Runx2 heterozygosity alters homeostasis of the periodontal complex.

BACKGROUND AND OBJECTIVE: Haploinsufficiency of Runx2 (Runx2+/- ) causes dental anomalies. However, little is known about the involvement of Runx2 in the maintenance of dentin, cementum, and the periodontal ligament (PDL) during adulthood. This study aimed to observe the effects of Runx2+/- on homeostasis of the periodontal complex. MATERIALS AND METHODS: A total of 14 three-month-old Runx2+/- mice and their wild-type littermates were examined using micro-computed tomography, histology, and immunohistochemistry. Phenotypic alterations in the dentin, cementum, and PDL were characterized and quantified. RESULTS: Haploinsufficiency of Runx2 caused cellular changes in the PDL space including reduction of cell proliferation and apoptosis, and irregular attachment of the collagen fibers in the PDL space into the cementum. Absence of continuous thickness of cementum was also observed in Runx2+/- mice. CONCLUSION: Runx2 is critical for cementum integrity and attachment of periodontal fibers. Because of its importance to cementum homeostasis, Runx2 is essential for homeostasis of periodontal complex.

Regulation of nuclear DNA damage response by mitochondrial morphofunctional pathway.

Cells are constantly challenged by genotoxic stresses that can lead to genome instability. The integrity of the nuclear genome is preserved by the DNA damage response (DDR) and repair. Additionally, these stresses can induce mitochondria to transiently hyperfuse; however, it remains unclear whether canonical DDR is linked to these mitochondrial morphological changes. Here, we report that the abolition of mitochondrial fusion causes a substantial defect in the ATM-mediated DDR signaling. This deficiency is overcome by the restoration of mitochondria fusion. In cells with fragmented mitochondria, genotoxic stress-induced activation of JNK and its translocation to DNA lesion are lost. Importantly, the mitochondrial fusion machinery of MFN1/MFN2 associates with Sab (SH3BP5) and JNK, and these interactions are indispensable for the Sab-mediated activation of JNK and the ATM-mediated DDR signaling. Accordingly, the formation of BRCA1 and 53BP1 foci, as well as homology and end-joining repair are impaired in cells with fragmented mitochondria. Together, these data show that mitochondrial fusion-dependent JNK signaling is essential for the DDR, providing vital insight into the integration of nuclear and cytoplasmic stress signals.

Development of nucleocapsid-specific monoclonal antibodies for SARS-CoV-2 and their ELISA diagnostics on an automatic microfluidic device.

Coronavirus disease 2019 (COVID-19) pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection has threatened public health globally, and the emergence of viral variants has exacerbated an already precarious situation. To prevent further spread of the virus and determine government action required for virus control, accurate and rapid immunoassays for SARS-CoV-2 diagnosis are urgently needed. In this study, we generated monoclonal antibodies (mAbs) against the SARS-CoV-2 nucleocapsid protein (NP), compared their reactivity using an enzyme-linked immunosorbent assay (ELISA), and selected four mAbs designated 1G6, 3E10, 3F10, and 5B6 which have higher reactivity to NP and viral lysates of SARS-CoV-2 than other mAbs. Using an epitope mapping assay, we identified that 1G6 detected the C-terminal domain of SARS-CoV-2 NP (residues 248-364), while 3E10 and 3F10 bound to the N-terminal domain (residues 47-174) and 3F10 detected the N-arm region (residues 1-46) of SARS-CoV-2 NP. Based on the epitope study and sandwich ELISA, we selected the 1G6 and 3E10 Abs as an optimal Ab pair and applied them for a microfluidics-based point-of-care (POC) ELISA assay to detect the NPs of SARS-CoV-2 and its variants. The integrated and automatic microfluidic system could operate the serial injection of the sample, the washing solution, the HRP-conjugate antibody, and the TMB substrate solution simply by controlling air purge via a single syringe. The proposed Ab pair-equipped microsystem effectively detected the NPs of SARS-CoV-2 variants as well as in clinical samples. Collectively, our proposed platform provides an advanced protein-based diagnostic tool for detecting SARS-CoV-2.

A Versatile Strategy for Achieving Fast-Charging Batteries via Interfacial Engineering: Pseudocapacitive Potassium Storage without Nanostructuring.

The rapid transport of alkali ions in electrodes is a long-time dream for fast-charging batteries. Though electrode nanostructuring has increased the rate-capability, its practical use is limited because of the low tap density and severe irreversible reactions. Therefore, development of a strategy to design fast-charging micron-sized electrodes without nanostructuring is of significant importance. Herein, a simple and versatile strategy to accelerate the alkali ion diffusion behavior in micron-sized electrode is reported. It is demonstrated that the diffusion rate of K+ ions is significantly improved at the hetero-interface between orthorhombic Nb2 O5 (001) and monoclinic MoO2 (110) planes. Lattice distortion at the hetero-interface generates an inner space large enough for the facile transport of K+ ions, and electron localization near oxygen-vacant sites further enhances the ion diffusion behavior. As a result, the interfacial-engineered micron-sized anode material achieves an outstanding rate capability in potassium-ion batteries (KIBs), even higher than nanostructured orthorhombic Nb2 O5  which is famous for fast-charging electrodes. This is the first study to develop an intercalation pseudocapacitive micron-sized anode without nanostructuring for fast-charging and high volumetric energy density KIBs. More interestingly, this strategy is not limited to K+ ion, but also applicable to Li+ ion, implying the versatility of interfacial engineering for alkali ion batteries.

Driving Simulator Brake Reaction Parameters After Total Hip Arthroplasty According to Different Surgical Approaches.

BACKGROUND: The aim of this study is to validate the point of normalization of braking following total hip arthroplasty (THA) and to determine the relevance of the surgical approach. METHODS: Brake reaction parameters (BRPs), including brake reaction time, total brake time, and brake pedal depression force were measured in 90 patients who underwent primary arthroplasty of the right hip (42 with direct anterior approach and 48 with posterolateral approach) using a modern driving simulator. The driving parameters were measured preoperatively and every 2 weeks postoperatively until the eighth week. BRPs were measured in 40 subjects without hip problems, and the results were used as a control. Statistical assessment was performed to analyze when the patients' reaction to braking recovered to that of the control group with respect to different surgical approaches and also according to the pain. RESULTS: Preoperative BRPs of the patients undergoing THA were prolonged compared to the control group and were normalized at the sixth week following the operation. Although BRPs of the direct anterior approach group showed significantly better improvement compared to the posterolateral approach group (total brake time at week 2, brake reaction time and brake pedal depression at week 4), both groups reached baseline value at week 6. In addition, we found no correlation between the pain score and BRPs. CONCLUSION: The results of the current study indicate that the response to braking events normalizes at 6 weeks following THA in young active patients and is irrelevant to the surgical approach.

Polymer Interface-Dependent Morphological Transition toward Two-Dimensional Porous Inorganic Nanocoins as an Ultrathin Multifunctional Layer for Stable Lithium-Sulfur Batteries.

Two-dimensional (2D) porous inorganic nanomaterials have intriguing properties as a result of dimensional features and high porosity, but controlled production of circular 2D shapes is still challenging. Here, we designed a simple approach to produce 2D porous inorganic nanocoins (NCs) by integrating block copolymer (BCP) self-assembly and orientation control of microdomains at polymer-polymer interfaces. Multicomponent blends containing BCP and homopoly(methyl methacrylate) (hPMMA) are designed to undergo macrophase separation followed by microphase separation. The balanced interfacial compatibility of BCP allows perpendicularly oriented lamellar-assembly at the interfaces between BCP-rich phase and hPMMA matrix. Disassembly of lamellar structures and calcination yield ultrathin 2D inorganic NCs that are perforated by micropores. This approach enables control of the thickness, size, and chemical composition of the NCs. 2D porous and acidic aluminosilicate NC (AS-NC) is used to fabricate an ultrathin and lightweight functional separator for lithium-sulfur batteries. The AS-NC layer acts as an ionic sieve to selectively block lithium polysulfides. Abundant acid sites chemically capture polysulfides, and micropores physically exclude them, so sulfur utilization and cycle stability are increased.

Synthesis and evaluation of sulfonyl piperazine LpxH inhibitors.

The UDP-2,3-diacylglucosamine pyrophosphate hydrolase LpxH is essential in lipid A biosynthesis and has emerged as a promising target for the development of novel antibiotics against multidrug-resistant Gram-negative pathogens. Recently, we reported the crystal structure of Klebsiella pneumoniae LpxH in complex with 1 (AZ1), a sulfonyl piperazine LpxH inhibitor. The analysis of the LpxH-AZ1 co-crystal structure and ligand dynamics led to the design of 2 (JH-LPH-28) and 3 (JH-LPH-33) with enhanced LpxH inhibition. In order to harness our recent findings, we prepared and evaluated a series of sulfonyl piperazine analogs with modifications in the phenyl and N-acetyl groups of 3. Herein, we describe the synthesis and structure-activity relationship of sulfonyl piperazine LpxH inhibitors. We also report the structural analysis of an extended N-acyl chain analog 27b (JH-LPH-41) in complex with K. pneumoniae LpxH, revealing that 27b reaches an untapped polar pocket near the di-manganese cluster in the active site of K. pneumoniae LpxH. We expect that our findings will provide designing principles for new LpxH inhibitors and establish important frameworks for the future development of antibiotics against multidrug-resistant Gram-negative pathogens.

Cyclic Peptide Mimotopes for the Detection of Serum Anti-ATIC Autoantibody Biomarker in Hepato-Cellular Carcinoma.

Tumor-associated (TA) autoantibodies have been identified at the early tumor stage before developing clinical symptoms, which holds hope for early cancer diagnosis. We identified a TA autoantibody from HBx-transgenic (HBx-tg) hepatocellular carcinoma (HCC) model mouse, characterized its target antigen, and examined its relationship to human HCC. The mimotopes corresponding to the antigenic epitope of TA autoantibody were screened from a random cyclic peptide library and used for the detection of serum TA autoantibody. The target antigen of the TA autoantibody was identified as an oncogenic bi-functional purine biosynthesis protein, ATIC. It was upregulated in liver cancer tissues of HBx-tg mouse as well as human HCC tissues. Over-expressed ATIC was also secreted extracellularly via the cancer-derived exosomes, which might cause auto-immune responses. The cyclic peptide mimotope with a high affinity to anti-ATIC autoantibody, CLPSWFHRC, distinguishes between serum samples from HCC patients and healthy subjects with 70.83% sensitivity, 90.68% specificity (AUC = 0.87). However, the recombinant human ATIC protein showed a low affinity to anti-ATIC autoantibody, which may be incompatible as a capture antigen for serum TA autoantibody. This study indicates that anti-ATIC autoantibody can be a potential HCC-associated serum biomarker and suggests that autoantibody biomarker's efficiency can be improved by using antigenic mimicry to native antigens present in vivo.

Rose (Rosa gallica) Petal Extract Suppress Proliferation, Migration, and Invasion of Human Lung Adenocarcinoma A549 Cells through via the EGFR Signaling Pathway.

We sought to investigate the effect of rose petal extract (RPE) on the proliferation, migration, and invasion of cancer cells. RPE significantly inhibited the growth of lung and colorectal cancer cell lines, with rapid suppression of A549 lung cancer cells at low concentrations. These effects occurred concomitantly with downregulation of the cell proliferation mediators PCNA, cyclin D1, and c-myc. In addition, RPE suppressed the migration and invasion of A549 cells by inhibiting the expression and activity of matrix metalloproteinase-2 and matrix metalloproteinase-9 (MMP-2 and -9). We hypothesize that the suppressive activity of RPE against lung cancer cell proliferation and early metastasis occurs via the EGFR-MAPK and mTOR-Akt signaling pathways. These early results highlight the significant potency of RPE, particularly for lung cancer cells, and warrant further investigation.

Red Ginseng Improves Exercise Endurance by Promoting Mitochondrial Biogenesis and Myoblast Differentiation.

Red ginseng has been reported to elicit various therapeutic effects relevant to cancer, diabetes, neurodegenerative diseases, and inflammatory diseases. However, the effect of red ginseng on exercise endurance and skeletal muscle function remains unclear. Herein, we sought to investigate whether red ginseng could affect exercise endurance and examined its molecular mechanism. Mice were fed with red ginseng extract (RG) and undertook swimming exercises to determine the time to exhaustion. Animals fed with RG had significantly longer swimming endurance. RG treatment was also observed to enhance ATP production levels in myoblasts. RG increased mRNA expressions of mitochondrial biogenesis regulators, NRF-1, TFAM, and PGC-1α, which was accompanied by an elevation in mitochondrial DNA, suggesting an enhancement in mitochondrial energy-generating capacity. Importantly, RG treatment induced phosphorylation of p38 and AMPK and upregulated PGC1α expression in both myoblasts and in vivo muscle tissue. In addition, RG treatment also stimulated C2C12 myogenic differentiation. Our findings show that red ginseng improves exercise endurance, suggesting that it may have applications in supporting skeletal muscle function and exercise performance.

Delphinidin inhibits epidermal growth factor-induced epithelial-to-mesenchymal transition in hepatocellular carcinoma cells.

Epithelial-to-mesenchymal transition (EMT), important cellular process in metastasis of primary tumors, is characterized by loss of their cell polarity, disruption of cell-cell adhesion, and gain certain properties of mesenchymal phenotype that enable migration and invasion. Delphinidin is a member of anthocyanidin belong to flavonoid groups, known as having pharmacological and physiological effects including anti-tumorigenic, antioxidative, anti-inflammatory, and antiangiogenic effects. However, the effects of delphinidin on EMT is rarely investigated. Epidermal growth factor (EGF) is known as a crucial inducer of EMT in various cancer including hepatocellular carcinoma (HCC). To determine whether delphinidin inhibits EGF-induced EMT in HCC cells, antiproliferative effect of delphinidin on Huh7 and PLC/PRF/5 cells were measured by Cell Counting Kit-8 assay. As a result, delphinidin inhibited cell proliferation in a dose-dependent manner. Based on the result of proliferation, to measure the effects of delphinidin on EGF-induced EMT, we designated a proper concentration of delphinidin, which is not affected to cell proliferation. We found that delphinidin inhibits morphological changes from epithelial to mesenchymal phenotype by EGF. Moreover, delphinidin increased the messenger RNA and protein expression of E-cadherin and decreased those of Vimentin and Snail in EGF-induced HCC cells. Also, delphinidin prevented motility and invasiveness of EGF-induced HCC cells through suppressing activation of matrix metalloproteinase 2, EGF receptor (EGFR), AKT, and extracellular signal-regulated kinase (ERK). Taken together, our findings demonstrate that delphinidin inhibits EGF-induced EMT by inhibiting EGFR/AKT/ERK signaling pathway in HCC cells.

Artificial Intelligent Model With Neural Network Machine Learning for the Diagnosis of Orthognathic Surgery.

Diagnosis and treatment planning are the most important steps in the orthognathic surgery for the successful treatment. The purpose of this study was to develop a new artificial intelligent model for surgery/non-surgery decision and extraction determination, and to evaluate the performance of this model. The sample used in this study consisted of 316 patients in total. Of the total sample, 160 were planned with surgical treatment and 156 were planned with non-surgical treatment. The input values of artificial neural network were obtained from 12 measurement values of the lateral cephalogram and 6 additional indexes. The artificial intelligent model of machine learning consisted of 2-layer neural network with one hidden layer. The learning was carried out in 3 stages, and 4 best performing models were adopted. Using these models, decision-making success rates of surgery/non-surgery, surgery type, and extraction/non-extraction were calculated. The final diagnosis success rate was calculated by comparing the actual diagnosis with the diagnosis obtained by the artificial intelligent model. The success rate of the model showed 96% for the diagnosis of surgery/non-surgery decision, and showed 91% for the detailed diagnosis of surgery type and extraction decision. This study suggests the artificial intelligent model using neural network machine learning could be applied for the diagnosis of orthognathic surgery cases.

Microbial changes in biofilms on composite resins with different surface roughness: An in vitro study with a multispecies biofilm model.

STATEMENT OF PROBLEM: The single-species biofilm method cannot represent the interaction and complex functions of microorganisms associated with oral biofilms. PURPOSE: The purpose of this in vitro study was to investigate microbial changes in biofilms on composite resins of varying surface roughness by using a multispecies biofilm model with early-colonizing streptococci, middle colonizer, and late-colonizing gram-negative anaerobes. MATERIAL AND METHODS: Composite resin disks were prepared with different roughness: SR180, SR400, SR1500, and SRGlass roughened with 180-, 400-, and 1500-grit silicon carbide paper and glass (control surface without surface roughening). Surface roughness was analyzed by confocal laser scanning and scanning electron microscopy. After multispecies biofilms had been grown on the composite resin surfaces, the adhesion of Streptococcus mutans, Streptococcus sobrinus, Porphyromonas gingivalis, Aggregatibacter actinomycetemcomitans, and of total bacteria was determined after 1 (T1) and 4 (T2) days. Differences in surface roughness among the 4 groups were tested with 1-way ANOVA. Multifactorial analysis of variance was used to determine the time-related differences in the bacterial composition with respect to surface roughness (α=.05). RESULTS: The order of SR, from highest to lowest, was SR180 (1.45 ±0.11 µm), SR400 (0.62 ±0.05 µm), SR1500 (0.35 ±0.02 µm), and SRGlass (0.15 ±0.01 µm) (SR180>SR400>SR1500>SRGlass, P<.001). Increased surface roughness was not proportional to bacterial adhesion. Significant differences in the adhesion of total bacteria was only found between SRGlass and SR180 (SR180>SRGlass, P=.029). The adhesion of S. mutans and S. sobrinus to SR180 and SR400 was higher than that to SRGlass (SR180=SR400>SRGlass; S. mutans, P=.003; S. sobrinus, P=.002). However, the adhesion of A. actinomycetemcomitans and P. gingivalis to composite resin was not significantly influenced by surface roughness. Adhesion of total bacteria, S. mutans, and S. sobrinus increased from T1 to T2 (T1T2; A. actinomycetemcomitans, P<.001; P. gingivalis, P=.013). CONCLUSIONS: Decreased adhesion of cariogenic streptococci and total bacteria was observed at surface roughness values of around 0.15 µm. Periodic finishing of surface roughness should be considered to minimize the adhesion of cariogenic streptococci to composite resin surfaces.

A Comprehensive Review of Materials with Catalytic Effects in Li-S Batteries: Enhanced Redox Kinetics.

Lithium-sulfur batteries (LSBs) are cost-effective and high-energy-density batteries. However, the insulating nature of active materials, the shuttle effect, and slow redox kinetics lead to severe capacity decay and low rate capabilities. Numerous multimodal approaches have been attempted to tackle these issues and have pushed the cycle stability and energy density to higher levels. Recently, accelerating the redox kinetics using catalytic materials has been considered as a means to realize high-performance LSBs. In this Minireview, we provide an insightful overview of the advances in the design of LSB catalytic materials and mechanistic descriptions of their catalytic activities.

Identification of anti-SF3B1 autoantibody as a diagnostic marker in patients with hepatocellular carcinoma.

BACKGROUND: Tumor-associated (TA) autoantibodies, which are generated by the immune system upon the recognition of abnormal TA antigens, are promising biomarkers for the early detection of tumors. In order to detect autoantibody biomarkers effectively, antibody-specific epitopes in the diagnostic test should maintain the specific conformations that are as close as possible to those presenting in the body. However, when using patients' serum as a source of TA autoantibodies the characterization of the autoantibody-specific epitope is not easy due to the limited amount of patient-derived serum. METHODS: To overcome these limits, we constructed a B cell hybridoma pool derived from a hepatocellular carcinoma (HCC) model HBx-transgenic mouse and characterized autoantibodies derived from them as tumor biomarkers. Their target antigens were identified by mass spectrometry and the correlations with HCC were examined. With the assumption that TA autoantibodies generated in the tumor mouse model are induced in human cancer patients, the enzyme-linked immunosorbent assays (ELISA) based on the characteristics of mouse TA autoantibodies were developed for the detection of autoantibody biomarkers in human serum. To mimic natural antigenic structures, the specific epitopes against autoantibodies were screened from the phage display cyclic random heptapeptide library, and the streptavidin antigens fused with the specific epitopes were used as coating antigens. RESULTS: In this study, one of HCC-associated autoantibodies derived from HBx-transgenic mouse, XC24, was characterized. Its target antigen was identified as splicing factor 3b subunit 1 (SF3B1) and the high expression of SF3B1 was confirmed in HCC tissues. The specific peptide epitopes against XC24 were selected and, among them, XC24p11 cyclic peptide (-CDATPPRLC-) was used as an epitope of anti-SF3B1 autoantibody ELISA. With this epitope, we could effectively distinguish between serum samples from HCC patients (n = 102) and healthy subjects (n = 85) with 73.53% sensitivity and 91.76% specificity (AUC = 0.8731). Moreover, the simultaneous detection of anti-XC24p11 epitope autoantibody and AFP enhanced the efficiency of HCC diagnosis with 87.25% sensitivity and 90.59% specificity (AUC = 0.9081). CONCLUSIONS: ELISA using XC24p11 peptide epitope that reacts against anti-SF3B1 autoantibody can be used as a novel test to enhance the diagnostic efficiency of HCC.

Dioscin suppresses TGF-ß1-induced epithelial-mesenchymal transition and suppresses A549 lung cancer migration and invasion.

Epithelial-to-mesenchymal transition (EMT), an important cellular process, occurs during cancer development and progression, has a crucial role in metastasis by enhancing the motility of tumor cells. Dioscin is a polyphenolic component isolated from Phyllanthus amarus, which exhibits a wide range of pharmacological and physiological activities, such as anti-tumor, anti-inflammatory, anti-obesity, anti-fungal, and anti-viral activities. However, the possible role of dioscin in the EMT is unclear. We investigated the suppressive effect of dioscin on the EMT. Transforming growth factor-beta 1 (TGF-ß1) is known to induce EMT in a number of cancer cell types and promote lung adenocarcinoma migration and invasion. To verify the inhibitory role of dioscin in lung cancer migration and invasion, we investigated the use of dioscin as inhibitors of TGF-ß1-induced EMT in A549 lung cancer cells in vitro. Here, we found that dioscin prominently increased expression of the epithelial marker E-cadherin and expression of the mesenchymal marker N-cadherin and Snail during the TGF-ß1-induced EMT. In addition, dioscin inhibited the TGF-ß1-induced increase in cell migration and invasion of A549 lung cancer cells. Also, dioscin remarkably inhibited TGF-ß1-regulated activation of MMP-2/9, Smad2, and p38. Taken together, our findings provide new evidence that dioscin suppresses lung cancer migration, and invasion in vitro by inhibiting the TGF-ß1-induced EMT.

Combined treatment with zingerone and its novel derivative synergistically inhibits TGF-ß1 induced epithelial-mesenchymal transition, migration and invasion of human hepatocellular carcinoma cells.

The epithelial-mesenchymal transition (EMT) is an important cellular process during which polarized epithelial cells become motile mesenchymal cells, which promote cancer metastasis. Ginger, the rhizome of Zingiber officinale, is extensively used in cooking worldwide and also as a traditional medicinal herb with antioxidant, anti-inflammatory and anticancer properties. Several pungent compounds have been identified in ginger, including zingerone, which has anticancer potential. However, the role of zingerone in EMT is unclear. We investigated the synergistic effect of zingerone and its derivative on EMT. Transforming growth factor-beta 1 (TGF-ß1) induces the EMT to promote hepatocellular carcinoma metastasis, including migration and invasion. To understand the repressive role of the combination of zingerone and its derivative (ZD 2) in hepatocellular carcinoma metastasis, we investigated the potential use of each compound of ginger, such as zingerone, ZD 2 and 6-shogaol, or the mixture of zingerone and ZD 2 (ZD 2-1) as inhibitors of TGF-ß1 induced EMT development in SNU182 hepatocellular carcinoma cells in vitro. We show that ZD 2-1, but not zingerone, ZD 2 and 6-shogaol significantly increased expression of the epithelial marker E-cadherin and repressed Snail upregulation and expression of the mesenchymal marker N-cadherin during initiation of the TGF-ß1 induced EMT. In addition, ZD 2-1 inhibited the TGF-ß1 induced increase in cell migration and invasion of SNU182 hepatocellular carcinoma cells. Furthermore, ZD 2-1 significantly inhibited TGF-ß1 regulated matrix metalloproteinase-2/9 and activation of Smad2/3. We also found that ZD 2-1 inhibited nuclear translocation of NF-κB, activation of p42/44 MAPK/AP1 signaling pathway in the TGF-ß1 induced EMT. Our findings provide new evidence that combined treatment with ZD 2, novel zingerone derivative, and zingerone synergistically suppresses hepatocellular carcinoma metastasis in vitro by inhibiting the TGF-ß1 induced EMT.

Delphinidin inhibits BDNF-induced migration and invasion in SKOV3 ovarian cancer cells.

Brain-derived neurotrophic factor (BDNF), the TrkB ligand, is associated with aggressive malignant behavior, including migration and invasion, in tumor cells and a poor prognosis in patients with various types of cancer. Delphinidin is a diphenylpropane-based polyphenolic ring structure-harboring compound, which exhibits a wide range of pharmacological activities, anti-tumor, anti-oxidant, anti-inflammatory, anti-angiogenic and anti-mutagenic activity. However, the possible role of delphinidin in the cancer migration and invasion is unclear. We investigated the suppressive effect of delphinidin on the cancer migration and invasion. Thus, we found that BDNF enhanced cancer migration and invasion in SKOV3 ovarian cancer cell. To exam the inhibitory role of delphinidin in SKOV3 ovarian cancer migration and invasion, we investigated the use of delphinidin as inhibitors of BDNF-induced motility and invasiveness in SKOV3 ovarian cancer cells in vitro. Here, we found that delphinidin prominently inhibited the BDNF-induced increase in cell migration and invasion of SKOV3 ovarian cancer cells. Furthermore, delphinidin remarkably inhibited BDNF-stimulated expression of MMP-2 and MMP-9. Also, delphinidin antagonized the phosphorylation of Akt and nuclear translocation of NF-κB permitted by the BDNF in SKOV3 ovarian cancer cells. Taken together, our findings provide new evidence that delphinidin suppressed the BDNF-induced ovarian cancer migration and invasion through decreasing of Akt activation.

Effect of yttrium-90 radioembolization on outcomes in Asian patients with early to advanced stage hepatocellular carcinoma.

AIM: The aim of this study was to investigate the effect of yttrium-90 radioembolization on the outcome of Asian patients with early to advanced stage hepatocellular carcinoma (HCC). METHODS: Sixty-two patients were screened and 50 patients (80.6%) were eligible. Response was evaluated using the Response Evaluation Criteria in Solid Tumors (RECIST), and overall survival was estimated using the Kaplan-Meier method. RESULTS: The Barcelona Clinic Liver Cancer (BCLC) stage was A in 40% of patients, B in 24%, and C in 36%; 66% of patients had hepatitis B virus infections. According to RECIST criteria, partial responses occurred in 40% of patients, and stable disease was achieved in 46%. Tumor response was significantly associated with BCLC stage (P = 0.003). The median overall time to progression was 5.8 months (range, 0.9-46.1 months). Follow-up treatments after radioembolization were carried out in 31 patients due to remnant HCC (n = 18) or HCC progression (n = 13). The median overall survival was 40.9 months (95% confidence interval, 10.2-71.6 months). Treatment was tolerable except for one lung toxicity and two hepatic toxicities. CONCLUSION: Yttrium-90 radioembolization appears to be well tolerated and effective in Asian patients with BCLC stage A-C HCC. Follow-up treatments after radioembolization can be safely provided.

Endoscopic resection for duodenal subepithelial tumors: a single-center experience.

BACKGROUND: Subepithelial tumors (SETs) in the gastrointestinal tract are often incidentally found during endoscopic examinations. Although the utility and safety of endoscopic resection (ER) of SETs in the esophagus and stomach have been described, data about the ER of duodenal SETs remain scant. Therefore, we aimed to investigate the clinical outcomes associated with the ER of duodenal SETs and to assess possible predictive factors for incomplete resection. METHODS: We conducted a retrospective observational study of 62 patients (64 lesions) that underwent ER of duodenal SETs between June 2005 and December 2015 at the Pusan National University Hospital. The therapeutic outcomes from ER and procedure-related complications were analyzed. RESULTS: Endoscopic mucosal resection (EMR) was performed in 38 tumors, EMR with a ligation device (EMR-L) in 18 and endoscopic submucosal dissection (ESD) in 8. The overall en bloc resection and complete ER rates were 96.9 % (62/64) and 100 % (64/64), respectively. The complete pathologic resection rate was 76.6 % (49/64). Multivariate logistic regression analyses determined that the macroscopic type (Yamada type I or II; odds ratio [OR] 6.460, 95 % confidence interval [CI] 1.569-37.458, p = 0.027) and the treatment method (ESD; OR 7.178, 95 % CI 1.291-39.323, p = 0.024) were independently associated with incomplete pathologic resection. The procedure-related bleeding and perforation rates were 6.3 % and 4.7 %, respectively. No recurrences were observed in patients who had undergone complete ER at a median follow-up period of 20 months (range 6-112 months). CONCLUSION: ER is an effective, safe, and feasible treatment for duodenal SETs, especially when the SET is located in the deep mucosal layer and/or the submucosal layer.