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Article: Identification and characterization of extrachromosomal circular DNA in Wei and Large White pigs by high-throughput sequencing.

Wen, Aiyou / Zhang, Wei / Xu, Jingen / Wang, Kunping / Hu, Hong

2023 Volume 10, Page(s) 1085474

Abstract: Wei pig (WP) and Large White pig (LP) are fatty and lean breeds, respectively. Extrachromosomal ...

Abstract	Wei pig (WP) and Large White pig (LP) are fatty and lean breeds, respectively. Extrachromosomal circular DNA (eccDNA) plays an important role in regulating signaling pathway processes of cell. However, there are few reports regarding the eccDNA and ecDNA profiles in WP and LP. The present work aimed to investigate the eccDNA and ecDNA profiles between WP and LP. Three WPs and three LPs (100 ± 1.3 kg) were selected for analysis of eccDNA and ecDNA in the ear samples. Results showed that there were 39,686,953,656-58,411,217,258 and 53,824,168,657-58,311,810,737 clean data for WP and LP, respectively. Sequencing yielded 15,587-25,479 and 71,123-79,605 eccDNAs from the ear samples of WP and LP, respectively. There were 15,111 and 22,594 eccDNA-derived genes in the WP and LP, respectively, and 13,807 eccDNA-derived genes were common in the ear samples of both pigs. Sequencing yielded 13-19 and 27-43 ecDNAs in the ears of WP and LP, respectively. There were 1,005 and 1,777 ecDNA-derived genes in WP and LP, respectively, and 351 ecDNA-derived genes were common in the ear samples of both pigs. The most significant KEGG pathways of eccDNA-derived genes were axon guidance, focal adhesion, metabolic pathways, MAPK signaling pathway, Hedgehog signaling pathway, microRNAs in cancer, tight junction, phospholipase D signaling pathway, endocytosis, and sphingolipid signaling pathway. Furthermore, the most significant KEGG pathways of ecDNA-derived genes were olfactory transduction, B cell receptor signaling pathway, and chemical carcinogenesis. The eccDNA00044301 was lower abundance, while the ecDNA00000060 was higher abundance in WP compared with that in LP. Summary, we found that eccDNAs and ecDNAs are common in WP and LP and occur in sizes large enough to carry one or several partial or complete genes. These findings have expanded the knowledge repertoire of circular DNA in pig and will provide a reference for the use of pigs as a medical model and help discovery of new genetic markers to select high-quality breeds.
Language	English
Publishing date	2023-02-03
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2834243-4
ISSN	2297-1769
ISSN	2297-1769
DOI	10.3389/fvets.2023.1085474
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Article ; Online: Identification and characterization of extrachromosomal circular DNA in Wei and Large White pigs by high-throughput sequencing

Aiyou Wen / Wei Zhang / Jingen Xu / Kunping Wang / Hong Hu

Frontiers in Veterinary Science, Vol

2023 Volume 10

Abstract: Wei pig (WP) and Large White pig (LP) are fatty and lean breeds, respectively. Extrachromosomal ...

Abstract	Wei pig (WP) and Large White pig (LP) are fatty and lean breeds, respectively. Extrachromosomal circular DNA (eccDNA) plays an important role in regulating signaling pathway processes of cell. However, there are few reports regarding the eccDNA and ecDNA profiles in WP and LP. The present work aimed to investigate the eccDNA and ecDNA profiles between WP and LP. Three WPs and three LPs (100 ± 1.3 kg) were selected for analysis of eccDNA and ecDNA in the ear samples. Results showed that there were 39,686,953,656–58,411,217,258 and 53,824,168,657–58,311,810,737 clean data for WP and LP, respectively. Sequencing yielded 15,587–25,479 and 71,123–79,605 eccDNAs from the ear samples of WP and LP, respectively. There were 15,111 and 22,594 eccDNA-derived genes in the WP and LP, respectively, and 13,807 eccDNA-derived genes were common in the ear samples of both pigs. Sequencing yielded 13–19 and 27–43 ecDNAs in the ears of WP and LP, respectively. There were 1,005 and 1,777 ecDNA-derived genes in WP and LP, respectively, and 351 ecDNA-derived genes were common in the ear samples of both pigs. The most significant KEGG pathways of eccDNA-derived genes were axon guidance, focal adhesion, metabolic pathways, MAPK signaling pathway, Hedgehog signaling pathway, microRNAs in cancer, tight junction, phospholipase D signaling pathway, endocytosis, and sphingolipid signaling pathway. Furthermore, the most significant KEGG pathways of ecDNA-derived genes were olfactory transduction, B cell receptor signaling pathway, and chemical carcinogenesis. The eccDNA00044301 was lower abundance, while the ecDNA00000060 was higher abundance in WP compared with that in LP. Summary, we found that eccDNAs and ecDNAs are common in WP and LP and occur in sizes large enough to carry one or several partial or complete genes. These findings have expanded the knowledge repertoire of circular DNA in pig and will provide a reference for the use of pigs as a medical model and help discovery of new genetic markers to select high-quality breeds.
Keywords	eccDNA ; ecDNA ; Wei pig ; Large White pig ; high-throughput sequencing ; Veterinary medicine ; SF600-1100
Subject code	630
Language	English
Publishing date	2023-02-01T00:00:00Z
Publisher	Frontiers Media S.A.
Document type	Article ; Online
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Article ; Online: Revealing the improvement of diabetes by Si Wei Jiang Huang Tang San through ERK/HIF1α signaling pathway via network pharmacology.

Xu, Tianshu / He, Ping / namWangdu, So / Xu, Chunyang / Hou, Biyu / Ma, Peng / Wang, Zijing / Zhang, Li / Du, Guanhua / Ring, Tse / Ji, Tengfei / Qiang, Guifen

Journal of ethnopharmacology

2023 Volume 319, Issue Pt 2, Page(s) 117254

Abstract: Ethnopharmacological relevance: Si Wei Jiang Huang Tang San (SWJHTS) is ...

Abstract	Ethnopharmacological relevance: Si Wei Jiang Huang Tang San (SWJHTS) is a traditional Tibetan medicine prescription for the treatment of urethritis, frequent urination, and urgency, composed of four traditional Chinese medicines: Curcumae longae rhizoma, Berberidis cortex, Tribuli fructus, and Phyllanthi fructus. However, whether SWJHTS exhibits hypoglycemic efficacy and its specific mechanism remain unclear. Aim of the study: In this study, we aimed to investigate the anti-diabetic effects of SWJHTS and elucidate the underlying mechanism. Materials and methods: HPLC-MS method was used to identify the key components of four kinds of traditional Chinese medicine (Curcumae longae rhizoma, Berberidis cortex., Tribuli fructus, and Phyllanthi fructus) which composed SWJHTS and determine their structure. Normal mice and 145 mg/kg STZ-induced type 1 diabetic mice were treated with three doses of SWJTHS by oral gavage. Body weight, 24h food and water intake, fasting blood glucose, glucose tolerance and other indicators were measured to evaluate the hypoglycemic effect of SWJHTS. OMIM, Genecards and other databases were used to collect targets of diabetes, and HPLC-MS results and TCMSP database information were used to collect drug component targets. Bioinformatics methods such as pathway enrichment analysis and molecular docking were used to predict the key targets of SWJHTS. The gene and protein expressions of HIF1α and ERK signaling pathways in HepG2 cells treated with SWJHTS were detected by RT-PCR and Western blot. Results: A total of 181 components were identified, including curcumin, palmatine, and berberine, etc. The in vivo studies showed that SWJHTS could significantly lower fasting blood glucose levels and improve the symptoms of polydipsia, polyphagia, and polyuria in diabetic mice. Furthermore, we identified HIF1α as the potential key target of SWJHTS against diabetes utilizing network pharmacology approach and in silico molecular docking. Subsequently, we experimentally confirmed that SWJHTS could suppress the high glucose-induced upregulation of HIF1α expression, which mediated the glucose consumption in HepG2 cells. The ERK signaling pathway was further found to be activated by the SWJHTS as the upstream of HIF1α. Conclusions: SWJHTS can improve glucose metabolism by targeting the ERK/HIF1α signaling pathway; hence might be a prospective anti-diabetic drug for diabetic patients as traditional Tibetan medicine.
MeSH term(s)	Humans ; Animals ; Mice ; Blood Glucose ; Diabetes Mellitus, Experimental/drug therapy ; Molecular Docking Simulation ; Network Pharmacology ; Signal Transduction ; Hypoglycemic Agents/pharmacology ; Hypoglycemic Agents/therapeutic use ; Drugs, Chinese Herbal/pharmacology ; Drugs, Chinese Herbal/therapeutic use
Chemical Substances	Tribulus extract (4X4HLN92OT) ; Blood Glucose ; Hypoglycemic Agents ; Drugs, Chinese Herbal
Language	English
Publishing date	2023-09-29
Publishing country	Ireland
Document type	Journal Article
ZDB-ID	134511-4
ISSN	1872-7573 ; 0378-8741
ISSN (online)	1872-7573
ISSN	0378-8741
DOI	10.1016/j.jep.2023.117254
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Article ; Online: Zuotai (β-HgS)-containing 70 Wei Zhen-Zhu-Wan differs from mercury chloride and methylmercury on hepatic cytochrome P450 in mice.

Nie, Yu / Xu, Shang-Fu / Lu, Yan-Liu / Zhao, Xiu-Rong / Li, Cen / Wei, Li-Xin / Liu, Jie

F1000Research

2021 Volume 10, Page(s) 203

Abstract: Background: ...

Abstract	Background:
MeSH term(s)	Animals ; Chlorides ; Cytochrome P-450 Enzyme System ; Liver ; Mercuric Chloride ; Mercury ; Mercury Compounds ; Methylmercury Compounds ; Mice
Chemical Substances	Chlorides ; Mercury Compounds ; Methylmercury Compounds ; zuotai ; Mercuric Chloride (53GH7MZT1R) ; Cytochrome P-450 Enzyme System (9035-51-2) ; Mercury (FXS1BY2PGL)
Language	English
Publishing date	2021-03-11
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2699932-8
ISSN	2046-1402 ; 2046-1402
ISSN (online)	2046-1402
ISSN	2046-1402
DOI	10.12688/f1000research.40667.2
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Article ; Online: Qi Wei anti-burn Tincture remodels liver metabolic pathways and treats burn wounds efficiently.

Wang, Shuai / Zhou, Hui / Cui, Weiqi / Zhang, Junwei / Wu, Deqiao / Zhang, Nan / Xu, Xia

Journal of burn care & research : official publication of the American Burn Association

2022

Abstract: This work aims to elucidate the molecular mechanism of Qi Wei anti-burn Tincture (QW ... Qi Wei anti-burn Tincture treatment did promote the healing of the burn wounds on Kunming mice ... that Qi Wei anti-burn Tincture reprogramed the above metabolic processes in the liver. Furthermore ...

Abstract	This work aims to elucidate the molecular mechanism of Qi Wei anti-burn Tincture (QW) on wound healing in burnt mice using metabolomics and molecular biology techniques. A scald model was first established in Kunming mice. After treatment, biochemical indicators for liver function and burnt skin tissues were then evaluated via biochemical detection and HE staining respectively. Liver tissues were further analyzed for differential metabolites, inflammatory factors, and mRNA levels of cytokines using metabolomics and molecular biology techniques. Involved metabolic pathways were also identified using software. Qi Wei anti-burn Tincture treatment did promote the healing of the burn wounds on Kunming mice with a downregulation of ALP, ALT, AST to normal levels. In mouse liver tissue, the contents of glutamine, aspartic acid, succinic acid and citrulline were significantly reduced, while the contents of 5-hydroxyproline, taurine, hypotaurine and glutamic acid significantly increased. These major differential compounds are involved in the arginine metabolic pathway, nitrogen excretion, and the metabolism of taurine and hypotaurine, suggesting that Qi Wei anti-burn Tincture reprogramed the above metabolic processes in the liver. Furthermore, the application of Qi Wei anti-burn Tincture increased the expression of TGF-β1 and FGF-2, and reduced the levels of TNF-α, IL-1β, IL-6 and reactive oxygen species in the liver of mice induced by burn injury. This study found that Qi Wei anti-burn Tincture treatment promoted metabolic pathway remodeling in liver, which might be a potential mechanism for Qi Wei anti-burn Tincture to treat burn wounds.
Language	English
Publishing date	2022-11-19
Publishing country	England
Document type	Journal Article
ZDB-ID	2224246-6
ISSN	1559-0488 ; 1559-047X
ISSN (online)	1559-0488
ISSN	1559-047X
DOI	10.1093/jbcr/irac175
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Article ; Online: Identification of absorbed compounds of Xiao Yao San Jia Wei and pharmacokinetic study in depressed rats by force swimming stress.

Shan, Chenxiao / Li, Jia / Sun, Bo / Zhou, Runze / Xu, Min / Zhao, Qiulong / Ren, Ping / Wen, Hongmei / Huang, Xi

RSC advances

2022 Volume 12, Issue 8, Page(s) 4455–4468

Abstract: Xiao-Yao-San-Jia-Wei (XYSJW) is a commonly prescribed formulation for depression and anorexia ...

Abstract	Xiao-Yao-San-Jia-Wei (XYSJW) is a commonly prescribed formulation for depression and anorexia in the Jiang Su Province Hospital of Chinese Medicine. Unfortunately, the proper dosage of this formulation is still unclear due to its limited chemical and pharmacokinetic profiles. Thus, in the present study, a sensitive, precise, and rapid procedure for the identification of absorbed compounds (Cs) in the plasma of depressed rats together with a pharmacokinetic analysis was established with the help of ultra-flow liquid chromatography coupled with quadrupole time-of-flight mass spectrometry (UFLC-Q-TOF MS/MS) and ultra-flow liquid chromatography coupled with electrospray ionization triple quadrupole tandem mass spectrometry (UFLC-QQQ MS/MS). Based on the characteristic fragmentation, neutral loss, mass defect filter, relevant literature and reference standards, 225 Cs in the XYSJW extract and 20 Cs in the plasma of the depressed rats were tentatively recognized
Language	English
Publishing date	2022-02-04
Publishing country	England
Document type	Journal Article
ISSN	2046-2069
ISSN (online)	2046-2069
DOI	10.1039/d1ra08778a
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Article ; Online: A new non-stationary standardised streamflow index using the climate indices and the optimal anthropogenic indices as covariates in the Wei River Basin, China

Mingming Ren / Shanhu Jiang / Liliang Ren / Baisha Weng / Menghao Wang / Hao Cui / Chong-Yu Xu

Journal of Hydrology: Regional Studies, Vol 51, Iss , Pp 101649- (2024)

2024

Abstract: Study region: Catchment area above the Huaxian station along the Wei River Basin, China. Study ... applicable to the variable streamflow sequence of the Wei River Basin based on the climate index and ... model is more suitable for quantifying anthropogenic factors in the Wei River Basin. The NSSI performs ...

Abstract	Study region: Catchment area above the Huaxian station along the Wei River Basin, China. Study focus: This study attempts to construct a new Non-stationary Standardized Streamflow Index (NSSI) applicable to the variable streamflow sequence of the Wei River Basin based on the climate index and the optimal anthropogenic index, and analyse the drought characteristics of the basin. The climate index is used to quantify climate change factors and three anthropogenic indices are used to quantify the factor of human activities, including the reservoir index, the human-induced index calculated based on the Variable Infiltration Capacity (VIC) hydrological model and the Long Short-Term Memory (LSTM) model machine learning approach, respectively. New hydrological insights for the region: The human-induced index based on the LSTM model is more suitable for quantifying anthropogenic factors in the Wei River Basin. The NSSI performs better than the SSI in drought identification. The NSSI based on the LSTM model can capture more frequent severe drought and extreme drought events. The frequency of severe drought and extreme drought is higher in summer and autumn than in the others. The NSSI can better characterize the hydrological drought processes under a non-stationary condition, thus it can provide a more effective reference for regional drought assessment and related policy-making from the perspective of a changing environment.
Keywords	Non-stationary standardized streamflow index ; Hydrological drought ; Climate index ; Anthropogenic index ; Physical geography ; GB3-5030 ; Geology ; QE1-996.5
Subject code	550
Language	English
Publishing date	2024-02-01T00:00:00Z
Publisher	Elsevier
Document type	Article ; Online
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Book ; Online: A Galois Connection Approach to Wei-Type Duality Theorems

Xu, Yang / Kan, Haibin / Han, Guangyue

2020

Abstract: In $1991$, Wei proved a duality theorem that established an interesting connection between ... Wei's duality theorem and its various extensions, henceforth referred to as Wei-type duality theorems ... result in this paper is a general Wei-type duality theorem for two Galois connections between finite ...

Abstract	In $1991$, Wei proved a duality theorem that established an interesting connection between the generalized Hamming weights of a linear code and those of its dual code. Wei's duality theorem has since been extensively studied from different perspectives and extended to other settings. In this paper, we re-examine Wei's duality theorem and its various extensions, henceforth referred to as Wei-type duality theorems, from a new Galois connection perspective. Our approach is based on the observation that the generalized Hamming weights and the dimension/length profiles of a linear code form a Galois connection. The central result in this paper is a general Wei-type duality theorem for two Galois connections between finite subsets of $\mathbb{Z}$, from which all the known Wei-type duality theorems can be recovered. As corollaries of our central result, we prove new Wei-type duality theorems for $w$-demimatroids defined over finite sets and $w$-demi-polymatroids defined over modules with a composition series, which further allows us to unify and generalize all the known Wei-type duality theorems established for codes endowed with various metrics. Comment: 38 pages, with some revisions in the previous version; this work has been submitted to IEEE Transactions on Information Theory for possible publication
Keywords	Computer Science - Information Theory
Subject code	516
Publishing date	2020-11-27
Publishing country	us
Document type	Book ; Online
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Article ; Online: Proteomics analysis reveals suppression of IL-17 signaling pathways contributed to the therapeutic effects of Jia-Wei Bu-Shen-Yi-Qi formula in a murine asthma model.

Qin, Jingjing / Wuniqiemu, Tulake / Wei, Ying / Teng, Fangzhou / Cui, Jie / Sun, Jing / Yi, La / Tang, Weifeng / Zhu, Xueyi / Xu, Weifang / Dong, Jingcheng

Phytomedicine : international journal of phytotherapy and phytopharmacology

2021 Volume 95, Page(s) 153803

Abstract: Background: Jia-Wei Bu-Shen-Yi-Qi formula (JWBSYQF), a Chinese herbal formula, is a commonly used ...

Abstract	Background: Jia-Wei Bu-Shen-Yi-Qi formula (JWBSYQF), a Chinese herbal formula, is a commonly used prescription for treating asthma patients. However, the targeted proteins associated with JWBSYQF treatment remain unknown. Purpose: Present study aims to evaluate the therapeutic efficacy of JWBSYQF and identify the targeted proteins in addition to functional pathways. Study design: The ovalbumin (OVA)-induced murine asthma model was established to explore the therapeutic effect of JWBSYQF treatment. Proteomic profiling and quantifications were performed using data-independent acquisition (DIA) methods. Differentially expressed proteins (DEPs) were validated via western blot (WB) and immunohistochemistry (IHC). Methods: A murine asthma model was made by OVA sensitization and challenge, and JWBSYQF (2.25, 4.50, 9,00 g/kg body weight) or dexamethasone (1 mg/ kg body weight) were administered orally. Airway hyperresponsiveness (AHR) to methacholine (Mch), inflammatory cell counts and classification in bronchoalveolar lavage fluid (BALF), lung histopathology, and cytokine levels were measured. Furthermore, DIA proteomic analyses were performed to explore the DEPs targeted by JWBSYQF and were further validated by WB and IHC. Results: Our results exhibited that JWBSYQF attenuated AHR which was mirrored by decreased airway resistance and increased lung compliance. In addition, JWBSYQF-treated mice showed reduced inflammatory score, mucus hypersecretion, as well as reduced the number of BALF leukocytes along with decreased content of BALF Th2 inflammatory cytokines (IL-4, IL-5, IL-13) and serum IgE. Proteomics analysis identified 704 DEPs between the asthmatic mice and control group (MOD vs CON), and 120 DEPs between the JWBSYQF-treatment and the asthmatic mice (JWB-M vs MOD). A total of 33 overlapped DEPs were identified among the three groups. Pathway enrichment analysis showed that DEPs were significantly enriched in IL-17 signaling pathway, in which DEPs, Lcn2, TGF-β1, Gngt2, and Ppp2r5e were common DEPs between three experimental groups. WB and IHC results further validated expressional levels and tendency of these proteins. Our results also showed that JWBSYQF affects mitogen activated protein kinase (MAPK) and nuclear factor-κB (NF-κB) signaling pathways, that are activated by IL-17 signaling. Conclusion: The present study suggested that JWBSYQF could attenuate AHR and airway inflammation in OVA-induced asthmatic mice. In addition, proteomics analysis revealed that suppression of IL-17 signaling pathways contributes to the therapeutic effects of JWBSYQF.
MeSH term(s)	Animals ; Asthma/drug therapy ; Bronchoalveolar Lavage Fluid ; Cytokines ; Disease Models, Animal ; Drugs, Chinese Herbal/pharmacology ; Interleukin-17 ; Lung ; Mice ; Mice, Inbred BALB C ; Ovalbumin ; Proteomics ; Signal Transduction
Chemical Substances	Cytokines ; Drugs, Chinese Herbal ; Interleukin-17 ; Ovalbumin (9006-59-1)
Language	English
Publishing date	2021-10-19
Publishing country	Germany
Document type	Journal Article
ZDB-ID	1205240-1
ISSN	1618-095X ; 0944-7113
ISSN (online)	1618-095X
ISSN	0944-7113
DOI	10.1016/j.phymed.2021.153803
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Article: 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.

You, Leiming / Zhang, Shen / Li, Ting'an / Sang, Xiaopu / Li, Kunyu / Wang, Wei / Gao, Xinhui / Wu, Jiarui / Huang, Guangrui / Wang, Ting / Xu, Anlong

Chinese medicine

2021 Volume 16, Issue 1, Page(s) 4

Abstract: ... in the traditional Chinese medicine (TCM)-defined Pi-qi-deficiency syndrome (PQDS) and Pi-wei damp-heat syndrome (PDHS) resulting ...

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.
Language	English
Publishing date	2021-01-06
Publishing country	England
Document type	Journal Article
ZDB-ID	2260322-0
ISSN	1749-8546
ISSN	1749-8546
DOI	10.1186/s13020-020-00416-9
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