Publications by authors named "Jingyan Li"

62 Publications

Essential Oil-Rich Chinese Formula Luofushan-Baicao Oil Inhibits the Infection of Influenza A Virus through the Regulation of NF-B P65 and IRF3 Activation.

Evid Based Complement Alternat Med 2021 30;2021:5547424. Epub 2021 Aug 30.

Guangdong Provincial Key Laboratory of New Drug Screening, School of Pharmaceutical Sciences, Southern Medical University, Guangzhou 510515, China.

Background: Luofushan-Baicao Oil (LBO) is an essential oil-rich traditional Chinese medicine (TCM) formula that is commonly used to treat cold, cough, headache, sore throat, swelling, and pain. However, the anti-influenza activities of LBO and the underlying mechanism remain to be investigated.

Methods: The anti-influenza activity of LBO was tested with methyl thiazolyl tetrazolium (MTT) and plaque assays. The effects of LBO on the expressions of viral nucleoprotein and cytokines were evaluated. In the polyinosinic-polycytidylic acid- (Poly I: C-) induced inflammation model, the influences of LBO on the expression of cytokines and the activation of NF-B P65 (P65) and interferon regulatory factor 3 (IRF3) were tested. After influenza A virus (IVA) infection, mice were administered with LBO for 5 days. The lung index, histopathologic change, the expression of viral protein, P65, and IRF3 in the lung tissue were measured. The levels of proinflammatory cytokines in serum were examined.

Results: , LBO could significantly inhibit the infection of IVA, decrease the formation of plaques, and reduce the expression of viral nucleoprotein and cytokines. LBO could also effectively downregulate the expression of interleukin-1 (IL-1), interleukin-6 (IL-6), and interferon- and the activation of P65 and IRF3 in Poly I:C-treated cells. In the IVA-infected mice model, inhalation of LBO with atomizer could decrease the lung index, alleviate the pathological injury in the lung tissue, and reduce the serum levels of IL-1 and IL-6. LBO could significantly downregulate the expression of viral protein (nucleoprotein, PB2, and matrix 2 ion channel) and the phosphorylation of P65 and IRF3 in the lungs of mice.

Conclusion: The therapeutic effects of LBO on treating influenza might result from the regulation of the immune response of IVA infection. LBO can be developed as an alternative therapeutic agent for influenza prevention.
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http://dx.doi.org/10.1155/2021/5547424DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8421167PMC
August 2021

HO-1 nuclear accumulation and interaction with NPM1 protect against stress-induced endothelial senescence independent of its enzymatic activity.

Cell Death Dis 2021 Jul 26;12(8):738. Epub 2021 Jul 26.

Department of Pharmacology and Toxicology, School of Pharmaceutical Sciences, National and Local United Engineering Lab of Druggability and New Drugs Evaluation, Guangdong Engineering Laboratory of Druggability and New Drug Evaluation, Guangdong Provincial Key Laboratory of New Drug Design and Evaluation, Sun Yat-sen University, Guangzhou, China.

Heme oxygenase-1 (HO-1) has attracted accumulating attention for its antioxidant enzymatic activity. However, the exact regulatory role of its non-enzymatic activity in the cardiovascular system remains unaddressed. Here, we show that HO-1 was accumulated in the nuclei of stress-induced senescent endothelial cells, and conferred protection against endothelial senescence independent of its enzymatic activity. Overexpression of ΔHO-1, a truncated HO-1 without transmembrane segment (TMS), inhibited HO-induced endothelial senescence. Overexpression of ΔHO-1, the catalytically inactive form of ΔHO-1, also exhibited anti-senescent effect. In addition, infection of recombinant adenovirus encoding ΔHO-1 with three nuclear localization sequences (NLS), alleviated endothelial senescence induced by knockdown of endogenous HO-1 by CRISPR/Cas9. Moreover, repression of HO-1 nuclear translocation by silencing of signal peptide peptidase (SPP), which is responsible for enzymatic cleavage of the TMS of HO-1, exacerbated endothelial senescence. Mechanistically, nuclear HO-1 interacted with NPM1 N-terminal portion, prevented NPM1 translocation from nucleolus to nucleoplasm, thus disrupted NPM1/p53/MDM2 interactions and inhibited p53 activation by NPM1, finally resisted endothelial senescence. This study provides a novel understanding of HO-1 as a promising therapeutic strategy for vascular senescence-related cardiovascular diseases.
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http://dx.doi.org/10.1038/s41419-021-04035-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8313700PMC
July 2021

PEX5 prevents cardiomyocyte hypertrophy via suppressing the redox-sensitive signaling pathways MAPKs and STAT3.

Eur J Pharmacol 2021 Sep 24;906:174283. Epub 2021 Jun 24.

Department of Pharmacology and Toxicology, School of Pharmaceutical Sciences; National and Local United Engineering Lab of Druggability and New Drugs Evaluation; Guangdong Engineering Laboratory of Druggability and New Drug Evaluation; Guangdong Provincial Key Laboratory of New Drug Design and Evaluation, Sun Yat-sen University, China. Electronic address:

Peroxisomal biogenesis factor 5 (PEX5) is a member of peroxisome biogenesis protein family which serves as a shuttle receptor for the import of peroxisome matrix protein. The function of PEX5 on cardiomyocyte hypertrophy remained to be elucidated. Our study demonstrated that the protein expression level of PEX5 was declined in primary neonatal rat cardiomyocytes treated with phenylephrine (PE) and hearts from cardiac hypertrophic rats induced by abdominal aortic constriction (AAC). Overexpression of PEX5 alleviated cardiomyocyte hypertrophy induced by PE, while silencing of PEX5 exacerbated cardiomyocyte hypertrophy. PEX5 improved redox imbalance by decreasing cellular reactive oxygen species level and preserving peroxisomal catalase. Moreover, PEX5 knockdown aggravated PE-induced activation of redox-sensitive signaling pathways, including mitogen-activated protein kinase (MAPK) pathway and signal transducer and activator of transcription 3 (STAT3); whereas PEX5 overexpression suppressed activation of MAPK and STAT3. But PEX5 did not affect PE-induced phosphorylation of mammalian target of rapamycin (mTOR). In conclusion, the present study suggests that PEX5 protects cardiomyocyte against hypertrophy via regulating redox homeostasis and inhibiting redox-sensitive signaling pathways MAPK and STAT3.
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http://dx.doi.org/10.1016/j.ejphar.2021.174283DOI Listing
September 2021

The poly(ADP-ribosyl)ation of BRD4 mediated by PARP1 promoted pathological cardiac hypertrophy.

Acta Pharm Sin B 2021 May 14;11(5):1286-1299. Epub 2020 Dec 14.

Department of Pharmacology and Toxicology, School of Pharmaceutical Sciences, National and Local United Engineering Lab of Druggability and New Drugs Evaluation, Guangdong Engineering Laboratory of Druggability and New Drug Evaluation, Guangdong Provincial Key Laboratory of New Drug Design and Evaluation, Sun Yat-sen University, Guangzhou 510006, China.

The bromodomain and extraterminal (BET) family member BRD4 is pivotal in the pathogenesis of cardiac hypertrophy. BRD4 induces hypertrophic gene expression by binding to the acetylated chromatin, facilitating the phosphorylation of RNA polymerases II (Pol II) and leading to transcription elongation. The present study identified a novel post-translational modification of BRD4: poly(ADP-ribosyl)ation (PARylation), that was mediated by poly(ADP-ribose)polymerase-1 (PARP1) in cardiac hypertrophy. BRD4 silencing or BET inhibitors JQ1 and MS417 prevented cardiac hypertrophic responses induced by isoproterenol (ISO), whereas overexpression of BRD4 promoted cardiac hypertrophy, confirming the critical role of BRD4 in pathological cardiac hypertrophy. PARP1 was activated in ISO-induced cardiac hypertrophy and facilitated the development of cardiac hypertrophy. BRD4 was involved in the prohypertrophic effect of PARP1, as implied by the observations that BRD4 inhibition or silencing reversed PARP1-induced hypertrophic responses, and that BRD4 overexpression suppressed the anti-hypertrophic effect of PARP1 inhibitors. Interactions of BRD4 and PARP1 were observed by co-immunoprecipitation and immunofluorescence. PARylation of BRD4 induced by PARP1 was investigated by PARylation assays. In response to hypertrophic stimuli like ISO, PARylation level of BRD4 was elevated, along with enhanced interactions between BRD4 and PARP1. By investigating the PARylation of truncation mutants of BRD4, the C-terminal domain (CTD) was identified as the PARylation modification sites of BRD4. PARylation of BRD4 facilitated its binding to the transcription start sites (TSS) of hypertrophic genes, resulting in enhanced phosphorylation of RNA Pol II and transcription activation of hypertrophic genes. The present findings suggest that strategies targeting inhibition of PARP1-BRD4 might have therapeutic potential for pathological cardiac hypertrophy.
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http://dx.doi.org/10.1016/j.apsb.2020.12.012DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8148063PMC
May 2021

Infant rhesus macaques as a non-human primate model of Bordetella pertussis infection.

BMC Infect Dis 2021 May 3;21(1):407. Epub 2021 May 3.

Institute of Medical Biology, Chinese Academy of Medical Science & Peking Union Medical College, Kunming, 650118, Yunnan, China.

Background: The prevalent resurgence of pertussis has recently become a critical public health problem worldwide. To understand pertussis pathogenesis and the host response to both the pathogen and vaccines, a suitable pertussis animal model, particularly a non-human primate model, is necessary. Recently, a non-human primate pertussis model was successfully established with baboons. Rhesus macaques have been shown to be ideal animal models for several infectious diseases, but a model of infectious pertussis has not been established in these organisms. Studies on rhesus macaque models of pertussis were performed in the 1920s-1930s, but limited experimental details are available. Recent monkey pertussis models have not been successful because the typical clinical symptoms and transmission have not been achieved.

Methods: In the present study, infant rhesus macaques were challenged with Bordetella pertussis (B.p) using an aerosol method to evaluate the feasibility of this system as an animal model of pertussis.

Results: Upon aerosol infection, monkeys infected with the recently clinically isolated B.p strain 2016-CY-41 developed the typical whooping cough, leukocytosis, bacteria-positive nasopharyngeal wash (NPW), and interanimal transmission of pertussis. Both systemic and mucosal humoral responses were induced by B.p.

Conclusion: These results demonstrate that a model of pertussis was successfully established in infant rhesus macaques. This model provides a valuable platform for research on pertussis pathogenesis and evaluation of vaccine candidates.
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http://dx.doi.org/10.1186/s12879-021-06090-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8091708PMC
May 2021

Mechanism and therapeutic strategies of depression after myocardial infarction.

Psychopharmacology (Berl) 2021 Jun 16;238(6):1401-1415. Epub 2021 Feb 16.

Guangdong Key Laboratory for Translational Cancer Research of Chinese Medicine, Joint Laboratory for Translational Cancer Research of Chinese Medicine of the Ministry of Education of the People's Republic of China, International Institute for Translational Chinese Medicine, School of Pharmaceutical Science, Guangzhou University of Chinese Medicine, Guangzhou, 510006, Guangdong, China.

Depression resulted as an important factor associated with the myocardial infarction (MI) prognosis. Patients with MI also have a higher risk for developing depression. Although the issue of depression after MI has become a matter of clinical concern, the molecular mechanism underlying depression after MI remains unclear, whereby several strategies suggested have not got ideal effects, such as selective serotonin reuptake inhibitors. In this review, we summarized and discussed the occurrence mechanism of depression after MI, such as 5-hydroxytryptamine (5-HT) dysfunction, altered hypothalamus-pituitary-adrenal (HPA) axis function, gut microbiota imbalance, exosomal signal transduction, and inflammation. In addition, we offered a succinct overview of treatment, as well as some promising molecules especially from natural products for the treatment of depression after MI.
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http://dx.doi.org/10.1007/s00213-021-05784-0DOI Listing
June 2021

Epigenetics-based therapeutics for myocardial fibrosis.

Life Sci 2021 Apr 9;271:119186. Epub 2021 Feb 9.

School of Pharmaceutical Science, Guangzhou University of Chinese Medicine, Guangzhou, Guangdong 510006, China. Electronic address:

Myocardial fibrosis (MF) is a reactive remodeling process in response to myocardial injury. It is mainly manifested by the proliferation of cardiac muscle fibroblasts and secreting extracellular matrix (ECM) proteins to replace damaged tissue. However, the excessive production and deposition of extracellular matrix, and the rising proportion of type I and type III collagen lead to pathological fibrotic remodeling, thereby facilitating the development of cardiac dysfunction and eventually causing heart failure with heightened mortality. Currently, the molecular mechanisms of MF are still not fully understood. With the development of epigenetics, it is found that epigenetics controls the transcription of pro-fibrotic genes in MF by DNA methylation, histone modification and noncoding RNAs. In this review, we summarize and discuss the research progress of the mechanisms underlying MF from the perspective of epigenetics, including the newest m6A modification and crosstalk between different epigenetics in MF. We also offer a succinct overview of promising molecules targeting epigenetic regulators, which may provide novel therapeutic strategies against MF.
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http://dx.doi.org/10.1016/j.lfs.2021.119186DOI Listing
April 2021

Environmentally relevant concentration of sulfamethoxazole-induced oxidative stress-cascaded damages in the intestine of grass carp and the therapeutic application of exogenous lycopene.

Environ Pollut 2021 Apr 27;274:116597. Epub 2021 Jan 27.

College of Wildlife and Protected Area, Northeast Forestry University, Harbin, 150040, Heilongjiang, PR China. Electronic address:

Due to the unreasonable use and discharge of the aquaculture industry, over standard of the antibiotics has been frequent in different types of water environments, causing adverse effects on aquatic organisms. Lycopene (LYC) is an esculent carotenoid, which is considered to be a strong antioxidant. This study was designed to explore the therapeutic effect of LYC on antibiotic (sulfamethoxazole (SMZ)) induced intestinal injury in grass carp Ctenopharyngodon idella. The 120 carps (the control, LYC, SMZ, and co-administration groups) were treated for 30 days. We found that treatment with LYC significantly suppressed SMZ-induced intestinal epithelial cell damage and tight junction protein destruction through histopathological observation, transmission electron microscopy and detection of related genes (Claudin-1/3/4, Occludin and zonula occludens (ZO)-1/2). Furthermore, LYC mitigated SMZ-induced dysregulation of oxidative stress markers, including elevated malondialdehyde (MDA) levels, and consumed super oxide dimutese (SOD), catalase (CAT) activities and glutathione (GSH) content. In the same treatment, LYC reduced inflammation and apoptosis by a detectable change in pro-inflammatory factors (tumor necrosis factor-alpha (TNF-β), interleukin (IL)-1β, IL-6 and IL-8), anti-inflammatory factors (transforming growth factor-beta (TGF-β) and IL-10) and pro-apoptosis related genes (p53, p53 upregulated modulator of apoptosis (PUMA), Bax/Bcl-2 ratio, caspase-3/9). In addition, activation of autophagy (as indicated by increased autophagy-related genes through AMPK/ATK/MTOR signaling pathway) under the stress of SMZ was also dropped back to the original levels by LYC co-administration. Collectively, our findings identified that LYC can serve as a protectant agent against SMZ-induced intestinal injury.
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http://dx.doi.org/10.1016/j.envpol.2021.116597DOI Listing
April 2021

PRMT5 Prevents Cardiomyocyte Hypertrophy via Symmetric Dimethylating HoxA9 and Repressing HoxA9 Expression.

Front Pharmacol 2020 10;11:600627. Epub 2020 Dec 10.

Laboratory of Pharmacology and Toxicology, School of Pharmaceutical Sciences, National and Local United Engineering Lab of Druggability and New Drugs Evaluation, Guangdong Engineering Laboratoty of Druggability and New Drug Evaluation, Guangdong Provincial Key Laboratory of New Drug Design and Evaluation, Higher Education Mega Center, Sun Yat-Sen University, Guangzhou, China.

The present study reveals a link between protein arginine methyltransferase 5 (PRMT5) and Homebox A9 (HoxA9) in the regulation of cardiomyocyte hypertrophy. In cardiomyocyte hypertrophy induced by β-adrenergic receptor agonist isoprenaline (ISO), PRMT5 expression was decreased while HoxA9 was upregulated. Silencing of PRMT5 or inhibition of PRMT5 by its pharmacological inhibitor EPZ augmented the expressions of cardiomyocyte hypertrophic genes brain natriuretic peptide (BNP) and β-Myosin Heavy Chain (β-MHC), whereas overexpression of PRMT5 inhibited ISO-induced cardiomyocyte hypertrophy, suggesting that PRMT5 ameliorates cardiomyocyte hypertrophy. On the contrary, HoxA9 promoted cardiomyocyte hypertrophy, as implied by the gain-of-function and loss-of-function experiments. HoxA9 was involved in the regulation of PRMT5 in cardiomyocyte hypertrophy, since HoxA9 knockdown prevented si-RPMT5-induced cardiomyocyte hypertrophy, and HoxA9 expression impaired the anti-hypertrophic effect of PRMT5. Co-immunoprecipitation experiments revealed that there were physical interactions between PRMT5 and HoxA9. The symmetric dimethylation level of HoxA9 was decreased by ISO or EPZ treatment, suggesting that HoxA9 is methylated by PRMT5. Additionally, PRMT5 repressed the expression of HoxA9. Chromatin immunoprecipitation (ChIP) assay demonstrated that HoxA9 could bind to the promoter of BNP, and that this binding affinity was further enhanced by ISO or EPZ. In conclusion, this study suggests that PRMT5 symmetric dimethylates HoxA9 and represses HoxA9 expression, thus impairing its binding to BNP promoter and ultimately protecting against cardiomyocyte hypertrophy. These findings provide a novel insight of the mechanism underlying the cardiac protective effect of PRMT5, and suggest potential therapeutic strategies of PRMT5 activation or HoxA9 inhibition in treatment of cardiac hypertrophy.
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http://dx.doi.org/10.3389/fphar.2020.600627DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7793800PMC
December 2020

Single-cell analysis reveals the purification and maturation effects of glucose starvation in hiPSC-CMs.

Biochem Biophys Res Commun 2021 01 2;534:367-373. Epub 2020 Dec 2.

Collaborative Innovation Center for Prevention and Treatment of Cardiovascular Disease, Key Laboratory of Medical Electrophysiology of Ministry of Education, Institute of Cardiovascular Research, Southwest Medical University, Luzhou, 646000, China. Electronic address:

Human-induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) play a critical role in most translational and clinical applications. Although glucose starvation (GS) has been evaluated during cellular purification, there has been no comprehensive evaluation of the transcriptional heterogeneity of these cells. Here, we applied GS for 3 days starting at day 10 of differentiation, and then, harvested hiPSC-CMs at day 20 for single-cell RNA sequencing (scRNA-seq). We found that GS dramatically reduced the proportion of non-cardiomyocytes cells and increased the number of late-stage cardiomyocytes. We also recorded an increase in the expression of MYH6, MYH7, ACTN2, TNNT2, and several other genes associated with the structural and functional maturation of cardiomyocytes. Further analysis indicated that these changes were focused on the signaling pathways involved in the regulation of the actin cytoskeleton, cardiac muscle development, and cardiac muscle contraction. Finally, pseudotime analysis revealed that GS hiPSC-CMs developed in a more mature direction. Together, these results suggest that GS treatment improves the purity and maturation of hiPSC-CMs, which should increase the feasibility of hiPSC-CMs applications.
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http://dx.doi.org/10.1016/j.bbrc.2020.11.076DOI Listing
January 2021

Histone Demethylase JMJD3 Mediated Doxorubicin-Induced Cardiomyopathy by Suppressing SESN2 Expression.

Front Cell Dev Biol 2020 29;8:548605. Epub 2020 Sep 29.

School of Pharmaceutical Sciences, Sun Yat-sen University, Guangzhou, China.

Jumonji domain-containing 3 (JMJD3) protein, a histone demethylase protein, specifically catalyzes the demethylation of H3K27 (H3K27me3) and regulates gene expression. Sestrin2 (SESN2), a stress-inducible protein, protected against doxorubicin (DOX)-induced cardiomyopathy by regulating mitophagy and mitochondrial function. Here, the expression of JMJD3 was increased and that of SESN2 was decreased in both the heart samples from patients with dilated cardiomyopathy and chronic DOX-stimulation induced cardiomyopathy. Inhibition or knockdown of JMJD3 attenuated DOX-induced cardiomyocytes apoptosis, mitochondrial injury and cardiac dysfunction. However, JMJD3 overexpression aggravated DOX-induced cardiomyopathy, which were relieved by SESN2 overexpression. JMJD3 inhibited the transcription of SESN2 by reducing tri-methylation of H3K27 in the promoter region of SESN2. In conclusion, JMJD3 negatively regulated SESN2 via decreasing H3K27me3 enrichment in the promoter region of SESN2, subsequently inducing mitochondrial dysfunction and cardiomyocytes apoptosis. Targeting the JMJD3-SESN2 signaling axis may be a potential therapeutic strategy to protect against DOX-mediated cardiomyopathy.
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http://dx.doi.org/10.3389/fcell.2020.548605DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7552667PMC
September 2020

Plumula Nelumbinis: A review of traditional uses, phytochemistry, pharmacology, pharmacokinetics and safety.

J Ethnopharmacol 2021 Feb 2;266:113429. Epub 2020 Oct 2.

Joint Laboratory for Translational Cancer Research of Chinese Medicine of the Ministry of Education of the People's Republic of China, International Institute for Translational Chinese Medicine, School of Pharmaceutical Sciences, Guangzhou University of Chinese Medicine, Guangzhou, Guangdong, 510006, China. Electronic address:

Ethnopharmacological Relevance: Plumula Nelumbinis, the green embryo of the mature seeds of Nelumbo nucifera Gaertn, has a medical history of over 400 years. It is widely used for clearing the heart and heat, calming the mind, and promoting astringent essence and hemostasis in traditional Chinese medicine. Moreover, it usually dual use as food and medicine. This review aimed to evaluate the therapeutic potential of Plumula Nelumbinis by summarizing its botany, traditional uses, phytochemistry, pharmacology, pharmacokinetics and safety.

Methods: This review summarized published studies on Plumula Nelumbinis in the Chinese Pharmacopoeia and literature databases including PubMed, Web of Science, Baidu Scholar, Wiley and China Knowledge Resource Integrated Database (CNKI), and limits the different research articles in botany, traditional uses, phytochemistry, pharmacology, pharmacokinetics and safety about Plumula Nelumbinis.

Results: Plumula Nelumbinis is used to treat hypertension, arrhythmia, severe aplastic anemia, insomnia, encephalopathy and gynecological disease in traditional Chinese medicine and clinical studies. More than 130 chemicals have been isolated and identified from Plumula Nelumbinis, including alkaloids, flavonoids, polysaccharides and volatile oil. In addition, pharmacological effects, such as protective effects against cardiovascular diseases, neurological diseases, lung and kidney injury, anti-inflammatory and anticancer activities, were also evaluated by in vitro and in vivo studies. Moreover, the potential signaling pathways regulated by Plumula Nelumbinis in cardiovascular and neurological diseases and perspectives on Plumula Nelumbinis research were discussed.

Conclusion: Plumula Nelumbinis, a commonly used Chinese medicine, has a variety of traditional and modern therapeutic uses. Some traditional uses, especially the treatment of cardiovascular and neurological diseases, have been verified by pharmacological investigation. However, the pharmacological molecular mechanisms, pharmacokinetics and toxicology of Plumula Nelumbinis are still incomplete. In the future, a series of systematic studies on active compounds identification, pharmacological mechanism clarification, quality and safety evaluation are necessary.
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http://dx.doi.org/10.1016/j.jep.2020.113429DOI Listing
February 2021

Histone H4R3 symmetric di-methylation by Prmt5 protects against cardiac hypertrophy via regulation of Filip1L/β-catenin.

Pharmacol Res 2020 11 31;161:105104. Epub 2020 Jul 31.

Laboratory of Pharmacology and Toxicology, School of Pharmaceutical Sciences; National and Local United Engineering Lab of Druggability and New Drugs Evaluation; Guangdong Engineering Laboratory of Druggability and New Drug Evaluation; Guangdong Provincial Key Laboratory of New Drug Design and Evaluation, Sun Yat-sen University, No.132 East Wai-huan Road, Higher Education Mega Center, Guangzhou 510006, Guangdong, China. Electronic address:

Background And Purpose: Although histone lysine methylation has been extensively studied for their participation in pathological cardiac hypertrophy, the potential regulatory role of histone arginine methylation remains to be elucidated. The present study focused on H4R3 symmetric di-methylation (H4R3me2s) induced by protein arginine methyltransferase 5 (Prmt5), and explored its epigenetic regulation and underlying mechanisms in cardiomyocyte hypertrophy.

Methods And Results: 1. The expressions of Prmt5 and H4R3me2s were suppressed in cardiac hypertrophy models in vivo and in vitro; 2. Prmt5 silencing or its inhibitor EPZ, or knockdown of cooperator of Prmt5 (Copr5) to disrupt H4R3me2s, facilitated cardiomyocyte hypertrophy, whereas overexpression of wild type Prmt5 rather than the inactive mutant protected cardiomyocytes against hypertrophy; 3. ChIP-sequence analysis identified Filip1L as a target gene of Prmt5-induced H4R3me2s; 4. Knockdown or inhibition of Prmt5 impaired Filip1L transcription and subsequently prevented β-catenin degradation, thus augmenting cardiomyocyte hypertrophy.

Conclusions: The present study reveals that Prmt5-induced H4R3me2s ameliorates cardiomyocyte hypertrophy by transcriptional upregulation of Filip1L and subsequent enhancement of β-catenin degradation. Deficiency of Prmt5 and the resulting suppression of H4R3me2s might facilitate the development of pathological cardiac hypertrophy. Prmt5 might serve as a key epigenetic regulator in pathological cardiac hypertrophy.
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http://dx.doi.org/10.1016/j.phrs.2020.105104DOI Listing
November 2020

Kinase inhibitor roscovitine as a PB2 cap-binding inhibitor against influenza a virus replication.

Biochem Biophys Res Commun 2020 06 13;526(4):1143-1149. Epub 2020 Apr 13.

Guangdong Provincial Key Laboratory of New Drug Screening, Guangzhou Key Laboratory of Drug Research for Emerging Virus Prevention and Treatment, School of Pharmaceutical Sciences, Southern Medical University, Guangzhou, 510515, PR China; State Key Laboratory of Organ Failure Research, Guangdong Provincial Institute of Nephrology, Southern Medical University, Guangzhou, 510515, China. Electronic address:

In this study, we examined the impact of roscovitine, a cyclin-dependent kinase inhibitor (CDKI) that has entered phase I and II clinical trials, on influenza A viruses (IAVs) and its antiviral mechanism. The results illustrated that roscovitine inhibited multiple subtypes of influenza strains dose-dependently, including A/WSN/1933(H1N1), A/Aichi/2/68 (H3N2) and A/FM1/47 (H1N1) with IC value of 3.35 ± 0.39, 7.01 ± 1.84 and 5.99 ± 1.89 μM, respectively. Moreover, roscovitine suppressed the gene transcription and genome replication steps in the viral life cycle. Further mechanistic studies indicated that roscovitine reduced viral polymerase activity and bound specifically to the viral PB2cap protein by fluorescence polarization assay (FP) and surface plasmon resonance (SPR). Therefore, we believed roscovitine, as a PB2cap inhibitor, was a prospective antiviral agent to be developed as therapeutic treatment against influenza A virus infection.
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http://dx.doi.org/10.1016/j.bbrc.2020.04.034DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7152910PMC
June 2020

Structure-activity relationship of flavonoid bifunctional inhibitors against Zika virus infection.

Biochem Pharmacol 2020 07 6;177:113962. Epub 2020 Apr 6.

Guangdong Provincial Key Laboratory of New Drug Screening, Guangzhou Key Laboratory of Drug Research for Emerging Virus Prevention and Treatment, School of Pharmaceutical Sciences, Southern Medical University, Guangzhou, China. Electronic address:

Zika virus (ZIKV) infection is a global public health problem due to its rapid spread and the possibility of causing microcephaly. Currently, no specific antivirals against ZIKV are available for treatment. In the present study, several flavonoids (galangin, kaempferide, quercetin, myricetin and EGCG) were found to reduce ZIKV induced plaques and viral RNA copies with negligible cytotoxic effects on host cells. In addition, inhibition of ZIKV propagation by flavonoids showed structure-activity relationship. Our results demonstrate flavonoids as inhibitors of ZIKV entry and NS2B-NS3 protease. Hence, these flavonoids could be used as potential bifunctional drugs for treating ZIKV infections.
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http://dx.doi.org/10.1016/j.bcp.2020.113962DOI Listing
July 2020

Preparation of P-g-CN-WS nanocomposite and its application in photoelectrochemical detection of 5-formylcytosine.

J Colloid Interface Sci 2020 Mar 1;561:348-357. Epub 2019 Nov 1.

College of Chemistry and Material Science, Shandong Agricultural University, Taian 271018, PR China.

DNA formylation (5-formylcytosine, 5fC) is a major epigenetic modification involved in alterations in the DNA double helix structure and protein identification. Due to the low amount in all mammalian tissues and cells, it is necessary to develop a rapid, sensitive and efficient method for detecting 5fC for further understanding the biological functions of 5fC. Thus, a novel PEC biosensor was constructed using P-g-CN-WS nanocomposite as photoactive material. Firstly, AuNPs/P-g-CN-WS/ITO electrode was prepared as substrate electrode. Secondly, the probe DNA and complementary DNA (containing 5fC base) was modified to the electrode surface based on the formation of Au-S bonds between AuNPs and thiol group on the probe DNA and hybridization, respectively. Finally, the amino functionalized MnO nanoflowers were further modified to the electrode surface by covalent interaction between the aldehyde group on the 5fC and the amino group on MnO nanoflowers. The sensitive and specific detection of 5fC can be achieved by oxidizing ascorbic acid with MnO nanoflowers and quenching the photoactivity of P-g-CN-WS nanocomposite. The sensor has a detection range of 0.01-200 nM and a detection limit of 3.8 pM. Moreover, this sensor has excellent detection specificity, stability and reproducibility.
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http://dx.doi.org/10.1016/j.jcis.2019.10.117DOI Listing
March 2020

Sex-Based Differences in Diabetes Prevalence and Risk Factors: A Population-Based Cross-Sectional Study Among Low-Income Adults in China.

Front Endocrinol (Lausanne) 2019 25;10:658. Epub 2019 Sep 25.

Department of Neurology, Tianjin Medical University General Hospital, Tianjin, China.

The prevalence of diabetes mellitus (DM) among adults has reached epidemic proportions worldwide, including China. In China, sex-based differences in the prevalence and risk factors of DM may exist, particularly among low-income individuals. Thus, we assessed these differences in the prevalence of DM and its risk factors in a low-income Chinese population. Residents aged ≥45 years without histories of strokes or cardiovascular disease were recruited for this study. Multivariate logistic regression analyses were performed to assess the association of risk factors with DM prevalence. This study included 3,725 participants (41.2%, men; 58.8%, women). The mean age of the women (61.12 years) was higher than that of the men (59.14 years, < 0.001). There was no significant sex-based difference in DM prevalence (men, 14.1%; women, 14.5%). Overweight, obesity, high triglyceride levels, and hypertension were independent risk factors for DM in both sexes. However, high-density lipoprotein-cholesterol levels were negatively associated with DM risk among men [odds ratio (OR), 0.544; 95% confidence interval (CI), 0.355-0.833; = 0.005]. Among women, advanced age and high low-density lipoprotein-cholesterol levels were independent risk factors for DM; there was a higher DM risk for women aged 55-74 years than for those aged 45-54 years; however, physical activity was associated with an increased risk of DM (OR, 1.705; 95% CI, 1.195-2.432; = 0.003). These findings suggest a crucial need to implement individualized blood pressure, weight, and lipid managements in low-income populations in China to reduce the burden of DM, especially among older women.
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http://dx.doi.org/10.3389/fendo.2019.00658DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6773800PMC
September 2019

Chrysophanol protects against doxorubicin-induced cardiotoxicity by suppressing cellular PARylation.

Acta Pharm Sin B 2019 Jul 1;9(4):782-793. Epub 2018 Nov 1.

School of Pharmaceutical Sciences, Sun Yat-sen University, Guangzhou 510006, China.

The clinical application of doxorubicin (DOX) in cancer chemotherapy is limited by its life-threatening cardiotoxic effects. Chrysophanol (CHR), an anthraquinone compound isolated from the rhizome of L., is considered to play a broad role in a variety of biological processes. However, the effects of CHR׳s cardioprotection in DOX-induced cardiomyopathy is poorly understood. In this study, we found that the cardiac apoptosis, mitochondrial injury and cellular PARylation levels were significantly increased in H9C2 cells treated by Dox, while these effects were suppressed by CHR. Similar results were observed when PARP1 activity was suppressed by its inhibitors 3-aminobenzamide (3AB) and ABT888. Ectopic expression of PARP1 effectively blocked this CHR׳s cardioprotection against DOX-induced cardiomyocyte injury in H9C2 cells. Furthermore, pre-administration with both CHR and 3AB relieved DOX-induced cardiac apoptosis, mitochondrial impairment and heart dysfunction in Sprague-Dawley rat model. These results revealed that CHR protects against DOX-induced cardiotoxicity by suppressing cellular PARylation and provided critical evidence that PARylation may be a novel target for DOX-induced cardiomyopathy.
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http://dx.doi.org/10.1016/j.apsb.2018.10.008DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6663922PMC
July 2019

Chiral metallic glass nanolattices with combined lower density and improved auxeticity.

Phys Chem Chem Phys 2019 Oct 25;21(37):20588-20594. Epub 2019 Jun 25.

Research School of Chemistry, Energy Change Institute, Australian National University, Canberra ACT, 2601, Australia.

Auxetic materials are promising structural and functional candidates due to their unique lateral expansion when stretched, however, bulk metallic glasses (MGs) could not show any auxeticity because of their intrinsic isotropic nature. Here we construct chiral CuZr metallic glass nanolattices with cavities, and investigate their auxeticity and underlying mechanism with molecular dynamics simulations. It is found that, compared to monolithic MGs, all the chiral metallic glass nanolattices (CMGNs) exhibit improved auxeticity and lower density. For CMGNs with cavities, the negative Poisson's ratio and ultimate tensile strength (UTS) increase first and then decrease with increasing cavity radius, with the cavity radius of 2.5 nm being the most favorable for auxeticity and enhanced UTS. The auxetic mechanism is attributed to the competition between rotation behavior and non-affine deformation under tension. Our study not only reveals the mechanism of auxeticity in CMGNs having cavities but also provides a feasible method to optimize their auxetic performance and density by structure designing of MGs.
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http://dx.doi.org/10.1039/c9cp02545fDOI Listing
October 2019

Trends in the prevalence, awareness, treatment and control of diabetes in rural areas of northern China from 1992 to 2011.

J Diabetes Investig 2020 Jan 27;11(1):241-249. Epub 2019 Jun 27.

Department of Neurology, Tianjin Medical University General Hospital, Tianjin, China.

Aims/introduction: The worldwide prevalence of diabetes mellitus has been increasing over the past decades, particularly in developing countries. Because of the lack of information regarding changes in diabetes mellitus prevalence, awareness, treatment and control in rural China, we assessed these trends - overall and in the context of related health conditions - to explore the impact of these primary health issues on these rates in a poorly educated, rural population.

Materials And Methods: Diabetes mellitus prevalence, awareness, treatment and control rates were compared between two surveys carried out in 1992 and 2011. The residents of three villages, aged 35-64 years, were recruited for this study.

Results: In 1992, 1,091 individuals were interviewed and, in 2011, 2,338 individuals were interviewed. Between the two surveys, the overall diabetes mellitus prevalence in the study population was lower in 1992 than that in 2011 (P < 0.001); among men, the prevalence was 5.2-fold higher in 2011 than in 1992 (10.5 vs 1.7%) and nearly 4.3-fold higher (11.2 vs 2.1%) among women. Men aged 35-44 years, with >6 years of education, stage I hypertension and being overweight, had a higher prevalence of diabetes mellitus in 2011 than in 1992. Similarly, for the same time periods, there was also a higher diabetes mellitus prevalence among women aged 55-64 years, with 1-6 years of education, stage III hypertension and who were overweight. However, there were no significant changes in diabetes mellitus awareness, treatment or control in this population.

Conclusions: These results suggest that particular efforts must be made to enhance diabetes mellitus prevention, control and public awareness in rural communities in China.
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http://dx.doi.org/10.1111/jdi.13095DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6944834PMC
January 2020

Gene markers for exon capture and phylogenomics in ray-finned fishes.

Ecol Evol 2019 Apr 5;9(7):3973-3983. Epub 2019 Mar 5.

Shanghai Universities Key Laboratory of Marine Animal Taxonomy and Evolution, Key Laboratory of Exploration and Utilization of Aquatic Genetic Resources (Shanghai Ocean University), Ministry of Education, Shanghai National Demonstration Center for Experimental Fisheries Science Education (Shanghai Ocean University) Shanghai China.

Gene capture coupled with the next-generation sequencing has become one of the preferred methods of subsampling genomes for phylogenomic studies. Many exon markers have been developed in plants, sharks, frogs, reptiles, fishes, and others, but no universal exon markers have been tested in ray-finned fishes. Here, we identified a suite of "single-copy" protein-coding sequence (CDS) markers through comparing eight fish genomes, and tested them empirically in 83 species (33 families and nine orders or higher clades: Acipenseriformes, Lepisosteiformes, Elopomorpha, Osteoglossomorpha, Clupeiformes, Cypriniformes, Gobiaria, Carangaria, and Eupercaria; sensu Betancur et al. 2013). Sorting the markers according to their completeness and phylogenetic decisiveness in taxa tested resulted in a selection of 4,434 markers, which were proven to be useful in reconstructing phylogenies of the ray-finned fishes at different taxonomic levels. We also proposed a strategy of refining baits (probes) design a posteriori based on empirical data. The markers that we have developed may greatly enrich the batteries of exon markers for phylogenomic study in ray-finned fishes.
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http://dx.doi.org/10.1002/ece3.5026DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6468074PMC
April 2019

Sex Differences in the Prevalence, Awareness, Treatment, and Control of Diabetes Mellitus Among Adults Aged 45 Years and Older in Rural Areas of Northern China: A Cross-Sectional, Population-Based Study.

Front Endocrinol (Lausanne) 2019 14;10:147. Epub 2019 Mar 14.

Department of Neurology, Tianjin Medical University General Hospital, Tianjin, China.

Diabetes mellitus (DM) has reached epidemic proportions among adults worldwide, with China having the world's largest population of individuals with the disease. Although the consequences of low rates of awareness, treatment, and control of DM are understood, sex-related differences in these rates remain unknown. We assessed sex-related differences in the prevalence, awareness, treatment, and control of DM in a low-income, rural population in China. Individuals ≥45 years old without cardiovascular disease were recruited into this study. The prevalence, awareness, treatment, and control of DM in both men and women were assessed after accounting for age, educational level, body mass index, and blood pressure. A total of 3,725 participants (women, 58.8%) were included. A male preponderance in the prevalence of DM was found among individuals aged 45-54 years, whereas there was a female preponderance among patients aged 65-74 years and among those who were illiterate. Among individuals with >6 years of formal education, overweight individuals, and normotensive individuals, there was greater DM awareness among women than among men. There was also a higher DM treatment rate among overweight women than among overweight men. However, better disease control was observed among men than among women for individuals aged 55-64-years, those with 1-6 years of education, and those with stage II hypertension. These results suggest that DM awareness should be improved among men and that regular DM screening should be implemented for men, especially young men. In addition, disease education and management should be strengthened for elderly women, especially those with low levels of education. Further studies are necessary to explore this situation among a representative population sample in China in order to establish a valid protocol against DM.
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http://dx.doi.org/10.3389/fendo.2019.00147DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6426742PMC
March 2019

Factors suggesting relapse of Grave's disease after first radioiodine therapy. Analysis of 607 cases.

Hell J Nucl Med 2019 Jan-Apr;22(1):64-69. Epub 2019 Mar 7.

Department of Nuclear Medicine, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou, China.

Objective: Despite the effectiveness of radioiodine therapy (RIT), a few patients are refractory and show relapse, warranting repeated RIT (RRIT). The purpose of this study is to explore the risk factors for RRIT.

Subjects And Methods: We retrospectively analyzed 607 cases treated with iodine-131 (I) between January 2013 and June 2016. Patients were categorized into two groups: RRIT (n=76) or non-RRIT (n=531). Univariate analysis and a final multivariate model were used to determine the risk factors for RRIT. P<0.05 indicated significance. After a mean 314.5MBq dose of I, 76 patients underwent secondary therapy.

Results: In the univariate analysis, the differences in terms of age, gender, family history of hyperthyroidism, course of disease, 24-hour I uptake, curve shape of I uptake, dose of I, thyroid peroxidase antibody, and thyrotrophin receptor antibody were not statistically significant (P>0.05). Anti-thyroid drug (ATD) treatment history, thyroid mass and dose of I were statistically significant (P values: 0.001, <0.001 and <0.001, respectively). Binary logistic analysis of factors that lead to repeated RIT showed a higher probability of ATD treatment history [OR=2.919, 95%CI (1.424, 5.982), P=0.003] and thyroid mass [OR=1.042, 95%CI(1.031, 1.052), P<0.001] associated with RRIT.

Conclusion: Patients treated with ATD before radioiodine treatment and with larger thyroid mass are at a higher risk for repeated radioiodine treatment.
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http://dx.doi.org/10.1967/s002449910961DOI Listing
July 2019

SIRT6 Suppresses NFATc4 Expression and Activation in Cardiomyocyte Hypertrophy.

Front Pharmacol 2018 8;9:1519. Epub 2019 Jan 8.

Department of Pharmacology and Toxicology, School of Pharmaceutical Sciences, Sun Yat-sen University, Guangzhou, China.

NFATc4, a member from the Nuclear Factor of Activated T cells (NFATs) transcription factor family, plays a pivotal role in the development of cardiac hypertrophy. NFATc4 is dephosphorylated by calcineurin and translocated from the cytoplasm to the nucleus to regulate the expression of hypertrophic genes, like brain natriuretic polypeptide (BNP). The present study identified SIRT6, an important subtype of NAD dependent class III histone deacetylase, to be a negative regulator of NFATc4 in cardiomyocyte hypertrophy. In phenylephrine (PE)-induced hypertrophic cardiomyocyte model, overexpression of SIRT6 by adenovirus infection or by plasmid transfection repressed the protein and mRNA expressions of NFATc4, elevated its phosphorylation level, prevented its nuclear accumulation, subsequently suppressed its transcriptional activity and downregulated its target gene BNP. By contrast, mutant of SIRT6 without deacetylase activity (H133Y) did not demonstrate these effects, suggesting that the inhibitory effect of SIRT6 on NFATc4 was dependent on its deacetylase activity. Moreover, the effect of SIRT6 overexpression on repressing BNP expression was reversed by NFATc4 replenishment, whereas the effect of SIRT6 deficiency on upregulating BNP was recovered by NFATc4 silencing. Mechanistically, interactions between SIRT6 and NFATc4 might possibly facilitate the deacetylation of NFATc4 by SIRT6, thereby preventing the activation of NFATc4. In conclusion, the present study reveals that SIRT6 suppresses the expression and activation of NFATc4. These findings provide more evidences of the anti-hypertrophic effect of SIRT6 and suggest SIRT6 as a potential therapeutic target for cardiac hypertrophy.
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http://dx.doi.org/10.3389/fphar.2018.01519DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6331469PMC
January 2019

Sirtuin 1 represses PKC-ζ activity through regulating interplay of acetylation and phosphorylation in cardiac hypertrophy.

Br J Pharmacol 2019 02 9;176(3):416-435. Epub 2018 Dec 9.

Department of Pharmacology and Toxicology, School of Pharmaceutical Sciences, National and Local United Engineering Lab of Druggability and New Drugs Evaluation, Sun Yat-sen University, Guangzhou, Guangdong, China.

Background And Purpose: Activation of PKC-ζ is closely linked to the pathogenesis of cardiac hypertrophy. PKC-ζ can be activated by certain lipid metabolites such as phosphatidylinositol (3,4,5)-trisphosphate and ceramide. However, its endogenous negative regulators are not well defined. Here, the role of the sirtuin1-PKC-ζ signalling axis and the underlying molecular mechanisms were investigated in cardiac hypertrophy.

Experimental Approach: Cellular hypertrophy in cultures of cardiac myocytes, from neonatal Sprague-Dawley rats, was monitored by measuring cell surface area and the mRNA levels of hypertrophic biomarkers. Interaction between sirtuin1 and PKC-ζ was investigated by co-immunoprecipitation and confocal immunofluorescence microscopy. Sirtuin1 activation was enhanced by resveratrol treatment or Ad-sirtuin1 transfection. A model of cardiac hypertrophy in Sprague-Dawley rats was established by abdominal aortic constriction surgery or induced by isoprenaline in vivo.

Key Results: Overexpression of PKC-ζ led to cardiac hypertrophy and increased activity of NF-κB, ERK1/2 and ERK5, which was ameliorated by sirtuin1 overexpression. Enhancement of sirtuin1 activity suppressed acetylation of PKC-ζ, hindered its binding to phosphoinositide-dependent kinase 1 and inhibited PKC-ζ phosphorylation in cardiac hypertrophy. Consequently, the downstream pathways of PKC-ζ' were suppressed in cardiac hypertrophy. This regulation loop suggests a new role for sirtuin1 in mediation of cardiac hypertrophy.

Conclusions And Implications: Sirtuin1 is an endogenous negative regulator for PKC-ζ and mediates its activity via regulating the acetylation and phosphorylation in the pathogenesis of cardiac hypertrophy. Targeting the sirtuin1-PKC-ζ signalling axis may suggest a novel therapeutic approach against cardiac hypertrophy.
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http://dx.doi.org/10.1111/bph.14538DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6329629PMC
February 2019

sFRP1 has a biphasic effect on doxorubicin-induced cardiotoxicity in a cellular location-dependent manner in NRCMs and Rats.

Arch Toxicol 2019 02 30;93(2):533-546. Epub 2018 Oct 30.

School of Pharmaceutical Sciences, Guangzhou Higher Education Mega Center, Sun Yat-sen University, 132 East Waihuan Road, Guangzhou, 510006, People's Republic of China.

Doxorubicin (Dox) is an effective anticancer drug, however, its clinical application is restricted by the life-threatening cardiotoxic effects. Secreted Frizzled-related protein 1 (sFRP1) has been reported to participate in both the cancer and cardiovascular diseases and was one of the differential expression genes in normal hearts compared with Dox-treated hearts. Thus, it is important to reveal the potential role of sFRP1 in Dox-induced cardiotoxicity. Here, we show that sFRP1 has a biphasic effect on Dox-induced cardiotoxicity in a location-dependent manner. The secretion of sFRP1 was significantly increased in Dox-treated neonatal rat cardiomyocytes (NRCMs) (1 µM) and SD rats (5 mg/kg/injection at day 1, 5, and 9, i.p.). Adding the anti-sFRP1 antibody (0.5 µg/ml) and inhibiting sFRP1 secretion by caffeine (5 mM) both relieved Dox-induced cardiotoxicity through activating Wnt/β-catenin signaling, whereas increasing the secretion of sFRP1 by heparin (100 µg/ml) had the opposite effect. The intracellular level of sFRP1 was significantly decreased after Dox treatment both in vitro and in vivo. Knockdown of sFRP1 by sgRNA aggravated Dox-induced cardiotoxicity, while moderate overexpression of sFRP1 by Ad-sFRP1 exhibited protective effect. Besides, poly(ADP-ribosyl) polymerase-1 (PARP1) was screened as an interacting partner of sFRP1 in NRCMs by mass spectrometry. Our results suggested that the intracellular sFRP1 protected NRCMs from Dox-induced cardiotoxicity by interacting with PARP1. Thus, our results provide a novel evidence that sFRP1 has a biphasic effect on Dox-induced cardiotoxicity. In addition, the oversecretion of sFRP1 might be used as a biomarker to indicate the occurrence of cardiotoxicity induced by Dox treatment.
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http://dx.doi.org/10.1007/s00204-018-2342-5DOI Listing
February 2019

Immune Evasion of Enteroviruses Under Innate Immune Monitoring.

Front Microbiol 2018 14;9:1866. Epub 2018 Aug 14.

Institute of Medical Biology, Yunnan Key Laboratory of Vaccine Research and Development on Severe Infectious Disease, Chinese Academy of Medical Sciences and Peking Union Medical College, Kunming, China.

As a major component of immunological defense against a great variety of pathogens, innate immunity is capable of activating the adaptive immune system. Viruses are a type of pathogen that proliferate parasitically in cells and have multiple strategies to escape from host immune pressure. Here, we review recent studies of the strategies and mechanisms by which enteroviruses evade innate immune monitoring.
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http://dx.doi.org/10.3389/fmicb.2018.01866DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6102382PMC
August 2018

The Association between G2385R and Phenotype of Parkinson's Disease in Asian Population: A Meta-Analysis of Comparative Studies.

Parkinsons Dis 2018 10;2018:3418306. Epub 2018 Jul 10.

Department of Neurology, Shaanxi Provincial People's Hospital, Third Affiliated Hospital of Medical College, Xi'an Jiaotong University, Xi'an, Shaanxi 710068, China.

Numerous studies have investigated the relationship between the G2385R variant and clinical characteristics in Parkinson's disease (PD), but the results have been inconsistent. This study investigated whether the G2385R variant was associated with a unique clinical phenotype of PD in the Asian population, using a meta-analysis. The PubMed, Web of Science, EMBASE, CNKI, and WANFANG databases were searched until September 2017. The strict selection criteria and exclusion criteria were determined, and mean differences (MD) or odds ratios (OR) with 95% confidence intervals (CI) were used to assess the strength of associations. Statistical analyses and graphics were performed using Review Manager 5.3. Sixteen related case-control studies were included in the meta-analysis. The G2385R carriers significantly more often presented a family history (OR: 1.98; 95% CI: 1.16-3.39; =0.01) and had a longer disease duration (MD = 0.47, 95% CI: 0.01-0.93, =0.04) and a higher MMSE score (MD = 1.02, 95% CI: 0.43-1.62 =0.0007) than G2385R noncarriers. There were no significant differences in sex distribution, age at onset, initial symptoms, motor symptoms, depression, levodopa-equivalent dose, and related complications between G2385R-carrier and G2385R-noncarrier PD patients. Our results suggested that most of the clinical characteristics of PD patients with G2385R mutations are similar to those of G2385R noncarriers among Asian PD patients, except for the more common family history, relatively longer disease duration, and higher MMSE scores in the former group.
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http://dx.doi.org/10.1155/2018/3418306DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6079378PMC
July 2018

Heme oxygenase-1 ameliorates oxidative stress-induced endothelial senescence via regulating endothelial nitric oxide synthase activation and coupling.

Aging (Albany NY) 2018 Jul;10(7):1722-1744

Laboratory of Pharmacology and Toxicology, School of Pharmaceutical Sciences; National and Local United Engineering Lab of Druggability and New Drugs Evaluation; Guangdong Provincial Key Laboratory of New Drug Design and Evaluation, Sun Yat-sen University, Guangzhou, 510006, China.

Aim: Premature senescence of vascular endothelial cells is a leading cause of various cardiovascular diseases. Therapies targeting endothelial senescence would have important clinical implications. The present study was aimed to evaluate the potential of heme oxygenase-1 (HO-1) as a therapeutic target for endothelial senescence.

Methods And Results: Upregulation of HO-1 by Hemin or adenovirus infection reversed HO-induced senescence in human umbilical vein endothelial cells (HUVECs); whereas depletion of HO-1 by siRNA or HO-1 inhibitor protoporphyrin IX zinc (II) (ZnPP) triggered HUVEC senescence. Mechanistically, overexpression of HO-1 enhanced the interaction between HO-1 and endothelial nitric oxide synthase (eNOS), and promoted the interaction between eNOS and its upstream kinase Akt, thus resulting in an enhancement of eNOS phosphorylation at Ser1177 and a subsequent increase of nitric oxide (NO) production. Moreover, HO-1 induction prevented the decrease of eNOS dimer/monomer ratio stimulated by HO via its antioxidant properties. Contrarily, HO-1 silencing impaired eNOS phosphorylation and accelerated eNOS uncoupling. , Hemin treatment alleviated senescence of endothelial cells of the aorta from spontaneously hypertensive rats, through upregulating eNOS phosphorylation at Ser1177.

Conclusions: HO-1 ameliorated endothelial senescence through enhancing eNOS activation and defending eNOS uncoupling, suggesting that HO-1 is a potential target for treating endothelial senescence.
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http://dx.doi.org/10.18632/aging.101506DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6075439PMC
July 2018

Phylogenomic analysis on the exceptionally diverse fish clade Gobioidei (Actinopterygii: Gobiiformes) and data-filtering based on molecular clocklikeness.

Mol Phylogenet Evol 2018 11 20;128:192-202. Epub 2018 Jul 20.

Shanghai Universities Key Laboratory of Marine Animal Taxonomy and Evolution, Shanghai, China; Shanghai Collaborative Innovation for Aquatic Animal Genetics and Breeding, Shanghai, China; National Demonstration Center for Experimental Fisheries Science Education (Shanghai Ocean University), China. Electronic address:

The use of genome-scale data to infer phylogenetic relationships has gained in popularity in recent years due to the progress made in target-gene capture and sequencing techniques. Data filtering, the approach of excluding data inconsistent with the model from analyses, presumably could alleviate problems caused by systematic errors in phylogenetic inference. Different data filtering criteria, such as those based on evolutionary rate and molecular clocklikeness as well as others have been proposed for selecting useful phylogenetic markers, yet few studies have tested these criteria using phylogenomic data. We developed a novel set of single-copy nuclear coding markers to capture thousands of target genes in gobioid fishes, a species-rich lineages of vertebrates, and tested the effects of data-filtering methods based on substitution rate and molecular clocklikeness while attempting to control for the compounding effects of missing data and variation in locus length. We found that molecular clocklikeness was a better predictor than overall substitution rate for phylogenetic usefulness of molecular markers in our study. In addition, when the 100 best ranked loci for our predictors were concatenated and analyzed using maximum likelihood, or combined in a coalescent-based species-tree analysis, the resulting trees showed a well-resolved topology of Gobioidei that mostly agrees with previous studies. However, trees generated from the 100 least clocklike frequently recovered conflicting, and in some cases clearly erroneous topologies with strong support, thus indicating strong systematic biases in those datasets. Collectively these results suggest that data filtering has the potential improve the performance of phylogenetic inference when using both a concatenation approach as well as methods that rely on input from individual gene trees (i.e. coalescent species-tree approaches), which may be preferred in scenarios where incomplete lineage sorting is likely to be an issue.
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http://dx.doi.org/10.1016/j.ympev.2018.07.018DOI Listing
November 2018
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