作者: Pang, Qiling ; Tang, Zhaoxin ; Huang, Riming ; Wu, Shaofeng ; Tang, Lixuan ; Jiang, Xuanxuan ; Wan, Fang ; Zhong, Gaolong ; Hu, Lianmei ; Lan, Juan

Arsenic is a toxic heavy metal widely found in the natural environment and has adverse effects on the health of waterfowl and human. Curcumin (CUR), a natural pigment of the golden spice turmeric, exhibits excellent anti-tumor, anti-inflammatory and anti-oxidant activities. But the effects of CUR on duck spleen exposed to arsenic remain largely unknown. In this study, 75 ducks were divided randomly into Control, L-ATO, M-ATO, H-ATO and CUR + H-ATO groups to systematically analyze the underlying role of CUR. The results showed that arsenic trioxide (ATO) led to growth retardation of ducks, hyaline degeneration and sparse cell arrangement on their spleen. And in the ATO-exposed ducks, the levels of immunoglobulins (Ig; IgA, IgG, IgM) in the serum and the expression of autophagy-related genes (Atg5, P62, LC3I, LC3II, LC3II/I, Beclin-1) were significantly upregulated compared with the control ducks. Moreover, ATO also activated NF-κB signal pathway and upregulated the expression of pro-inflammatory cytokines (TNF-α, IFN-γ, IL-1β, IL-2, IL-18). Meanwhile, application of CUR alleviated the ATO toxicity with the release of growth inhibition, and the reduced hyaline degeneration and distortion of the spleen capsule. CUR also suppressed ATO-induced NF-κB activation, pro-inflammatory cytokine addition and expression of autophagy-related genes. Overall, these results suggested that CUR might exert a protective effect against ATO-induced immunosuppression in ducks via anti-inflammation and autophagy restoring.

2021-12-01·Research in Veterinary Science3区 · 农林科学

Immune B cell responsiveness to single-dose intradermal vaccination against Mycoplasma hyopneumoniae

3区 · 农林科学

Article

作者: Ferrari, Luca ; Cavalli, Valeria ; Martelli, Paolo ; Saleri, Roberta ; De Angelis, Elena ; Andrani, Melania ; Borghetti, Paolo

Mycoplasma hyopneumoniae is a major pathogen affecting pig herds and vaccination is the most utilized approach, despite providing partial protection. Age at vaccination, the delivery route, and vaccination protocol can influence vaccine efficacy. The influence of age and the presence of maternally-derived antibodies at vaccination on single-dose needle-less intradermal (ID) administration of an inactivated bacterin-based vaccine (Porcilis® M Hyo ID Once) were assessed in conventional pigs under field conditions. The induction of IgA+ and IgG+ B cell responses and the expression of the activation markers TLR2, TLR7, CCR9, and CCR10 were determined in PBMC. Vaccination at 4 weeks efficiently elicited an anamnestic antibody response associated with TLR2 and TLR7 upregulation. Although animals vaccinated at 1 week did not show seroconversion and a recall response upon infection, the responsiveness of Mycoplasma-recalled IgA+ B cells suggests the activation of mucosal immune cells after vaccination and infection. Vaccination at 1 week induced TLR2, TLR7, and CCR9 upregulation, suggesting the potential for systemic and local activation of immune cell trafficking between blood and target tissues. Vaccination at 4 weeks induced a CCR10 increase, suggesting that recalled IgA+ and IgG+ B cells can display an activated status upon infection. The antibody response after Mycoplasma infection in 4-week-old ID-vaccinated pigs was associated with TLR2 and CCR10 increases, confirming the potential use of this vaccination schedule for the safe and efficient delivery of single-dose M. hyopneumoniae vaccines. ID vaccination, especially at 4 weeks, was associated with a great degree of protection against enzootic pneumonia (EP)-like lung lesions.

2021-02-05·EMBO Molecular Medicine1区 · 医学

MOTS‐c promotes phosphorodiamidate morpholino oligomer uptake and efficacy in dystrophic mice

1区 · 医学

ArticleOA

作者: Moulton, Hong M ; Yin, HaiFang ; Bittner, Scott ; Ran, Ning ; Geng, Mengyuan ; Lin, Caorui ; Wu, Yingjie ; Han, Gang ; Leng, Ling

Antisense oligonucleotide (AO)-mediated exon-skipping therapies show promise in Duchenne muscular dystrophy (DMD), a devastating muscular disease caused by frame-disrupting mutations in the DMD gene. However, insufficient systemic delivery remains a hurdle to clinical deployment. Here, we demonstrate that MOTS-c, a mitochondria-derived bioactive peptide, with an intrinsic muscle-targeting property, augmented glycolytic flux and energy production capacity of dystrophic muscles in vitro and in vivo, resulting in enhanced phosphorodiamidate morpholino oligomer (PMO) uptake and activity in mdx mice. Long-term repeated administration of MOTS-c (500 μg) and PMO at the dose of 12.5 mg/kg/week for 3 weeks followed by 12.5 mg/kg/month for 3 months (PMO-M) induced therapeutic levels of dystrophin expression in peripheral muscles, with up to 25-fold increase in diaphragm of mdx mice over PMO alone. PMO-M improved muscle function and pathologies in mdx mice without detectable toxicity. Our results demonstrate that MOTS-c enables enhanced PMO uptake and activity in dystrophic muscles by providing energy and may have therapeutic implications for exon-skipping therapeutics in DMD and other energy-deficient disorders.

100 项与二甲双胍/瑞格列净相关的药物交易

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