural patterns in plant use and guide medicinal plant discovery: an example from Pterocarpus (Leguminosae)

The study of traditional knowledge of medicinal plants has led to discoveries that have helped combat diseases and improve healthcare. However, the development of quantitative measures that can assist our quest for new medicinal plants has not greatly advanced in recent years. Phylogenetic tools have entered many scientific fields in the last two decades to provide explanatory power, but have been overlooked in ethnomedicinal studies. Several studies show that medicinal properties are not randomly distributed in plant phylogenies, suggesting that phylogeny shapes ethnobotanical use. Nevertheless, empirical studies that explicitly combine ethnobotanical and phylogenetic information are scarce.In this study, we borrowed tools from community ecology phylogenetics to quantify significance of phylogenetic signal in medicinal properties in plants and identify nodes on phylogenies with high bioscreening potential. To do this, we produced an ethnomedicinal review from extensive literature research and a multi-locus phylogenetic hypothesis for the pantropical genus Pterocarpus (Leguminosae: Papilionoideae). We demonstrate that species used to treat a certain conditions, such as malaria, are significantly phylogenetically clumped and we highlight nodes in the phylogeny that are significantly overabundant in species used to treat certain conditions. These cross-cultural patterns in ethnomedicinal usage in Pterocarpus are interpreted in the light of phylogenetic relationships.This study provides techniques that enable the application of phylogenies in bioscreening, but also sheds light on the processes that shape cross-cultural ethnomedicinal patterns. This community phylogenetic approach demonstrates that similar ethnobotanical uses can arise in parallel in different areas where related plants are available. With a vast amount of ethnomedicinal and phylogenetic information available, we predict that this field, after further refinement of the techniques, will expand into similar research areas, such as pest management or the search for bioactive plant-based compounds

Yucatec Maya medicinal plants versus nonmedicinal plants: indigenous characterization and selection

Medicinal plants are an important part of the environment as it is perceived by Mexican indigenous groups. The aim of this study, which was conducted over a period of 18 months in three Yucatec Mayan communities, is to better understand the selection criteria for medicinal plants. An important group of selection criteria are the flavor and aroma of plants. The absence of smell or taste indicates that the taxon has no potential medical value. Medicinal plants are more often considered to be sweet or aromatic (to smell good) or astringent, while a similar percentage of medicinal and nonmedicinal plants are considered bitter, spicy, acidic, or bad smelling. The relationship between the ethnobotanical data obtained for the individual plants and the secondary plant products (natural products) prominent in each species is specifically addressed in this paper. It shows that an understanding of the indigenous concepts used to distinguish medicinal from nonmedicinal species has considerable heuristic value