Tendinopathies are at the frontier of advanced responses to health challenges and sectoral policy targets. Cell-based therapy holds great promise for tendon disorder resolution. To verify the role of stepwise trans-differentiation of amniotic epithelial stem cells (AECs) in tendon regeneration, in the present research three different AEC subsets displaying an epithelial (eAECs), mesenchymal (mAECs), and tendon-like (tdAECs) phenotype were allotransplanted in a validated experimental sheep Achilles tendon injury model. Tissue healing was analyzed adopting a comparative approach at two early healing endpoints (14 and 28 days). All three subsets of transplanted cells were able to accelerate regeneration: mAECs with a lesser extent than eAECs and tdAECs as indicated in the summary of the total histological scores (TSH), where at day 28 eAECs and tdAECs had better significant scores with respect to mAEC-treated tendons (p < 0.0001). In addition, the immunomodulatory response at day 14 showed in eAEC-transplanted tendons an upregulation of pro-regenerative M2 macrophages with respect to mAECs and tdAECs (p < 0.0001). In addition, in all allotransplanted tendons there was a favorable IL10/IL12 compared to CTR (p < 0.001). The eAECs and tdAECs displayed two different underlying regenerative mechanisms in the tendon. The eAECs positively influenced regeneration mainly through their greater ability to convey in the host tissue the shift from pro-inflammatory to pro-regenerative responses, leading to an ordered extracellular matrix (ECM) deposition and blood vessel remodeling. On the other hand, the transplantation of tdAECs acted mainly on the proliferative phase by impacting the density of ECM and by supporting a prompt recovery, inducing a low cellularity and angle alignment of the host cell compartment. These results support the idea that AECs lay the groundwork for production of different cell phenotypes that can orient tendon regeneration through a crosstalk with the host tissue. In particular, the obtained evidence suggests that eAECs are a practicable and efficient strategy for the treatment of acute tendinopathies, thus reinforcing the grounds to move their use towards clinical practice.
Manure produced by livestock activity is a dangerous product capable of causing serious environmental pollution. Agronomic management practices on the use of manure may transform the target from a waste to a resource product. Experiments performed on comparison of manure with standard chemical fertilizers (CF) were studied under a double cropping per year regime (alfalfa, model I; Italian ryegrass-corn, model II; barley-seed sorghum, model III; and horse-bean-silage sorghum, model IV). The total amount of manure applied in the annual forage crops of the model II, III and IV was 158, 140 and 80 m3 ha−1, respectively. The manure applied to soil by broadcast and injection procedure provides an amount of nitrogen equal to that supplied by CF. The effect of manure applications on animal feeding production and biochemical soil characteristics was related to the models. The weather condition and manures and CF showed small interaction among treatments. The number of MFU ha−1 of biomass crop gross product produced in autumn and spring sowing models under manure applications was 11,769, 20,525, 11,342, 21,397 in models I through IV, respectively. The reduction of MFU ha−1 under CF ranges from 10.7% to 13.2% those of the manure models. The effect of manure on organic carbon and total nitrogen of topsoil, compared to model I, stressed the parameters as CF whose amount was higher in models II and III than model IV. In term of percentage the organic carbon and total nitrogen of model I and treatment with manure was reduced by about 18.5 and 21.9% in model II and model III and 8.8 and 6.3% in model IV, respectively. Manure management may substitute CF without reducing gross production and sustainability of cropping systems, thus allowing the opportunity to recycle the waste product for animal forage feeding.
Buffalo breeding is common in Southern Italy. Dystocia compromises dam's and newborn health and welfare. Difficult parturition could be solved through prompt calving assistance, even if the identification of the beginning of delivery is challenging.
In the present work, mice overexpressing mutant amyloid precursor protein (Tg2576), a transgenic model of Alzheimer's disease (AD), are used to investigate a specific lipid profile over the course of disease progression. Using a targeted lipidomic approach, plasma levels of N‐acylethanolamines with different length and unsaturation at presymptomatic, mild‐symptomatic, and symptomatic disease stages are measured. Moreover, N‐acylethanolamines are also assessed in the brain areas most affected in AD. The ethanolamides of palmitic, oleic, arachidonic, eicosapentaenoic, and docosahexaenoic acids do not show any significant alteration in blood of Tg2576 mice at the different stages analyzed, as compared to wild‐type. Except for N‐docosahexaenoylethanolamine, a general tendency to decrease is instead detected for all measured N‐acylethanolamines in the cortex, hippocampus, striatum, and cerebellum of symptomatic Tg2576 mice. Together, the data can help to redefine the range of lipid‐associated signals in Alzheimer pathophysiology. Practical Application: The development of novel therapies for AD is strongly narrowed not only by the lack of a full comprehension of underlying pathophysiological mechanisms but also by the absence of affordable, reliable, and noninvasive biomarkers. Hence, there is the practical necessity to acquire accessible blood biomarkers to provide rapid, cost‐effective, and critical information to timely identify disease stage and implement preventive strategies aimed at slowing down cognitive decline. In this study, a targeted lipidomics investigation of N‐acylethanolamines at different stages of disease progression, clearly indicates that the discovery of innovative blood biomarkers should be refocused on different indices of deranged lipid metabolism for a realistic prediction of the risk of AD. It is investigated that potential alterations of N‐acylethanolamines content during disease development in a transgenic mouse model of Alzheimer's disease (AD). Circulating and central N‐acylethanolamine levels did not show any alteration in Tg2576 mice at different disease stages.
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