Perceptual learning substantially improves visual discrimination and detection ability, which has been associated with visual cortical plasticity. However, little is known about the dynamic changes in neuronal response properties over the course of training. Using chronically implanted multielectrode arrays, we were able to capture day-by-day spatiotemporal dynamics of neurons in the primary visual cortex (V1) of monkeys trained to detect camouflaged visual contours. We found progressive strengthening and accelerating in both facilitation of neurons encoding the contour elements and suppression of neurons responding to the background components. The enhancement of this figure-ground contrast in V1 was closely correlated with improved behavioral performance on a daily basis. Decoding accuracy of a simple linear classifier based on V1 population responses also paralleled the animal's behavioral changes. Our results indicate that perceptual learning shapes the V1 population code to allow a more efficient readout of task-relevant information.
Sustained activation of NLRP3 inflammasome and release of neutrophil extracellular traps (NETs) impair wound healing of diabetic foot ulcers (DFUs). Our previous study reported that milk fat globule epidermal growth factor VIII (MFG-E8) attenuates tissue damage in systemic lupus erythematosus. However, the functional effect of MFG-E8 on “NLRP3 inflammasome-NETs” inflammatory loop in wound healing of diabetes is not completely elucidated. In this study, neutrophils from DFU patients are susceptible to undergo NETosis, releasing more NETs. The circulating levels of NET components neutrophil elastase and proteinase 3 and inflammatory cytokines IL-1β and IL-18 were significantly elevated in DFU patients compared with healthy controls or diabetic patients, in spite of higher levels of MFG-E8 in DFU patients. In Mfge8−/− diabetic mice, skin wound displayed exaggerated inflammatory response, including leukocyte infiltration, excessive activation of NLRP3 inflammasome (release of higher IL-1β, IL-18, and TNF-α), largely lodged NETs, resulting in poor angiogenesis and wound closure. When stimulated with high-dose glucose or IL-18, MFG-E8-deficient neutrophils release more NETs than WT neutrophils. After administration of recombinant MFG-E8, IL-18-primed NETosis of WT or Mfge8−/− neutrophils was significantly inhibited. Furthermore, NET and mCRAMP (component of NETs, the murine equivalent of cathelicidin LL-37 in human)-mediated activation of NLRP3 inflammasome and production of IL-1β/IL-18 were significantly elevated in Mfge8−/− macrophages compared with WT macrophages, which were also significantly dampened by the administration of rmMFG-E8. Therefore, our study demonstrated that as inhibitor of the “NLRP3 inflammasome-NETs” inflammatory loop, exogenous rMFG-E8 improves angiogenesis and accelerates wound healing, highlighting possible therapeutic potential for DFUs.
BackgroundNLPR3 is an important gene that belongs to the family of NOD-like receptors and is thought to play an important role in psoriasis. The aim of the present study was to investigate the expression of NLRP3 in psoriasis biopsy samples and to assess the possible correlation of its expression with that of interleukin IL-1β and Caspase-1.Material/MethodsThe mRNA expression was checked by qRT-PCR. The expression of the proteins was checked by Western blotting. The distribution of the proteins was determined by immunohistochemistry.ResultsThe results of our study indicate that the expression of NLRP3 was significantly upregulated in all the psoriatic biopsy samples as indicated by qRT-PCR and Western blotting. The expression of NLRP3 in psoriatic samples was 3.5 to 4.3 times higher than the expression of NLRP3 in normal skin biopsy samples. Moreover, our results indicated that the expression levels of IL-1β were higher as compared to the normal skin biopsy samples. Relative to the expression of IL-1β in normal skin biopsy samples, the expression of IL-1β was about 2.7–4.6 times higher. Additionally, the expression of caspase-1 was considerably upregulated in the psoriatic samples. Caspase-1 gene expression was 2.2–3.4 times higher than in normal skin biopsy samples.ConclusionsNLPR3 may prove to be an important therapeutic target for psoriasis.
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