Publications by authors named "Long-Fei Li"

23 Publications

  • Page 1 of 1

Cytochalasans and azaphilones: suitable chemotaxonomic markers for the Chaetomium species.

Appl Microbiol Biotechnol 2021 Nov 14;105(21-22):8139-8155. Epub 2021 Oct 14.

College of Pharmaceutical Sciences, Key Laboratory of Pharmaceutical Quality Control of Hebei Province, Key Laboratory of Medicinal Chemistry and Molecular Diagnostics of Education Ministry of China, Hebei University, Baoding, 071002, People's Republic of China.

The accurate taxonomic concept of the fungal Chaetomium species has been a hard work due to morphological similarity. Chemotaxonomy based on secondary metabolites is a powerful tool for taxonomical purposes, which could be used as an auxiliary reference to solve the problems encountered in the classification of Chaetomium. Among secondary metabolites produced by Chaetomium, cytochalasans and azaphilones exhibited a pattern of distribution and frequency of occurrence that establish them as chemotaxonomic markers for the Chaetomium species. This review attempted to elucidate the composition of the Chaetomium species and its relationship with classical taxonomy by summarizing the pattern of cytochalasans and azaphilones distribution and biosynthesis in the Chaetomium species. KEY POINTS: • Secondary metabolites from the genus Chaetomium are summarized. • Cytochalasans and azaphilones could be characteristic metabolites of the Chaetomium species. • Cytochalasans and azaphilones could be used to analyze for taxonomical purposes.
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http://dx.doi.org/10.1007/s00253-021-11630-2DOI Listing
November 2021

Pra-C exerts analgesic effect through inhibiting microglial activation in anterior cingulate cortex in complete Freund's adjuvant-induced mouse model.

Mol Pain 2021 Jan-Dec;17:1744806921990934

Department of Pharmacy, Precision Pharmacy and Drug Development Center, Tangdu Hospital, Fourth Military Medical University, Xi'an, China.

Chronic pain is highly prevalent worldwide and severely affects daily lives of patients and family members. Praeruptorin C (Pra-C) is a main active ingredient derived from Dunn, traditionally used as antibechic, anti-bronchitis and anti-hypertension drug. Here, we evaluated the effects of Pra-C in a chronic inflammatory pain mouse model induced by complete Freund's adjuvant (CFA) injection. Pra-C (3 mg/kg) treatment for just 3 days after CFA challenge relieved CFA-induced mechanical allodynia and hindpaw edema in mice. In the anterior cingulate cortex (ACC), Pra-C treatment inhibited microglia activation and reduced levels of proinflammatory cytokines, TNF-α and IL-1β, and suppressed upregulation of glutamate receptors caused by CFA injection. In addition, Pra-C attenuated neuronal hyperexcitability in ACC of CFA-injected mice. In vitro studies confirmed the analgesic effect of Pra-C was due to its inhibitory ability on microglial activation. In conclusion, Pra-C administration had a certain effect on relieving chronic pain by inhibiting microglial activation, attenuating proinflammatory cytokine releasing and regulating excitatory synaptic proteins in the ACC of the CFA-injected mice.
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http://dx.doi.org/10.1177/1744806921990934DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7894694PMC
October 2021

Post-treatment with glycyrrhizin can attenuate hepatic mitochondrial damage induced by acetaminophen in mice.

Exp Biol Med (Maywood) 2021 05 20;246(10):1219-1227. Epub 2020 Dec 20.

Department of Pharmacy, Tangdu Hospital, Fourth Military Medical University, Xi'an 710032, China.

Overdose of acetaminophen (APAP) is responsible for the most cases of acute liver failure worldwide. Hepatic mitochondrial damage mediated by neuronal nitric oxide synthase- (nNOS) induced liver protein tyrosine nitration plays a critical role in the pathophysiology of APAP hepatotoxicity. It has been reported that pre-treatment or co-treatment with glycyrrhizin can protect against hepatotoxicity through prevention of hepatocellular apoptosis. However, the majority of APAP-induced acute liver failure cases are people intentionally taking the drug to commit suicide. Any preventive treatment is of little value in practice. In addition, the hepatocellular damage induced by APAP is considered to be oncotic necrosis rather than apoptosis. In the present study, our aim is to investigate if glycyrrhizin can be used therapeutically and the underlying mechanisms of APAP hepatotoxicity protection. Hepatic damage was induced by 300 mg/kg APAP in balb/c mice, followed with administration of 40, 80, or 160 mg/kg glycyrrhizin 90 min later. Mice were euthanized and harvested at 6 h post-APAP. Compared with model controls, glycyrrhizin post-treatment attenuated hepatic mitochondrial and hepatocellular damages, as indicated by decreased serum glutamate dehydrogenase, alanine aminotransferase, and aspartate aminotransferase activities as well as ameliorated mitochondrial swollen, distortion, and hepatocellular necrosis. Notably, 80 mg/kg glycyrrhizin inhibited hepatic nNOS activity and its mRNA and protein expression levels by 16.9, 14.9, and 28.3%, respectively. These results were consistent with the decreased liver nitric oxide content and liver protein tyrosine nitration indicated by 3-nitrotyrosine staining. Moreover, glycyrrhizin did not affect the APAP metabolic activation, and the survival rate of ALF mice was increased by glycyrrhizin. The present study indicates that post-treatment with glycyrrhizin can dose-dependently attenuate hepatic mitochondrial damage and inhibit the up-regulation of hepatic nNOS induced by APAP. Glycyrrhizin shows promise as drug for the treatment of APAP hepatotoxicity.
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http://dx.doi.org/10.1177/1535370220977823DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8142107PMC
May 2021

Rubinoboletus ballouii polysaccharides exhibited immunostimulatory activities through toll-like receptor-4 via NF-κB pathway.

Phytother Res 2021 Apr 18;35(4):2108-2118. Epub 2020 Nov 18.

Institute of Chinese Medicine, The Chinese University of Hong Kong, Shatin, Hong Kong SAR, China.

The biological activities of water-soluble components of edible mushroom Rubinoboletus ballouii (RB) were seldom reported. Polysaccharides of RB (RBP) were prepared and well-characterized using chemical analyses. The immunomodulatory properties of RBP were investigated using human monocyte-derived dendritic cells (moDC) in vitro, and cyclophosphamide (CTX)-induced immunosuppressive mouse model. Results showed that RBP was found to contain 80.6% (w/w) of neutral sugars including D-fucose, D-mannose, D-glucose and D-galactose (1.7:1.4:1.0:1.8), and 12.5% (w/w) of proteins, which composed of glutamine, threonine, serine, etc. RBP could promote the maturation of moDC and increase the secretion of IL-12p40, IL-10, and TNF-α. Furthermore, the stimulation of IL-12p40 production was inhibited by pretreatment with toll-like receptor (TLR)-4 blocker or NF-κB pathway blocker, suggesting that the activation of moDC by RBP was mediated through NF-κB pathway via TLR-4 receptor. On the other hand, in CTX-treated mice, RBP restored the loss of CD34 CD45 hematopoietic stem cells and increased IL-2 production in sera and splenocytes culture supernatant, as well as up-regulated the percentage of CD4 T helper lymphocyte in mice splenocytes. These findings strongly suggested that RBP are the active ingredients of RB responsible for its immunostimulatory actions and deserved to be further investigated as cancer supplements.
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http://dx.doi.org/10.1002/ptr.6958DOI Listing
April 2021

Hydride Transfer Initiated Redox-Neutral Cascade Cyclizations of Aurones: Facile Access to [6,5] Spirocycles.

Org Lett 2020 04 18;22(7):2537-2541. Epub 2020 Mar 18.

School of Chemistry and Pharmaceutical Sciences, Qingdao Agricultural University, Qingdao, 266109, China.

Reported herein is the hydride transfer initiated redox-neutral cascade cyclizations of aurones, providing a variety of [6,5] spiro-heterocycles in satisfactory yields and good diastereoselectivities.
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http://dx.doi.org/10.1021/acs.orglett.0c00309DOI Listing
April 2020

-Alkylation-Initiated Redox-Neutral [5 + 2] Annulation of 3-Alkylindoles with -Aminobenzaldehydes: Access to Indole-1,2-Fused 1,4-Benzodiazepines.

Org Lett 2019 11 7;21(22):8904-8908. Epub 2019 Nov 7.

Shandong Province Key Laboratory of Applied Mycology, College of Chemistry and Pharmaceutical Sciences , Qingdao Agricultural University , Qingdao 266109 , China.

Described herein is an unprecedented -alkylation-initiated redox-neutral [5 + 2] annulation of 3-alkylindoles with -aminobenzaldehydes via a cascade -alkylation/dehydration/[1,5]-hydride transfer/Friedel-Crafts alkylation sequence. A series of indole-1,2-fused 1,4-benzodiazepines are facilely constructed in moderate to good yields in one step. This protocol features excellent regioselectivity, metal-free conditions, high step economy, and wide substrate scope.
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http://dx.doi.org/10.1021/acs.orglett.9b03011DOI Listing
November 2019

Redox-Neutral Cascade Dearomatization of Indoles via Hydride Transfer: Divergent Synthesis of Tetrahydroquinoline-Fused Spiroindolenines.

J Org Chem 2019 11 22;84(21):13935-13947. Epub 2019 Oct 22.

College of Chemical and Environmental Engineering , Shandong University of Science and Technology , Qingdao 266590 , China.

The redox-neutral cascade dearomatization of indoles with -aminobenzaldehydes has been realized via the hydride transfer strategy, achieving the condition- and substrate-controlled divergent synthesis of tetrahydroquinoline-fused spiroindolenines. The integration of hydride transfer-involved C(sp)-H functionalization with dearomatization provides a promising platform for the construction of structurally diverse molecules.
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http://dx.doi.org/10.1021/acs.joc.9b02110DOI Listing
November 2019

[Protective effect of ginsenoside Rb₁ on doxorubicin-induced myocardial autophagy].

Zhongguo Zhong Yao Za Zhi 2017 Apr;42(7):1365-1369

Institute of Radiation Medicine Science, Academy of Military Medical Sciences, Beijing 100850, China.

Ginsenoside Rb₁ (Rb₁), which is one of the main ingredients derived from Panax ginseng, has been found to have extensive pharmacological activities including antioxidant, anti-inflammatory, anticancer properties. In this study, the effect of Rb₁ on doxorubicin-induced myocardial autophagy was studied with H9c2 as the study object. CCK-8 method, transmission electron microscope observation, fluorescence staining observation and Western blot were used to detect changes in H9c2 cell proliferation and autophagy after treatment. According to the results, doxorubicin could cause cell viability decrease, significant increase in the LC3-Ⅱ/LC3-I ratio and down-regulation of the expression of p62. Pretreatment with ginsenoside Rb₁ inhibited cell viability decrease and increase in doxorubicin-induced autophagic structure and LC3-Ⅱ/LC3-I ratio, and down-regulation of the expression of p62. In conclusion, doxorubicin could induce H9c2 cell death and induce autophagy, and ginsenoside Rb₁ showed a protective effect on DOX-induced cardiotoxicity, which may be correlated with suppression of DOX-induced autophagy.
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http://dx.doi.org/10.19540/j.cnki.cjcmm.20170222.009DOI Listing
April 2017

A novel vascular-targeting peptide for gastric cancer delivers low-dose TNFα to normalize the blood vessels and improve the anti-cancer efficiency of 5-fluorouracil.

Peptides 2017 Nov 29;97:54-63. Epub 2017 Sep 29.

Laboratory of Molecular Pharmacology, Department of Pharmacology, School of Pharmacy, Southwest Medical University, Luzhou, PR China; School of Pharmaceutical Engineering & Life Science, Changzhou University, Changzhou, PR China; Laboratory of Molecular Pharmacology, Department of Pharmacology, School of Pharmacy, Southwest Medical University, 319 Zhongshan Road, Luzhou, PR China. Electronic address:

Various vascular-targeted agents fused with tumor necrosis factor α (TNFα) have been shown to improve drug absorption into tumor tissues and enhance tumor vascular function. TCP-1 is a peptide selected through in vivo phage library biopanning against a mouse orthotopic colorectal cancer model and is a promising agent for drug delivery. This study further investigated the targeting ability of TCP-1 phage and peptide to blood vessels in an orthotopic gastric cancer model in mice and assessed the synergistic anti-cancer effect of 5-fluorouracil (5-FU) with subnanogram TNFα targeted delivered by TCP-1 peptide. In vivo phage targeting assay and in vivo colocalization analysis were carried out to test the targeting ability of TCP-1 phage/peptide. A targeted therapy for improvement of the therapeutic efficacy of 5-FU and vascular function was performed through administration of TCP-1/TNFα fusion protein in this model. TCP-1 phage exhibited strong homing ability to the orthotopic gastric cancer after phage injection. Immunohistochemical staining suggested that and TCP-1 phage/TCP-1 peptide could colocalize with tumor vascular endothelial cells. TCP-1/TNFα combined with 5-FU was found to synergistically inhibit tumor growth, induce apoptosis and reduce cell proliferation without evident toxicity. Simultaneously, subnanogram TCP-1/TNFα treatment normalized tumor blood vessels. Targeted delivery of low-dose TNFα by TCP-1 peptide can potentially modulate the vascular function of gastric cancer and increase the drug delivery of chemotherapeutic drugs.
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http://dx.doi.org/10.1016/j.peptides.2017.09.020DOI Listing
November 2017

Polysaccharides of Dendrobium officinale Kimura & Migo protect gastric mucosal cell against oxidative damage-induced apoptosis in vitro and in vivo.

J Ethnopharmacol 2017 Aug 4;208:214-224. Epub 2017 Jul 4.

Institute of Chinese Medicine, The Chinese University of Hong Kong, Shatin, New Territories, Hong Kong Special Administrative Region, China; State Key Laboratory of Phytochemistry and Plant Resources in West China, The Chinese University of Hong Kong, Shatin, New Territories, Hong Kong Special Administrative Region, China; Shenzhen Research Institute, The Chinese University of Hong Kong, Shenzhen, Guangdong, China. Electronic address:

Ethnopharmacological Relevance: Dendrobium officinale Kimura & Migo (DO) is a valuable Traditional Chinese Medicine to nourish stomach, in which polysaccharides are identified as active ingredients. However, limited scientific evidences have been reported on the gastroprotective efficacy of DO. The aim of the current study was to investigate the protective effects and underlying mechanism of polysaccharides from DO(DOP) on gastric mucosal injury.

Material And Methods: For in vitro study, HFE145 cells were pretreated with DOP before induction of cell apoptosis by HO. Cell apoptosis and related proteins expression were detected. In the in vivo study, absolute ethanol was administered orally to induce gastric mucosal injury in rat. The gastric mucosal injury area and histological examination were used to evaluate the effects of DOP treatment on the recovery of the gastric mucosal injury.

Results: HO treatment for 6h significantly induced cell apoptosis in HFE145 cells. However, the destructive effects of HO on HFE 145 cells could be reversed by the pretreatment with DOP. The increased ROS level induced by HO for 4h was reduced after DOP pretreatment. The number of apoptotic cells in both early and late apoptosis stages decreased significantly and the nuclei morphology changes were improved with DOP pretreatment. Furthermore, DOP inhibited caspase 3 activation and PARP cleavage, downregulated Bax expression and upregulated Bcl2 expression in cell model. Further study revealed that pretreatment of DOP inhibited p -NF-κBp65/NF-κBp65 level, indicating DOP inhibited HO-mediated apoptosis via suppression of NF-κB activation. In addition, DOP treatment could ameliorate gastric mucosal injury and inhibit mucin loss induced by ethanol in animal model. DOP treatment also interfered with ethanol-induced apoptosis process by downregulating Bax/Bcl2 ratio in gastric mucosa.

Conclusions: The present study was the first one to demonstrate the gastroprotective effect of DOP through inhibiting oxidative stress-induced apoptosis. This study provided a solid evidence for the potential use of DO as a therapy or health supplement for gastric mucosal diseases.
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http://dx.doi.org/10.1016/j.jep.2017.07.006DOI Listing
August 2017

Vitamin D and Cancer Stem Cells in the Gastrointestinal Tract.

Curr Med Chem 2017 ;24(9):918-927

School of Biomedical Sciences, Faculty of Medicine, The Chinese University of Hong Kong, Shatin, N.T., Hong Kong. China.

Vitamin D has been widely used as a dietary supplement for the prevention and treatment of bone disorders. Epidemiological and preclinical studies demonstrated the anticancer action of vitamin D in a variety of cancers including those in the gastrointestinal (GI) tract. In these studies the inhibitory action of vitamin D on cancer stem cells (CSCs) has been a focus and is also an important subject to revolutionize the therapeutic potential of vitamin D on cancer treatment. Here, we summarize the involvement of CSC markers and factors and also their signaling pathways in the development of cancers in the esophagus, stomach, colon, pancreas and also liver. It is also evidenced that vitamin D could inhibit these markers and factors and their related signaling pathways to suppress tumor progression. All these information could provide new strategies in repurposing vitamin D as therapeutic agent to inhibit cancers in the GI tract.
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http://dx.doi.org/10.2174/0929867324666170214110633DOI Listing
July 2017

The Roles of Histone Demethylase UTX and JMJD3 (KDM6B) in Cancers: Current Progress and Future Perspectives.

Curr Med Chem 2016 ;23(32):3687-3696

Rm 521A, School of Biomedical Sciences, Faculty of Medicine, The Chinese University of Hong Kong, Shatin, N.T., Hong Kong, China.

Aberrant epigenetic reprogramming occurs frequently in the development of tumors. Histone H3 lysine 27 trimethylation (H3K27me3) exerts a repressive epigenetic mark on a large number of genes. UTX and JMJD3 are the only two histone demethylases which activate gene expression via demethylating H3K27me3 to H3K27me2 or H3K27me1. Current studies show that dysregulation of these two proteins are heavily linked to oncogenesis in various tissue types. Accumulating evidence suggested that there is remarkable therapeutic potential of targeting JMJD3 or UTX in different types of cancer. Herein, we shall give a brief review on the functional roles of JMJD3 and UTX in cancers and evaluate the available compounds and agents targeting UTX and JMJD3. Finally, we also discuss the several modalities that target UTX and JMJD3 for cancer therapy. This review will help to develop novel strategies to abolish or restore effects of UTX and JMJD3 in the pathogenesis of cancer.
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http://dx.doi.org/10.2174/0929867323666160725093522DOI Listing
January 2016

Vascular-targeted TNFα and IFNγ inhibits orthotopic colorectal tumor growth.

J Transl Med 2016 06 24;14(1):187. Epub 2016 Jun 24.

Laboratory for Molecular Pharmacology, Department of Pharmacology, School of Pharmacy, Southwest Medical University, Luzhou, People's Republic of China.

Background: Tumor necrosis factor alpha (TNFα) and interferon gamma (IFNγ) were originally identified to show potent anti-tumor activity and immunomodulatory capability. Unfortunately, several clinical studies of relevant cancer therapy did not observe significant response in maximum tolerated dose whether given alone or in combination. We have identified a tumor vasculature homing peptide (TCP-1 peptide) which targets only the vasculature of colorectal tumors but not normal blood vessels in animals and humans. In the current study, the antitumor effect of TCP-1/TNFα and TCP-1/IFNγ alone or in combination was studied in orthotopic colorectal tumor model.

Methods: TCP-1/TNFα and TCP-1/IFNγ recombinant proteins were prepared and i.v. injected to study the in vivo anticancer effect in orthotopic colorectal tumor model. Tumor apoptosis was determined by TUNEL staining and cleaved caspase-3 immunofluorescent staining. Tumor infiltrating lymphocytes were analyzed by immunofluorescent staining and flow cytometry. Western-blot was performed to examine the expression of proteins. Cell apoptosis was measured by Annexin V/PI flow cytometry.

Results: Targeted delivery of TNFα or IFNγ by TCP-1 peptide exhibited better antitumor activity than unconjugated format by inducing more tumor apoptosis and also enhancing antitumor immunity shown by increased infiltration of T lymphocytes inside the tumor. More importantly, combination therapy of TCP-1/TNFα and TCP-1/IFNγ synergistically suppressed tumor growth and alleviated systematic toxicity associated with untargeted therapy. This combination therapy induced massive apoptosis/secondary necrosis in the tumor.

Conclusions: Taken together, our data demonstrate TCP-1 is an efficient drug carrier for targeted therapy of colorectal cancer (CRC). TCP-1/TNFα combined with TCP-1/IFNγ is a promising combination therapy for CRC.
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http://dx.doi.org/10.1186/s12967-016-0944-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4919862PMC
June 2016

Miltirone induced mitochondrial dysfunction and ROS-dependent apoptosis in colon cancer cells.

Life Sci 2016 Apr 9;151:224-234. Epub 2016 Mar 9.

School of Biomedical Sciences, Faculty of Medicine, The Chinese University of Hong Kong, Hong Kong, China. Electronic address:

Aims: To study the characteristics of miltirone-induced anti-colon cancer effects.

Materials And Methods: Cell viability was detected using MTT assay. LDH (lactate dehydrogenase) leakage was detected using CytoTox96® non-radioactive cytotoxicity kit. Apoptosis was detected by FCM (flow cytometry). Caspase activation was determined by chemiluminescence or western blotting. AIF (apoptosis-inducing factor) expression in the cell fraction was determined by western blotting. ROS (reactive oxygen species), MMP (mitochondrial membrane potential) and mitochondrial mass were determined by confocal microscope. Intracellular calcium was detected by both FCM and confocal microscope. To determine the roles of ROS and Ca(2+) in the pro-apoptotic activity of miltirone, colon cancer cells were pretreated with kinds of antioxidants, dicoumarol, calpeptin or BAPTA-AM in some cases.

Key Findings: Miltirone exhibited potent cytotoxicity on colon cancer cells with a better selectivity than that of dihydrotanshinone. The pro-apoptotic activity of miltirone was p53- and ROS-dependent. In detail, miltirone induced direct mitochondrial damage, including significant decrease of mitochondrial ROS, MMP, mass and increase of intracellular ROS and Ca(2+). NQO1 (quinone oxidoreductase1) was supposed to be a defender for the cytotoxicity induced by miltirone in colon cancer cells. Furthermore, miltirone induced time- and concentration-dependent translocation of AIF and activation of caspases.

Significance: In this study, ROS- and p53-dependent apoptosis induced by miltirone on colon cancer cells was firstly revealed. Strong positive feedback between mitochondrial dysfunction and accumulation of intracellular Ca(2+) was suggested to be the characteristic of the anti-colon cancer activity of miltirone.
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http://dx.doi.org/10.1016/j.lfs.2016.02.083DOI Listing
April 2016

Gallic Acid Is the Major Active Component of Cortex Moutan in Inhibiting Immune Maturation of Human Monocyte-Derived Dendritic Cells.

Molecules 2015 Sep 10;20(9):16388-403. Epub 2015 Sep 10.

State Key Laboratory of Phytochemistry and Plant Resources in West China, Institute of Chinese Medicine, the Chinese University of Hong Kong, Hong Kong, China.

Atopic dermatitis (AD) is a widely prevalent and chronically relapsing inflammatory skin disease. Penta Herbs Formula (PHF) is efficacious in improving the quality of life and reducing topical corticosteroid used in children with AD and one of the active herbs it contains is Cortex Moutan. Recent studies showed that altered functions of dendritic cells (DC) were observed in atopic individuals, suggesting that DC might play a major role in the generation and maintenance of inflammation by their production of pro-inflammatory cytokines. Hence, the aims of the present study were to identify the major active component(s) of Cortex Moutan, which might inhibit DC functions and to investigate their possible interactions with conventional corticosteroid on inhibiting the development of DC from monocytes. Monocyte-derived dendritic cells (moDC) culture model coupled with the high-speed counter-current chromatography (HSCCC), high pressure liquid chromatography (HPLC) and Liquid Chromatography-Mass Spectrometry (LCMS) analyses were used. Gallic acid was the major active component from Cortex Moutan which could dose dependently inhibit interleukin (IL)-12 p40 and the functional cluster of differentiation (CD) surface markers CD40, CD80, CD83 and CD86 expression from cytokine cocktail-activated moDC. Gallic acid could also lower the concentration of hydrocortisone required to inhibit the activation of DC.
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http://dx.doi.org/10.3390/molecules200916388DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6331828PMC
September 2015

MicroRNA-related single-nucleotide polymorphism of XPO5 is strongly correlated with the prognosis and chemotherapy response in advanced non-small-cell lung cancer patients.

Tumour Biol 2016 Feb 10;37(2):2257-65. Epub 2015 Sep 10.

Department of Thoracic and Cardiac Surgery, The Fourth People's Hospital of Wuxi City, Jiangnan University, No. 200, Huihe Road, Wuxi, 214062, People's Republic of China.

This study was performed to investigate if the microRNA-related single-nucleotide polymorphisms (miR-SNPs) of XPO5 gene predicted the prognosis and pathological features of advanced non-small-cell lung cancer patients receiving chemotherapy. A total of 131 advanced non-small-cell lung cancer (NSCLC) patients were recruited. MicroRNA (miRNA) binding site prediction software was adopted for the prediction and screening of SNPs in XPO5 and miRNA binding regions. Polymerase chain reaction (PCR) amplification was further performed. Time-dependent survival-free curves were constructed using the Kaplan-Meier technique. Univariate and the multivariate survival analyses were conducted for confirmation of prognostic factor for advanced NSCLC patients receiving chemotherapy. There were no significant differences of SNP distribution frequencies between groups, without statistical significance (P > 0.05). Included clinical pathological features and chemotherapy regimens showed no apparent statistical significance in influencing the curative effect of chemotherapy in advanced NSCLC patients (all P > 0.05). While the objective response rate (ORR) in patients who carried AA and AC genotype was 35.48 and 51.22 %, respectively, with statistically significant difference (P < 0.05). Univariate survival analysis indicated that patients who carried AA genotype showed a significantly lower 5-year survival rate to those who carried AC genotype (P < 0.05). And, considering pathological features, statistical significance was found in patients with different pathological types, lymph node metastasis, differentiation degree, T staging, and pathological staging (all P < 0.05). Multivariate analysis results indicated that the SNP sites of rs11077 might be an independent prognostic factor of advanced NSCLC patients receiving chemotherapy (risk ratio [RR] = 0.346; 95 % confidence interval [95 % CI] = 0.174-0.685, P = 0.002). Other clinical features were all considered to have no apparent effect in influencing the prognostic outcomes of advanced NSCLC patients receiving chemotherapy except lymph node metastasis (P < 0.05). miR-SNP rs11077 of XPO5 may be independently connected with the prognosis and chemotherapy response of advanced NSCLC patients, and patients with AC genotype have relatively improved prognostic outcomes and better curative effect of chemotherapy than those with AA allele of XPO5. Further, lymph node metastasis may be also involved in influencing the prognosis of advanced NSCLC patients.
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http://dx.doi.org/10.1007/s13277-015-3980-3DOI Listing
February 2016

Chronic inflammation and colorectal cancer: the role of vascular endothelial growth factor.

Curr Pharm Des 2015 ;21(21):2960-7

Lo Kwee-Seong Integrated Biomedical Sciences Building, School of Biomedical Sciences, Faculty of Medicine, The Chinese University of Hong Kong, Shatin, Hong Kong, China.

Colorectal cancer (CRC) is the third most frequently diagnosed cancer in males and the second in females worldwide. Accumulating evidence has demonstrated that patients with chronic inflammation in bowels have an increased risk to develop CRC. Various inflammatory cells and mediators produced during chronic inflammation are orchestrated through different molecular signaling pathways and lead to the formation of a microenvironment in favor of tumorigenesis. Vascular endothelial growth factor (VEGF), which can be induced by chronic inflammation, plays a pivotal role in tumor angiogenesis as well as tumor growth and metastasis. Antiangiogenic therapy targeting VEGF and its signaling pathways represents a promising strategy to inhibit colorectal tumorigenesis. Indeed, anti-angiogenic agents modulating VEGF ligands and their receptors have already exhibited great potential in treating patients with CRC, especially when combined with conventional chemotherapeutic agents. This review discusses the promoting role of chronic inflammation in colorectal tumorigenesis at different stages including tumor initiation, promotion, progression and metastasis, highlighting the contributory role of VEGF in angiogenesis during the development from chronic inflammation to CRC. It also describes the clinical significance of anti- VEGF therapy in the treatment of such disease.
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http://dx.doi.org/10.2174/1381612821666150514104244DOI Listing
March 2016

Vascular-targeted TNFα improves tumor blood vessel function and enhances antitumor immunity and chemotherapy in colorectal cancer.

J Control Release 2015 Jul 21;210:134-46. Epub 2015 May 21.

School of Biomedical Sciences, Faculty of Medicine, The Chinese University of Hong Kong, Hong Kong, PR China. Electronic address:

Delivery and penetration of chemotherapeutic drugs into neoplasm through the tumor vasculature are essential mechanisms to enhance the efficiency of chemotherapy. "Vascular targeting" strategy focuses on promoting the infiltration of chemotherapeutic drugs into neoplastic tissues. In this study, we achieved a targeted therapy by coupling tumor necrosis factor α (TNFα) with TCP-1, a novel vascular-targeting peptide, in an orthotopic colorectal cancer model in mice. High dose of TCP-1-conjugated TNFα (TCP-1/TNFα: 5μg/mouse) displayed potent antitumor activity by inducing apoptosis and reducing microvessel number in tumors than unconjugated TNFα, with no evidence of increased toxicity. In the combined therapy, the antitumor action of 5-fluorouracil (5-FU) was potentiated when the mice were pretreated with a low dose of TNFα (1ng/mouse) and to a greater extent by the same concentration of TCP-1/TNFα. In this regard, TCP-1/TNFα combined with 5-FU synergistically inhibited the tumor growth, induced apoptosis and reduced cell proliferation. More importantly, TCP-1/TNFα normalized the tumor vasculature and facilitated the infiltration of immune cells to neoplasm as well as attenuated the immunosuppressing effects of TNFα in bone marrow and spleen. At the same time, TCP-1/TNFα significantly improved 5-FU absorption into the tumor mass. Taken together, these findings underscore the therapeutic potential of TCP-1 as a drug carrier in cancer therapy. TCP-1 is a novel vascular-targeting peptide and appears to be a promising agent for drug delivery. TCP-1 fused with TNFα holds great promise for colorectal cancer therapy.
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http://dx.doi.org/10.1016/j.jconrel.2015.05.282DOI Listing
July 2015

Modeling of TRPV₄-C₁ -mediated calcium signaling in vascular endothelial cells induced by fluid shear stress and ATP.

Biomech Model Mechanobiol 2015 10 11;14(5):979-93. Epub 2015 Jan 11.

Department of Biomedical Engineering, Faculty of Electronic Information and Electrical Engineering, Dalian University of Technology, No. 2, Linggong Rd., Dalian, 116023, China.

The calcium signaling plays a vital role in flow-dependent vascular endothelial cell (VEC) physiology. Variations in fluid shear stress and ATP concentration in blood vessels can activate dynamic responses of cytosolic-free [Formula: see text] through various calcium channels on the plasma membrane. In this paper, a novel dynamic model has been proposed for transient receptor potential vanilloid 4 [Formula: see text]-mediated intracellular calcium dynamics in VECs induced by fluid shear stress and ATP. Our model includes [Formula: see text] signaling pathways through P2Y receptors and [Formula: see text] channels (indirect mechanism) and captures the roles of the [Formula: see text] compound channels in VEC [Formula: see text] signaling in response to fluid shear stress (direct mechanism). In particular, it takes into account that the [Formula: see text] compound channels are regulated by intracellular [Formula: see text] and [Formula: see text] concentrations. The simulation studies have demonstrated that the dynamic responses of calcium concentration produced by the proposed model correlate well with the existing experimental observations. We also conclude from the simulation studies that endogenously released ATP may play an insignificant role in the process of intracellular [Formula: see text] response to shear stress.
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http://dx.doi.org/10.1007/s10237-015-0647-3DOI Listing
October 2015

In vivo and in vitro anti-tumor and anti-metastasis effects of Coriolus versicolor aqueous extract on mouse mammary 4T1 carcinoma.

Phytomedicine 2014 Jul-Aug;21(8-9):1078-87. Epub 2014 May 22.

Institute of Chinese Medicine, The Chinese University of Hong Kong, Shatin, New Territories, Hong Kong; State Key Laboratory of Phytochemistry and Plant Resources in West China, The Chinese University of Hong Kong, Shatin, New Territories, Hong Kong. Electronic address:

Coriolus versicolor (CV), a medicinal mushroom widely consumed in Asian countries, has been demonstrated to be effective in stimulation of immune system and inhibition of tumor growth. The present study aimed to investigate the anti-tumor and anti-metastasis effects of CV aqueous extract in mouse mammary carcinoma 4T1 cells and in 4T1-tumor bearing mouse model. Our results showed that CV aqueous extract (0.125-2 mg/ml) did not inhibit 4T1 cell proliferation while the non-cytotoxic dose of CV extract (1-2 mg/ml) significantly inhibited cell migration and invasion (p<0.05). Besides, the enzyme activities and protein levels of MMP-9 were suppressed by CV extract significantly. Animal studies showed that CV aqueous extract (1 g/kg, orally-fed daily for 4 weeks) was effective in decreasing the tumor weight by 36%, and decreased the lung metastasis by 70.8% against untreated control. Besides, micro-CT analysis of the tumor-bearing mice tibias indicated that CV extract was effective in bone protection against breast cancer-induced bone destruction as the bone volume was significantly increased. On the other hand, CV aqueous extract treatments resulted in remarkable immunomodulatory effects, which was reflected by the augmentation of IL-2, 6, 12, TNF-α and IFN-γ productions from the spleen lymphocytes of CV-treated tumor-bearing mice. In conclusion, our results demonstrated for the first time that the CV aqueous extract exhibited anti-tumor, anti-metastasis and immunomodulation effects in metastatic breast cancer mouse model, and could protect the bone from breast cancer-induced bone destruction. These findings provided scientific evidences for the clinical application of CV aqueous extract in breast cancer patients.
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http://dx.doi.org/10.1016/j.phymed.2014.04.020DOI Listing
April 2015

Modeling of progesterone-induced intracellular calcium signaling in human spermatozoa.

J Theor Biol 2014 Jun 2;351:58-66. Epub 2014 Mar 2.

Faculty of Electronic Information and Electrical Engineering, Dalian University of Technology, No. 2, Linggong Rd., Dalian 116023, China. Electronic address:

Calcium ion is a secondary messenger of mammalian spermatozoa. The dynamic change of its concentration plays a vital role in the process of sperm motility, capacitation, acrosome and fertilization. Progesterone released by the cumulus cells, as a potent stimulator of fertilization, can activate the calcium channels on the plasma membrane, which in turn triggers the dynamic change of intracellular calcium concentration. In this paper, a mathematical model of calcium dynamic response in mammalian spermatozoa induced by progesterone is proposed and numerical simulation of the dynamic model is conducted. The results show that the dynamic response of calcium concentration predicted by the model is in accordance with experimental evidence. The proposed dynamic model can be used to explain the phenomena observed in the experiments and predict new phenomena to be revealed by experimental investigations, which will provide the basis to quantitatively investigate the fluid mechanics and biochemistry for the sperm motility induced by progesterone.
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http://dx.doi.org/10.1016/j.jtbi.2014.02.026DOI Listing
June 2014

Two immunosuppressive compounds from the mushroom Rubinoboletus ballouii using human peripheral blood mononuclear cells by bioactivity-guided fractionation.

Phytomedicine 2013 Oct 3;20(13):1196-202. Epub 2013 Jul 3.

Institute of Chinese Medicine, The Chinese University of Hong Kong, Shatin, N. T., Hong Kong SAR, China; State Key Laboratory of Phytochemistry and Plant Resources in West China (CUHK), The Chinese University of Hong Kong, Shatin, N. T., Hong Kong SAR, China.

Rubinoboletus ballouii is an edible mushroom wildly grown in Yunnan province, China. Up till now, little was known about the chemical and biological properties of this mushroom. The aim of this study was to investigate the immunomodulatory effects of the ethanolic extract of Rubinoboletus ballouii and its fractions on human peripheral blood mononuclear cells (PBMCs) using bioactivity-guided fractionation. The crude extract of the fruiting bodies of RB was fractionated by high-speed counter current chromatography (HSCCC). Twelve fractions were obtained and the third fraction (Fraction C) exerted the most potent anti-inflammatory activities in mitogen-activated PBMCs. Further fractionation of fraction C led to the isolation of two single compounds which were elucidated as 1-ribofuranosyl-s-triazin-2(1H)-one and pistillarin, respectively. The results showed that both 1-ribofuranosyl-s-triazin-2(1H)-one and pistillarin exhibited significant immunosuppressive effects on phytohemagglutinin (PHA)-stimulated human PBMCs by inhibiting [methyl-(3)H]-thymidine uptake and inflammatory cytokines productions such as tumor necrosis factor (TNF)-α, interleukin (IL)-10, interferon (IFN)-γ and IL-1β. Besides, 1-ribofuranosyl-s-triazin-2(1H)-one was firstly found in natural resources, and pistillarin was also isolated from the family Boletaceae for the first time. They exhibited great potential in developing as anti-inflammatory reagents.
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http://dx.doi.org/10.1016/j.phymed.2013.06.005DOI Listing
October 2013

[Association between aggressive behaviors and COMT Val158Met and 5-HTTLPR polymorphisms in children].

Zhongguo Dang Dai Er Ke Za Zhi 2011 May;13(5):361-4

Mental Health Institute, Second Xiangya Hospital, Central South University, Changsha 410011, China.

Objective: To investigate the association between aggressive behaviors and catechol-O-methyltransferase (COMT) single nucleotide polymorphism at position 158 from a valine to a methionine (Val158Met) as well as serotonin (5-HT) transporter gene linked polymorphic region (5-HTTLPR) in children.

Methods: A total of 68 children who were exposed to domestic violence were recruited. The frequencies of genotypes and alleles of COMT Val158Met and 5-HTTLPR were examined by polymerase chain reaction (PCR) and restriction fragment length polymorphism (RFLP) techniques. A comparison was conducted between 24 children with high scores of aggressive problems and 44 control children with low scores of aggressive problems according to Child Behavior Checklist (for parents).ResultsThere were no significant differences in genotypes of COMT Val158Met (χ2=1.612, P=0.447) and 5-HTTLPR (χ2=1.807, P=0.405) between the two groups. There were also no significant differences in the frequencies of alleles of COMT Val158Met (χ2=1.648, P=0.119) and 5-HTTLPR(χ2=0.403, P=0.527) in the two groups.

Conclusions: COMT Val158Met and 5-HTTLPR might not be the susceptible genes of children's aggression, suggesting that children's aggressive behaviors might be affected by multivariate factors.
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May 2011
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