Development and Validation of Nomograms to Provide Individualized Predictions of Sur-vival Benefits from Surgery in Patients with Intermediate/Advanced Hepatocel-lular Carcinoma

( Wen-tao Yan ),( Jia-he Wang ),( Ming-da Wang ),( Zheng Wang ),( Bing Quan ),( Ya-hao Zhou ),( Wei-min Gu ),( Hong Wang ),( Ting-hao Chen ),( Tian Yang ) 대한간학회 2018 춘·추계 학술대회 (KASL) Vol.2018 No.1

Aims: According to the BCLC treatment guidelines, surgery does not be recommended for intermediate/advanced hepatocellular carcinoma (HCC). In real world, however, liver resections are often performed in patients with intermediate/ advanced but resectable HCC, especially in the East. Methods: We retrospectively evaluated multicentric data of 1,325 patients newly diagnosed with intermediate/advanced HCC who underwent curative resection. We randomly divided the subjects into development (n = 875) and validation (n = 450) samples. Multivariate Cox proportional hazards models were developed and separately validated on the basis of patients’ clinicopathological variables assessed for associations with 1-year recurrence and 3-year mortality. The discriminatory accuracy of these models was compared with conventional tools by analyzing receiver operating characteristic (ROC) curves. Results: He statistical nomograms built based on performance status, Child-Pugh grade, portal hypertension, preoperative alpha-fetoprotein level, tumor rupture, largest tumor diameter, tumor number, macrovascular and microvascular invasion, and satellites had good calibration and discriminatory abilities, with c-indices of 0.70 (1-year recurrence) and 0.68 (3-year survival), respectively. These models showed satisfactory goodness-of-fit and discrimination abilities in the validation cohort (c-index, 0.68 for 1-year recurrence and 0.69 for 3-year survival). The areas under the ROC curve using these nomograms exceeded those of traditional staging systems, indicating superior discriminatory capability (c-indices, 0.60-0.63 and 0.56-0.62, respectively). Conclusions: Our proposed online nomograms, which present graphically postoperative prognostic models for recurrence and survival in patients with intermediate/advanced but resectable HCC, offer valuable guidance to surgeons and hepatologists for individually predicting survival benefits from surgery and planning recurrence surveillance and adjuvant therapy.

Characterization and Antioxidant Activity of the Exopolysaccharide Produced by Bacillus amyloliquefaciens GSBa-1

( Wen Zhao ),( Jian Zhang ),( Yun-yun Jiang ),( Xiao Zhao ),( Xiao-na Hao ),( Liu Li ),( Zhen-nai Yang ) 한국미생물생명공학회(구 한국산업미생물학회) 2018 Journal of microbiology and biotechnology Vol.28 No.8

The exopolysaccharide (EPS) produced by Bacillus amyloliquefaciens GSBa-1 was isolated and purified by ethanol precipitation, and DEAE-cellulose and Sepharose CL-6B chromatographies. The molecular mass of the purified EPS was determined to be 54 kDa. Monosaccharide analysis showed that the EPS was composed of predominantly glucose, and it was further confirmed by NMR spectroscopy to be α-glucan that consisted of a trisaccharide repeating unit with possible presence of two α-(1→3) and one α-(1→6) glucosidic linkages. Microstructural analysis showed that the EPS appeared as ellipsoid or globose with a smooth surface. The EPS had a degradation temperature at 240℃. Furthermore, the EPS had strong DPPH and hydroxyl radical scavenging activities, and moderate superoxidant anion scavenging and metal ion-chelating activities. This is the first characterization of a glucan produced by B. amyloliquefaciens with strong antioxidant activity. The results of this study suggest the potential of the EPS from B. amyloliquefaciens GSBa-1 to serve as a natural antioxidant for application in functional products.

Mitochondrial citrate accumulation drives alveolar epithelial cell necroptosis in lipopolysaccharide-induced acute lung injury

Yang Hui-Hui,Jiang Hui-Ling,Tao Jia-Hao,Zhang Chen-Yu,Xiong Jian-Bing,Yang Jin-Tong,Liu Yu-Biao,Zhong Wen-Jing,Guan Xin-Xin,Duan Jia-Xi,Zhang Yan-Feng,Liu Shao-Kun,Jiang Jian-Xin,Zhou Yong,Guan Cha-Xi 생화학분자생물학회 2022 Experimental and molecular medicine Vol.54 No.-

Necroptosis is the major cause of death in alveolar epithelial cells (AECs) during acute lung injury (ALI). Here, we report a previously unrecognized mechanism for necroptosis. We found an accumulation of mitochondrial citrate (citratemt) in lipopolysaccharide (LPS)-treated AECs because of the downregulation of Idh3α and citrate carrier (CIC, also known as Slc25a1). shRNA- or inhibitor–mediated inhibition of Idh3α and Slc25a1 induced citratemt accumulation and necroptosis in vitro. Mice with AEC-specific Idh3α and Slc25a1 deficiency exhibited exacerbated lung injury and AEC necroptosis. Interestingly, the overexpression of Idh3α and Slc25a1 decreased citratemt levels and rescued AECs from necroptosis. Mechanistically, citratemt accumulation induced mitochondrial fission and excessive mitophagy in AECs. Furthermore, citratemt directly interacted with FUN14 domain-containing protein 1 (FUNDC1) and promoted the interaction of FUNDC1 with dynamin-related protein 1 (DRP1), leading to excessive mitophagy-mediated necroptosis and thereby initiating and promoting ALI. Importantly, necroptosis induced by citratemt accumulation was inhibited in FUNDC1-knockout AECs. We show that citratemt accumulation is a novel target for protection against ALI involving necroptosis.

Aberrant Expression of Pim-3 Promotes Proliferation and Migration of Ovarian Cancer Cells

Zhuang, Hao,Zhao, Man-Yin,Hei, Kai-Wen,Yang, Bai-Cai,Sun, Li,Du, Xue,Li, Yong-Mei Asian Pacific Journal of Cancer Prevention 2015 Asian Pacific journal of cancer prevention Vol.16 No.8

Pim kinase-3(Pim-3), a member of serine/threonine protein kinases, has been implicated in multiple human cancers and involved in Myc-induced tumorigenesis. However, little is known regarding its expression and biological function in human ovarian cancer. In this study we showed that the clinical significance and biological functions of Pim-3 in ovarian cancer and found that higher Pim-3 mRNA level are detected in ovarian cancer tissues than those in normal ovarian tissues. There are significant correlations between higher Pim-3 expression levels with the FIGO stage, histopathological subtypes, and distant metastasis in ovarian cancer patients. Lentivirus-mediated gene overexpression of Pim-3 significantly promotes the proliferation and migration of SKOV3 cell lines. Furthermore, MACC1 and Pim-3 expression were significantly correlated in human ovarian cancer cells, and overexpression of Pim-3 in ovary cancer cells increased MACC1 mRNA and protein expression. The data indicate that Pim-3 acts as a putative oncogene in ovary cancer and could be a viable diagnostic and therapeutic target for ovarian cancer.

A new aspect of an old friend: the beneficial effect of metformin on anti-tumor immunity

김경진,Wen-Hao Yang,정연상,차종호 생화학분자생물학회 2020 BMB Reports Vol.53 No.10

T-cell-based cancer immunotherapies, such as immune checkpoint blockers (ICBs) and chimeric antigen receptor (CAR)-Tcells, have significant anti-tumor effects against certain types of cancer, providing a new paradigm for cancer treatment. However, the activity of tumor infiltrating T-cells (TILs) can be effectively neutralized in the tumor microenvironment (TME) of most solid tumors, rich in various immunosuppressive factors and cells. Therefore, to improve the clinical outcomes of established T-cell-based immunotherapy, adjuvants that can comprehensively relieve multiple immunosuppressive mechanisms of TME are needed. In this regard, recent studies have revealed that metformin has several beneficial effects on anti-tumor immunity. In this mini-review, we understand the immunosuppressive properties of TME and how metformin comprehensively enhances anti-tumor immunity. Finally, we will discuss this old friend's potential as an adjuvant for cancer immunotherapy.

Applicability Analysis of Microseismic Technology in Tunnel Water Inrush Monitoring

Yan-hao Chen,Shuai Cheng,Li-Ping Li,Jun-yan Yang,Hong-liang Liu,Wen-feng Tu 대한토목학회 2021 KSCE JOURNAL OF CIVIL ENGINEERING Vol.25 No.7

Water inrush disaster is one of the most serious geological disasters in tunnel construction. There are still some problems in the existing researches, such as the activity information of surrounding rock is difficult to obtain, the mechanism of water inrush disaster is unclear, the correlation between water inrush disaster and microseismic (MS) information is missing, which have caused the water inrush disaster to be passively controlled. Combining with the practical experience of tunnel engineering, the application problems of MS technology in tunnel engineering is summarized, which provides ideas for monitoring of surrounding rock activity. The formation mechanism of water inrush disaster caused by rock mass fracturing and filling medium instability has been revealed. The MS characteristics of the water inrush channel in different water inrush disasters have also been revealed. The MS response characteristics of water inrush and rockburst disasters are compared, which provides guidance for the improvement of MS monitoring technology and the analysis of effective MS information. The compression failure test of limestone under saturated and natural conditions is carried out. The results show that the presence of water weakens the ability of rock to store energy. The acoustic emission (AE) phenomenon is weaker in the process of saturated limestone failure, which increases the difficulty of AE monitoring. The number of AE events of natural limestone and saturated limestone shows a slow increase to a sudden increase in the process stress loading, which can be regarded as an important precursor of rock failure.

pH-dependent release of platycodin mitigates its gastrointestinal mucosa irritation after oral administration in rats

Qin Chen,Wen-Wen Yang,Pan Shen,Qing-Ri Cao,Beom-Jin Lee,Jing-Hao Cui 대한약학회 2016 Archives of Pharmacal Research Vol.39 No.6

The present study aimed to evaluate the gastrointestinalmucosa irritation of three platycodin formulations. Platycodin-loaded core pellets were prepared viaextrusion–spheronization method and coated withEudragit L100-55 (L100) or Eudragit S100 (S100) forpH-dependent release. The release of platycodin D fromcoated pellets exhibited pH dependent release profiles. Thepharmacokinetic study in rats showed that Tmax of thecoated pellets were prolonged as compared to that of uncoatedpellets. The S100-coated pellets possess a lowerCmax and decreased AUC0–24h as compared to the L100-coated and uncoated pellets. Hematoxylin-eosin stainingand nuclear factor Kappa B (NF-jB) measurement werecarried out to observe the gastrointestinal mucosa irritations. The results revealed that the irritations of platycodinon the upper gastrointestinal mucosa are dose-dependent. However, no obvious irritation effect on the gastrointestinaltissues of rats was detected after oral administration ofthe coated pellets. In addition, the amount of NF-jB in thestomach of rats treated with the uncoated pellets was aboutfivefold higher as compared to that of the coated pellets. Insummary, the L100-coated platycodin pellets exhibitedhigher oral bioavailability and less gastrointestinal mucosairritations as compared to the other two formulations.

Evolution of Multi-temporal Landslides at Luhu, Miaoli County, Taiwan

( Che-ming Yang ),( Keng-hao Kang ),( Kuo-wei Li ),( Hui-jung Wang ),( Ching-ping Hsiao ),( Jyh-jong Liao ),( Yii-wen Pan ) 대한지질공학회 2019 대한지질공학회 학술발표회논문집 Vol.2019 No.2

A deep-seated landslide took place in Luhu, Miao-Li, Taiwan during intermittent rainfall in April 2018; initially, there were successive rock falls and gully erosion then leaded to a deep-seated landslide failure eventually. This study aims to understand the failure mechanism and the process of deep-seated failure. The study site is a steep anaclinal slope consisting of the Miocence Shihti Formation with thick sandstone, interbedded of sandstone and shale. We collected multi-temporal ortho-images and digital elevation (surface) models from 1980 to 2019 for geological investigation, geomorphological interpretation and numerical simulation. The images reveal several slope failures at 1998, 2003, 2005, 2009, 2015, 2017 and 2018 with various volume and failure types. The study area contains three sub-regions: the north, the northwest and the southwest slopes. The slope failure occurred repeatedly inside the north and the northwest slopes in the early stage. Gully erosion in the southwest slope progressed to a landslide on April 5, 2018 first and expanded to cover the deep-seated landslide failure in the northwest slope eventually; the slope failure resulted in a natural dam. After the landslide, several open cracks appeared near to the crown. The estimated maximum thickness, area and volume of the deep-seated landslide are ~60 m, 65,000 m2 and ~2 Mm3, respectively. Based on these results, we also performed a series of numerical simulation using the software RAMMS to interpret the run out and the deposition of this landslide case.

Physicochemical, Antibacterial Properties, and Compatibility of ZnO-NP/Chitosan/β-Glycerophosphate Composite Hydrogels

( Pingping Huang ),( Wen Su ),( Rui Han ),( Hao Lin ),( Jing Yang ),( Libin Xu ),( Lei Ma ) 한국미생물생명공학회 2022 Journal of microbiology and biotechnology Vol.32 No.4

In this study we aimed to develop novel ZnO-NP/chitosan/β-glycerophosphate (ZnO-NP/CS/β-GP) antibacterial hydrogels for biomedical applications. According to the mass fraction ratio of ZnO-NPs to chitosan, mixtures of 1, 3, and 5% ZnO-NPs/CS/β-GP were prepared. Using the test-tube inversion method, scanning electron microscopy and Fourier-transform infrared spectroscopy, the influence of ZnO-NPs on gelation time, chemical composition, and cross-sectional microstructures were evaluated. Adding ZnO-NPs significantly improved the hydrogel's antibacterial activity as determined by bacteriostatic zone and colony counting. The hydrogel's bacteriostatic mechanism was investigated using live/dead fluorescent staining and scanning electron microscopy. In addition, crystal violet staining and MTT assay demonstrated that ZnO-NPs/CS/β-GP exhibited good antibacterial activity in inhibiting the formation of biofilms and eradicating existing biofilms. CCK-8 and live/dead cell staining methods revealed that the cell viability of gingival fibroblasts (L929) cocultured with hydrogel in each group was above 90% after 24, 48, and 72 h. These results suggest that ZnO-NPs improve the temperature sensitivity and bacteriostatic performance of chitosan/β-glycerophosphate (CS/β-GP), which could be injected into the periodontal pocket in solution form and quickly transformed into hydrogel adhesion on the gingiva, allowing for a straightforward and convenient procedure. In conclusion, ZnO-NP/CS/β-GP thermosensitive hydrogels could be expected to be utilized as adjuvant drugs for clinical prevention and treatment of peri-implant inflammation.

Exercise Reduces Airway Smooth Muscle Contraction in Asthmatic Rats via Inhibition of IL-4 Secretion and Store-Operated Ca2+ Entry Pathway

Huang Jun-Hao,Gao Hui-Wen,Gao Dong-Dong,Yang Wei-Yue,Zhao Meng-Ke,Shen Bing,Hu Min 대한천식알레르기학회 2023 Allergy, Asthma & Immunology Research Vol.15 No.3

Purpose: Increased evidence has shown that aerobic exercise reduces airway hyperresponsiveness in asthmatic individuals. However, the underlying mechanisms of action remain elusive. This study aimed to investigate the effect of exercise on airway smooth muscle (ASM) contractile function in asthmatic rats, and uncover the possible involvement of interleukin 4 (IL-4) and the store-operated Ca2+ entry (SOCE) pathway. Methods: In this study, chicken ovalbumin was used to induce asthma in male Sprague-Dawley rats. The exercise group received moderate-intensity aerobic exercise training for 4 weeks. IL-4 concentrations in bronchoalveolar lavage fluid (BALF) samples were evaluated by enzyme linked immunosorbent assay. The contractile function of the ASM was investigated using tracheal ring tension experiments and intracellular Ca2+ imaging techniques. Western blot analysis was used to evaluate expression levels of calcium-release activated calcium (CRAC) channel protein (Orai) and stromal interaction molecule 1 (STIM1) in ASM. Results: Our data showed that the carbachol-stimulated, SOCE-mediated contraction of rat ASM was significantly increased in asthmatic rats, which could be abolished by exercise. Pharmacological studies revealed that GSK5498A and BTP-2, selective blockers of CRAC channels significantly inhibited SOCE-induced ASM contraction. In addition, exercise inhibited the up-regulation of IL-4 in BALF as well as STIM1 and Orai expression in the ASM of asthmatic rats. In line with these observations, we demonstrated that pretreatment of the ASM with IL-4 up-regulated the expression level of STIM1, Orai1 and Orai2, thereby promoting SOCE-mediated ASM contraction. Conclusions: The data in this study reveal that aerobic exercise may improve the ASM contractile function in asthmatic rats by inhibiting IL-4 secretion and by down-regulating the expression of STIM1, Orai1 and Orai2, thus decreasing excessive SOCE-mediated ASM contraction in asthmatic rats.