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• Mastitis is the inflammation of mammary glands and Staphylococcus aureus is a notorious in cow mastitis. • Influx of neutrophils/macrophages and Isolation/identification of the S. aureus in mammary gland tissues during mastitis. • The TLR2, TLR4, p-38, ERK, JNK, p-65 and IκBα proteins are over-expressed in mastitis. • Up-regulation of pro-inflammatory cytokines TNF-α, IL-1β and IL-6 expressions during mastitis suggested active immune response. Mastitis is the inflammation of mammary glands which causes huge economic loss in dairy cows. Inflammation, any tissue injury and pathogens in cow udder activate Toll-like Receptors (TLRs). Staphylococcus aureus (S. aureus) is the major cause of mastitis. In mastitis, activated TLRs initiate the NF-κB/MAPKs pathways which further trigger the gene expression associated with mastitis followed by innate immune response. In this study, pathogenic-induced gene expression profile of pro-inflammatory cytokines in mammary gland tissues, was investigated in mastitis. The Hematoxylin and Eosin (H & E) results indicated severe histopathological changes in infected tissues. Western blot results suggested the over expressions of TLR2/TLR4 with NF-κB/MAPKs pathways activation in infected tissues. qRT-PCR results revealed the gene expression associated with TLR2/TLR4-mediated NF-κB/MAPKs pathways in infected tissues in comparison with non-infected. Statistical analysis of mRNA and relative protein expression levels indicated the up-regulation of pro-inflammatory cytokines (TNF-α, IL-1β and IL-6) in infected tissues rather than non-infected tissues. These results suggested that the up-regulation of gene expression levels implicated the underlying regulatory pathways for proper immune function in mammary glands. In conclusion, our study might give new insights for investigation and better understanding of mammary gland pathophysiology and TLRs and NF-κB/MAPKs-mediated gene expression of pro-inflammatory cytokines. [ABSTRACT FROM AUTHOR]

Acute lung Injury (ALI) is the clinical syndrome of parenchymal lung disease, leading to an extremely high mortality. The pathogenesis of ALI is suggested to be a consequence of uncontrolled inflammation. Lipopolysaccharide (LPS)-induced ALI mice model is often used for the mechanism. Studies show that TGF-beta activated kinase 1 (MAP3K7) binding protein 1/2 (TAB2) plays a crucial role in LPS-induced inflammation response. Furthermore, microRNA-142a-3p (miR-142a-3p) has been observed to be involved in inflammation-induced disease. Thus, we investigated the role of miR-142a-3p and TAB2 on LPS-induced ALI, which involved the TLR4/TAB2/NF-κB signaling. ALI and normal lung tissues were collected to access the relative expression of pro-inflammatory cytokines and miR-142a-3p. Histopathological examination and Wet to Dry weight ratios of lung tissues were used to access the establishment of ALI models. Raw264.7 cells were transfected with si-TAB2 or miR-142a-3p mimics to elucidate the role of TAB2 or miR-142a-3p in the inflammatory cascade in ALI. Additionally, the relationship between miR-142a-3p and TAB2 was validated by dual-luciferase report system. Our study discovered that miR-142-3p was up-regulated both in LPS-induced ALI mice model and RAW264.7 cells model. MiR-142a-3p mimics group experienced significant decrease in the secretion of pro-inflammatory cytokines as a result of the inhibition of NF-κB signaling pathway. Bioinformatics database showed that the adaptor protein, TAB2, was critical in this pathway and it is the target gene of miR-142a-3p. Their relation was first confirmed by us via dual-luciferase report system. Results of our study demonstrated that miR-142a-3p exerts as a protective role in LPS-induced ALI through down-regulation of NF-κB signaling pathway. • Acute lung Injury (ALI) is the clinical syndrome of parenchymal lung disease with extremely high mortality. • TGF-beta activated kinase 1 (MAP3K7) binding protein 1/2 (TAB2) plays a crucial role in LPS-induced inflammation response, which is negatively regulated by microRNA-142a-3p (miR-142a-3p). • Raw264.7 cells transfected with si-TAB2 or miR-142a-3p mimic showed significant decrease in the inflammatory cascade activation in ALI, indicating a promising therapeutic target for ALI. • The results of our study revealed that miR-142a-3p acted as a protective substance in LPS-induced ALI through down-regulation of NF-κB signaling pathway by targeting TAB2. [ABSTRACT FROM AUTHOR]

Purpose: To determine the protective effects of liquiritin on corticosterone-induced neurotoxicity in rat pheochromocytoma (PC12) cells. Methods: Neurotoxicity in PC12 cells was induced by different concentrations of corticosterone. Proliferation of PC12 cells was evaluated using CCK8 assay kits, while apoptosis was determined by flow cytometry. Results: The results indicate that corticosterone inhibited the proliferation of PC12 cells time- and dosedependently. The inhibitory effect (0.2 mM) was ameliorated by liquiritin. Furthermore, the cell apoptosis rate and protein level of caspase 3 in PC12 cells induced by corticosterone were ameliorated by liquiritin (1 and 2 mg/mL) treatment. Moreover, the protective effect of liquiritin (2 mg/mL) on corticosterone induced neurotoxicity in PC12 cells was weakened by K252a (the specific TrkB inhibitor) treatment. In addition, the protein level of brain-derived neurotrophic factor (BDNF) and (tyrosine-kinase receptor) TrkB showed a reverse trend to caspase 3. Conclusion: Liquiritin shows protective effects against neurotoxicity induced by corticosterone in PC12 cells, and these effects are exerted via up-regulating BDNF/TrkB signaling. [ABSTRACT FROM AUTHOR]

Acute lung injury (ALI) is considered as an uncontrolled inflammatory response that can leads to acute respiratory distress syndrome (ARDS), which limits the therapeutic strategies. Ginsenosides Rb1 (Rb1), an active ingredient obtained from Panax ginseng , possesses a broad range of pharmacological and medicinal properties, comprising the anti-inflammatory, anti-oxidant, and anti-tumor activities. Therefore, the purpose of the present study was to investigate the protective effects of Rb1 against S. aureus-induced (ALI) through regulation of Nuclear factor erythroid 2-related factor 2 (Nrf2) and mitochondrial-mediated apoptotic pathways in mice (in-vivo), and RAW264.7 cells (in-vitro). For that purpose, forty Kunming mice were randomly assigned into four treatment groups; (1) Control group (phosphate buffer saline (PBS); (2) S. aureus group; (3) S. aureus + Rb1 (20 mg/kg) group; and (4) Rb1 (20 mg/kg) group. The 20 μg/mL dose of Rb1 was used in RAW264.7 cells. In the present study, we found that Rb1 treatment reduced ALI-induced oxidative stress via suppressing the accumulation of malondialdehyde (MDA) and myeloperoxidase (MPO) and increase the antioxidant enzyme activities of superoxidase dismutase 1 (SOD1), Catalase (CAT), and glutathione peroxidase 1 (Gpx1). Similarly, Rb1 markedly increased messenger RNA (mRNA) expression of antioxidant genes (SOD1, CAT and Gpx1) in comparison with ALI group. The histopathological results showed that Rb1 treatment ameliorated ALI-induced hemorrhages, hyperemia, perivascular edema and neutrophilic infiltration in the lungs of mice. Furthermore, Rb1 enhanced the antioxidant defense system through activating the Nrf2 signaling pathway. Our findings showed that Rb1 treated group significantly up-regulated mRNA and protein expression of Nrf2 and its downstream associated genes down-regulated by ALI in vivo and in vitro. Moreover, ALI significantly increased the both mRNA and protein expression of mitochondrial-apoptosis-related genes (Bax, caspase-3, caspase-9, cytochrome c and p53), while decreased the Bcl-2. In addition, Rb1 therapy significantly reversed the mRNA and protein expression of these mitochondrial-apoptosis-related genes, as compared to the ALI group in vivo and in vitro. Taken together, Rb1 alleviates ALI-induced oxidative injury and apoptosis by modulating the Nrf2 and mitochondrial signaling pathways in the lungs of mice. Image 1 • Rb1, is obtained from Panax ginseng , having anti-oxidant and anti-apoptotic properties. • Rb1, save lung from S. aureus -induced oxidative damage via Nrf2 pathway. • Rb1, alleviates ALI-induced apoptosis by modulating mitochondrial signaling. [ABSTRACT FROM AUTHOR]