Diminazene aceturate (DIZE), an angiotensin-converting enzyme 2 (ACE2) activator, exerts anti-inflammatory and antifibrotic effects in a variety of human chronic diseases. However, the role of DIZE in kidney fibrosis and the underlying mechanism remain unclear. Therefore, we investigated the effects of DIZE on the progression of renal fibrosis after unilateral ureteral obstruction (UUO), a well-established model of chronic kidney disease. Methods: C57BL/6 female or male mice were subjected to right UUO. Mice received 15 mg/kg DIZE or vehicle (saline) daily. On the 7th day after UUO, kidneys were collected for analysis of renal fibrosis (α-smooth muscle actin, phosphorylated SMAD3, transforming growth factor (TGF)-β, Masson’s trichrome, and Sirius red staining), inflammation (macrophage infiltration, proinflammatory cytokines/ chemokines), apoptosisecrotic cell death (TUNEL and periodic acid-Schiff staining), and ACE2 activity and messenger RNA (mRNA) expression. Results: Treatment with DIZE exacerbated renal fibrosis by upregulating the profibrotic TGF-β/SMAD3 pathway, proinflammatory cytokine/chemokines (interleukin [IL]-1β, monocyte chemoattractant protein-1, IL-6, and macrophage inflammatory protein-2) levels, M2 macrophage accumulation (CD206, IL-4, IL-10, and CX3CL1), and apoptoticecrotic cell death in the obstructed kidneys of female mice but not male mice. However, DIZE treatment had no effect on ACE2 activity or mRNA expression. Conclusion: DIZE exacerbates UUO-induced renal fibrosis by aggravating tubular damage, apoptosis, and inflammation through independent of angiotensin (1–7), angiotensin II levels, and ACE2 expression/activity, rather than protecting against renal fibrosis after UUO. DIZE also has powerful effects on recruiting macrophages, including the M2-polarized subtype, in female UUO mice.

Renal fibrosis is characterized by the accumulation of extracellular matrix and inflammatory cells and kidney dysfunction, which is a major pathway in the progression of chronic kidney disease (CKD). Accumulating evidence indicates that oxidative stress plays a critical role in the initiation and progression of CKD via proinflammatory and profibrotic signaling pathways. Fisetin (3,3′,4′,7-tetrahydroxyflavone) has biological activities including antioxidant, anti-inflammatory, and anti-aging effects. Therefore, we evaluated the antifibrotic effects of fisetin on unilateral ureteral obstruction (UUO)-induced kidneys. Methods: C57BL/6 female mice were subjected to right UUO and intraperitoneally injected every other day with fisetin (25 mg/kg/ day) or vehicle from 1 hour before surgery to 7 days after surgery. Kidney samples were analyzed for renal fibrosis (α-smooth muscle actin [α-SMA] expression, collagen deposition, and transforming growth factor [TGF] β1/SMAD3 signaling pathway), oxidative damage (4-HNE and 8-OHdG expression), inflammation (proinflammatory cytokine/chemokine, macrophage, and neutrophil infiltration), and apoptosis (TUNEL staining). Cultured human proximal tubule cells were treated with fisetin before TGF-β to confirm the TGF-β downstream pathway (SMAD2/3 phosphorylation). Results: We found that fisetin treatment protected against renal fibrosis by inhibiting the phosphorylation of SMAD3, oxidative damage, inflammation, apoptotic cell death, and accumulation of profibrotic M2 macrophages in the obstructed kidneys. In cultured human proximal tubular cells, fisetin treatment inhibited TGF-β1–induced phosphorylation of SMAD3 and SMAD2. Conclusion: Fisetin alleviates kidney fibrosis to protect against UUO-induced renal fibrosis, and could be a novel therapeutic drug for obstructive nephropathy.

Transmembrane protein 115 (TMEM115) is a membrane protein; considering the potential of membrane proteins as biomarkers for various pathological conditions, we aimed to examine the value of TMEM115 as a potential biomarker for improving the prognosis and treatment of liver hepatocellular carcinoma (LIHC) in this study. Online databases including the Tumor Immune Estimation Resource, UALCAN, Gene Expression Profiling Interactive Analysis version 2, OSlihc, and human Protein Atlas were used. The analysis suggested that TMEM115 expression in LIHC was higher compared to normal tissues; further, TMEM115 expression was confirmed to be related with poor prognosis in LIHC. Higher protein expression levels of TMEM115 were observed in LIHC tissues than in normal tissues. Tumor infiltration by immune cells was confirmed to be correlated with the expression of TMEM115. High TMEM115 expression and immune cell infiltration were further related to poor prognosis in LIHC. We also confirmed a correlation between TMEM115 and TP53 mutations. In conclusion, we confirmed that TMEM115 expression is correlated with tumor-infiltrating immune cells and poor prognosis in LIHC and that TMEM115 shows potential as a prognostic biomarker in LIHC.

Objectives: The prognostic significance of CDC42 effector protein 2 (CDC42EP2) and its association with tumor-infiltrating immune cells (TIICs) have not been explored in liver hepatocellular carcinoma (LIHC). This study aims to assess the potential prognostic value of CDC42EP2 by conducting a comprehensive analysis of online databases pertaining to LIHC. Methods: We evaluated the potential of CDC42EP2 as a prognostic biomarker by utilizing online databases such as TIMER, GEPIA2, KM, OSlihc, HPA, and LinkedOmics. Results: In LIHC, we observed that the mRNA and protein expression of CDC42EP2 were upregulated compared to normal tissues. Upregulated CDC42EP2 expression was associated with a worse prognosis based on the clinicopathological characteristics of patients with LIHC. Furthermore, CDC42EP2 was positively associated with TIICs. In the co-expression and functional enrichment analyses of CDC42EP2, 11,416 genes showed positive associations with CDC42EP2 while 8,008 genes showed negative associations. CDC42EP2-related co-expression genes were involved in protein localization to the endoplasmic reticulum, translational initiation, and RNA catabolic processes in gene set enrichment analysis-Gene Ontology (GSEA-GO), and regulated the ribosome, spliceosome, and primary immune deficiency in the GSEA-Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway. In a survival map, 23 and 17 genes that exhibited positive associations with CDC42EP2 showed a significant hazard ratio (HR) for overall survival and disease-free survival, respectively. Conclusion Our findings demonstrated that CDC42EP2 is a novel prognostic biomarker and a potential tumor immune therapeutic target in patients with LIHC.

DNA methyltransferase 3B (DNMT3B), one of DNA methyltransferases has many roles in DNA methylation and cancer pathogenesis. However, its clinical and prognostic value was not studied in hepatocellular carcinoma (HCC). In this study, we analyzed DNMT3B expression in HCC by public big data, The Cancer Genome Atlas. Primary data about total 360 HCC were downloaded and its clinicopathological implication was analyzed. M stage (p = 0.07) and pathologic stage (p = 0.04) were associated with DNMT3B expression, though M stage did not get a statistical significance. And alpha fetoprotein level was positively correlated with DNMT3B expression (p < 0.001). Higher DNMT3B expression predicted shorter overall survival in HCC patients (p < 0.05). Disease-free survival was shorter in HCC with lower DNMT3B expression, within borderline statistical significance (p = 0.081). It suggested that DNMT3B expression may have an important role in HCC prognosis and its detail mechanism should be confirmed further.

Glioblastoma multiforme (GBM) is the most lethal type of brain tumor and its prognosis was extremely poor. Here, we studied the clinical and prognostic value of telomerase reverse transcriptase (TERT) and GA Binding Protein Transcription Factor Subunit Beta 1 longer (GABPB1L) mRNA expression in GBM by using open big data. In total 152 GBM patients, gene expressions were downloaded from the Cancer Genome Atlas (TCGA) data and its values were statistically analyzed. TCGA data showed that GABPB1L mRNA expression levels did not correlate with those of TERT mRNA (r = -0.027, p = 0.744). GABPB1L and TERT expressions in GBM were associated with subtype by gene expression. GABPB1L (562.7 ± 76.8 days vs. 479.1 ± 5.8 days, p = 0.401) and TERT (468.1 ± 43.6 days vs. 565.3 ± 75.8 days, p = 0.403) expression was not associated with GBM prognosis. However, disease-free survival was tended to be different in GBM patients according to TERT and GABPB1L expressions though it did not get statistical significance (2122.6 ± 160.2 days vs. 1381.1 ± 244.0 days, p = 0.072). These genes may contribute to the GBM pathogenesis and its further study should be performed in GBM patients and cell lines.

Objectives: The aims of this study were to investigate the expression of Yes-associated protein 1 (YAP1), its prognostic significance, and the correlation between YAP1 and telomerase in various cancers. Methods: The Gene Expression Profiling Interactive Analysis database was used to analyze RNA sequencing data and the survival rate of patients with various cancers in The Cancer Genome Atlas (TCGA) database. PrognoScan was used to analyze the prognostic value of YAP1 expression in various cancers. Tumor Immune Estimation Resource was used to determine the correlation between YAP1 expression and telomerase in various cancer types based on TCGA data. Results: The analysis suggested that YAP1 was differentially expressed between tissues of various cancers and non-tumor tissues. High YAP1 expression was also related to a poor prognosis in adrenocortical carcinoma, bladder urothelial carcinoma, and pancreatic adenocarcinoma. Moreover, YAP1 expression was correlated with the expression of telomerase reverse transcriptase and telomerase RNA component in various cancer types. Conclusion These results suggest that YAP1 is a potential biomarker with prognostic significance and relevance for oncogene research in various cancer types. The correlation between the expression of YAP1 and telomere-associated genes will help to understand their cancer-promoting mechanisms and interactions.

Anatomy is knowledge about structure and function of human body. However, with on medical course the vast amount of content, many students have difficulties and burdens about anatomy. The purpose of this study was to investigate the effect of bingo game to improve understanding and learning effect of anatomy. This study was carried out in September, 2018, at 53 medical students. After conducting the bingo, the students were asked about the usefulness, grade reflection, concern, continuation, necessity, appropriate time and interest of bingo. And the relationship between bingo results and grades was also investigated. A total of seven bingo games were with an average of 3.6 bingo (0-11). There was a positive response to the usefulness (3.74 ± 0.92), interest (3.94 ± 0.82), continuation (3.55 ± 1.10), necessity (3.51 ± 1.01), and concern (3.72 ± 1.01) of bingo. However, the appropriateness of the time was neutral (3.26 ± 1.02), and there were negative opinions about grade reflection of bingo (1.40 ± 0.86). The grade of anatomy subject showed a positive correlation with the results of the bingo, but did not reach statistical significance (r = 207, p = 0.088). In addition to anatomy, histology, microbiology, and pharmacology were also considered to be useful educational methods for bingo. Bingo may be useful in medical school curriculum, especially in Anatomy. More research is needed to improve learning efficiency through bingo.

Anatomy is knowledge about structure and function of human body. However, with on medical course the vast amount of content, many students have difficulties and burdens about anatomy. The purpose of this study was to investigate the effect of bingo game to improve understanding and learning effect of anatomy. This study was carried out in September, 2018, at 53 medical students. After conducting the bingo, the students were asked about the usefulness, grade reflection, concern, continuation, necessity, appropriate time and interest of bingo. And the relationship between bingo results and grades was also investigated. A total of seven bingo games were with an average of 3.6 bingo (0-11). There was a positive response to the usefulness (3.74 ± 0.92), interest (3.94 ± 0.82), continuation (3.55 ± 1.10), necessity (3.51 ± 1.01), and concern (3.72 ± 1.01) of bingo. However, the appropriateness of the time was neutral (3.26 ± 1.02), and there were negative opinions about grade reflection of bingo (1.40 ± 0.86). The grade of anatomy subject showed a positive correlation with the results of the bingo, but did not reach statistical significance (r = 207, p = 0.088). In addition to anatomy, histology, microbiology, and pharmacology were also considered to be useful educational methods for bingo. Bingo may be useful in medical school curriculum, especially in Anatomy. More research is needed to improve learning efficiency through bingo.

BACKGROUND: Rapid identification of the causative agent among potential bacterial and viral pathogens is important for the management of acute respiratory disease. In this study, we evaluated the analytical performance and clinical usefulness of a recently-introduced multiplex PCR assay, Seeplex(TM)Pneumobacter detection kit (Seegene Inc., Korea) for the identification of respiratory bacterial pathogens. METHODS: One hundred and eighty one nasopharyngeal aspirates were collected from pediatric patients with respiratory symptoms and analysed by multiplex PCR for the detection of Streptococcus pneumoniae (S.P), Haemophilus influenzae (H.I), Mycoplasma pneumoniae (M.P), Chlamydophila pneumoniae (C.P), Bordetella pertussis (B.P) and Legionella pneumophila (L.P). A comparison of multiplex PCR with conventional culture for the isolation of S.P and H.I was performed on 112 specimens. The cross reactivity of multiplex PCR was also evaluated. RESULTS: Of 181 cases, 81 cases were positive by multiplex PCR (44.8%): 52 cases for S.P (28.7%), 47 cases for H.I (26.0%), 9 cases for M.P (5.0%), 3 cases for B.P (1.7%) and 1 case for C.P (0.6%) including multiple infection cases. The agreement rates between multiplex PCR and culture for S.P and H.I were 92.9% (kappa index=0.84, P<0.001) and 91.1% (kappa index=0.75, P<0.001), respectively. There was no cross reactivity with common bacterial and viral pathogens. CONCLUSIONS: Seeplex(TM) Pneumobacter detection kit could be a useful screening tool for the rapid detection of respiratory bacterial pathogens. Further studies with lower respiratory tract specimens would be needed for the clinical evaluation of S. pneumoniae and H. influenzae detected by multiplex PCR.
Adolescent ; Bacterial Infections/*diagnosis ; Child ; Child, Preschool ; DNA, Bacterial/analysis ; Female ; Humans ; Infant ; Infant, Newborn ; Male ; Mycoplasma pneumoniae/*isolation & purification ; Pneumonia, Mycoplasma/diagnosis ; *Polymerase Chain Reaction ; Reagent Kits, Diagnostic ; Respiratory Tract Infections/*diagnosis/microbiology ; Sensitivity and Specificity