Dairy cows receiving a prolonged high-concentrate diet express an elevated concentration of lipopolysaccharides (LPSs) in the peripheral blood circulation, accompanied by a series of systemic inflammatory responses; however, the specific impacts of inflammation are yet to be determined. Cecropin-like antimicrobial peptides have become a research hotspot regarding antimicrobial peptides because of their excellent anti-inflammatory activities, and cecropin A is a major member of the cecropin family. To elucidate the mechanism of cecropin A as anti-inflammatory under the condition of sub-acute ruminal acidosis (SARA) in dairy cows, we induced inflammation in bEECs with LPS (10 µg/mL) and then added cecropin A (25 µM). Afterwards, we detected three categories of indexes including oxidative stress indices, inflammation-related genes, and apoptosis-related genes in bovine endometrial epithelial cells (bEECs). The results indicated that cecropin A has the ability to reduce inflammatory factors TNF-α, IL-1β, and IL-8 and inhibit the MAPK pathway to alleviate inflammation. In addition, cecropin A is able to reduce reactive oxygen species (ROS) levels and alleviates LPS-induced oxidative stress and mitochondrial dysfunction by downregulating NADPH Oxidase (NOX), and upregulating catalase (CAT), glutathione peroxidase (GPX), and superoxide dismutase (SOD). Furthermore, cecropin A demonstrates the ability to inhibit apoptosis by suppressing the mitochondrial-dependent apoptotic pathway, specifically Fas/FasL-caspase-8/-3. The observed increase in the Bcl-2/Bax ratio, a known apoptosis regulator, further supports this finding. In conclusion, our study presents novel solutions for addressing inflammatory responses associated with SARA.

Background: Alzheimer disease (AD) is the most common neurodegenerative disorder leading to dementia in the elderly worldwide. Wnt signaling participates in multiple aspects of cellular function, and contributes to synapse formation, synaptic activity and neurogenesis in the brain, and dysfunction of Wnt signaling may aggravate the pathogenesis and progression of AD. Wnt2b has been studied in cancers or tumor‐related diseases, while the roles of Wnt2b in AD is still unknown. Wnt2b is also characterized as a mitochondria‐expressed protein which shuttles between mitochondria and the nucleus, and mitochondrial dysfunction contributes to the development and progression of the pathological process that underlies AD, especially at the early stage. This study investigated the relationship between plasma Wnt2b levels and AD, and explored the effect of Wnt2b on mitochondrial dysfunction in AD.Method: Normal cognitive (NC) and AD subjects, AD transgenic mice and in vitro model were used to investigated the roles of Wnt2b in abnormalities in canonical Wnt signaling and mitochondria in AD. RT‐qPCR, immunoblotting and immunofluorescence analysis were performed to assay canonical Wnt sign aling. Mitochondrial structure was analyzed by electron microscopy. Flow cytometry was used to examine the intracellular calcium and neuronal apoptosis.Result: In this study, we found plasma Wnt2b levels were lower in AD patients than NC subjects and positively correlated with cognitive performance (Figure 1). Similarly, Wnt2b was reduced in the hippocampus of AD mice and in vitro models (Figure 1). Next, Wnt2b overexpression and recombinant Wnt2b was used to endogenously (Figure 2) and exogenously (Figure 3) upregulate Wnt2b levels. Upregulation of Wnt2b could effectively prevent downregulation of canonical Wnt signaling, mitochondrial dysfunction in in vitro AD models. Subsequently, intracellular calcium overload and neuronal damage were ameliorated.Conclusion: Our study highlights that Wnt2b decline is associated with cognitive impairment in AD, and Our findings may advance the understanding of the importance of Wnt family in AD, and we propose that Wnt2b might be a potential diagnostic indicator and therapeutic target for AD.