Integrative Pharmacology Powers the Active Components Detection and Mechanism Exploration of Wang Bi Granules Acting on Rheumatoid Arthritis
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA750804 | ENA |
REPOSITORIES: ENA
Similar Datasets
Project description:Wang Bi Granule (WBG), composed of 16 botanical drugs and 1 animal drug, is clinically used to treat “Wang Bi” syndrome, which mainly refers to later rheumatoid arthritis (RA) in modern medicine, as well as ankylosing spondylitis, tuberculous arthritis, and Kashin-Beck disease characterized by joint pain and swelling deformation. However, its chemical composition and pharmacological mechanisms have not been clarified. Therefore, in the present study we aimed to characterize the chemical components of WBG and explore its mechanism in treating RA using integrative pharmacology, including chemical composition detection, efficacy evaluation, and mechanism exploration. We employed UPLC-QTOF-MS/MS to describe the chemical profile of WBG, TNF-α-stimulated RAW264.7 cells to simulate inflammatory process of RA and evaluate the anti-inflammatory effect of WBG, and network pharmacology to mine the mechanism of WBG acting on RA. As a result, a total of 278 chemical components were identified or tentatively characterized and the water extract of WBG improved the imbalance of inflammation by regulating 179 differential genes in RAW264.7 cells induced by TNF-α. 55 key active constituents were obtained based on the interactions among “components’ targets, RA-related genes, and differential genes (WBG vs TNF-α group)”, which may ameliorate RA conditions by regulating 161 hub genes that mainly involved in inflammation-immune related pathways. The present study, for the first time, employed integrative pharmacology to characterize the chemical profile of WBG and reveal its mechanism against RA through inflammation-immune regulation system.
2022-06-01 | GSE181156 | GEO
Project description:Wang Bi Tablet (WBT) exhibits effective power in clinic during the treatment of rheumatoid arthritis (RA) in China. We aimed to employ the “integrative pharmacology strategy”, including rapid analysis of chemical composition, pharmacological experiment, and network pharmacology analysis, to delineate the main active components and reveal the underlying mechanism of WBT acting on RA. UPLC-QTOF-MS/MS provided the chemical fingerprint of WBT and UNIFI 1.8 software assisted in chemical composition identification by matching the MSE raw data to the in-house library. The anti-inflammatory effect of WBT was evaluated in TNF-α- stimulated RAW264.7 cells by ELISA and transcriptome sequencing. Network pharmacology analysis was carried out based on Integrative Pharmacology-based Network Computational Research Platform of Traditional Chinese Medicine (TCMIP V2.0, http://www.tcmip.cn/). Functional enrichment and network visualization was performed by DAVID v6.8 and NaviGator v3.0 respectively. Altogether, 293 chemical constituents were preliminarily identified or tentatively characterized in the extract of WBT, and it could effectively against inflammatory response in TNF-α-stimulated RAW264.7 cells. One hundred and thirty-five hub genes were delineated based on the network construction of “Anti-inflammatory Core Genes-Putative Targets-RA genes”, which were mainly involved in inflammation-immune regulation, closely relating to the occurrence and development of RA, such as Cytokine-cytokine receptor interaction, Chemokine signaling pathway, etc., Forty-eight key active constituents were selected according to the frequency binding to hub targets and contents in WBT, corresponding to 13 herbal medicines. In summary, it is the first time to explore the active constituents and underlying mechanism of WBT acting on RA using integrative pharmacology strategy, which may provide an efficient way for the analysis of chemical constituents and exploration of pharmacological mechanism of TCM.
2021-05-10 | GSE165272 | GEO
Project description:Bacillus bombysepticus str. wang Genome sequencing
| PRJNA242213 | ENA
Project description:Anadara kagoshimensis isolate:LNHKY-WANG Genome sequencing and assembly
| PRJNA649077 | ENA
Project description:Cell division ensures that both genetic information and non-genetic contents are inherited by daughter cells. Whereas considerable detail has been learned about the processing of intact or damaged DNA during the cell cycle (Branzei & Foiani, 2008; Klaasen et al., 2022),(Bakhoum & Cantley, 2018),(Hustedt & Durocher, 2016), how daughter cells deal with other forms of inherited damage is unknown. Here we identified a special kind of cytoplasmic granules responsible for the compartmentalisation of parental RNA damage. We found that ultraviolet (UV)-induced RNA, but not DNA, damage triggered assembly of this unique type of granules characterized by the presence of RNA helicase DHX9. By developing a novel methodology, FANCI, we discovered that DHX9 granules are enriched in damaged intron RNA and pre-mRNA-binding proteins, which is in contrast to other classical stress granules (SGs) that are composed of mature mRNA. Intron damage impeded proper splicing and intron decay, and induced generation of circRNA and dsRNA in the granules. Moreover, we showed that intron damage induced DHX9 granules assembled specifically in postmitotic daughter cells and triggered a cellular dsRNA immune response. Condensation with dsRNA is crucial for DHX9 localization to the granules and the modulation of dsRNA in these granules by DHX9 was crucial for daughter cell survival. Our observations revealed that DHX9 granules constitute a dedicated non-membrane-bound cytoplasmic compartment that protects daughter cells from parental damaged RNA.
2023-11-11 | GSE218180 | GEO
Project description: Not available
| S-EPMC8213436 | biostudies-literature
Project description:P granules in C. elegans are required for fertility and function to maintain germ cell identity and pluripotency. Sterility in the absence of P granules is often accompanied by the mis-expression of soma-specific proteins and the initiation of somatic differentiation in germ cells. To investigate whether this is caused by the accumulation of somatic transcripts, we performed mRNA-seq on dissected germlines with and without P granules. Strikingly, we found that somatic transcripts do not increase in the young adult germline when P granules are impaired. Instead, we found that impairing P granules causes sperm-specific mRNAs to become highly overexpressed. This includes the accumulation of major sperm protein (MSP) transcripts in germ cells, a phenotype that is suppressed by feminization of the germline. A core component of P granules, the endo-siRNA-binding Argonaute protein CSR-1, has recently been ascribed with the ability to license transcripts for germline expression. However, impairing CSR-1 has very little effect on the accumulation of its mRNA targets. Instead, we found that CSR-1 functions with P granules to prevent MSP and sperm-specific mRNAs from being transcribed in the hermaphrodite germline. These findings suggest that P granules protect germline integrity through two different mechanisms, by 1) preventing the inappropriate expression of somatic proteins at the level of translational regulation, and by 2) functioning with CSR-1 to limit the domain of sperm-specific expression at the level of transcription. Four biological replicates of each condition (empty vector control, P granule RNAi, and CSR-1 RNAi germlines) were collected for total RNA.
2015-05-20 | E-GEOD-67954 | biostudies-arrayexpress
Project description:In C. elegans nematodes, components of liquid-like germ granules were shown to be required for transgenerational small RNA inheritance. Surprisingly, we show here that mutants with defective germ granules can nevertheless inherit potent small RNA-based silencing responses, but some of the mutants lose this ability after many generations of homozygosity. Animals mutated in pptr-1, which is required for stabilization of P granules in the early embryo, display extraordinarily strong heritable RNAi responses, lasting for tens of generations. Intriguingly, the RNAi capacity of descendants derived from mutants defective in the core germ granules proteins MEG-3 and MEG-4 is determined by the genotype of the ancestors, and changes transgenerationally. Further, whether the meg-3/4 mutant alleles were present in the paternal or maternal lineages lead to different transgenerational consequences. Small RNA inheritance, rather than maternal contribution of the germ granules themselves, mediates the transgenerational defects in RNAi of meg-3/4 mutants and their progeny. Accordingly, germ granule defects lead to heritable genome-wide mis-expression of endogenous small RNAs. Upon disruption of germ granules, hrde-1 mutants can inherit RNAi although HRDE-1 was previously thought to be absolutely required for RNAi inheritance. We propose that germ granules sort and shape the RNA pool, and that small RNA inheritance maintains this activity for multiple generations.
2019-07-31 | GSE128112 | GEO
Project description:To investigate the mode of action of ccc_R08, a first-in-class orally available HBV cccDNA inhibitor, we designed and implemented two orthogonal and complementary approaches: a forward pharmacology approach and a reverse pharmacology approach. Bioinformatics analysis integrating biological knowledge with the observations from both approaches offered us preliminary insights into the mode of action of ccc_R08.
2022-12-30 | GSE214515 | GEO