• BMB Reports
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• v.46 no.8
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• pp.422-427
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• 2013

Although BMP9 is highly capable of promoting osteogenic differentiation of mesenchymal stem cell (MSCs), the molecular mechanism involved remains to be fully elucidated. Here, we explore the possible involvement and detail role of JNKs (c-Jun N-terminal kinases) in BMP9-induced osteogenic differentiation of MSCs. It was found that BMP9 stimulated the activation of JNKs in MSCs. BMP9-induced osteogenic differentiation of MSCs was dramatically inhibited by JNKs inhibitor SP600125. Moreover, BMP9-activated Smads signaling was decreased by SP600125 treatment in MSCs. The effects of inhibitor are reproduced with adenoviruses expressing siRNA targeted JNKs. Taken together, our results revealed that JNKs was activated in BMP9-induced osteogenic differentiation of MSCs. What is most noteworthy, however, is that inhibition of JNKs activity resulted in reduction of BMP9-induced osteogenic differentiation of MSCs, implying that activation of JNKs is essential for BMP9 osteoinductive activity.

• Journal of Microbiology and Biotechnology
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• v.29 no.2
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• pp.230-234
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• 2019

Currently, the genetic modification of Aspergillus oryzae is mainly dependent on protoplast-mediated transformation (PMT). In this study, we established a dual selection marker system in an industrial A. oryzae 3.042 strain by using Agrobacterium tumefaciens-mediated transformation (ATMT). We first constructed a uridine/uracil auxotrophic A. oryzae 3.042 strain and a pyrithiamine (PT)-resistance binary vector. Then, we established the ATMT system by using uridine/uracil auxotrophy and PT-resistance genes as selection markers. Finally, a dual selection marker ATMT system was developed. This study demonstrates a useful dual selection marker transformation system for genetic manipulations of A. oryzae 3.042.

• Asian Pacific Journal of Cancer Prevention
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• v.15 no.21
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• pp.9077-9083
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• 2014

Background: This study aimed to summarize the potential diagnostic value of serum DKK1 levels in cancer detection. Materials and Methods: Serum DKK1 was measured using enzyme-linked immunosorbent assay in a case-control study. Then we performed a meta-analysis and the pooled sensitivity, specificity, diagnostic odds ratio, and summary receiver operating characteristic (sROC) curves were used to evaluate the overall test performance. Results: Serum DKK1 levels were found to be significantly upregulated in gastric cancer as compared to controls. ROC curve analysis revealed an AUC of 0.636, indicating the test has the potential to diagnose cancer with poor accuracy. The summary estimates of the pooled sensitivity, specificity and diagnostic odds ratio in meta-analysis were 0.55 with a 95% confidence interval (CI) (0.53-0.57), 0.86 (95%CI, 0.84-0.88) and 12.25 (95%CI, 5.31-28.28), respectively. The area under the sROC was 0.85. Subgroup analysis revealed that the diagnostic accuracy of serum DKK1 in lung cancer (sensitivity: 0.69 with 95%CI, 0.66-0.74; specificity: 0.95 with 95%CI, 0.92-0.97; diagnostic odds ratio: 44.93 with 95%CI, 26.19-77.08) was significantly higher than for any other cancer. Conclusions: Serum DKK1 might be useful as a noninvasive method for confirmation of cancer diagnosis, particularly in the case of lung cancer.

• BMB Reports
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• v.45 no.4
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• pp.247-252
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• 2012

Although previous studies have demonstrated that BMP9 is highly capable of inducing osteogenic differentiation of mesenchymal stem cells, the molecular mechanism involved remains to be fully elucidated. In this study, we showed that BMP9 simultaneously promotes the activation of Smad1/5/8, p38 and ERK1/2 in C3H10T1/2 cells. Knockdown of Smad4 with RNA interference reduced nuclear translocation of Smad1/5/8, and disrupted BMP9-induced osteogenic differentiation. BMP9-induced osteogenic differentiation was blocked by p38 inhibitor SB203580, whereas enhanced by ERK1/2 inhibitor PD98059. SB203580 decreased BMP9-activated Smads singling, and yet PD98059 stimulated Smads singling in C3H10T1/2 cells. The effects of inhibitor were reproduced with adenovirus expressing siRNA targeted p38 and ERK1/2, respectively. Taken together, our findings revealed that Smads, p38 and ERK1/2 are involved in BMP9-induced osteogenic differentiation. Also, it is noteworthy that p38 and ERK1/2 may play opposing regulatory roles in mediating BMP9-induced osteogenic differentiation of C3H10T1/2 cells.

• Korean Journal of Radiology
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• v.21 no.5
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• pp.550-560
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• 2020

Objective: To evaluate the interobserver agreement, diagnostic value, and associated clinical factors of automated breast ultrasound (ABUS) coronal features in differentiating breast lesions. Materials and Methods: This study enrolled 457 pathologically confirmed lesions in 387 female (age, 46.4 ± 10.3 years), including 377 masses and 80 non-mass lesions (NMLs). The unique coronal features, including retraction phenomenon, hyper- or hypoechoic rim (continuous or discontinuous), skipping sign, and white wall sign, were defined and recorded. The interobserver agreement on image type and coronal features was evaluated. Furthermore, clinical factors, including the lesion size, distance to the nipple or skin, palpability, and the histological grade were analyzed. Results: Among the 457 lesions, 296 were malignant and 161 were benign. The overall interobserver agreement for image type and all coronal features was moderate to good. For masses, the retraction phenomenon was significantly associated with malignancies (p < 0.001) and more frequently presented in small and superficial invasive carcinomas with a low histological grade (p = 0.027, 0.002, and < 0.001, respectively). Furthermore, continuous hyper- or hypoechoic rims were predictive of benign masses (p < 0.001), whereas discontinuous rims were predictive of malignancies (p < 0.001). A hyperechoic rim was more commonly detected in masses more distant from the nipple (p = 0.027), and a hypoechoic rim was more frequently found in large superficial masses (p < 0.001 for both). For NMLs, the skipping sign was a predictor of malignancies (p = 0.040). Conclusion: The coronal plane of ABUS may provide useful diagnostic value for breast lesions.

• Journal of Korean Medical classics
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• v.22 no.4
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• pp.241-247
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• 2009

Body constitution research in Korean traditional medicine adopt the diagnosis and treatment theory of "image-differentiation[body constitution differentiation, disease differentiation] in combination with syndrome differentiation diagnostic model and symptoms and signs of herbal property belong to image" as its core, which is key national medical science research project of State Administration of Traditional Chinese Medicine, the project brought up 4 key scientific problem ? body constitution differentiation theory, correlation theory of body constitution and disease, body constitution adjustable theory and symptoms and signs of herbal property belong to image theory. In body constitution pathology, it brought up "correlation between body constitution and symptoms", "differentiation between body constitution and symptoms" which increase the diagnostic level and diagnostic accuracy rate. In the condition of pathology, it obviously has low reliability according to body constitution differentiation, sometimes happen the description not comply with body constitution and disease symptoms, which lead to decrease the clinic diagnostic and treatment level, treatment effect not satisfying too. Now taking 4 key scientific achievement as criterion to illustrate the body constitution and disease symptoms.

• Asian Pacific Journal of Cancer Prevention
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• v.16 no.2
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• pp.551-557
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• 2015

Background: Differentiating morphologic features based on hematoxylin-eosin (HE) staining is the most common method to classify pathological subtypes of non-small-cell lung cancer (NSCLC). However, its accuracy and inter-observer reproducibility in pathological diagnosis of poorly differentiated NSCLC remained to be improved. Materials and Methods: We attempted to explore the role of immunohistochemistry (IHC) staining in diagnosing pulmonary squamous cell carcinoma (SQCC) with poorly differentiated features by HE staining or with elevated serum adenocarcinoma-specific tumor markers (AD-TMs). We also compared the difference of epidermal growth factor receptor (EGFR) mutation rate between patients with confirmed SQCC and those with revised pathological subtype. Logistic regression analyses were used to test the association between different factors and diagnostic accuracy. Results: A total of 132 patients who met the eligible criteria and had adequate specimens for IHC confirmation were included. Pathological revised cases in poor differentiated subgroup, biopsy samples and high-level AD-TMs cases were more than those with high/moderate differentiation, surgical specimens and normal-level AD-TMs. Moreover, biopsy sample was a significant factor decreasing diagnostic accuracy of pathological subtype (OR, 4.037; 95% CI 1.446-11.267, p=0.008). Additionally, EGFR mutation rate was higher in patients with pathological diagnostic changes than those with confirmed SQCC (16.7% vs 4.4%, p=0.157). Conclusions: Diagnosis based on HE staining only might cause pathological misinterpretation in NSCLC patients with poor differentiation or high-level AD-TMs, especially those with biopsy samples. HE staining and IHC should be combined as pathological diagnostic standard. The occurrence of EGFR mutations in pulmonary SQCC might be overestimated.

• Asian Pacific Journal of Cancer Prevention
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• v.15 no.8
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• pp.3525-3531
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• 2014

Objective: Fluorine-18-fluorodeoxyglucose positron emission tomography (18F-FDG-PET) is a new technique for identifying different malignant tumors using different uptake values between tumor cells and normal tissues. Here we assessed the diagnostic accuracy of 18F-FDG-PET in patients with testicular cancer by pooling data of existing trials in a meta-analysis. Methods: PubMed/MEDLINE, Embase and Cochrane Central Trials databases were searched and studies published in English relating to the diagnostic value of FDG-PET for testicular cancer were collected. The summary receiver operating characteristic (SROC) curve was used to examine the FDG-PET accuracy. Results: A total of 16 studies which included 957 examinations in 807 patients (median age, 31.1 years) were analyzed. A meta-analysis was performed to combine the sensitivity and specificity and their 95% confidence intervals (CIs), from diagnostic odds ratio (DOR), positive likelihood ratios (PLR), negative likelihood ratio (NLR). SROC were derived to demonstrate the diagnostic accuracy of FDG-PET for testicular cancer. The pooled sensitivity and specificity were 0.75 (95% confidence interval (CI), 0.70-0.80) and 0.87 (95% CI, 0.84-0.89), respectively. The pooled DOR was 35.6 (95% CI, 12.9-98.3). The area under the curve (AUC) was 0.88. The pooled PLR and pooled NLR were 7.80 (95% CI, 3.73-16.3) and 0.31 (95% CI, 0.23-0.43), respectively. Conclusion: In patients with testicular cancer, 18F-FDG-PET demonstrated a high SROC area, and could be a potentially useful tool if combined with other imaging methods such as MRI and CT. Nevertheless, the literature focusing on the use of 18F-FDG-PET in this setting still remains limited.

• The Journal of the Society of Korean Medicine Diagnostics
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• v.22 no.1
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• pp.1-10
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• 2018

Objectives The purpose of this study is to compare the representative differential diagnosis methods of blood stasis pattern used in Korea, China and Japan, and then to characterize each diagnostic method. Methods Through the journal databases, we have selected representative tools that were developed for differential diagnosis of blood stasis pattern in Korea, China and Japan. In order to characterize the selected check-lists or questionnaires, we investigated the number of items, contents, score calculation method, internal consistency, and accuracy of each selected tool. Results A total of four diagnostic tools were finally selected; quantitative diagnosis scale of blood stasis syndrome (QDSBSS), diagnostic criteria for blood stasis (DCBS), blood stasis questionnaire (BSQ), and blood stasis syndrome questionnaire (BSSQ). The key points in the differential diagnosis for blood stasis were different for each of the diagnostic tool. The key point was oral mucosa (including tongue) status in the QDSBSS. Meanwhile it was abdominal pain/resistance in the DCBS, and general pain in the BSQ. Accuracy of the QDSBSS, the BSQ and the BSSQ were powerful but all of them was not generalized. Conclusions Therefore, it is desirable to select and apply a plurality of appropriate tools according to the characteristics of the blood stasis patients.

• BMB Reports
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• v.46 no.2
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• pp.107-112
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• 2013

Although BMP6 is highly capable of inducing osteogenic differentiation of mesenchymal progenitor cells (MPCs), the molecular mechanism involved remains to be fully elucidated. Using dominant negative (dn) mutant form of type I and type II $TGF{\beta}$ receptors, we demonstrated that three dn-type I receptors (dnALK2, dnALK3, dnALK6), and three dn-type II receptors (dnBMPRII, dnActRII, dnActRIIB), effectively diminished BMP6-induced osteogenic differentiation of MPCs. These findings suggested that ALK2, ALK3, ALK6, BMPRII, ActRII and ActRIIB are essential for BMP6-induced osteogenic differentiation of MPCs. However, MPCs in this study do not express ActRIIB. Moreover, RNA interference of ALK2, ALK3, ALK6, BMPRII and ActRII inhibited BMP6-induced osteogenic differentiation in MPCs. Our results strongly suggested that BMP6-induced osteogenic differentiation of MPCs is mediated by its functional $TGF{\beta}$ receptors including ALK2, ALK3, ALK6, BMPRII, and ActRII.