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.

Promoting effect of the Maillard reaction products produced during the stir-frying process of Hordei Fructus Germinatus on the intestinal absorption of active ingredients in Hordei Fructus Germinatus

Lu Wu,Li Xia Tan,Fen Fang Gong,Yu Xia,Rui Ge Chu,Hua Sheng Yang 한국식품과학회 2021 Food Science and Biotechnology Vol.30 No.5

This study was designed to evaluate theabsorption promoting capacity of Maillard Reaction Products(MRPs) produced during the stir-frying process ofHordei Fructus Germinatus on catechin, ferulic acid,quercetin and kaempferol by the ex vivo rat everted gut sacmodel, in situ single-pass intestinal perfusion model andthe whole animal model. Moreover, verapamil, EDTA andmannitol were used for determining the transport mechanismof catechin, ferulic acid, quercetin and kaempferol. The tight junction (TJ) proteins including zonula occudens-1(ZO-1) and claudin-1 were chosen to investigate thepromoting mechanism of MRPs by quantitative real-timePCR (qRT-PCR) and western blot analyses. The resultsshowed that the MRPs produced during the stir-fryingprocess of Hordei Fructus Germinatus could improve theintestinal absorption of catechin, ferulic acid, quercetin andkaempferol. And the absorption-promoting effect of MRPswas related to chelating effect and the reduced expressionof claudin-1 and ZO-1. Our results suggested that MRPscould be promising oral absorption promoters, which mightbe another processing mechanism of Hordei FructusGerminatus.

Maillard Reaction Products of Stir Fried Hordei Fructus Germinatus Are Important for Its Efficacy in Treating Functional Dyspepsia

Lu Wu,Yan Lai,Ying Wang,Lixia Tan,Lizhen Wen,Huasheng Yang 한국식품영양과학회 2020 Journal of medicinal food Vol.23 No.4

Hordei Fructus Germinatus (HFG) has been used as a traditional medicine to treat functional dyspepsia (FD) in China. Stir fried HFG (F-HFG) containing Maillard reaction products (MRPs) is used more widely than the raw HFG (R-HFG). However, the exact mechanisms in its functionality remain unclear. This article investigated the effect of R-HFG, F-HFG, and MRPs on brain-gut peptides, gut microbiota, and digestive enzymes using an FD animal mode. After administration of R-HFG, F-HFG, and MRPs, higher mRNA expression level of gastrin (GAS) and lower mRNA expression level of vasoactive intestinal peptide (VIP) were exhibited in F-HFG and MRPs rats than R-HFG rats (P < .05). Furthermore, compared with the R-HFG group, the contents of motilin (MTL) and GAS showed an upward tendency, whereas the contents of VIP and chokcystokinin (CCK) showed a downward tendency in the F-HFG group. In addition, bacterial communities in the control, F-HFG, and MRPs groups clustered closely to one another, and bacterial communities in the model and recovery groups clustered together, whereas the bacterial communities in the R-HFG group were clustered into a category. Moreover, there were no apparent differences in brain-gut peptides and gut microbiota between the F-HFG and MRPs groups. However, after the oral administration of R-HFG, F-HFG, and MRPs, the level of digestive enzyme did not show a significant change as compared with the recovery group. These results indicated that the stronger effect of F-HFG could be attributed to the MRPs produced during stir frying, and MRPs possessed the effect of regulating brain-gut peptides and gut microbiota.

HYERS-ULAM STABILITY OF DERIVATIONS IN FUZZY BANACH SPACE: REVISITED

Gang Lu,Yuanfeng Jin,Gang Wu,Sungsik Yun 한국수학교육학회 2018 純粹 및 應用數學 Vol.25 No.2

Lu et al. [27] dened derivations on fuzzy Banach spaces and fuzzy Lie Banach spaces and proved the Hyers-Ulam stability of derivations on fuzzy Banach spaces and fuzzy Lie Banach spaces. It is easy to show that the denitions of derivations on fuzzy Banach spaces and fuzzy Lie Banach spaces are wrong and so the results of [27] are wrong. Moreover, there are a lot of seroius problems in the statements and the proofs of the results in Sections 2 and 3. In this paper, we correct the denitions of biderivations on fuzzy Banach algebras and fuzzy Lie Banach algebras and the statements of the results in [27], and prove the corrected theorems.

The Predictive Value of Pre-therapeutic Serum Gamma-glutamyl transferase in Efficacy and Adverse Reactions to Neoadjuvant Chemotherapy among Breast Cancer Patients

Lu Sun,Wenjin Yin,Ziping Wu,Yaohui Wang,Jinsong Lu 한국유방암학회 2020 Journal of breast cancer Vol.23 No.5

Purpose: Gamma-glutamyl transferase (GGT) has been reported as being involved in tumor progression. Previous studies documented a potential relationship between serum GGT level and survival outcome in several types of human malignancies. However, the association between serum GGT levels and response to neoadjuvant chemotherapy (NAC) has not yet been reported. The present study aimed to evaluate the association between pre-therapeutic serum GGT level and the efficacy, long-term survival, and adverse reactions of NAC and to investigate its role in predicting NAC sensitivity in patients with breast cancer. Methods: A total of 129 patients were recruited and stratified into 2 groups according to serum GGT level (< 29 U/L and ≥ 29 U/L). The association between pre-therapeutic serum GGT levels and clinicopathological parameters was examined. The correlation between pre-therapeutic serum GGT levels and pathological complete response (pCR) was analyzed using univariate and multivariate logistic regression. Survival analyses of relapse-free survival (RFS) and disease-free survival (DFS) were performed. Pearson's χ2 test and multivariate logistic regression model were used to analyze the correlation between pre-therapeutic serum GGT levels and adverse reactions. Results: Pre-therapeutic serum GGT levels were associated with pCR among breast cancer patients treated with NAC. Multivariate analysis showed that low-level GGT significantly increased pCR rate. Patients in the high-level GGT group had poorer survival than those in the low-level GGT group. Subgroup analysis demonstrated that serum GGT level was potentially related to RFS and DFS in the hormone receptor-positive group. Low levels of GGT are significantly associated with a higher incidence of neutropenia. Conclusion: Pre-therapeutic serum GGT level is an independent and novel biomarker for predicting the efficiency, prognosis, and adverse reactions to NAC in breast cancer patients. Patients with low pre-therapeutic serum GGT levels are more likely to have higher pCR rates, better RFS and DFS, and higher hematologic toxicity.

High Mobility Group Box 1 Protein Is Methylated and Transported to Cytoplasm in Clear Cell Renal Cell Carcinoma

Wu, Fei,Zhao, Zuo-Hui,Ding, Sen-Tai,Wu, Hai-Hu,Lu, Jia-Ju Asian Pacific Journal of Cancer Prevention 2013 Asian Pacific journal of cancer prevention Vol.14 No.10

Background: The high mobility group box 1 (HMGB1) protein is a widespread nuclear protein present in most cell types. It typically locates in the nucleus and functions as a nuclear cofactor in transcription regulation. However, HMGB1 can also localize in the cytoplasm and be released into extracellular matrix, where it plays critical roles in carcinogenesis and inflammation. However, it remains elusive whether HMGB1 is relocated to cytoplasm in clear cell renal cell carcinoma (ccRCC). Methods: Nuclear and cytoplasmic proteins were extracted by different protocols from 20 ccRCC samples and corresponding adjacent renal tissues. Western blotting and immunohistochemistry were used to identify the expression of HMGB1 in ccRCC. To elucidate the potential mechanism of HMGB1 cytoplasmic translocation, HMGB1 proteins were enriched by immunoprecipitation and analyzed by mass spectrometry (MS). Results: The HMGB1 protein was overexpressed and partially localized in cytoplasm in ccRCC samples (12/20, 60%, p<0.05). Immunohistochemistry results indicated that ccRCC of high nuclear grade possess more HMGB1 relocation than those with low grade (p<0.05). Methylation of HMGB1 at lysine 112 in ccRCC was detected by MS. Bioinformatics analysis showed that post-translational modification might affect the binding ability to DNA and mediate its translocation. Conclusion: Relocation of HMGB1 to cytoplasm was confirmed in ccRCC. Methylation of HMGB1 at lysine 112 might the redistribution of this cofactor protein.

Rheological and Thermal Properties of Acrylonitrile-Acrylamide Copolymers: Influence of Polymerization Temperature

Wu Xueping,Lu Chunxiang,Wu Gangping,Zhang Rui,Ling Licheng The Korean Fiber Society 2005 Fibers and polymers Vol.6 No.2

An attempt was made to correlate the polymerization temperature and rheological and thermal properties of acrylonitrile (AN)-acrylamide (AM) copolymers. The copolymers were synthesized at different polymerization temperature. The copolymer structure was characterized by gel permeation chromatography (GPC) and Infrared spectrum (IR). The rheological and thermal properties were investigated by a viscometer and differential scanning calorimeter-thermogrametric (DSC-TG) analysis, respectively. When the polymerization temperature increased from $41^{\circ}C\;to\;65^{\circ}C$, the molecular weight $(\bar{M}_w)$ of copolymers decreased from 1,090,000 to 250,000, while its conversion increased from $18\%\;to\;63\%$, and the polymer composition changed slightly. To meet the requirements of carbon fibers, the rheological and thermal properties of products were also investigated. It was found that the relationship between viscosity and $\bar{M}_w$ was nonlinear and the viscosity index (n) decreased from 3.13 to 2.69, when the solution temperature increased from $30^{\circ}C\;to\;65^{\circ}C$. This suggests the dependence of viscosity upon $\bar{M}_w$ is higher at lower solution temperature. According to the result of activation energy, the sensivity of viscosity to solution temperature is higher for AN-AM copolymers synthesized at higher polymerization temperature. The result of thermal analysis shows that the copolymers obtained at higher polymerization temperature are easier to cyclization evidenced from lower initiation temperature. The weight loss behavior changed irregularly with polymerization temperature due to irregular change of liberation heat.

An Iterative Calculation Method for Internal Forces and Deformation of Curved Tunnel Lining

Lu-yuan Wu,Meng Li,Hai-bo Bai,Yong-feng Yun,Hui Li,Yi Feng 대한토목학회 2024 KSCE Journal of Civil Engineering Vol.28 No.4

The accurate prediction of lining forces and deformations is crucial for the design of arched tunnel lining. However, in traditional tunnel structural mechanics methods, the distribution shape of the surrounding rock elastic resistance (SRER), as well as the zero point and maximal point locations of SRER, are not clearly defined. In this paper, an iterative calculation method is proposed based on the gradual convergence of the unitized values of SRER and total displacement (TD) of the lining, and the one-to-one functional relationship between the two in the stability process of the surrounding rock and lining. In this method involves using the initial displacement caused by the pressure of the surrounding rock pressure is used to initiate the iterative process, and iterative calculation is carried out until the errors between the unitized value of SRER and the unitized value of TD of the lining structure meet the error requirements. This enables precise determination of the SRER and TD. In order to verify the effectiveness of the proposed method, a case study is conducted on the tunnel of Lianghe Expressway tunnel in Yunnan province, China . The results showed that when the semi-lining structure is divided into unit blocks and the average error of consistency is required to be less than 1e-3, it takes about 20 iterations are needed to meet the error requirement. Furthermore, the accuracy of the calculated results is verified through site-measuring experiments. This method provides an effective tool for failure analysis of arched tunnel lining structures.

Attenuation of Experimental Autoimmune Hepatitis in Mice with Bone Mesenchymal Stem Cell-Derived Exosomes Carrying MicroRNA-223-3p

Lu, Feng-Bin,Chen, Da-Zhi,Chen, Lu,Hu, En-De,Wu, Jin-Lu,Li, Hui,Gong, Yue-Wen,Lin, Zhuo,Wang, Xiao-Dong,Li, Ji,Jin, Xiao-Ya,Xu, Lan-Man,Chen, Yong-Ping Korean Society for Molecular and Cellular Biology 2019 Molecules and cells Vol.42 No.12

MicroRNA-223-3p (miR-223-3p) is one of the potential microRNAs that have been shown to alleviate inflammatory responses in pre-clinical investigations and is highly encased in exosomes derived from bone mesenchymal stem cells (MSC-exosomes). MSC-exosomes are able to function as carriers to deliver microRNAs into cells. Autoimmune hepatitis is one of the challenging liver diseases with no effective treatment other than steroid hormones. Here, we examined whether MSC-exosomes can transfer miR-223-3p to treat autoimmune hepatitis in an experimental model. We found that MSC-exosomes were successfully incorporated with miR-223-3p and delivered miR-223-3p into macrophages. Moreover, there was no toxic effect of exosomes on the macrophages. Furthermore, treatments of either exosomes or exosomes with miR-223-3p successfully attenuated inflammatory responses in the liver of autoimmune hepatitis and inflammatory cytokine release in both the liver and macrophages. The mechanism may be related to the regulation of miR-223-3p level and STAT3 expression in the liver and macrophages. These results suggest that MSC-exosomes can be used to deliver miR-223-3p for the treatment of autoimmune hepatitis.

Anti-tumor Effects of Penfluridol through Dysregulation of Cholesterol Homeostasis

Wu, Lu,Liu, Yan-Yang,Li, Zhi-Xi,Zhao, Qian,Wang, Xia,Yu, Yang,Wang, Yu-Yi,Wang, Yi-Qin,Luo, Feng Asian Pacific Journal of Cancer Prevention 2014 Asian Pacific journal of cancer prevention Vol.15 No.1

Background: Psychiatric patients appear to be at lower risk of cancer. Some antipsychotic drugs might have inhibitory effects on tumor growth, including penfluridol, a strong agent. To test this, we conducted a study to determine whether penfluridol exerts cytotoxic effects on tumor cells and, if so, to explore its anti-tumor mechanisms. Methods: Growth inhibition of mouse cancer cell lines by penfluridol was determined using the 3-(4, 5-dimethylthiazol-2-yl)-2, 5-diphenyltetrazolium bromide (MTT) assay. Cytotoxic activity was determined by clonogenic cell survival and trypan blue assays. Animal tumor models of these cancer cells were established and to evaluate penfluridol for its anti-tumor efficacy in vivo. Unesterified cholesterol in cancer cells was examined by filipin staining. Serum total cholesterol and tumor total cholesterol were detected using the cholesterol oxidase/p-aminophenazone (CHOD-PAP) method. Results: Penfluridol inhibited the proliferation of B16 melanoma (B16/F10), LL/2 lung carcinoma (LL/2), CT26 colon carcinoma (CT26) and 4T1 breast cancer (4T1) cells in vitro. In vivo penfluridol was particularly effective at inhibiting LL/2 lung tumor growth, and obviously prolonged the survival time of mice bearing LL/2 lung tumors implanted subcutaneously. Accumulated unesterified cholesterol was found in all of the cancer cells treated with penfluridol, and this effect was most evident in LL/2, 4T1 and CT26 cells. No significant difference in serum cholesterol levels was found between the normal saline-treated mice and the penfluridol-treated mice. However, a dose-dependent decrease of total cholesterol in tumor tissues was observed in penfluridol-treated mice, which was most evident in B16/F10-, LL/2-, and 4T1-tumor-bearing mice. Conclusion: Our results suggested that penfluridol is not only cytotoxic to cancer cells in vitro but can also inhibit tumor growth in vivo. Dysregulation of cholesterol homeostasis by penfluridol may be involved in its anti-tumor mechanisms.