High-Concentrate Feeding to Dairy Cows Induces Apoptosis via the NOD1/Caspase-8 Pathway in Mammary Epithelial Cells.

(1) Background: The effects of a high-concentrate (HC) diet in inducing mammary epithelial cell apoptosis in dairy cows via the NOD1/Caspase-8 pathway have never been investigated before the current study. (2) Methods: Twelve Holstein Frisian cows at mid-lactation were selected to conduct this research. The animals were randomly allocated to two groups (n = 6), and both groups received one of two diets: a low-concentrate (LC) (forage: concentrate 6:4) or a high-concentrate (HC) (forage: concentrate 4:6) diet. Furthermore, an enzyme activity assay, tunnel cell assay, RT-qPCR, western blotting, and an immunofluorescence antibody (IFA) assay were performed to elucidate the effect of an HC diet in the mammary gland of dairy cows. (3) Results: The tunnel cell assay revealed a significant number of apoptotic cells in HC group, and the concentration of Caspase-3, and Caspase-8 was higher in the HC group than in the LC group. NOD1, Rip-2, Caspase-3, Caspase-8, Caspase-9, and Bax mRNA expressions, and NOD1, Caspase-3, Caspase-8, and Bax protein expressions, in the HC group were markedly higher than those in the LC group. Furthermore, Bcl-2 mRNA and protein expressions were markedly decreased in the HC compared to those in the LC group. (4) Conclusions: A HC diet fed to dairy cows incites subacute ruminal acidosis (SARA), which increases the iE-DAP concentration and induces apoptosis in the mammary gland via the NOD1/Caspase-8 pathway.

Synthesis of Tilmicosin Nanostructured Lipid Carriers for Improved Oral Delivery in Broilers: Physiochemical Characterization and Cellular Permeation.

This study aimed to develop nanostructured lipid carriers (NLCs) for improved oral absorption of tilmicosin (TMS) in broilers. Thus, palmitic acid, lauric acid, and stearic acid were selected as solid lipids to formulate TMS-pNLCs, TMS-lNLCs, and TMS-sNLCs, respectively. They showed similar physicochemical properties and meanwhile possessed excellent storage and gastrointestinal stability. The TMS interacted with the lipid matrix and was encapsulated efficiently in NLCs in an amorphous structure. NLCs could enhance oral absorption of TMS compared to 10% tilmicosin phosphate solution in broilers, among which the TMS-sNLCs were the most efficient drug delivery carriers, with a relative oral bioavailability of 203.55%. NLCs could inhibit the efflux of P-glycoprotein (P-pg) toward TMS, which may be involved with improved oral absorption. Taken together, these types of solid lipids influenced the enhanced level of NLCs toward oral bioavailability of TMS, and the sNLCs proved to be the most promising oral delivery carriers of TMS.

Lipopolysaccharide derived from the digestive tract triggers an inflammatory response in the uterus of mid-lactating dairy cows during SARA.

BACKGROUND: The aims of the current study were to evaluate the inflammatory response in cow uterus and to explore the molecular mechanism triggered by high concentrate-induced subacute ruminal acidosis (SARA) in mid-lactating dairy cows. Twelve mid-lactating Holstein cows with an average weight of 455 kg were allocated into two groups subjected to two diets for 18-weeks either a low-concentrate (LC) group containing 4:6 (NDF: NFC) and a high-concentrate (HC) group containing 6:4 (non-forage carbohydrates, NFC): (neutral detergent fiber, NDF) ratio based on dry matter. RESULTS: The HC group showed lower ruminal pH and higher lipopolysaccharide (LPS) concentrations in both the rumen and peripheral plasma compared to the LC group. The LPS concentrations in the rumen fluid and the peripheral plasma were found significantly increased in the HC group compared to the LC group. The concentrations of IL-1ß, TNF-α and IL-6 were significantly higher in the HC group compared to the LC group. The uterus of SARA cows revealed elevated mRNA concentrations of nuclear transcription factors and pro-inflammatory cytokines, which confirmed the presence of inflammation. The occurrence of uterine inflammation was further validated by the increased protein expression of NF-κB-p65 and its active phosphorylated variant in the uterus of SARA cows. Similarly, the inflammatory genes TLR4, LBP, MyD88, TRAF-6, NF-κB, IL-6, IL-8, TNF-α and IL-1ß were significantly upregulated in the uterus of the HC versus the LC group. CONCLUSION: Therefore, the results indicated that LPS derived from the rumen triggered the genes associated with inflammation in the uterus of mid-lactating dairy cows fed a high-concentrate diet, causing endometritis.