IRF7 mediates MCP-1 in adipocyte

Hypertrophy, associated with adipocyte dysfunction, causes increased pro-inflammatory adipokine, and abnormal glucose and lipid metabolism, leading to insulin resistance and obesity-related-health problems. By combining DNA microarray and genomic data analyses to predict DNA binding motifs, we identified the transcription factor Interferon Regulatory Factor 7 (IRF7) as a possible regulator of genes related to adipocyte hypertrophy. To investigate the role of IRF7 in adipocytes, we examined gene expression patterns in 3T3-L1 cells infected with a retrovirus carrying the IRF7 gene and found that enforced IRF7 expression induced the expression of monocyte chemoattractant protein-1 (MCP-1), a key initial adipokine in the chronic inflammation of obesity. CRISPR/Cas9 mediated-suppression of IRF7 significantly reduced MCP-1 mRNA. Luciferase assays, chromatin immunoprecipitation PCR analysis and gel shift assay showed that IRF7 transactivates the MCP-1 gene by binding to its proximal Interferon Stimulation Response Element (ISRE), a putative IRF7 binding motif. IRF7 knockout mice exhibited lower expression of MCP-1 in epidydimal white adipose tissue under high-fat feeding conditions, suggesting the transcription factor is physiologically important for inducing MCP-1. Taken together, our results suggest that IRF7 transactivates MCP-1 mRNA in adipocytes, and it may be involved in the adipose tissue inflammation associated with obesity

Importance of feeding status evaluation in older patients undergoing hemodialysis

Older hospitalized patients undergoing hemodialysis are increasingly experiencing malnutrition caused by dysphagia. However, only a few studies have focused on this problem. We used the Kuchikara Taberu Balance Chart (KTBC) to evaluate the patients’ feeding status and examined its association with their nutritional status and prognosis. This study included elderly patients undergoing hemodialysis who were hospitalized at Nagasaki Renal Center for > 3 days between June 2021 and February 2022. In total, 82 inpatients were included [mean age, 73.4 ± 10.0 years; men, 57.3%; median dialysis vintage, 79.0 months (interquartile range, 37.3–164.8)]. We classified patients with lower than the median KTBC score (57 points) as being at risk for dysphagia; 37 patients (45.1%) were at risk for dysphagia. Spearman’s rank correlation coefficient (ρ) elucidated that the KTBC total score was significantly associated with each nutritional indicator [serum albumin level (ρ = 0.505, p < 0.001); geriatric nutritional risk index (ρ = 0.600, p < 0.001); and nutritional risk index (ρ = -0.566, p < 0.001)]. The KTBC score was also closely associated with the body mass index (ρ = 0.228, p = 0.04). Patients with a lower KTBC score showed poor prognosis (log-rank test: p = 0.001), and age- and sex-adjusted Cox proportional analysis showed that the KTBC score was associated with life prognosis (hazard ratio, 0.90; 95% confidential interval, 0.86–0.94; p < 0.001). Therefore, we concluded that the patients at risk of dysphagia, identified using the KTBC score, were malnourished and had a poor prognosis. Hence, the evaluation of dysphagia using the KTBC is encouraged to prevent malnutrition in vulnerable older patients undergoing hemodialysis

Transcription factors Foxo3a and Foxo1 couple the E3 ligase Cbl-b to the induction of Foxp3 expression in induced regulatory T cells

The transcription factor Foxp3 is essential for optimal regulatory T (T reg) cell development and function. Here, we show that CD4+ T cells from Cbl-b RING finger mutant knockin or Cbl-b–deficient mice show impaired TGF-β–induced Foxp3 expression. These T cells display augmented Foxo3a phosphorylation, but normal TGF-β signaling. Expression of Foxo3a rescues Foxp3 expression in Cbl-b–deficient T cells, and Foxo3a deficiency results in defective TGF-β–driven Foxp3 induction. A Foxo3a-binding motif is present in a proximal region of the Foxp3 promoter, and is required for Foxo3a association. Foxo1 exerts similar effects as Foxo3a on Foxp3 expression. This study reveals that Foxo factors promote transcription of the Foxp3 gene in induced T reg cells, and thus provides new mechanistic insight into Foxo-mediated T cell regulation

Effects of recombinant human soluble thrombomodulin on neutrophil extracellular traps in the kidney of a mouse model of endotoxin shock

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Association of circulating histone H3 and high mobility group box 1 levels with postoperative prognostic indicators in intensive care unit patients: a single-center observational study

Objectives: Damage associated molecular patterns (DAMPs) levels are associated with sepsis severity and prognosis. Histone and high mobility group box 1 (HMGB1) levels are also potential indicators of prognosis. We investigated the relationship between serum histone H3 and HMGB1 levels and the illness severity score and prognosis in postoperative patients. Methods: Postoperative serum histone H3 and HMGB1 levels in 39 intensive care unit (ICU) patients treated at our institution were measured. The correlation between peak histone H3 and HMGB1 levels in each patient and clinical data (age, sex, surgical time, length of ICU stay, and survival after ICU discharge), which also included the patients’ illness severity score, was examined. Results: Histone H3 but not HMGB1 levels were positively correlated with surgical time, the Sequential Organ Failure Assessment score, the Japanese Association for Acute Medicine acute phase disseminated intravascular coagulation diagnosis score, and the length of ICU stay. Both histone H3 and HMGB1 levels were negatively correlated with age. However, survival post-ICU discharge was not correlated with histone H3 or HMGB1 levels. Conclusions: Histone H3 levels are correlated with severity scores and the length of ICU stay. Serum histone H3 and HMGB1 levels are elevated postoperatively. These DAMPs, however, are not prognostic indicators in postoperative ICU patients