scholarly journals Bioinformatics and Network Pharmacology Identify the Therapeutic Role and Potential Mechanism of Melatonin in AD and Rosacea

2021 ◽  
Vol 12 ◽  
Author(s):  
Huaxiong Zhang ◽  
Yiya Zhang ◽  
Yangfan Li ◽  
Yaling Wang ◽  
Sha Yan ◽  
...  
Keyword(s):  
Regulatory Networks ◽  
Target Genes ◽  
Network Pharmacology ◽  
Therapeutic Role ◽  
Therapeutic Drugs ◽  
Pharmacological Targets ◽  
Huvec Cells ◽  
The Common

Rosacea is significantly associated with dementia, particularly Alzheimer’s disease (AD). However, the common underlying molecular mechanism connecting these two diseases remains limited. This study aimed to reveal the common molecular regulatory networks and identify the potential therapeutic drugs for rosacea and AD. There were 747 overlapped DEGs (ol-DEGs) that were detected in AD and rosacea, enriched in inflammation-, metabolism-, and apoptosis-related pathways. Using the TF regulatory network analysis, 37 common TFs and target genes were identified as hub genes. They were used to predict the therapeutic drugs for rosacea and AD using the DGIdb/CMap database. Among the 113 predicted drugs, melatonin (MLT) was co-associated with both RORA and IFN-γ in AD and rosacea. Subsequently, network pharmacology analysis identified 19 pharmacological targets of MLT and demonstrated that MLT could help in treating AD/rosacea partly by modulating inflammatory and vascular signaling pathways. Finally, we verified the therapeutic role and mechanism of MLT on rosacea in vivo and in vitro. We found that MLT treatment significantly improved rosacea-like skin lesion by reducing keratinocyte-mediated inflammatory cytokine secretion and repressing the migration of HUVEC cells. In conclusion, this study contributes to common pathologies shared by rosacea and AD and identified MLT as an effective treatment strategy for rosacea and AD via regulating inflammation and angiogenesis.

scholarly journals Bioinformatic and experimental findings to indicate anti-cancer targets and mechanisms of calycosin against nasopharyngeal carcinoma

2020 ◽  
Author(s):  
Fangxian Liu ◽  
Qijin Pan ◽  
Liangliang Wang ◽  
Shijiang Yi ◽  
Peng Liu ◽  
...  
Keyword(s):  
Nasopharyngeal Carcinoma ◽  
Molecular Mechanisms ◽  
Apoptotic Cell ◽  
Cell Number ◽  
Network Pharmacology ◽  
Tunel Staining ◽  
Pharmacological Targets ◽  
Experimental Findings

Abstract Background: Calycosin is a naturally-occurring phytoestrogen that reportedly exerts anti- nasopharyngeal carcinoma (NPC) effects. Nevertheless, the molecular mechanisms for anti-NPC using calycosin remain unrevealed. Methods: Thus, a network pharmacology was used to uncover anti-NPC pharmacological targets and mechanisms of calycosin. Additionally, validated experiments were conducted to validate the bioinformatic findings of calycosin for treating NPC. Results: As results, bioinformatic assays showed that the predictive pharmacological targets of calycosin against NPC were TP53, MAPK14, CASP8, MAPK3, CASP3, RIPK1, JUN, ESR1, respectively. And the top 20 biological processes and pharmacological mechanisms of calycosin against NPC were identified accordingly. In clinical data, NPC samples showed positive expression of MAPK14, reduced TP53, CASP8 expressions. In studies in vitro and in vivo, calycosin-dosed NPC cells resulted in reduced cell proliferation, promoted cell apoptosis. In TUNEL staining, calycosin exhibited elevated apoptotic cell number. And immunostaining assays resulted in increased TP53, CASP8 positive cells, and reduced MAPK14 expressions in calycosin-dosed NPC cells and tumor-bearing nude mice. Conclusion: Altogether, these bioinformatic findings reveal optimal pharmacological targets and mechanisms of calycosin against NPC, following with representative identification of human and preclinical experiments. Notably, some of original biotargets may be potentially used to treat NPC.

scholarly journals A Network Pharmacology-based Study of the Potential Mechanism of Bushenhuoxue Formula in Treating Osteoarthritis

2020 ◽  
Author(s):  
Xiong Wen ◽  
Cai Xianhua
Keyword(s):  
Signaling Pathway ◽  
Protein Interactions ◽  
Diabetic Complications ◽  
Target Genes ◽  
Endocrine Resistance ◽  
Network Pharmacology ◽  
Potential Mechanism ◽  
Apoptosis Rate

Abstract Background: To investigate the potential mechanism underlying the efficacy of BuShenHuoXue (BSHX) formula on Osteoarthritis (OA) and its molecular mechanism. Materials and Methods: Data as for bioactive chemicals of individual herb in BSHX formula and their targets were collected from Traditional Chinese Medicine Systems Pharmacology database and OA-associated targets from Gene Expression Omnibus database, compound-disease target network and protein-protein interactions network were built, picturized and analyzed by Cytoscape. Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathway enrichment of key targets were carried out and analyzed to probe into the core pathway and their main functions further. The chondrocytes of SD rats were cultured in vitro, and 50μg/ml IL-1βwas added to the chondrocytes to induce apoptosis. Different concentrations of quercetin were added to the experimental group and the apoptosis rate of chondrocytes, the difference of the expression of SELE, MMP2, and COL1 genes and their protein expression level were further detected. Results: A total of 104 candidate chemicals and 42 crossing targets were screened out. Leading target genes are PTGS2, NCOA2 and HSP90AA1, whereas quercetin and luteolin are principal ingredients. Potential pathways against OA are AGE-RAGE signaling pathway in diabetic complications, Relaxin signaling pathway, IL-17 signaling pathway, Tyrosine metabolism and Endocrine resistance. Our study showed that quercetin could inhibit the apoptosis of chondrocytes induced by IL-1β, decrease SELE, MMP2 and COL1 mRNA expression, likewise decrease the expression of SELE, MMP2 and COL1 protein. Conclusion: This study investigated the bioactive chemicals, crossing targets and possible mechanisms of BSHX formula against OA by network pharmacology strategy, results suggests that quercetin in BSHX formula may target on SELE, MMP2, and COL1 genes and then inhibit the progression of OA through the AGE-RAGE signaling pathway in diabetic complications. By the mechanism of reducing the apoptosis rate of SD rat chondrocytes and down-regulation the expression of genes involved in inflammation, we made sure that quercetin as principal ingredient can protect the cartilage. In addition, the conclusion of this study still need to be confirmed by in vivo and vitro experiments.

scholarly journals Identification on the potential mechanism of Radix pueraria on colon cancer based on network pharmacology

2021 ◽  
Author(s):  
Yi Li ◽  
Chunli Zhang ◽  
Xiaohan Ma ◽  
Liuqing Yang ◽  
Huijun Ren
Keyword(s):  
Colon Cancer ◽  
Chinese Medicine ◽  
Target Genes ◽  
Enrichment Analysis ◽  
In Vivo Studies ◽  
Network Pharmacology ◽  
Biological Mechanism ◽  
Active Components

Abstract Radix Puerariae (RP), a dry root of the Pueraria lobata (Willd.) Ohwi, is used to treat a variety of diseases, including cancer. Several in vitro and in vivo studies have demonstrated the efficacy of RP in the treatment of colon cancer (CC). However, the biological mechanism of RP in the treatment of colon cancer remains unclear. In this study, the active component of RP and its potential molecular mechanism against CC were studied by network pharmacology and enrichment analysis. The methods adopted included screening of active ingredients of Chinese medicine, prediction of target genes of Chinese medicine and disease, construction of protein interaction network, and GO and KEGG Enrichment Analysis. Finally, the results of network pharmacology were further validated by molecular docking experiments and cell experiments. 8 active constituents and 14 potential protein targets were screened from RP, including EGFR, JAK2 and SRC. The biological mechanism of RP against CC was analyzed by studying the relationship between active components, targets, and enrichment pathway. This provides a basis for understanding the clinical application of RP in CC.

scholarly journals A network pharmacology-based approach to explore potential targets of Caesalpinia pulcherima: an updated prototype in drug discovery

2020 ◽  
Vol 10 (1) ◽  
Author(s):  
Nikhil S. Sakle ◽  
Shweta A. More ◽  
Santosh N. Mokale
Keyword(s):  
Breast Cancer ◽  
Target Genes ◽  
Docking Study ◽  
Network Pharmacology ◽  
Egfr Expression ◽  
Target Network ◽  
Anti Fungal ◽  
Compound Target

Abstract Caesalpinia pulcherima (CP) is a traditional herb used for the treatment of asthma, bronchitis, cancer, anti-bacterial, anti-fungal and as abortifacient. In the present study, bioactive components and potential targets in the treatment of breast cancer validated through in silico, in vitro and in vivo approach. The results for the analysis were as among 29 components, only four components were found active for further study which proved the use of CP as a multi-target herb for betterment of clinical uses. The results found by PPI states that our network has significant interactions which include the ESR-1, ESR-2, ESRRA, MET, VEGF, FGF, PI3K, PDK-1, MAPK, PLK-1, NEK-2, and GRK. Compound-target network involves 4 active compound and 150 target genes which elucidate the mechanisms of drug action in breast cancer treatment. Furthermore, on the basis of the above results the important proteins were fetched for the docking study which helps in predicting the possible interaction between components and targets. The results of the western blotting showed that CP regulates ER and EGFR expression in MCF-7 cell. In addition to this animal experimentation showed that CP significantly improved immunohistological status in MNU induced carcinoma rats. Network pharmacology approach not only helps us to confirm the study of the chosen target but also gave an idea of compound-target network as well as pathways associated to the CP for treating the complex metabolic condition as breast cancer and they importance for experimental verification.

scholarly journals Downregulation of miR-142a Contributes to the Enhanced Anti-Apoptotic Ability of Murine Chronic Myelogenous Leukemia Cells

2021 ◽  
Vol 11 ◽  
Author(s):  
Zhiwei Chen ◽  
Yinyin Xie ◽  
Dan Liu ◽  
Ping Liu ◽  
Fei Li ◽  
...  
Keyword(s):  
Transgenic Mice ◽  
Chronic Myelogenous Leukemia ◽  
Regulatory Networks ◽  
Target Genes ◽  
Expression Profiles ◽  
Myelogenous Leukemia ◽  
Integrated Analysis ◽  
Apoptotic Pathway

BackgroundLeukemic stem cell (LSC) is thought to be responsible for chronic myelogenous leukemia (CML) initiation and relapse. However, the inherent regulation of LSCs remains largely obscure. Herein, we integratedly analyzed miRNA and gene expression alterations in bone marrow (BM) Lin-Sca1+c-Kit+ cells (LSKs) of a tet-off inducible CML mouse model, Scl/tTA-BCR/ABL (BA).MethodsScl/tTA and TRE-BA transgenic mice were crossed in the presence of doxycycline to get double transgenic mice. Both miRNA and mRNA expression profiles were generated from BM LSKs at 0 and 3 weeks after doxycycline withdrawal. The target genes of differentially expressed miRNAs were predicted, followed by the miRNA-mRNA network construction. In vitro and in vivo experiments were further performed to elucidate their regulation and function in CML progression.ResultsAs a result of the integrated analysis and experimental validation, an anti-apoptotic pathway emerged from the fog. miR-142a was identified to be downregulated by enhanced ERK-phosphorylation in BA-harboring cells, thereby relieving its repression on Ciapin1, an apoptosis inhibitor. Moreover, miR-142a overexpression could partially rescue the abnormal anti-apoptotic phenotype and attenuate CML progression.ConclusionTaken together, this study explored the miRNA-mRNA regulatory networks in murine CML LSKs and demonstrated that ERK-miR-142a-Ciapin1 axis played an essential role in CML pathogenesis.

scholarly journals Reconstruction of dynamic regulatory networks reveals signaling-induced topology changes associated with germ layer specification

2021 ◽  
Author(s):  
Emily Y Su ◽  
Abby Spangler ◽  
Qin Bian ◽  
Jessica Y Kasamoto ◽  
Patrick Cahan
Keyword(s):  
Signaling Pathways ◽  
Cell Fate ◽  
Regulatory Networks ◽  
Target Genes ◽  
Dynamic Networks ◽  
Dynamic Network ◽  
Primitive Streak ◽  
Reconstruction Methods

Elucidating regulatory relationships between transcription factors (TFs) and target genes is fundamental to understanding how cells control their identity and behavior. Computational gene regulatory network (GRN) reconstruction methods aim to map this control by inferring relationships from transcriptomic data. Unfortunately, existing methods are imprecise, may be computationally burdensome, and do not illustrate how networks transition from one topology to another. Here we present Epoch, a computational network reconstruction tool that leverages single cell transcriptomics to infer dynamic network structures. Epoch performs favorably when benchmarked on reconstruction of synthetically generated, in vivo, and in vitro data. To illustrate the usefulness of Epoch, we used it to identify the dynamic networks underpinning directed differentiation of mouse ESC guided by multiple primitive streak induction treatments. Our analysis demonstrates that modulating signaling pathways drives topological network changes that shape cell fate potential. We also find that Peg3 is a central contributor to the rewiring of the pluripotency network to favor mesoderm specification. By integrating signaling pathways with GRN structures, we traced how Wnt activation and PI3K suppression govern mesoderm and endoderm specification, respectively. The methods presented here are available in the R package Epoch, and provide a foundation for future work in understanding the biological implications of dynamic regulatory structures.

scholarly journals Exploring the Mechanism of Action of Banxia Baizhu Tianma Decoction against Preeclampsia by a Network Pharmacology Approach

2021 ◽  
Vol 2021 ◽  
pp. 1-15
Author(s):  
Shuqing Cheng ◽  
Xijuan Liu ◽  
Aner Chen ◽  
Haibo Li ◽  
Lulu Yan
Keyword(s):  
Animal Model ◽  
Signaling Pathway ◽  
Target Genes ◽  
Network Pharmacology ◽  
Trophoblast Cells ◽  
Pathway Gene ◽  
Stat Signaling ◽  
Proliferation And Invasion

Background. Banxia Baizhu Tianma Decoction (BBTD) is a traditional Chinese medicine (TCM) and has been revealed to promote symptoms of preeclampsia (PE) in clinical practice. However, its mechanisms of action and molecular targets for the treatment of PE are not clear. Method. The potential mechanisms of the BBTD against PE were explored using network pharmacology approach and bioinformatic analysis. The PE animal model was induced by phosphatidylserine/dioleoyl-phosphatidylcholine. The effects of BBTD in the treatment of PE were evaluated in vitro and in vivo. The expressions of RNA and proteins were measured by quantitative real-time polymerase chain reaction and western blotting, respectively. The cell behavior was detected using the MMT assay, Transwell assay, and flow cytometry assay. Results. A total of 173 active compounds of BBTD with 346 targets were identified, and 516 target genes related to PE were also identified from databases. 195 candidate targets for BBTD were screened from the merged PPI network of BBTD-target proteins and PE-related targets. The pathway enrichment analyses showed that the BBTD had the potential to influence a variety of biological pathways. Further pathway-gene network analysis suggested BBTD may improve symptoms of PE via several genes, including MDM2, TP53, RELA, MYC, AKT1, and EGFR. The validation results demonstrated that BBTD treatment promoted pregnancy outcome in the PE animal model. Meanwhile, BBTD regulated the gene expression of MDM2, TP53, RELA, MYC, and EGFR and inhibited the EGFR-JAK/STAT signaling pathway in placental tissue and trophoblast cells. In addition, BBTD promoted the proliferation and invasion and reduced the apoptosis of trophoblast cells. Conclusion. BBTD improved PE by inhibiting the EGFR-JAK/STAT signaling pathway and promoting the proliferation and invasion and reduced the apoptosis of trophoblast cells.

The Application of the Cold Atmospheric Plasma-Activated Solutions in Cancer Treatment

2018 ◽  
Vol 18 (6) ◽  
pp. 769-775 ◽  
Author(s):  
Dayun Yan ◽  
Jonathan H. Sherman ◽  
Michael Keidar
Keyword(s):  
Cancer Treatment ◽  
Atmospheric Plasma ◽  
Current Status ◽  
Cold Atmospheric Plasma ◽  
Anti Cancer ◽  
Long Time ◽  
Key Topics ◽  
The Common

Background: Over the past five years, the cold atmospheric plasma-activated solutions (PAS) have shown their promissing application in cancer treatment. Similar as the common direct cold plasma treatment, PAS shows a selective anti-cancer capacity in vitro and in vivo. However, different from the direct cold atmospheric plasma (CAP) treatment, PAS can be stored for a long time and can be used without dependence on a CAP device. The research on PAS is gradually becoming a hot topic in plasma medicine. Objectives: In this review, we gave a concise but comprehensive summary on key topics about PAS including the development, current status, as well as the main conclusions about the anti-cancer mechanism achieved in past years. The approaches to make strong and stable PAS are also summarized.

scholarly journals Stu2p binds tubulin and undergoes an open-to-closed conformational change

2006 ◽  
Vol 172 (7) ◽  
pp. 1009-1022 ◽  
Author(s):  
Jawdat Al-Bassam ◽  
Mark van Breugel ◽  
Stephen C. Harrison ◽  
Anthony Hyman
Keyword(s):  
Conformational Change ◽  
Conformational Transition ◽  
Budding Yeast ◽  
Microtubule Dynamics ◽  
Open Structure ◽  
Microtubule Associated Proteins ◽  
Associated Proteins ◽  
The Common

Stu2p from budding yeast belongs to the conserved Dis1/XMAP215 family of microtubule-associated proteins (MAPs). The common feature of proteins in this family is the presence of HEAT repeat–containing TOG domains near the NH2 terminus. We have investigated the functions of the two TOG domains of Stu2p in vivo and in vitro. Our data suggest that Stu2p regulates microtubule dynamics through two separate activities. First, Stu2p binds to a single free tubulin heterodimer through its first TOG domain. A large conformational transition in homodimeric Stu2p from an open structure to a closed one accompanies the capture of a single free tubulin heterodimer. Second, Stu2p has the capacity to associate directly with microtubule ends, at least in part, through its second TOG domain. These two properties lead to the stabilization of microtubules in vivo, perhaps by the loading of tubulin dimers at microtubule ends. We suggest that this mechanism of microtubule regulation is a conserved feature of the Dis1/XMAP215 family of MAPs.

scholarly journals Novel Identified Circular Transcript of RCAN2, circ-RCAN2, Shows Deviated Expression Pattern in Pig Reperfused Infarcted Myocardium and Hypoxic Porcine Cardiac Progenitor Cells In Vitro

2021 ◽  
Vol 22 (3) ◽  
pp. 1390
Author(s):  
Julia Mester-Tonczar ◽  
Patrick Einzinger ◽  
Johannes Winkler ◽  
Nina Kastner ◽  
Andreas Spannbauer ◽  
...  
Keyword(s):  
Myocardial Infarction ◽  
Progenitor Cells ◽  
Regulatory Networks ◽  
Circular Rnas ◽  
Cardiac Progenitor Cells ◽  
Tissue Samples ◽  
Healthy Myocardium ◽  
Acute Mi

Circular RNAs (circRNAs) are crucial in gene regulatory networks and disease development, yet circRNA expression in myocardial infarction (MI) is poorly understood. Here, we harvested myocardium samples from domestic pigs 3 days after closed-chest reperfused MI or sham surgery. Cardiac circRNAs were identified by RNA-sequencing of rRNA-depleted RNA from infarcted and healthy myocardium tissue samples. Bioinformatics analysis was performed using the CIRIfull and KNIFE algorithms, and circRNAs identified with both algorithms were subjected to differential expression (DE) analysis and validation by qPCR. Circ-RCAN2 and circ-C12orf29 expressions were significantly downregulated in infarcted tissue compared to healthy pig heart. Sanger sequencing was performed to identify the backsplice junctions of circular transcripts. Finally, we compared the expressions of circ-C12orf29 and circ-RCAN2 between porcine cardiac progenitor cells (pCPCs) that were incubated in a hypoxia chamber for different time periods versus normoxic pCPCs. Circ-C12orf29 did not show significant DE in vitro, whereas circ-RCAN2 exhibited significant ischemia-time-dependent upregulation in hypoxic pCPCs. Overall, our results revealed novel cardiac circRNAs with DE patterns in pCPCs, and in infarcted and healthy myocardium. Circ-RCAN2 exhibited differential regulation by myocardial infarction in vivo and by hypoxia in vitro. These results will improve our understanding of circRNA regulation during acute MI.

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