LncRNA- and circRNA-associated competing endogenous RNA (ceRNA) networks in leukocytes in traditional Chinese medicine (TCM)-defined Pi-qi-deficiency syndrome and Pi-wei damp-heat syndrome resulting from chronic atrophic gastritis

2021 ◽  
Author(s):  
Leiming You ◽  
Wei Wang ◽  
Kunyu Li ◽  
Xiaopu Sang ◽  
Ting’an Li ◽  
...  
Keyword(s):  
Gene Regulation ◽  
Chinese Medicine ◽  
Traditional Chinese Medicine ◽  
Atrophic Gastritis ◽  
Regulatory Networks ◽  
Chronic Atrophic Gastritis ◽  
Deficiency Syndrome ◽  
Competing Endogenous Rna ◽  
Relationship Networks ◽  
Heat Syndrome

Abstract Background To investigate lncRNA/circRNA-associated competing endogenous RNA (ceRNA)-gene regulation underlying leukocyte functions and characteristics, especially the potential ceRNA biomarkers, implicated in traditional Chinese medicine (TCM)-defined Pi-qi-deficiency syndrome (PQDS) and Pi-wei damp-heat syndrome (PDHS) resulting from chronic atrophic gastritis (CAG). Methods Based on RNA-sequencing approach, comparing with healthy control population, we identified the PDHS- or PQDS-specific lncRNAs/circRNAs in leukocytes, especially the Zheng (syndrome)-specific ceRNAs and their corresponding ceRNA regulatory networks, further decoding their potential functions and pathways. Results Despite being the TCM-defined Zhengs resulting from the same disease of CAG, the Zheng-specific lncRNAs/circRNAs in leukocytes were not same in PQDS and PDHS. There were the Zheng-specific lncRNA/circRNA-associated ceRNAs identified in the leukocytes, and their corresponding ceRNA regulatory networks were generated, including the ceRNA-gene binary relationship networks and the miRNA-centered ceRNA-miRNA-gene triple relationship networks. In the generated Zheng-specific ceRNA networks, the PQDS-specific ceRNA-governed genes in leukocytes, keeping more complex interactions with each other, were enriched in pathways related to MAPK signaling, receptor tyrosine kinases signaling as well as complement and coagulation cascades. Notably, the enriched pathways associated with adherens junction, focal adhesion, ECM-receptor interaction, ECM-organization and cell surface interactions, were implicated in cell-to-cell adhesion/junction and communication, probably contributing to the characteristics and functions of leukocytes. The PDHS-specific ceRNA-regulated genes, seemed to have no more interactions with each other, were enriched in the biological processes related to regulation of cell morphogenesis, neutrophil activation and degranulation, and lymphocyte mediated immunity such as B-cell receptor signaling, complement and coagulation cascades, and regulation of NK/T-cell mediated cytotoxicity. Importantly, the five exosome-encapsuled ceRNAs, containing ZFAS1 (NR_036658.2), AL353719.1 (ENST00000566847), LOH12CR2 (NR_024061.1) and two new lncRNAs (TCONS_00038035 and TCONS_00027600), particularly higher expression in the leukocytes in PQDS rather than PDHS, could be the potential ceRNA biomarkers for differentiation of the TCM-defined PQDS and PDHS among CAG patients. Conclusions These results may provide new insights into the characteristic and functional changes of leukocytes in the two TCM Zhengs, especially the Zheng-specific ceRNA-mediated gene regulation underlying leukocyte characteristics and functions, with potential leukocyte biomarkers for future application in integrative medicine.

scholarly journals Integrated analyses of miRNA and mRNA profiles in leukocytes and serums in traditional Chinese medicine (TCM)-defined Pi-qi-deficiency syndrome and Pi-wei damp-heat syndrome resulting from chronic atrophic gastritis

2020 ◽  
Author(s):  
Leiming You ◽  
Shen Zhang ◽  
Ting’an Li ◽  
Xiaopu Sang ◽  
Kunyu Li ◽  
...  
Keyword(s):  
Cell Adhesion ◽  
Chinese Medicine ◽  
Mirna Gene ◽  
Chronic Atrophic Gastritis ◽  
Deficiency Syndrome ◽  
Serum Biomarkers ◽  
Gene Interactions ◽  
Functional Changes ◽  
Cell To Cell Adhesion ◽  
Heat Syndrome

Abstract Background: To investigate the microRNA (miRNA)-gene interactions underlying leukocyte functions and characteristics, especially the potential serum biomarkers, implicated in the traditional Chinese medicine (TCM)-defined Pi-qi-deficiency syndrome (PQDS) and Pi-wei damp-heat syndrome (PDHS) resulting from chronic atrophic gastritis (CAG). Methods: Using RNA/miRNA-sequencing approach, compared with healthy control population, we identified the PDHS- or PQDS-specific miRNAs and genes in leukocytes or serums, especially the Zheng (syndrome)-specific miRNA-gene interactions, and further decoded their functions and pathways. Results: Despite being the TCM-defined Zhengs resulting from the same disease of CAG, the Zheng-specific genes and miRNAs were not same. The PDHS-specific leukocyte genes were mainly involved in defense and immune responses, including NOD-like receptor signaling and several synapses-related pathways. The expression upregulation of PDHS-specific genes enriched in the neutrophil degranulation pathway, indicated the enhanced leukocyte degranulation activation. The PQDS-specific genes in leukocytes were implicated in inflammatory response, extracellular matrix (ECM) organization and collagen catabolism. They could be enriched in MAPK and IL17 signaling and helper T cell differentiation pathways, especially the pathways associated with cell-to-cell adhesion/junction and communication such as cell adhesion molecules, ECM organization and ECM-receptor interaction, probably contributing to the characteristics and functions of leukocytes. Also, the experimentally-supported miRNA-gene interactions, concerned with COL4A2, COL26A1, SPP1 and PROCR, were implicated in the regulation of pathways related to cell-to-cell adhesion/junction and communication, suggesting the potential roles of the PQDS-specific miRNA-gene interactions for the characteristic and functional changes of leukocytes. Interestingly, the PQDS-specific miRNAs in the serums and the corresponding leukocytes, seemed to have the common roles in contributing to the characteristics and functions of leukocytes. Importantly, the hsa-miR-122-5p could be a potential biomarker, capable of being contained and carried in plasma exosomes and much higher expression in both the leukocytes and corresponding serums in the CAG patients with PQDS rather than PDHS. Conclusions: These results may provide new insights into the characteristic and functional changes of leukocytes in the two Zhengs, PDHS and PQDS, especially the miRNA-mediated gene regulation underlying leukocyte characteristics and functions, with potential leukocyte and serum biomarkers for future application in integrative medicine.Trial registration: ClinicalTrials.gov, NCT02915393. Registered on September 17, 2016.

Mechanism of E Lian Granule Reversing Chronic Atrophic Gastritis With Intestinal Metaplasia Based on Integrated Pharmacology and GEO Gene Chip

2021 ◽  
Author(s):  
Sizhen Gu ◽  
Yan Xue ◽  
Shigui Xue ◽  
Yini Tang ◽  
Zhehao Hu ◽  
...  
Keyword(s):  
Molecular Docking ◽  
Chinese Medicine ◽  
Traditional Chinese Medicine ◽  
Atrophic Gastritis ◽  
Intestinal Metaplasia ◽  
Precancerous Lesions ◽  
Chronic Atrophic Gastritis ◽  
Network Computing ◽  
Active Components ◽  
Gene Chips

Abstract Background: This study aimed to explore the main components and targets of E-Lian granule through which it reversed chronic atrophic gastritis with intestinal metaplasia, based on the traditional Chinese Medicine Integrated Pharmacology Network Computing Research Platform V2.0 (TCMIP V2.0) combined with GEO gene chips. It also aimed to construct various networks to predict and analyze the mechanism of E-Lian granule in treating gastric precancerous lesions. Methods: The effective traditional Chinese medicine components and targets of E-Lian granule prescription were obtained using TCMIP V2.0. The disease targets were collected using the TCMIP V2.0 platform and the verified gene chips in the GEO database, and the “drug components–targets” network, “compound–targets protein interaction network,” and “core compound targets–pathways network” were constructed using Cytoscape 3.6.1. The reliability of the predicted components and targets was verified using Pymol 1.7.2.1 and Autodock Vina 1.1.2 reverse molecular docking. Results: A total of 262 unique active components and 680 potential active targets of E-Lian granule were obtained. Moreover, 2247 unique disease targets of chronic atrophic gastritis with intestinal metaplasia were obtained by searching the “Disease/Symptom Target Database” combined with the GEO chip (GSE78523) and GeneCard database. Further, 178 complex targets and 38 complex core targets were obtained using Venn and Filter, respectively, such as ALB, TNF, PTGS2, RHOA, ESR1, HRAS, JUN, FOS, CASP3 and so forth. The GO and KEGG nrichment analyses showed that E-Lian granule reversed gastric precancerous lesions not only through the direct intervention of the cancer pathway, gastric cancer pathway, and epithelial signal transduction in Helicobacter pylori infection but also through PI3K/AKT, VEGF, MAPK, cAMP, cGMP, Th1/Th2,and other pathways. It also had a significant correlation with cholinergic, 5-hydroxytryptamine, dopaminergic, and other gastrointestinal hormone-related signals. Finally, the core target verified in the GSE78523 chip was successfully used to dock with the active components of E-Lian granules. The reliability of the prediction was also verified. Conclusions: The components and molecular mechanism of E-Lian granule in reversing chronic atrophic gastritis with intestinal metaplasia were predicted by integrated pharmacology, GEO chip, and reverse molecular docking, providing an important theoretical basis for further study of the effective substances and mechanism of E-Lian granule in treating chronic atrophic gastritis.

scholarly journals Integrated analyses of miRNA and mRNA profiles in leukocytes and serums in traditional Chinese medicine (TCM)-defined Pi-qi-deficiency syndrome and Pi-wei damp-heat syndrome resulting from chronic atrophic gastritis

2021 ◽  
Vol 16 (1) ◽  
Author(s):  
Leiming You ◽  
Shen Zhang ◽  
Ting’an Li ◽  
Xiaopu Sang ◽  
Kunyu Li ◽  
...  
Keyword(s):  
Cell Adhesion ◽  
Chinese Medicine ◽  
Mirna Gene ◽  
Chronic Atrophic Gastritis ◽  
Deficiency Syndrome ◽  
Serum Biomarkers ◽  
Gene Interactions ◽  
Functional Changes ◽  
Cell To Cell Adhesion ◽  
Heat Syndrome

Abstract Background To investigate the microRNA (miRNA)-gene interactions underlying leukocyte functions and characteristics, especially the potential serum biomarkers, implicated in the traditional Chinese medicine (TCM)-defined Pi-qi-deficiency syndrome (PQDS) and Pi-wei damp-heat syndrome (PDHS) resulting from chronic atrophic gastritis (CAG). Methods Using RNA/miRNA-sequencing approach, compared with healthy control population, we identified the PDHS- or PQDS-specific miRNAs and genes in leukocytes or serums, especially the Zheng (syndrome)-specific miRNA-gene interactions, and further decoded their functions and pathways. Results Despite being the TCM-defined Zhengs resulting from the same disease of CAG, the Zheng-specific genes and miRNAs were not same. The PDHS-specific leukocyte genes were mainly involved in defense and immune responses, including NOD-like receptor signaling and several synapses-related pathways. The expression upregulation of PDHS-specific genes enriched in the neutrophil degranulation pathway, indicated the enhanced leukocyte degranulation activation. The PQDS-specific genes in leukocytes were implicated in inflammatory response, extracellular matrix (ECM) organization and collagen catabolism. They could be enriched in MAPK and IL17 signaling and helper T cell differentiation pathways, especially the pathways associated with cell-to-cell adhesion/junction and communication such as cell adhesion molecules, ECM organization and ECM-receptor interaction, probably contributing to the characteristics and functions of leukocytes. Also, the experimentally-supported miRNA-gene interactions, concerned with COL4A2, COL26A1, SPP1 and PROCR, were implicated in the regulation of pathways related to cell-to-cell adhesion/junction and communication, suggesting the potential roles of the PQDS-specific miRNA-gene interactions for the characteristic and functional changes of leukocytes. Interestingly, the PQDS-specific miRNAs in the serums and the corresponding leukocytes, seemed to have the common roles in contributing to the characteristics and functions of leukocytes. Importantly, the hsa-miR-122-5p could be a potential biomarker, capable of being contained and carried in plasma exosomes and much higher expression in both the leukocytes and corresponding serums in the CAG patients with PQDS rather than PDHS. Conclusions These results may provide new insights into the characteristic and functional changes of leukocytes in the two Zhengs, PDHS and PQDS, especially the miRNA-mediated gene regulation underlying leukocyte characteristics and functions, with potential leukocyte and serum biomarkers for future application in integrative medicine. Trial registration ClinicalTrials.gov, NCT02915393. Registered on September 17, 2016.

scholarly journals Differences in the Composition of Vaginal Microbiota between Women Exhibiting Spleen-Deficiency Syndrome and Women with Damp-Heat Syndrome, Two of the Most Common Syndromes of Vaginitis in Traditional Chinese Medicine

2019 ◽  
Vol 2019 ◽  
pp. 1-11 ◽  
Author(s):  
Wei Xian Lin ◽  
Xin Du ◽  
Li Lin Yang ◽  
Si Yun Chen ◽  
Wei Yu Qiu ◽  
...  
Keyword(s):  
Chinese Medicine ◽  
Traditional Chinese Medicine ◽  
Deficiency Syndrome ◽  
Vaginal Microbiota ◽  
Vaginal Microbiome ◽  
Ancient Medicine ◽  
Spleen Deficiency ◽  
Significant Difference ◽  
Heat Syndrome ◽  
Spleen Deficiency Syndrome

Spleen-deficiency syndrome and damp-heat syndrome are the two most common syndromes of vaginitis in traditional Chinese medicine (TCM). Although it is known that the vaginal microbiota is closely associated with vaginitis, present studies have not fully elucidated the relationship between the composition of the vaginal microbiome and type of TCM syndrome because of the limitations in the present reductionist approaches. Samples of vaginal secretions were collected from patients with bacterial vaginitis and healthy subjects with spleen-deficiency syndrome and damp-heat syndrome, in order to analyze the constitution of the vaginal microflora using 16S rRNA sequencing methods that encompass taxonomic units, alpha diversity rarefaction curves, and principal component analyses. This prospective study indicated that there was a statistically significant difference in the composition of the vaginal microbiome between patients with spleen-deficiency syndrome and patients with damp-heat syndrome. Streptococcus was the dominant microbiota in patients with spleen-deficiency syndrome. This can serve as a biomarker for differentiating spleen-deficiency syndrome and damp-heat syndrome. In addition, as indicated by the findings on the samples, patients with bacterial vaginitis of dominant abundance in Pseudomonadaceae might be prone to manifest spleen-deficiency syndrome, while patients with bacterial vaginitis of dominant abundance in Prevotella might be prone to manifest damp-heat syndrome. These present findings can provide a new approach to acquire a scientific understanding of the syndromes of TCM, which in turn would benefit the development of personalized medicine, in terms of ancient medicine and complex biological systems.

scholarly journals Efficacy and Safety of Elian Granules in Treating Chronic Atrophic Gastritis: Study Protocol For a Randomized, Double-Blind, Placebo-Controlled, Multicenter Clinical Trial

2021 ◽  
Author(s):  
Zhijian Gu ◽  
Jun Cong ◽  
Biao Gong ◽  
Rong Cen ◽  
Yongqi Chen ◽  
...  
Keyword(s):  
Clinical Trial ◽  
Chinese Medicine ◽  
Traditional Chinese Medicine ◽  
Atrophic Gastritis ◽  
Intestinal Metaplasia ◽  
Chronic Atrophic Gastritis ◽  
Efficacy And Safety ◽  
Multicenter Clinical Trial ◽  
Double Blind ◽  
Double Blind Placebo

Abstract Background: Multifocal atrophic gastritis and intestinal metaplasia are considered to be important links of the gastric precancerous cascade. But, there is a lack of definite therapeutic drugs for them. Many studies have shown traditional Chinese medicine is effective and no serious side effects have been identified. However, the studies that have been carried out were not scientifically rigorous trials. Our aim is to design a high-quality trial for a Chinese patent medicine, Elian granules, to investigate the efficacy and safety of this drug in treating chronic atrophic gastritis patients with or without intestinal metaplasia.Methods: This is a phase Ⅱ, randomized, double-blind, placebo-controlled, multicenter clinical trial. A total of 240 participants will be assigned to treatment group or placebo control group with a 1:1 ratio. Then, the experimental drug or placebo will be taken with boiling water,2 small bags (24.2g) each time, twice times a day, half an hour after each meal for 24 weeks. The primary outcome is to observe gastric mucosal histological changes after 6 months in patients with atrophic gastritis with or without intestinal metaplasia based on OLGA/OLGIM. The secondary outcome included dyspepsia symptom score and quality of life scale.Discussion: This study is designed to evaluate the efficacy and safety of Elian granule in a randomized, double-blind, placebo-controlled, multicenter manner. This trial may not only provide evidence for a phase III clinical trial, but also a vision of an alternative option for chronic atrophic gastritis(CAG) treatment.Trial registration: The registration number, ChiMCTR2000003929, was assigned by the Registry Platform For Evidence Based Traditional Chinese Medicine on 13 September 2020.

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