We investigated the anti-aging effects of Ludwigia octovalvis (Jacq.) P. H. Raven (Onagraceae), an extract of which is widely consumed as a healthful drink in a number of countries. Using the fruit fly, Drosophila melanogaster, as a model organism, we demonstrated that L. octovalvis extract (LOE) significantly extended fly lifespan on a high, but not a low, calorie diet, indicating that LOE may regulate lifespan through a dietary restriction (DR)-related pathway. LOE also attenuated age-related cognitive decline in both flies and in the senescence-accelerated-prone 8 (SAMP8) mouse, without causing any discernable negative trade-offs, including water intake, food intake, fecundity, or spontaneous motor activity. LOE contained high levels of polyphenols and flavonoids, which possess strong DPPH radical scavenging activity, and was shown to attenuate paraquat-induced oxidative damage and lethality in flies. Gas chromatography-mass spectrometry (GC-MS) analyses identified 17 known molecules, of which β-sitosterol and squalene were the two most abundant. We further demonstrated that β-sitosterol was capable of extending lifespan, likely through activating AMP-activated protein kinase (AMPK) in the fat body of adult flies. Taken together, our data suggest that LOE is a potent anti-aging intervention with potential for treating age-related disorders.

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Nociceptors, the high-threshold primary sensory neurons that trigger pain, interact with immune cells in the periphery to modulate innate immune responses. Whether they also participate in adaptive and humoral immunity is, however, not known. In this study, we probed if nociceptors have a role in distinct airway and skin models of allergic inflammation. In both models, the genetic ablation and pharmacological silencing of nociceptors substantially reduced inflammatory cell infiltration to the affected tissue. Moreover, we also found a profound and specific deficit in IgE production in these models of allergic inflammation. Mechanistically, we discovered that the nociceptor-released neuropeptide substance P helped trigger the formation of antibody-secreting cells and their release of IgE. Our findings suggest that nociceptors, in addition to their contributions to innate immunity, play a key role in modulating the adaptive immune response, particularly B cell antibody class switching to IgE.

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Nociceptor neurons play a crucial role in maintaining the body's equilibrium by detecting and responding to potential dangers in the environment. However, this function can be detrimental during allergic reactions, since vagal nociceptors can contribute to immune cell infiltration, bronchial hypersensitivity, and mucus imbalance, in addition to causing pain and coughing. Despite this, the specific mechanisms by which nociceptors acquire pro-inflammatory characteristics during allergic reactions are not yet fully understood. In this study, we aimed to investigate the molecular profile of airway nociceptor neurons during allergic airway inflammation and identify the signals driving such reprogramming. Using retrograde tracing and lineage reporting, we identified a class of inflammatory vagal nociceptor neurons that exclusively innervate the airways. Using an ovalbumin mouse model of airway inflammation, we found that these neurons undergo significant reprogramming characterized by the upregulation of the NPY receptor Npy1r, along with Il6. A screening of asthma-driving cytokines revealed that IL-13 drives part of this reprogramming, including Npy1r overexpression via the JAK/STAT6 pathway, while IL-1β induces IL-6 expression and release. Additionally, we observed that sympathetic neurons release NPY in the bronchoalveolar fluid of asthmatic mice, which limits the excitability of nociceptor neurons. In summary, allergic airway inflammation reprograms airway nociceptor neurons to acquire a pro-inflammatory phenotype, characterized by the release of IL-6, while a compensatory mechanism involving NPY1R limits nociceptor neurons' activity.

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RATIONALE: IL-26 is a potential biomarker of inflammation in asthmatics. METHODS:The study included 10 healthy subjects (controls), 10 obese subjects without lung pathologies, 10 non-obese asthmatics (NOA) (BMI -18.5-24.9 kg/m2), and 40 obese asthmatics (OA) (BMI -25.0-49.9 kg/ m2). Spirometry with reversibility and both exhaled breath condensate (EBC) and blood samples collected. IL-26, interleukin-4 (IL-4), interleukin-10(IL-10), and high sensitive C reactive protein (hs-CRP) were measured by ELISA. Receiver Operating Characteristic (ROC) area under the curve (AUC) was used assessing IL-26 as a biomarker. RESULTS: NOA had reversible airway obstruction, reduced FEV1, FEV1/FVC, FVC 25/75, and positive post bronchodilator test (PBT), significantly increased serum levels of IL-10, IL-4, and slightly increased IL-26, with significantly increased exhaled IL-26 versus controls. The obese subjects had normal spirometry without obstruction, or differences in serum IL-26, IL-10, and IL-4 versus controls but significantly increased hs-CRP with no difference in exhaled IL-26, IL-10, and hs-CRP versus controls. OA had reduced FEV1, FEV1/FVC, and FEV25-75 versus NOA with elevated IL-26, IL-10, IL-4, and hs-CRP versus controls with partial similarity with both NOA (elevated IL-26, IL-10, and IL-4) and obese subjects (elevated hs-CRP). OA had reduced exhaled IL-26 versus NOA and elevated exhaled IL-10 versus obese subjects. Exhaled IL-26 distinguished NOA from controls, ROC analysis (area: 0.9700) showed 100% sensitivity/ 80% specificity; asthmatics versus non-asthmatics; and (area: 0.9620) showed 94% sensitivity and 80% specificity distinguishing all asthmatics from non-asthmatics (area: 0.9280) showing 94% sensitivity /80% specificity. CONCLUSIONS: IL-26 is novel biomarker for asthma inflammation.