scholarly journals FABP5 enhances malignancies of lower-grade gliomas via canonical activation of NF-κB signaling

2020 ◽  
Author(s):  
Jia Wang ◽  
Wahafu Alafate ◽  
Yichang Wang ◽  
Wei Wu ◽  
Jianyang Xiang ◽  
...  
Keyword(s):  
Nuclear Factor Kappa B ◽  
Epithelial Mesenchymal Transition ◽  
Lower Grade ◽  
Nuclear Factor ◽  
Fatty Acid Binding ◽  
Mesenchymal Transition ◽  
Molecular Stratification ◽  
Nuclear Factor Kappa ◽  
Grade Ii ◽  
Factor Α

Abstract Background Lower-grade gliomas (LGGs) are grade II/III gliomas based on the WHO classification with significant genetic heterogeneity and clinical properties. Traditional histological classification of gliomas has been challenged by the improvement of molecular stratification, however, the reproducibility and diagnostic accuracy of LGGs classification remain poor. Methods In this study, we derived all relevant data of LGGs including TCGA and CGGA databases from official websites. Bioinformatic analyses unveiled the clinical significance of FABP5 and its potential downstream targets. IHC, qRT-PCR and western blot assays were further conducted to validate those bioinformatic findings. Moreover, lentiviral transduction assays were performed to evaluate the function of FABP5 in patient-derived cell lines. Results We identified fatty acid binding protein 5 (FABP5) as one of the most enriched genes in malignant LGGs and elevated FABP5 revealed severe outcomes in LGGs. Functionally, lentiviral suppression of FABP5 reduced malignant characters including proliferation, cloning formation, migration, invasion and TMZ resistance, contrarily, the malignancies of LGGs were enhanced by exogenous overexpression of FABP5. Mechanistically, epithelial-mesenchymal transition (EMT) was correlated to FABP5 expression in LGGs and tumor necrosis factor α (TNFα)-dependent NF-κB signaling was involved in this process. Furthermore, FABP5 induced phosphorylation of inhibitor of nuclear factor kappa-B kinase α (IKKα) thus activated nuclear factor kappa-B (NF-κB) signaling. Conclusion Taken together, our study indicated that FABP5 enhances malignancies of LGGs through canonical activation of NF-κB signaling, which could be used as individualized prognostic biomarker and potential therapeutic target of LGGs.

Caffeic acid abrogates 1,3-dichloro-2-propanol-induced hepatotoxicity by upregulating nuclear erythroid-related factor 2 and downregulating nuclear factor-kappa B

2019 ◽  
Vol 38 (9) ◽  
pp. 1092-1101 ◽  
Author(s):  
TO Ajiboye ◽  
RA Ajala-Lawal ◽  
AB Adeyiga
Keyword(s):  
Caffeic Acid ◽  
Nuclear Factor Kappa B ◽  
Protein Carbonyl ◽  
Related Factor ◽  
Nuclear Factor ◽  
Oxidative Stress Biomarkers ◽  
Acid Pretreatment ◽  
Nuclear Factor Kappa ◽  
Phosphoinositide 3 Kinase ◽  
Factor Α

1,3-dichloro-2-propanol is a food-borne contaminant reported to cause liver injury. In this study, we evaluated the protective influence of caffeic acid on 1,3-dichloro-2-propanol-induced hepatotoxicity in rats. Rats were randomized into five groups (A–E). Rats received distilled water or caffeic acid (10 or 20 mg/kg body weight) for 7 days. In addition, rats were challenged with 1,3-dichloro-2-propanol on day 7. Caffeic acid prevented 1,3-dichloro-2-propanol-mediated alterations in alkaline phosphatase, alanine and aspartate aminotransferases, albumin and total bilirubin in the serum of rats. Furthermore, caffeic acid lowered superoxide ion, hydrogen peroxide and cytochrome P2E1 while increasing the activities of superoxide dismutase, catalase and glutathione S-transferase in the liver of 1,3-dichloro-2-propanol-treated rats. Caffeic acid raised the levels of nuclear erythroid-related factor 2 (Nrf-2), protein kinase A and phosphoinositide 3-kinase. Caffeic acid pretreatment annulled 1,3-dichloro-2-propanol-mediated alterations in the oxidative stress biomarkers; caspase-3, glutathione, malondialdehyde, protein carbonyl and fragmented DNA, in the liver of rats. Contrastingly, caffeic acid lowered 1,3-dichloro-2-propanol-mediated increase in the levels of nuclear factor-kappa B (NF-κB), tumour necrosis factor-α, interleukin-1β (IL-1β) and IL-6. In addition, caffeic acid preserved the morphological features of 1,3-dichloro-2-propanol-treated rats. Results from this study revealed that caffeic acid protects against 1,3-dichloro-2-propanol-induced hepatotoxicity by enhancing the cytoprotective enzymes through Nrf-2 while lowering inflammation through NF-κB.

Immunohaematological status and mRNA expression of the genes encoding interleukin-6, nuclear-factor kappa B, and tumor-necrosis factor-α in the spleen of broilers supplemented with dietary rutin

2019 ◽  
Vol 59 (8) ◽  
pp. 1454 ◽  
Author(s):  
Ashraf Awad ◽  
Asmaa W. Zaglool ◽  
Samah R. Khalil
Keyword(s):  
Interleukin 6 ◽  
Nuclear Factor Kappa B ◽  
Lymphoid Organ ◽  
Feed Additive ◽  
Nuclear Factor ◽  
Nuclear Factor Kappa ◽  
Immune Parameters ◽  
Genes Encoding ◽  
Factor Α ◽  
Necrosis Factor

Rutin, also known as vitamin P or rutoside, has been explored for many pharmacological activities. Apples, tea leaves, and many other plants contain rutin as one of the active constituents. Haematological, immunological indices and the expression of inflammatory cytokine genes in spleen tissue were assessed to investigate the influence of different levels of dietary rutin supplement (0.25, 0.5, or 1 g/kg diet) on the immune response of broilers. After 6 weeks, rutin-fed chickens showed an increase in the haematological indices, including the number of blood lymphocytes. Similarly, serum total protein and globulin were also elevated. By contrast, serum cholesterol, triglycerides and liver enzymes were lower in the experimental birds than in the control birds. Moreover, compared with the control birds, there was no significant change in the bilirubin concentration, either total or direct, and kidney-function indices in response to rutin supplementation in the experimental birds. Among the immune parameters examined, lysozyme activity, nitric oxide concentrations, and immunologlobulin M (IgM) production were significantly higher in rutin-fed birds than in the control birds; however, there was no significant effect of rutin at any concentration on the IgG and IgA concentrations and lymphoid organ weight. Of the cytokine-encoding genes studied, the genes encoding interleukin-6, nuclear-factor kappa B, and tumour-necrosis factor-α were upregulated in the spleen of the experimental birds, while the expression of interferon gamma-encoding gene was unaffected in the experimental birds. Here, rutin promoted the immune strength in birds mainly at 1 g/kg diet, suggesting that rutin is a promising feed additive for broilers.

Reduced inflammatory and phagocytotic responses following normobaric hypoxia exercise despite evidence supporting greater immune challenge

2020 ◽  
Vol 45 (6) ◽  
pp. 628-640
Author(s):  
Garrett W. Hill ◽  
Trevor L. Gillum ◽  
Ben J. Lee ◽  
Phebe A. Romano ◽  
Zach J. Schall ◽  
...  
Keyword(s):  
Nuclear Factor Kappa B ◽  
Treadmill Exercise ◽  
Normobaric Hypoxia ◽  
Repeated Measure ◽  
Intercellular Adhesion Molecule ◽  
Nuclear Factor ◽  
Fatty Acid Binding ◽  
Nuclear Factor Kappa ◽  
Inflammatory Status ◽  
Tnf Α

This study examined changes in immune markers following sustained treadmill exercise in normobaric hypoxia. Ten subjects performed 1 h of treadmill exercise (65% maximal oxygen uptake) under normoxic (NORM: fraction of inspired oxygen (FIO2) = 20.9%) and normobaric hypoxic (HYP: FIO2 = 13.5%) conditions. Blood samples, collected before, after (Post), 1 h after (1-Post), and 4 h after (4-Post) exercise, were assayed for plasma cytokines (interleukin (IL)-1RA/IL-1β/IL-8/tumor necrosis factor alpha (TNF-α)) and markers of leukocyte activation (macrophage inflammatory protein-1β (MIP-1β)/myeloperoxidase (MPO)/soluble intercellular adhesion molecule-1 (sICAM-1)) using ELISA. Pro- to anti-inflammatory cytokine ratios (TNF-α/IL-1RA; IL-1β/IL-1RA) were calculated. Peripheral blood mononuclear cells (PBMC) were analyzed for changes in inflammatory status (phosphorylated nuclear factor kappa B/nuclear factor kappa B) using Western Blot. Data were analyzed with 2-way (condition × time) repeated-measure ANOVAs with Newman–Keuls post hoc tests. MIP-1β was elevated at 1-Post HYP exercise (+11%; p < 0.01) but did not increase following exercise in NORM. TNF-α/IL-1RA and IL-1β/IL-1RA ratios were both reduced (p < 0.05) following HYP exercise (−16% and −52%, respectively, at 1-Post and −7% and −32%, respectively, at 4-Post). IL-8 increased (p < 0.05) at Post and 1-Post NORM (+33% and +57%, respectively) and HYP (+60% and +83%, respectively) exercise, but was not different between conditions (p > 0.05). Interestingly, plasma sICAM-1 did not increase (p > 0.05) following NORM exercise but was increased (p < 0.05) at Post (+17%), 1-Post (+16%), and 4-Post (+14%) HYP exercise. There was also a delayed peak in plasma MPO concentrations following HYP exercise and PBMC exhibited a reduced (p < 0.05) inflammatory capacity at Post (−38%) and 1-Post (−49%). Novelty Following HYP exercise, participants exhibited (i) circulatory bias towards anti-inflammation; (ii) elevated sICAM; (iii) delayed peak in plasma MPO; and (iv) diminished inflammatory response in PBMC. Collectively, these data suggest immunosuppression. This is undesirable, given that elevated MIP-1β (reported here) and elevated intestinal fatty acid binding protein (reported previously) both suggest higher lipopolysaccharide concentrations following HYP exercise.

Baicalin Inhibits Kidney Inflammation in Mice with Diabetic Nephropathy by Modulating Toll-like Receptor 4/Nuclear Factor-Kappa B Signaling Pathway

2020 ◽  
Vol 19 (1) ◽  
pp. 115-119
Author(s):  
Benyong Wang ◽  
Ning Zhao ◽  
Pingyue Ma ◽  
Qunhong Xu ◽  
Qi Chen
Keyword(s):  
Diabetic Nephropathy ◽  
Signaling Pathway ◽  
Nuclear Factor Kappa B ◽  
Kidney Tissue ◽  
Control Group ◽  
Nuclear Factor ◽  
Toll Like Receptor ◽  
Toll Like Receptor 4 ◽  
Nuclear Factor Kappa ◽  
Factor Α

We have explored the effect of baicalin, an anti-inflammatory agent, on the outcome of diabetic nephropathy. To this end, we used 6 weeks old C57BL/6J male diabetic mice exhibiting nephropathy. The treatment with baicalin exhibited significant improvement in the renal function, histopathological changes, and expression of inflammatory markers. Moreover, the expression of interleukin-6, tumor necrosis factor-α, and interleukin-1β in kidney tissue of the mice in baicalin group were significantly downregulated compared to the control group (P ‹ 0.05). The expression of toll-like receptor 4, myeloid differentiation factor 88, and nuclear factor-kappa B proteins in the kidney of baicalin-treated mice were remarkably downregulated compared to the control group. Taken together, we conclude that baicalin may exert its protective effect on kidney by inhibiting inflammation through toll-like receptor 4/nuclear factor-kappa B signaling pathway in mice with diabetic nephropathy.

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