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Solving the reproductive barriers of dairy cows has become one of the most critical factors determining the dairy industry's development. Clinically, inflammation disease like endometritis is the most crucial cause in reducing dairy production's financial viability. MiR-193 family can induce cell apoptosis and differentiation has been reported in various diseases. LGR4 plays a vital role in reproductive system development and immune system regulation, and it is closely related to animal reproductive function and cytokine regulation. In this study, we observed a negative relationship between miR-193a-3p and LGR4 expression level in both inflammatory tissues and cells. The expression level of miR-193a-3p and LGR4 in bovine endometrial epithelial cells (BENDs) is regulated by lipopolysaccharide (LPS) stimulation time and dose-dependent. Subsequently, miR-193a-3p mimics and inhibitors were used to explore its functions in the inflammation response process, finding that overexpression of miR-193a-3p markedly increases the expression level of pro-inflammatory cytokines induced by LPS, such as IL-1β, IL-6 and TNF-α, while the group in which transfected inhibitor is on the contrary. Of note, immunofluorescence and western blot results showed that miR-193a-3p enhanced LPS-induced NF-κB p65 phosphorylation through targeting LGR4, whereas inhibiting miR-193a-3p could suppress the activation of NF-κB pathway significantly. In conclusion, our study firstly reported the mechanism by which miR-193a-3p targets LGR4 to elevate the inflammatory response in bovine endometrium injury, thereby implying that knockdown miR-193a-3p may lay the theoretical and practical basis for drug development of alleviating endometritis in dairy cows.

Endometritis in dairy cows is a major economic problem worldwide; without advances in lifestyle management and drug treatment, it causes high morbidity and death. Micro ribonucleic acid (miRNAs) these days is seen as an important part of gene control networks. It is a class of small nucleotides 20-25, single-stranded RNA molecules. In endometritis, the inflammatory response caused by the gram-negative bacteria Escherichia coli (E. coli) alters the expression of miRNA which can regulate the innate immune system. This manuscript reviews (1) the interaction of miRNAs with the signaling of NF-κB and dysregulation of miRNAs and NF-κB activity in endometritis and (2) the activity of miR-let-7c, miR-148a, and miR-488 in NF-κB activation and their effect on endometritis. Cows with reduced immunity are more vulnerable to transition diseases, such as endometritis. During post-partum, cows undergo stress, metabolic disorders, hormonal imbalance, negative energy balance, and changes in diet. One of the many categories of regulatory molecules, which explain its natural function and pathological impact on NF-κB dysregulation, is important to inform the complexity of the immune system and to develop treatments for endometritis. It shows that miRNAs could have multiple applications in veterinary medicine. Nevertheless, a comprehensive study of is essential which should be aimed at exploring the role of microRNA at physiological level and its effect due to dysfunction and dysregulation.

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.

Hederacoside-C (HDC) is a biological active ingredient, extracted from the leaves of Hedera helix. It has been reported to have anti-inflammatory properties. However, the effects of HDC on Staphylococcus aureus (S. aureus)-induced mastitis have not been reported yet. Here, we evaluated the anti-inflammatory effects of HDC on S. aureus-induced mastitis both in vivo on mammary gland tissues and in vitro on RAW 264.7 cells. The ascertained histopathological changes and MPO activity revealed that HDC defended mammary glands from tissue destruction and inflammatory cell infiltration induced by S. aureus. The results of ELISA, western blot, and qRT-PCR indicated that HDC significantly inhibited the expressions IL-6, IL-1β, and TNF-α and enhanced the IL-10 by downregulating and upregulating their relevant genes, respectively. Furthermore, HDC markedly suppressed the TLR2 and TLR4 expressions by attenuating the MAPKs (p38, ERK, JNK) and NF-κB (p65 and IκBα) pathways followed by decreasing the phosphorylation of p38, ERK, JNK, p65, and IκBα. The above parameters enhanced the mammary gland defense and reduced inflammation. These findings suggested that HDC may have the potential to be an effective anti-inflammatory drug for the S. aureus-induced mice mastitis and in RAW 264.7 cells.

Objective Staphylococcus aureus (S. aureus), one of Gram-positive pathogen, is frequently associated with acute lung inflammation. The central feature of S. aureus acute lung inflammation are pulmonary dysfunctioning and impeded host defence response, which cause failure in inflammatory cytokines homeostasis and leads to serious tissue damage. However, the role of the Mer receptor tyrosine kinase (MerTK) in the lung following S. aureus infection remains elusive. Here, we investigate whether MerTK alleviates S. aureus induced uncontrolled inflammation through negatively regulating toll-like receptor 2 and 6 (TLR2/ TLR6) via suppressor of cytokine signalling 1, 3 (SOCS1/SOCS3). Methods and results We found in mice lung tissues and RAW 264.7 macrophages upon S. aureus infection activates TLR2 and TLR6 driven mitogen-activated protein kinases (MAPKs) and nuclear factor kappa B (NF-κB) signalling pathways, resulting in production of inflammatory cytokines including tumour necrosis factor-α (TNF-α), interleukin 1β (IL-1β), interleukin 6 (IL-6). Furthermore, S. aureus-infection groups showed a significant up-regulation of MerTK which serves as mediator of SOCS1 and SOCS3. Subsequently, through feedback mechanism SOCS1/3 degrade Mal, resulting in inhibition of downstream TLR mediated inflammatory pathways. Moreover, MerTK−/− mice lung tissues and silencing MerTK in RAW 264.7 inhibited the S. aureus-induced activation of MerTK, which significantly upregulated the phosphorylation of crucial protein in MAPKs (ERK, JNK, p38) and NF-κB (IĸBα, p65) signalling pathways, as well as the production of pro-inflammatory cytokines. Conclusion Collectively, these findings indicate the important role of MerTK in self-regulatory resolution of S. aureus-induced inflammatory pathways and cytokines through intrinsic SOCS1 and SOCS3 repressed feedback on TLR2, TLR6 both in vivo and in vitro.

Acute lung injury (ALI) is clinically characterized by excessive inflammation leading to acute respiratory distress syndrome (ARDS), having high morbidity and mortality both in human and animals. Ginsenoside Rb1 (Rb1) is a major primary bioactive component extracted by Panax ginseng, which has numerous pharmacological functions such as anti-cancer, anti-inflammatory, and antioxidant. However, the anti-inflammatory effects of Rb1 in Staphylococcus aureus (S. aureus)-induced ALI in mice have not been investigated. The aim of the current study was to determine the anti-inflammatory influence of Rb1 on S. aureus-induced ALI in mice, and to explore its possible underlying principle mechanisms in RAW 264.7 macrophage cells. The results of physical morphology, histopathological variation and wet-to-dry weight ratio of lungs revealed that Rb1 significantly attenuated S. aureus-induced lung injury. Furthermore, qPCR results displayed that Rb1 inhibited IL-1β, IL-6 and TNF-α production both in vivo and in vitro. The activation of Toll-like receptor 2 (TLR2) by S. aureus was inhibited by application of Rb1 as confirmed by results of immunofluorescence assay. The expression of NF-kB and MAPK signaling proteins revealed that Rb1 significantly attenuated the phosphorylation of p65, ERK, as well as JNK. Altogether, the results of this experiment presented that Rb1 has ability to protect S. aureus-induced ALI in mice by attenuating TLR-2-mediated NF-kB and MAPK signaling pathways. Consequently, Rb-1 might be a potential medicine in the treatment of S. aureus-induced lung inflammation.

Acute lung inflammation is one among the top of infectious diseases. It is a pulmonary dysfunctional disease. It breaks the physiological coordination in the structures and functions of respiratory system. There are a few effective treatments to minimize the mortality of acute lung inflammation. It was induced by Staphylococcus aureus (S. aureus) via nasal instillation of mice. The common ivy (Hedera helix) is the most significant medicinal plant and considered as a traditional medicinal plant. The most active ingredient in the extract of ivy plant was Hederacoside-C (HDC). The purpose of this study was to investigate its anti-inflammatory effects on induced acute lung inflammation in vivo and (RAW 264.7 cells) in vitro and to elucidate its anti-inflammatory mechanisms. HDC was administered intraperitoneally 1 h after infection until 24 h. The dose was repeated every 8 h for three successful doses. Mice treated with HDC significantly reduced the pulmonary edema, white blood cells, wet-dry ratio (W/D) and myeloperoxidase (MPO) activity. HDC attenuated protein expression levels of MAPKs including p38, ERK, JNK and NF-κB including p65 and IκB-α pathways analyzed by ELISA. HDC also suppressed the protein expressions of TLR2 & TLR4 detected by Western blot. HDC also downregulated the gene expression of pro-inflammatory cytokines including IL-6, IL-1β and TNF-α, but upregulated the gene expression of an anti-inflammatory cytokine IL-10 analyzed by qRT-PCR. In conclusion, our results stated that HDC could inhibit the S. aureus induced acute lung inflammation and it may be a potential therapeutic drug against acute lung inflammation.