Synergistic Effects of Leflunomide and Benazepril in Streptozotocin-Induced Diabetic Nephropathy

Jin, Hua,Piao, Shang Guo,Jin, Ji Zhe,Jin, Ying Shun,Cui, Zhen Hua,Jin, Hai Feng,Zheng, Hai Lan,Li, Jin Ji,Jiang, Yu Ji,Yang, Chul Woo,Li, Can S.Karger 2014 The Nephron Journals Vol.126 No.3

<P>Abstract</P><P><B><I>Background:</I></B> Leflunomide (LEF) and benazepril have renoprotective effects on diabetic nephropathy (DN) through their anti-inflammatory and anti-fibrotic activities. This study investigated whether combined treatment using LEF and benazepril affords superior protection compared with the respective monotherapies. <B><I>Methods:</I></B> Diabetes was induced with streptozotocin (STZ, 65 mg/kg) by intraperitoneal injection in male Wistar rats. Two weeks after STZ injection, diabetic rats were treated daily for 12 weeks with LEF (10 mg/kg), benazepril (10 mg/kg), or a combination of both. Basic parameters (body weight, fasting blood glucose level, and 24 h urinary protein excretion), histopathology, inflammatory [inflammatory cell infiltration (ED-1), monocyte chemoattractant protein-1 (MCP-1), and Toll-like receptor-2 (TLR-2)] and glomerulosclerotic factors [transforming growth factor-β<SUB>1</SUB> (TGF-β<SUB>1</SUB>) and connective tissue growth factor (CTGF)], and oxidative stress (8-hydroxy-2'-deoxyguanosine, 8-OHdG) were studied. <B><I>Results:</I></B> Benazepril or LEF treatment significantly prevented body weight loss and 24 h urinary protein excretion induced by diabetes; combined treatment with LEF and benazepril further improved these parameters compared with giving each drug alone (all p < 0.01). Increased expression of inflammatory (MCP-1 and TLR-2) and glomerulosclerotic (TGF-β<SUB>1</SUB> and CTGF) factors in diabetic rat kidney was reduced by treatment with either LEF or benazepril and was further reduced by the combined administration of the two drugs (p < 0.01). These effects were accompanied by suppression of urinary 8-OHdG excretion. There was no significant between-group difference in blood glucose level. <B><I>Conclusions:</I></B> LEF treatment lessens DN, and combined treatment with LEF and benazepril provides synergistic effects in preventing DN.</P><P>© 2014 S. Karger AG, Basel</P>

Angiopoietin-1 and Angiopoietin-2 Expression Imbalance Influence in Early Period After Subarachnoid Hemorrhage

Hua Gu,Zhen-Hai Fei,Yi-Qi Wang,Jian-Guo Yang,Chao-Hui Zhao,Yong Cai,Xing-Ming Zhong 대한배뇨장애요실금학회 2016 International Neurourology Journal Vol.20 No.4

Purpose: Microvascular endothelial integrity is important for maintaining the blood-brain barrier (BBB). However, subarachnoid hemorrhage (SAH) disrupts this integrity, making the BBB dysfunctional—an important pathophysiological change after SAH. Angiopoietin-1 (Ang-1) and angiopoietin-2 (Ang-2) regulate microvascular permeability by balancing each other’s expression. Methods: This study investigated the dynamics of Ang-1 and Ang-2 expression after SAH and the protective effect of Ang-1 on BBB functioning using an endovascular puncture model of rat SAH. The Ang-1 and Ang-2 expression in brain tissue was determined by immunohistochemistry. In addition, Western blotting was used to estimate Ang-1 and Ang-2 concentration and to compare them at 6–72 hours post-SAH cortex and hippocampus. Evans blue viability assay was used to evaluate BBB permeability, and neurological testing was implemented to evaluate neurological impairment during SAH. Results: It was found that following SAH, Ang-1 expression decreases and Ang-2 expression increases in the cortex, hippocampus, and microvessels. The Ang-1/Ang-2 ratio decreased as quickly as 6 hours after SAH and reached its lowest 1 day after SAH. Finally, it was found that exogenous Ang-1 reduces SAH-associated BBB leakage and improves neurological function in post-SAH rats. Conclusions: Our findings suggest that the equilibrium between Ang-1 and Ang-2 is broken in a period shortly after SAH, and the treatment of exogenous Ang-1 injection alleviates neurological dysfunctions through decreasing BBB destruction.

Pan-cancer Analysis of Tumor Mutational Burden and Homologous Recombination DNA Damage Repair Using Targeted Next-Generation Sequencing

Hai-Yun Wang,Ling Deng,Ying-Qing Li,Xiao Zhang,Ya-Kang Long,Xu Zhang,Yan-Fen Feng,Yuan He,Tao Tang,Xin-Hua Yang,Fang Wang 대한암학회 2021 Cancer Research and Treatment Vol.53 No.4

Purpose Current variability in methods for tumor mutational burden (TMB) estimation and reporting demonstrates the urgent need for a homogeneous TMB assessment approach. Here, we compared TMB distributions in different cancer types using two customized targeted panels commonly used in clinical practice. Materials and Methods TMB spectra of 295- and 1021-gene panels in multiple cancer types were compared using targeted next-generation sequencing (NGS). The TMB distributions across a diverse cohort of 2,332 cancer cases were then investigated for their associations with clinical features. Treatment response data were collected for 222 patients who received immune-checkpoint inhibitors (ICIs) and their homologous recombination DNA damage repair (HR-DDR) and programmed death-ligand 1 (PD-L1) expression were additionally assessed and compared with the TMB and response rate. Results The median TMB between gene panels was similar despite a wide range in TMB values. The highest TMB was eight and 10 in patients with squamous cell carcinoma and esophageal carcinoma according to the classification of histopathology and cancer types, respectively. Twenty-three out of 103 patients (22.3%) were HR-DDR–positive and could benefit from ICI therapy; out of those 23 patients, seven patients had high TMB (p=0.004). Additionally, PD-L1 expression was not associated with TMB or treatment response among patients receiving ICIs. Conclusion Targeted NGS assays demonstrated the ability to evaluate TMB in pan-cancer samples as a tool to predict response to ICIs. In addition, TMB integrated with HR-DDR–positive status could be a significant biomarker for predicting ICI response in patients.

HDAC6 siRNA Inhibits Proliferation and Induces Apoptosis of HeLa Cells and its Related Molecular Mechanism

Qin, Hai-Xia,Cui, Hong-Kai,Pan, Ying,Yang, Jun,Ren, Yan-Fang,Hua, Cai-Hong,Hua, Fang-Fang,Qiao, Yu-Huan Asian Pacific Journal of Cancer Prevention 2012 Asian Pacific journal of cancer prevention Vol.13 No.7

Objective: To investigate the effects of histone deacetylase 6 (HDAC6) siRNA on cell proliferation and cell apoptosis of the HeLa cervical carcinoma cell line and the molecular mechanisms involved. Methods: Division was into three groups: A, the untreated group; B, the control siRNA group; and C, the HDAC6 siRNA group. Lipofectamine 2000 was used for siRNA transfection, and Western blot analysis was used to determine the protein levels. Cell proliferation and apoptosis were characterized using a CCK-8 assay and flow cytometry, respectively. Results: HDAC6 protein expression in the HDAC6 siRNA-transfection group was significantly lower (P < 0.05) than in the untreated and control siRNA groups. The CCK-8 kit results demonstrated that the proliferation of HeLa cells was clearly inhibited in the HDAC6 siRNA transfection group (P < 0.05). In addition, flow cytometry revealed that the early apoptotic rate ($26.0%{\pm}0.87%$) was significantly elevated (P < 0.05) as compared with the untreated group ($10.6%{\pm}1.19%$) and control siRNA group ($8.61%{\pm}0.98%$). Furthermore, Western blot analysis indicated that bcl-2 protein expression in the HDAC6 siRNA-transfection group was down-regulated, whereas the expression of p21 and bax was up-regulated. Conclusion: HDAC6 plays an essential role in the occurrence and development of cervical carcinoma, and the down-regulation of HDAC6 expression may be useful molecular therapeutic method.

Efficacy of Pap Test in Combination with ThinPrep Cytological Test in Screening for Cervical Cancer

Chen, Hua,Shu, Hui-Min,Chang, Zhou-Lin,Wang, Zhi-Feng,Yao, Hai-Hong,Zhu, Hong-Mei,Lu, Tian-Mei,Ma, Qiang-Yan,Yang, Bin-Lie Asian Pacific Journal of Cancer Prevention 2012 Asian Pacific journal of cancer prevention Vol.13 No.4

Background: Our aim was to investigate the efficacy of the Pap test in combination with the ThinPrep cytological test (TCT) in screening for cervical cancer in China. Design: From March 2006 to October 2008, 988 women with the mean age $46.4{\pm}10.5$ years (range, 23-80 years) were recruited to receive cervical cancer screening. Pap test results ${\geq}$ grade III and TCT findings ${\geq}$ ASCUS/AGUS were considered abnormal. Subjects with a Pap test result ${\geq}$ grade IIb received TCT. Colposcopy and biopsies were performed in all participants, and final diagnosis was based on pathological findings. The sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV) and Youden index for predicting CIN I or above were determined. Results: The sensitivity, specificity, PPV, NPV and Youden index of the Pap test were 43.1%, 97.2%, 70.0%, 91.9%, and 40.3%, respectively. The same values for TCT in predicting CIN were 80.0%, 63.2%, 16.0%, 97.3%, and 43.2%, respectively. The two tests in combination gave values for predicting CIN of 64.8%, 87.6%, 43.6%, 94.4%, and 53.5%, respectively. Combined testing exhibited the highest Youden index (53.4%). Conclusion: The Pap test with a reduced threshold in combination with the TCT has high sensitivity and high specificity in screening for cervical cancer.

Associations of hypoxia inducible factor-1a gene polymorphisms with susceptibility to digestive tract cancers: a case–control study and meta-analysis

Zhi-Hai Ni,Xian-Jun Liang,Jing-Gang Mo,Yi Zhang,Jian-Hua Liang,Yu-Sha Yang,Yong Zhou,Zhao-Hua Li,Jian-Liang Zhang,Yin-Lu Ding,Peng Zhang,Jin-Qing Wang 한국유전학회 2015 Genes & Genomics Vol.37 No.11

We aim to investigate the correlations of hypoxia inducible factor-1a (HIF-1a) C1772T (rs11549465) and G1790A (rs11549467) gene polymorphisms with digestive tract cancers. A sum of 267 digestive tract cancers patients were hospitalized in Taizhou Central Hospital of Zhejiang Province as case group between December 2012 and December 2014. Additionally, 275 healthy people who had a physical examination in our hospital at the same time were selected as control group. Polymerase chain reaction-restriction fragment length polymorphism was utilized for detecting allele and genotype frequency of different locus in case and control group. Meta-analysis was performed using Comprehensive Metaanalysis 2.0 (Biostat Inc., Englewood, New Jersey, USA). Our result showed statistical significance only exists in family history of cancer between case and control group (P\0.05). Both C1772T (rs11549465) and G1790A (rs11549467) polymorphisms showed positive correlations with an increasing risk of digestive tract cancers. The frequencies of TT genotype of C1772T (rs11549465) and GA, AA genotypes of G1790A (rs11549467) polymorphisms in case group were evidently higher compared with the controls (all P\0.05). Besides, the comparison of allele and dominant models of HIF-1a C1772T (rs11549465) and G1790A (rs11549467) between two groups showed a significant difference (all P\0.05). Meta-analysis results further confirmed that the onset risk of digestive tract cancers may be improved under allele and dominant models of HIF-1a C1772T (rs11549465) and G1790A (rs11549467) (all P\0.05). Single nucleotide polymorphisms of HIF-1a C1772T (rs11549465) and G1790A (rs11549467) may play a role in development of digestive tract cancers.

Cable anomaly detection driven by spatiotemporal correlation dissimilarity measurements of bridge grouped cable forces

Ting-Hua Yi,Dong-Hui Yang,Hai-Lun Gu,Zhanjun Wu 국제구조공학회 2022 Smart Structures and Systems, An International Jou Vol.30 No.6

Stayed cables are the key components for transmitting loads in cable-stayed bridges. Therefore, it is very important to evaluate the cable force condition to ensure bridge safety. An online condition assessment and anomaly localization method is proposed for cables based on the spatiotemporal correlation of grouped cable forces. First, an anomaly sensitive feature index is obtained based on the distribution characteristics of grouped cable forces. Second, an adaptive anomaly detection method based on the <i>k</i>-nearest neighbor rule is used to perform dissimilarity measurements on the extracted feature index, and such a method can effectively remove the interference of environment factors and vehicle loads on online condition assessment of the grouped cable forces. Furthermore, an online anomaly isolation and localization method for stay cables is established, and the complete decomposition contributions method is used to decompose the feature matrix of the grouped cable forces and build an anomaly isolation index. Finally, case studies were carried out to validate the proposed method using an in-service cable-stayed bridge equipped with a structural health monitoring system. The results show that the proposed approach is sensitive to the abnormal distribution of grouped cable forces and is robust to the influence of interference factors. In addition, the proposed approach can also localize the cables with abnormal cable forces online, which can be successfully applied to the field monitoring of cables for cable-stayed bridges.

Design of Acquisition and Control System of Granary Supervisory Control and Data Acquisition System

Li-hua Wu,Jia-yu Yao,Xi-rong Lin,Hai-yang Zhang 보안공학연구지원센터 2015 International Journal of Multimedia and Ubiquitous Vol.10 No.6

Grain stored in granary is easily spoiled due to accumulated hear or humidity if not monitored and maintained properly. Supervisory control and data acquisition (SCADA) system is commonly used in granary to provide real-time storage information. Major functionalities in the granary SCADA system is usually provided by an acquisition and control system based on single chip computer installed inside or near the granary. Based on theoretical and commissioning data, the design of the acquisition and control system was introduced in this paper. The acquisition and control system is able to acquire real-time data of temperature, humidity and concentration of CO2 inside the granary. It also provides the functionalities of open/shut the granary windows, as well as turning on/off the high-power roller shutter doors and blowers. Users are able to obtain real-time monitored data and control the system accordingly.

QTL mapping and identification of candidate genes for cold tolerance at the germination stage in wild rice

Pan Ying-Hua,Nong Bao-Xuan,Chen Lei,Yang Xing-Hai,Xia Xiu-Zhong,Zhang Zong-Qiong,Qing Dong-Jin,Gao Ju,Huang Cheng-Cui,Li Dan-Ting,Deng Guo-Fu 한국유전학회 2023 Genes & Genomics Vol.45 No.7

Background Cold damage stress significantly affects rice growth (germination and seedling) and causes serious losses in yield in temperate and high-altitude areas around the globe. Objective This study aimed to explore the cold tolerance (CT) locus of rice and create new cold-tolerant germplasm. We constructed a chromosome segment substitution line (CSSL) with strong CT and fine mapped quantitative trait loci (QTLs) associated with CT by performing the whole-genome resequencing of CSSL with phenotypes under cold treatment. Methods A chromosome CSSL, including 271 lines from a cross between the cold-tolerant wild rice Y11 (Oryza rufipogon Griff.) and the cold-sensitive rice variety GH998, was developed to map QTLs conferring CT at the germination stage. The whole-genome resequencing was performed on CSSL for mapping QTLs of associated with CT at the germination stage. Results A high-density linkage map of the CSSLs was developed using the whole-genome resequencing of 1484 bins. The QTL analysis using 615,466 single-nucleotide polymorphisms (SNPs) led to the identification of 2 QTLs related to germination rate at low-temperature on chromosome 8 (qCTG-8) and chromosome 11 (qCTG-11). The qCTG-8 and qCTG-11 explained 14.55% and 14.31% of the total phenotypic variation, respectively. We narrowed down qCTG-8 and qCTG-11 to 195.5 and 78.83-kb regions, respectively. The expression patterns of important candidate genes in different tissues, and of RNA-sequencing (RNA-seq) in CSSLs, were identified based on gene sequences in qCTG-8 and qCTG-11 cold-induced expression analysis. LOC_Os08g01120 and LOC_Os08g01390 were identified as candidate genes in qCTG-8, and LOC_Os11g32880 was identified as a candidate gene in qCTG-11. Conclusions This study demonstrated a general method that could be used to identify useful loci and genes in wild rice and aid in the future cloning of candidate genes of qCTG-8 and qCTG-11. The CSSLs with strong CT were supported for breeding cold-tolerant rice varieties.

Effect of TLR4 and B7-H1 on Immune Escape of Urothelial Bladder Cancer and its Clinical Significance

Wang, Yong-Hua,Cao, Yan-Wei,Yang, Xue-Cheng,Niu, Hai-Tao,Sun, Li-Jiang,Wang, Xin-Sheng,Liu, Jing Asian Pacific Journal of Cancer Prevention 2014 Asian Pacific journal of cancer prevention Vol.15 No.3

Background/Aim: Toll-like receptor 4 (TLR4) and B7-H1, both normally expressed restricted to immune cells, are found to be aberrantly expressed in a majority of human tumors and may play important roles in regulation of tumor immunity. It has been shown that urothelial bladder cancer (UBC) patients can manifest tumoral immune escape which may be a potential critical factor in tumor pathogenesis and progression. However, so far, the mechanisms of UBC-related immune escape have not been clarified. The aim of this study was to investigate the effect of TLR4 and B7-H1 on immune escape of UBC. Methods: Bladder cancer T24 cells were pre-incubated with LPS and co-cultured with tumor specific CTLs. CTL cytotoxicity and apoptosis rates were measured by MTT assay and flow cytometry, respectively. The effects of an ERK inhibitor on B7-H1 expression and CTL cytotoxicity against T24 cells were also evaluated. In addition, TLR4, B7-H1 and PD-1 protein expression was analyzed by immunohistochemistry in 60 UBC specimens and 10 normal urothelia. Results: TLR4 activation protected T24 cells from CTL killing via B7-H1 overexpression. However PD98059, an inhibitor of ERK, enhanced CTL killing of T24 cells by reducing B7-H1 expression. TLR4 expression was generally decreased in UBC specimens, while B7-H1 and PD-1 were greatly overexpressed. Moreover, expression of both B7-H1 and PD-1 was significantly associated with UICC stage and WHO grade classification. Conclusions: TLR4 and B7-H1 may contribute to immune escape of UBC. Targeting B7-H1 or the ERK pathway may offer new immunotherapy strategies for bladder cancer.