Robust identification of genetic alterations is important for the diagnosis and subsequent treatment of tumors. Screening for genetic alterations using tumor tissue samples may lead to biased interpretations because of the heterogeneous nature of the tumor mass. Liquid biopsy has been suggested as an attractive tool for the non-invasive follow-up of cancer treatment outcomes. In this study, we aimed to verify whether the mutations identified in primary tumor tissue samples could be consistently detected in plasma cell–free DNA (cfDNA) by digital polymerase chain reaction (dPCR). We first examined the genetic alteration profiles of three colorectal cancer (CRC) tissue samples by targeted next-generation sequencing (NGS) and identified 11 non-silent amino acid changes across six cancer-related genes (APC, KRAS, TP53, TERT, ARIDIA, and BRCA1). All three samples had KRAS mutations (G12V, G12C, and G13D), which were well-known driver events. Therefore, we examined the KRAS mutations by dPCR. When we examined the three KRAS mutations by dPCR using tumor tissue samples, all of them were consistently detected and the variant allele frequencies (VAFs) of the mutations were almost identical between targeted NGS and dPCR. When we examined the KRAS mutations using the plasma cfDNA of the three CRC patients by dPCR, all three mutations were consistently identified. However, the VAFs were lower (range, 0.166% to 2.638%) than those obtained using the CRC tissue samples. In conclusion, we confirmed that the KRAS mutations identified from CRC tumor tissue samples were consistently detected in the plasma cfDNA of the three CRC patients by dPCR.

Robust identification of genetic alterations is important for the diagnosis and subsequent treatment of tumors. Screening for genetic alterations using tumor tissue samples may lead to biased interpretations because of the heterogeneous nature of the tumor mass. Liquid biopsy has been suggested as an attractive tool for the non-invasive follow-up of cancer treatment outcomes. In this study, we aimed to verify whether the mutations identified in primary tumor tissue samples could be consistently detected in plasma cell–free DNA (cfDNA) by digital polymerase chain reaction (dPCR). We first examined the genetic alteration profiles of three colorectal cancer (CRC) tissue samples by targeted next-generation sequencing (NGS) and identified 11 non-silent amino acid changes across six cancer-related genes (APC, KRAS, TP53, TERT, ARIDIA, and BRCA1). All three samples had KRAS mutations (G12V, G12C, and G13D), which were well-known driver events. Therefore, we examined the KRAS mutations by dPCR. When we examined the three KRAS mutations by dPCR using tumor tissue samples, all of them were consistently detected and the variant allele frequencies (VAFs) of the mutations were almost identical between targeted NGS and dPCR. When we examined the KRAS mutations using the plasma cfDNA of the three CRC patients by dPCR, all three mutations were consistently identified. However, the VAFs were lower (range, 0.166% to 2.638%) than those obtained using the CRC tissue samples. In conclusion, we confirmed that the KRAS mutations identified from CRC tumor tissue samples were consistently detected in the plasma cfDNA of the three CRC patients by dPCR.
Bias (Epidemiology) ; Biopsy ; Colorectal Neoplasms ; Diagnosis ; DNA ; Follow-Up Studies ; Gene Frequency ; Humans ; Mass Screening ; Plasma ; Polymerase Chain Reaction

This study was performed to assess the antiapoptotic effect of canine platelet-rich plasma (PRP) treated on the canine adipose-derived mesenchymal stem cells (cMSCs) under cold ischemic conditions. The effect of preventing apoptosis of cMSCs was evaluated in the apoptotic condition induced by cold ischemic injury in vitro. To determine the progression of apoptosis, the changes in cell nucleus were observed using 4',6-diamidino-2-phenylindole (DAPI) fluorescence staining. In addition, we examined the mitochondrial membrane potential (MMP) and caspase-3 activity. When the cold hypoxic injury was applied to cMSCs, the apoptotic change was observed by DAPI staining, mitochondrial staining for MMP, and caspase-3 assay. PRP significantly decreased the number of apoptotic cells. Nuclear shrinkage and fragmentation of apoptotic cells in control groups were observed by DAPI staining. The MMP was recovered by the treatment of PRP. In addition, when the luminescence intensity was measured for caspase-3 activity, the value was significantly higher in the PRP treated groups than the control groups. The results of this study showed that the PRP may have a beneficial effect on apoptosis induced by cold ischemic injury.

5-Aminosalicylate agents are the main therapeutic agents for ulcerative colitis. Balsalazide is a prodrug of 5-aminosalicylate and has fewer side effects than the other 5-aminosalicylate agents. Pulmonary complications resembling granulomatosis with polyangiitis in ulcerative colitis are extremely rare. Here, we report a patient with ulcerative colitis on balsalazide presenting respiratory symptoms and multiple pulmonary nodules from a chest radiography that was pathologically diagnosed with a limited form of granulomatosis with polyangiitis with bronchiolitis obliterans organizing pneumonia-like variant. To our knowledge, this is the first report of a balsalazide-induced limited form of granulomatosis with polyangiitis with bronchiolitis obliterans organizing pneumonia-like variant.
Bronchiolitis ; Bronchiolitis Obliterans ; Colitis, Ulcerative ; Humans ; Mesalamine ; Multiple Pulmonary Nodules ; Phenylhydrazines ; Thorax ; Ulcer ; Wegener Granulomatosis

OBJECTIVE: To evaluate flow pattern characteristics in the ascending aorta (AA) with four-dimensional (4D)-flow MRI and to determine predictors of aortic dilatation late after tetralogy of Fallot (TOF) repair. MATERIALS AND METHODS: This study included 44 patients with repaired TOF (25 males and 19 females; mean age, 28.9 ± 8.4 years) and 11 volunteers (10 males and 1 female, mean age, 33.7 ± 8.8 years) who had undergone 4D-flow MRI. The aortic diameters, velocity, wall shear stress (WSS), flow jet angle (FJA), and flow displacement (FD) at the level of the sinotubular junction (STJ) and mid-AA were compared between the repaired TOF and volunteer groups. The hemodynamic and clinical parameters were also compared between the aortic dilatation and non-dilatation subgroups in the repaired TOF group. RESULTS: The diameters of the sinus of Valsalva, STJ, and AA were significantly higher in the repaired TOF group than in the volunteer group (p = 0.002, p < 0.001, and p = 0.013, respectively). The FJAs at the STJ and AA were significantly greater in the repaired TOF group (p < 0.001 and p = 0.003, respectively), while velocities and WSS parameters were significantly lower. FD showed no statistically significant difference (p = 0.817). In subgroup analysis, age at TOF repair was significantly higher (p = 0.039) and FJA at the level of the AA significantly greater (p = 0.003) and mean WSS were significantly lower (p = 0.039) in the aortic dilatation group. FD were higher in the aortic dilatation group without statistical significance (p = 0.217). CONCLUSION: Patients with repaired TOF have an increased FJA, dilated AA, and secondarily decreased WSS. In addition to known risk factors, flow eccentricity may affect aortic dilatation in patients with repaired TOF.
Aorta ; Dilatation ; Female ; Hemodynamics ; Humans ; Magnetic Resonance Imaging ; Male ; Risk Factors ; Sinus of Valsalva ; Tetralogy of Fallot ; Volunteers

Nociceptin/orphanin FQ (N/OFQ) and its receptor, nociceptin opioid peptide (NOP) receptor, are localized in brain areas implicated in depression including the amygdala, bed nucleus of the stria terminalis, habenula, and monoaminergic nuclei in the brain stem. N/OFQ inhibits neuronal excitability of monoaminergic neurons and monoamine release from their terminals by activation of G protein-coupled inwardly rectifying K⁺ channels and inhibition of voltage sensitive calcium channels, respectively. Therefore, NOP receptor antagonists have been proposed as a potential antidepressant. Indeed, mounting evidence shows that NOP receptor antagonists have antidepressant-like effects in various preclinical animal models of depression, and recent clinical studies again confirmed the idea that blockade of NOP receptor signaling could provide a novel strategy for the treatment of depression. In this review, we describe the pharmacological effects of N/OFQ in relation to depression and explore the possible mechanism of NOP receptor antagonists as potential antidepressants.
Amygdala ; Antidepressive Agents ; Brain ; Brain Stem ; Calcium Channels ; Depression ; Habenula ; Models, Animal ; Neurons ; Neuropeptides ; Opioid Peptides ; Receptors, Drug ; Septal Nuclei

Purpose: To assess the added value of radiomics models from preoperative chest CT in predicting the presence of spread through air spaces (STAS) in the early stage of surgically resected lung adenocarcinomas using multiple validation datasets. Materials and Methods: This retrospective study included 550 early-stage surgically resected lung adenocarcinomas in 521 patients, classified into training, test, internal validation, and temporal validation sets (n=211, 90, 91, and 158, respectively). Radiomics features were extracted from the segmented tumors on preoperative chest CT, and a radiomics score (Rad-score) was calculated to predict the presence of STAS. Diagnostic performance of the conventional model and the combined model, based on a combination of conventional and radiomics features, for the diagnosis of the presence of STAS were compared using the area under the curve (AUC) of the receiver operating characteristic curve. Results: Rad-score was significantly higher in the STAS-positive group compared to the STAS-negative group in the training, test, internal, and temporal validation sets. The performance of the combined model was significantly higher than that of the conventional model in the training set {AUC: 0.784 [95% confidence interval (CI): 0.722–0.846] vs. AUC: 0.815 (95% CI: 0.759–0.872), p=0.042}. In the temporal validation set, the combined model showed a significantly higher AUC than that of the conventional model (p=0.001). The combined model showed a higher AUC than the conventional model in the test and internal validation sets, albeit with no statistical significance. Conclusion A quantitative CT radiomics model can assist in the non-invasive prediction of the presence of STAS in the early stage of lung adenocarcinomas.

The global obesity epidemic and associated metabolic diseases require alternative biological targets for new therapeutic strategies. In this study, we show that a phytochemical sulfuretin suppressed adipocyte differentiation of preadipocytes and administration of sulfuretin to high fat diet-fed obese mice prevented obesity and increased insulin sensitivity. These effects were associated with a suppressed expression of inflammatory markers, induced expression of adiponectin, and increased levels of phosphorylated ERK and AKT. To elucidate the molecular mechanism of sulfuretin in adipocytes, we performed microarray analysis and identified activating transcription factor 3 (Atf3) as a sulfuretin-responsive gene. Sulfuretin elevated Atf3 mRNA and protein levels in white adipose tissue and adipocytes. Consistently, deficiency of Atf3 promoted lipid accumulation and the expression of adipocyte markers. Sulfuretin’s but not resveratrol’s anti-adipogenic effects were diminished in Atf3 deficient cells, indicating that Atf3 is an essential factor in the effects of sulfuretin. These results highlight the usefulness of sulfuretin as a new anti-obesity intervention for the prevention of obesity and its associated metabolic diseases.
Activating Transcription Factor 3 ; Adipocytes ; Adiponectin ; Adipose Tissue, White ; Animals ; Diet* ; Insulin Resistance ; Metabolic Diseases* ; Mice ; Mice, Obese* ; Microarray Analysis ; Obesity* ; RNA, Messenger

BACKGROUND/OBJECTIVES: Ginseng extract (GSE) and taurine (TR) are widely used antifatigue resources in functional foods. However, the mechanism underlying the antifatigue effects of GSE and TR are still unclear. Hence, we investigated whether GSE and TR have synergistic effects against fatigue in mice.MATERIALS/METHODS: L6 cells were treated with different concentrations of TR and GSE, and cell viability was determined using 2-(4-iodophenyl)-3-(4-nitrophenyl)-5-(2,4-disulfophenyl)-2H-tetrazolium. Oxidative stress was analyzed by immunocytochemistry using MitoTracker™ Red FM and an anti-8-oxoguanine antibody. Respiratory gas analysis was performed to investigate metabolism. Expression of an activated protein kinase was analyzed using immunohistochemistry. Gene expression of cluster of differentiation 36 and pyruvate dehydrogenase lipoamide kinase isozyme 4 was measured using reverse transcription– polymerase chain reaction. Mice were orally administered TR, GSE, or their combination for 30 days, and then fatigue-related parameters, including lactate, blood urea nitrogen, and glycogen, were measured after forced swimming. RESULTS: TR and GSE reduced oxidative stress levels in hydrogen peroxide-stimulated L6 cells and enhanced the oxygen uptake and lipid metabolism in mice after acute exercise. After oral administration of TR or GSE for 30 days, the fatigue-related parameters did not change in mice. However, the mice administered GSE (400 mg/kg/day) alone for 30 days could swim longer than those from the other groups. Further, no synergistic effect was observed after the swimming exercise in mice treated with the TR and GSE combination for 30 days. CONCLUSIONS Taken together, our data suggest that TR and GSE may exert antifatigue effects in mice after acute exercise by enhancing oxygen uptake and lipid oxidation.