Mesenchymal stem cells (MSCs) regulate immune cell activity by expressing tumor necrosis factor-α (TNF-α)-stimulated gene 6 (TSG-6) in inflammatory environments; however, whether anti-inflammatory responses affect TSG-6 expression in MSCs is not well understood. Therefore, we investigated whether transforming growth factor-β (TGF-β) regulates TSG-6 expression in adipose tissue-derived stem cells (ASCs) and whether effective immunosuppression can be achieved using ASCs and TGF-β signaling inhibitor A83-01. TGF-β significantly decreased TSG-6 expression in ASCs, but A83-01 and the p38 inhibitor SB202190 significantly increased it. However, in septic C57BL/6 mice, A83-01 further reduced the survival rate of the lipopolysaccharide (LPS)-treated group and ASC transplantation did not improve the severity induced by LPS. ASC transplantation alleviated the severity of sepsis induced by LPS+A83-01. In co-culture of macrophages and ASCs, A83-01 decreased TSG-6 expression whereas A83-01 and SB202190 reduced Cox-2 and IDO-2 expression in ASCs. These results suggest that TSG-6 expression in ASCs can be regulated by high concentrations of pro-inflammatory cytokines in vitro and in vivo, and that A83-01 and SB202190 can reduce the expression of immunomodulators in ASCs. Therefore, our data suggest that co-treatment of ASCs with TGF-β or p38 inhibitors is not adequate to modulate inflammation.

Malnutrition is very complex in patients with end-stage renal disease (ESRD) and is associated with poor prognosis. This is because hemodynamic changes, hormonal changes, persistent inflammatory reactions, and fluid overloads are more complicated as uremia is worsening. Bio-impedance spectroscopy (BIS) is a useful method to estimate fluid balance (Overhydration/ extracellular water, OH/ECW) and nutritional status (Phase angle, PhA). We aimed to evaluate the volume and nutritional status by BIS and to investigate the relationship between the appetite regulating hormones and the parameters of BIS in patients with stage 5 chronic kidney disease not undergoing dialysis (CKD5-ND). We enrolled a total of 91 CKD5-ND patients. We measured routine serum markers including albumin and NT-proBNP and the appetite regulating hormones, leptin and ghrelin. We defined poor nutritional status as a PhA < 4.5°, and proper nutritional status as a PhA ≥ 4.5°. We also evaluated each patient’s nutritional status by assessing their geriatric nutritional risk index (GNRI) and their volume status by measuring NT-proBNP. Forty-one patients (45%) had poor nutritional status. Patients with a poor nutritional status had significantly higher OH/ECW (29.6 ± 12.7% vs. 6.2 ± 10.3%, p<0.001) and lower levels of leptin (3.8 ± 3.1 vs. 7.0 ± 6.2 ng/mL, p = 0.004) than those with proper nutritional status. PhA was associated with GNRI (r = 0.597, P<0.001) and NT-proBNP was associated with OH/ECW (r = 0.384, P<0.001). Leptin was negatively correlated with OH/ECW (r = -0.288, p = 0.006). In contrast, leptin was positively correlated with PhA (r = 0.263, p = 0.012). In multivariate logistic regression, high level of leptin (OR 7.00, 95% CI 1.74–28.10) was associated with proper nutrition, while an increased OH/ECW (OR 0.65, 95% CI 0.51–0.84) was associated with poor nutrition. Our study demonstrates that CKD5-ND patients with poor nutrition generally also suffer from excessive body fluid. Low leptin level suggests poor nutrition in CKD5-ND patients. PhA could be used as a nutritional index for ESRD patients.

Background and Objectives: Critically ill surgical patients are susceptible to various postoperative complications, including acute kidney injury (AKI) and multiorgan distress syndrome (MODS). These complications intensify patient suffering and significantly increase morbidity and mortality rates. This study aimed to identify the biomarkers for predicting AKI and MODS in critically ill surgical patients. Materials and Methods: We prospectively enrolled critically ill surgical patients admitted to the intensive care unit via the emergency department between July 2022 and July 2023. A total of 83 patients were recruited, and their data were used to analyze MODS. Three patients who showed decreased creatinine clearance at the initial presentation were excluded from the analysis for AKI. Patient characteristics and laboratory parameters including white blood cell (WBC) count, neutrophil count, delta neutrophil index, urine and serum β2-microglobulin, and urine serum mitochondrial DNA copy number (mtDNAcn) were analyzed to determine the reliable biomarker to predict AKI and MODS. Results: The following parameters were independently correlated with MODS: systolic blood pressure (SBP), initial neutrophil count, and platelet count, according to a logistic regression model. The optimal cut-off values for SBP, initial neutrophil count, and platelet count were 113 mmHg (sensitivity 66.7%; specificity 73.9%), 8.65 (X³) (10⁹/L) (sensitivity 72.2%; specificity 64.6%), and 195.0 (X³) (10⁹/L) (sensitivity 66.7%; specificity 81.5%), respectively. According to the logistic regression model, diastolic blood pressure (DBP) and initial urine mtDNAcn were independently correlated with AKI. The optimal cut-off value for DBP and initial urine mtDNAcn were 68.5 mmHg (sensitivity 61.1%; specificity 79.5%) and 1225.6 copies/μL (sensitivity 55.6%; specificity 95.5%), respectively. Conclusions: SBP, initial neutrophil count, and platelet count were independent predictors of MODS in critically ill patients undergoing surgery. DBP and initial urine mtDNAcn levels were independent predictors of AKI in critically ill surgical patients. Large-scale multicenter prospective studies are needed to confirm our results.