Oxidative stress consistently affects lactation length and quality in dairy cows. Oxidative stress in the mammary gland of high-yielding dairy cows is a serious problem. Therefore, we studied the ...role of butyrate in dairy cow oxidative stress and further elucidated the mechanism of the antioxidative action of mammary epithelial cells in dairy cows. Oxidative stress and activated GPR109A were present in high-yielding dairy cows. Then, bovine mammary epithelial cells (BMECs) were isolated, and oxidative stress-related protein expression was measured, confirming that sodium butyrate (NaB) exerted antioxidant effects through GPR109A, NRF2 and H3K9/14 acetylation. To further study the antioxidative mechanism of butyrate in dairy cows, we also confirmed that butyrate promoted NRF2 nuclear accumulation and H3K9/14 acetylation through the AMPK signaling pathway by western blotting. Additionally, we preliminarily clarified the interaction between NRF2 and H3K9/14 acetylation by Co-IP and ChIP. Butyrate activated the AMPK signaling pathway through GPR109A to promote NRF2 nuclear accumulation and H3K9/14 acetylation, subsequently exerting antioxidant effects through the synergistic functions of these two processes. Then, we studied the effect of butyrate on oxidative stress in dairy cows in vivo, and the results were consistent with those in vitro. Therefore, butyrate played an antioxidant and antiapoptotic role through the GPR109A/AMPK/NRF2 signaling pathway, while H3K9/14 acetylation could promote NRF2 transcription and enhance the antioxidant capacity of BMECs.
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•The mechanism of GPR109A in antioxidation was studied for the first time.•The interaction of Nrf2 and H3K9/14 in antioxidative stress was identified.•The effect of GPR109A on histone acetylation was preliminarily clarified.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Background/Aims: Butyric acid plays an important role in maintaining intestinal health. Butyric acid has received special attention as a short-chain fatty acid, but its role in protecting the ...intestinal barrier is poorly characterized. Butyric acid not only provides energy for epithelial cells but also acts as a histone deacetylase inhibitor; it is also a natural ligand for G protein-coupled receptor 109A (GPR109A). A GPR109A analog was expressed in Sus scrofa and mediated the anti-inflammatory effects of beta-hydroxybutyric acid. This study investigated the effects of butyrate on growth performance, diarrhea symptoms, and tight junction protein levels in 21-day-old weaned piglets. We also studied the mechanism by which butyric acid regulates intestinal permeability. Methods: Twenty-four piglets that had been weaned at an age of 21 days were divided randomly into 2 equal groups: basal diet group and sodium butyrate + basal diet group. Diarrhea rate, growth performance during 3 weeks of feeding on these diets were observed, the lactulose-mannitol ratio in urine were detected by High Performance Liquid Chromatography, the expression levels of tight junction proteins in the intestinal tract and related signaling molecules, such as GPR109A and Akt, in the colon were examined by quantitative real-time PCR or western blot analyses on day 21. Caco-2 cells were used as a colon cell model and cultured with or without sodium butyrate to assess the expression of tight junction proteins and the activation of related signaling molecules. GPR109A-short hairpin RNA (shRNA) and specific antagonists of Akt and ERK1/2 were used as signaling pathway inhibitors to elucidate the mechanism by which butyric acid regulates the expression of tight junction proteins and the colonic epithelial barrier. Results: The sodium butyrate diet alleviated diarrhea symptoms and decreased intestinal permeability without affecting the growth of early weaned piglets. The expression levels of the tight junction proteins Claudin-3, Occludin, and zonula occludens 1 were up-regulated by sodium butyrate in the colon and Caco-2 cells. GPR109A knockdown using shRNA or blockade of the Akt signaling pathway in Caco-2 cells suppressed sodium butyrate-induced Claudin-3 expression. Conclusions: Sodium butyrate acts on the Akt signaling pathway to facilitate Claudin-3 expression in the colon in a GPR109A-dependent manner.
Mastitis, an inflammation of mammary gland, is a serious disease that affects the health of dairy cows around the world. Myricetin, a flavonoid from Bayberry, has been reported to suppress various ...inflammatory response. The aim of this study was to evaluate the effect of myricetin on lipopolysaccharide (LPS)‐induced in vivo and in vitro mastitis model and clarify the underlying mechanism. In vivo experiments, myricetin attenuated the severity of inflammatory lesion and neutrophil infiltration. Moreover, myricetin pretreatment induced a significant decrease in the activity of myeloperoxidase (MPO) and the production of TNF‐α, IL‐6, and IL‐1β triggered by LPS. Myricetin pretreatment could also increase the integrity of the blood–milk barrier and upregulate the tight junction proteins in LPS‐induced mice mastitis. In vitro, myricetin inhibited LPS‐induced inflammatory response in mice mammary epithelial cells (mMECs). In the further mechanism studies, we found that the anti‐inflammatory effect of myricetin was mediated by inhibiting LPS‐induced phosphorylation of AKT, IKK‐α, IκB‐α, and P65 in vivo and in vitro. Collectively, these data suggested that myricetin effectively ameliorated the inflammatory response by inhibiting the AKT/IKK/NF‐κB signaling pathway and repairing the integrity of blood–milk barrier in LPS‐induced mice mastitis.
Myricetin administration significantly alleviates lipopolysaccharide (LPS)‐induced inflammatory response via inhibiting AKT/IKK/NF‐κB signaling pathway and repairing blood–milk barrier via upregulating the protein levels of claudin‐3, occludin, and ZO‐1 in LPS‐induce mice mastitis.
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SAZU, SBCE, SBMB, UL, UM, UPUK
Parkinson's disease (PD) is a common neurodegenerative disease characterized by selective loss of dopaminergic neurons in the substantia nigra (SN). Neuroinflammation induced by over-activation of ...microglia leads to the death of dopaminergic neurons in the pathogenesis of PD. Therefore, downregulation of microglial activation may aid in the treatment of PD. Polydatin (PLD) has been reported to pass through the blood-brain barrier and protect against motor degeneration in the SN. However, the molecular mechanisms underlying the effects of PLD in the treatment of PD remain unclear. The present study aimed to determine whether PLD protects against dopaminergic neurodegeneration by inhibiting the activation of microglia in a rat model of lipopolysaccharide (LPS)-induced PD. Our findings indicated that PLD treatment protected dopaminergic neurons and ameliorated motor dysfunction by inhibiting microglial activation and the release of pro-inflammatory mediators. Furthermore, PLD treatment significantly increased levels of p-AKT, p-GSK-3β
, and Nrf2, and suppressed the activation of NF-κB in the SN of rats with LPS-induced PD. To further explore the neuroprotective mechanism of PLD, we investigated the effect of PLD on activated microglial BV-2 cells. Our findings indicated that PLD inhibited the production of pro-inflammatory mediators and the activation of NF-κB pathways in LPS-induced BV-2 cells. Moreover, our results indicated that PLD enhanced levels of p-AKT, p-GSK-3β
, and Nrf2 in BV-2 cells. After BV-2 cells were pretreated with MK2206 (an inhibitor of AKT), NP-12 (an inhibitor of GSK-3β), or Brusatol (BT; an inhibitor of Nrf2), treatment with PLD suppressed the activation of NF-κB signaling pathways and the release of pro-inflammatory mediators in activated BV-2 cells via activation of the AKT/GSK3β-Nrf2 signaling axis. Taken together, our results are the first to demonstrate that PLD prevents dopaminergic neurodegeneration due to microglial activation via regulation of the AKT/GSK3β-Nrf2/NF-κB signaling axis.
High‐producing dairy cows are prone to oxidative stress due to their high secretion and strong metabolism, and excessive oxidative stress may cause the apoptosis of bovine mammary epithelial cells ...(bMECs). Myricetin (Myr) has been shown to have a wide range of pharmaceutical activities. The aim of this study was to evaluate the effect of Myr on hydrogen peroxide (H2O2)‐induced oxidative stress and apoptosis in bMECs and to clarify the underlying mechanism. bMECs were pretreated with or without Myr and then stimulated with H2O2. The results showed that Myr significantly increased the total antioxidant capacity and superoxide dismutase levels and decreased the malondialdehyde (MDA) and reactive oxygen species (ROS) levels in a model of oxidative stress induced by H2O2 in bMECs. Mechanistic studies found that Myr inhibited H2O2‐induced oxidative stress in bMECs through the adenosine monophosphate‐activated protein kinase/nuclear factor erythroid‐2 related factor 2 (AMPK/NRF2) signaling pathway. Additional research found that Myr could also inhibit H2O2‐induced apoptosis in bMECs through NRF2. These data suggest that Myr effectively alleviated oxidative stress and apoptosis in H2O2‐induced bMECs through the activation of the AMPK/NRF2 signaling pathway.
Hydrogen peroxide (H2O2) inhibited the activity of adenosine monophosphate‐activated protein kinase/nuclear factor erythroid‐2 related factor 2 (AMPK/NRF2) signaling and promoted the release of reactive oxygen species in bovine mammary epithelial cells, which induced oxidative stress, damage mitochondria, and cause apoptosis. Myricetin administration significantly alleviated H2O2‐induced oxidative stress and the apoptosis response by activating AMPK/NRF2 signaling.
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SAZU, SBCE, SBMB, UL, UM, UPUK
Previous studies have shown the effects of vitamins on the development of the mammary gland. However, the role of niacin in this process has not been reported. Therefore, the aim of this study is to ...investigate the effects of niacin on mammary gland development in pubertal mice and to use a mouse mammary epithelial cell line to study the underlying mechanism. The results showed that niacin could activate the AKT/mTOR and ERK signaling pathways and increase phosphorylation of 4EBP1 to promote the synthesis of cell proliferation markers, leading to the dissociation of the Rb-E2F1 complex in mMECs. In addition, 0.5% niacin promoted mammary duct development, increased the expression of cyclin D1/D3 and PCNA and activated Akt/mTOR and ERK1/2 in the mammary glands of pubertal mice. These results strongly suggest that niacin stimulates mammary gland development in pubertal mice through the Akt/mTOR and ERK1/2 signaling pathways.
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EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
Mastitis is an acute clinical inflammatory response. The occurrence and development of mastitis seriously disturb women's physical and mental health. Licochalcone A, a phenolic compound in
, has ...anti-inflammatory properties. Here, we examined the effect of licochalcone A on blood-milk barrier and inflammatory response in LPS-induced mice mastitis.
, we firstly established mice models of mastitis by canal injection of LPS to mammary gland, and then detected the effect of licochalcone A on pathological indexes, inflammatory responses and blood-milk barrier in this model.
, Mouse mammary epithelial cells (mMECs) were treated with licochalcone A prior to the incubation of LPS, and then the inflammatory responses, tight junction which is the basic structure of blood-milk barrier were analyzed. Last, we elucidated the anti-inflammatory mechanism by examining the activation of mitogen-activated protein kinase
MAPK) and AKT/NF-κB signaling pathways
and
.
The
results showed that licochalcone A significantly decreased the histopathological impairment and the inflammatory responses, and improved integrity of blood-milk barrier. The
results demonstrated that licochalcone A inhibited LPS-induced inflammatory responses and increase the protein levels of ZO-1, occludin, and claudin3 in mMECs. The
and
mechanistic study found that the anti-inflammatory effect of licochalcone A in LPS-induced mice mastitis was mediated by MAPK and AKT/NF-κB signaling pathways.
Our experiments collectively indicate that licochalcone A protected against LPS-induced mice mastitis via improving the blood-milk barrier integrity and inhibits the inflammatory response by MAPK and AKT/NF-κB signaling pathways.
It has been reported that the proliferation and apoptosis of mammary epithelial cells affect milk production. Therefore, ensuring adequate mammary epithelial cells is expected to enhance milk ...production. This study is devoted to studying the effects of kisspeptin‐10 (Kp‐10), a peptide hormone composed of 10 amino acids, on bovine mammary epithelial cell (bMEC) proliferation and exploring the underlying mechanism of its action. bMECs were treated with various concentrations of Kp‐10 (1, 10, 100, and 1,000 nM), and 100 nM Kp‐10 promoted the proliferation of the bMECs. Kp‐10 promoted the cell cycle transition from G1 to the S and G2 phases, increased the protein levels of Cyclin D1 and Cyclin D3, and reduced the expression levels of the p21 gene. This study also showed that inhibition of G protein‐coupled receptor 54 (GPR54), AKT, mTOR, and ERK1/2 reduced the proliferation of the bMECs that had been induced by Kp‐10. In addition, Kp‐10 decreased the complexes formed by Rb and E2F1 and increased the expression levels of the E2F1 target genes. These results indicate that Kp‐10 promotes bMEC proliferation by activating GPR54 and its downstream signaling pathways.
The proliferation of bovine mammary epithelial cells can increase milk production. We found that Kisspeptin‐10 promotes the proliferation of bovine mammary epithelial cells by activating the GPR54 and its downstream signaling pathways.
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SAZU, SBCE, SBMB, UL, UM, UPUK
Parkinson's disease (PD) is caused by the loss of dopaminergic (DA) neurons in the midbrain substantia nigra (SN). Neuroinflammation, which is marked by microglial activation, plays a very important ...role in the pathogenesis of PD. Pro-inflammatory mediators produced by activated microglia could damage DA neurons. Hence, the inhibition of microglial activation may provide a new approach for treating PD. Galangin has been shown to inhibit inflammation in a variety of diseases, but not PD. In this study, we aimed to investigate the anti-inflammatory effect of galangin and the underlying mechanisms in Lipopolysaccharide (LPS) induced PD models. We first examined the protective effect of galangin in the LPS-induced PD rat model. Specifically, we investigated the effects on motor dysfunction, microglial activation, and the loss of DA neurons. Then, galangin was used to detect the impact on the inflammatory responses and inflammatory signaling pathways in LPS-induced BV-2 cells. The in vivo results showed that galangin dose-dependently attenuates the activation of microglia, the loss of DA neurons, and motor dysfunction. In vitro, galangin markedly inhibited LPS-induced expression of tumor necrosis factor α (TNF-α), interleukin-6 (IL-6) and interleukin-1β (IL-1β), cyclooxygenase 2 (COX-2), and induced nitric oxide synthase (iNOS) via associating with the phosphorylation of c-JUN N-terminal Kinase (JNK), p38, protein kinase B (AKT), and nuclear factor κB (NF-κB) p65. Collectively, the results indicated that galangin has a role in protecting DA neurons by inhibiting microglial activation.
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IZUM, KILJ, NUK, PILJ, PNG, SAZU, UL, UM, UPUK
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