Publications by authors named "Chengyuan Liang"

29 Publications

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Syringa microphylla Diels: A comprehensive review of its phytochemical, pharmacological, pharmacokinetic, and toxicological characteristics and an investigation into its potential health benefits.

Phytomedicine 2021 Dec 12;93:153770. Epub 2021 Oct 12.

Zhuhai Jinan Selenium Source Nanotechnology Co., Ltd., Hengqin New Area, Zhuhai 519030, PR China.

Background: Syringa microphylla Diels is a plant in the family Syringa Linn. For hundreds of years, its flowers and leaves have been used as a folk medicine for the treatment of cough, inflammation, colds, sore throat, acute hepatitis, chronic hepatitis, early liver cirrhosis, fatty liver, and oesophageal cancer.

Purpose: For the first time, we have comprehensively reviewed information on Syringa microphylla Diels that is not included in the Pharmacopoeia, clarified the pharmacological mechanisms of Syringa microphylla Diels and its active ingredients from a molecular biology perspective, compiled in vivo and in vitro animal experimental data and clinical data, and summarized the toxicology and pharmacokinetics of Syringa microphylla Diels. The progress in toxicology research is expected to provide a theoretical basis for the development of new drugs from Syringa microphylla Diels, a natural source of compounds that are potentially beneficial to human health.

Methods: The PubMed, Google Scholar, China National Knowledge Infrastructure, Web of Science, SciFinder Scholar and Thomson Reuters databases were utilized to conduct a comprehensive search of published literature as of July 2021 to find original literature related to Syringa microphylla Diels and its active ingredients.

Results: To date, 72 compounds have been isolated and identified from Syringa microphylla Diels, and oleuropein, verbascoside, isoacteoside, echinacoside, forsythoside B, and eleutheroside B are the main active components. These compounds have antioxidant, antibacterial, anti-inflammatory, and neuroprotective effects, and their safety and effectiveness have been demonstrated in long-term traditional applications. Molecular pharmacology experiments have indicated that the active ingredients of Syringa microphylla Diels exert their pharmacological effects in various ways, primarily by reducing oxidative stress damage via Nrf2/ARE pathway regulation, regulating inflammatory factors and inducing apoptosis through the MAPK and NF-κB pathways.

Conclusion: This comprehensive review of Syringa microphylla Diels provides new insights into the correlations among molecular mechanisms, the importance of toxicology and pharmacokinetics, and potential ways to address the limitations of current research. As Syringa microphylla Diels is a natural low-toxicity botanical medicine, it is worthy of development and utilization and is an excellent choice for treating various diseases.
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http://dx.doi.org/10.1016/j.phymed.2021.153770DOI Listing
December 2021

Foresight regarding drug candidates acting on the succinate-GPR91 signalling pathway for non-alcoholic steatohepatitis (NASH) treatment.

Biomed Pharmacother 2021 Dec 12;144:112298. Epub 2021 Oct 12.

Hydrogen Medicine Center of Taishan Academy of Medical Sciences, Taian City Central Hospital, Taian 271000, PR China. Electronic address:

Non-alcoholic fatty liver disease (NAFLD) is the most common chronic liver disease, and it is a liver manifestation of metabolic syndrome, with a histological spectrum from simple steatosis to non-alcoholic steatohepatitis (NASH). NASH can evolve into progressive liver fibrosis and eventually lead to liver cirrhosis. The pathological mechanism of NASH is multifactorial, involving a series of metabolic disorders and changes that trigger low-level inflammation in the liver and other organs. In the pathogenesis of NASH, the signal transduction pathway involving succinate and the succinate receptor (G-protein-coupled receptor 91, GPR91) regulates inflammatory cell activation and liver fibrosis. This review describes the mechanism of the succinate-GPR91 signalling pathway in NASH and summarizes the drugs that act on this pathway, with the aim of providing a new approach to NASH treatment.
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http://dx.doi.org/10.1016/j.biopha.2021.112298DOI Listing
December 2021

Current Landscape and Future Perspective of Oxazolidinone Scaffolds Containing Antibacterial Drugs.

J Med Chem 2021 08 14;64(15):10557-10580. Epub 2021 Jul 14.

Zhuhai Jinan Selenium Source Nanotechnology Co., Ltd., Hengqin New Area, Zhuhai 519030, P. R. China.

The widespread use of antibiotics has made the problem of bacterial resistance increasingly serious, and the study of new drug-resistant bacteria has become the main direction of antibacterial drug research. Among antibiotics, the fully synthetic oxazolidinone antibacterial drugs linezolid and tedizolid have been successfully marketed and have achieved good clinical treatment effects. Oxazolidinone antibacterial drugs have good pharmacokinetic and pharmacodynamic characteristics and unique antibacterial mechanisms, and resistant bacteria are sensitive to them. This Perspective focuses on reviewing oxazolidinones based on the structural modification of linezolid and new potential oxazolidinone drugs in the past 10 years, mainly describing their structure, antibacterial activity, safety, druggability, and so on, and discusses their structure-activity relationships, providing insight into the reasonable design of safer and more potent oxazolidinone antibacterial drugs.
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http://dx.doi.org/10.1021/acs.jmedchem.1c00480DOI Listing
August 2021

Transcriptome Analysis of Light-Regulated Monoterpenes Biosynthesis in Leaves of L.

Plants (Basel) 2021 May 7;10(5). Epub 2021 May 7.

Jiangsu Key Laboratory for the Research and Utilization of Plant Resources, Institute of Botany, Jiangsu Province and Chinese Academy of Sciences (Nanjing Botanical Garden Mem. Sun Yat-Sen), Nanjing 210014, China.

Light is a key environmental aspect that regulates secondary metabolic synthesis. The essential oil produced in mint ( L.) leaves is used widely in the aromatics industry and in medicine. Under low-light treatment, significant reductions in peltate glandular trichome densities were observed. GC-MS analysis showed dramatically reduced essential oil and menthol contents. Light affected the peltate glandular trichomes' development and essential oil yield production. However, the underlying mechanisms of this regulation were elusive. To identify the critical genes during light-regulated changes in oil content, following a 24 h darkness treatment and a 24 h recovery light treatment, leaves were collected for transcriptome analysis. A total of 95,579 unigenes were obtained, with an average length of 754 bp. About 56.58% of the unigenes were annotated using four public protein databases: 10,977 differentially expressed genes (DEGs) were found to be involved in the light signaling pathway and monoterpene synthesis pathway. Most of the TPs showed a similar expression pattern: downregulation after darkness treatment and upregulation after the return of light. In addition, the genes involved in the light signal transduction pathway were analyzed. A series of responsive transcription factors (TFs) were identified and could be used in metabolic engineering as an effective strategy for increasing essential oil yields.
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http://dx.doi.org/10.3390/plants10050930DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8148558PMC
May 2021

Genome-Wide Analysis of Terpene Synthase Gene Family in and Catalytic Activity Analysis of a Single Terpene Synthase.

Genes (Basel) 2021 04 2;12(4). Epub 2021 Apr 2.

College of Forest, Nanjing Forestry University, Nanjing 210037, China.

Terpenoids are a wide variety of natural products and terpene synthase (TPS) plays a key role in the biosynthesis of terpenoids. plants are rich in essential oils, whose main components are terpenoids, and their biosynthetic pathways have been basically elucidated. However, there is a lack of systematic identification and study of TPS in plants. In this work, we genome-widely identified and analyzed the gene family in , a model plant for functional genomic research in the genus . A total of 63 genes were identified in the genome sequence assembly, which could be divided into six subfamilies. The subfamily had the largest number of genes, which might be related to the abundant monoterpenoids in plants. The subfamily had 18 members and showed a significant species-specific expansion compared with other sequenced Lamiaceae plant species. The 63 genes could be mapped to nine scaffolds of the genome sequence assembly and the distribution of these genes is uneven. Tandem duplicates and fragment duplicates contributed greatly to the increase in the number of genes in . The conserved motifs (RR(X)8W, NSE/DTE, RXR, and DDXXD) were analyzed in TPSs, and significant differentiation was found between different subfamilies. Adaptive evolution analysis showed that were subjected to purifying selection after the species-specific expansion, and some amino acid residues under positive selection were identified. Furthermore, we also cloned and analyzed the catalytic activity of a single terpene synthase, , which belongs to the subfamily. could encode a limonene synthase and catalyze the biosynthesis of limonene, an important precursor of essential oils from the genus . This study provides useful information for the biosynthesis of terpenoids in the genus .
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http://dx.doi.org/10.3390/genes12040518DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8066702PMC
April 2021

Overview of all-trans-retinoic acid (ATRA) and its analogues: Structures, activities, and mechanisms in acute promyelocytic leukaemia.

Eur J Med Chem 2021 Aug 15;220:113451. Epub 2021 Apr 15.

Medical College, Guizhou University, Guiyang, 550025, PR China. Electronic address:

All-trans-retinoic acid (ATRA) is effective for preventing cancer and treating skin diseases and acute promyelocytic leukaemia (APL). These pharmacological effects of ATRA are mainly mediated by retinoid X receptors (RXRs) and retinoic acid receptors (RARs). This article provides a comprehensive overview of the clinical progress on and the molecular mechanisms of ATRA in the treatment of APL. ATRA can promote the transcriptional activation of differentiation-related genes and regulate autophagy by inhibiting mTOR, which results in anti-APL effects. In detail, the structures, pharmacological effects, and clinical studies of 68 types of ATRA analogues are described. These compounds have excellent antitumour therapeutic potential and could be used as lead compounds for further development and research.
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http://dx.doi.org/10.1016/j.ejmech.2021.113451DOI Listing
August 2021

An update review of emerging small-molecule therapeutic options for COVID-19.

Biomed Pharmacother 2021 May 3;137:111313. Epub 2021 Feb 3.

Zhuhai Jinan Selenium Source Nanotechnology Co., Ltd., Hengqin New Area, Zhuhai, 519030, PR China. Electronic address:

The SARS-CoV-2 outbreak and pandemic that began near the end of 2019 has posed a challenge to global health. At present, many candidate small-molecule therapeutics have been developed that can inhibit both the infection and replication of SARS-CoV-2 and even potentially relieve cytokine storms and other related complications. Meanwhile, host-targeted drugs that inhibit cellular transmembrane serine protease (TMPRSS2) can prevent SARS-CoV-2 from entering cells, and its combination with chloroquine and dihydroorotate dehydrogenase (DHODH) inhibitors can limit the spread of SARS-CoV-2 and reduce the morbidity and mortality of patients with COVID-19. The present article provides an overview of these small-molecule therapeutics based on insights from medicinal chemistry research and focuses on RNA-dependent RNA polymerase (RdRp) inhibitors, such as the nucleoside analogues remdesivir, favipiravir and ribavirin. This review also covers inhibitors of 3C-like protease (3CL), papain-like protease (PL) and other potentially innovative active ingredient molecules, describing their potential targets, activities, clinical status and side effects.
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http://dx.doi.org/10.1016/j.biopha.2021.111313DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7857046PMC
May 2021

RNA-dependent RNA polymerase (RdRp) inhibitors: The current landscape and repurposing for the COVID-19 pandemic.

Eur J Med Chem 2021 Mar 21;213:113201. Epub 2021 Jan 21.

Zhuhai Jinan Selenium Source Nanotechnology Co., Ltd., Hengqin New Area, Zhuhai, 519030, PR China. Electronic address:

The widespread nature of several viruses is greatly credited to their rapidly altering RNA genomes that enable the infection to persist despite challenges presented by host cells. Within the RNA genome of infections is RNA-dependent RNA polymerase (RdRp), which is an essential enzyme that helps in RNA synthesis by catalysing the RNA template-dependent development of phosphodiester bonds. Therefore, RdRp is an important therapeutic target in RNA virus-caused diseases, including SARS-CoV-2. In this review, we describe the promising RdRp inhibitors that have been launched or are currently in clinical studies for the treatment of RNA virus infections. Structurally, nucleoside inhibitors (NIs) bind to the RdRp protein at the enzyme active site, and nonnucleoside inhibitors (NNIs) bind to the RdRp protein at allosteric sites. By reviewing these inhibitors, more precise guidelines for the development of more promising anti-RNA virus drugs should be set, and due to the current health emergency, they will eventually be used for COVID-19 treatment.
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http://dx.doi.org/10.1016/j.ejmech.2021.113201DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7826122PMC
March 2021

A GPAT1 Mutation in Arabidopsis Enhances Plant Height but Impairs Seed Oil Biosynthesis.

Int J Mol Sci 2021 Jan 14;22(2). Epub 2021 Jan 14.

Jiangsu Key Laboratory for the Research and Utilization of Plant Resources, Institute of Botany, Jiangsu Province and Chinese Academy of Sciences (Nanjing Botanical Garden Mem. Sun Yat-Sen), Nanjing 210014, China.

Glycerol-3-phosphate acyltransferases (GPATs) play an important role in glycerolipid biosynthesis, and are mainly involved in oil production, flower development, and stress response. However, their roles in regulating plant height remain unreported. Here, we report that Arabidopsis GPAT1 is involved in the regulation of plant height. GUS assay and qRT-PCR analysis in Arabidopsis showed that is highly expressed in flowers, siliques, and seeds. A loss of function mutation in was shown to decrease seed yield but increase plant height through enhanced cell length. Transcriptomic and qRT-PCR data revealed that the expression levels of genes related to gibberellin (GA) biosynthesis and signaling, as well as those of cell wall organization and biogenesis, were significantly upregulated. These led to cell length elongation, and thus, an increase in plant height. Together, our data suggest that knockout of impairs glycerolipid metabolism in Arabidopsis, leading to reduced seed yield, but promotes the biosynthesis of GA, which ultimately enhances plant height. This study provides new evidence on the interplay between lipid and hormone metabolism in the regulation of plant height.
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http://dx.doi.org/10.3390/ijms22020785DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7829857PMC
January 2021

A novel long non-coding RNA PCLN16 facilitates androgen receptor signaling in prostate cancer.

Biochem Biophys Res Commun 2021 01 30;537:78-84. Epub 2020 Dec 30.

Department of Pharmacy, Xinjiang Medical University, Urumqi 830011, Xinjiang, PR China. Electronic address:

The prostate cancer (PCa) poses serious threat to men's health. The androgen receptor (AR) is essential for normal prostate development and prostate cancer progression. We identified a novel lncRNA PCLN16 which is significantly correlated with AR signaling during prostate cancer progression. The AR-regulated PCLN16 was abundantly overexpressed in localized or metastatic prostate cancer tissues and AR-dependent cell lines. PCLN16 silence suppressed AR signaling and tumor growth. PCLN16 interacted with Huntingtin interacting protein 1 (HIP1) transcript to reduce HIP1 degradation. Therefore, PCLN16 could augment AR signaling via a novel positive feedback loop. Our experiments support an oncogenic role for PCLN16 and suggest that PCLN16 might serve as a potential target for therapeutic intervention.
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http://dx.doi.org/10.1016/j.bbrc.2020.12.043DOI Listing
January 2021

Esculin and ferric citrate-incorporated sturgeon skin gelatine as an antioxidant film for food packaging to prevent contamination.

Food Funct 2020 Oct;11(10):9129-9143

School of Food and Bioengineering, Shaanxi University of Science & Technology, Xi'an 710021, P.R. China.

Herein, a sturgeon skin gelatine film combined with esculin and ferric citrate was developed as an edible food packaging material to prevent Enterococcus faecalis (E. faecalis) contamination. E. faecalis is able to hydrolyse esculin in the film, and then the hydrolysed product, esculetin, combines with ferric citrate to form a brown-black phenol iron complex. This phenomenon can be observed easily after 48 h of contamination under visible light, and it can be determined under 365 nm ultraviolet light with high sensitivity. With the addition of esculin and ferric citrate, the film showed better mechanical properties and water vapour permeability than those of the unmodified gelatine. When an increased amount of esculin was added, an increase in thermal stability, antioxidant activity, and antioxidant stability of the film was observed. These physicochemical characteristics are beneficial for developing a packaging material for food storage that mitigates foodborne illness caused by E. faecalis.
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http://dx.doi.org/10.1039/d0fo01510eDOI Listing
October 2020

The development of Coronavirus 3C-Like protease (3CL) inhibitors from 2010 to 2020.

Eur J Med Chem 2020 Nov 6;206:112711. Epub 2020 Aug 6.

Laboratory for Medicinal Chemistry (FFW), Ghent University, Ottergemsesteenweg 460, B9000, Gent, Belgium. Electronic address:

This review fully describes the coronavirus 3CL peptidomimetic inhibitors and nonpeptidic small molecule inhibitors developed from 2010 to 2020. Specifically, the structural characteristics, binding modes and SARs of these 3CL inhibitors are expounded in detail by division into two categories: peptidomimetic inhibitors mainly utilize electrophilic warhead groups to covalently bind the 3CL Cys145 residue and thereby achieve irreversible inhibition effects, whereas nonpeptidic small molecule inhibitors mainly interact with residues in the S1', S1, S2 and S4 pockets via hydrogen bonds, hydrophobic bonds and van der Waals forces. Based on the emerging PROTAC technology and the existing 3CL inhibitors, 3CL PROTAC degraders are hypothesised to be next-generation anti-coronavirus drugs.
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http://dx.doi.org/10.1016/j.ejmech.2020.112711DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7409838PMC
November 2020

A promising antiviral candidate drug for the COVID-19 pandemic: A mini-review of remdesivir.

Eur J Med Chem 2020 Sep 6;201:112527. Epub 2020 Jun 6.

Institute of Antibiotics, Huashan Hospital, Fudan University, Shanghai, 200040, PR China. Electronic address:

Remdesivir (GS-5734), a viral RNA-dependent RNA polymerase (RdRP) inhibitor that can be used to treat a variety of RNA virus infections, is expected to be an effective treatment for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. On May 1, 2020, The U.S. Food and Drug Administration (FDA) has granted Emergency Use Authorization (EUA) for remdesivir to treat COVID-19 patients. In light of the COVID-19 pandemic, this review presents comprehensive information on remdesivir, including information regarding the milestones, intellectual properties, anti-coronavirus mechanisms, preclinical research and clinical trials, and in particular, the chemical synthesis, pharmacology, toxicology, pharmacodynamics and pharmacokinetics of remdesivir. Furthermore, perspectives regarding the use of remdesivir for the treatment of COVID-19 are also discussed.
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http://dx.doi.org/10.1016/j.ejmech.2020.112527DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7834743PMC
September 2020

De novo transcriptomic analysis of light-induced flavonoid pathway, transcription factors in the flower buds of .

Trees (Berl West) 2020 2;34(1):267-283. Epub 2019 Nov 2.

2Nanjing Forestry University, Nanjing, 210037 China.

Key Message: Transcriptomic analysis of the relationship between gene expression patterns and flavonoid contents in the flower buds of under light-induced conditions, especially the flavonoid pathway genes and transcription factors.

Abstract: Flos Lonicerae Japonicae (FLJ), the flower buds of Thunb., has been used to treat some human diseases including severe respiratory syndromes and hand-foot-and-mouth diseases owing to its putative antibacterial, and antiviral effects. Luteoloside is a flavonoid that is used by the Chinese Pharmacopoeia to evaluate the quality of FLJ. Light is an important environmental factor that affects flavonoid biosynthesis in the flower buds of . However, how light triggers increases in flavonoid production remains unclear. To enhance our understanding of the mechanism involved in light-regulated flavonoid biosynthesis, we sequenced the transcriptomes of exposed to three different light conditions: 100% light intensity (CK), 50% light intensity (LI50), and 25% light intensity (LI25) using an Illumina HiSeq 4000 System. A total of 77,297 unigenes with an average length of 809 bp were obtained. Among them, 43,334 unigenes (56.06%) could be matched to at least one biomolecular database. Additionally, 4188, 1545 and 1023 differentially expressed genes (DEGs) were identified by comparative transcriptomics LI25-vs-CK, LI50-vs-CK, and LI25-vs-LI50, respectively. Of note, genes known to be involved in flavonoid biosynthesis, such as 4-coumarate coenzyme A ligase (4CL), and chalcone synthase (CHS) were up-regulated. In addition, a total of 1649 transcription factors (TFs) were identified and divided into 58 TF families; 98 TFs exhibited highly dynamic changes in response to light intensity. Quantitative real-time PCR (qRT-PCR) was used to test the expression profiles of the RNA sequencing (RNA-Seq) data. This study offers insight into how transcriptional expression pattern is influenced by light in the flower buds of , and will enhance the understanding of molecular mechanisms of flavonoid biosynthesis in response to light in .
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http://dx.doi.org/10.1007/s00468-019-01916-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7223627PMC
November 2019

Overview of cannabidiol (CBD) and its analogues: Structures, biological activities, and neuroprotective mechanisms in epilepsy and Alzheimer's disease.

Eur J Med Chem 2020 Apr 22;192:112163. Epub 2020 Feb 22.

School of Food and Bioengineering, Shaanxi University of Science & Technology, Xi'an, 710021, PR China. Electronic address:

Herein, 11 general types of natural cannabinoids from Cannabis sativa as well as 50 (-)-CBD analogues with therapeutic potential were described. The underlying molecular mechanisms of CBD as a therapeutic candidate for epilepsy and neurodegenerative diseases were comprehensively clarified. CBD indirectly acts as an endogenous cannabinoid receptor agonist to exert its neuroprotective effects. CBD also promotes neuroprotection through different signal transduction pathways mediated indirectly by cannabinoid receptors. Furthermore, CBD prevents the glycogen synthase kinase 3β (GSK-3β) hyperphosphorylation caused by Aβ and may be developed as a new therapeutic candidate for Alzheimer's disease.
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http://dx.doi.org/10.1016/j.ejmech.2020.112163DOI Listing
April 2020

Long non-coding RNA mortal obligate RNA transcript suppresses tumor cell proliferation in prostate carcinoma by inhibiting glucose uptake.

Oncol Lett 2019 Oct 5;18(4):3787-3791. Epub 2019 Aug 5.

Department of Pharmacy, Shaanxi University of Science and Technology, Xi'an, Shaanxi 710021, P.R. China.

A previous study reported the decreased expression of long non-coding RNA mortal obligate RNA transcript (lncRNA MORT) in 16 types of cancer, while the functionality of lncRNA MORT in cancer biology remains unknown. Therefore, the present study was conducted to characterize the functionality of lncRNA MORT in prostate carcinoma, a common cancer type worldwide. lncRNA MORT expression level was downregulated in tumor tissues compared with that in the adjacent healthy tissues of patients with prostate carcinoma. Expression of lncRNA MORT in tumor tissues was influenced by tumor size, but not by tumor metastasis. Overexpression of lncRNA MORT inhibited glucose uptake and glucose transporter 1 (GLUT-1) expression in prostate carcinoma cell lines; GLUT-1 overexpression upregulated glucose uptake and attenuated the effects of lncRNA MORT overexpression on glucose uptake, but did not significantly affect the expression of lncRNA MORT. Overexpression of lncRNA MORT inhibited, while GLUT-1 overexpression promoted the proliferation of prostate carcinoma cells. In addition, GLUT-1 overexpression attenuated the effects of lncRNA MORT on cell proliferation. Therefore, lncRNA MORT may inhibit cancer cell proliferation in prostate carcinoma by preventing glucose uptake.
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http://dx.doi.org/10.3892/ol.2019.10711DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6732952PMC
October 2019

Ectopic Expression of a R2R3-MYB Transcription Factor Gene from Increases Flavonoid Accumulation in .

Int J Mol Sci 2019 Sep 11;20(18). Epub 2019 Sep 11.

Institute of Botany, Jiangsu Province and Chinese Academy of Sciences (Nanjing Botanical Garden Mem. Sun Yat-Sen), Nanjing 210014, China.

Thunb. is a widely used medicinal plant and is rich in a variety of active ingredients. Flavonoids are one of the important components in and their content is an important indicator for evaluating the quality of this herb. To study the regulation of flavonoid biosynthesis in , an R2R3-MYB transcription factor gene was isolated and characterized. Bioinformatics analysis indicated that belonged to the subgroup 7, with a typical R2R3 DNA-binding domain and conserved subgroup 7 motifs. The transcriptional level of was proportional to the total flavonoid content during the development of flowers. Subcellular localization analysis revealed that LjaMYB12 localized to the nucleus. Transactivation activity assay indicated that LjaMYB12 was a transcriptional activator. Then, ectopic expression of in Arabidopsis could increase PAL activity and flavonoid content and promote transcription of a range of flavonoid biosynthetic genes. Interestingly, the fold changes of downstream genes in the flavonoid biosynthetic pathway were significantly higher than that of the upstream genes, which suggested that may have different regulatory patterns for the upstream and downstream pathways of flavonoid biosynthesis. The results provided here will effectively facilitate the study of subgroup 7 MYBs and transcriptional regulation of flavonoid biosynthesis in .
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http://dx.doi.org/10.3390/ijms20184494DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6770605PMC
September 2019

Review of the molecular mechanisms of Ganoderma lucidum triterpenoids: Ganoderic acids A, C2, D, F, DM, X and Y.

Eur J Med Chem 2019 Jul 20;174:130-141. Epub 2019 Apr 20.

Laboratory of Hematologic Diseases, Affiliated Hospital of Guangdong Medical University, Zhanjiang, 524001, PR China. Electronic address:

Ganoderma lucidum is a multi-purpose plant medicine that is homologous to functional food. The most attractive properties of G. lucidum are its immunomodulatory and antitumour activities, which are mainly attributed to the following two major active components: G. lucidum polysaccharides and G. lucidum triterpenoids (GLTs). GLTs are effective as supplemental therapies and improve health when combined with other medications to treat hepatitis, fatigue syndrome, and prostate cancer. However, research investigating the mechanism and application of G. lucidum or GLTs in the treatment of diseases remains preliminary in terms of both the utilization efficacy and product type. This review offers comprehensive insight into the pharmacological activities of GLTs and their potential applications in the development of functional foods and nutraceuticals. Specifically, 83 GLTs were selected, and their molecular structures and chemical formulas were described. We also describe 7 ganoderic acids that are currently at different stages of clinical trials (ganoderic acids A, C2, D, F, DM, X and Y). The related pharmacodynamic mechanisms and targeted signalling proteins were further analysed. Notably, the specific relationship between autophagy and apoptosis induced by ganoderic acid DM is summarized here for the first time.
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http://dx.doi.org/10.1016/j.ejmech.2019.04.039DOI Listing
July 2019

Bruton's tyrosine kinase (BTK) inhibitors in treating cancer: a patent review (2010-2018).

Expert Opin Ther Pat 2019 04;29(4):217-241

a Department of Medicinal Chemistry, School of Pharmacy, Health Science Center , Xi'an Jiaotong University , Xi'an , Shaanxi P.R. China.

Introduction: Bruton's tyrosine kinase (BTK) plays a critical role in the regulation of survival, proliferation, activation and differentiation of B-lineage cells. It participates by regulating multiple cellular signaling pathways, including B cell receptor and FcR signaling cascades. BTK is abundantly expressed and constitutively active in the pathogenesis of B cell hematological malignancies, as well as several autoimmune diseases. Therefore, BTK is considered as an attractive target for treatment of B-lineage lymphomas, leukemias, and some autoimmune diseases. Many industry and academia efforts have been made to explore small molecular BTK inhibitors.

Areas Covered: This review aims to provide an overview of the patented BTK inhibitors for the treatment of cancer from 2010 to 2018.

Expert Opinion: BTK inhibitors attract much interest for their therapeutic potential in the treatment of cancers and autoimmune diseases, especially for B cell hematological malignancies. In 2013, ibrutinib was approved by the FDA as the first-in-class BTK inhibitors for the treatment of mantle cell lymphoma (MCL) and chronic lymphocytic leukemia (CLL), and now it is also undergoing clinical evaluation for other indications in either single or combined therapy. It is clear that BTK inhibitors can provide a promising clinical benefit in treating B-lineage lymphomas and leukemias.
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http://dx.doi.org/10.1080/13543776.2019.1594777DOI Listing
April 2019

A Multi-Module Electrodynamic Exciter with a Variable Pole-Arc Ratio Disk Halbach Array for a High-Bandwidth Dynamic Torsional Stiffness Test.

Sensors (Basel) 2019 Mar 13;19(6). Epub 2019 Mar 13.

State Key Laboratory of Digital Manufacturing Equipment and Technology, Huazhong University of Science and Technology, Wuhan 430074, China.

In this paper, a multi-module electrodynamic exciter based on moving-magnet disk voice coil motor is presented to meet the demands of high torque and high bandwidth in a dynamic torsional stiffness test. A variable pole-arc ratio disk Halbach array (VPAR-DHA) is proposed, so that both high torque density and low rotor inertia can be obtained through enhancing the magnetic field in the working range. The analytical quasi-3-D model of VPAR-DHA was set up by using the harmonic function method, with the consideration of end-effects by a correction function. Electromagnetic structure optimization was carried out with the analytical model, and verified by 3-D finite-element (FEM) results. The proposed design was experimentally tested and verified with a prototype that achieved a peak dynamic torque output of 40 Nm at a frequency of 120 Hz, and a stroke of ±1°. The proposed method can also be easily extended to satisfy various demands of dynamic torsional stiffness test.
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http://dx.doi.org/10.3390/s19061272DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6470660PMC
March 2019

The deregulation of miR-133b is associated with poor prognosis in bladder cancer.

Pathol Res Pract 2019 Feb 24;215(2):354-357. Epub 2018 Nov 24.

Department of Pharmacy, Shaanxi University of Science & Technology, Xi'an, 710021, PR China.

Background: MicroRNAs (miRNAs) are single-stranded, endogenous, non-coding RNAs that are increased or decreased in almost all cancer types, and they paly crucial roles in the tumorigenesis as well as development.

Materials And Methods: 90 patients diagnosed with bladder cancer were enrolled in the present study. The bladder cancer tissues or adjacent normal tissues were obtained from the tumor area or adjacent normal zone. The expression level of miR-133b was examined by quantitative real-time polymerase chain reaction assay (qRT-PCR). Survival curves were displayed by the Kaplan-Meier method, and differences between two survival curves were calculated by the log-rank test.

Results: The expression levels of miR-133b in bladder tissues were significantly decreased when compared with the matched adjacent normal bladder tissues (P < 0.05). Moreover, miR-133b expression levels are significantly associated with lymphatic invasion (P = 0.026), distant metastasis (P = 0.025), tumor grade (P = 0.038), as well as the muscle invasion status (P < 0.001). The log-rank test indicated that patients with decreased miR-133b expression underwent poorer overall survival (P = 0.007). Furthermore, multivariate Cox regression analysis showed that the expression level of miR-133b (P = 0.024) was an independent factor for predicting the overall survival in patients with bladder cancer.

Conclusions: The present study showed that miR-133b might be associated with bladder cancer progression, and its down-regulation might be a biomarker for poor prognosis of bladder cancer.
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http://dx.doi.org/10.1016/j.prp.2018.11.018DOI Listing
February 2019

Transcriptome Analysis of JA Signal Transduction, Transcription Factors, and Monoterpene Biosynthesis Pathway in Response to Methyl Jasmonate Elicitation in L.

Int J Mol Sci 2018 Aug 10;19(8). Epub 2018 Aug 10.

Institute of Botany, Jiangsu Province and Chinese Academy of Sciences, Nanjing 210014, China.

L. has important economic value for its abundance in essential oils. Menthol is the main component of essential oils, which is certainly the best-known monoterpene for its simple structure and wide applications. However, the regulation of menthol biosynthesis remains elusive in . In this study, transcriptome sequencing of with MeJA treatment was applied to illustrate the transcriptional regulation of plant secondary metabolites, especially menthol biosynthesis. Six sequencing libraries were constructed including three replicates for both control check (CK) and methyl jasmonate (MeJA) treatment and at least 8 Gb clean bases was produced for each library. After assembly, a total of 81,843 unigenes were obtained with an average length of 724 bp. Functional annotation indicated that 64.55% of unigenes could be annotated in at least one database. Additionally, 4430 differentially expressed genes (DEGs) with 2383 up-regulated and 2047 down-regulated transcripts were identified under MeJA treatment. Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment indicated that "Monoterpenoid biosynthesis" was one of the most significantly enriched pathways in metabolism. Subsequently, DEGs involved in JA signal transduction, transcription factors, and monoterpene biosynthesis were analyzed. 9 orthologous genes involved in menthol biosynthesis were also identified. This is the first report of a transcriptome study of and will facilitate the studies of monoterpene biosynthesis in the genus .
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http://dx.doi.org/10.3390/ijms19082364DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6121529PMC
August 2018

The development of Bruton's tyrosine kinase (BTK) inhibitors from 2012 to 2017: A mini-review.

Eur J Med Chem 2018 May 23;151:315-326. Epub 2018 Mar 23.

School of Pharmaceutical Sciences, Guru Ghasidas Central University, Bilaspur (C.G.), 495009, India. Electronic address:

Bruton's tyrosine kinase (BTK) has emerged as a promising drug target for multiple diseases, particularly haematopoietic malignancies and autoimmune diseases related to B lymphocytes. This review focuses on the diverse, small-molecule inhibitors of BTK kinase that have shown good prospects for clinical application. Individual examples of these inhibitors, including both reversible and irreversible inhibitors and a recently developed reversible covalent inhibitor of BTK, are discussed. Considerable progress has been made in the development of irreversible inhibitors, most of which target the SH3 pocket and the cysteine 481 residue of BTK. The present review also surveys the pharmacological advantages and deficiencies of both reversible and irreversible BTK drugs, with a focus on the structure-activity relationship (SARs) and binding modes of representative drugs, which could inspire critical thinking and new ideas for developing potent BTK inhibitors with less unwanted off-target effects.
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http://dx.doi.org/10.1016/j.ejmech.2018.03.062DOI Listing
May 2018

Identification and analysis of CYP450 genes from transcriptome of and expression analysis of chlorogenic acid biosynthesis related CYP450s.

PeerJ 2017 12;5:e3781. Epub 2017 Sep 12.

Institute of Botany, Jiangsu Province and Chinese Academy of Sciences, Nanjing, China.

Background: is an important medicinal plant that has been widely used in traditional Chinese medicine for thousands of years. The pharmacological activities of are mainly due to its rich natural active ingredients, most of which are secondary metabolites. CYP450s are a large, complex, and widespread superfamily of proteins that participate in many endogenous and exogenous metabolic reactions, especially secondary metabolism. Here, we identified CYP450s in transcriptome and analyzed CYP450s that may be involved in chlorogenic acid (CGA) biosynthesis.

Methods: The recent availability of transcriptome provided opportunity to identify CYP450s in this herb. BLAST based method and HMM based method were used to identify CYP450s in transcriptome. Then, phylogenetic analysis, conserved motifs analysis, GO annotation, and KEGG annotation analyses were conducted to characterize the identified CYP450s. qRT-PCR was used to explore expression patterns of five CGA biosynthesis related CYP450s.

Results: In this study, 151 putative CYP450s with complete cytochrome P450 domain, which belonged to 10 clans, 45 families and 76 subfamilies, were identified in transcriptome. Phylogenetic analysis classified these CYP450s into two major branches, A-type (47%) and non-A type (53%). Both types of CYP450s had conserved motifs in . The differences of typical motif sequences between A-type and non-A type CYP450s in were similar with other plants. GO classification indicated that non-A type CYP450s participated in more molecular functions and biological processes than A-type. KEGG pathway annotation totally assigned 47 CYP450s to 25 KEGG pathways. From these data, we cloned two (CYP98A subfamily) and three (CYP73A subfamily) that may be involved in biosynthesis of CGA, the major ingredient for pharmacological activities of . qRT-PCR results indicated that two exhibited oppositing expression patterns during the flower development and exhibited a similar expression pattern with CGA concentration measured by HPLC. The expression patterns of three were quite different and the expression pattern of was quite similar with that of .

Discussion: Our results provide a comprehensive identification and characterization of CYP450s in . Five CGA biosynthesis related were cloned and their expression patterns were explored. The different expression patterns of two and three may be due to functional divergence of both substrate and catalytic specificity during plant evolution. The co-expression pattern of and strongly suggested that they were under coordinated regulation by the same transcription factors due to same elements in their promoters. In conclusion, this study provides insight into CYP450s and will effectively facilitate the research of biosynthesis of CGA in .
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http://dx.doi.org/10.7717/peerj.3781DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5600180PMC
September 2017

Synthesis and in vitro and in vivo antitumour activity study of 11-hydroxyl esterified bergenin/cinnamic acid hybrids.

Eur J Med Chem 2017 Jun 3;133:319-328. Epub 2017 Apr 3.

Faculty of Pharmacy, Shaanxi University of Science and Technology, Xi'an 710021, People's Republic of China. Electronic address:

Fourteen bergenin/cinnamic acid hybrids were synthesized, characterized and evaluated for their antitumour activity both in vitro and in vivo. The most potent compound, 5c, arrested HepG2 cells (IC = 4.23 ± 0.79 μM) in the G2/M phase and induced cellular apoptosis. Moreover, compound 5c was also found to suppress the tumour growth in Heps xenograft-bearing mice with low toxicity. In the mechanistic study, 5c administration ignited a mitochondria-mediated apoptosis pathway of HepG2 cell death. Furthermore, 5c activated Akt-dependent pathways and further decreased the expression of the Bcl-2 family of proteins. The downstream mitochondrial p53 translocation was also significantly activated, accompanied by an increase of the caspase-9, caspase-3 activation. These data imply that bergenin/cinnamic acid hybrids could serve as novel Akt/Bcl-2 inhibitors for further preclinical studies.
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http://dx.doi.org/10.1016/j.ejmech.2017.03.053DOI Listing
June 2017

Pharmacological Activities and Synthesis of Esculetin and Its Derivatives: A Mini-Review.

Molecules 2017 Mar 2;22(3). Epub 2017 Mar 2.

Faculty of Finance and Economics, Guangzhou Vocational College of Science and Technology, Guangzhou 510550, China.

Esculetin, synonymous with 6,7-dihydroxycoumarin, is the main active ingredient of the traditional Chinese medicine . The twig skin or trunk bark of are used by herb doctors as a mild, bitter liver and gallbladder meridians' nontoxic drug as well as dietary supplement. Recently, with a variety of novel esculetin derivatives being reported, the molecular mechanism research as well as clinical application of and esculetin are becoming more attractive. This mini-review will consolidate what is known about the biological activities, the mechanism of esculetin and its synthetic derivatives over the past decade in addition to providing a brief synopsis of the properties of esculetin.
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http://dx.doi.org/10.3390/molecules22030387DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6155195PMC
March 2017

Effective Synthesis of Nucleosides Utilizing O-Acetyl-Glycosyl Chlorides as Glycosyl Donors in the Absence of Catalyst: Mechanism Revision and Application to Silyl-Hilbert-Johnson Reaction.

Molecules 2017 Jan 5;22(1). Epub 2017 Jan 5.

Faculty of Pharmacy, Shaanxi University of Science & Technology, 6 Xuefu Road, Xi'an 710021, China.

An effective synthesis of nucleosides using glycosyl chlorides as glycosyl donors in the absence of Lewis acid has been developed. Glycosyl chlorides have been shown to be pivotal intermediates in the classical silyl-Hilbert-Johnson reaction. A possible mechanism that differs from the currently accepted mechanism advanced by Vorbrueggen has been proposed and verified by experiments. In practice, this catalyst-free method provides easy access to Capecitabine in high yield.
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http://dx.doi.org/10.3390/molecules22010084DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6155650PMC
January 2017

Synthesis, in vitro and in vivo antitumor activity of symmetrical bis-Schiff base derivatives of isatin.

Eur J Med Chem 2014 Mar 13;74:742-50. Epub 2013 Jun 13.

School of Pharmacy, Jiangsu University, Zhenjiang 212013, PR China. Electronic address:

Eighteen symmetrical bis-Schiff base derivatives of isatin were synthesized by condensation of the natural or synthetic isatins with hydrazine and were evaluated for their in vitro and in vivo antitumor activities. More than half of the obtained compounds showed potent cytotoxicity according to the MTT assay on five different human cancer cell lines (i.e. HeLa, SGC-7901, HepG2, U251, and A549), with compound 3b 3,3'-(hydrazine-1,2-diylidene)bis (5-methylindolin-2-one) being the most potent compound on HepG2 (IC₅₀ ∼ 4.23 μM). 3b was also found to be able to inhibit substantially the tumor growth on the HepS-bearing mice at a dose of 40 mg/kg. The real-time live cell imaging and tracking in the H2B-labeled HeLa cells revealed that 3b could induce mitosis interference and apoptosis-associated cell death. In mechanism study, 3b arrested the cell cycle at the G2/M phase in HepG2 cells by down-regulating the expression of cyclin B1 and cdc 2.
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http://dx.doi.org/10.1016/j.ejmech.2013.04.040DOI Listing
March 2014

Ultrasound-promoted greener synthesis of novel trifurcate 3-substituted-chroman-2,4-dione derivatives and their drug-likeness evaluation.

Molecules 2012 Nov 28;17(12):14146-58. Epub 2012 Nov 28.

School of Pharmacy, China Pharmaceutical University, Nanjing 210009, Jiangsu, China.

An efficient and convenient approach for one-pot synthesis of 3-substituted chroman-2,4-diones via a three-component reaction of aromatic aldehydes, 4-hydroxy-coumarins and diverse pyrazolone derivatives was described. The combinatorial synthesis for this methodology was achieved by applying ultrasound irradiation in the absence of activator while making use of water as green solvent. Additionally, novel chroman-2,4-dione derivatives attached to an edaravone moiety represent an exploitable source of brand new anticancer agents. In comparison with conventional methods, experimental simplicity, good functional group tolerance, excellent yields, short routine, and atom efficiency are prominent features of this sonocatalyzed procedure.
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http://dx.doi.org/10.3390/molecules171214146DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6268048PMC
November 2012
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