Kim DJ, et al. J Gastric Cancer. 2024 Dec;25:e8. https://doi.org/10.5230/jgc.2025.25.e8

The pro-inflammatory cytokines tumor necrosis factor-alpha (TNF-α) and interleukin (IL)-1β upregulate TNF-α-stimulated gene 6 (TSG-6); however, current knowledge about the optimal conditions for TSG-6 expression in mesenchymal stem cells (MSCs) is limited. Here, we investigated whether TSG-6 expression varies depending on the polarization state of macrophages co-cultured with adipose tissue-derived stem cells (ASCs) and analyzed the optimal conditions for TSG-6 expression in ASCs. TSG-6 expression increased in ASCs co-cultured with M0, M1, and M2 macrophages indirectly; among them, M1 macrophages resulted in the highest increase in TSG-6 expression in ASCs. TSG-6 expression in ASCs dramatically increased by combination (but not single) treatment of TNF-α, IL-1β, interferon-gamma (IFN-γ), and lipopolysaccharide (LPS). In addition, phosphorylation of signal transducer and activator of transcription (STAT) 1/3 was observed in response to IFN-γ and LPS treatment but not TNF-α and/or IL-1β. STAT1/3 activation synergistically increased TNF-α/IL-1β-dependent TSG-6 expression, and JAK inhibitors suppressed TSG-6 expression both in ASCs and macrophages. In LX-2 hepatic stellate cells, TSG-6 inhibited TGF-β-induced Smad3 phosphorylation, resulting in decreased α-smooth muscle actin (SMA) expression. Moreover, fibrotic activities of LX-2 cells induced by TGF-β were dramatically decreased after indirect co-culture with ASCs and M1 macrophages. These results suggest that a comprehensive inflammatory microenvironment may play an important role in determining the therapeutic properties of ASCs by increasing TSG-6 expression through STAT1/3 activation.

Liver organoids generated with single or multiple cell types have been used to investigate liver fibrosis development, toxicity, pathogenesis, and drug screening. However, organoid generation is limited by the availability of cells isolated from primary tissues or differentiated from various stem cells. To ensure cell availability for organoid formation, we investigated whether liver organoids could be generated with cell-line-based Huh-7 hepatocellular carcinoma cells, macrophages differentiated from THP-1 monocytes, and LX-2 hepatic stellate cells (HSCs) and primary liver sinusoidal endothelial cells (LSECs). In liver organoids, hepatocyte-, LSEC-, macrophage-, and HSC-related gene expression increased relative to that in two-dimensional (2D)-cultured Huh-7/LSEC/THP-1/LX-2 cells without Matrigel. Thioacetamide (TAA) increased α-smooth muscle actin expression in liver organoids but not in 2D-cultured cells, whereas in TAA-treated organoids, the expression of hepatic and LSEC markers decreased and that of macrophage and HSC markers increased. TAA-induced fibrosis was suppressed by treatment with N-acetyl-L-cysteine or tumor-necrosis-factor-stimulated gene 6 protein. The results showed that liver toxicants could induce fibrotic and inflammatory responses in liver organoids comprising Huh-7/LSEC/macrophages/LX-2 cells, resulting in fibrotic liver organoids. We propose that cell-line-based organoids can be used for disease modeling and drug screening to improve liver fibrosis treatment.

Background: The use of biomarkers to predict patient outcomes may be crucial for patients admitted to the intensive care unit (ICU) following surgery because biomarkers guide clinicians in tailoring treatment plans accordingly. Therefore, we aimed to identify potential biomarkers to predict the prognosis of patients with Fournier’s gangrene (FG) admitted to the ICU after surgery.Methods: We enrolled patients with FG admitted to our Hospital between January 2013 and December 2022. We retrospectively analyzed patient characteristics, factors related to management, scores known to be associated with the prognosis of FG, and laboratory data.Results: The study population included 28 survivors and 13 nonsurvivors. The initial serum lactate level taken in the emergency department; white blood cell, neutrophil, and platelet counts; delta neutrophil index and international normalized ratio; albumin, glucose, HCO3, and postoperative lactate levels; and the laboratory risk indicator for necrotizing fasciitis differed between survivors and nonsurvivors. Postoperative lactate and initial albumin levels were independent predictors of mortality in patients with FG. In the receiver operating characteristic curve analysis, the postoperative lactate level was the best indicator of mortality (area under the curve, 0.877; 95% confidence interval, 0.711–1.000). The optimal cutoff postoperative lactate level for predicting mortality was 3.0 mmol/L (sensitivity, 80.0%; specificity, 95.0%).Conclusions: Postoperative lactate and initial albumin levels could be potential predictors of mortality in patients with FG admitted to the ICU after surgery, and the optimal cutoff postoperative lactate and initial albumin levels to predict mortality were 3.0 mmol/L and 3.05 g/dl, respectively. Large-scale multicenter prospective studies are required to confirm our results.

Pediatric trauma patients are increasing, and trauma is the leading cause of death in children. Pancreatic injury is known as the fourth most common solid organ injury, but the diagnosis of pancreatic injury is often delayed due to the retroperitoneal location of the pancreas and the low sensitivity and specificity of diagnostic tests. Endoscopic retrograde cholangiopancreatography (ERCP) is an important test for the diagnosis and treatment of various biliary tract and pancreatic diseases. However, cases of performing ERCP in traumatic pancreatic injury in children have been rarely reported. Thus, we aimed to evaluate the usefulness of ERCP in traumatic pancreatic injury in children. Between January 1983 and December 2022, pediatric patients under the age of 18 who were treated for traumatic pancreatic injury at a single institution were recruited and retrospectively analyzed. Patient characteristics and clinical outcomes were assessed. Thirty-one patients were enrolled in this study. Among them, 15 (48.4%) patients underwent ERCP. The time to diet was significantly longer in the ERCP group. There were no statistically significant differences in other characteristics between the ERCP and the non-ERCP group. In nine (60%) patients of the ERCP group, ERCP was used for therapeutic intervention or as a decision-making tool for surgery, and was used to resolve pancreas-related complications. ERCP may be useful for the diagnosis and treatment of traumatic pancreatic injury in children. In addition, ERCP can be safely applied in children, and complications related to ERCP also may not increase. When obscure pancreatic injury is suspected, it is necessary to consider performing ERCP.

Ko JW, et al. Ann Surg Treat Res. 2020 Dec;99(6):352-361. https://doi.org/10.4174/astr.2020.99.6.352