The global distribution of brucellosis and high incidence in certain areas of the world warrant the development of a safer and efficacious vaccine. For the past 10 years, we have focused our attention on the development of a safer, but still highly protective, live attenuated vaccine for human and animal use. We have demonstrated the safety and protective efficacy of the vaccine candidates 16M⌬vjbR and S19⌬vjbR against homologous and heterologous challenge in multiple immunocompetent animal models, including mice and deer. In the present study, we conducted a series of experiments to determine the safety of the vaccine candidates in interferon regulatory factor-1-knockout (IRF-1 ؊/؊ ) mice. IRF-1 ؊/؊ mice infected with either wild-type Brucella melitensis 16M or the vaccine strain Brucella abortus S19 succumb to the disease within the first 3 weeks of infection, which is characterized by a marked granulomatous and neutrophilic inflammatory response that principally targets the spleen and liver. In contrast, IRF-1 ؊/؊ mice inoculated with either the 16M⌬vjbR or S19⌬vjbR vaccine do not show any clinical or major pathological changes associated with vaccination. Additionally, when 16M⌬vjbR-or S19⌬vjbR-vaccinated mice are challenged with wild-type Brucella melitensis 16M, the degree of colonization in multiple organs, along with associated pathological changes, is significantly reduced. These findings not only demonstrate the safety and protective efficacy of the vjbR mutant in an immunocompromised mouse model but also suggest the participation of lesser-known mechanisms in protective immunity against brucellosis.
Alzheimer's disease (AD) is a common neurodegenerative disorder characterized by the accumulation of misfolded amyloid-β (Aβ) peptides, which is caused by an imbalance between Aβ production and clearance. Picroside II (Picr II), the principal active constituent of Picrorhizakurroa Royle ex Benth, possesses a range of pharmacological properties, such as anti-inflammatory, antioxidant, and antiapoptotic effects. However, the exact role of Picr II in AD is not yet fully understood. In this study, we investigated the effects of Picr II on AD and found that it inhibited amyloid precursor protein (APP) processing by enhancing autophagy rather than through the ubiquitin-proteasome pathway, resulting in a reduction in Aβ production. Furthermore, Picr II treatment improved the decline in autophagy, which was due not only to an increase in autophagic flux but also to an increase in the fusion of autophagosomes with lysosomes. Most importantly, daily treatment with Picr II (20 mg/kg, i.p.) throughout the experiment rescued the learning and memory in Aβ-treated mice. Taken together, these results suggest that Picr II may have a potent neuroprotective effect against Aβ-induced memory decline by enhancing autophagy, indicating that Picr II may be a promising therapeutic agent for AD.
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