Publications by authors named "Kangfeng Jiang"

54 Publications

Fisetin Ameliorates the Inflammation and Oxidative Stress in Lipopolysaccharide-Induced Endometritis.

J Inflamm Res 2021 5;14:2963-2978. Epub 2021 Jul 5.

Department of Veterinary Medicine, College of Animal Sciences, Zhejiang University, Hangzhou, 310058, Zhejiang, People's Republic of China.

Purpose: Fisetin is a natural flavone of polyphenol, which widely exists in many fruits and vegetables and has many pharmacological activities. However, the mechanism involved remains largely unknown. Here, we investigate the mechanisms of fisetin on the inflammatory response and oxidative stress in LPS-induced endometritis model and bovine endometrial epithelial cell line (BEND).

Methods: The function of fisetin was analyzed by network pharmacology. Effects of increasing doses of fisetin on inflammation and oxidative stress are studied in BALB/c mice with LPS-induced endometritis. The underlying mechanisms of antioxidant activity of fisetin were further explored in LPS-stimulated BEND cells.

Results: The results showed that fisetin significantly alleviated LPS-induced inflammatory injury and oxidative stress both in vivo and in vitro. Further studies found that fisetin greatly inhibited the LPS stimulated TLR4 expression and nuclear translocation of nuclear factor-κB (NF-κB), thus reducing the pro-inflammatory mediators secretion. Silencing TLR4 reduced LPS-induced inflammatory responses. Moreover, we observed that fisetin evidently decreased ROS production but activated Nrf2/HO-1 pathway in LPS-stimulated BEND cells. To further explore the role of Nrf2 in fisetin-induced HO-1 protein expression, the specific siRNA was used to silence Nrf2 expression. Silencing Nrf2 abrogated the inhibitory effects of fisetin on LPS-induced pro-inflammatory cytokines TNF-α, IL-1β secretion, NADPH oxidase-4 (Nox4) and ROS production.

Conclusion: In conclusion, fisetin effectively protected against LPS-induced oxidative stress and inflammatory responses which may be closely correlated to inhibition of TLR4-mediated ROS/NF-κB and activation of the Nrf2/HO-1 pathway.
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http://dx.doi.org/10.2147/JIR.S314130DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8275103PMC
July 2021

Ginsenoside Rb1 protects from Staphylococcus aureus-induced oxidative damage and apoptosis through endoplasmic reticulum-stress and death receptor-mediated pathways.

Ecotoxicol Environ Saf 2021 Aug 23;219:112353. Epub 2021 May 23.

College of Veterinary Medicine, Huazhong Agricultural University, Wuhan, China. Electronic address:

Acute lung injury (ALI) is acute uncontrolled inflammation of lung tissue that leads to high fatality both in human and animals. Staphylococcus aureus (S. aureus) could be an opportunistic, versatile bacterial etiology of ALI. Ginsenoside Rb1 (Rb1) is extracted from the Panax ginseng, which displays a wide range of biological and pharmacological effects. However, protective effects of Rb1 in S. aureus-induced ALI though endoplasmic reticulum (ER) stress and death receptor-mediated pathways have not yet been reported. Therefore, present study was planned with the aims to investigate the antioxidant and anti-apoptotic properties of Rb1 through regulation of ER stress as well as death receptor-mediated pathways in ALI induced by S. aureus in mice. In this study, four groups of healthy Kunming mice (n = 48) were used. The S. aureus (80 µl; 1 ×10 CFU/10 µl) was administered intranasally to establish mice model of ALI. After 24 h of onset of S. aureus-induced ALI, the mice were injected thrice with Rb1 (40 mg/kg) intraperitoneally six hours apart. Histopathology, enzyme linked immunosorbent assay (ELISA), real time quantitative polymerase chain reaction (RT-qPCR), Immunohistochemistry and western blotting assay were employed in the current study. Our results suggested that Rb1 administration save lungs from pulmonary injury by reducing wet to dry (W/D) ratio, protein levels, total cells, neutrophilic count, reactive oxygen species (ROS), myeloperoxidase (MPO), malondialdehyde (MDA), superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (Gpx)1 depletion. Meanwhile, Rb1 therapy ameliorated histopathology alteration of lung tissue and pro-inflammatory cytokines secretion. The gene expression of ER stress marker (PERK, AFT-6, IRE1 and CHOP) were upregulated markedly (P < .05) in S. aureus-instilled groups, which was reduced by Rb1 administration that is reveled from the result findings of the RT-qPCR and immunoblot assay. The results of immunohistochemistry for CHOP indicated the increased expression in S. aureus groups which in turn ameliorated by Rb1 treatment. The mRNA expression demonstrated that death receptor-associated genes (FasL, Fas, FADD and caspase-8) showed up-regulation in S. aureus group. The similar findings were observed for the protein expression of caspase-8, FADD and Fas. Rb1 treatment markedly (P < .05) reversed protein and mRNA expression levels of these death receptor-associated genes when compared to the S. aureus group. Taken together, Rb1 attenuated S. aureus-induced oxidative damage via the ER stress-mediated pathway and apoptosis through death receptor-mediated pathway. Conclusively, our findings provide an insight into preventive mechanism of Rb1 in ALI caused by S. aureus and hence proven a scientific baseline for the therapeutic application of Rb1.
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http://dx.doi.org/10.1016/j.ecoenv.2021.112353DOI Listing
August 2021

Upregulated-gene expression of pro-inflammatory cytokines, oxidative stress and apoptotic markers through inflammatory, oxidative and apoptosis mediated signaling pathways in Bovine Pneumonia.

Microb Pathog 2021 Jun 1;155:104935. Epub 2021 May 1.

College of Veterinary Medicine, Huazhong Agricultural University, Wuhan, China. Electronic address:

Pneumonia is the acute inflammation of lung tissue and is multi-factorial in etiology. Staphylococcus aureus (S. aureus) is a harmful pathogen present as a normal flora of skin and nares of dairy cattle. In bovine pneumonia, S. aureus triggers to activates Toll-Like Receptors (TLRs), that further elicits the activation of the inflammation via NF-κB pathway, oxidative stress and apoptotic pathways. In the current study, pathogen-associated gene expression of the pro-inflammatory cytokines, oxidative stress and apoptotic markers in the lung tissue of cattle was explored in bovine pneumonia. Fifty lung samples collected from abattoir located in Wuhan city, Hubei, China. Histopathologically, thickening of alveolar wall, accumulation of inflammatory cells and neutrophils in perivascular space, hyperemia, hemorrhages and edema were observed in infected lungs as compared to non-infected lung samples. Furthermore, molecular identification and characterization were carried by amplification of S. aureus-specific nuc gene (270 base pairs) from the infected and non-infected lung samples to identify the S. aureus. Moreover, qPCR results displayed that relative mRNA levels of TLR2, TLR4, pro-inflammatory gene (IL-1β, IL-6 and TNF-α) and apoptosis-associated genes (Bax, caspase-3 and caspase-9) were up-regulated except Bcl-2, which is antiapoptotic in nature, and oxidative stress related genes (Nrf2, NQO1, HO-1 and GCLC) which was down-regulated in infected pulmonary group. The relative protein expression of NF-κB, mitochondria-mediated apoptosis gene was up-regulated while Bcl-2 and Nrf2 pathway genes were downregulated in infected cattle lungs. Our findings revealed that genes expression levels of inflammatory mediators, oxidative stress and apoptosis were associated with host immunogenic regulatory mechanisms in the lung tissue during infection. Conclusively, the present study provides insights of active immune response via TLRs-mediated inflammatory, oxidative damage, and apoptotic paradox.
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http://dx.doi.org/10.1016/j.micpath.2021.104935DOI Listing
June 2021

MicroRNA: Could It Play a Role in Bovine Endometritis?

Inflammation 2021 Apr 27. Epub 2021 Apr 27.

Department of Clinical Veterinary Medicine, College of Veterinary Medicine, Huazhong Agricultural University, Wuhan, 430070, People's Republic of China.

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.
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http://dx.doi.org/10.1007/s10753-021-01458-3DOI Listing
April 2021

Enforced expression of miR-92b blunts lipopolysaccharide-mediated inflammatory injury by activating the PI3K/AKT/β-catenin pathway via targeting PTEN.

Int J Biol Sci 2021 25;17(5):1289-1301. Epub 2021 Mar 25.

College of Veterinary Medicine, Yunnan Agricultural University, Kunming 650201, Yunnan, People's Republic of China.

Endometritis is a reproductive disorder characterized by an inflammatory response in the endometrium, which causes significant economic losses to the dairy farming industry. MicroRNAs (miRNAs) are implicated in the inflammatory response and immune regulation following infection by pathogenic bacteria. Recent miRNA microarray analysis showed an altered expression of miR-92b in cows with endometritis. In the present study, we set out to investigate the regulatory mechanism of miR-92b in endometritis. Here, qPCR results first validated that miR-92b was down-regulated during endometritis. And then, bovine endometrial epithelial cells (BEND cells) stimulated by high concentration of lipopolysaccharide (LPS) were employed as an inflammatory injury model. Our data showed that overexpression of miR-92b significantly suppressed the activation of Toll-like receptor 4 (TLR4) and nuclear factor-κB (NF-κB) in LPS-stimulated BEND cells, thereby reducing pro-inflammatory cytokines release and inhibiting cell apoptosis. Looking into the molecular mechanisms of regulation of inflammatory injury by miR-92b, we observed that overexpression of miR-92b restrained TLR4/NF-κB by activating the phosphatidylinositol 3-kinase/protein kinase B (PI3K/AKT)/β-catenin pathway. Furthermore, the luciferase reporter assay suggested that miR-92b targeted inhibition of phosphatase and tensin homolog (PTEN), an inhibitor of the PI3K/AKT/β-catenin pathway. Importantly, experiments confirmed that up-regulation of miR-92b attenuated the pathological injury in an experimental murine model of LPS-induced endometritis. Collectively, these findings show that enforced expression of miR-92b alleviates LPS-induced inflammatory injury by activating the PI3K/AKT/β-catenin pathway via targeting PTEN, suggesting a potential application for miR-92b-based therapy to treat endometritis or other inflammatory diseases.
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http://dx.doi.org/10.7150/ijbs.56933DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8040465PMC
March 2021

IFN-τ Attenuates LPS-Induced Endometritis by Restraining HMGB1/NF-κB Activation in bEECs.

Inflammation 2021 Aug 18;44(4):1478-1489. Epub 2021 Feb 18.

Department of Clinical Veterinary Medicine, College of Veterinary Medicine, Huazhong Agricultural University, Wuhan, 430070, People's Republic of China.

Endometritis is a common inflammatory disease in uterine tissues that leads to animal infertility. Among the causes, Escherichia coli infection is one of the main reasons. Interferon-tau (IFN-τ) is the initial pregnancy signal for ruminant embryos and can induce immune tolerance in humans and other species. However, there are scarce reports on whether IFN-τ has a regulatory effect on endometrial inflammatory damage through HMGB1-NF-κB signalling. The purpose of this study was to investigate the regulatory mechanism of IFN-τ in HMGB1-NF-κB signalling in LPS-induced endometritis. ELISA and qPCR were used to detect the expression of LPS-induced pro-inflammatory cytokines in bovine endometrial epithelial cells (bEECs or BEND) under IFN-τ intervention, and the levels of HMGB1, p-IKK and p-p65 were detected by Western blotting. The nuclear translocation of NF-κB p65 was determined through immunofluorescence. In addition, bEECs were transfected with si-HMGB1 to elucidate the key role of HMGB1 and IFN-τ in the endometrial inflammatory cascade. The results indicated that IFN-τ inhibits the expression of related pro-inflammatory cytokines in an inflammatory injury model of bovine endometrial epithelial cells induced by LPS. Furthermore, experiments have proven that IFN-τ has protective effects on E. coli endotoxin-induced endometritis in mice in vivo. IFN-τ inhibited the HMGB1-NF-κB axis and significantly reduced the secretion of pro-inflammatory cytokines, the expression of HMGB1 protein and the levels of IKK and NF-κB p65 phosphorylation. In summary, our results showed that IFN-τ resists E. coli endotoxin-induced endometritis by attenuating HMGB1/NF-κB signalling.
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http://dx.doi.org/10.1007/s10753-021-01433-yDOI Listing
August 2021

Correction to: Methylseleninic Acid Suppresses Breast Cancer Growth via the JAK2/STAT3 Pathway.

Reprod Sci 2021 Feb;28(2):614

Department of Clinical Veterinary Medicine, College of Veterinary Medicine, Huazhong Agricultural University, Wuhan, 430070, People's Republic of China.

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http://dx.doi.org/10.1007/s43032-020-00353-wDOI Listing
February 2021

MiR-505 as an anti-inflammatory regulator suppresses HMGB1/NF-κB pathway in lipopolysaccharide-mediated endometritis by targeting HMGB1.

Int Immunopharmacol 2020 Nov 20;88:106912. Epub 2020 Aug 20.

Department of Clinical Veterinary Medicine, College of Veterinary Medicine, Huazhong Agricultural University, Wuhan 430070, People's Republic of China. Electronic address:

Endometritis is characterized by severe inflammation and tissue damage. It is a common clinical disease that causes infertility due to infectious diseases of the reproductive system. MicroRNAs (miRNAs) are the current focus of research on the regulation of the inflammatory process and play a vital role in various inflammatory diseases. The highly conserved miR-505 regulates the mechanism of lipopolysaccharide (LPS) induced endometritis, but the extent to which pro-inflammatory genes are activated remains unclear. The results of this study showed that the expression of miR-505 was significantly down-regulated in mouse endometritis tissue and LPS-stimulated BEND cells. The study also showed that overexpression of miR-505 significantly suppressed the production of the pro-inflammatory cytokines IL-1β, IL-6 and TNF-α, and this effect was reversed by inhibiting the expression of miR-505. Moreover, miR-505 inhibited the expression of HMGB1 by targeting its 3'-UTR, thereby inhibiting the activation of HMGB1/NF-κB signalling. Taken together, the results of this study further confirmed that miR-505, as an anti-inflammatory agent, regulates the activation of the HMGB1/NF-κB signalling pathway through negative feedback.
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http://dx.doi.org/10.1016/j.intimp.2020.106912DOI Listing
November 2020

6-Gingerol exerts anti-inflammatory effects and protective properties on LTA-induced mastitis.

Phytomedicine 2020 May 26;76:153248. Epub 2020 May 26.

Department of Clinical Veterinary Medicine, College of Veterinary Medicine, Huazhong Agricultural University, Wuhan 430070, People's Republic of China. Electronic address:

Background: Mastitis has a severe impact on human health and breastfeeding. Gram-positive bacteria are one of the most common pathogens, of which lipoteichoic acid (LTA) serves as the main pathogenic factor. Bio-active extractions from herbs is regarded as an alternative method to antibiotics. 6-Gingerol is used for the treatment of tumors and inhibition of inflammation in liver and gallbladder.

Purpose: To determine whether 6-gingerol can be used as a therapeutic medicine for mastitis.

Results: In this article, we used mice as the animal model and RAW264.7/PMECs as cell models. Western blot was for detecting the expression of proteins in NF-κB/MAPK signaling pathways and MMPs/TIMPs. MPO was for the detection of the amount of immune cells. H&E, immunohistochemistry and immunofluorescence were used for locating and detecting the expression of proteins. The detection of inflammatory cytokines was conducted by ELISA and RT-qPCR. We found that the NF-κB/MAPK signaling pathways, formation of ECM, production of inflammatory cytokines and injury to mammary gland cells were attenuated both in vivo and in vitro when 6-gingerol was administered.

Conclusion: We discovered the function and efficacy of 6-gingerol as a therapeutic compound in LTA-induced mastitis and its probable mechanism of action.
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http://dx.doi.org/10.1016/j.phymed.2020.153248DOI Listing
May 2020

Ginsenoside Rb 1: A novel therapeutic agent in Staphylococcusaureus-induced Acute Lung Injury with special reference to Oxidative stress and Apoptosis.

Microb Pathog 2020 Jun 12;143:104109. Epub 2020 Mar 12.

Department of Clinical Veterinary Medicine, College of Veterinary Medicine, Huazhong Agricultural University, Wuhan, 430070, People's Republic of China. Electronic address:

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.
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http://dx.doi.org/10.1016/j.micpath.2020.104109DOI Listing
June 2020

MicroRNA-182 supplies negative feedback regulation to ameliorate lipopolysaccharide-induced ALI in mice by targeting TLR4.

J Cell Physiol 2020 09 31;235(9):5925-5937. Epub 2020 Jan 31.

Department of Clinical Veterinary Medicine, College of Veterinary Medicine, Huazhong Agricultural University, Wuhan, People's Republic of China.

Acute lung injury (ALI), characterized by increased excessive pulmonary inflammation, is a pervasive inflammatory disease with clinically high incidence. MicroRNA (miRNAs) have been associated with the progression of multiple diseases and are regarded as novel regulators of inflammation. However, it remains largely unknown whether the miRNAs-mediated regulatory mechanism has an effect on lipopolysaccharide (LPS)-induced inflammation in ALI. We discovered that miR-182 distinctly lessened expression in the lung tissue of mice with ALI and macrophages stimulated by LPS. We also found that overexpression of miR-182 significantly cut down the secretion of inflammatory cytokines, while this change was reversed by inhibition of miR-182. In addition, miR-182 suppressed the activation of NF-κB by targeting TLR4 expression. And it was confirmed that miR-182 directly regulated TLR4 expression at the posttranscriptional level by binding to the 3'-UTR of TLR4. Together, these data suggested that inhibition of TLR4 expression assuaged LPS-stimulated inflammation through negative feedback regulation of miR-182.
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http://dx.doi.org/10.1002/jcp.29504DOI Listing
September 2020

miR-148a suppresses inflammation in lipopolysaccharide-induced endometritis.

J Cell Mol Med 2020 01 22;24(1):405-417. Epub 2019 Nov 22.

Department of Clinical Veterinary Medicine, College of Veterinary Medicine, Huazhong Agricultural University, Wuhan, China.

Endometritis is a postnatal reproductive disorder disease, which leads to great economic losses for the modern dairy industry. Emerging evidence indicates that microRNAs (miRNAs) play a pivotal role in a variety of diseases and have been identified as critical regulators of the innate immune response. Recent miRNome profile analysis revealed an altered expression level of miR-148a in cows with endometritis. Therefore, the present study aims to investigate the regulatory role of miR-148a in the innate immune response involved in endometritis and estimate its potential therapeutic value. Here, we found that miR-148a expression in lipopolysaccharide (LPS)-stimulated endometrial epithelial cells was significantly decreased. Our results also showed that overexpression of miR-148a using agomiR markedly reduced the production of pro-inflammatory cytokines, such as IL-1β and TNF-α. Moreover, overexpression of miR-148a also suppressed NF-κB p65 activation by targeting the TLR4-mediated pathway. Subsequently, we further verified that miR-148a repressed TLR4 expression by binding to the 3'-UTR of TLR4 mRNA. Additionally, an experimental mouse endometritis model was employed to evaluate the therapeutic value of miR-148a. In vivo studies suggested that up-regulation of miR-148a alleviated the inflammatory conditions in the uterus as evidenced by H&E staining, qPCR and Western blot assays, while inhibition of miR-148a had inverse effects. Collectively, pharmacologic stabilization of miR-148a represents a novel therapy for endometritis and other inflammation-related diseases.
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http://dx.doi.org/10.1111/jcmm.14744DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6933404PMC
January 2020

miR-488 mediates negative regulation of the AKT/NF-κB pathway by targeting Rac1 in LPS-induced inflammation.

J Cell Physiol 2020 05 31;235(5):4766-4777. Epub 2019 Oct 31.

Department of Clinical Veterinary Medicine, College of Veterinary Medicine, Huazhong Agricultural University, Wuhan, China.

Endometritis is an inflammatory change in the structure of the endometrium due to various causes and is a common cause of infertility. Studies have confirmed that microRNAs (miRNAs) play a key regulatory role in various inflammatory diseases. However, the miRNA-mediated mechanism of endometrial inflammation induced by lipopolysaccharides (LPS) remains unclear. In this study, real-time quantitative polymerase chain reaction, Western blot analysis, immunofluorescence and Rac family small GTPase 1 (Rac1) interference were used to reveal the overexpression of miR-488 in the LPS-induced bovine uterus, and the effect of protein kinase B κ-light chain enhancement of the nuclear factor-activated B cells (AKT/NF-κB) pathway in intimal epithelial cells. The results showed that the expression of inflammatory cytokines such as interleukin-1β (IL-1β), IL-6, and tumor necrosis factor-α in the experimental group was significantly lower than that in the control group when miR-488 was overexpressed. Similar results were observed in the expression levels of p-AKT, p-IKK, and p-p65 proteins. In addition, the dual-luciferase reporter system confirmed that miRNA-488 may directly target the 3'-untranslated region of Rac1. In turn, the expression of Rac1 was inhibited. Moreover, the nuclear translocation of NF-κB was inhibited, and meanwhile, the accumulation of reactive oxygen species (ROS) in the cells was reduced. Thus, we provide basic data for the negative regulation of miR-488 in LPS-induced inflammation by inhibiting ROS production and the AKT/NF-kB pathway in intimal epithelial cells.
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http://dx.doi.org/10.1002/jcp.29354DOI Listing
May 2020

MicroRNA-106a Provides Negative Feedback Regulation in Lipopolysaccharide-Induced Inflammation by targeting TLR4.

Int J Biol Sci 2019 22;15(11):2308-2319. Epub 2019 Aug 22.

Department of Clinical Veterinary Medicine, College of Veterinary Medicine, Huazhong Agricultural University, Wuhan 430070, People's Republic of China. College of Veterinary Medicine, Huazhong Agricultural University, Wuhan, 430070, People's Republic of China.

Acute lung injury (ALI) is a common clinical disease with high incidence and mortality rate, which is characterized by severe inflammatory response and tissues damage. MicroRNAs (miRNAs) have been regarded as novel regulators of inflammation, and play an important role in various inflammatory diseases. However, it remains unknown whether the regulatory mechanisms mediated by miR-106a is involved in LPS-induced ALI. In this study, we found that expression of miR-106a was significantly decreased in lung tissues of ALI mice and LPS-stimulated macrophages. We also revealed that over-expression of miR-106a significantly decreased the production of pro-inflammatory cytokines, including IL-1β, IL-6 and TNF-α, whereas this effect was reversed by the inhibition of miR-106a. Moreover, miR-106a inhibits NF-κB activation by targeting TLR4 expression. We further demonstrated that miR-106a inhibited TLR4 expression via binding directly to the 3'-UTR of TLR4. Taken together, the results of the present study illuminated that miR-106a is a negative feedback regulator in LPS-stimulated inflammation through TLR4/NF-κB signaling pathway.
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http://dx.doi.org/10.7150/ijbs.33432DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6775322PMC
May 2020

MicroRNA-188-5p promotes apoptosis and inhibits cell proliferation of breast cancer cells via the MAPK signaling pathway by targeting Rap2c.

J Cell Physiol 2020 03 20;235(3):2389-2402. Epub 2019 Sep 20.

Department of Clinical Veterinary Medicine, College of Veterinary Medicine, Huazhong Agricultural University, Wuhan, China.

Breast cancer is a common malignancy that is highly lethal with poor survival rates and immature therapeutics that urgently needs more effective and efficient therapies. MicroRNAs are intrinsically involved in different cancer remedies, but their mechanism in breast cancer has not been elucidated for prospective treatment. The function and mechanism of microRNA-188-5p (miR-188) have not been thoroughly investigated in breast cancer. In our study, we found that the expression of miR-188 in breast cancer tissues was obviously reduced. Our findings also revealed the abnormal overexpression of miR-188 in 4T1 and MCF-7 cells significantly suppressed cell proliferation and migration and also enhanced apoptosis. miR-188 induced cell cycle arrest in the G1 phase. To illuminate the molecular mechanism of miR-188, Rap2c was screened as a single target gene by bioinformatics database analysis and was further confirmed by dual-luciferase assay. Moreover, Rap2c was found to be a vital molecular switch for the mitogen-activated protein kinase signaling pathway in tumor progression by decreasing apoptosis and promoting proliferation and migration. In conclusion, our results revealed that miR-188 is a cancer progression suppressor and a promising future target for breast cancer therapy.
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http://dx.doi.org/10.1002/jcp.29144DOI Listing
March 2020

Peripheral Circulating Exosome-Mediated Delivery of miR-155 as a Novel Mechanism for Acute Lung Inflammation.

Mol Ther 2019 10 15;27(10):1758-1771. Epub 2019 Jul 15.

Department of Clinical Veterinary Medicine, College of Veterinary Medicine, Huazhong Agricultural University, Wuhan 430070, People's Republic of China. Electronic address:

Emerging evidence has revealed that excessive activation of macrophages may result in an adverse lung inflammation involved in sepsis-related acute lung injury (ALI). However, it has never been clearly identified whether peripheral circulating serum exosomes participate in the pathogenesis of sepsis-related ALI. Therefore, the purposes of our study were to investigate the effect of serum exosomes on macrophage activation and elucidate a novel mechanism underlying sepsis-related ALI. Here we found that exosomes were abundant in the peripheral blood from ALI mice and selectively loaded microRNAs (miRNAs), such as miR-155. In vivo experiments revealed that intravenous injection of serum exosomes harvested from ALI mice, but not control mice, increased the number of M1 macrophages in the lung, and it caused lung inflammation in naive mice. In vitro, we demonstrated that serum exosomes from ALI mice delivered miR-155 to macrophages, stimulated nuclear factor κB (NF-κB) activation, and induced the production of tumor necrosis factor alpha (TNF-α) and interleukin (IL)-6. Furthermore, we also showed that serum exosome-derived miR-155 promoted macrophage proliferation and inflammation by targeting SHIP1 and SOCS1, respectively. Collectively, our data suggest the important role of circulating exosomes secreted into peripheral blood as a key mediator of septic lung injury via exosome-shuttling miR-155.
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http://dx.doi.org/10.1016/j.ymthe.2019.07.003DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6822235PMC
October 2019

Glycitin alleviates lipopolysaccharide-induced acute lung injury via inhibiting NF-κB and MAPKs pathway activation in mice.

Int Immunopharmacol 2019 Oct 12;75:105749. Epub 2019 Jul 12.

Department of Clinical Veterinary Medicine, College of Veterinary Medicine, Huazhong Agricultural University, Wuhan 430070, People's Republic of China. Electronic address:

Acute lung injury (ALI) is a pulmonary diffuse dysfunction disease caused by immoderate inflammatory response breaking the coordination of physiological structures and functions, and there are very few effective treatments to reduce high morbidity of ALI in critical patients. Glycitin is a natural ingredient derived from the seeds of leguminous plants and may have potent anti-inflammation features. The purpose of this study was to investigate the anti-inflammation effect of glycitin on LPS-induced ALI in mice and elucidate its possible anti-inflammatory mechanisms. The results of histopathological changes, the wet/dry weight ratio as well as the myeloperoxidase (MPO) activity indicated that glycitin obviously alleviated the lung injury induced by LPS. In addition, qPCR and ELISA results found that glycitin could dose-dependently decrease the expressions of pro-inflammatory cytokines IL-1β, IL-6, and TNF-α. Western blotting was performed to revealed that glycitin inhibited the activation of NF-κB and MAPKs signaling pathways by suppressing the expression of TLR4 protein and the phosphorylation of IKKβ, IκBα, p65, p38, ERK, and JNK. All data indicated that glycitin could protect lung tissues from LPS-induced inflammation via inhibiting TLR4-mediated NF-κB and MAPKs signaling pathways.
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http://dx.doi.org/10.1016/j.intimp.2019.105749DOI Listing
October 2019

miR-497a-5p attenuates lipopolysaccharide-induced inflammatory injury by targeting IRAK2.

J Cell Physiol 2019 12 30;234(12):22874-22883. Epub 2019 May 30.

Department of Clinical Veterinary Medicine, College of Veterinary Medicine, Huazhong Agricultural University, Wuhan, People's Republic of China.

Acute lung injury (ALI) is a severe acute inflammatory reaction of the lungs caused by a variety of factors, which can lead to a high mortality rate. MicroRNAs are a novel therapeutic molecule that play a vital role in many diseases. However, its mechanism of action in lipopolysaccharide (LPS)-induced mouse ALI is not clear. The study aimed to investigate the mechanism of action of miR-497 in LPS-induced ALI. As a result, it was found that the expression of miR-497 in the inflammatory reaction showed a decrease in time and dose trends. Importantly, miR-497 reduced LPS-induced expression levels of related inflammatory factors. In addition, we also demonstrated that IRAK2 is a direct target molecule of miR-497. Interestingly, we further found that miR-497 inhibits the expression of IRAK2 by targeting IRAK2-3'UTR. Therefore, miR-497 can partially negatively regulate the activation of IRAK2-NF-κB pathway in LPS-induced inflammatory responses.
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http://dx.doi.org/10.1002/jcp.28850DOI Listing
December 2019

Ginsenoside Rb1 ameliorates Staphylococcus aureus-induced Acute Lung Injury through attenuating NF-κB and MAPK activation.

Microb Pathog 2019 Jul 4;132:302-312. Epub 2019 May 4.

Department of Clinical Veterinary Medicine, College of Veterinary Medicine, Huazhong Agricultural University, Wuhan, 430070, People's Republic of China. Electronic address:

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.
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http://dx.doi.org/10.1016/j.micpath.2019.05.003DOI Listing
July 2019

Targeting the ROS/PI3K/AKT/HIF-1α/HK2 axis of breast cancer cells: Combined administration of Polydatin and 2-Deoxy-d-glucose.

J Cell Mol Med 2019 05 28;23(5):3711-3723. Epub 2019 Mar 28.

Department of Clinical Veterinary Medicine, College of Veterinary Medicine, Huazhong Agricultural University, Wuhan, People's Republic of China.

It is well established that cancer cells depend upon aerobic glycolysis to provide the energy they need to survive and proliferate. However, anti-glycolytic agents have yielded few positive results in human patients, in part due to dose-limiting side effects. Here, we discovered the unexpected anti-cancer efficacy of Polydatin (PD) combined with 2-deoxy-D-glucose (2-DG), which is a compound that inhibits glycolysis. We demonstrated in two breast cell lines (MCF-7 and 4T1) that combination treatment with PD and 2-DG induced cell apoptosis and inhibited cell proliferation, migration and invasion. Furthermore, we determined the mechanism of PD in synergy with 2-DG, which decreased the intracellular reactive oxygen (ROS) levels and suppressed the PI3K/AKT pathway. In addition, the combined treatment inhibited the glycolytic phenotype through reducing the expression of HK2. HK2 deletion in breast cancer cells thus improved the anti-cancer activity of 2-DG. The combination treatment also resulted in significant tumour regression in the absence of significant morphologic changes in the heart, liver or kidney in vivo. In summary, our study demonstrates that PD synergised with 2-DG to enhance its anti-cancer efficacy by inhibiting the ROS/PI3K/AKT/HIF-1α/HK2 signalling axis, providing a potential anti-cancer strategy.
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http://dx.doi.org/10.1111/jcmm.14276DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6484306PMC
May 2019

MiRNA profiling of plasma-derived exosomes from dairy cows during gestation.

Theriogenology 2019 May 7;130:89-98. Epub 2019 Mar 7.

Department of Clinical Veterinary Medicine, College of Veterinary Medicine, Huazhong Agricultural University, Wuhan, 430070, People's Republic of China. Electronic address:

Exosomes, one kind of extracellular vesicles, are released under abnormal and normal physiological conditions. An understanding of plasma-derived exosomal microRNA (miRNA) profiles during pregnancy will significantly contribute to knowledge of maternal-fetal communication in ruminants. In this study, we isolated plasma-derived exosomes from dairy cows during early (∼60 days, gestational day (G_D) 60), mid (∼150 days, G_D 150) and late (∼240 days, G_D 240) pregnancy. Exosomal miRNA profiles were revealed using RNA sequencing technology, and the abundance of exosomal miRNAs between each stage were compared. In the G_D150 vs. G_D60, G_D240 vs. G_D60 and G_D240 vs. G_D150stages, there were 23, 32 and 29 miRNAs, respectively, significantly differentially enriched. Significant annotations for protein binding and transport- or immunoregulatory-related categories or pathways were found for the predicted target genes of these miRNAs. In addition, we further identified specific exosomal miRNAs for each pregnancy stage, including the following: bta-miR-499, bta-miR-16a, bta-miR-20a, bta-miR-223, and bta-miR-128 in the G_D60 stage; bta-miR-493, bta-miR-127, and bta-miR-143 in the G_D150 stage; and bta-miR-122, bta-miR-182, bta-miR-183, bta-miR-200b, and bta-miR-200c in the G_D240 stage. Our findings provide new insight into maternal-fetal communication during pregnancy. Future studies will use these data to identify and characterize specific exosomal miRNA regulatory mechanisms in the maternal-fetal immune response.
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http://dx.doi.org/10.1016/j.theriogenology.2019.03.001DOI Listing
May 2019

Matrine alleviates Staphylococcus aureus lipoteichoic acid-induced endometritis via suppression of TLR2-mediated NF-κB activation.

Int Immunopharmacol 2019 May 26;70:201-207. Epub 2019 Feb 26.

Department of Clinical Veterinary Medicine, College of Veterinary Medicine, Huazhong Agricultural University, Wuhan 430070, People's Republic of China. Electronic address:

Endometritis is one of the main diseases that causes great economic losses in the dairy industry. Recent studies have shown that matrine extracted from the traditional Chinese herb Sophora flavescens is an alkaloid with a broad range of bioactivities. Here, we aimed to investigate the protective effects of matrine on Staphylococcus aureus lipoteichoic acid (LTA)-induced endometritis in mice and elucidate the possible molecular mechanisms in vitro. Histopathological changes showed that matrine remarkably attenuated the uterus injury in a mouse model of LTA-induced endometritis. qPCR and ELISA results showed that matrine dose-dependently reduced the expression of pro-inflammatory cytokines (TNF-α and IL-1β). To further elucidate the underlying mechanisms of this protective effect of matrine, LTA-stimulated bovine endometrial epithelial cells (bEECs) were employed in this study. The results demonstrated that TLR2 expression and its downstream nuclear factor (NF)-κB activation were both suppressed by matrine treatment. Furthermore, a small interference RNA targeting TLR2 gene mimicked matrine in its inhibition on LTA-induced activation of TLR2 and NF-κB. In conclusion, these findings suggest the protective effect of matrine against LTA-induced endometritis through negative regulation of TLR2-mediated NF-κB pathway.
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http://dx.doi.org/10.1016/j.intimp.2019.02.033DOI Listing
May 2019

MiR-128 mediates negative regulation in Staphylococcus aureus induced inflammation by targeting MyD88.

Int Immunopharmacol 2019 May 22;70:135-146. Epub 2019 Feb 22.

Department of Clinical Veterinary Medicine, College of Veterinary Medicine, Huazhong Agricultural University, Wuhan, China. Electronic address:

Acute lung injury (ALI) is a common clinical syndrome of excessive uncontrolled inflammatory response in lung tissues with high mortality rates and limited therapeutic approaches. MicroRNAs (miRNAs) are a class of small non-coding RNAs which attach at 3'UTR of mRNA for further regulation of diverse proteins. MiRNAs are a current focus in regulating the inflammatory processes. The extent of pro-inflammatory gene activated against Staphylococcus aureus (S. aureus) is still unclear. Myeloid differentiation primary response 88 (MyD88) is involved in gram positive bacteria-induced lung inflammation by Toll-like receptors (TLRs). Then MyD88 activates NF-κB through IRAKs which are in charge of inflammation. Target prediction analyses revealed MyD88, a result of projections from multiple bio-websites, to be a putative target of miR-128. Here we probe the expression of the MyD88 and miRNA in mode of inflammation. We found up-regulated expression of MyD88 and down-regulation of miR-128 after S. aureus infection in mouse lung tissues and RAW264.7 cells via qPCR and western blotting (WB) analysis. Moreover, MyD88-miR-128 interaction was validated by luciferase assays. Then, we proved that miR-128 expression caused a reduction in IκBα and p65 phosphorylation and resulted in significant reduction in secretion of inflammatory cytokines, being consistent with the deletion of MyD88 in macrophages. It revealed that miR-128 specifically blocked the further development of inflammation through MyD88 down-regulation. Finally, we demonstrated a novel role of miR-128 that it mediates negative regulation in S. aureus induced inflammation by targeting MyD88.
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http://dx.doi.org/10.1016/j.intimp.2018.11.024DOI Listing
May 2019

Sodium houttuyfonate inhibits LPS‑induced mastitis in mice via the NF‑κB signalling pathway.

Mol Med Rep 2019 Mar 10;19(3):2279-2286. Epub 2019 Jan 10.

Department of Clinical Veterinary Medicine, College of Veterinary Medicine, Huazhong Agricultural University, Wuhan, Hubei 430070, P.R. China.

Sodium houttuyfonate (SH) has been indicated to play an important anti‑inflammatory role. Previous studies have confirmed that SH can inhibit the NF‑κB pathway in lipopolysaccharide (LPS)‑induced mastitis in bovine mammary epithelial cells. However, the effects of SH on LPS‑induced mastitis in animals should be verified to further evaluate its actual value. In the present study, the anti‑inflammatory effects of SH were investigated in mouse models and a mouse mammary epithelial cell line. Hematoxylin and eosin staining (H&E) showed that SH therapy significantly alleviated the pathological changes in mammary glands. Myeloperoxidase (MPO) activity analysis demonstrated that SH substantially decreased MPO activity in vivo. RT‑qPCR results showed that SH reduced the expression of interleukin (IL)‑1, IL‑6 and tumor necrosis factor α both in vivo and in vitro. In addition, western blot results indicated that SH suppressed the phosphorylation of nuclear factor kappa‑light‑chain‑enhancer of activated B‑cells (NF‑κB) p65 protein and reduced the degradation of inhibitor of kappa light polypeptide gene enhancer in B‑cells alpha protein in vivo and in vitro. These results demonstrated that SH ameliorates LPS‑induced mastitis by inhibiting the NF‑κB pathway.
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http://dx.doi.org/10.3892/mmr.2019.9846DOI Listing
March 2019

Methylseleninic Acid Suppresses Breast Cancer Growth via the JAK2/STAT3 Pathway.

Reprod Sci 2019 06 9;26(6):829-838. Epub 2018 Dec 9.

Department of Clinical Veterinary Medicine, College of Veterinary Medicine, Huazhong Agricultural University, Wuhan, 430070, People's Republic of China.

Previous studies show that methylseleninic acid (MSA), which is the most common selenium derivative used as a drug in humans, exerts specific cytotoxic effects in several cancer cell types. However, the complex mechanism of these effects has not been fully elucidated. Here, we demonstrate by Cell Counting Kit-8 in mouse breast cancer cell line 4T1 that MSA inhibits cell viability in a concentration-dependent (5, 10, 20 μmol/L) and time-dependent (6, 12, 24 hours) manner. Flow cytometry, Western blot, and Reverse Transcription-Polymerase Chain Reaction (RT-PCR) analyses indicated that MSA inhibits cancer cell invasion and induces apoptosis by the activation of caspase-3, poly ADP ribose polymerase 1 (PARP1), and BCL2-associated X. Furthermore, MSA demonstrated anticancer activity by inhibiting the Janus kinase 2/signal transducers and activators of transcription 3 (JAK2/STAT3) pathway. The MSA treatment for 24 hours decreased the phosphorylation of JAK2 and STAT3 in 4T1 cells by Western blot. We also confirmed this with the use of a JAK2 chemical inhibitor, AG490, as a positive control. In a 4T1 orthotopic allograft model, morphological and TdT-mediated dUTP nick-end labeling analyses showed that MSA treatment (1.5 mg/kg/weight) for 28 days inhibits tumor growth consistent with the clinical anticancer drug cyclophosphamide. Our observations demonstrate that MSA is a potent anticancer drug in breast cancer and uncovered a key role of the JAK2/STAT3 pathway in modulating tumor growth.
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http://dx.doi.org/10.1177/1933719118815582DOI Listing
June 2019

MicroRNA let-7c Improves LPS-Induced Outcomes of Endometritis by Suppressing NF-κB Signaling.

Inflammation 2019 Apr;42(2):650-657

Department of Clinical Veterinary Medicine, College of Veterinary Medicine, Huazhong Agricultural University, Wuhan, 430070, People's Republic of China.

Endometritis is a common inflammatory disease which endangers human and animal reproductive health. MicroRNA (miRNA) let-7c plays an important role in the inflammatory process; however, the regulatory underlying mechanism of let-7c in endometritis is unclear. In this study, we confirmed that let-7c was significantly reduced in LPS-induced mouse endometritis model, and overexpression of let-7c was able to effectively reduce uterine tissue damage caused by lipopolysaccharide (LPS), and then, a LPS-induced bovine endometrial epithelial cell (BEND) line was used to mimic the inflammatory model in vitro. Our data showed that overexpression of let-7c significantly reduced the expression of pro-inflammatory cytokines in BEND cells induced by LPS. Meanwhile, immunofluorescence and western blotting results showed that let-7c significantly inhibited LPS-induced phosphorylation of NF-κB, thereby inhibiting downstream pro-inflammatory cytokine expression. Taken together, our results suggested that let-7c ameliorates LPS-induced endometritis by attenuating the expression of pro-inflammatory cytokines via inhibition of the activation of NF-κB.
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http://dx.doi.org/10.1007/s10753-018-0922-4DOI Listing
April 2019

Shikonin exerts anti-inflammatory effects in LPS-induced mastitis by inhibiting NF-κB signaling pathway.

Biochem Biophys Res Commun 2018 10 14;505(1):1-6. Epub 2018 Sep 14.

Department of Clinical Veterinary Medicine, College of Veterinary Medicine, Huazhong Agricultural University, Wuhan, 430070, People's Republic of China. Electronic address:

Previous studies have shown that shikonin(SHI), the bioactive naphthoquinone constituent extracted from Chinese herb Lithospermum Erythrorhizon, possesses the potential to confront inflammation, and has little concerns towards drug residues comparing with antibiotics. While mastitis in dairy industry always trigger great harm to milk yields, effects of SHI on lipopolysaccharides (LPS)-induced mastitis should be measured. Here, we demonstrate anti-inflammatory effects of SHI on LPS-challenged mastitis and elucidate the potential signaling pathway both in vivo and in vitro. As a result, SHI administration mice significantly suffered less impairment of mammary gland and less recruitment of neutrophils than LPS administration mice. SHI significantly suppressed the expression of p-IκBα and p-p65, which are the critical proteins functioning in NF-kB signaling pathway. qPCR results indicate decreasing level of upstream pro-inflammatory cytokines in tissues, such as TNF-α, IL-1β, and IL-6. The results are corresponding with the results in vitro, suggesting the potential usage of SHI as a therapeutic medicine in mastitis.
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http://dx.doi.org/10.1016/j.bbrc.2018.08.198DOI Listing
October 2018

Sodium selenite induces apoptosis via ROS-mediated NF-κB signaling and activation of the Bax-caspase-9-caspase-3 axis in 4T1 cells.

J Cell Physiol 2019 03 14;234(3):2511-2522. Epub 2018 Sep 14.

Department of Clinical Veterinary Medicine, College of Veterinary Medicine, Huazhong Agricultural University, Wuhan, China.

Sodium selenite (SSE), a source of inorganic selenium, has been widely used as a clinical cancer treatment, but the precise molecular mechanisms of SSE remain to be elucidated. Our in vitro experiments have confirmed that SSE treatment causes a transient increase in intracellular reactive oxygen species (ROS) levels, resulting in the inhibition of nuclear transcription factor-κB (NF-κB) signaling and p65 and nuclear factor of kappa light polypeptide gene enhancer in B-cells inhibitor, alpha phosphorylation levels in 4T1 cells. The inhibition of NF-κB subsequently increased the expression of the apoptosis gene B-cell lymphoma-2-associated X (Bax) and downregulated the transcription of antiapoptosis genes, such as B-cell lymphoma-2, cellular inhibitor of apoptosis 1, and X-linked inhibitor of apoptosis. Additionally, the accumulation of ROS caused mitochondrial dysfunction, leading to the activation of caspase-9 and -3, thereby resulting in apoptosis. However, modulation of the ROS level by the chemical inhibitor N-acetyl-cysteine reversed these events. Similarly, in vitro murine syngeneic breast tumor models showed that SSE inhibits tumor growth by promoting apoptosis. These results indicate that SSE induces apoptosis via ROS-mediated inhibition of NF-κB signaling and activation of the Bax-caspase-9-caspase-3 axis.
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http://dx.doi.org/10.1002/jcp.26783DOI Listing
March 2019

Magnoflorine Ameliorates Lipopolysaccharide-Induced Acute Lung Injury via Suppressing NF-κB and MAPK Activation.

Front Pharmacol 2018 30;9:982. Epub 2018 Aug 30.

Department of Clinical Veterinary Medicine, College of Veterinary Medicine, Huazhong Agricultural University, Wuhan, China.

Acute lung injury (ALI) which is featured by a strong pulmonary inflammation, is a major cause of morbidity and mortality in critically ill patients. Magnoflorine, a quaternary alkaloid isolated from Chinese herb Magnolia or Aristolochia, has been reported to have potent anti-inflammatory properties. However, the effect of magnoflorine on lipopolysaccharide (LPS)-induced ALI in mice has not been reported. The purpose of the present study is to investigate the anti-inflammatory effect of magnoflorine on LPS-induced ALI and elucidate its possible molecular mechanisms in RAW264.7 cells. The results of histopathological changes as well as the myeloperoxidase (MPO) activity indicated that magnoflorine significantly alleviated the lung injury induced by LPS. In addition, qPCR results showed that magnoflorine dose-dependently decreased the expression of pro-inflammatory cytokines TNF-α, IL-1β, and IL-6. Immunofluorescence assay also confirmed that the level of Toll-like receptor 4 (TLR4) induced by LPS was inhibited by magnoflorine treatment. Further experiments were performed using Western blotting to detect the expression of related proteins in the NF-κB and MAPK signaling pathways. The results showed that magnoflorine suppressed the levels of phosphorylated p65, IκBα, p38, ERK, and JNK. In conclusion, all data indicate that magnoflorine could protect against LPS-induced inflammation in ALI at least partially by inhibiting TLR4-mediated NF-κB and MAPK signaling pathways.
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http://dx.doi.org/10.3389/fphar.2018.00982DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6125611PMC
August 2018

The Potential Therapeutic Role of miR-223 in Bovine Endometritis by Targeting the NLRP3 Inflammasome.

Front Immunol 2018 22;9:1916. Epub 2018 Aug 22.

Department of Clinical Veterinary Medicine, College of Veterinary Medicine, Huazhong Agricultural University, Wuhan, China.

Bovine endometritis affects milk production and reproductive performance in dairy cows and causes serious economic loss. The underlying molecular mechanisms or signaling pathways of bovine endometritis remain unclear. In this study, we attempted to determine the expression mechanism of mir-223 in endometritis of dairy cows and evaluate its potential therapeutic value. We first confirmed that there was an increased level of miR-223 in endometritis, and then, an LPS-induced bovine endometrial epithelial cell (BEND) line was used to mimic the inflammatory model . Our data showed that activation of NF-κB promoted the transcription of miR-223, thus inhibiting activation of the inflammatory mediator NLRP3 and its mediation of IL-1β production to protect against inflammatory damage. Meanwhile, studies showed that inhibition of mir-223 resulted in an enhanced pathology of mice during LPS-induced endometritis, while overexpression of mir-223 attenuated the inflammatory conditions in the uterus. In summary, our study highlights that miR-223 serves both to constrain the level of NLRP3 activation and to act as a protective factor in the inflammatory response and thus provides a future novel therapeutic modality for active flares in cow endometritis and other inflammatory diseases.
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http://dx.doi.org/10.3389/fimmu.2018.01916DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6113393PMC
September 2019
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