Transcription factor-κB Signaling Research Articles

Preparation of Cod Skin Collagen Peptides/Chitosan-Based Temperature-Sensitive Gel and Its Anti-Photoaging Effect in Skin.

Photoaging decreases quality of life and increases the risk of skin cancer, underscoring the urgent need to explore natural, high-efficacy, anti-skin photoaging (SP) active substances. In this study, a gel (CS/CSCPs/β-GP gel) was prepared using chitosan (CS) and sodium β-glycerophosphate (β-GP) through crosslinking with small molecular CSCPs as the carried drug. We evaluated its structural characteristics and properties. The effect of CS/CSCPs/β-GP gel on the degree of ultraviolet (UV)-induced skin aging of mice was investigated through comparative analysis of skin damage, the integrity of collagen tissues and elastic fibers, levels of reactive oxygen species (ROS) and key inflammatory factors (tumor necrosis factor [TNF]-α and interleukin [IL]-1β, IL-6, and IL-10), and tissue expression of matrix metalloproteinase-3 (MMP-3) after repeated UV irradiation in a nude mice SP model. The results showed that CS/CSCPs/β-GP gel was successfully prepared and had the desired characteristics. Compared with CSCPs alone, the CS/CSCPs/β-GP gel more evidently improved typical photoaging characteristics on mouse dorsal skin. It also increased the moisture content, causing the skin to become glossy and elastic. Pathological skin analysis revealed that this peptide-carrying gel can effectively inhibit epidermal thickening, reduce tissue inflammatory infiltration, suppress collagen fiber degradation, increase the collagen content, alleviate structural elastic fiber damage, and significantly inhibit abnormal MMP-3 expression. In addition, biochemical analysis showed that the CS/CSCPs/β-GP gel can effectively inhibit the elevated expressions of ROS and key proinflammatory factors (TNF-α, IL-1β, IL-6) in photoaging skin tissues and promote expression of the anti-inflammatory factor IL-10. SP can cause many clinical skin diseases, such as solar freckle-like nevus, solar keratosis, cutaneous melanoma, and squamous cell carcinoma. CSCPs are a high-efficacy anti-SP natural active substance and CS/CSCPs/β-GP gel can synergistically enhance the CSCPs' anti-SP effect. The mechanism is likely related to the inhibited activation of ROS/nuclear transcription factor-κB signaling and the expression of downstream inflammatory factors.

Potential of Omega-3 Polyunsaturated Fatty Acids in Managing Chemotherapy- or Radiotherapy-Related Intestinal Microbial Dysbiosis.

Chemotherapy- or radiotherapy-related intestinal microbial dysbiosis is one of the main causes of intestinal mucositis. Cases of bacterial translocation into peripheral blood and subsequent sepsis occur as a result of dysfunction in the intestinal barrier. Evidence from recent studies depicts the characteristics of chemotherapy- or radiotherapy-related intestinal microbial dysbiosis, which creates an imbalance between beneficial and harmful bacteria in the gut. Decreases in beneficial bacteria can lead to a weakening of the resistance of the gut to harmful bacteria, resulting in robust activation of proinflammatory signaling pathways. For example, lipopolysaccharide (LPS)-producing bacteria activate the nuclear transcription factor-κB signaling pathway through binding with Toll-like receptor 4 on stressed epithelial cells, subsequently leading to secretion of proinflammatory cytokines. Nevertheless, various studies have found that the omega-3 (n-3) polyunsaturated fatty acids (PUFAs) such as docosahexaenoic acid and eicosapentaenoic acid can reverse intestinal microbial dysbiosis by increasing beneficial bacteria species, including Lactobacillus, Bifidobacterium, and butyrate-producing bacteria, such as Roseburia and Coprococcus. In addition, the n-3 PUFAs decrease the proportions of LPS-producing and mucolytic bacteria in the gut, and they can reduce inflammation as well as oxidative stress. Importantly, the n-3 PUFAs also exert anticancer effects in colorectal cancers. In this review, we summarize the characteristics of chemotherapy- or radiotherapy-related intestinal microbial dysbiosis and introduce the contributions of dysbiosis to the pathogenesis of intestinal mucositis. Next, we discuss how n-3 PUFAs could alleviate chemotherapy- or radiotherapy-related intestinal microbial dysbiosis. This review provides new insights into the clinical administration of n-3 PUFAs for the management of chemotherapy- or radiotherapy-related intestinal microbial dysbiosis.

Mediated mechanism of NDRG2 in the regulation of neutrophil nuclear transcription factor-κB signaling pathway through the deubiquitylating enzyme of Zc3h12d

To explore the role NDRG2/Zc3h12d in the regulation of neutrophil nuclear transcription factor-κB signaling pathway and the underlying mechanisms. Sixteen HBE cells were incubated with lipopolysaccharide (LPS) to establish airway mucus hypersecretion model, which was transfected with NDRG2 or Zc3h12d siRNA. The cells were divided into 5 groups: a LPS+NDRG2 siRNA (Group A), a LPS+ NDRG2 and Zc3h12d siRNAs (Group B), a LPS+Zc3h12d siRNA (Group C), a LPS+ empty plasmid (Group D), and a negative control group (Group E). The reverse transcription-polymerase chain reaction (RT-PCR) was used to measure the expression level of mucin (MUC) 5AC mRNA. The levels of MUC5AC and the inflammatory factors were examined by the enzyme-linked immunosorbent assay (ELISA). The NF-κB p65 and the Zc3h12d protein levels were measured by Western blot. The MUC5C expression was further examined by laser confocal method. Compared with Group B, the levels of MUC5AC mRNA and protein in Group A were decreased (P<0.05), there was no significant difference in the MUC5AC mRNA and MUC5AC protein levels between the Group B and the Group C (P>0.05). Compared with Group D, the MUC5AC (mRNA and protein) and inflammatory factor levels in the Group A were significantly decreased (P<0.05); compared with Group E, after incubation with LPS, the levels of MUC5AC (mRNA and protein) and inflammatory factors in the Group D was increased, with significantly difference (P<0.05). NDRG2 can regulate the function of NF-κB signaling pathway through the deubiquitylating enzyme of Zc3h12d.

Vascular protective potential of the total flavanol glycosides from Abacopteris penangiana via modulating nuclear transcription factor-κB signaling pathway and oxidative stress

"Sanxuelian", the rhizome of Abacopteris penangiana (AP), is traditionally used in Chinese medicine for the treatment of blood circulation stasis, hemorheology barriers, edema and inflammation for patients of metabolic syndrome. This study was to investigate the protective effect of the total flavanol glycosides from AP (FAP) on diabetic vascular impairments by measuring the extents of oxidative stress and inflammatory response in mice. The experimental aortic pathology in diabetic mice was induced by fed on high-fat diet and injected with streptozotocin. The activities of FAP on attenuating aortas injuries, hypoglycemic, hypolipidemic, inhibiting oxidative stress and anti-inflammation were investigated. Additionally, the aortic expressions of nuclear transcription factor-κB (NFκB) were determined by western blot and immunohistochemistry analysis. Furthermore, the effects of FAP on human umbilical vein endothelia cells (HUVECs) were studied. In animal study, the results showed that FAP enhanced the activities of antioxidant enzymes and attenuated the levels of proinflammatory cytokines. The plasma lipid profiles and glucose level in FAP treated groups were significantly decreased along with the vascular impairments were alleviated. Moreover, the aortic expression of NFκB was decreased. In cellular experiment, FAP could inhibit the apoptosis of HUVECs induced by H(2)O(2). The results indicated that FAP had hypolipidemic, hypoglycemic and vascular protective activities and represented a potential herb for the treatment of aortic pathology involved with metabolic syndrome.

Fish-oil supplementation induces antiinflammatory gene expression profiles in human blood mononuclear cells

Background:Polyunsaturated fatty acids can have beneficial effects on human immune cells, such as peripheral blood mononuclear cells (PBMCs). However, the mechanisms of action of polyunsaturated fatty acids on immune cells are still largely unknown. Objective:The objective was to examine the effects of supplementation with the polyunsaturated fatty acids eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) on whole-genome PBMC gene expression profiles, in healthy Dutch elderly subjects participating in a double-blind trial, by using whole-genome transcriptomics analysis. Design:The subjects were randomly allocated to 1 of 3 groups:1) consumption of 1.8 g EPA+DHA/d (n = 36),2) consumption of 0.4 g EPA+DHA/d (n = 37), or3) consumption of 4.0 g high–oleic acid sunflower oil (HOSF)/d (n = 38). All supplements were given in capsules. Before and after 26 wk of intervention, blood samples were collected. Microarray analysis was performed on PBMC RNA from 23 subjects who received 1.8 g EPA+DHA/d and 25 subjects who received HOSF capsules. Quantitative real-time polymerase chain reaction was performed in all 111 subjects. Results:A high EPA+DHA intake changed the expression of 1040 genes, whereas HOSF intake changed the expression of only 298 genes. EPA+DHA intake resulted in a decreased expression of genes involved in inflammatory- and atherogenic-related pathways, such as nuclear transcription factorκB signaling, eicosanoid synthesis, scavenger receptor activity, adipogenesis, and hypoxia signaling. Conclusion:These results are the first to show that intake of EPA+DHA for 26 wk can alter the gene expression profiles of PBMCs to a more antiinflammatory and antiatherogenic status. This trial was registered at clinicaltrials.gov as NCT00124852.