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Article ; Online: Regulatory Role of the RNA N6-Methyladenosine Modification in Immunoregulatory Cells and Immune-Related Bone Homeostasis Associated With Rheumatoid Arthritis

Danping Fan / Ya Xia / Cheng Lu / Qinbin Ye / Xiaoyu Xi / Qiong Wang / Zheng Wang / Chengyuan Wang / Cheng Xiao

Frontiers in Cell and Developmental Biology, Vol

2021 Volume 8

Abstract: Rheumatoid arthritis (RA) is a systemic autoimmune disease for which the etiology has not been fully elucidated. Previous studies have shown that the development of RA has genetic and epigenetic components. As one of the most highly abundant RNA ... ...

Abstract	Rheumatoid arthritis (RA) is a systemic autoimmune disease for which the etiology has not been fully elucidated. Previous studies have shown that the development of RA has genetic and epigenetic components. As one of the most highly abundant RNA modifications, the N6-methyladenosine (m6A) modification is necessary for the biogenesis and functioning of RNA, and modification aberrancies are associated with various diseases. However, the specific functions of m6A in the cellular processes of RA remain unclear. Recent studies have revealed the relationship between m6A modification and immune cells associated with RA. Therefore, in this review, we focused on discussing the functions of m6A modification in the regulation of immune cells and immune-related bone homeostasis associated with RA. In addition, to gain a better understanding of the progress in this field of study and provide the proper direction and suggestions for further study, clinical application studies of m6A modification were also summarized.
Keywords	RNA N6-methyladenosine ; immunoregulatory cells ; bone homeostasis ; rheumatoid arthritis ; epigenetics ; Biology (General) ; QH301-705.5
Subject code	616
Language	English
Publishing date	2021-01-01T00:00:00Z
Publisher	Frontiers Media S.A.
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: LncRNA HOTAIR-mediated Wnt/β-catenin network modeling to predict and validate therapeutic targets for cartilage damage

Wei Zhou / Xiaojuan He / Ziyi Chen / Danping Fan / Yonghua Wang / Hui Feng / Ge Zhang / Aiping Lu / Lianbo Xiao

BMC Bioinformatics, Vol 20, Iss 1, Pp 1-

2019 Volume 13

Abstract: Abstract Background Cartilage damage is a crucial feature involved in several pathological conditions characterized by joint disorders, such as osteoarthritis and rheumatoid arthritis. Accumulated evidences showed that Wnt/β-catenin pathway plays a role ... ...

Abstract	Abstract Background Cartilage damage is a crucial feature involved in several pathological conditions characterized by joint disorders, such as osteoarthritis and rheumatoid arthritis. Accumulated evidences showed that Wnt/β-catenin pathway plays a role in the pathogenesis of cartilage damage. In addition, it is experimentally documented that lncRNA (long non-coding RNA) HOTAIR plays a key role in the regulation of Wnt/β-catenin pathway based on directly decreased WIF-1 expression. Further, it is reported that Wnt/β-catenin pathway is a potent pathway to regulate the expression of MMP-13, which is responsible for degradation of collagen type II in articular cartilage. It is increasingly recognized that systems modeling approach provides an opportunity to understand the complex relationships and direct quantitative analysis of dynamic network in various diseases. Results A dynamic network of lncRNA HOTAIR-mediated Wnt/β-catenin pathway regulating MMP-13 is developed to investigate the dynamic mechanism of the network involved in the pathogenesis of cartilage damage. Based on the network modeling, the potential therapeutic intervention point Axin is predicted and confirmed by the experimental validation. Conclusions Our study provides a promising strategy for revealing potential dynamic mechanism and assessing potential targets which contribute to the prevention of the pathological conditions related to cartilage damage.
Keywords	LncRNA HOTAIR ; Dynamic network ; Therapeutic targets ; Dynamic mechanism ; Cartilage damage ; Computer applications to medicine. Medical informatics ; R858-859.7 ; Biology (General) ; QH301-705.5
Subject code	629
Language	English
Publishing date	2019-07-01T00:00:00Z
Publisher	BMC
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Zhuang Gu Guan Jie Wan

Bin Liu / Danping Fan / Wen Sun / Kang Zheng / Guoming Pang / Xiaojuan He / Cheng Xiao / Cheng Lu

Evidence-Based Complementary and Alternative Medicine, Vol

Reasonable Application Can Alleviate the Liver Injury for Osteoarthritis Treatment

2018 Volume 2018

Abstract: The potential toxicity of herbal drugs, particularly drug-induced liver injury (DILI), has received extensive attention as the use of Chinese herbal medicine has rapidly increased globally. As a classic Chinese patent medicine, Zhuang Gu Guan Jie Wan ( ... ...

Abstract	The potential toxicity of herbal drugs, particularly drug-induced liver injury (DILI), has received extensive attention as the use of Chinese herbal medicine has rapidly increased globally. As a classic Chinese patent medicine, Zhuang Gu Guan Jie Wan (ZGGJW) has been brought into focus recently because of its satisfactory therapeutic effects on osteoarthritis (OA) as well as its unanticipated side effects. This study aimed to decipher the puzzling phenomenon of liver injury developing in response to ZGGJW that varies by the subtype of OA. Normal, anterior cruciate ligament transaction (ACLT) and partial medial meniscectomy (MMx) induced OA and ovariectomy combined with ACLT and partial MMx induced rat models were used and treated orally with ZGGJW or distilled water for 30 days. The results from histopathology, biochemistry, and immunohistochemistry showed that ZGGJW induced liver injury, increased the level of malondialdehyde (MDA), and decreased the levels of total antioxidation capability (T-AOC), superoxide dismutase (SOD), interleukin-22 (IL-22), and signal transducer and activator of transcription factor 3 (STAT3) in the liver of normal rats, while liver injury was alleviated and showed different tendencies in the above markers for ACLT and partial MMx induction rats and ovariectomy combined with ACLT and partial MMx induction rats after ZGGJW treatment. In the OA disease states, hepatic injury induced by ZGGJW could be associated with an impairment in antioxidant capacity and the high levels of IL-22 and STAT3 after ZGGJW treatment may be responsible for the slight hepatic injury of ZGGJW based on the subtype of OA. This study provides a novel approach to better understanding of the risks and limitations when using potentially toxic Chinese patent medicine in clinical applications.
Keywords	Other systems of medicine ; RZ201-999
Subject code	610
Language	English
Publishing date	2018-01-01T00:00:00Z
Publisher	Hindawi Limited
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Human Umbilical Mesenchymal Stem Cells Display Therapeutic Potential in Rheumatoid Arthritis by Regulating Interactions Between Immunity and Gut Microbiota via the Aryl Hydrocarbon Receptor

Xiaoya Li / Cheng Lu / Danping Fan / Xiangchen Lu / Ya Xia / Hongyan Zhao / Huihui Xu / Yongliang Zhu / Jingtao Li / Honglin Liu / Cheng Xiao

Frontiers in Cell and Developmental Biology, Vol

2020 Volume 8

Abstract: BackgroundRheumatoid arthritis (RA) is an autoimmune disease that may be associated with gut microbiota via the aryl hydrocarbon receptor (AhR). Human umbilical mesenchymal stem cells (HUMSCs) have therapeutic potential against RA, but the underlying ... ...

Abstract	BackgroundRheumatoid arthritis (RA) is an autoimmune disease that may be associated with gut microbiota via the aryl hydrocarbon receptor (AhR). Human umbilical mesenchymal stem cells (HUMSCs) have therapeutic potential against RA, but the underlying mechanism has not been fully elucidated. The purpose of this study was to explore the mechanism of action of HUMSCs in rats with collagen-induced arthritis (CIA).MethodHUMSCs (1 × 106) were transplanted into each rat with CIA. The tissue localization of HUMSCs and the therapeutic effects in the ankles were assessed. The immune status and expression of immune-related genes and proteins in related lymphoid tissues were subsequently tested. Furthermore, the levels of immune-related factors in serum and the changes in gut microbiota in the ileum were detected, and the levels of indole and their derivatives in plasma and the levels of AhR in the ileum were evaluated.ResultsHUMSCs homed to the popliteal lymph node (PLN), mesenteric lymph node (MLN), ankle cartilage, and ileum mucosa in rats with CIA. The transplantation of HUMSCs reduced the pathology scores and the degree of bone damage in the ankles. The immune status of T regulatory cells (Tregs) and T helper (Th)17 cells and the gene expression levels of interleukin (IL)-10, transforming growth factor (TGF)-β1, and IL-17A were altered in the PLN, which is the lymph tissue closest to the nidus, and the MLN, which is one of the gut-associated lymphoid tissues (GALTs). The proportion and function of B cells, Tregs, and Th17 cells were regulated in other GALTs, namely, Peyer’s patches and the lamina propria. The gene expression of TGF-β1 and IL-17A and protein expression of IL-10, TGF-β1, IL-17A, IL-22, and immunoglobulin A (IgA) were modulated in the ileum, and the serum levels of IL-10, TGF-β1, IL-17A, IL-1β, and tumor necrosis factor (TNF)-α were regulated in the rats with CIA. The relative abundances of the genera Bacteroides and Bacillus were increased in the HUMSCs-treated rat with CIA; in addition, the levels of ...
Keywords	human umbilical mesenchymal stem cells ; rheumatoid arthritis ; host immunity ; gut microbiota ; aryl hydrocarbon receptor ; Biology (General) ; QH301-705.5
Subject code	610
Language	English
Publishing date	2020-03-01T00:00:00Z
Publisher	Frontiers Media S.A.
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Identification of Constituents Affecting the Secretion of Pro-Inflammatory Cytokines in LPS-Induced U937 Cells by UHPLC-HRMS-Based Metabolic Profiling of the Traditional Chinese Medicine Formulation Huangqi Jianzhong Tang

Xuehong Nöst / Eva-Maria Pferschy-Wenzig / Stefanie Nikles / Xiaojuan He / Danping Fan / Aiping Lu / Jimmy Yuk / Kate Yu / Giorgis Isaac / Rudolf Bauer

Molecules, Vol 24, Iss 17, p

2019 Volume 3116

Abstract: Within non-communicable diseases, chronic inflammatory conditions represent one of the biggest challenges for modern medicine. Traditional Chinese Medicine (TCM) has been practiced over centuries and has accumulated tremendous empirical knowledge on the ... ...

Abstract	Within non-communicable diseases, chronic inflammatory conditions represent one of the biggest challenges for modern medicine. Traditional Chinese Medicine (TCM) has been practiced over centuries and has accumulated tremendous empirical knowledge on the treatment of such diseases. Huangqi Jianzhong Tang (HQJZT) is a famous TCM herbal formula composed of Radix Astragali, Ramulus Cinnamomi, Radix et Rhizoma Glycyrrhizae Praeparata cum Melle, Radix Paeoniae Alba, Rhizoma Zingiberis Recens, Fructus Jujubae and Saccharum Granorum (maltose), which has been used for the treatment of various chronic inflammatory gastrointestinal diseases. However, there is insufficient knowledge about its active constituents and the mechanisms responsible for its effects. The present study aimed at identifying constituents contributing to the bioactivity of HQJZT by combining in vitro cytokine production assays and LC-MS metabolomics techniques. From the HQJZT decoction as well as from its single herbal components, extracts of different polarities were prepared. Phytochemical composition of the extracts was analyzed by means of UPLC-QTOF-MS/MS. The inhibitory effects of the extracts on TNF-α, IL-1β and IFN-γ production were studied in U937 cells. Phytochemical and pharmacological bioactivity data were correlated by orthogonal projection to latent structures discriminant analysis (OPLS-DA) in order to identify those HQJZT constituents which may be relevant for the observed pharmacological activities. The investigations resulted in the identification of 16 HQJZT constituents, which are likely to contribute to the activities observed in U937 cells. Seven of them, namely calycosin, formononetin, astragaloside I, liquiritigenin, 18β-glycyrrhetinic acid, paeoniflorin and albiflorin were unambiguously identified. The predicted results were verified by testing these compounds in the same pharmacological assays as for the extracts. In conclusion, the anti-inflammatory activity of HQJZT could be substantiated by in vitro pharmacological ...
Keywords	Huangqi Jianzhong Tang ; Astragalus mongholicus ; Cinnamomum cassia ; Glycyrrhiza uralensis ; Paeonia lactiflora ; Zingiber officinalis ; Ziziphus jujube ; UPLC-QTOF-MS ; metabolomics ; TNF-α ; IL-1β ; IFN-γ ; Organic chemistry ; QD241-441
Subject code	540
Language	English
Publishing date	2019-08-01T00:00:00Z
Publisher	MDPI AG
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Corrigendum to ‘Osteoblastic PLEKHO1 contributes to joint inflammation in rheumatoid arthritis’ [EBioMedicine 41 (2019) 538–555]

Xiaojuan He / Jin Liu / Chao Liang / Shaikh Atik Badshah / Kang Zheng / Lei Dang / Baosheng Guo / Defang Li / Cheng Lu / Qingqing Guo / Danping Fan / Yanqin Bian / Hui Feng / Lianbo Xiao / Xiaohua Pan / Cheng Xiao / BaoTing Zhang / Ge Zhang / Aiping Lu

EBioMedicine, Vol 52, Iss , Pp - (2020)

2020

Keywords	Medicine ; R ; Medicine (General) ; R5-920
Language	English
Publishing date	2020-02-01T00:00:00Z
Publisher	Elsevier
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Metabolic profiling of the traditional Chinese medicine formulation Yu Ping Feng San for the identification of constituents relevant for effects on expression of TNF-α, IFN-γ, IL-1β and IL-4 in U937 cells.

Stefanie, Nikles / Marlene, Monschein / Huiqin, Zou / Yong, Liu / Xiaojuan, He / Danping, Fan / Aiping, Lu / Kate, Yu / Giorgis, Isaac / Bauer, Rudolf

Journal of pharmaceutical and biomedical analysis

2017 Volume 145, Page(s) 219–229

Abstract: Yu Ping Feng San (YPFS) is a classical TCM formulation which has been traditionally used for treatment of immune system related diseases such as chronic bronchitis, allergic rhinitis and asthma. The formula is a mixture of Radix Saposhnikoviae (Fangfeng), ...

Abstract	Yu Ping Feng San (YPFS) is a classical TCM formulation which has been traditionally used for treatment of immune system related diseases such as chronic bronchitis, allergic rhinitis and asthma. The formula is a mixture of Radix Saposhnikoviae (Fangfeng), Radix Astragali (Huangqi), and Rhizoma Atractylodis macrocephalae (Baizhu). TLC- and LC-DAD-ESI-MS/MS methods have been developed for the analysis of the metabolic profiles of the single herbs and of the formula. Decoctions and ASE extracts were analyzed in order to trace components of the individual herbs in YPFS. Nine constituents of Radix Saposhnikoviae, ten constituents of Radix Astragali and five constituents of Rhizoma Atractylodis macrocephalae have been assigned in the chemical profiles of the formula, which now allow the standardisation of YPFS. The pharmacological testing showed that all extracts significantly inhibited expression of TNF-α, IFN-γ, and IL-1β in U937 cells, while the inhibition of IL-4 was consistently low. Compared to conventional analyses which are focused on a limited set of compounds, metabolomics approaches, together with novel data processing tools, enable a more holistic comparison of the herbal extracts. In order to identify the constituents which are relevant for the immunomodulatory effects of the formula, metabolomics studies (PCA, OPLS-DA) have been performed using UPLC/QTOF MS data.
Language	English
Publishing date	2017-10-25
Publishing country	England
Document type	Journal Article
ZDB-ID	604917-5
ISSN	1873-264X ; 0731-7085
ISSN (online)	1873-264X
ISSN	0731-7085
DOI	10.1016/j.jpba.2017.03.049
Database	MEDical Literature Analysis and Retrieval System OnLINE

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Article ; Online: Osteoblastic PLEKHO1 contributes to joint inflammation in rheumatoid arthritisResearch in context

EBioMedicine, Vol 41, Iss , Pp 538-

2019 Volume 555

Abstract: Background: Osteoblasts participating in the inflammation regulation gradually obtain concerns. However, its role in joint inflammation of rheumatoid arthritis (RA) is largely unknown. Here, we investigated the role of osteoblastic pleckstrin homology ... ...

Abstract	Background: Osteoblasts participating in the inflammation regulation gradually obtain concerns. However, its role in joint inflammation of rheumatoid arthritis (RA) is largely unknown. Here, we investigated the role of osteoblastic pleckstrin homology domain-containing family O member 1 (PLEKHO1), a negative regulator of osteogenic lineage activity, in regulating joint inflammation in RA. Methods: The level of osteoblastic PLEKHO1 in RA patients and collagen-induced arthritis (CIA) mice was examined. The role of osteoblastic PLEKHO1 in joint inflammation was evaluated by a CIA model and a K/BxN serum-transfer arthritis (STA) model which were induced in osteoblast-specific Plekho1 conditional knockout mice and mice expressing high Plekho1 exclusively in osteoblasts, respectively. The effect of osteoblastic PLEKHO1 inhibition was explored in a CIA mice model and a non-human primate arthritis model. The mechanism of osteoblastic PLEKHO1 in regulating joint inflammation were performed by a series of in vitro studies. Results: PLEKHO1 was highly expressed in osteoblasts from RA patients and CIA mice. Osteoblastic Plekho1 deletion ameliorated joint inflammation, whereas overexpressing Plekho1 only within osteoblasts exacerbated local inflammation in CIA mice and STA mice. PLEKHO1 was required for TRAF2-mediated RIP1 ubiquitination to activate NF-κB for inducing inflammatory cytokines production in osteoblasts. Moreover, osteoblastic PLEKHO1 inhibition diminished joint inflammation and promoted bone formation in CIA mice and non-human primate arthritis model. Conclusions: These data strongly suggest that the highly expressed PLEKHO1 in osteoblasts contributes to joint inflammation in RA. Targeting osteoblastic PLEKHO1 may exert dual therapeutic action of alleviating joint inflammation and promoting bone formation in RA. Keywords: Osteoblast, PLEKHO1, Rheumatoid arthritis, Inflammation, Bone formation
Keywords	Medicine ; R ; Medicine (General) ; R5-920
Subject code	616
Language	English
Publishing date	2019-03-01T00:00:00Z
Publisher	Elsevier
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Triptolide Modulates TREM-1 Signal Pathway to Inhibit the Inflammatory Response in Rheumatoid Arthritis

Danping Fan / Xiaojuan He / Yanqin Bian / Qingqing Guo / Kang Zheng / Yukun Zhao / Cheng Lu / Baoqin Liu / Xuegong Xu / Ge Zhang / Aiping Lu

International Journal of Molecular Sciences, Vol 17, Iss 4, p

2016 Volume 498

Abstract: Triptolide (TP), an active component isolated from Tripterygiumwilfordii Hook F, has therapeutic potential against rheumatoid arthritis (RA). However, the underlying molecular mechanism has not been fully elucidated. The aim of this study is to ... ...

Abstract	Triptolide (TP), an active component isolated from Tripterygiumwilfordii Hook F, has therapeutic potential against rheumatoid arthritis (RA). However, the underlying molecular mechanism has not been fully elucidated. The aim of this study is to investigate the mechanisms of TP acting on RA by combining bioinformatics analysis with experiment validation. The human protein targets of TP and the human genes of RA were found in the PubChem database and NCBI, respectively. These two dataset were then imported into Ingenuity Pathway Analysis (IPA) software online, and then the molecular network of TP on RA could be set up and analyzed. After that, both in vitro and in vivo experiments were done to further verify the prediction. The results indicated that the main canonical signal pathways of TP protein targets networks were mainly centered on cytokine and cellular immune signaling, and triggering receptors expressed on myeloid cells (TREM)-1 signaling was searched to be the top one shared signaling pathway and involved in the cytokine and cellular immune signaling. Further in vitro experiments indicated that TP not only remarkably lowered the levels of TREM-1 and DNAX-associated protein (DAP)12, but also significantly suppressed the activation of janus activating kinase (JAK)2 and signal transducers and activators of transcription (STAT)3. The expression of tumor necrosis factor (TNF)-α, interleukin (IL)-1β and IL-6 in lipopolysaccharides (LPS)-stimulated U937 cells also decreased after treatment with TP. Furthermore, TREM-1 knockdown was able to interfere with the inhibition effects of TP on these cytokines production. In vivo experiments showed that TP not only significantly inhibited the TREM-1 mRNA and DAP12 mRNA expression, and activation of JAK2 and STAT3 in ankle of rats with collagen-induced arthritis (CIA), but also remarkably decreased production of TNF-α, IL-1β and IL-6 in serum and joint. These findings demonstrated that TP could modulate the TREM1 signal pathway to inhibit the inflammatory response in RA.
Keywords	Triptolide ; rheumatoid arthritis ; TREM-1 signal pathway ; bioinformatics analysis ; Biology (General) ; QH301-705.5 ; Chemistry ; QD1-999
Subject code	572
Language	English
Publishing date	2016-04-01T00:00:00Z
Publisher	MDPI AG
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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