Background and Objectives: Although the clinical consequences of advanced heart failure (HF) may be similar across different etiologies of cardiomyopathies, their proteomic expression may show substantial differences in relation to underlying pathophysiology. We aimed to identify myocardial tissue–based proteomic characteristics and the underlying molecular pathophysiology in non-ischemic cardiomyopathy with different etiologies. Methods: Comparative extensive proteomic analysis of the myocardium was performed in nine patients with biopsy-proven non-ischemic cardiomyopathies (3 dilated cardiomyopathy [DCM], 2 hypertrophic cardiomyopathy [HCM], and 4 myocarditis) as well as five controls using tandem mass tags combined with liquid chromatography–mass spectrometry.Differential protein expression analysis, Gene Ontology (GO) analysis, and Ingenuity Pathway Analysis (IPA) were performed to identify proteomic differences and molecular mechanisms in each cardiomyopathy type compared to the control. Proteomic characteristics were further evaluated in accordance with clinical and pathological findings. Results: The principal component analysis score plot showed that the controls, DCM, and HCM clustered well. However, myocarditis samples exhibited scattered distribution. IPA revealed the downregulation of oxidative phosphorylation and upregulation of the sirtuin signaling pathway in both DCM and HCM. Various inflammatory pathways were upregulated in myocarditis with the downregulation of Rho GDP dissociation inhibitors. The molecular pathophysiology identified by extensive proteomic analysis represented the clinical and pathological properties of each cardiomyopathy with abundant proteomes. Conclusions Different etiologies of non-ischemic cardiomyopathies in advanced HF exhibit distinct proteomic expression despite shared pathologic findings. The benefit of tailored management strategies considering the different proteomic expressions in non-ischemic advanced HF requires further investigation.

Background and Objectives: Although the clinical consequences of advanced heart failure (HF) may be similar across different etiologies of cardiomyopathies, their proteomic expression may show substantial differences in relation to underlying pathophysiology. We aimed to identify myocardial tissue–based proteomic characteristics and the underlying molecular pathophysiology in non-ischemic cardiomyopathy with different etiologies. Methods: Comparative extensive proteomic analysis of the myocardium was performed in nine patients with biopsy-proven non-ischemic cardiomyopathies (3 dilated cardiomyopathy [DCM], 2 hypertrophic cardiomyopathy [HCM], and 4 myocarditis) as well as five controls using tandem mass tags combined with liquid chromatography–mass spectrometry.Differential protein expression analysis, Gene Ontology (GO) analysis, and Ingenuity Pathway Analysis (IPA) were performed to identify proteomic differences and molecular mechanisms in each cardiomyopathy type compared to the control. Proteomic characteristics were further evaluated in accordance with clinical and pathological findings. Results: The principal component analysis score plot showed that the controls, DCM, and HCM clustered well. However, myocarditis samples exhibited scattered distribution. IPA revealed the downregulation of oxidative phosphorylation and upregulation of the sirtuin signaling pathway in both DCM and HCM. Various inflammatory pathways were upregulated in myocarditis with the downregulation of Rho GDP dissociation inhibitors. The molecular pathophysiology identified by extensive proteomic analysis represented the clinical and pathological properties of each cardiomyopathy with abundant proteomes. Conclusions Different etiologies of non-ischemic cardiomyopathies in advanced HF exhibit distinct proteomic expression despite shared pathologic findings. The benefit of tailored management strategies considering the different proteomic expressions in non-ischemic advanced HF requires further investigation.

Background and Objectives: Although the clinical consequences of advanced heart failure (HF) may be similar across different etiologies of cardiomyopathies, their proteomic expression may show substantial differences in relation to underlying pathophysiology. We aimed to identify myocardial tissue–based proteomic characteristics and the underlying molecular pathophysiology in non-ischemic cardiomyopathy with different etiologies. Methods: Comparative extensive proteomic analysis of the myocardium was performed in nine patients with biopsy-proven non-ischemic cardiomyopathies (3 dilated cardiomyopathy [DCM], 2 hypertrophic cardiomyopathy [HCM], and 4 myocarditis) as well as five controls using tandem mass tags combined with liquid chromatography–mass spectrometry.Differential protein expression analysis, Gene Ontology (GO) analysis, and Ingenuity Pathway Analysis (IPA) were performed to identify proteomic differences and molecular mechanisms in each cardiomyopathy type compared to the control. Proteomic characteristics were further evaluated in accordance with clinical and pathological findings. Results: The principal component analysis score plot showed that the controls, DCM, and HCM clustered well. However, myocarditis samples exhibited scattered distribution. IPA revealed the downregulation of oxidative phosphorylation and upregulation of the sirtuin signaling pathway in both DCM and HCM. Various inflammatory pathways were upregulated in myocarditis with the downregulation of Rho GDP dissociation inhibitors. The molecular pathophysiology identified by extensive proteomic analysis represented the clinical and pathological properties of each cardiomyopathy with abundant proteomes. Conclusions Different etiologies of non-ischemic cardiomyopathies in advanced HF exhibit distinct proteomic expression despite shared pathologic findings. The benefit of tailored management strategies considering the different proteomic expressions in non-ischemic advanced HF requires further investigation.

Background and Objectives: Although the clinical consequences of advanced heart failure (HF) may be similar across different etiologies of cardiomyopathies, their proteomic expression may show substantial differences in relation to underlying pathophysiology. We aimed to identify myocardial tissue–based proteomic characteristics and the underlying molecular pathophysiology in non-ischemic cardiomyopathy with different etiologies. Methods: Comparative extensive proteomic analysis of the myocardium was performed in nine patients with biopsy-proven non-ischemic cardiomyopathies (3 dilated cardiomyopathy [DCM], 2 hypertrophic cardiomyopathy [HCM], and 4 myocarditis) as well as five controls using tandem mass tags combined with liquid chromatography–mass spectrometry.Differential protein expression analysis, Gene Ontology (GO) analysis, and Ingenuity Pathway Analysis (IPA) were performed to identify proteomic differences and molecular mechanisms in each cardiomyopathy type compared to the control. Proteomic characteristics were further evaluated in accordance with clinical and pathological findings. Results: The principal component analysis score plot showed that the controls, DCM, and HCM clustered well. However, myocarditis samples exhibited scattered distribution. IPA revealed the downregulation of oxidative phosphorylation and upregulation of the sirtuin signaling pathway in both DCM and HCM. Various inflammatory pathways were upregulated in myocarditis with the downregulation of Rho GDP dissociation inhibitors. The molecular pathophysiology identified by extensive proteomic analysis represented the clinical and pathological properties of each cardiomyopathy with abundant proteomes. Conclusions Different etiologies of non-ischemic cardiomyopathies in advanced HF exhibit distinct proteomic expression despite shared pathologic findings. The benefit of tailored management strategies considering the different proteomic expressions in non-ischemic advanced HF requires further investigation.

Background: Axitinib, a potent and selective inhibitor of vascular endothelial growth factor (VEGF) receptor (VEGFR) tyrosine kinase 1,2 and 3, is used in chemotherapy because it inhibits tumor angiogenesis by blocking the VEGF/VEGFR pathway. In veterinary medicine, attempts have been made to apply tyrosine kinase inhibitors with anti-angiogenic effects to tumor patients, but there are no studies on axitinib in canine mammary gland tumors (MGTs). Objectives: This study aimed to confirm the antitumor activity of axitinib in canine mammary gland cell lines. Methods: We treated canine MGT cell lines (CIPp and CIPm) with axitinib and conducted CCK, wound healing, apoptosis, and cell cycle assays. Additionally, we evaluated the expression levels of angiogenesis-associated factors, including VEGFs, PDGF-A, FGF-2, and TGF-β1, using quantitative real-time polymerase chain reaction. Furthermore, we collected canine peripheral blood mononuclear cells (PBMCs), activated them with concanavalin A (ConA) and lipopolysaccharide (LPS), and then treated them with axitinib to investigate changes in viability. Results: When axitinib was administered to CIPp and CIPm, cell viability significantly decreased at 24, 48, and 72 h (p < 0.001), and migration was markedly reduced (6 h, p < 0.05; 12 h, p < 0.005). The apoptosis rate significantly increased (p < 0.01), and the G2/M phase ratio showed a significant increase (p < 0.001). Additionally, there was no significant change in the viability of canine PBMCs treated with LPS and ConA. Conclusion In this study, we confirmed the antitumor activity of axitinib against canine MGT cell lines. Accordingly, we suggest that axitinib can be applied as a new treatment for patients with canine MGTs.

Water beads are dangerous foreign bodies causing intestinal obstruction in young children because the beads absorb water and are radiolucent. Although the features lead to progressive intestinal obstruction, it is difficult to diagnose ingestion of the beads by imaging studies. For the diagnosis, ultrasonography is safe, fast, and accurate. The imaging modality can show intestinal water beads as spherical, anechoic, smoothly demarcated cysts. This characteristic finding may be more useful in rapid and accurate diagnosis than computed tomography scan. We report a case of an 8-month-old boy who obtained a timely sonographic diagnosis of water bead-induced small bowel obstruction in the emergency department.

Background: Mesenchymal stem cells (MSCs) have been investigated as therapeutic agents for inflammatory bowel disease (IBD). Stimulation of MSCs with pro-inflammatory cytokines is an approach to enhance their immunomodulatory effects. However, further investigation is required to support their application in immune-mediated disorders and companion animals. Objectives: This study aimed to assess the therapeutic effect of tumor necrosis factor (TNF)-α-stimulated feline adipose tissue-derived MSCs (fAT-MSCs) in a dextran sulfate sodium (DSS)-induced colitis mouse model. Methods: Colitis mice was made by drinking water with 3% DSS and fAT-MSCs were injected intraperitoneally. Colons were collected on day 10. The severity of the disease was evaluated and compared. Raw 264.7 cells were cultured with the conditioned medium to determine the mechanism, using quantitative real-time polymerase chain reaction and enzyme-linked immunosorbent assay. Results: TNF-α-stimulated fAT-MSCs more improved severity of DSS-induced colitis in disease activity, colon length, histologic score, and inflammatory cytokine. In sectionized colon tissues, the group comprising TNF-α-stimulated fAT-MSCs had higher proportion of CD11b + CD206 + macrophages than in the other groups. In vitro, TNF-α-stimulation increased cyclooxygenase-2 (COX-2) expression and prostaglandin E2 (PGE2 ) secretion from fAT-MSCs. The conditioned medium from TNF-α-stimulated fAT-MSCs enhanced the expression of interleukin-10 and arginase-1 in LPS-activated Raw 264.7 cells. Conclusions These results represent that TNF-α-stimulated fat-mscs ameliorate the inflamed colon more effectively. Furthermore, we demonstrated that the effectiveness was interlinked with the COX-2/PGE2 pathway.

Background: Several T-cell response assays for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) are available; however, their comparability and correlations with antibody responses remain unclear. We compared four SARS-CoV-2 T-cell response assays and two anti-SARS-CoV-2 spike antibody assays. Methods: We enrolled 89 participants who had received a booster dose of the BNT162b2 vaccine after two doses of the ChAdOx1 or BNT162b2 vaccine. Fifty-six participants without breakthrough infection (BI) (ChAdOx1/BNT162b2 group: N=27; BNT162b2 group: N=29) and 33 with BI were included. We evaluated two whole-blood interferon-gamma release assays (IGRAs) (QuantiFERON and Euroimmun), T-SPOT.COVID, an in-house enzyme-linked immunospot (ELISPOT) assay (targeting the spike and nucleocapsid peptides of wild-type and Omicron SARS-CoV-2), Abbott IgG II Quant, and Elecsys Anti-S, using Mann–Whitney U, Wilcoxon signed-rank, and Spearman’s correlation tests. Results: The correlations between the IGRAs and between the ELISPOT assays (ρ=0.60–0.70) were stronger than those between the IGRAs and ELISPOT assays (ρ=0.33–0.57). T-SPOT.COVID showed a strong correlation with Omicron ELISPOT (ρ=0.70). The anti-spike antibody assays showed moderate correlations with T-SPOT.COVID, Euroimmun IGRA, and ELISPOT (ρ=0.43–0.62). Correlations tended to be higher in the BI than in the noninfected group, indicating that infection induces a stronger immune response. Conclusions T-cell response assays show moderate to strong correlations, particularly when using the same platform. T-SPOT.COVID exhibits potential for estimating immune responses to the Omicron variant. To accurately define SARS-CoV-2 immune status, both T-cell and B-cell response measurements are necessary.

Purpose: Up to 20% of patients with biliary tract cancer (BTC) have alterations in DNA damage response (DDR) genes, including homologous recombination (HR) genes. Therefore, the DDR pathway could be a promising target for new drug development in BTC. We aim to investigate the anti-tumor effects using poly(ADP-ribose) polymerase (PARP) and WEE1 inhibitors in BTC. Materials and Methods: We used 10 BTC cell lines to evaluate an anti-tumor effect of olaparib (a PARP inhibitor) and AZD1775 (a WEE1 inhibitor) in in vitro. Additionally, we established SNU869 xenograft model for in vivo experiments. Results: In this study, we observed a modest anti-proliferative effect of olaparib. DNA double-strand break (DSB) and apoptosis were increased by olaparib in BTC cells. However, olaparib-induced DNA DSB was repaired through the HR pathway, and G2 arrest was induced to secure the time for repair. As AZD1775 typically regulates the G2/M checkpoint, we combined olaparib with AZD1775 to abrogate G2 arrest. We observed that AZD1775 downregulated p-CDK1, a G2/M cell cycle checkpoint protein, and induced early mitotic entry. AZD1775 also decreased CtIP and RAD51 expression and disrupted HR repair. In xenograft model, olaparib plus AZD1775 treatment reduced tumor growth more potently than did monotherapy with either drug. Conclusion This is the first study to suggest that olaparib combined with AZD1775 can induce synergistic anti-tumor effects against BTC. Combination therapy that blocks dual PARP and WEE1 has the potential to be further clinically developed for BTC patients.

Purpose: The soluble form programmed death-ligand 1 (sPDL1) has immunosuppressive properties and is being studied as a candidate biomarker for immuno-oncology drug development. We measured the serum sPDL1 at pre-and post-chemotherapy and evaluated its prognostic implication and dynamics during chemotherapy in advanced gastric cancer (GC). Materials and Methods: We prospectively enrolled 68 GC patients who were candidates for palliative standard first-line chemotherapy, and serially collected blood at baseline and after one cycle of chemotherapy, at the best response and after disease progression. sPDL1 was measured using an enzyme-linked immunosorbent assay. Response to chemotherapy, overall survival (OS), progressionfree survival (PFS) and other prognostic factors including neutrophil-lymphocyte ratio (NLR) were obtained. The cut-off value of sPDL1 levels for survival analysis was found using C-statistics. Results: The median baseline sPDL1 was 0.8 ng/mL (range, 0.06 to 6.06 ng/mL). The median OS and PFS were 14.9 months and 8.0 months, respectively. sPDL1 and NLR showed a weak positive correlation (Spearman’s rho=0.301, p=0.013). Patients with low levels of sPDL1 at diagnosis (< 1.92 ng/mL) showed a better OS and PFS than patients with a high sPDL1. The baseline sPDL1 before treatment was higher in the progressive disease group than in the stable disease and partial response groups. Patients whose sPDL1 increased after the first cycle of chemotherapy showed worse PFS and OS. Following disease progression, sPDL1 increased compared with the baseline. Conclusion sPDL1 at prechemotherapy confers a prognostic value for PFS and OS in GC patients under palliative first-line chemotherapy. Dynamics of sPDL1 during chemotherapy correlates with disease progression.