A Novel Molecular Grading Model: Combination of Ki67 and VEGF in Predicting Tumor Recurrence and Progression in Non-invasive Urothelial Bladder Cancer

Chen, Jun-Xing,Deng, Nan,Chen, Xu,Chen, Ling-Wu,Qiu, Shao-Peng,Li, Xiao-Fei,Li, Jia-Ping Asian Pacific Journal of Cancer Prevention 2012 Asian Pacific journal of cancer prevention Vol.13 No.5

Purpose: To assess efficacy of Ki67 combined with VEGF as a molecular grading model to predict outcomes with non-muscle invasive bladder cancer (NMIBC). Materials: 72 NMIBC patients who underwent transurethral resection (TUR) followed by routine intravesical instillations were retrospectively analyzed in this study. Univariate and multivariate analyses were performed to confirm the prognostic values of the Ki67 labeling index (LI) and VEGF scoring for tumor recurrence and progression. Results: The novel molecular grading model for NMIBC contained three molecular grades including mG1 (Ki67 $LI{\leq}25%$, VEGF $scoring{\leq}8$), mG2 (Ki67 LI>25%, VEGF $scoring{\leq}8$; or Ki67 $LI{\leq}25%$, VEGF scoring > 8), and mG3 (Ki67 LI > 25%, VEGF scoring > 8), which can indicate favorable, intermediate and poor prognosis, respectively. Conclusions: The described novel molecular grading model utilizing Ki67 LI and VEGF scoring is helpful to effectively and accurately predict outcomes and optimize personal therapy.

White-Matter Hyperintensities and Lacunar Infarcts Are Associated with an Increased Risk of Alzheimer’s Disease in the Elderly in China

Shuai Ye,Shuyang Dong,Jun Tan,Le Chen,Hai Yang,Yang Chen,Zeyan Peng,Yingchao Huo,Juan Liu,Mingshan Tang,Yafei Li,Huadong Zhou,Yong Tao 대한신경과학회 2019 Journal of Clinical Neurology Vol.15 No.1

Background and Purpose This study investigated the contribution of white-matter hyperintensities (WMH) and lacunar infarcts (LI) to the risk of Alzheimer’s disease (AD) in an elderly cohort in China. Methods Older adults who were initially cognitively normal were examined with MRI at baseline, and followed for 5 years. WMH were classified as mild, moderate, or severe, and LI were classified into a few LI (1 to 3) or many LI (≥4). Cognitive function was assessed using the Mini Mental State Examination and the Activities of Daily Living scale. Results Among the 2,626 subjects, 357 developed AD by the end of the 5-year follow-up period. After adjusting for age and other potential confounders, having only WMH, having only LI, and having both WMH and LI were associated with an increased risk of developing AD compared with having neither WMH nor LI. Moderate and severe WMH were associated with an increased risk of developing AD compared with no WMH. Furthermore, patients with many LI had an increased risk of developing AD compared with no LI. Conclusions Having moderate or severe WMH and many LI were associated with an increased risk of developing AD, with this being particularly striking when both WMH and LI were present.

Synthesis of full concentration gradient cathode studied by high energy X-ray diffraction

Li, Yan,Xu, Rui,Ren, Yang,Lu, Jun,Wu, Huiming,Wang, Lifen,Miller, Dean J.,Sun, Yang-Kook,Amine, Khalil,Chen, Zonghai Elsevier 2016 Nano energy Vol.19 No.-

<P><B>Abstract</B></P> <P>Nickel-rich metal oxides have been widely pursued as promising cathode materials for high energy-density lithium-ion batteries. Nickel-rich lithium transition metal oxides can deliver a high specific capacity during cycling, but can react with non-aqueous electrolytes. In this work, we have employed a full concentration gradient (FCG) design to provide a nickel-rich core to deliver high capacity and a manganese-rich outer layer to provide enhanced stability and cycle life. <I>In situ</I> high-energy X-ray diffraction was utilized to study the structural evolution of oxides during the solid-state synthesis of FCG lithium transition metal oxide with a nominal composition of LiNi<SUB>0.6</SUB>Mn<SUB>0.2</SUB>Co<SUB>0.2</SUB>O<SUB>2</SUB>. We found that both the pre-heating step and the sintering temperature were critical in controlling phase separation of the transition metal oxides and minimizing the content of Li<SUB>2</SUB>CO<SUB>3</SUB> and NiO, both of which deteriorate the electrochemical performance of the final material. The insights revealed in this work can also be utilized for the design of other nickel-rich high energy-density cathode materials.</P> <P><B>Highlights</B></P> <P> <UL> <LI> Solid-state synthesis of FCG cathode is investigated by <I>in situ</I> XRD. </LI> <LI> Covariance analysis and Rietveld refinement are used to analyze the HEXRD data. </LI> <LI> Synthetic optimization of FCG cathode with excellent electrochemical performance. </LI> </UL> </P> <P><B>Graphical abstract</B></P> <P>Benefit from the covariance analysis and Rietveld refinement of <I>in situ</I> HEXRD data during the solid state synthesis, we can optimized the solid state synthesis conditions in a short time. And the full concentration gradient cathode composites (nickel-rich core and manganese-rich outer layer) with excellent electrochemical performance are obtained.</P> <P>[DISPLAY OMISSION]</P>

A large-area free-standing graphene oxide multilayer membrane with high stability for nanofiltration applications

Chen, Long,Li, Yanhui,Chen, Lina,Li, Na,Dong, Chenglong,Chen, Qiong,Liu, Beibei,Ai, Qing,Si, Pengchao,Feng, Jinkui,Zhang, Lin,Suhr, Jonghwan,Lou, Jun,Ci, Lijie Elsevier 2018 CHEMICAL ENGINEERING JOURNAL -LAUSANNE- Vol.345 No.-

<P><B>Abstract</B></P> <P>A flexible and free-standing graphene oxide and nylon 6 (GO@nylon 6) multilayer nanofiltration membrane was prepared by a layer-by-layer assembly process. The combination of electrospinning and electrospraying technique was employed, which can facilely prepare large-area membrane with size of 20 × 30 cm. The mechanical stability of multilayer membrane has enhanced significantly due to the tightly locked structure achieved by nylon 6 nanofibers network. The novel GO@nylon 6–13 multilayer nanofiltration membrane demonstrated a pure water flux up to 11.15 L m<SUP>−2</SUP> h<SUP>−1</SUP> bar<SUP>−1</SUP>, while keeping high organic dye rejection rate (>95% for methylene blue, and >99% for methyl orange). The rejections rate of the Na<SUB>2</SUB>SO<SUB>4</SUB>, NaCl, CuSO<SUB>4</SUB>, and Pb(NO<SUB>3</SUB>)<SUB>2</SUB> were 56.5%, 27.6%, 36.7%, and 18.9%, respectively. Furthermore, GO@nylon 6–13 multilayer nanofiltration membrane also demonstrated a high flux of some common organic solvents (8.4, 5.3, and 0.8 L m<SUP>−2</SUP> h<SUP>−1</SUP> bar<SUP>−1</SUP> for methanol, ethanol, and NMP, respectively), showing excellent chemical stability for separation process in those solvents.</P> <P><B>Highlights</B></P> <P> <UL> <LI> Large-area GO@nylon 6 multilayer nanofiltration membrane was prepared. </LI> <LI> The multilayer structure enhances the mechanical stability. </LI> <LI> The multilayer membrane demonstrates a high water flux. </LI> <LI> The multilayer membrane shows high rejection rate for organic dyes. </LI> </UL> </P> <P><B>Graphical abstract</B></P> <P>Photograph and cross-section SEM image of GO@nylon 6 multilayer nanofiltration membrane, the inset shows the water contact angle.</P> <P>[DISPLAY OMISSION]</P>

Pharmacological blockade of cholesterol trafficking by cepharanthine in endothelial cells suppresses angiogenesis and tumor growth

Lyu, Junfang,Yang, Eun Ju,Head, Sarah A.,Ai, Nana,Zhang, Baoyuan,Wu, Changjie,Li, Ruo-Jing,Liu, Yifan,Yang, Chen,Dang, Yongjun,Kwon, Ho Jeong,Ge, Wei,Liu, Jun O.,Shim, Joong Sup Elsevier 2017 Cancer letters Vol.409 No.-

<P><B>Abstract</B></P> <P>Cholesterol is an important modulator of membrane protein function and signaling in endothelial cells, thus making it an emerging target for anti-angiogenic agents. In this study, we employed a phenotypic screen that detects intracellular cholesterol distribution in endothelial cells (HUVEC) and identified 13 existing drugs as cholesterol trafficking inhibitors. Cepharanthine, an approved drug for anti-inflammatory and cancer management use, was amongst the candidates, which was selected for in-depth mechanistic studies to link cholesterol trafficking and angiogenesis. Cepharanthine inhibited the endolysosomal trafficking of free-cholesterol and low-density lipoprotein in HUVEC by binding to Niemann-Pick disease, type C1 (NPC1) protein and increasing the lysosomal pH. The blockade of cholesterol trafficking led to a cholesterol-dependent dissociation of mTOR from the lysosomes and inhibition of its downstream signaling. Cepharanthine inhibited angiogenesis in HUVEC and in zebrafish in a cholesterol-dependent manner. Furthermore, cepharanthine suppressed tumor growth in vivo by inhibiting angiogenesis and it enhanced the antitumor activity of the standard chemotherapy cisplatin in lung and breast cancer xenografts in mice. Altogether, these results strongly support the idea that cholesterol trafficking is a viable drug target for anti-angiogenesis and that the inhibitors identified among existing drugs, such as cepharanthine, could be potential anti-angiogenic and antitumor agents.</P> <P><B>Highlights</B></P> <P> <UL> <LI> A phenotypic screen identified 13 existing drugs, including cepharanthine, as cholesterol trafficking inhibitors. </LI> <LI> Cepharanthine inhibited lysosomal cholesterol trafficking by binding to NPC1 protein and increasing the lysosomal pH. </LI> <LI> The blockade of cholesterol trafficking led to a cholesterol-dependent dissociation of mTOR from the lysosomes. </LI> <LI> Cepharanthine inhibited angiogenesis in HUVEC and in zebrafish in a cholesterol-dependent manner. </LI> <LI> Cepharanthine treatment enhanced the antitumor activity of cisplatin in lung and breast cancer xenografts in mice. </LI> </UL> </P>

Organization process of the hierarchical structures in microbially synthesized polyhydroxyalkanoates

Jun Xu,Bao-Hua Guo,Qiong Wu,Jin-Chun Chen,Guo-Qiang Chen,Jian-Jun Zhou,Yong Jiang,Lin Li 한국물리학회 2007 Current Applied Physics Vol.7 No.s1

cess of the high-order structures in biomaterials. Real-time Fourier transform infrared spectroscopy and optical microscopy demon-strated that helical segments formed along with the spherulite growth. Atomic force microscopy revealed the details of growth,twisting and branching of lamellar crystals. Cooperative packing of these twisting lamellae led to regular banded spherulites observedunder polarized light microscopy. Real-time observation on the crystallization process provided richer information than the characterization of the final structures; consequently, it provides deeper insight into the organization mechanism of the hierarchical structures.

Puerarin pretreatment attenuates cardiomyocyte apoptosis induced by coronary microembolization in rats by activating the PI3K/Akt/GSK-3β signaling pathway

Chen, Zhi-Qing,Zhou, You,Huang, Jun-Wen,Chen, Feng,Zheng, Jing,Li, Hao-Liang,Li, Tao,Li, Lang The Korean Society of Pharmacology 2021 The Korean Journal of Physiology & Pharmacology Vol.25 No.2

Coronary microembolization (CME) is associated with cardiomyocyte apoptosis and cardiac dysfunction. Puerarin confers protection against multiple cardiovascular diseases, but its effects and specific mechanisms on CME are not fully known. Hence, our study investigated whether puerarin pretreatment could alleviate cardiomyocyte apoptosis and improve cardiac function following CME. The molecular mechanism associated was also explored. A total of 48 Sprague-Dawley rats were randomly divided into CME, CME + Puerarin (CME + Pue), sham, and sham + Puerarin (sham + Pue) groups (with 12 rats per group). A CME model was established in CME and CME + Pue groups by injecting 42 ㎛ microspheres into the left ventricle of rats. Rats in the CME + Pue and sham + Pue groups were intraperitoneally injected with puerarin at 120 mg/kg daily for 7 days before operation. Cardiac function, myocardial histopathology, and cardiomyocyte apoptosis index were determined via cardiac ultrasound, hematoxylin-eosin (H&E) and hematoxylin-basic fuchsin-picric acid (HBFP) stainings, and TdT-mediated dUTP nick-end labeling (TUNEL) staining, respectively. Western blotting was used to measure protein expression related to the phosphoinositide 3-kinase (PI3K)/protein kinase B (Akt)/glycogen synthase kinase-3β (GSK-3β) pathway. We found that, puerarin significantly ameliorated cardiac dysfunction after CME, attenuated myocardial infarct size, and reduced myocardial apoptotic index. Besides, puerarin inhibited cardiomyocyte apoptosis, as revealed by decreased Bax and cleaved caspase-3, and up-regulated Bcl-2 and PI3K/Akt/GSK-3β pathway related proteins. Collectively, puerarin can inhibit cardiomyocyte apoptosis and thus attenuate myocardial injury caused by CME. Mechanistically, these effects may be achieved through activation of the PI3K/Akt/GSK-3β pathway.

Hyperglycemia-induced accumulation of advanced glycosylation end products in fibroblast-like synoviocytes promotes knee osteoarthritis

Li Qingxian,Wen Yinxian,Wang Linlong,Chen Biao,Chen Jun,Wang Hui,Chen Liaobin 생화학분자생물학회 2021 Experimental and molecular medicine Vol.53 No.-

Osteoarthritis (OA) is significantly associated with diabetes, but how hyperglycemia induces or aggravates OA has not been shown. The synovium plays a critical role in cartilage metabolism and substance exchange. Herein, we intended to investigate whether and how hyperglycemia affects the occurrence and progression of OA by influencing the synovium. In patients with knee OA and diabetes (DM OA), we found a more severe inflammatory response, higher endoplasmic reticulum stress (ERS) levels, and more advanced glycosylation end products (AGEs) accumulation in the synovium than in patients without diabetes. Subsequently, we found similar results in the DM OA group in a rat model. In the in vitro cocultivation system, high glucose-stimulated AGEs accumulation, ERS, and inflammation in rat fibroblast-like synoviocytes (FLSs), which resulted in chondrocyte degeneration due to inflammatory factors from FLSs. Furthermore, in the synovium of the DM OA group and FLSs treated with high glucose, the expression of glucose transporter 1 (GLUT1) and its regulatory factor hypoxia-inducible factor (HIF)-1α was increased significantly. Inhibitors of HIF-1α, GLUT1 or AGEs receptors attenuated the effect of high glucose on chondrocyte degradation in the FLS-chondrocyte coculture system. In summary, we demonstrated that hyperglycemia caused AGEs accumulation in FLSs via the HIF-1α-GLUT1 pathway, which increases the release of inflammatory factors from FLSs, subsequently inducing chondrocyte degradation and promoting OA progression.

Structural and Functional Neural Alterations in Internet Addiction: A Study Protocol for Systematic Review and Meta-Analysis

Jun-Li Liu,Jing-Ting Sun,Hui-Lin Hu,Hao-Yuan Wang,Yun-Xi Kang,Tian-Qi Chen,Zhu-Hong Chen,Yu-Xuan Shang,Yu-Ting Li,Bo Hu,Rui Liu 대한신경정신의학회 2023 PSYCHIATRY INVESTIGATION Vol.20 No.1

A growing number of neuroimaging studies have revealed abnormal brain structural and functional alterations in subjects with internet addiction (IA), however, with conflicting conclusions. We plan to conduct a systematic review and meta-analysis on the studies of voxelbased morphometry (VBM) and resting-state functional connectivity (rsFC), to reach a consolidated conclusion and point out the future direction in this field. A comprehensive search of rsFC and VBM studies of IA will be conducted in the PubMed, Cochrane Library, and Web of Science databases to retrieve studies published from the inception dates to August 2021. If the extracted data are feasible, activation likelihood estimation and seed-based d mapping methods will be used to meta-analyze the brain structural and functional changes in IA patients. This study will hopefully reach a consolidated conclusion on the impact of IA on human brain or point out the future direction in this field.

JCAD deficiency attenuates activation of hepatic stellate cells and cholestatic fibrosis

Li Xie,Hui Chen,Li Zhang,Yue Ma,Yuan Zhou,Yong-Yu Yang,Chang Liu,Yu-Li Wang,Ya-Jun Yan,Jia Ding,Xiao Teng,Qiang Yang,Xiu-Ping Liu,Jian Wu 대한간학회 2024 Clinical and Molecular Hepatology(대한간학회지) Vol.30 No.2

Background/Aims: Cholestatic liver diseases including primary biliary cholangitis (PBC) are associated with active hepatic fibrogenesis, which ultimately progresses to cirrhosis. Activated hepatic stellate cells (HSCs) are the main fibrogenic effectors in response to cholangiocyte damage. JCAD regulates cell proliferation and malignant transformation in nonalcoholic steatoheaptitis-associated hepatocellular carcinoma (NASH-HCC). However, its participation in cholestatic fibrosis has not been explored yet. Methods: Serial sections of liver tissue of PBC patients were stained with immunofluorescence. Hepatic fibrosis was induced by bile duct ligation (BDL) in wild-type (WT), global JCAD knockout mice (JCAD-KO) and HSC-specific JCAD knockout mice (HSC-JCAD-KO), and evaluated by histopathology and biochemical tests. In situ-activated HSCs isolated from BDL mice were used to determine effects of JCAD on HSC activation. Results: In consistence with staining of liver sections from PBC patients, immunofluorescent staining revealed that JCAD expression was identified in smooth muscle α-actin (α-SMA)-positive fibroblast-like cells and was significantly up-regulated in WT mice with BDL. JCAD deficiency remarkably ameliorated BDL-induced hepatic injury and fibrosis, as documented by liver hydroxyproline content, when compared to WT mice with BDL. Histopathologically, collagen deposition was dramatically reduced in both JCAD-KO and HSC-JCAD-KO mice compared to WT mice, as visualized by Trichrome staining and semi-quantitative scores. Moreover, JCAD deprivation significantly attenuated in situ HSC activation and reduced expression of fibrotic genes after BDL. Conclusions: JCAD deficiency effectively suppressed hepatic fibrosis induced by BDL in mice, and the underlying mechanisms are largely through suppressed Hippo-YAP signaling activity in HSCs.