Publications by authors named "Xiaofei Luan"

8 Publications

  • Page 1 of 1

Regulating Gut Microbiome: Therapeutic Strategy for Rheumatoid Arthritis During Pregnancy and Lactation.

Front Pharmacol 2020 11;11:594042. Epub 2020 Nov 11.

Department of Pharmacy, Women's Hospital, School of Medicine, Zhejiang University, Hangzhou, China.

Rheumatoid arthritis (RA) is an autoimmune disease characterized by synovial inflammation and bone destruction. Microbial infection is considered to be the most important inducement of RA. The pregnancy planning of women in childbearing age is seriously affected by the disease activity of RA. Gut microbiome, related to immunity and inflammatory response of the host. At present, emerging evidence suggested there are significant differences in the diversity and abundance of gut microbiome during pregnancy and lactation, which may be associated with the fluctuation of RA disease activity. Based on these research foundations, we pioneer the idea of regulating gut microbiome for the treatment of RA during pregnancy and lactation. In this review, we mainly introduce the potential treatment strategies for controlling the disease activity of RA based on gut microbiome during pregnancy and lactation. Besides, we also briefly generalize the effects of conventional anti-rheumatic drugs on gut microbiome, the effects of metabolic changes during pregnancy on gut microbiome, alteration of gut microbiome during pregnancy and lactation, and the effects of anti-rheumatic drugs commonly used during pregnancy and lactation on gut microbiome. These will provide a clear knowledge framework for researchers in immune-related diseases during pregnancy. Regulating gut microbiome may be a potential and effective treatment to control the disease activity of RA during pregnancy and lactation.
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http://dx.doi.org/10.3389/fphar.2020.594042DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7748111PMC
November 2020

Letrozole combined with oral contraceptives versus oral contraceptives alone in the treatment of endometriosis-related pain symptoms: a pilot study.

Gynecol Endocrinol 2021 Jan 16;37(1):51-55. Epub 2020 Sep 16.

Hainan General Hospital, Haikou, China.

Background: To compare the efficacy and the tolerability of letrozole combined with oral contraceptives versus oral contraceptives alone in treating endometriosis-related pain.

Methods: A total of 820 women with endometriosis presented with endometriosis-related pain were enrolled with this study. Patients were randomly treated either with letrozole (2.5 mg/day) combined with oral contraceptives ( or oral contraceptives () alone for 6 months. Changes in pain symptoms during treatment and in 1 months after treatment, 6-month follow-up and 12-month follow-up were evaluated. Adverse effects of each treatment protocol were recorded.

Results: At completion of treatment, the intensity of chronic pelvic pain continued to decrease during treatment and at 1-month after treatment it was significantly lower than at 6-month follow-up and baseline level both in LE + oral contraceptives group (Mean ± SD,1.5 ± 1.4) and in oral contraceptives alone group(Mean ± SD,2.9 ± 1.2).The intensity of chronic pelvic pain and deep dyspareunia was significantly decrease at both 1-month after treatment and 6-month follow-up.

Conclusions: This treatment for endometriosis is a promising new modality that warrants further investigation.
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http://dx.doi.org/10.1080/09513590.2020.1807502DOI Listing
January 2021

Sustained delivery of 17β-estradiol by human amniotic extracellular matrix (HAECM) scaffold integrated with PLGA microspheres for endometrium regeneration.

Drug Deliv 2020 Dec;27(1):1165-1175

Department of Pharmacy, Women's Hospital, School of Medicine, Zhejiang University, Hangzhou, China.

The endometrial injury usually results in intrauterine adhesions (IUAs). However, there is no effective treatment to promote the regeneration of the endometrium currently. The decellularized amnion membrane (AM) is a promising material in human tissue repair and regeneration due to its biocompatibility, biodegradability, as well as the preservation of abundant bioactive components. Here, an innovative drug-delivering system based on human amniotic extracellular matrix (HAECM) scaffolds were developed to facilitate endometrium regeneration. The 17β-estradiol (E) loaded PLGA microspheres (E-MS) were well dispersed in the scaffolds without altering their high porosity. E released from E-MS-HAECM scaffolds showed a decreased initial burst release followed with a sustained release for 21 days, which coincided with the female menstrual cycle. Results of cell proliferation suggested E-MS-HAECM scaffolds had good biocompatibility and provided more biologic guidance of endometrial cell proliferation except for mechanical supports. Additionally, the mRNA expression of growth factors in endometrial cells indicated that HAECM scaffolds could upregulate the expression of EGF and IGF-1 to achieve endometrium regeneration. Therefore, these advantages provide the drug-loaded bioactive scaffolds with new choices for the treatments of IUAs.
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http://dx.doi.org/10.1080/10717544.2020.1801891DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7470125PMC
December 2020

DEC1 binding to the proximal promoter of CYP3A4 ascribes to the downregulation of CYP3A4 expression by IL-6 in primary human hepatocytes.

Biochem Pharmacol 2012 Sep 21;84(5):701-711. Epub 2012 Jun 21.

Department of Biomedical and Pharmaceutical Sciences, University of Rhode Island, Kingston, Rhode Island, 02881, USA.

In this study, we provided molecular evidences that interleukin-6 (IL-6) contributed to the decreased capacity of oxidative biotransformation in human liver by suppressing the expression of cytochrome P450 3A4 (CYP3A4). After human hepatocytes were treated with IL-6, differentially expressed in chondrocytes 1 (DEC1) expression rapidly increased, and subsequently, the CYP3A4 expression decreased continuously. Furthermore, the repression of CYP3A4 by IL-6 occurred after the increase of DEC1 in primary human hepatocytes. In HepG2 cells, knockdown of DEC1 increased the CYP3A4 expression and its enzymatic activity. In addition, it partially abolished the decreased CYP3A4 expression as well as its enzymatic activity induced by IL-6. Consistent with this, overexpression of DEC1 markedly reduced the CYP3A4 promoter activity and the CYP3A4 expression as well as its enzymatic activity. Using sequential truncation and site directed mutagenesis of CYP3A4 proximal promoter with DEC1 construct, we showed that DEC1 specifically bound to CCCTGC sequence in the proximal promoter of CYP3A4, which was validated by EMSA and ChIP assay. These findings suggest that the repression of CYP3A4 by IL-6 is achieved through increasing the DEC1 expression in human hepatocytes, the increased DEC1 binds to the CCCTGC sequence in the promoter of CYP3A4 to form CCCTGC-DEC1 complex, and the complex downregulates the CYP3A4 expression and its enzymatic activity.
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http://dx.doi.org/10.1016/j.bcp.2012.06.010DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4088276PMC
September 2012

Lipopolysaccharide down-regulates carbolesterases 1 and 2 and reduces hydrolysis activity in vitro and in vivo via p38MAPK-NF-κB pathway.

Toxicol Lett 2011 Mar 13;201(3):213-20. Epub 2011 Jan 13.

Department of Pharmacology, Nanjing Medical University, 140 Han Zhong Rd., Nanjing, Jiangsu 210029, China.

Carboxylesterases constitute a class of enzymes that hydrolyze drugs containing such functional groups as carboxylic acid ester, amide, and thioester. Hydrolysis of many drugs is reduced in liver diseases such as hepatitis and cirrhosis. In this study, we have demonstrated, in vitro and in vivo, treatment with LPS decreased the expression of HCE1 and HCE2 and the capacity of hydrolytic activity. In HepG2 cells, the decreased expression by LPS occurred at both mRNA and protein levels. Both HCE1 and HCE2 promoters were significantly repressed by LPS, and the repression was comparable with the decrease in HCE1 and HCE2 mRNA, suggesting the transrepression is responsible for suppressed expression. Further study showed that both PDTC, a NF-κB inhibitor, and SB203580, a p38MAPK inhibitor, could abolish the repression of HCE1 and HCE2 mediated by LPS, but U0126, a selective ERK1/2 inhibitor, could not do so, suggesting the repression of HCE1 and HCE2 by LPS through the p38MAPK-NF-κB pathway. In addition, being pretreated with LPS, HepG2 cells altered the cellular responsiveness to ester therapeutic agents, including clopidogrel (hydrolyzed by HCE1) and irinotecan (hydrolyzed by HCE2). The altered cellular responsiveness occurred at low micromolar concentrations, suggesting that suppressed expression of carboxylesterases by LPS has profound pharmacological and toxicological consequences, particularly with those that are hydrolyzed in an isoform-specific manner. This study provides new insight into the understanding of the pharmacological and toxicological effects and the mechanisms for repressing drug metabolism enzymes in inflammation.
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http://dx.doi.org/10.1016/j.toxlet.2011.01.002DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8284319PMC
March 2011

Byakangelicin induces cytochrome P450 3A4 expression via transactivation of pregnane X receptors in human hepatocytes.

Br J Pharmacol 2011 Jan;162(2):441-51

Department of Pharmacology, Nanjing Medical University, Jiangsu, China.

Background And Purpose: Byakangelicin is found in extracts of the root of Angelica dahurica, used in Korea and China as a traditional medicine to treat colds, headache and toothache. As byakangelicin can inhibit the effects of sex hormones, it may increase the catabolism of endogenous hormones. Therefore, this study investigated the effects of byakangelicin on the cytochrome P450 isoform cytochrome (CY) P3A4 in human hepatocytes.

Experimental Approach: Cultures of human hepatocytes and a hepatoma cell line (Huh7 cells) were used. mRNA and protein levels were measured by quantitative reverse transcription-polymerase chain reaction and Western blot. Plasmid constructs and mutants were prepared by cloning and site-directed mutagenesis. Reporter (luciferase) activity was determined by transient co-transfection experiments.

Key Results: In human primary hepatocytes, byakangelicin markedly induced the expression of CYP3A4 both at the mRNA level (approximately fivefold) and the protein level (approximately threefold) but did not affect expression of human pregnane X receptor (hPXR). In reporter assays, byakangelicin activated CYP3A4 promoter in a concentration-dependent manner (EC₅₀ = 5 µM), and this activation was enhanced by co-transfection with hPXR. Further reporter assays demonstrated that the eNR4 binding element in the CYP3A4 promoter was required for the transcriptional activation of CYP3A4 by byakangelicin.

Conclusions And Implications: Byakangelicin induced expression and activity of CYP3A4 in human hepatocytes. This induction was achieved by the transactivation of PXR and not by increased expression of PXR. Therefore, byakangelicin is likely to increase the expression of all PXR target genes (such as MDR1) and induce a wide range of drug-drug interactions.
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http://dx.doi.org/10.1111/j.1476-5381.2010.01069.xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3031064PMC
January 2011

Aquaporin-4 knockout enhances astrocyte toxicity induced by 1-methyl-4-phenylpyridinium ion and lipopolysaccharide via increasing the expression of cytochrome P4502E1.

Toxicol Lett 2010 Oct 6;198(2):225-31. Epub 2010 Jul 6.

Department of Pharmacology, Nanjing Medical University, 140 Hanzhong Road, Nanjing, Jiangsu 210029, China.

The role of aquaporin-4 (AQP4) in the regulation of astrocytes function has been widely investigated. However, there is little information about its contribution to the drug metabolism enzymes such as Cytochrome P4502E1. In the present study, we investigated whether AQP4 is involved in the process of the cell damage caused by MPP(+) and LPS through regulating the expression of CYP2E1 in astrocytes. Compared to the wild-type, in primary astrocytes, AQP4 knockout increased the cell damage and the reactive oxygen species (ROS) production which were induced by MPP(+), LPS and ethanol. Notably, AQP4 knockout enhanced the up-regulation of the expression of CYP2E1 in astrocytes exposed to MPP(+), LPS and ethanol. Furthermore, Diallylsulphide (DAS), a CYP2E1 inhibitor, partially or almost abolished the cell injury and the ROS production of the astrocytes induced by MPP(+) and LPS. These findings indicate AQP4 protects astrocytes from the damage caused by MPP(+) and LPS through reducing the ROS production correlation to the diminished expression of CYP2E1.
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http://dx.doi.org/10.1016/j.toxlet.2010.06.023DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2936815PMC
October 2010

Pregnane X receptor is required for interleukin-6-mediated down-regulation of cytochrome P450 3A4 in human hepatocytes.

Toxicol Lett 2010 Sep 9;197(3):219-26. Epub 2010 Jun 9.

Department of Pharmacology, Nanjing Medical University, Nanjing, Jiangsu 210029, China.

Cytochrome P450 3A4 (CYP3A4) is the most abundant cytochrome P450 enzyme in human liver and metabolizes more than 60% of prescribed drugs in human body. Patients with liver conditions such as cirrhosis show increased secretion of cytokines (e.g., interleukin-6) and decreased capacity of oxidation of many drugs. In this study, we provided molecular evidence that cytokine secretion directly contributed to the decreased capacity of oxidative biotransformation in human liver. After human hepatocytes were treated with IL-6, the expression of CYP3A4 decreased at both mRNA and protein levels, so did the CYP3A4 enzymatic activity. Meanwhile, the repression of CYP3A4 by IL-6 occurred after the decrease of pregnane X receptor (PXR) in human hepatocytes. The PXR-overexpressed cells (transfected with human PXR) increased the CYP3A4 mRNA level, and the repression of CYP3A4 by IL-6 was greater in the PXR-overexpressed cells than in the control cells. Further, PXR knockdown (transfected with siPXR construct) decreased the CYP3A4 mRNA level with less repression by IL-6 than in the control cells transfected with corresponding vector. Collectively, our study suggests that PXR is necessary for IL-6-mediated repression of the CYP3A4 expression in human hepatocytes.
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http://dx.doi.org/10.1016/j.toxlet.2010.06.003DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2932899PMC
September 2010
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