Inferences of individual differences in response to tripterysium glycosides across patients with Rheumatoid arthritis using a novel ceRNA regulatory axis

Zhang, Yanqiong; Wang, Xiaoyue; Li, Weijie; Wang, Hailong; Yin, Xiaoli; Jiang, Funeng; Su, Xiaohui; Chen, Wenjia; Li, Taixian; Mao, Xia; Guo, Min-Qun; Jiang, Quan; Lin, Na

doi:10.1002/ctm2.185

Cited by 16 publications

(9 citation statements)

References 22 publications

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“…However, clinical trials of anti-inflammatory agents with favorable short-term outcomes are only just beginning to be published, and it will take a long time for the large-scale use of the corresponding drugs [ 9 ]. Tw HF is used in the treatment of a wide spectrum of inflammatory and autoimmune diseases due to its conspicuous anti-inflammatory and immunosuppressive effects [ 13 , 20 , 21 ]. In the current study, we focused on the TwHF -based Chinese patent prescription CRT, which have been indicated to exert good immunomodulatory and anti-inflammatory effects in previous studies [ 28 ].…”

Section: Discussionmentioning

confidence: 99%

“…NF-kB signaling is the key pathway to tissue inflammation, because NF-kB may control the expression of inflammatory cytokines, chemokines and adhesion molecules, all of which play a key role in controlling inflammation [ 20 , 35 – 38 ]. In addition, the inhibition of NF-kB may effectively alleviate renal inflammation and fibrosis caused by persistent hyperglycemia in DKD [ 25 ].…”

Section: Discussionmentioning

confidence: 99%

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Repurposing a clinically approved prescription Colquhounia root tablet to treat diabetic kidney disease via suppressing PI3K/AKT/NF-kB activation

Liu

et al. 2022

Chin Med

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Background Growing clinical evidences show the potentials of Colquhounia root tablet (CRT) in alleviating diabetic kidney disease (DKD). However, its pharmacological properties and underlying mechanisms remain unclear. Methods ‘Drug target-Disease gene’ interaction network was constructed and the candidate network targets were screened through evaluating node genes' topological importance. Then, a DKD rat model induced by high-fat diet/streptozotocin was established and used to determine pharmacological effects and network regulatory mechanisms of CRT against DKD, which were also verified using HK2 cell model induced by high glucose. Results The candidate network targets of CRT against DKD were involved into various type II diabetes-related and nephropathy-related pathways. Due to the topological importance of the candidate network targets and the important role of the imbalance between immunity and inflammation in the pathogenesis of DKD, PI3K/AKT/NF-кB signaling-mediated immune-modulatory and anti-inflammatory actions of CRT were selected to be experimentally verified. On the basis of high-fat diet (HFD) / streptozotocin (STZ)-induced DKD rat model, CRT effectively reduced the elevated level of blood glucose, decreased the accumulation of renal lipid, suppressed inflammation and the generation of ECM proteins, and ameliorated kidney function and the renal histopathology through inhibiting the activation of PI3K, AKT and NF-кB proteins, reducing the nuclear accumulation of NF-кB protein and the serum levels of downstream cytokines, which were in line with the in vitro findings. Conclusions Our data suggest that CRT may be the promising candidate drug for treating DKD via reversing the imbalance of immune-inflammation system mediated by the PI3K/AKT/NF-кB/IL-1β/TNF-α signaling.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Repurposing a clinically approved prescription Colquhounia root tablet to treat diabetic kidney disease via suppressing PI3K/AKT/NF-kB activation

Liu

et al. 2022

Chin Med

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“…The ceRNA hypothesis has been proven to be involved in the development and progression of various autoimmune diseases, such as MG, rheumatoid arthritis, and SLE ( 12 , 13 , 34 ). Previous research on the ceRNA network of MG showed that MALAT-1/miR-338-3p/MSL and SNHG16/let-7c-5p/IL-10 may participate in the regulation of MG ( 14 , 15 ).…”

Section: Discussionmentioning

confidence: 99%

“…Salmena presented a competitive endogenous RNA (ceRNA) hypothesis which proposed that messenger RNA (mRNA) can crosstalk with noncoding RNA by competitive binding to the same microRNA through common microRNA response elements ( 10 , 11 ). In recent years, various researchers have confirmed that this regulatory mechanism exists widely in the pathogenesis of several autoimmune diseases, including Systemic lupus erythematosus (SLE) ( 12 ), rheumatoid arthritis ( 13 ), and MG. Wang and colleagues found that SNHG16 could compete with interleukin-10 by binding to let-7c-5p in peripheral blood mononuclear cells (PBMCs) of patients with MG ( 14 , 15 ). The elevated SNHG16 in the peripheral blood of patients with MG increased the expression of IL-10, which promoted B-cell activation and was associated with anti-AChR antibody production in juvenile MG ( 14 ).…”

Section: Introductionmentioning

confidence: 99%

The LINC00452/miR-204/CHST4 Axis Regulating Thymic Tregs Might Be Involved in the Progression of Thymoma-Associated Myasthenia Gravis

et al. 2022

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BackgroundMyasthenia gravis (MG) is an autoimmune disease that mainly affects neuromuscular junctions and is usually associated with immune disorders in the thymoma. The competitive endogenous RNA (ceRNA) hypothesis has been demonstrated to be an intrinsic mechanism regulating the development of several autoimmune diseases; however, the mechanism where the ceRNA network regulates immune cells in patients with thymoma-associated MG (TAMG) has rarely been explored.MethodsRNA-seq data and clinical information of 124 patients with thymoma were obtained from The Cancer Genome Atlas (TCGA) database. The patients were divided into two groups according to whether they were diagnosed with MG. We applied the propensity score matching method to reduce the incidence of baseline confounders. We then constructed a ceRNA network with differentially expressed RNAs between the groups based on four public databases. The expression of genes of interest was validated by qPCR. Moreover, we predicted the immune cells that infiltrated the thymoma and then analyzed the association between immune cells and RNA in the ceRNA network. To further determine the function of the mRNAs associated with immune cells in patients with TAMG, we performed gene set enrichment analysis in thymoma patients with MG.ResultsAfter matching, 94 patients were included in the following analysis. A total of 847 mRNAs, 409 lncRNAs, and 45 miRNAs were differentially expressed between the groups. The ceRNA network, including 18 lncRNAs, four miRNAs, and 13 mRNAs, was then constructed. We then confirmed that CHST4 and LINC00452, miR-204-3p and miR-204-5p were differentially expressed between patients with TAMG and thymoma patients without MG (NMG) by qPCR. Moreover, we found that the percentage of predicted regulatory T (Treg) cells was significantly decreased in patients with TAMG. Further analysis indicated that the LINC00452/miR-204/CHST4 axis might regulate thymic regulatory T cells (Tregs) in the progression of MG.ConclusionsIn this research, we constructed a ceRNA network involved in the progression of TAMG, discovered that thymic Tregs were significantly decreased in patients with TAMG, and assumed that the LINC00452/miR-204/CHST4 axis may regulate thymic Tregs in the development of TAMG. These findings may deepen our understanding of the roles of the ceRNA network in regulating TAMG and highlight the function of CHST4 in recruiting peripheral T cells in the progression of TAMG.

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“…Therefore, it will be interesting to explore the candidate ceRNA axis related to the clinical outcome of TGT treatment. Following our identification of outcome biomarkers for TGT treatment based on mRNA and miRNA regulatory networks, we recently highlighted a novel ceRNA axis 98 . In detail, we found that lncRNA ENST00000494760 overexpression might sponge miR‐654‐5p to promote C1QC expression in patients with RA.…”

Section: Clinical Application and Therapeutic Efficacymentioning

confidence: 96%

Tripterygium wilfordii: An inspiring resource for rheumatoid arthritis treatment

Zhang

Mao

et al. 2020

Medicinal Research Reviews

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125

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Tripterygium wilfordii Hook F (TwHF)‐based therapy is among the most efficient and crucial therapeutics for the treatment of rheumatoid arthritis (RA), which indicates that TwHF is a potential source of novel anti‐RA drugs. However, accumulating studies have observed that TwHF‐based therapy induces multi‐organ toxicity, which prevents the wide use of this herb in clinical practice, although several recent studies have attempted to reduce the toxicity of TwHF. Notably, our research group developed a “Clinical Practice Guideline for Tripterygium Glycosides/Tripterygium wilfordii Tablets in the Treatment of Rheumatoid Arthritis” (No. T/CACM 1337‐2020) approved by the China Association of Chinese Medicine to standardize the clinical application of TwHF‐based therapy and thus avoid adverse effects. Although great strides have been made toward the characterization of TwHF‐based therapy and revealing its underlying pharmacological and toxicological mechanisms, several crucial gaps in knowledge remain as potential barriers to enhance its therapeutic effects on the premise of safety assurance. This review offers a global view of TwHF, ranging from its chemical constituents, quality control, clinical observations, and underlying pharmacological mechanisms to toxic manifestations and mechanisms. We focus on the important and emerging aspects of this field and highlight the major challenges and strategies for using novel techniques and approaches to gain new insights into unresolved questions. We hope that this review will improve the understanding of TwHF application and draw increasing interdisciplinary attention from clinicians that practice both Chinese and Western medicine, basic researchers, and computer scientists.

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Inferences of individual differences in response to tripterysium glycosides across patients with Rheumatoid arthritis using a novel ceRNA regulatory axis

Abstract: contributed equally to this study.

Cited by 16 publications

References 22 publications

Repurposing a clinically approved prescription Colquhounia root tablet to treat diabetic kidney disease via suppressing PI3K/AKT/NF-kB activation

Repurposing a clinically approved prescription Colquhounia root tablet to treat diabetic kidney disease via suppressing PI3K/AKT/NF-kB activation

The LINC00452/miR-204/CHST4 Axis Regulating Thymic Tregs Might Be Involved in the Progression of Thymoma-Associated Myasthenia Gravis

Tripterygium wilfordii: An inspiring resource for rheumatoid arthritis treatment

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