OTUD7A Regulates Inflammation- and Immune-Related Gene Expression in Goose Fatty Liver

OTU deubiquitinase 7A (OTUD7A) can suppress inflammation signaling pathways, but it is unclear whether the gene can inhibit inflammation in goose fatty liver. In order to investigate the functions of OTUD7A and identify the genes and pathways subjected to the regulation of OTUD7A in the formation of goose fatty liver, we conducted transcriptomic analysis of cells, which revealed several genes related to inflammation and immunity that were significantly differentially expressed after OTUD7A overexpression. Moreover, the expression of interferon-induced protein with tetratricopeptide repeats 5 (IFIT5), tumor necrosis factor ligand superfamily member 8 (TNFSF8), sterile alpha motif domain-containing protein 9 (SAMD9), radical S-adenosyl methionine domain-containing protein 2 (RSAD2), interferon-induced GTP-binding protein Mx1 (MX1), and interferon-induced guanylate binding protein 1-like (GBP1) was inhibited by OTUD7A overexpression but induced by OTUD7A knockdown with small interfering RNA in goose hepatocytes. Furthermore, the mRNA expression of IFIT5, TNFSF8, SAMD9, RSAD2, MX1, and GBP1 was downregulated, whereas OTUD7A expression was upregulated in goose fatty liver after 12 days of overfeeding. In contrast, the expression patterns of these genes showed nearly the opposite trend after 24 days of overfeeding. Taken together, these findings indicate that OTUD7A regulates the expression of inflammation- and immune-related genes in the development of goose fatty liver.

RNAseq of TGF-β receptor type I kinase-dependent genes in oral fibroblast exposed to milk

Background Milk is a rich source of natural growth factors that may support oral tissue homeostasis and wound healing. We had shown earlier that blocking TGF-β receptor type I kinase with the inhibitor SB431542 abolished the expression of IL11 and other genes in human gingival fibroblasts exposed to the aqueous fraction of milk. Our aim was to identify the entire signature of TGF-β receptor type I kinase-dependent genes regulated by the aqueous fraction of human milk. Result RNAseq revealed 99 genes being strongly regulated by milk requiring activation of the SB431542-dependent TGF-β receptor type I kinase. Among the SB431542-dependent genes is IL11 but also cadherins, claudins, collagens, potassium channels, keratins, solute carrier family proteins, transcription factors, transmembrane proteins, tumor necrosis factor ligand superfamily members, and tetraspanin family members. When focusing on our candidate gene, we could identify D609 to suppress IL11 expression, independent of phospholipase C, sphinosine-1 phosphate synthesis, and Smad-3 phosphorylation and its nuclear translocation. In contrast, genistein and blocking phosphoinositide 3-kinases by wortmannin and LY294002 increased the milk-induced IL11 expression in gingival fibroblasts. Conclusion Taken together, our data revealed TGF-β receptor type I kinase signaling to cause major changes of the genetic signature of gingival fibroblasts exposed to aqueous fraction of human milk.

Proposed Anti-Inflammatory Diet Reduces Inflammation in Compliant, Weight-Stable Patients with Rheumatoid Arthritis in a Randomized Controlled Crossover Trial

ABSTRACT Background It is unclear to what extent adjuvant dietary intervention can influence inflammation in rheumatoid arthritis (RA). Objectives The objective was to assess the effects of dietary manipulation on inflammation in patients with RA. Methods In a crossover design, participants [n = 50, 78% females, median BMI (in kg/m2) 27, median age 63 y] were randomly assigned to begin with either a 10-wk portfolio diet of proposed anti-inflammatory foods (i.e., a high intake of fatty fish, whole grains, fruits, nuts, and berries) or a control diet resembling a Western diet with a 4-mo washout in between. This report evaluates the secondary outcome markers of inflammation among participants with stable medication. Analyses were performed using a linear mixed ANCOVA model. Results There were no significant effects on CRP or ESR in the group as a whole. In those with high compliance (n = 29), changes in ESR within the intervention diet period differed significantly compared with changes within the control diet period (mean: –5.490; 95% CI: –10.310, –0.669; P = 0.027). During the intervention diet period, there were lowered serum concentrations of C-X-C motif ligand 1 (CXCL1) (mean: –0.268; 95% CI: –0.452, –0.084;P = 0.006), CXCL5 (mean: –0.278; 95% CI: –0.530, –0.026 P = 0.031), CXCL6 (mean: –0.251; 95% CI: –0.433, –0.069; P = 0.009), and tumor necrosis factor ligand superfamily member 14 (TNFSF14) (mean: –0.139; 95% CI: –0.275, –0.002; P = 0.047) compared with changes within the control diet period. Conclusion A proposed anti-inflammatory diet likely reduced systemic inflammation, as indicated by a decreased ESR in those who completed the study with high compliance (n = 29). These findings warrant further studies to validate our results, and to evaluate the clinical relevance of changes in CXCL1, CXCL5, CXCL6, and TNFSF14 in patients with RA.

Association of TNFSF4 polymorphisms with systemic lupus erythematosus: a meta-analysis

Objective To more precisely estimate the association between the tumor necrosis factor ligand superfamily member 4 (TNFSF4) gene polymorphisms and systemic lupus erythematosus (SLE) susceptibility, we performed a meta-analysis on the association of the following single nucleotide polymorphisms (SNPs) of TNFSF4 with SLE: rs1234315, rs844648, rs2205960, rs704840, rs844644, rs10489265. Methods A literature-based search was conducted using PubMed, MEDLINE, Embase, Web of Science databases, and Cochrane Library databases to identify all relevant studies. And the association of TNFSF4 gene polymorphisms and SLE susceptibility was evaluated by pooled odds ratio (OR) with 95% confidence interval (CI). Results The meta-analysis produced overall OR of 1.42 (95% CI 1.36–1.49, P < 0.00001), 1.41 (95% CI 1.36–1.46, P < 0.00001) and 1.34 (95% CI 1.26–1.42, P < 0.00001) for the rs2205960, rs1234315 and rs704840 polymorphisms respectively, confirming these three SNPs confer a significant risk for the development of SLE. On the other hand, the meta-analysis produced overall OR of 0.92 (95% CI 0.70–1.21, P = 0.54) for the rs844644 polymorphism, suggesting no significant association. And no association was also found between either rs844648 1.11 (OR 1.11, 95% CI 0.86–1.43, P = 0.41) or rs10489265 (OR 1.17, 95% CI 0.94–1.47, P = 0.17) polymorphism with SLE susceptibility, respectively. Conclusions Our meta-analysis demonstrated that the TNFSF4 rs2205960, rs1234315 and rs844840 SNPs was significantly associated with an increased risk of SLE.

Circulating proteins protect against renal decline and progression to end-stage renal disease in patients with diabetes

Diabetic kidney disease (DKD) and its major clinical manifestation, progressive renal decline that leads to end-stage renal disease (ESRD), are a major health burden for individuals with diabetes. The disease process that underlies progressive renal decline comprises factors that increase risk as well as factors that protect against this outcome. Using untargeted proteomic profiling of circulating proteins from individuals in two independent cohorts with type 1 and type 2 diabetes and varying stages of DKD followed for 7 to 15 years, we identified three elevated plasma proteins—fibroblast growth factor 20 (OR, 0.69; 95% CI, 0.54 to 0.88), angiopoietin-1 (OR, 0.72; 95% CI, 0.57 to 0.91), and tumor necrosis factor ligand superfamily member 12 (OR, 0.75; 95% CI, 0.59 to 0.95)—that were associated with protection against progressive renal decline and progression to ESRD. The combined effect of these three protective proteins was demonstrated by very low cumulative risk of ESRD in those who had baseline concentrations above median for all three proteins, whereas the cumulative risk of ESRD was high in those with concentrations below median for these proteins at the beginning of follow-up. This protective effect was shown to be independent from circulating inflammatory proteins and clinical covariates and was confirmed in a third cohort of diabetic individuals with normal renal function. These three protective proteins may serve as biomarkers to stratify diabetic individuals according to risk of progression to ESRD and might also be investigated as potential therapeutics to delay or prevent the onset of ESRD.

Tumor necrosis factor ligand-related molecule 1A affects the intestinal mucosal barrier function by promoting Th9/interleukin-9 expression

Objectives To investigate the effect of tumor necrosis factor ligand-related molecule 1A (TL1A) on the intestinal mucosal barrier in mice with chronic colitis. Methods Male TL1A-overexpressing transgenic mice and male C57BL/6 wild-type mice were used to establish a dextran sodium sulfate (DSS)-induced colitis model. The expression of occludin and claudin-1 was observed. Bacterial distribution in the intestinal mucosa and Th9/interleukin (IL)-9 expression were detected. In vitro co-culture systems of naive CD4+ T cells and Caco-2 cells were established and TL1A was added. Changes in transepithelial electrical resistance and IL-9 expression were measured. CD4+IL-9 cells were detected by flow cytometry. Results DSS mice showed a significant down-regulation of occludin and claudin-1 compared with controls. Expression levels of occludin, zonulin-1, and claudin-1 in the Caco-2+TGF-β+IL-4+TL1A group were significantly lower than in the Caco-2+TGF-β+IL-4 group. Bacterial distribution was clearly disordered in the DSS group. Transmembrane resistance of the Caco-2+TGF-β+IL-4+TL1A group was significantly lower and IL-9 expression significantly higher than in the Caco-2+TGF-β+IL-4 group. Conclusions TL1A overexpression promotes destruction of the intestinal mucosal barrier in mice with chronic colitis. The underlying mechanism may be associated with the promoting role of TL1A in Th9/IL-9 expression, which further destroys the mucosal barrier.

Role of Extrinsic Apoptotic Signaling Pathway during Definitive Erythropoiesis in Normal Patients and in Patients with β-Thalassemia

Apoptosis is a process of programmed cell death which has an important role in tissue homeostasis and in the control of organism development. Here, we focus on information concerning the role of the extrinsic apoptotic pathway in the control of human erythropoiesis. We discuss the role of tumor necrosis factor α (TNFα), tumor necrosis factor ligand superfamily member 6 (FasL), tumor necrosis factor-related apoptosis-inducing (TRAIL) and caspases in normal erythroid maturation. We also attempt to initiate a discussion on the observations that mature erythrocytes contain most components of the receptor-dependent apoptotic pathway. Finally, we point to the role of the extrinsic apoptotic pathway in ineffective erythropoiesis of different types of β-thalassemia.