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Article ; Online: Monomeric compounds from natural products for the treatment of pulmonary fibrosis: a review.

Li, Zhuqing / Yang, Yanyong / Gao, Fu

2024

Abstract: Pulmonary fibrosis (PF) is the end stage of lung injury and chronic lung diseases that results in diminished lung function, respiratory failure, and ultimately mortality. Despite extensive research, the pathogenesis of this disease remains elusive, and ... ...

Abstract	Pulmonary fibrosis (PF) is the end stage of lung injury and chronic lung diseases that results in diminished lung function, respiratory failure, and ultimately mortality. Despite extensive research, the pathogenesis of this disease remains elusive, and effective therapeutic options are currently limited, posing a significant clinical challenge. In addition, research on traditional Chinese medicine and naturopathic medicine is hampered by several complications due to complex composition and lack of reference compounds. Natural product monomers, possessing diverse biological activities and excellent safety profiles, have emerged as potential candidates for preventing and treating PF. The effective anti-PF ingredients identified can be generally divided into flavonoids, saponins, polysaccharides, and alkaloids. Specifically, these monomeric compounds can attenuate inflammatory response, oxidative stress, and other physiopathological processes of the lung through many signaling pathways. They also improve pulmonary factors. Additionally, they ameliorate epithelial-mesenchymal transition (EMT) and fibroblast-myofibroblast transdifferentiation (FMT) by regulating multiple signal amplifiers in the lungs, thereby mitigating PF. This review highlights the significant role of monomer compounds derived from natural products in reducing inflammation, oxidative stress, and inhibiting EMT process. The article provides comprehensive information and serves as a solid foundation for further exploration of new strategies to harness the potential of botanicals in the treatment of PF.
Language	English
Publishing date	2024-05-09
Publishing country	Switzerland
Document type	Journal Article ; Review
ZDB-ID	1080058-x
ISSN	1568-5608 ; 0925-4692
ISSN (online)	1568-5608
ISSN	0925-4692
DOI	10.1007/s10787-024-01485-0
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Article ; Online: Letter by Li et al Regarding Article, "Circulating MicroRNA-122-5p Is Associated With a Lack of Improvement in Left Ventricular Function After Transcatheter Aortic Valve Replacement and Regulates Viability of Cardiomyocytes Through Extracellular Vesicles".

Li, Qi / Li, Zhuqing / Lu, Chengzhi

Circulation

2023 Volume 147, Issue 4, Page(s) e66–e67

MeSH term(s)	Humans ; Transcatheter Aortic Valve Replacement ; Ventricular Function, Left/physiology ; Circulating MicroRNA ; Myocytes, Cardiac ; Aortic Valve/surgery ; Aortic Valve Stenosis/surgery ; Extracellular Vesicles ; Treatment Outcome ; MicroRNAs
Chemical Substances	Circulating MicroRNA ; MIRN122 microRNA, human ; MicroRNAs
Language	English
Publishing date	2023-01-23
Publishing country	United States
Document type	Letter ; Comment
ZDB-ID	80099-5
ISSN	1524-4539 ; 0009-7322 ; 0069-4193 ; 0065-8499
ISSN (online)	1524-4539
ISSN	0009-7322 ; 0069-4193 ; 0065-8499
DOI	10.1161/CIRCULATIONAHA.122.062221
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Article ; Online: Macrophage Phenotypic Changes on FN-Coated Physical Gradient Hydrogels.

Li, Zhuqing / Bratlie, Kaitlin M

ACS applied bio materials

2021 Volume 4, Issue 9, Page(s) 6758–6768

Abstract: The chemical and physical properties are two crucial cues when designing tissue engineering scaffold to mimic living tissue. Macrophages, the major players in the immune response, react rapidly to microenvironmental signals, including gradients of ... ...

Abstract	The chemical and physical properties are two crucial cues when designing tissue engineering scaffold to mimic living tissue. Macrophages, the major players in the immune response, react rapidly to microenvironmental signals, including gradients of physical or chemical cues. Spatiotemporal gradients can modulate cell behavior, such as polarization, proliferation, and adhesion. Here, we studied macrophage phenotypic changes on untreated and fibronectin (FN)-coated methacrylated gellan gum with varying stiffnesses. The compressive moduli of hydrogel with different stiffnesses ranged from ∼5 to 30 kPa. Fibronectin was chemically attached to the substrate to facilitate macrophage proliferation, adhesion, and polarization. Classically (M1) and alternatively (M2) activated macrophages were cultured on both untreated and FN-coated gels. FN-coated substrates elevated cell numbers and enhanced macrophage spreading. The urea/nitrite ratio indicated that untreated rigid substrates shifted both polarizations toward a more proinflammatory phenotype. FN-coated substrates had no impact on M1 polarization. In contrast, FN-coated stiffer gels polarized M2 cells toward an anti-proinflammatory state based on arginine activity and CD206 expression. In addition, macrophage polarization on the softer gel was not influenced by the neighboring cells cultured on the stiffer side of the gel. Using mechanical gradients to control macrophage polarization can be a useful tool in ensuring a proper healing response and for tissue engineering.
MeSH term(s)	Fibronectins/pharmacology ; Hydrogels/pharmacology ; Macrophage Activation ; Macrophages ; Phenotype
Chemical Substances	Fibronectins ; Hydrogels
Language	English
Publishing date	2021-08-25
Publishing country	United States
Document type	Journal Article
ISSN	2576-6422
ISSN (online)	2576-6422
DOI	10.1021/acsabm.1c00489
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Article ; Online: The Influence of Polysaccharides-Based Material on Macrophage Phenotypes.

Li, Zhuqing / Bratlie, Kaitlin M

Macromolecular bioscience

2021 Volume 21, Issue 8, Page(s) e2100031

Abstract: Macrophage polarization is a key factor in determining the success of implanted tissue engineering scaffolds. Polysaccharides (derived from plants, animals, and microorganisms) are known to modulate macrophage phenotypes by recognizing cell membrane ... ...

Abstract	Macrophage polarization is a key factor in determining the success of implanted tissue engineering scaffolds. Polysaccharides (derived from plants, animals, and microorganisms) are known to modulate macrophage phenotypes by recognizing cell membrane receptors. Numerous studies have developed polysaccharide-based materials into functional biomaterial substrates for tissue regeneration and pharmaceutical application due to their immunostimulatory activities and anti-inflammatory response. They are used as hydrogel substrates, surface coatings, and drug delivery carriers. In addition to their innate immunological functions, the newly endowed physical and chemical properties, including substrate modulus, pore size/porosity, surface binding chemistry, and the mole ratio of polysaccharides in hybrid materials may regulate macrophage phenotypes more precisely. Growing evidence indicates that the sulfation pattern of glycosaminoglycans and proteoglycans expressed on polarized macrophages leads to the changes in protein binding, which may alter macrophage phenotype and influence the immune response. A comprehensive understanding of how different types of polysaccharide-based materials alter macrophage phenotypic changes can be beneficial to predict transplantation/implantation outcomes. This review focuses on recent advances in promoting wound healing and balancing macrophage phenotypes using polysaccharide-based substrates/coatings and new directions to address the limitations in the current understanding of macrophage responses to polysaccharides.
MeSH term(s)	Animals ; Biocompatible Materials/metabolism ; Biocompatible Materials/pharmacology ; Macrophages/metabolism ; Phenotype ; Polysaccharides/pharmacology ; Tissue Scaffolds/chemistry
Chemical Substances	Biocompatible Materials ; Polysaccharides
Language	English
Publishing date	2021-05-10
Publishing country	Germany
Document type	Journal Article ; Review
ZDB-ID	2039130-4
ISSN	1616-5195 ; 1616-5187
ISSN (online)	1616-5195
ISSN	1616-5187
DOI	10.1002/mabi.202100031
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Article ; Online: Fibroblasts treated with macrophage conditioned medium results in phenotypic shifts and changes in collagen organization.

Li, Zhuqing / Bratlie, Kaitlin M

Materials science & engineering. C, Materials for biological applications

2021 Volume 122, Page(s) 111915

Abstract: In tissue regeneration, the goal is to regenerate tissue similar to what was damaged or missing while preventing fibrotic scarring, which may lead to decreased mechanical strength and dissimilar tissue characteristics compared to native tissue. We ... ...

Abstract	In tissue regeneration, the goal is to regenerate tissue similar to what was damaged or missing while preventing fibrotic scarring, which may lead to decreased mechanical strength and dissimilar tissue characteristics compared to native tissue. We believe collagen orientation plays a critical role in wound contraction and scarring and that it is modulated by myofibroblasts. We used macrophage conditioned medium to simulate complex events that can influence the fibroblast phenotype during the wound healing process. In addition to examining the effect of macrophage phenotype on fibroblasts, we inhibited focal adhesion kinase (FAK), Rho-associated protein kinase (ROCK), and myosin II for fibroblasts cultured on both tissue culture plastic and methacrylated gellan gum to understand how different pathways and materials influence fibroblast responses. Collagen orientation, α-SMA expression, focal adhesion area, and cell migration were altered by inhibition of FAK, ROCK, or myosin II and macrophage phenotype, along with the substrate. An increase in either focal adhesion area or α-smooth muscle actin (α-SMA) expression correlated with an aligned collagen orientation. Gellan gum hydrogels upregulated α-SMA expression in ROCK inhibited conditioned media and downregulated the FAK area in FAK and ROCK inhibited conditioned media. Myosin II had no impact on the α-SMA expression on the substrate compared to coverslip except for M2 conditioned medium. Gellan gum hydrogel significantly increased cell migration under FAK and Myosin II mediated conditioned media and unconditioned media. Collectively, our study examined how macrophage phenotype influences fibroblast response, which would be beneficial in controlling scar tissue formation.
MeSH term(s)	Actins ; Animals ; Cells, Cultured ; Collagen ; Culture Media, Conditioned/pharmacology ; Fibroblasts ; Macrophages ; Mice ; NIH 3T3 Cells ; Phenotype ; RAW 264.7 Cells
Chemical Substances	Actins ; Culture Media, Conditioned ; Collagen (9007-34-5)
Language	English
Publishing date	2021-01-29
Publishing country	Netherlands
Document type	Journal Article
ZDB-ID	2012160-X
ISSN	1873-0191 ; 0928-4931
ISSN (online)	1873-0191
ISSN	0928-4931
DOI	10.1016/j.msec.2021.111915
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Article ; Online: Effect of RGD functionalization and stiffness of gellan gum hydrogels on macrophage polarization and function.

Li, Zhuqing / Bratlie, Kaitlin M

Materials science & engineering. C, Materials for biological applications

2021 Volume 128, Page(s) 112303

Abstract: Macrophages, the primary effector cells in the immune response, respond rapidly to the physical or chemical properties of biomaterial implants. Balanced macrophage polarization, phagocytosis, and migration would be beneficial for implant success and ... ...

Abstract	Macrophages, the primary effector cells in the immune response, respond rapidly to the physical or chemical properties of biomaterial implants. Balanced macrophage polarization, phagocytosis, and migration would be beneficial for implant success and tissue regeneration. Here, we investigated macrophage phenotypic changes, phagocytosis, and migration in response to RGD functionalized surfaces and changes in stiffness of gellan gum hydrogels. We also inhibited the RhoA pathway. The compressive moduli ranged from ~5 to 30 kPa. Cell population and cell spreading area of classically activated macrophages (M(LPS)) and alternatively activated macrophages (M(IL-4)) are promoted on RGD modified hydrogel. ROCK inhibitor induced the opposite effect on the cell spreading of both M(LPS) and M(IL-4) macrophages on RGD modified hydrogels. Macrophage polarization was found to be stiffness-driven and regulated by the RGD motif and blocked by the RhoA pathway. RGD functionalized hydrogel shifted M(IL-4) cells toward a more pro-inflammatory phenotype, while ROCK inhibition shifted M(LPS) cells to a more anti-inflammatory phenotype. Both M(LPS) and M(IL-4) cells on untreated hydrogels shifted to a more pro-inflammatory phenotype in the presence of aminated-PS particles. The RGD motif had a significant impact on cellular uptake, whereas cellular uptake was stiffness driven on untreated hydrogels. Cell migration of M(LPS) and M(IL-4) cells had ROCK-dependent migration. The stiffness of gellan gum hydrogels had no influence on macrophage migration rate. Collectively, our results showed that gellan gum hydrogels can be used to direct immune response, macrophage infiltration, and phagocytosis.
MeSH term(s)	Hydrogels/pharmacology ; Macrophage Activation ; Macrophages ; Oligopeptides ; Polysaccharides, Bacterial
Chemical Substances	Hydrogels ; Oligopeptides ; Polysaccharides, Bacterial ; gellan gum (7593U09I4D)
Language	English
Publishing date	2021-07-09
Publishing country	Netherlands
Document type	Journal Article
ZDB-ID	2012160-X
ISSN	1873-0191 ; 0928-4931
ISSN (online)	1873-0191
ISSN	0928-4931
DOI	10.1016/j.msec.2021.112303
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Article ; Online: Involvement of the crosstalk between Nrf2 and NF-κB pathways regulated by SIRT1 in myocardial ischemia/reperfusion injury.

Li, Qi / Li, Zhuqing / Li, Tingting / Liu, Chunlei / Lu, Chengzhi

International journal of cardiology

2022 Volume 355, Page(s) 44

MeSH term(s)	Humans ; Myocardial Reperfusion Injury/metabolism ; Myocardium/metabolism ; NF-E2-Related Factor 2/metabolism ; NF-kappa B/metabolism ; Oxidative Stress ; Reperfusion Injury/metabolism ; Sirtuin 1/metabolism
Chemical Substances	NF-E2-Related Factor 2 ; NF-kappa B ; SIRT1 protein, human (EC 3.5.1.-) ; Sirtuin 1 (EC 3.5.1.-)
Language	English
Publishing date	2022-03-10
Publishing country	Netherlands
Document type	Letter ; Comment
ZDB-ID	779519-1
ISSN	1874-1754 ; 0167-5273
ISSN (online)	1874-1754
ISSN	0167-5273
DOI	10.1016/j.ijcard.2022.03.019
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Article ; Online: Molecular characterization of allergic constitution based on network pharmacology and multi-omics analysis methods.

Sun, Pengcheng / Liu, Xing / Wang, Yi / Shen, Rongmin / Chen, Xuemei / Li, Zhuqing / Cui, Diankun / Wang, Ji / Wang, Qi

Medicine

2024 Volume 103, Issue 7, Page(s) e36892

Abstract: The objective of this study was to identify critical pathways associated with allergic constitution. Shared genes among allergic rhinitis (AR), asthma (AA), and atopic dermatitis (AD) were extracted from the GWAS catalog. RNA-seq data of AR, AA, and AD ... ...

Abstract	The objective of this study was to identify critical pathways associated with allergic constitution. Shared genes among allergic rhinitis (AR), asthma (AA), and atopic dermatitis (AD) were extracted from the GWAS catalog. RNA-seq data of AR, AA, and AD from gene expression omnibus (GEO) database were preprocessed and subjected to differential gene expression analysis. The differentially expressed genes (DEGs) were merged using the Robust Rank Aggregation (RRA) algorithm. Weighted gene co-expression network analysis (WGCNA) was performed to identify modules associated with allergies. Components of Guominkang (GMK) were obtained from 6 databases and activate components were identified by SwissADME website. Utilizing the SwissTarget Prediction, PharmMapper, SymMap, and HERB, the targets of GMK were predicted and subsequently validated using gene chip data from our team previous study. Differentially expressed proteins (DEPs) related to the allergic constitution were also extracted based on a previous study. Pathway enrichment analysis was performed using KOBAS-i on the GWAS, RRA, WGCNA modules, DEPs, and GMK targets. P values from multi-omics datasets were combined by meta-analysis, and Bonferroni correction was applied. The significant pathways were further validated using Gene Set Enrichment Analysis (GSEA) with intervention data of GMK. The GWAS results yielded 172 genes. Four datasets AR1, AA1, AD1, and AD2 were acquired from GSE75011, GSE125916, and GSE184237. The RRA algorithm identified 19 upregulated and 20 downregulated genes. WGCNA identified 5 significant modules, with the blue and turquoise modules displaying a moderate correlation with allergies. By performing network pharmacology analysis, we identified 127 active ingredients of GMK and predicted 618 targets. Validation using gene chip data confirmed 107 GMK targets. Single-omics pathway analysis was conducted using KOBAS-i, and 39 significant pathways were identified across multiple omics datasets. GSEA analysis using GMK intervention data identified 11 of 39 significant pathways as the final key pathways associated with the allergic constitution. Through multi-omics integrated pathway analysis, we identified 11 critical pathways of allergic constitution, including TH1 and TH2 cell differentiation, TLR cascade, and TH17 cell differentiation. Identifying these pathways suggests that the observed alterations at the pathway level may play significant roles in the molecular characteristics of the allergic constitution.
MeSH term(s)	Humans ; Multiomics ; Network Pharmacology ; Gene Expression Profiling/methods ; Rhinitis, Allergic/genetics ; Dermatitis, Atopic/genetics ; Asthma/genetics
Language	English
Publishing date	2024-02-16
Publishing country	United States
Document type	Meta-Analysis ; Journal Article
ZDB-ID	80184-7
ISSN	1536-5964 ; 0025-7974
ISSN (online)	1536-5964
ISSN	0025-7974
DOI	10.1097/MD.0000000000036892
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Article: Methylation-driven mechanisms of allergic rhinitis during pollen and non-pollen seasons using integrated bioinformatics analysis.

Sun, Pengcheng / Wang, Yi / Liu, Xing / Li, Zhuqing / Cui, Diankun / Li, Qianru / Wang, Qi / Wang, Ji

Frontiers in genetics

2024 Volume 15, Page(s) 1242974

Abstract: Background: Allergic rhinitis (AR) is a widespread allergic airway disease that results from a complex interplay between genetic and environmental factors and affects approximately 10%-40% of the global population. Pollen is a common allergen, and ... ...

Abstract	Background: Allergic rhinitis (AR) is a widespread allergic airway disease that results from a complex interplay between genetic and environmental factors and affects approximately 10%-40% of the global population. Pollen is a common allergen, and exposure to pollen can cause epigenetic changes. However, the mechanism underlying pollen-induced DNA methylation changes and their potential effects on the allergic march are still unclear. The purpose of this study was to explore the methylation-driven mechanisms of AR during the pollen and non-pollen seasons using bioinformatics analysis and to investigate their relationship with asthma. Methods: We downloaded DNA methylation and gene expression data from the GEO database (GSE50387: GSE50222, GSE50101) and identified differentially methylated positions (DMPs) and differentially expressed genes (DEGs) during the pollen and non-pollen seasons using the CHAMP and limma packages. Through correlation analysis, we identified methylation-driven genes and performed pathway enrichment analysis to annotate their functions. We incorporated external data on AR combined with asthma (GSE101720) for analysis to identify key CpGs that promote the transformation of AR to asthma. We also utilized external data on olive pollen allergy (GSE54522) for analysis to validate the methylation-driven genes. Weighted correlation network analysis (WGCNA) was employed to identify gene modules significantly correlated with pollen allergy. We extracted genes related to the key methylation-driven gene Results: We identified 20 and 24 CpG-Gene pairings during the pollen and non-pollen seasons. After incorporating external data from GSE101720, we found that Conclusion: We identified methylation-driven genes and their related pathways during the pollen and non-pollen seasons in patients with AR and identified key CpGs that promote the transformation of AR into asthma due to pollen exposure. This study provides new insights into the underlying molecular mechanisms of the transformation of AR to asthma.
Language	English
Publishing date	2024-04-18
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2606823-0
ISSN	1664-8021
ISSN	1664-8021
DOI	10.3389/fgene.2024.1242974
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Article ; Online: A network analysis of the long-term quality of life and mental distress of COVID-19 survivors 1 year after hospital discharge.

Peng, Pu / Wang, Yaqi / Li, Zhuqing / Zhou, Yanan / Wang, Ji / Qu, Miao / Liu, Tieqiao

Frontiers in public health

2023 Volume 11, Page(s) 1223429

Abstract: Objectives: COVID-19 survivors suffer from persistent mental distress and impaired quality of life (QOL) after recovery from the infection. However, the symptom-symptom interaction between these psychological variables remained unexplored. The present ... ...

Abstract	Objectives: COVID-19 survivors suffer from persistent mental distress and impaired quality of life (QOL) after recovery from the infection. However, the symptom-symptom interaction between these psychological variables remained unexplored. The present study aimed to determine the symptom network of mental distress (depression, anxiety, sleep disturbance, fatigue, and post-traumatic stress disorder) and their association with QOL among 535 COVID-19 survivors 1 year after hospital discharge. Methods: 9-item Patient Health Questionnaire, 7-item Generalized Anxiety Disorder Scale, Chalder fatigue scale, Impact of Event Scale-Revised, Pittsburgh Sleep Quality Index, and 36-Item Short-Form Health Survey were applied to measure depression, anxiety, fatigue, PTSD, sleep disturbances, and QOL, respectively. Two networks were estimated using Gaussian graphical model. Network 1 consisted of mental symptoms to determine the central and bridge symptoms. Network 2 additionally included QOL to determine which mental symptoms were mostly related to QOL. Results: 60% of the COVID-19 survivors experienced mental distress 1 year after hospital discharge. Uncontrollable and excessive worry, psychomotor symptoms, intrusion, and daytime dysfunction were the most central symptoms. Daytime dysfunction and fatigue (especially mental fatigue and loss of energy) served as the bridge symptoms across the mental distress network and exhibited the most substantial association with QOL. Conclusion: Our study demonstrated several key symptoms that played a vital role in mental distress and QOL among COVID-19 survivors. Prompt screening and targeted interventions for these symptoms might hold great promise in preventing mental distress and improving QOL in COVID-19 survivors.
MeSH term(s)	Humans ; Quality of Life/psychology ; Patient Discharge ; COVID-19/epidemiology ; Sleep Wake Disorders ; Survivors/psychology ; Hospitals
Language	English
Publishing date	2023-07-28
Publishing country	Switzerland
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2711781-9
ISSN	2296-2565 ; 2296-2565
ISSN (online)	2296-2565
ISSN	2296-2565
DOI	10.3389/fpubh.2023.1223429
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