miR-638 is a new biomarker for outcome prediction of non-small cell lung cancer patients receiving chemotherapy

Fang Wang,Jian-fang Lou,Yan Cao,Xin-hui Shi,Peng Wang,Jian Xu,Er-fu Xie,Ting Xu,Rui-hong Sun,Jianyu Rao,Pu-wen Huang,Shi-yang Pan,Hong Wang 생화학분자생물학회 2015 Experimental and molecular medicine Vol.47 No.-

MicroRNAs (miRNAs), a class of small non-coding RNAs, mediate gene expression by either cleaving target mRNAs or inhibiting their translation. They have key roles in the tumorigenesis of several cancers, including non-small cell lung cancer (NSCLC). The aim of this study was to investigate the clinical significance of miR-638 in the evaluation of NSCLC patient prognosis in response to chemotherapy. First, we detected miR-638 expression levels in vitro in the culture supernatants of the NSCLC cell line SPC-A1 treated with cisplatin, as well as the apoptosis rates of SPC-A1. Second, serum miR-638 expression levels were detected in vivo by using nude mice xenograft models bearing SPC-A1 with and without cisplatin treatment. In the clinic, the serum miR-638 levels of 200 cases of NSCLC patients before and after chemotherapy were determined by quantitative real-time PCR, and the associations of clinicopathological features with miR-638 expression patterns after chemotherapy were analyzed. Our data helped in demonstrating that cisplatin induced apoptosis of the SPC-A1 cells in a dose- and time-dependent manner accompanied by increased miR-638 expression levels in the culture supernatants. In vivo data further revealed that cisplatin induced miR-638 upregulation in the serum derived from mice xenograft models, and in NSCLC patient sera, miR-638 expression patterns after chemotherapy significantly correlated with lymph node metastasis. Moreover, survival analyses revealed that patients who had increased miR-638 levels after chemotherapy showed significantly longer survival time than those who had decreased miR-638 levels. Our findings suggest that serum miR-638 levels are associated with the survival of NSCLC patients and may be considered a potential independent predictor for NSCLC prognosis.

Parkinson’s Disease with Fatigue: Clinical Characteristics and Potential Mechanisms Relevant to α-Synuclein Oligomer

Li-Jun Zuo,Shu-Yang Yu,Fang Wang,Yanghui Xia,Ying-Shan Piao,Yang Du,Teng-Hong Lian,Rui-Dan Wang,Qiu-Jin Yu,Ya-Jie Wang,Xiao-Min Wang,Piu Chan,Sheng-Di Chen,Yongjun Wang,Wei Zhang 대한신경과학회 2016 Journal of Clinical Neurology Vol.12 No.2

Background and Purpose The aim of this study was to identify the clinical characteristics and potential mechanisms relevant to pathological proteins in Parkinson’s disease (PD) patients who experience fatigue. Methods PD patients (n=102) were evaluated using a fatigue severity scale and scales for motor and nonmotor symptoms. The levels of three pathological proteins—α-synuclein oligomer, β-amyloid (Aβ)1-42, and tau—were measured in 102 cerebrospinal fluid (CSF) samples from these PD patients. Linear regression analyses were performed between fatigue score and the CSF levels of the above-listed pathological proteins in PD patients. Results The frequency of fatigue in the PD patients was 62.75%. The fatigue group had worse motor symptoms and anxiety, depression, and autonomic dysfunction. The CSF level of α-synuclein oligomer was higher and that of Aβ1-42 was lower in the fatigue group than in the non-fatigue group. In multiple linear regression analyses, fatigue severity was significantly and positively correlated with the α-synuclein oligomer level in the CSF of PD patients, after adjusting for confounders. Conclusions PD patients experience a high frequency of fatigue. PD patients with fatigue have worse motor and part nonmotor symptoms. Fatigue in PD patients is associated with an increased α-synuclein oligomer level in the CSF

Metastasis associated genomic aberrations in stage II rectal cancer

Hong Zhao,Zhi-Zhou Shi,Rui Jiang,Dong-Bing Zhao,Hai-Tao Zhou,Jian-Wei Liang,Xin-Yu Bi,Jian-Jun Zhao,Zhi-Yu Li,Jian-Guo Zhou,Zhen Huang,Ye-Fan Zhang,Jian Wang,Xin Xu,Yan Cai,Ming-Rong Wang,Yu Zhang 한국유전학회 2016 Genes & Genomics Vol.38 No.11

Genomic aberrations of rectal carcinoma, especially DNA copy number changes associated with metastasis were largely unclear. We aim to identify the metastasis associated biomarkers in stage II rectal cancer. Formalin-fixed, paraffin-embedded primary tumor tissues of stage II rectal carcinoma were analyzed by array-based comparative genomic hybridization, and genomic aberrations were identified by Genomic Workbench and SAM software. Copy number changes and mRNA expressions were validated by Real-time PCR in an independent rectal cancer samples. The results showed that the most frequent gains in stage II rectal cancer were at 1q21.2-q23.1, 3p21.31, 11q12.2-q23.3, 12q24.11-q24.31, 12q13.11-q14.1 and losses in 18q11.2-q23, 17q21.33-q22, 13q31.1-q31.3, 21q21.1-q21.3, 8p23.3-p23.1 and 4q22.1-q23. Twenty-two amplifications and five homozygous deletions were also identified. We further found that S100A1 (1q21.3-q23.1), MCM7 (7q22.1) and JUND (19p13.11) were amplified and overexpressed in stage II rectal cancer. Interestingly, the genomic aberrations affected 14 signaling pathways including VEGF signaling pathway and fatty acid metabolism. Most importantly, loss of 13q31.1-q34 and gain of 1q44 were associated with distant metastasis. Our results indicated that these metastasis associated genomic changes may be useful to reveal the pathogenesis of rectal cancer metastasis and identify candidate biomarkers.

Clinical Utility of Haptoglobin in Combination with CEA, NSE and CYFRA21-1 for Diagnosis of Lung Cancer

Wang, Bing,He, Yu-Jie,Tian, Ying-Xing,Yang, Rui-Ning,Zhu, Yue-Rong,Qiu, Hong Asian Pacific Journal of Cancer Prevention 2014 Asian Pacific journal of cancer prevention Vol.15 No.22

Purpose: To investigate the clinical value in lung cancer of a combination of four serum tumor markers, haptoglobin (Hp), carcinoembryonic antigen (CEA), neuron specific enolase (NSE) as well as the cytokeratin 19 fragment (CYFRA21-1). Materials and Methods: Serum Hp (with immune-turbidimetric method), CEA, NSE, CYFRA21-1 (with chemiluminescence method) level were assessed in 193 patients with lung cancer, 87 patients with benign lung disease and 150 healthy controls. Differences of expression were compared among groups, and joint effects of these tumor markers for the diagnosis of lung cancer were analyzed. Results: Serum tumor marker levels in patients with lung cancer were obviously higher than those with benign lung disease and normal controls (p<0.01). The sensitivities of Hp, CEA, NSE and CYFRA21-1 were 43.5%, 40.9%, 23.3% and 41.5%, with specificities of 90.7%, 99.2%, 97.9% and 97.9%. Four tumor markers combined together could produce a positive detection rate of 85.0%, significantly higher than that of any single test. With squamous carcinomas, the positive detection rates with Hp and CYFRA21-1 were higher than that of other markers. In the adenocarcinoma case, the positive detection rate of CEA was higher than that of other markers. For small cell carcinomas, the positive detection rate of NSE was highest. The area under receiver operating characteristic curve ($AUC^{ROC}$) of Hp in squamous carcinoma (0.805) was higher than in adenocarcinoma (0.664) and small cell carcinoma (0.665). Conclusions: Hp can be used as a new serum tumor marker for lung cancer. Combination detection of Hp, CEA, NSE and CYFRA21-1 could significantly improve the sensitivity and specificity in diagnosis of lung cancer, and could be useful for pathological typing.

Overexpression of Long Non-Coding RNA HOTAIR Promotes Tumor Growth and Metastasis in Human Osteosarcoma

Wang, Bo,Su, Yun,Yang, Qun,Lv, Decheng,Zhang, Weiguo,Tang, Kai,Wang, Hong,Zhang, Rui,Liu, Yang Korean Society for Molecular and Cellular Biology 2015 Molecules and cells Vol.38 No.5

Human osteosarcoma usually presented a high tendency to metastatic spread and caused poor outcomes, however, the underlying mechanism was still largely unknown. In the present study, using a series of in vitro experiments and an animal model, we investigated the roles of HOX antisense intergenic RNA (HOTAIR) during the proliferation and invasion of osteosarcoma. According with our results, HOTAIR was commonly overexpressed in osteosarcoma, which significantly correlated with advanced tumor stage, highly histological grade and poor prognosis. In vitro and in vivo experiments demonstrated that knockdown of HOTAIR could notably suppress cellular proliferation, inhibit invasion and decrease the secretion of MMP2 and MMP9 in osteosarcoma. Collectively, our results suggested that HOTAIR might be a potent therapeutic target for osteosarcoma.

Macrophage-secreted Exosomes Delivering miRNA-21 Inhibitor can Regulate BGC-823 Cell Proliferation

Wang, Jian-Jun,Wang, Ze-You,Chen, Rui,Xiong, Jing,Yao, Yong-Liang,Wu, Jian-Hong,Li, Guang-Xin Asian Pacific Journal of Cancer Prevention 2015 Asian Pacific journal of cancer prevention Vol.16 No.10

Exosomes, membranous nanovesicles, naturally carry bio-macromolecules or miRNA and play impoetant roles in tumor pathogenesis. Here, we showed that macrophages cell-derived exosomes can function as vehicles to deliver exogenous miR-21 inhibitor into BGC-823 gastric cancer cells. Exosomes loaded with miR-21inhibitor significantly increased miR-21 levels in BGC-823, but miR-21inhibitor loaded in exosomes exerted an opposite effect. miRNA transfected with exosomes had less cellular toxicity to host cells compared to conventional transfection methods. The miR-21inhibitor loaded exosomes promoted the migration ability and reduced apoptosis of BGC-823 gastric cancer cells. These observations indicate that miR-21 acts as a tumor promoter by targeting the PDCD4 gene and preventing apoptosis of gastric cancer cells through inhibition of PDCD4 expression. Furthermore, exosome -mediated miR-21 inhibitor delivery resulted in functionally more efficient inhibition and less cellular toxicity compared to conventional transfection methods. Similar approaches could be useful in modification of target biomolecules in vitro and in vivo. These findings contribute to our understanding of the functions of miR-21 and exosomes as a carrier for therapy of gastric cancer.

Effect of High Energy Shot Peening on the Microstructure and Mechanical Property of AZ31B Mg Alloy/HSLA350 Steel Lap Joints

Rui Li,Xinjian Yuan,Ting Li,Miao Hong,Shiwei Tao,Zhuo Chen,Ge Wang 한국정밀공학회 2021 International Journal of Precision Engineering and Vol.22 No.5

When using high energy shot peening (HESP) technology, the surface layer of the welded joints produced grain breakage and residual compressive stress. When the shot peening strength is the optimal parameter 0.10 MPa, the residual compressive stress reaches a maximum value of 74.02 MPa, dislocation density in welded joints increased significantly and the tensile shear strength of the joint was increased by 18.6% compared to the joint without HESP treatment (205 MPa), and the fracture position of the welded joint was located in the Al alloy base material, these were brought by fi ne grain strengthening and strain strengthening. When the shot peening strength was 0.05 MPa, the strength of the joint was also improved, but the fracture position of the joint was the same as that without HESP treatment, and they were all in the fusion zone. However, when the shot peening strength was further increased to 0.15 MPa, severe cracks appeared inside the joint, which deteriorates the strength of the Mg/steel joint.

Dimethyl Sulfoxide Suppresses Mouse 4T1 Breast Cancer Growth by Modulating Tumor-Associated Macrophage Differentiation

Rui Deng,Shi-min Wang,Tao Yin,Ting-hong Ye,Guo-bo Shen, Ling Li,Jing-yi Zhao,Ya-xiong Sang,Xiao-gang Duan,Yu-Quan Wei 한국유방암학회 2014 Journal of breast cancer Vol.17 No.1

Purpose: The universal organic solvent dimethyl sulfoxide (DMSO)can be used as a differentiation inducer of many cancer cells andhas been widely used as a solvent in laboratories. However, itseffects on breast cancer cells are not well understood. The aimof this study is to investigate the effect and associated mechanismsof DMSO on mouse breast cancer. Methods: We appliedDMSO to observe the effect on tumors in a mouse breast cancermodel. Tumor-associated macrophages (TAMs) were tested byflow cytometry. Ex vivo tumor microenvironment was imitated by4T1 cultured cell conditioned medium. Enzyme-linked immunosorbentassays were performed to detect interleukin (IL)-10 andIL-12 expression in medium. To investigate the cytotoxicity ofDMSO on TAMs, 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazoliumbromide (MTT) assays were performed. Results: We foundthat DMSO produced tumor retardation when injected into mouseperitoneal cavities in a certain concentration range (0.5–1.0 mg/g). Furthermore, as detected by flow cytometry, TAM subtypeswere found to be transformed. We further imitated a tumor microenvironmentin vitro by using 4T1 cultured cell conditionedmedium. Similarly, by using low concentration DMSO (1.0%–2.0% v/v), TAMs were induced to polarize to the classically activatedmacrophage (M1-type) and inhibited from polarizing intothe alternatively activated macrophage (M2-type) in the conditionedmedium. IL-10 expression in tumors was reduced, whileIL-12 was increased compared with the control. Furthermore, wereported that 2.0% (v/v) DMSO could lead to cytotoxicity in peritonealmacrophages after 48 hours in MTT assays. Conclusion:Our findings suggest that DMSO could exert antitumor effects in4T1 cancer-bearing mice by reversing TAM orientation and polarizationfrom M2- to M1-type TAMs. These data may providenovel insight into studying breast cancer immunotherapy.

Complete mitochondrial genome of a kind of snakehead fish Channa siamensis and its phylogenetic consideration

Rui Li,Gang Wang,Zheng‑Yong Wen,Yuan‑Chao Zou,Chuan‑Jie Qin,Yu Luo,Jun Wang,Gui‑Hong Chen 한국유전학회 2019 Genes & Genomics Vol.41 No.2

The snakehead fish, Channa siamensis, belongs to the genus of Channa (perciformes: Channidae) and was first reported by Günther in 1861. Despite it has been described approximately for 15 decades, the genetic information is limited and the taxon status of this kind of fish is still unclear. The primary objective of this study is to get more genomic data and calculate the taxon location of this kind of fish. The next generation sequencing method was used to obtain the whole mitochondrial DNA information, and bioinformatic analysis was performed to investigate the evolutionary status and taxon location of C. siamensis. The circular mitochondrial DNA was 16,570 bp in length, and which showed typical piscine structure and arrangement. The overall nucleotide composition was 29.28% A, 24.72% T, 30.71% C, 15.29% G, with 54.1% AT, respectively. Phylogenetic analyses using concatenated amino acid and nucleotide sequences of the 13 protein-coding genes with two different methods (Maximum likelihood and Bayesian analysis) both highly supported C. siamensis belongs to the genus Channa and shows a close relationship with C. micropeltes. These data will provide more useful information for a better understanding of the mitochondrial genomic diversities and evolution in fish as well as novel genetic markers for studying population genetics and species identification.

Genetic Diversity of Toxoplasma gondii Strains from Different Hosts and Geographical Regions by Sequence Analysis of GRA20 Gene

Hong-Rui Ning,Si-Yang Huang,Jin-Lei Wang,Qian-Ming Xu,Xing-Quan Zhu 대한기생충학열대의학회 2015 The Korean Journal of Parasitology Vol.53 No.3

Toxoplasma gondii is a eukaryotic parasite of the phylum Apicomplexa, which infects all warm-blood animals, including humans. In the present study, we examined sequence variation in dense granule 20 (GRA20) genes among T. gondii isolates collected from different hosts and geographical regions worldwide. The complete GRA20 genes were amplified from 16 T. gondii isolates using PCR, sequence were analyzed, and phylogenetic reconstruction was analyzed by maximum parsimony (MP) and maximum likelihood (ML) methods. The results showed that the complete GRA20 gene sequence was 1,586 bp in length among all the isolates used in this study, and the sequence variations in nucleotides were 0-7.9% among all strains. However, removing the type III strains (CTG, VEG), the sequence variations became very low, only 0-0.7%. These results indicated that the GRA20 sequence in type III was more divergence. Phylogenetic analysis of GRA20 sequences using MP and ML methods can differentiate 2 major clonal lineage types (type I and type III) into their respective clusters, indicating the GRA20 gene may represent a novel genetic marker for intraspecific phylogenetic analyses of T. gondii.