Cytokines of the IL-1 family are important modulators of obesity-induced inflammation and the development of systemic insulin resistance. Here we show that IL-1 family member IL-37, recently characterized as an anti-inflammatory cytokine, ameliorates obesity-induced inflammation and insulin resistance. Mice transgenic for human IL-37 (IL-37tg) exhibit reduced numbers of adipose tissue macrophages, increased circulating levels of adiponectin and preserved glucose tolerance and insulin sensitivity after 16 weeks of HFD. In vitro treatment of adipocytes with recombinant IL-37 reduces adipogenesis and activates AMPK signalling. In humans, elevated steady-state IL-37 adipose tissue mRNA levels are positively correlated with insulin sensitivity and a lower inflammatory status of the adipose tissue. These findings reveal IL-37 as an important anti-inflammatory modulator during obesityinduced inflammation and insulin resistance in both mice and humans, and suggest that IL-37 is a potential target for the treatment of obesity-induced insulin resistance and type 2 diabetes.

In Alzheimer’s disease (AD), there is a loss in cholinergic innervation targets of basal forebrain which has been implicated in substantial cognitive decline. Amyloid beta peptide (Aβ1–42) accumulates in AD that is highly toxic for basal forebrain cholinergic (BFC) neurons. Although the gonadal steroid estradiol is neuroprotective, the administration is associated with risk of off-target effects. Previous findings suggested that non-classical estradiol action on intracellular signaling pathways has ameliorative potential without estrogenic side effects. After Aβ1–42 injection into mouse basal forebrain, a single dose of 4-estren-3α, 17β-diol (estren), the non-classical estradiol pathway activator, restored loss of cholinergic cortical projections and also attenuated the Aβ1–42-induced learning deficits. Estren rapidly and directly phosphorylates c-AMP-response–element-binding-protein and extracellular-signal-regulated-kinase-1/2 in BFC neurons and restores the cholinergic fibers via estrogen receptor-α. These findings indicated that selective activation of non-classical intracellular estrogen signaling has a potential to treat the damage of cholinergic neurons in AD.

ObjectiveGout is characterised by severe interleukin (IL)-1-mediated joint inflammation induced by monosodium urate crystals. Since IL-37 is a pivotal anti-inflammatory cytokine suppressing the activity of IL-1, we conducted genetic and functional studies aimed at elucidating the role of IL-37 in the pathogenesis and treatment of gout.MethodsVariant identification was performed by DNA sequencing of all coding bases of IL37 using molecular inversion probe-based resequencing (discovery cohort: gout n=675, controls n=520) and TaqMan genotyping (validation cohort: gout n=2202, controls n=2295). Predictive modelling of the effects of rare variants on protein structure was followed by in vitro experiments evaluating the impact on protein function. Treatment with recombinant IL-37 was evaluated in vitro and in vivo in a mouse model of gout.ResultsWe identified four rare variants in IL37 in six of the discovery gout patients; p.(A144P), p.(G174Dfs*16), p.(C181*) and p.(N182S), whereas none emerged in healthy controls (Fisher’s exact p-value=0.043). All variants clustered in the functional domain of IL-37 in exon 5 (p-value=5.71×10−5). Predictive modelling and functional studies confirmed loss of anti-inflammatory functions and we substantiated the therapeutic potential of recombinant IL-37 in the treatment of gouty inflammation. Furthermore, the carrier status of p.(N182S)(rs752113534) was associated with increased risk (OR=1.81, p-value=0.031) of developing gout in hyperuricaemic individuals of Polynesian ancestry.ConclusionHere, we provide genetic as well as mechanistic evidence for the role of IL-37 in the pathogenesis of gout, and highlight the therapeutic potential of recombinant IL-37 for the treatment of gouty arthritis.

We present reversible magnetization measurements for applied fields in the range from 0.5 to 7 T made while varying the temperature for optimally doped BaFe1.8Co0.2As2 single crystals with Tc = 23.6 K. The rounding fluctuating magnetization was observed in the reversible range of magnetization for temperatures above 18 K. This fluctuation effect is quite small compared with that in high temperature cuprate superconductors, but is still large enough for obtaining the essence of the physical properties in this iron pnictide superconductor. This reversible magnetic fluctuation follows a three-dimensional scaling form in the critical fluctuation region for fields above 0.5 T, which indicates that this iron pnictide superconductor belongs to the class of three-dimensional superconductors.

Rebaudioside A is a promising natural alternative sweetener but they produce increased bitterness, astringency, and unpleasant aftertastes. Glycosylation and blending with different sweeteners are known to improve the sensory characteristics of rebaudioside A. The present study was conducted to identify the relative sweetness and sensory profile of glycosyl rebaudioside A (g-reb A). The relative sweetness of g-reb A compared to 5% sucrose was determined using the two-alternative forced choice method. The sensory profiles of g-reb A and its mixtures with allulose and maltitol (1:1 ratio) were compared to those of rebaudioside A, rebaudioside D, rebaudioside M, sucralose, allulose, maltitol, and sucrose using descriptive analysis conducted by eight trained panelists. The relative sweetness of g-reb A was 155, which was lower than that of rebaudioside A. In addition, the bitter taste and aftertaste, astringency, and sweet onset of g-reb A were decreased compared to those of rebaudioside A.