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.

Evaluation and Utilization of Xinjiang Melon (Cucumis melo ssp. melo) Germplasm Resources

Wu ming zhu,Yi hong ping,Feng jiong xin,Li jin song,Wang deng ming,Aken ya sheng,Zhang yong bing,Zhai wen qiang,Wu hai bo 한국원예학회 2006 한국원예학회 기타간행물 Vol.- No.-

MicroRNA-409-3p Inhibits Migration and Invasion of Bladder Cancer Cells via Targeting c-Met

Xin Xu,Liping Xie,Hong Chen,Yiwei Lin,Zhenghui Hu,Yeqing Mao,Jian Wu,Xianglai Xu,Yi Zhu,Shiqi Li,Xiangyi Zheng 한국분자세포생물학회 2013 Molecules and cells Vol.36 No.1

There is increasing evidence suggesting that dysregulation of certain microRNAs (miRNAs) may con-tribute to tumor progression and metastasis. Previous studies have shown that miR-409-3p is dysregulated in some malignancies, but its role in bladder cancer is still unknown. Here, we find that miR-409-3p is down-regulated in human bladder cancer tissues and cell lines. Enforced expression of miR-409-3p in bladder cancer cells significantly reduced their migration and invasion without affecting cell viability. Bioinformatics analysis identified the pro-metastatic gene c-Met as a potential miR-409-3p target. Further studies indicated that miR-409-3p suppressed the expression of c-Met by binding to its 3-untranslated region. Silencing of c-Met by small interfering RNAs phenocopied the effects of miR-409-3p overexpression, whereas restoration of c-Met in bladder cancer cells bladder cancer cells overexpressing miR-409-3p, partially reversed the suppressive effects of miR-409-3p. We further showed that MMP2 and MMP9 may be downstream effector proteins of miR-409-3p. These findings indicate that miR-409-3p could be a potential tumor suppressor in bladder cancer.

Risk Factors, Patterns, and Outcomes of Late Recurrence after Liver Resection for Patients with Hepatocellular Carcinoma (Analysis of a Multicenter Cohort over 15 Years)

( Xin-fei Xu ),( Jiong-jie Yu ),( Ju-dong Li ),( Hao Xing ),( Jun Han ),( Zhen-li Li ),( Han Wu ),( Han Zhang ),( Jian-hong Zhong ),( Yi- Sheng Huang ),( Ya-hao Zhou ),( Ting-hao Chen ),( Hong Wang ) 대한간학회 2018 춘·추계 학술대회 (KASL) Vol.2018 No.1

Aims: Late recurrence (> 2 years) after liver resection of hepatocellular carcinoma (HCC) is usually considered as multi-centric tumors or de novo cancer formation. We aimed to investigate risk factors, patterns and outcomes of late recurrence after HCC resection. Methods: From a multicenter database from 2001 to 2015, 734 patients who were alive and recurrence-free at 2 years after curative resection of initial HCC were enrolled into this retrospective study. Univariate and multivariate Cox-regression analysis were used to identify independent risk factors of late recurrence. Patterns, treatments and outcomes of late recurrence were investigated and analyzed. Results: During a median follow-up of 78.0 months after surgery, 303 patients (41.3%) developed late recurrence. Multivariate analysis revealed that cirrhosis, macroscopic vascular invasion, satellites, and tumor size > 5cm were independent risk factors of late recurrence. Among them, 273 (90.1%) were sole intrahepatic recurrence, 30 (9.9%) were concurrent intrahepatic and extrahepatic recurrence, and none of them was sole extrahepatic recurrence; 165 (54.4%) patients received curative treatments for recurrent HCC, including re-resection, transplantation and local ablation. Multivariate analysis showed regular postoperative surveillance and receiving curative treatments were two independent protective factors of prolonging survival for those patients with late recurrence. Conclusions: Late recurrence is correlated with cirrhosis and certain tumor-related characteristics of initial HCC. The patterns of late recurrence suggest that postoperative surveillance after 2 years of surgery could be adjusted and more targeted. Regular postoperative surveillance improves the probability to receive curative treatments again, yielding to better outcomes for patients with late recurrence.

Polymorphisms in Genes of the De Novo Lipogenesis Pathway and Overall Survival of Hepatocellular Carcinoma Patients Undergoing Transarterial Chemoembolization

Wu, You-Sheng,Bao, Deng-Ke,Dai, Jing-Yao,Chen, Cheng,Zhang, Hong-Xin,Yang, YeFa,Xing, Jin-Liang,Huang, Xiao-Jun,Wan, Shao-Gui Asian Pacific Journal of Cancer Prevention 2015 Asian Pacific journal of cancer prevention Vol.16 No.3

Aberrant expression of genes in de novo lipogenesis (DNL) pathway were associated with various cancers, including hepatocellular carcinoma (HCC). Single nucleotide polymorphisms (SNPs) of DNL genes have been reported to be associated with prognosis of some malignancies. However, the effects of SNPs in DNL genes on overall survival of HCC patients receiving transarterial chemoembolization (TACE) treatment are still unknown. In present study, nine SNPs in three genes (ACLY, ACACA and FASN) in DNL pathway were genotyped using the Sequenom iPLEX genotyping system in a hospital-based cohort with 419 HCC patients treated with TACE, and their associations with HCC overall survival were evaluated by Cox proportional hazard regression analysis under three genetic models (additive, dominant and recessive). Although we did not find any significant results in total analysis (all p>0.05), our stratified data showed that SNP rs9912300 in ACLY gene was significantly associated with overall survival of HCC patients with lower AFP level and SNP rs11871275 in ACACA gene was significantly associated with overall survival of HCC patients with higher AFP level. We further identified the significant interactions between AFP level and SNP rs9912300 or rs11871275 in the joint analysis. Conclusively, our data suggest that genetic variations in genes of DNL pathway may be a potential biomarker for predicting clinical outcome of HCC patients treated with TACE.

Model of Torsional Waves Based on Transverse and Layered One-Dimensional Component of Infinite Length

Wu Di,Kang Wei-Xin,Wang Hong-Ru,Liu Yu-Mei 보안공학연구지원센터 2016 International Journal of Hybrid Information Techno Vol.9 No.7

The dispersion of torsional wave in transverse and layered one-dimensional component of infinite length is investigated. The study is carried out by treating the one-dimensional component as a cylinder of infinite length firstly, Then put forward a way that the component is divided into a multilayer to analyze torsional wave propagation, the model is constructed in cylindrical coordinates for homogeneous and layered component, the governing equation of torsional wave was derived based on one-dimensional elastic theory and Whittaker’s function, obtain harmonic wave solution of the governing equation by making use of the boundary and continuity conditions of adjacent layers. Finally the result of numerical simulation illustrated the influence of component’s density and shear module on torsional angels and phase velocity. It has been observed the velocity is changing as the change of parameters of shear module and density according to the curve. The conclusion made shown the consistency with the classical theory, and the effective on model such as bearings, engineering mechanics and displacement of particles.

Quercetin Attenuates Visceral Hypersensitivity and 5-Hydroxytryptamine Availability in Postinflammatory Irritable Bowel Syndrome Rats: Role of Enterochromaffin Cells in the Colon

Hong-Yan Qin,Kai-hong Zang,Xiao Zuo,Xin-An Wu,Zhaoxiang Bian 한국식품영양과학회 2019 Journal of medicinal food Vol.22 No.7

Intestinal enterochromaffin (EC) cell hyperplasia and increased 5-hydroxytryptamine (5-HT) availability play key roles in the pathogenesis of abdominal hypersensitivity of irritable bowel syndrome (IBS). This study aims to study the effect of quercetin on visceral pain and 5-HT availability in postinflammatory IBS (PI-IBS) rats. PI-IBS model rats were administered quercetin by gavage at doses of 5, 10, and 20 mg/kg for 14 days. Compared with normal rats, the visceral pain threshold of PI-IBS rats was markedly decreased and the abdominal motor response to colon distension was markedly increased. The EC cell count and 5-HT level, as well as tryptophan hydroxylase (TPH) protein, were all significantly elevated in PI-IBS rats, while the 5-HT reuptake transporter (serotonin transporter) was reduced. Genes that are responsible for enteroendocrine cell differentiation, that is, Ngn3 and pdx1, were significantly increased in the PI-IBS group. Quercetin treatment markedly elevated the pain threshold pressure and decreased the visceral motor response of PI-IBS animals; and EC cell density and 5-HT level, as well as TPH expression, in the PI-IBS group were all reduced by quercetin. Quercetin treatment also significantly reduced colonic expression of Ngn3 and pdx1 of PI-IBS. Findings from the present study indicated that the analgesic effect of quercetin on PI-IBS may result from reduction of 5-HT availability in the colon, and the regulatory role of quercetin in endocrine progenitors may contribute to reduced EC cells.

The involvement of Parkin-dependent mitophagy in the anti-cancer activity of Ginsenoside

Xin Sun,Yeting Hong,Yuhan Shu,Caixia Wu,Guiqin Ye,Hanxiao Chen,Hongying Zhou,Ruilan Gao,Jianbin Zhang 고려인삼학회 2022 Journal of Ginseng Research Vol.46 No.2

Colon cancer, the third most frequent occurred cancer, has high mortality and extremely poor prognosis. Ginsenoside, the active components of traditional Chinese herbal medicine Panax ginseng, exerts antitumor effect in various cancers, including colon cancer. However, the detailed molecular mechanism of Ginsenoside in the tumor suppression have not been fully elucidated. Here, we chose the representative ginsenoside Rg3 and reported for the first time that Rg3 induces mitophagy in human colon cancer cells, which is responsible for its anticancer effect. Rg3 treatment leads to mitochondria damage and the formation of mitophagosome; when autophagy is inhibited, the clearance of damaged mitochondria can be reversed. Next, our results showed that Rg3 treatment activates the PINK1-Parkin signaling pathway and recruits Parkin and ubiquitin proteins to mitochondria to induce mitophagy. GO analysis of Parkin targets showed that Parkin interacts with a large number of mitochondrial proteins and regulates the molecular function of mitochondria. The cellular energy metabolism enzyme GAPDH is validated as a novel substrate of Parkin, which is ubiquitinated by Parkin. Moreover, GAPDH participates in the Rg3-induced mitophagy and regulates the translocation of Parkin to mitochondria. Functionally, Rg3 exerts the inhibitory effect through regulating the nonglycolytic activity of GAPDH, which could be associated with the cellular oxidative stress. Thus, our results revealed GAPDH ubiquitination by Parkin as a crucial mechanism for mitophagy induction that contributes to the tumor-suppressive function of ginsenoside, which could be a novel treatment strategy for colon cancer.

Disruption of endothelial barrier function is linked with hyposecretion and lymphocytic infiltration in salivary glands of Sjögren's syndrome

Cong, Xin,Zhang, Xue-Ming,Zhang, Yan,Wei, Tai,He, Qi-Hua,Zhang, Li-Wei,Hua, Hong,Lee, Sang-Woo,Park, Kyungpyo,Yu, Guang-Yan,Wu, Li-Ling Elsevier 2018 Biochimica et biophysica acta. Molecular basis of Vol.1864 No.10

<P><B>Abstract</B></P> <P>Sjögren's syndrome (SS) is an inflammatory autoimmune disease that causes hyposecretion in salivary glands. Endothelial tight junctions (TJs) play crucial roles in salivation and barrier function of blood vessels. However, whether the alteration of endothelial TJs were involved in pathogenesis of SS was still unknown. Here, the ultrastructure and function of endothelial TJs in submandibular glands (SMGs) were detected by transmission electron microscopy and in vivo paracellular permeability assay in different aged NOD mouse model for SS. CFSE-labeled lymphocytes were injected into tail vein to trace the infiltration, while claudin-5 expression and distribution were detected by immunofluorescence, qRT-PCR, and western blot. Results showed that the stimulated salivary flow rate was gradually decreased and lymphocytic infiltration was found as age increased in 12- and 21-week-old NOD mice, but not 7-week-old NOD mice. Blood vessels were dilated, while endothelial TJ width and paracellular tracer transport were increased in 12-week-old NOD mice. Moreover, the injected CFSE-labeled lymphocytes were observed in SMGs of 12-week-old NOD mice. Claudin-5 level was increased and relocalized from the apical portion of neighboring endothelial cells to lateral membranes and cytoplasm in 12-week-old NOD mice. Additionally, the alteration of claudin-5 expression and distribution was further confirmed in labial salivary glands and bilateral parotid glands from SS patients. In cultured human microvessel endothelial cell line (HMEC-1), IFN-γ stimulation significantly increased claudin-5 expression. Taken together, we identified that the endothelial TJ barrier was disrupted and contributed to the development of salivary hyposecretion and lymphocytic infiltration in SS.</P> <P><B>Highlights</B></P> <P> <UL> <LI> Endothelial tight junction barrier is disrupted in hyposecretory submandibular glands from Sjögren's syndrome mouse model </LI> <LI> The disrupted salivary endothelial barrier is linked with lymphocytic infiltration in Sjögren's syndrome mouse model </LI> <LI> The redistribution of claudin-5 is responsible for disrupted endothelial barrier in salivary glands from Sjögren's syndrome </LI> </UL> </P>

Novel Phage Display-Derived H5N1-Specific scFvs with Potential Use in Rapid Avian Flu Diagnosis

( Jie Wu ),( Xian Qiao Zeng ),( Hong Bin Zhang ),( Han Zhong Ni ),( Lei Pei ),( Li Rong Zou ),( Li Jun Liang ),( Xin Zhang ),( Jin Yan Lin ),( Chang Wen Ke ) 한국미생물 · 생명공학회 2014 Journal of microbiology and biotechnology Vol.24 No.5

The highly pathogenic avian influenza A (HPAI) viruses of the H5N1 subtype infect poultry and have also been spreading to humans. Although new antiviral drugs and vaccinations can be effective, rapid detection would be more efficient to control the outbreak of infections. In this study, a phage-display library was applied to select antibody fragments for HPAI strain A/Hubei/1/2010. As a result, three clones were selected and sequenced. A hemagglutinin inhibition assay of the three scFvs revealed that none exhibited hemagglutination inhibition activity towards the H5N1 virus, yet they showed a higher binding affinity for several HPAI H5N1 strains compared with other influenza viruses. An ELISA confirmed that the HA protein was the target of the scFvs, and the results of a protein structure simulation showed that all the selected scFvs bound to the HA2 subunit of the HA protein. In conclusion, the three selected scFVs could be useful for developing a specific detection tool for the surveillance of HPAI epidemic strains.