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      Steamed Panax notoginseng Attenuates Anemia in Mice With Blood Deficiency Syndrome via Regulating Hematopoietic Factors and JAK-STAT Pathway

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          Abstract

          Panax notoginseng (Burk.) F. H. Chen is a medicinal herb used to treat blood disorders since ancient times, of which the steamed form exhibits the anti-anemia effect and acts with a “blood-tonifying” function according to traditional use. The present study aimed to investigate the anti-anemia effect and underlying mechanism of steamed P. notoginseng (SPN) on mice with blood deficiency syndrome induced by chemotherapy. Blood deficiency syndrome was induced in mice by cyclophosphamide and acetylphenylhydrazine. A number of peripheral blood cells and organs (liver, kidney, and spleen) coefficients were measured. The mRNA expression of hematopoietic function-related cytokines in the bone marrow of mice was detected by RT-qPCR. The janus kinase-signal transducer and activator of transcription (JAK-STAT) signaling pathway was screened based on our previous analysis by network pharmacology. The expression of related proteins and cell cycle factors predicted in the pathway was determined by Western blot and RT-qPCR. SPN could significantly increase the numbers of peripheral blood cells and reverse the enlargement of spleen in a dose-dependent manner. The quantities of related hematopoietic factors in bone marrow were also increased significantly after SPN administration. SPN was involved in the cell cycle reaction and activation of immune cells through the JAK-STAT pathway, which could promote the hematopoiesis.

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          Most cited references63

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          Multiple functions of p21 in cell cycle, apoptosis and transcriptional regulation after DNA damage.

          An appropriate control over cell cycle progression depends on many factors. Cyclin-dependent kinase (CDK) inhibitor p21 (also known as p21(WAF1/Cip1)) is one of these factors that promote cell cycle arrest in response to a variety of stimuli. The inhibitory effect of P21 on cell cycle progression correlates with its nuclear localization. P21 can be induced by both p53-dependent and p53-independent mechanisms. Some other important functions attributed to p21 include transcriptional regulation, modulation or inhibition of apoptosis. These functions are largely dependent on direct p21/protein interactions and also on p21 subcellular localizations. In addition, p21 can play a role in DNA repair by interacting with proliferating cell nuclear antigen (PCNA). In this review, we will focus on the multiple functions of p21 in cell cycle regulation, apoptosis and gene transcription after DNA damage and briefly discuss the pathways and factors that have critical roles in p21 expression and activity.
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            TCM Database@Taiwan: The World's Largest Traditional Chinese Medicine Database for Drug Screening In Silico

            Rapid advancing computational technologies have greatly speeded up the development of computer-aided drug design (CADD). Recently, pharmaceutical companies have increasingly shifted their attentions toward traditional Chinese medicine (TCM) for novel lead compounds. Despite the growing number of studies on TCM, there is no free 3D small molecular structure database of TCM available for virtual screening or molecular simulation. To address this shortcoming, we have constructed TCM Database@Taiwan (http://tcm.cmu.edu.tw/) based on information collected from Chinese medical texts and scientific publications. TCM Database@Taiwan is currently the world's largest non-commercial TCM database. This web-based database contains more than 20,000 pure compounds isolated from 453 TCM ingredients. Both cdx (2D) and Tripos mol2 (3D) formats of each pure compound in the database are available for download and virtual screening. The TCM database includes both simple and advanced web-based query options that can specify search clauses, such as molecular properties, substructures, TCM ingredients, and TCM classification, based on intended drug actions. The TCM database can be easily accessed by all researchers conducting CADD. Over the last eight years, numerous volunteers have devoted their time to analyze TCM ingredients from Chinese medical texts as well as to construct structure files for each isolated compound. We believe that TCM Database@Taiwan will be a milestone on the path towards modernizing traditional Chinese medicine.
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              Human polymorphism at microRNAs and microRNA target sites.

              MicroRNAs (miRNAs) function as endogenous translational repressors of protein-coding genes in animals by binding to target sites in the 3' UTRs of mRNAs. Because a single nucleotide change in the sequence of a target site can affect miRNA regulation, naturally occurring SNPs in target sites are candidates for functional variation that may be of interest for biomedical applications and evolutionary studies. However, little is known to date about variation among humans at miRNAs and their target sites. In this study, we analyzed publicly available SNP data in context with miRNAs and their target sites throughout the human genome, and we found a relatively low level of variation in functional regions of miRNAs, but an appreciable level of variation at target sites. Approximately 400 SNPs were found at experimentally verified target sites or predicted target sites that are otherwise evolutionarily conserved across mammals. Moreover, approximately 250 SNPs potentially create novel target sites for miRNAs in humans. If some variants have functional effects, they might confer phenotypic differences among humans. Although the majority of these SNPs appear to be evolving under neutrality, interestingly, some of these SNPs are found at relatively high population frequencies even in experimentally verified targets, and a few variants are associated with atypically long-range haplotypes that may have been subject to recent positive selection.
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                Author and article information

                Contributors
                Journal
                Front Pharmacol
                Front Pharmacol
                Front. Pharmacol.
                Frontiers in Pharmacology
                Frontiers Media S.A.
                1663-9812
                21 January 2020
                2019
                : 10
                : 1578
                Affiliations
                [1] 1 Faculty of Life Science and Technology, Kunming University of Science and Technology , Kunming, China
                [2] 2 Institute of Biology Leiden, Leiden University , Leiden, Netherlands
                [3] 3 Fytagoras BV , Leiden, Netherlands
                [4] 4 LU-European Center for Chinese Medicine, Leiden University , Leiden, Netherlands
                [5] 5 SUBioMedicine BV , Leiden, Netherlands
                Author notes

                Edited by: Vincent Kam Wai Wong, Macau University of Science and Technology, Macau

                Reviewed by: Songxiao Xu, Artron BioResearch Inc., Canada; Lei Chen, Fujian Agriculture and Forestry University, China; Charles Jay Malemud, Case Western Reserve University, United States

                *Correspondence: Yin Xiong, yhsiung@ 123456163.com

                This article was submitted to Ethnopharmacology, a section of the journal Frontiers in Pharmacology

                Article
                10.3389/fphar.2019.01578
                6985777
                32038252
                dc9a27c5-cd27-4e0b-bd9f-b55ff53f3afa
                Copyright © 2020 Zhang, Zhang, Gao, Cui, Yang, van Duijn, Wang, Hu, Wang and Xiong

                This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

                History
                : 27 August 2019
                : 05 December 2019
                Page count
                Figures: 9, Tables: 4, Equations: 0, References: 71, Pages: 15, Words: 7329
                Funding
                Funded by: National Natural Science Foundation of China 10.13039/501100001809
                Funded by: Applied Basic Research Key Project of Yunnan 10.13039/501100005147
                Funded by: National Basic Research Program of China (973 Program) 10.13039/501100012166
                Categories
                Pharmacology
                Original Research

                Pharmacology & Pharmaceutical medicine
                steamed panax notoginseng,network pharmacology,jak-stat signaling pathway,anemia,blood deficiency syndrome,hematopoiesis

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