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      • SPON2 Promotes M1-like Macrophage Recruitment and Inhibits Hepatocellular Carcinoma Metastasis by Distinct Integrin–Rho GTPase–Hippo Pathways

        Zhang, Yan-Li,Li, Qing,Yang, Xiao-Mei,Fang, Fang,Li, Jun,Wang, Ya-Hui,Yang, Qin,Zhu, Lei,Nie, Hui-Zhen,Zhang, Xue-Li,Feng, Ming-Xuan,Jiang, Shu-Heng,Tian, Guang-Ang,Hu, Li-Peng,Lee, Ho-Young,Lee, Su-J American Association for Cancer Research 2018 Cancer research Vol.78 No.9

        <P>Matricellular protein SPON2 acts as an HCC suppressor and utilizes distinct signaling events to perform dual functions in HCC microenvironment.</P><P>Tumor-associated macrophages (TAM) represent key regulators of the complex interplay between cancer and the immune microenvironment. Matricellular protein SPON2 is essential for recruiting lymphocytes and initiating immune responses. Recent studies have shown that SPON2 has complicated roles in cell migration and tumor progression. Here we report that, in the tumor microenvironment of hepatocellular carcinoma (HCC), SPON2 not only promotes infiltration of M1-like macrophages but also inhibits tumor metastasis. SPON2-α4β1 integrin signaling activated RhoA and Rac1, increased F-actin reorganization, and promoted M1-like macrophage recruitment. F-Actin accumulation also activated the Hippo pathway by suppressing LATS1 phosphorylation, promoting YAP nuclear translocation, and initiating downstream gene expression. However, SPON2-α5β1 integrin signaling inactivated RhoA and prevented F-actin assembly, thereby inhibiting HCC cell migration; the Hippo pathway was not noticeably involved in SPON2-mediated HCC cell migration. In HCC patients, SPON2 levels correlated positively with prognosis. Overall, our findings provide evidence that SPON2 is a critical factor in mediating the immune response against tumor cell growth and migration in HCC.</P><P><B>Significance:</B> Matricellular protein SPON2 acts as an HCC suppressor and utilizes distinct signaling events to perform dual functions in HCC microenvironment.</P><P><B>Graphical Abstract:</B> http://cancerres.aacrjournals.org/content/canres/78/9/2305/F1.large.jpg. <I>Cancer Res; 78(9); 2305–17. ©2018 AACR</I>.</P><P><B>Graphical Abstract</B></P><P> [Figure]</P>

      • KCI등재

        Cordblood-Based High-Throughput Screening for Deafness Gene of 646 Newborns in Jinan Area of China

        Shou-Xia Li,Ding-Li Chen,Su-Bin Zhao,Li-Li Guo,Hai-Qin Feng,Xiao-Fang Zhang,Li-Li Ping,Zhi-Ming Yang,Cai-Xia Sun,Gen-Dong Yao 대한이비인후과학회 2015 Clinical and Experimental Otorhinolaryngology Vol.8 No.3

        Objectives. Infants with slight/mild or late-onset hearing impairment might be missed in universal newborn hearing screening (UNHS). We identified the mutation hot spot of common deaf gene in the newborns in Jinan area population by screening the mutation spot with neonate cord blood, in order to make clear whether the neonate cord blood for screening is feasible. Methods. Six hundred and forty-six newborns were subjected to both UNHS and genetic screening for deafness by using neonate cord blood. The newborn genetic screening targeted four deafness-associated genes, which were commonly found in the Chinese population including gap junction beta-2 protein (GJB2), gap junction beta-3 protein (GJB3), solute carrier family 26 member 4 (SLC26A4), and mtDNA 12S rRNA. The most common 20 spot mutations in 4 deaf genes were detected by MassARRAY iPLEX platform and mitochondrial 12S rRNA A1555G and C1494T mutations were sequenced using Sanger sequencing. Results. Among the 646 newborns, 635 cases passed the UNHS and the other 11 cases (1.7%) did not. Of the 11 failures, two cases were found to carry homozygous GJB2 p.R143W pathogenic mutation, one case was found to have heterozygous GJB2 235delC mutation, and another one case carried heterozygous GJB3 p.R180X pathogenic mutation. Six hundred and thirty-five babies passed the newborn hearing screening, in which 25 babies were identified to carry pathogenic mutations, including 12 heterozygotes (1.9%) for GJB2 235delC, eight heterozygotes (1.3%) for SLC26A4 IVS7-2A>G, one heterozygote (0.2%) for p.R409H, two homozygotes (0.3%) for m.1494C>T, and two homozygotes (0.3%) for m.1555A>G. Conclusion. Newborn genetic screening through the umbilical cord blood for common deafness-associated mutations may identify carriers sensitive to aminoglycoside antibiotic, and can effectively prevent or delay hearing loss occurs.

      • Neutrophil Count and the Inflammation-based Glasgow Prognostic Score Predict Survival in Patients with Advanced Gastric Cancer Receiving First-line Chemotherapy

        Li, Qing-Qing,Lu, Zhi-Hao,Yang, Li,Lu, Ming,Zhang, Xiao-Tian,Li, Jian,Zhou, Jun,Wang, Xi-Cheng,Gong, Ji-Fang,Gao, Jing,Li, Jie,Li, Yan,Shen, Lin Asian Pacific Journal of Cancer Prevention 2014 Asian Pacific journal of cancer prevention Vol.15 No.2

        Purpose: To explore the value of systemic inflammatory markers as independent prognostic factors and the extent these markers improve prognostic classification for patients with inoperable advanced or metastatic gastric cancer (GC) receiving palliative chemotherapy. Methods: We studied the prognostic value of systemic inflammatory factors such as circulating white blood cell count and its components as well as that combined to form inflammation-based prognostic scores (Glasgow Prognostic Score (GPS), Neutrophil-Lymphocyte Ratio (NLR), Platelet Lymphocyte Ratio (PLR), Prognostic Index (PI) and Prognostic Nutritional Index (PNI)) in 384 patients with inoperable advanced or metastatic gastric cancer (GC) receiving first-line chemotherapy. Univariate and multivariate analyses were performed to examine the impact of inflammatory markers on overall survival (OS). Results: Univariate analysis revealed that an elevated white blood cell, neutrophil and/or platelet count, a decreased lymphocyte count, a low serum albumin concentration, and high CRP concentration, as well as elevated NLR/PLR, GPS, PI, PNI were significant predictors of shorter OS. Multivariate analysis demonstrated that only elevated neutrophil count (HR 3.696, p=0.003) and higher GPS (HR 1.621, p=0.01) were independent predictors of poor OS. Conclusion: This study demonstrated elevated pretreatment neutrophil count and high GPS to be independent predictors of shorter OS in inoperable advanced or metastatic GC patients treated with first-line chemotherapy. Upon validation of these data in independent studies, stratification of patients using these markers in future clinical trials is recommended.

      • KCI등재

        Risk Factors for Anxiety in Major Depressive Disorder Patients

        Li-Min Xin,Lin Chen,Zhen-Peng Ji,Suo-Yuan Zhang,Jun Wang,Yan-Hong Liu,Da-Fang Chen,Fu-De Yang,Gang Wang,Yi-Ru Fang,Zheng Lu,Hai-Chen Yang,Jian Hu,Zhi-Yu Chen,Yi Huang,Jing Sun,Xiao-Ping Wang,Hui-Chun 대한정신약물학회 2015 CLINICAL PSYCHOPHARMACOLOGY AND NEUROSCIENCE Vol.13 No.3

        Objective: To analyze the sociodemographic and clinical factors related to anxiety in patients with major depressive disorder (MDD). Methods: This study involved a secondary analysis of data obtained from the Diagnostic Assessment Service for People with Bipolar Disorders in China (DASP), which was initiated by the Chinese Society of Psychiatry (CSP) and conducted from September 1, 2010 to February 28, 2011. Based on the presence or absence of anxiety-related characteristics, 1,178 MDD patients were classified as suffering from anxious depression (n=915) or non-anxious depression (n=263), respectively. Results: Compared with the non-anxious group, the anxious-depression group had an older age at onset (t=−4.39, p<0.001), were older (t=−4.69, p<0.001), reported more lifetime depressive episodes (z=−3.24, p=0.001), were more likely to experience seasonal depressive episodes (χ2=6.896, p=0.009) and depressive episodes following stressful life events (χ2=59.350, p <0.001), and were more likely to have a family history of psychiatric disorders (χ2=6.091, p=0.014). Their positive and total scores on the Mood Disorder Questionnaire (MDQ) and the 32-item Hypomania Checklist (HCL-32) (p<0.05) were also lower. The logistic regression analysis indicated that age (odds ratio [OR]=1.03, p<0.001), a lower total MDQ score (OR=0.94, p=0.011), depressive episodes following stressful life events (OR=3.04, p<0.001), and seasonal depressive episodes (OR=1.75, p=0.039) were significantly associated with anxious depression. Conclusion: These findings indicate that older age, fewer subclinical bipolar features, an increased number of depressive episodes following stressful life events, and seasonal depressive episodes may be risk factors for anxiety-related characteristics in patients with MDD.

      • SCIESCOPUSKCI등재
      • KCI등재

        Electrochemical control of the conversion of cellulose oligosaccharides into glucose

        Fang Yang,Qian Zhang,Hong-Xian Fan,Yang Li,Gang Li 한국공업화학회 2014 Journal of Industrial and Engineering Chemistry Vol.20 No.5

        This paper presents a novel method to convert cellulose oligosaccharides to glucose by using constant-potential electrolysis. Firstly experiments were performed to seek the optimum conditions and catalyst dosage to make the catalytic electrode, and it is found that the most active catalytic electrode (g-MnO2/graphite/PTFE) can be made using 5% g-MnO2 as catalysts which is prepared at calcinations temperature of 500 8C and calcinations time of 3 h. Following this, experiments were conducted to find the optimum operation conditions for the maximum glucose yield using the above-developed catalytic electrode. The results show that the maximum glucose yield of 72.4% can be achieved under the following operation conditions: electrolysis potential vs. SEC 1.0 V, pH value of 3 and electrolytic reaction time of 8 h. The cyclic voltammetry performance on MnO2/graphite/PTFE electrode suggests that g-MnO2 acts not only as electrode material but also as a catalyst. The g-MnO2 displays high electrocatalytic activity toward the breakage of b-1,4-glycoside bond of oligosaccharides and gives 100% selectivity to glucose. Crown Copyright

      • SCIESCOPUSKCI등재
      • KCI등재

        Implantation of Bone Marrow Mesenchymal Stem Cells into Small Intestinal Submucosa Improves Bile Duct Injury in Rabbits

        Li Ying,Wang Piao,Hu Xiao-dong,Zeng Jing-da,Fang Cheng,Gan Yu,Peng Fang-yi,Yang Xiao-li,Luo De,Li Bo,Su Song 한국조직공학과 재생의학회 2021 조직공학과 재생의학 Vol.18 No.5

        BACKGROUND: Bile duct injury (BDI), which may occur during cholecystectomy procedures and living-donor liver transplantation, leads to life-altering complications and significantly increased mortality and morbidity. Tissue engineering, as an emerging method, has shown great potential to treat BDI. Here, we aimed to explore the application of small intestinal submucosa (SIS) matrix composites with bone marrow mesenchymal stem cells (BMSCs) to treat BDI in a rabbit model. METHODS: Rabbit-derived BMSCs were used as seed cells. Porcine SIS was used as the support material. Five centimetres of the common bile duct was dissected, and 1/3–1/2 of the anterior wall diameter was transversely incised to construct the rabbit BDI model. Then, SIS materials without/with BMSCs were inserted into the common bile duct of the BDI rabbits. After 1, 2, 4, and 8 weeks of implantation, the common bile duct was removed. Haematoxylin and eosin (HE) staining was used to assess pathological alterations in the common bile duct, while immunohistochemical staining and western blotting were used to detect expression of the epithelial cell markers CK19 and E-cadherin. Scanning electron microscopy was used to evaluate BMSC growth. RESULTS: Compared with BMSCs alone, SIS-attached BMSCs had increased growth. HE staining showed that the injured bile duct healed well and that the complex gradually degraded as the time from implantation increased. Immunohistochemical staining and western blotting showed that compared with the control group, the in vivo complex group had significantly elevated expression levels of CK19 and E-cadherin. CONCLUSION: BMSC implantation into SIS could improve BDI in rabbits, which might have clinical value for BDI treatment. BACKGROUND: Bile duct injury (BDI), which may occur during cholecystectomy procedures and living-donor liver transplantation, leads to life-altering complications and significantly increased mortality and morbidity. Tissue engineering, as an emerging method, has shown great potential to treat BDI. Here, we aimed to explore the application of small intestinal submucosa (SIS) matrix composites with bone marrow mesenchymal stem cells (BMSCs) to treat BDI in a rabbit model. METHODS: Rabbit-derived BMSCs were used as seed cells. Porcine SIS was used as the support material. Five centimetres of the common bile duct was dissected, and 1/3–1/2 of the anterior wall diameter was transversely incised to construct the rabbit BDI model. Then, SIS materials without/with BMSCs were inserted into the common bile duct of the BDI rabbits. After 1, 2, 4, and 8 weeks of implantation, the common bile duct was removed. Haematoxylin and eosin (HE) staining was used to assess pathological alterations in the common bile duct, while immunohistochemical staining and western blotting were used to detect expression of the epithelial cell markers CK19 and E-cadherin. Scanning electron microscopy was used to evaluate BMSC growth. RESULTS: Compared with BMSCs alone, SIS-attached BMSCs had increased growth. HE staining showed that the injured bile duct healed well and that the complex gradually degraded as the time from implantation increased. Immunohistochemical staining and western blotting showed that compared with the control group, the in vivo complex group had significantly elevated expression levels of CK19 and E-cadherin. CONCLUSION: BMSC implantation into SIS could improve BDI in rabbits, which might have clinical value for BDI treatment.

      • KCI등재

        Selective extraction of thorium to directly form self-assembly solid from HNO3 solution

        Fang Zhang,Qiang Wu,Lei-Tao Sha,Yang Li,Xu-Xin Li,Ze-Yang Wang,Xuan Fu,Qing-Gang Huang,Bin Liu,Ze-Yi Yan 한국공업화학회 2023 Journal of Industrial and Engineering Chemistry Vol.123 No.-

        Based on ions exchange between [DMDSA]+[Cl]- (Dimethyl distearyl ammonium chloride) and N,Ndialkyl-succinamide acid (SCA), three novel bifunctional [DMDSA]+[SCA]- ionic liquids (ILs) were firstlysynthesized for extraction of thorium (IV) by self-assembly strategy. The simultaneous extraction andsolidification of Th(IV) were unexpectedly realized in one-step operation using the present ILs in HNO3solution, and more than 99% thorium (IV) was enriched and immediately aggregated into selfassemblysolid at the biphasic interface. The self-assembly solid was further identified by FT-IR, SEM withelement mapping EDS and XPS analysis, and revealing that the self-assembly extraction (SAE) was triggeredby the amphiphilic [DMDSA]+ cations. A three-step extraction mechanism dominated by [SCATh(NO3)4]- was proposed based on the slope analysis method and HRMS analysis. The self-assembly extractionof Th(IV) exhibited the extremely excellent selectivity in the presence of U(VI) and typical lanthanideelements including La(III), Eu(III) and Lu(III), and the separation factors reached 2516 for Th/U, 1885 forTh/La, 1512 for Th/Eu and 558 for Th/Lu, respectively. The proposed SAE strategy was proved to be anefficient method for one-step separation and solidification of thorium ions from U(VI) and/or lanthanides.

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