Identification of novel rheumatoid arthritis-associated MiRNA-204-5p from plasma exosomes

Wu Long-Fei,Zhang Qin,Mo Xing-Bo,Lin Jun,Wu Yang-Lin,Lu Xin,He Pei,Wu Jian,Guo Yu-Fan,Wang Ming-Jun,Ren Wen-Yan,Deng Hong-Wen,Lei Shu-Feng,Deng Fei-Yan 생화학분자생물학회 2022 Experimental and molecular medicine Vol.54 No.-

Rheumatoid arthritis (RA) is an autoimmune disease characterized by infiltration of immune cells in the synovium. However, the crosstalk of immune cells and synovial fibroblasts is still largely unknown. Here, global miRNA screening in plasma exosomes was carried out with a custom microarray (RA patients vs. healthy controls = 9:9). A total of 14 exosomal miRNAs were abnormally expressed in the RA patients. Then, downregulated expression of exosomal miR-204-5p was confirmed in both the replication (RA patients vs. healthy controls = 30:30) and validation groups (RA patients vs. healthy controls = 56:60). Similar to the findings obtained in humans, a decreased abundance of exosomal miR-204-5p was observed in mice with collagen-induced arthritis (CIA). Furthermore, Spearman correlation analysis indicated that plasma exosomal miR-204-5p expression was inversely correlated with disease parameters of RA patients, such as rheumatoid factor, erythrocyte sedimentation rate, and C-reactive protein. In vitro, our data showed that human T lymphocytes released exosomes containing large amounts of miR-204-5p, which can be transferred into synovial fibroblasts, inhibiting cell proliferation. Overexpression of miR-204-5p in synovial fibroblasts suppressed synovial fibroblast activation by targeting genes related to cell proliferation and invasion. In vivo assays found that administration of lentiviruses expressing miR-204-5p markedly alleviated the disease progression of the mice with CIA. Collectively, this study identified a novel RA-associated plasma exosomal miRNA-204-5p that mediates the communication between immune cells and synovial fibroblasts and can be used as a potential biomarker for RA diagnosis and treatment.

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.

Intravenous Flurbiprofen Axetil Enhances Analgesic Effect of Opioids in Patients with Refractory Cancer Pain by Increasing Plasma β-Endorphin

Wu, Ting-Ting,Wang, Zhi-Gang,Ou, Wu-Ling,Wang, Jun,Yao, Guo-Qing,Yang, Bo,Rao, Zhi-Guo,Gao, Jian-Fei,Zhang, Bi-Cheng Asian Pacific Journal of Cancer Prevention 2014 Asian Pacific journal of cancer prevention Vol.15 No.24

Background: The study aimed to investigate the analgesic effect of a combination of intravenous flurbiprofen axetil and opioids, and evaluate the relationship between refractory pain relief and plasma ${\beta}$-endorphin levels in cancer patients. Materials and Methods: A total of 120 cancer patients was randomly divided into two groups, 60 patients took orally morphine sulfate sustained-release tablets in group A, and another 60 patients receiving the combination treatment of intravenous flurbiprofen axetil and opioid drugs in group B. After 7 days, pain relief, quality of life improvement and side effects were evaluated. Furthermore, plasma ${\beta}$-endorphin levels were measured by radioimmunoassay. Results: With the combination treatment of intravenous intravenous flurbiprofen axetil and opioids, the total effective rate of pain relief rose to 91.4%, as compared to 82.1% when morphine sulfate sustained-release tablet was used alone. Compared with that of group A, the analgesic effect increased in group B (p=0.031). Moreover, satisfactory pain relief was associated with a significant increase in plasma ${\beta}$-endorphin levels. After the treatment, plasma ${\beta}$-endorphin level in group B was $62.4{\pm}13.5pg/ml$, which was higher than that in group A ($45.8{\pm}11.2pg/ml$) (p<0.05). Conclusions: Our results suggest the combination of intravenous flurbiprofen axetil and opioids can enhance the analgesic effect of opioid drugs by increasing plasma ${\beta}$-endorphin levels, which would offer a selected and reliable strategy for refractory cancer pain treatment.

Down-regulated MYH11 Expression Correlates with Poor Prognosis in Stage II and III Colorectal Cancer

Wang, Ren-Jie,Wu, Peng,Cai, Guo-Xiang,Wang, Zhi-Min,Xu, Ye,Peng, Jun-Jie,Sheng, Wei-Qi,Lu, Hong-Fen,Cai, San-Jun Asian Pacific Journal of Cancer Prevention 2014 Asian Pacific journal of cancer prevention Vol.15 No.17

The MYH11 gene may be related to cell migration and adhesion, intracellular transport, and signal transduction. However, its relationship with prognosis is still uncertain. The aim of this study was to investigate correlations between MYH11 gene expression and prognosis in 58 patients with stage II and III colorectal cancer. Quantitative real-time polymerase chain reaction was performed in fresh CRC tissues to examine mRNA expression, and immunohistochemistry was performed with paraffin-embedded specimens for protein expression. On univariate analysis, MYH11 expression at both mRNA and protein levels, perineural invasion and lymphovascular invasion were related to disease-free survival (p<0.05; log-rank test). Cancers with lower MYH11 expression were more likely to have a poor prognosis. Otherwise, MYH11 expression was unrelated to patient clinicopathological features. On multivariate analysis, low MYH11 expression proved to be an independent adverse prognosticator (p<0.05). These findings show that MYH11 can contribute to predicting prognosis in stage II and III colorectal cancers.

The genome of the mesopolyploid crop species Brassica rapa

Wang, Xiaowu,Wang, Hanzhong,Wang, Jun,Sun, Rifei,Wu, Jian,Liu, Shengyi,Bai, Yinqi,Mun, Jeong-Hwan,Bancroft, Ian,Cheng, Feng,Huang, Sanwen,Li, Xixiang,Hua, Wei,Wang, Junyi,Wang, Xiyin,Freeling, Michael Nature Publishing Group, a division of Macmillan P 2011 Nature genetics Vol.43 No.10

We report the annotation and analysis of the draft genome sequence of Brassica rapa accession Chiifu-401-42, a Chinese cabbage. We modeled 41,174 protein coding genes in the B. rapa genome, which has undergone genome triplication. We used Arabidopsis thaliana as an outgroup for investigating the consequences of genome triplication, such as structural and functional evolution. The extent of gene loss (fractionation) among triplicated genome segments varies, with one of the three copies consistently retaining a disproportionately large fraction of the genes expected to have been present in its ancestor. Variation in the number of members of gene families present in the genome may contribute to the remarkable morphological plasticity of Brassica species. The B. rapa genome sequence provides an important resource for studying the evolution of polyploid genomes and underpins the genetic improvement of Brassica oil and vegetable crops.

Mechanistic Analysis of Taxol-induced Multidrug Resistance in an Ovarian Cancer Cell Line

Wang, Ning-Ning,Zhao, Li-Jun,Wu, Li-Nan,He, Ming-Feng,Qu, Jun-Wei,Zhao, Yi-Bing,Zhao, Wan-Zhou,Li, Jie-Shou,Wang, Jin-Hua Asian Pacific Journal of Cancer Prevention 2013 Asian Pacific journal of cancer prevention Vol.14 No.9

Objectives: To establish a taxol-resistant cell line of human ovarian carcinoma (A2780/Taxol) and investigate its biological features. Methods: The drug-resistant cell line (A2780/Taxol) was established by continuous stepwise selection with increasing concentrations of Taxol. Cell morphology was assessed by microscopy and growth curves were generated with in vitro and in vivo tumor xenograft models. With rhodamine123 (Rh123) assays, cell cycle distribution and the apoptotic rate were analyzed by flow cytometry (FCM). Drug resistance-related and signal associated proteins, including P-gp, MRPs, caveolin-1, PKC-${\alpha}$, Akt, ERK1/2, were detected by Western blotting. Results: A2780/Taxol cells were established with stable resistance to taxol. The drug resistance index (RI) was 430.7. Cross-resistance to other drugs was also shown, but there was no significant change to radioresistance. Compared with parental cells, A2780/Taxol cells were significantly heteromorphous, with a significant delay in population doubling time and reduced uptake of Rh123 (p<0.01). In vivo, tumor take by A2780 cells was 80%, and tumor volume increased gradually. In contrast, with A2780/Taxol cells in xenograft models there was no tumor development. FCM analysis revealed that A2780/Taxol cells had a higher percentage of G0/G1 and lower S phase, but no changes of G2 phase and the apoptosis rate. Expression of P-gp, MRP1, MRP2, BCRP, LRP, caveolin-1, PKC-${\alpha}$, Phospho-ERK1/2 and Phospho-JNK protein was significantly up-regulated, while Akt and p38 MARK protein expression was not changed in A2780/Taxol cells. Conclusion: The A2780/Taxol cell line is an ideal model to investigate the mechanism of muti-drug resistance related to overexpression of drug-resistance associated proteins and activation of the PKC-${\alpha}/ERK$ (JNK) signaling pathway.

Relationship between EGFR Over-expression and Clinicopathologic Characteristics in Squamous Cell Carcinoma of the Esophagus: A Meta-analysis

Wang, Jun,Yu, Jin-Ming,Jing, Shao-Wu,Guo, Yin,Wu, Ya-Jing,Li, Na,Jiao, Wen-Peng,Wang, Li,Zhang, Yan-Jun Asian Pacific Journal of Cancer Prevention 2014 Asian Pacific journal of cancer prevention Vol.15 No.14

Over-expression of epidermal growth factor receptor (EGFR) has been identified as a common feature associated with clinical outcome in many types of cancer, including squamous cell carcinoma of the oesophagus (SCCO). However, the clinical importance of EGFR over-expression in SCCO remains unsettled as conflicting results exist. Therefore we carried out the present meta-analysis of published studies for clarification. A total of 13 studies including 1, 150 patients were enrolled. EGFR over-expression was positive in 722 of these cases. With EGFR over-expression, patients had higher depth of invasion, vascular invasion, and poor prognosis. However, expression had no relation with degree of differentiation, histological grade, lymph node metastasis, clinical stage or lymphatic invasion. EGFR over-expression is probably a valuable predictor for the T stage, vascular invasion and OS, and it could be used as a poor prognosis indicator for the esophageal SCC patients. Targeting therapy to EFGR should be considered to the combined treatment in SCCO.

A review of experimental methods for characterising composite viscosities of continuous fibre-reinforced polymer composites

Wang Jinhuo,Han Yang,Ge Xiaohong,Qi Zhengbing,Zhao Jun,Wang Rongwen,Wu Huawei,Han Taiping,Sun Shaoxun,Wang Hui,Lin Jia,Liu Yuejun,Kong Xiangsong,Chen Qiming,Zeng Xiangxu 한국유변학회 2023 Korea-Australia rheology journal Vol.35 No.2

Optimisation design of composite structures requires an accurate predictive model for forming behaviour. The simulation process contains a number of model parameters which include transverse and longitudinal viscosities of continuous fibrereinforced viscous composites, fundamental to predicting the shear rheology. Shearing the unidirectional composite along the fibre direction gives a measure of the longitudinal viscosity (LV), whilst shearing across or transverse to the fibre direction gives a measure of the transverse viscosity (TV). Numerous experimental work was conducted in the past to measure these two viscosities for various materials. However, conflicting measurements by different test methods were obtained and these apparent discrepancies had not yet been systematically investigated in any single study. This paper reviews previous work on characterisation techniques to further understand the cause of such discrepancy, and hence to improve measurement accuracy, which would benefit future work on theoretical modelling of the composite viscosities and optimisation simulation of composites forming. Some important findings, such as effects of resin-rich areas, contributory factors of elastic effects, non-Newtonian behaviour for composites with Newtonian matrix, aspect ratio and end effects of test samples, geometry effects of fibres and fibre rearrangement during shearing, existence of a mathematical relationship between LV and TV and necessary benchmarking exercise using Newtonian matrix composites, were summarised.

MiR-421 Regulates Apoptosis of BGC-823 Gastric Cancer Cells by Targeting Caspase-3

Wu, Jian-Hong,Yao, Yong-Liang,Gu, Tao,Wang, Ze-You,Pu, Xiong-Yong,Sun, Wang-Wei,Zhang, Xian,Jiang, Yi-Biao,Wang, Jian-Jun Asian Pacific Journal of Cancer Prevention 2014 Asian Pacific journal of cancer prevention Vol.15 No.13

MicroRNAs might act as oncogenes or tumor suppressors in cancer. Recent studies have shown that miR-421 is up-regulated in human gastric cancer. Here, we found that miR-421 was over-expressed in gastric cancer tissues and cell lines. Bioinformatics analysis predicted that the caspase-3 gene was a target of miR-421. Caspase-3 was negatively regulated by miR-421 at the post-transcriptional level. Bax and Bcl-2 were also regulated by miR-421. Moreover, tumor necrosis factor receptor-I and -II, death receptors in the apoptosis pathway, were up-regulated by miR-421. The over-expression of miR-421 promoted gastric cancer cell growth and inhibited apoptosis of the BGC-823 gastric cancer cell line. These observations indicate that miR-421 acts as a tumor promoter by targeting the caspase-3 gene and preventing apoptosis of gastric cancer cells through inhibition of caspase-3 expression. These findings contribute to our understanding of the functions of miR-421 in gastric cancer.

Prognostic Value of MGMT Promoter Methylation and TP53 Mutation in Glioblastomas Depends on IDH1 Mutation

Wang, Kai,Wang, Yin-Yan,Ma, Jun,Wang, Jiang-Fei,Li, Shao-Wu,Jiang, Tao,Dai, Jian-Ping Asian Pacific Journal of Cancer Prevention 2014 Asian Pacific journal of cancer prevention Vol.15 No.24

Several molecular markers have been proposed as predictors of outcome in patients with glioblastomas. We investigated the prognostic significance of $O^6$-methylguanine-DNA methyltransferase (MGMT) promoter methylation and TP53 mutation status dependent on isocitrate dehydrogenase 1 (IDH1) mutation in glioblastoma patients. A cohort of 78 patients with histologically confirmed glioblastomas treated with radiation therapy and chemotherapy were reviewed retrospectively. We evaluated the prognostic value of MGMT promoter methylation and TP53 mutation status with regard to progression-free survival (PFS) and overall survival (OS). It was revealed that mutations in IDH1, promoter methylation of MGMT, TP53 mutation, age, Karnofsky performance status (KFS), and extension of resection were independent prognostic factors. In patients with an IDH1 mutation, those with an MGMT methylation were associated with longer PFS (p=0.016) and OS (p=0.013). Nevertheless, the presence of TP53 mutation could stratify the PFS and OS of patients with IDH1 wild type (p=0.003 and 0.029 respectively, log-rank). The MGMT promoter methylation and TP53 mutation were associated with a favorable outcome of patients with and without mutant IDH1, respectively. The results indicate that glioblastomas with MGMT methylation or TP53 mutations have improved survival that may be influenced by IDH1 mutation status.