Publications by authors named "Yi-Ming Jiang"

20 Publications

  • Page 1 of 1

PXR mediates mifepristone-induced hepatomegaly in mice.

Acta Pharmacol Sin 2021 Mar 29. Epub 2021 Mar 29.

Guangdong Provincial Key Laboratory of New Drug Design and Evaluation, School of Pharmaceutical Sciences, Sun Yat-sen University, Guangzhou, 510006, China.

Mifepristone (Mif), an effective synthetic steroidal antiprogesterone drug, is widely used for medical abortion and pregnancy prevention. Due to its anti-glucocorticoid effect, high-dose Mif is also used to treat Cushing's syndrome. Mif was reported to active pregnane X receptor (PXR) in vitro and PXR can induce hepatomegaly via activation and interaction with yes-associated protein (YAP) pathway. High-dose Mif was reported to induce hepatomegaly in rats and mice, but the underlying mechanism remains unclear. Here, the role of PXR was studied in Mif-induced hepatomegaly in C57BL/6 mice and Pxr-knockout mice. The results demonstrated that high-dose Mif (100 mg · kg · d, i.p.) treatment for 5 days significantly induced hepatomegaly with enlarged hepatocytes and promoted proliferation, but low dose of Mif (5 mg · kg · d, i.p.) cannot induce hepatomegaly. The dual-luciferase reporter gene assays showed that Mif can activate human PXR in a concentration-dependent manner. In addition, Mif could promote nuclear translocation of PXR and YAP, and significantly induced the expression of PXR, YAP, and their target proteins such as CYP3A11, CYP2B10, UGT1A1, ANKRD, and CTGF. However, Mif (100 mg · kg · d, i.p.) failed to induce hepatomegaly in Pxr-knockout mice, as well as hepatocyte enlargement and proliferation, further indicating that Mif-induced hepatomegaly is PXR-dependent. In summary, this study demonstrated that PXR-mediated Mif-induced hepatomegaly in mice probably via activation of YAP pathway. This study provides new insights in Mif-induced hepatomegaly, and provides novel evidence on the crucial function of PXR in liver enlargement and regeneration.
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http://dx.doi.org/10.1038/s41401-021-00633-4DOI Listing
March 2021

Schisandrol B promotes liver enlargement via activation of PXR and YAP pathways in mice.

Phytomedicine 2021 Apr 17;84:153520. Epub 2021 Feb 17.

Guangdong Provincial Key Laboratory of New Drug Design and Evaluation, School of Pharmaceutical Sciences, Sun Yat-sen University, Guangzhou 510006, China; School of Pharmaceutical Sciences, Southern Medical University, Guangzhou 510515, China. Electronic address:

Background: Schisandrol B (SolB) is one of the bioactive components from a traditional Chinese medicine Schisandra chinensis or Schisandra sphenanthera. It has been demonstrated that SolB exerts hepatoprotective effects against drug-induced liver injury and promotes liver regeneration. It was found that SolB can induce hepatomegaly but the involved mechanisms remain unknown.

Purpose: This study aimed to explore the mechanisms involved in SolB-induced hepatomegaly.

Methods: Male C57BL/6 mice were injected intraperitoneally with SolB (100 mg/kg) for 5 days. Serum and liver samples were collected for biochemical and histological analyses. The mechanisms of SolB were investigated by qRT-PCR and western blot analyses, luciferase reporter gene assays and immunofluorescence.

Results: SolB significantly increased hepatocyte size and proliferation, and then promoted liver enlargement without liver injury and inflammation. SolB transactivated human PXR, activated PXR in mice and upregulated hepatic expression of its downstream proteins, such as CYP3A11, CYP2B10 and UGT1A1. SolB also significantly enhanced nuclear translocation of PXR and YAP in human cell lines. YAP signal pathway was activated by SolB in mice.

Conclusion: These findings demonstrated that SolB can significantly induce liver enlargement, which is associated with the activation of PXR and YAP pathways.
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http://dx.doi.org/10.1016/j.phymed.2021.153520DOI Listing
April 2021

AMPKα1 confers survival advantage of colorectal cancer cells under metabolic stress by promoting redox balance through the regulation of glutathione reductase phosphorylation.

Oncogene 2020 01 17;39(3):637-650. Epub 2019 Sep 17.

Sun Yat-sen University Cancer Center; State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou, 510060, Guangdong, China.

Patients with stage II or III colorectal cancer (CRC) exhibit various clinical outcomes after radical treatments. The 5-year survival rate was between 50 and 87%. However, the underlying mechanisms of the variation remain unclear. Here we show that AMPKα1 is overexpressed in CRC patient specimens and the high expression is correlated with poor patient survival. We further reveal a previously unrecognized function of AMPKα1, which maintains high level of reduced glutathione to keep reduction-oxidation reaction (redox) homeostasis under stress conditions, thus promoting CRC cell survival under metabolic stress in vitro and enhancing tumorigenesis in vivo. Mechanistically, AMPKα1 regulate the glutathione reductase (GSR) phosphorylation possibly through residue Thr507 which enhances its activity. Suppression of AMPKα1 by using nano-sized polymeric vector induces a favorable therapeutic effect, especially when in combination with oxaliplatin. Our study uncovers a novel function of AMPKα1 in redox regulation and identifies a promising therapeutic strategy for treatment of CRC.
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http://dx.doi.org/10.1038/s41388-019-1004-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6962094PMC
January 2020

Serum thrombospondin-2 is a candidate diagnosis biomarker for early non-small-cell lung cancer.

Biosci Rep 2019 07 25;39(7). Epub 2019 Jul 25.

Internal Medicine-Oncology, The First Hospital of Jiaxing, Jiaxing city, Zhejiang province 314001, China.

Thrombospondin-2 (THBS2) is a secreted protein overexpressed in numerous cancers and may function as a diagnostic tumor marker. The objective of the present study was to investigate the diagnostic performance of serum THBS2 in early stage non-small-cell lung cancer (NSCLC). Serum THBS2 and Cyfra21-1 level were evaluated in blood samples of 112 patients from NSCLC groups and 51 healthy control (HC) groups. Receiver operator characteristic (ROC) curves were used to evaluate the diagnostic significance. Serum THBS2 level was significantly up-regulated in NSCLC patients compared with healthy control subjects (<0.0001), and the postoperative THBS2 level decreased significantly (<0.0001). ROC curves analysis demonstrated that THBS2 was a comparable biomarker as Cyfra21-1 to distinguish early stage NSCLC or lung squamous cell carcinoma (SC) from healthy control subjects. And Cyfra21-1 was observed with significantly improved performances by the combination of THBS2 to distinguish early stage NSCLC (<0.05) as well as SC (<0.05) from the control subjects. In addition, THBS2 was estimated to perform well in the diagnosis of patients with Cyfra21-1-negative NSCLC (area under the curve [AUC] = 0.73). In summary, the present study suggested that serum THBS2 might be an early diagnostic biomarker for NSCLC.
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http://dx.doi.org/10.1042/BSR20190476DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6658726PMC
July 2019

The Antitumor Effect of Xihuang Pill on Treg Cells Decreased in Tumor Microenvironment of 4T1 Breast Tumor-Bearing Mice by PI3K/AKT~AP-1 Signaling Pathway.

Evid Based Complement Alternat Med 2018 23;2018:6714829. Epub 2018 Apr 23.

Medical College of Dalian University, Dalian 116622, China.

To study the antitumor effect of Xihuang pill (XHP) on the number of Treg cells in the tumor microenvironment of 4T1 breast tumor-bearing mice by PI3K/AKT/AP-1 pathway, a mouse model was established. Flow cytometry (FCM) and immunohistochemistry (IHC) were used to detect the number of Treg cells in the tumor microenvironment; terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) was used to detect the apoptosis of Treg cells in tumor microenvironment. Quantitative real-time PCR (RT-qPCR) was used to detect the mRNA expression of PI3K, AKT, and AP-1 in Treg cells in tumor microenvironment; immunofluorescence (IF) and Western Blot (WB) were used to detect the protein expression of PI3K, AKT, and AP-1 in Treg cells in tumor microenvironment. Compared with the naive control group, the tumor weight in XHP groups decreased significantly ( < 0.05); FCM and IHC results showed that the number of Treg cells in the tumor microenvironment decreased with the dose of XHP groups ( < 0.05); TUNEL staining showed that the number of Treg cells in tumor microenvironment increased with the dose of XHP groups ( < 0.05); RT-qPCR results showed that the mRNA expression of PI3K and AKT in Treg cells decreased with the dose of XHP groups, while RNA expression of AP-1 increased with the dose of XHP groups ( < 0.05); IF and WB results showed that the protein expression of PI3K and AKT in Treg cells decreased with the dose of XHP groups and the protein expression of AP-1 increased with the dose of XHP groups ( < 0.05). The results suggested that XHP decreased the number of Treg cells via inhibiting PI3K and AKT expression and upregulating AP-1 expression in Treg cells and then promoting the apoptosis of Treg cells. Thus, XHP could improve the immunosuppressive state of tumor microenvironment and reverse the immune escape to inhibit tumor growth.
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http://dx.doi.org/10.1155/2018/6714829DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5937580PMC
April 2018

Cantharidin Inhibits the Growth of Triple-Negative Breast Cancer Cells by Suppressing Autophagy and Inducing Apoptosis in Vitro and in Vivo.

Cell Physiol Biochem 2017 19;43(5):1829-1840. Epub 2017 Oct 19.

Department of General Surgery, Putuo Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai, China.

Background/aims: Cantharidin, a type of terpenoid secreted by the blister beetle Mylabris phalerata (Pallas), has attracted great attention in cancer therapy because of its potential anti-cancer activities. Here, we report the effects on apoptosis and autophagy in human triple-negative breast cancer (TNBC) cell lines after treatment with cantharidin and attempt to elucidate the underlying mechanisms.

Methods: MDA-MB-231 and MDA-MB-468 cells were treated with cantharidin and cell proliferation was examined using CCK-8 and clone formation assays. The expression of apoptosis- and autophagy-associated proteins was detected by western blotting. Cells were infected with lentivirus carrying the Beclin-1 gene, and MDA-MB-231-beclin1 (MB231-Bec) and MDA-MB-468-beclin-1(MB468-Bec) cells stably expressing Beclin-1 were established. Autophagic vacuoles in cells were observed with LC3 staining using fluorescence microscopy, and apoptotic cells were detected via flow cytometry. Tumor growth was assessed by subcutaneous inoculation of TNBC cells into BALB/c nude mice.

Results: Cantharidin inhibited the proliferation of MDA-MB-231 and MDA-MB-468 cells, and induced cell apoptosis. Cantharidin additionally inhibited the conversion of LC3 I to LC3 II and autophagosome formation by suppressing the expression of Beclin-1. Furthermore, overexpression of Beclin-1 in TNBC cells attenuated the cytotoxicity of cantharidin. In vivo, cantharidin inhibited the growth of MDA-MB-231 and MDA-MB-468 xenografts in nude mice by suppressing autophagy and inducing apoptosis, and Beclin-1 overexpression in TNBC cells reduced the efficacy of cantharidin.

Conclusions: Cantharidin inhibits autophagy by suppressing Beclin-1 expression and inducing apoptosis of TNBC cells in vitro and in vivo, thereby representing a potential strategy for the treatment of TNBC.
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http://dx.doi.org/10.1159/000484069DOI Listing
January 2018

Acidosis counteracts itch tachyphylaxis to consecutive pruritogen exposure dependent on acid-sensing ion channel 3.

Mol Pain 2017 Jan-Dec;13:1744806917721114

1 Department of Anatomy and Physiology, Collaborative Innovation Center for Brain Science, Shanghai Jiao Tong University School of Medicine, Shanghai, China.

Tachyphylaxis of itch refers to a markedly reduced scratching response to consecutive exposures of a pruritogen, a process thought to protect against tissue damage by incessant scratching and to become disrupted in chronic itch. Here, we report that a strong stimulation of the Mas-related G-protein-coupled receptor C11 by its agonist, Ser-Leu-Ile-Gly-Arg-Leu-NH (SL-NH) or bovine adrenal medulla 8-22 peptide, via subcutaneous injection in mice induces tachyphylaxis to the subsequent application of SL-NH to the same site. Notably, co-application of acid and SL-NH following the initial injection of the pruritogen alone counteracted itch tachyphylaxis by augmenting the scratching behaviors in wild-type but not in acid-sensing ion channel 3-null, animals. Using an activity-dependent silencing strategy, we identified that acid-sensing ion channel 3-mediated itch enhancement mainly occurred via the Mas-related G-protein-coupled receptor C11-responsive sensory neurons. Together, our results indicate that acid-sensing ion channel 3, activated by concomitant acid and certain pruritogens, constitute a novel signaling pathway that counteracts itch tachyphylaxis to successive pruritogenic stimulation, which likely contributes to chronic itch associated with tissue acidosis.
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http://dx.doi.org/10.1177/1744806917721114DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5533257PMC
April 2018

Loss of the Opa interacting protein 5 inhibits breast cancer proliferation through miR-139-5p/NOTCH1 pathway.

Gene 2017 Mar 1;603:1-8. Epub 2016 Dec 1.

Department of General Surgery, Putuo Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai 200062, PR China. Electronic address:

Opa interacting protein 5 (OIP5) has been reported to be over-expressed in several kinds of human cancer. However, the biological function and clinical significance of OIP5 in human breast cancer remains unknown. In this study, we found that OIP5 was notably over-expressed in breast cancer tissues compared with their corresponding nontumorous tissues. Statistical analysis showed a significant correlation of OIP5 expression with advanced clinical stage. Ablation OIP5 inhibited the proliferation of breast cancer cells. OIP5 over-expression inhibited hsa-miR-139-5p expression, antagonized its functions and led to the de-repression of its endogenous target NOTCH1, which was a core oncogene in promoting breast cancer progression. Our results suggested that OIP5 is a potential diagnosis biomarker and therapeutic target for breast cancer.
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http://dx.doi.org/10.1016/j.gene.2016.11.046DOI Listing
March 2017

SHCBP1 is over-expressed in breast cancer and is important in the proliferation and apoptosis of the human malignant breast cancer cell line.

Gene 2016 Aug 26;587(1):91-7. Epub 2016 Apr 26.

Department of General Surgery, Putuo Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai 200062, China. Electronic address:

Background: SHC SH2-binding protein 1, a member of Src homolog and collagen homolog (Shc) family, has been recently identified in different contexts in unbiased screening assays. It has been reported to be over-expressed in several malignant cancers.

Methods: Immunohistochemistry of SHCBP1 on 128 breast cancer tissues and adjacent normal tissues were used to evaluate the prognostic significance of SHCBP1. Survival analyses were performed by Kaplan-Meier method. CRISPR/CAS9 method was used to knockout SHCBP1 expression. CRISPR/CAS9 technology was used to knockout SHCBP1 in 2 breast cancer cell lines. MTT assay, BrdU assay, colony formation assay, cell cycle assay and apoptosis analysis in MCF-7 and MDA-MB-231 cell lines were carried out to evaluate the effects of SHCBP1 on breast cancer in vitro.

Results: Immunohistochemical analysis revealed SHCBP1 was significantly up-regulated in breast cancer tissues compared with adjacent normal tissues (82 of 128, 64%). Over-expressed SHCBP1 was correlated with advanced clinical stage and poorer survival. Ablation of SHCBP1 inhibited the proliferation in vitro. SHCBP1 knockout increased cyclin-dependent kinase inhibitor p21, and decreased the Cyclin B1 and CDK1.

Conclusion: Our study suggests SHCBP1 is dysregulated expressed in breast cancer and plays a critical role in cancer progression, which can be a potential prognosis predictor of breast cancer.
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http://dx.doi.org/10.1016/j.gene.2016.04.046DOI Listing
August 2016

Schisandrol B protects against acetaminophen-induced acute hepatotoxicity in mice via activation of the NRF2/ARE signaling pathway.

Acta Pharmacol Sin 2016 Mar 25;37(3):382-9. Epub 2016 Jan 25.

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

Aim: The nuclear factor erythroid 2-related factor 2 (NRF2) acts through the antioxidant response element (ARE) to regulate the expression of many detoxifying and antioxidant genes responsible for cytoprotective processes. We previously reported that Schisandrol B (SolB) isolated from Schisandra sphenanthera produced a protective effect against acetaminophen (APAP)-induced liver injury. In this study we investigated whether the NRF2/ARE signaling pathway was involved in this hepato-protective effect.

Methods: Male C57BL/6 mice were treated with SolB (200 mg · kg(-1) · d(-1), ig) for 3 d before injection of APAP (400 mg/kg, ip). Serum and liver tissue samples were collected 6 h later. The mRNA and protein expression were measured using qRT-PCR and Western blot assay, respectively. The activation of NRF2 was examined in HepG2 cells using luciferase reporter gene assay.

Results: SolB pretreatment significantly alleviated the hepatic injury (large patchy necrosis and hyperemia of the hepatic sinus), the increase of serum AST, ALT levels and hepatic MDA contents, and the decrease of liver and mitochondrial glutathione levels in APAP-treated mice. Furthermore, SolB pretreatment significantly increased nuclear accumulation of NRF2 and increased hepatic expression of NRF2 downstream proteins, including GCLC, GSR, NQO1, GSTs, MRP2, MRP3 and MRP4 in APAP-treated mice. Moreover, treatment with SolB (2.5-20 μmol/L) dose-dependently increased the activity of NRF2 reporter gene in HepG2 cells.

Conclusion: SolB exhibits a remarkable protective effect against APAP-induced hepatotoxicity, partially via activation of the NRF2/ARE pathway and regulation of NRF2 target genes, which induce detoxification and increase antioxidant capacity.
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http://dx.doi.org/10.1038/aps.2015.120DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4775844PMC
March 2016

ASIC3 Mediates Itch Sensation in Response to Coincident Stimulation by Acid and Nonproton Ligand.

Cell Rep 2015 Oct 1;13(2):387-98. Epub 2015 Oct 1.

Discipline of Neuroscience and Department of Anatomy, Histology and Embryology, Collaborative Innovation Center for Brain Science, Shanghai Key Laboratory for Tumor Microenvironment and Inflammation, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, China. Electronic address:

The regulation and mechanisms underlying itch sensation are complex. Here, we report a role for acid-sensing ion channel 3 (ASIC3) in mediating itch evoked by certain pruritogens during tissue acidosis. Co-administration of acid with Ser-Leu-Ile-Gly-Arg-Leu-NH2 (SL-NH2) increased scratching behavior in wild-type, but not ASIC3-null, mice, implicating the channel in coincident detection of acidosis and pruritogens. Mechanistically, SL-NH2 slowed desensitization of proton-evoked currents by targeting the previously identified nonproton ligand-sensing domain located in the extracellular region of ASIC3 channels in primary sensory neurons. Ablation of the ASIC3 gene reduced dry-skin-induced scratching behavior and pathological changes under conditions with concomitant inflammation. Taken together, our data suggest that ASIC3 mediates itch sensation via coincident detection of acidosis and nonproton ligands that act at the nonproton ligand-sensing domain of the channel.
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http://dx.doi.org/10.1016/j.celrep.2015.09.002DOI Listing
October 2015

Inhibiton of cytochrome P450 isoenzymes and P-gp activity by multiple extracts of Huang-Lian-Jie-Du decoction.

J Ethnopharmacol 2014 Oct 8;156:175-81. Epub 2014 Sep 8.

School of Pharmaceutical Sciences, Sun Yat-sen University, 132# Waihuan Dong Road, Guangzhou University City, Guangzhou 510006, China. Electronic address:

Ethnopharmacological Relevance: Huang-Lian-Jie-Du-Decotion (HLJDD), an important traditional Chinese medicine formula, has been used for various diseases in clinical practice, and thus has high potential to induce cytochrome P450 (CYP) isoenzymes/P-glycoprotein (P-gp) mediated herb-drug interactions (HDIs) with other co-administered drugs. The purpose of this study was to investigate the in vitro effects of multiple extracts including aqueous extracts, total flavonoids, iridoids, alkaloids from HLJDD on the activities of CYPs in rats (CYP1A2, CYP2C6, CYP2D2, CYP2E1 and CYP3A1) and P-gp, and then to predict potential interactions with co-administered drugs.

Materials And Methods: The effects of the four extracts from HLJDD on the CYPs activity were evaluated in rat liver microsomes incubation system, and then determined by LC-MS/MS-based CYPs probe substrate assay. Caco-2 cell monolayer was used to investigate the effect of the four extracts on the efflux of Rhodamine 123 to evaluate their influences on P-gp activity.

Results: The results show that total flavonoids and alkaloids exibited strong inhibition on rat CYP isoenzymes activities. Total flavonoids exhibited different inhibitory effects on CYPs activities with an order of CYP3A1>CYP2C6>CYP2E1>CYP1A2>CYP2D2, and the values of IC₅₀ were 4.24, 8.16, 17.56, 19.03, 29.51 μg/mL, respectively. Total alkaloids possessed similar inhibition on CYPs and could strongly inhibit the activity of CYP2D2 (IC₅₀=2.38 μg/mL), CYP3A1 (IC₅₀=2.61 μg/mL), CYP2E1 (IC₅₀=22.35 μg/mL), CYP1A2 (IC₅₀=23.2 μg/mL) and CYP2C6 (IC₅₀=43.09 μg/mL). Moderate degree of inhibition on CYPs activities was observed in aqueous and total iridoids extracts. Results from transport assay revealed that total flavonoids and alkaloids exhibited significant inhibitory effect on P-gp activity as evidenced by strong inhibition on the efflux of Rhodamine-123 with IC₅₀ of 104.6 and 82.6 μg/mL. But aqueous extract showed weak and iridoids had negligible effect on P-gp activity.

Conclusions: This study clearly demonstrated that total flavonoids and alkaloids from HLJDD can significantly inhibit the activities of CYPs and P-gp, which should be taken into consideration to predict any potential HDIs when HLJDD and its bioactive components are co-administered with other therapeutic drugs metabolized by CYPs or transported by P-gp.
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http://dx.doi.org/10.1016/j.jep.2014.08.044DOI Listing
October 2014

[Effect of kurarinol on peripheral blood CTL surface PD-1 expression of patients with chronic hepatitis B].

Zhonghua Shi Yan He Lin Chuang Bing Du Xue Za Zhi 2012 Dec;26(6):446-9

Wuxi Hospital for Infectious Diseases, China.

Objective: To explore the anti-viral mechanism of kurarinol through studying its influence on cytotoxic T lymphocyte (CTL) surface program death receptor-1 (PD-1) expression of patients with chronic hepatitis B (CHB).

Methods: 69 cases of CHB, HBV DNA > or = 10(4) copies/ml, HBeAg positive, human leukocyte antigen (HLA)-A2 positive, alanine aminotransferase (ALT) > 2 x upper limit of normal value(ULN).69 cases were randomly divided into two groups:34 cases in treatment group,600 mg of kurarinol glucose injection was used for intravenous dripping, once a day, one month later, 200 mg of kurarinol capsule was used orally,three times a day and 200 mg of silybin meglumine tablet was used orally, three times a day. 35 cases in control group, only silibin meglumine tablet was used, method and dosage were the same as those of treatment group. Three months later, their peripheral blood HBV specific CTL surface PD-1 expression, non-specific CTL surface PD-1 expression and level of HBV specific CTL,HBV DNA and HBeAg negative rate and liver functions were analyzed and compared.

Results: 3 months after treatment, peripheral blood HBV specific CTL surface PD-1 expression of the treatment group decreased compared with that before treatment (t = 2.39, P < 0.05), it also decreased compared with that of the control group 3 months after treatment (t = 2.26, P < 0.05), HBV specific CTL increased compared with that before treatment( t = 3.01, P < 0.01), it also increased compared with that of the control group after treatment (t = 2.65, P < 0.05). There was no significant difference of non-specific CTL surface PD-1 expression compared with that before treatment (P > 0.05), and there was no significant difference compared with that of the control group after treatment (P > 0.05). HBV DNA of 11 cases (32.5%) turned negative ( HBV DNA < 500 copies/ ml), higher than that of the control group after treatment (2 cases, 5.71%) chi2 = 7.99, P < 0.01, HBeAg of 9 cases (26.47%) turned negative, higher than that of the control group after treatment (1 case, 2.86%), chi2 = 7.75, P < 0.01.

Conclusion: Kurarinol can increase level of HBV specific CTL by down-regulating peripheral blood HBV specific CTL surface PD-1 expression of CHB patients, which may be one of the possible mechanisms that kurarinol can remove or inhibit HBV of CHB patients.
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December 2012

Acrolein induces Alzheimer's disease-like pathologies in vitro and in vivo.

Toxicol Lett 2013 Mar 4;217(3):184-91. Epub 2013 Jan 4.

Department of Traditional Chinese Medicine, The First Affiliated Hospital, Sun Yat-Sen University, Guangzhou 510080, China.

The pathologic mechanisms of Alzheimer's disease (AD) have not been fully uncovered. Acrolein, a ubiquitous dietary pollutant and by-product of oxidative stress, can induce cytotoxicity in neurons, which might play an important role in the etiology of AD. Here, we examined the effects of Acrolein on the AD pathologies in vitro and in vivo. We found Acrolein induced HT22 cells death in concentration- and time-dependent manners. Interestingly, Acrolein increased proteins' levels of amyloid precursor protein (APP), β-secretase (BACE-1) and the amyloid β-peptide transporter receptor for advanced glycation end products, and decreased A-disintegrin and metalloprotease (ADAM) 10 levels. In vivo, chronic oral exposure to Acrolein (2.5 mg/kg/day by intragastric gavage for 8 weeks) induced mild cognitive declination and pyknosis/atrophy of hippocampal neurons. The activity of superoxide dismutase was down-regulated while the level of malondialdehyde was up-regulated in rat brain. Moreover, Acrolein resulted in activation of astrocytes, up-regulation of BACE-1 in cortex and down-regulation of ADAM-10 in hippocampus and cortex. Taken together, our findings suggest that exposure to Acrolein induces AD-like pathology in vitro and in vivo. Scavenging Acrolein might be beneficial for the therapy of AD.
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http://dx.doi.org/10.1016/j.toxlet.2012.12.023DOI Listing
March 2013

[Study on effects of kurarinol combined with glycyrrhizic acid on cellular immunity of patients with chronic hepatitis B].

Zhonghua Shi Yan He Lin Chuang Bing Du Xue Za Zhi 2012 Apr;26(2):108-10

Wuxi Hospital for Infectious Diseases, 214005 China.

Objective: To explore effects of kurarinol combined with Diammonium Glycyrrhizinate on specific cellular immunity of patients with chronic hepatitis B (CHB).

Methods: Sixty-three CHB patients were randomly divided into two groups, 32 cases in group of kurarinol combined with Diammonium Glycyrrhizinate group (combined therapy group) were treated with 600 mg kurarinol glucose injection intravenously, once a day for one month, then 200 mg kurarinol capsule was used orally, three times a day for two months. 150 mg Diammonium Glycyrrhizinate for Injection was added to 250 ml 10% glucose injection for intravenous drip, once a day for one month, then 150 mg Diammonium Glycyrrhizinate capsule was used orally, three times a day for two months; 31 case in kurarinol group (single drug group) only used kurarinol, methods and dosage were the same as those of treatment group. HBV specific CTL, T cell subgroups, change of Th1 and Th2 level, HBV-DNA and HBeAg negative rate of the two groups were compared.

Results: Three months after treatment, HBV specific CTL, CD4 + and Th1 of combined therapy group were higher than those before treatment, and higher than those of single drug group after treatment (P < 0.01).

Conclusion: HBV-DNA and HBeAg negative rate between the two groups had no statistic significance (P > 0.05).

Conclusion: Kurarinol combined with Diammonium Glycyrrhizinate can further increase HBV specific CTL, CD4+ and Th1 level of CHB patients.
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April 2012

Effect of oxymatrine on specific cytotoxic T lymphocyte surface programmed death receptor-1 expression in patients with chronic hepatitis B.

Chin Med J (Engl) 2012 Apr;125(8):1434-8

Department of Hepatology, Wuxi Hospital for Infectious Diseases, Wuxi, Jiangsu 214005, China.

Background: Oxymatrine has certain antiviral effects in the treatment of chronic hepatitis B (CHB), but its exact mechanism is unclear. The objective of the present study was to explore oxymatrine's antiviral mechanism by studying its effect on the hepatitis B virus (HBV) specific cytotoxic T lymphocyte (CTL) surface programmed death receptor-1 (PD-1) expression in CHB patients.

Methods: Sixty-five CHB patients who had HBV DNA(3)10(4) copies/ml, positive HBeAg, positive human leukocyte antigen (HLA)-A2, alanine aminotransferase (ALT) > 2 x upper limit of normal value (ULN) were randomly divided into two groups: treatment group (n = 33), treated with an intravenous infusion of 600 mg oxymatrine in glucose solution once a day for a month, then with a 200 mg oxymatrine oral capsule three times a day, and a 200 mg silibin meglumine tablet three times a day; control group (n = 32) patients were treated only with silibin meglumine tablet, method and dosage were the same as those of treatment group. Three months later, peripheral blood HBV-specific CTL surface PD-1 expression, HBV-specific CTL level, HBV DNA, HBeAg, and results of liver function tests were analyzed and compared.

Results: Three months post-treatment, in the treatment group, peripheral blood HBV-specific CTL surface PD-1 expression ((19.42 ± 15.94)%) decreased significantly compared to the pretreatment level ((31.30 ± 24.06)%; P < 0.05), and decreased significantly compared to that of control group three months after treatment ((29.45 ± 21.62)%; P < 0.05). HBV-specific CTL level ((0.42 ± 0.07)%) significantly increased compared with the pretreatment ((0.29 ± 0.15)%; P < 0.01), and the control group posttreatment level was (0.31 ± 0.15)% (P < 0.05). HBV DNA level in 11 cases became negative (HBV DNA < 500 copies/ml, 33.33%), which was higher than that of the control group after treatment (two cases, 6.25%; χ(2) = 7.45, P < 0.01), HBeAg of nine cases turned negative (27.27%), which was higher than that of the control group after treatment (one case, 3.13%; χ(2) = 7.27, P < 0.01).

Conclusion: Oxymatrine could downregulate peripheral blood HBV-specific CTL surface PD-1 expression in CHB patients, increase HBV-specific CTL level, which may be one of the possible mechanisms by which oxymatrine clears or inhibits HBV in CHB patients.
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April 2012

Loss of imprinting and abnormal expression of the insulin-like growth factor 2 gene in gastric cancer.

Mol Carcinog 2011 May 25;50(5):390-6. Epub 2011 Jan 25.

Department of General Surgery, Putuo Hospital, University of Traditional Chinese Medicine in Shanghai, Shanghai, China.

This study examined the frequency of loss of imprinting (LOI) and expression of the insulin-like growth factor 2 (IGF2) gene, and their relationship to selected clinical and pathological factors, in a well defined series of 90 Chinese patients with gastric cancer (GC) and 90 matched patients (controls) diagnosed with nonmalignant conditions. Using peripheral blood and gastric tissue samples, polymerase chain reaction-based assays and restriction endonuclease (Apa I) digestion revealed 33 GC patients and 21 controls to be Apa I informative. LOI of IGF2 was positive in 48.5% (16/33) of primary GC tumor tissues, in 21.2% (7/33) of histologically normal adjacent gastric mucosa (AM) and in 12.1% (4/33) of distant gastric mucosa (DM), and in 15.2% (5/33) of peripheral blood lymphocytes (PBLs). The prevalence of IGF2 LOI in PBL was not statistically different between GC patients (5/33, 15.2%) and control subjects (2/21, 9.5%), P = 0.69. Although patients who were found to have LOI of IGF2 were more likely to have advanced stage gastric tumors (P = 0.04), no statistically significant differences in survival were found based on imprinting status. IGF2 LOI was associated with an increased expression of IGF2 level in both tumors (P < 0.01) and blood (P < 0.01). The results of this study implicate IGF2 LOI in the molecular pathogenesis of GC, most likely through increased IGF2 expression. Although the precise molecular mechanisms by which LOI of IGF2 increases GC risk require further study, LOI of IGF2 may be a potentially important clinical epigenetic marker to identify individuals at increased risk for gastric malignancy.
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http://dx.doi.org/10.1002/mc.20731DOI Listing
May 2011

[Expression of epithelial Na+ channel in human nasal polyp].

Zhonghua Er Bi Yan Hou Tou Jing Wai Ke Za Zhi 2009 Oct;44(10):861-5

Department of Otorhinolaryngology Head and Neck Surgery, Renji Hospital Affiliated to Shanghai Jiaotong University, 200001, China.

Objective: To evaluate the expression of epithelial sodium channel in nasal polyps and normal nasal mucosa and to characterize the ENaC-mediated Na(+) absorption and the mechanism of the liquid transport in human upper airway epithelia.

Methods: The tissue from 12 patients with nasal polyps (NP) and the normal ethmoid cornu mucosa (ECM) from 5 patients were obtained through endoscopic surgery. The expression of ENaC was detected by Immunofluorescence and the concentration of ENaC alpha, beta, gamma-mRNA were detected by RT real-time PCR.

Results: The ENaC in NP group (35.79 +/- 5.47) was higher than that in ECM group (22.17 +/- 5.43, t = 4.687, P < 0.01). The expression of ENaC-alpha, beta, gamma mRNA in NP group (respectively 2.06 +/- 0.42, 1.97 +/- 0.32, 1.96 +/- 0.54) was higher than that in ECM group (respectively 1.01 +/- 0.10, 0.98 +/- 0.08, 0.97 +/- 0.06; t = 5.482, 6.659, 4.036, all P < 0.01). The mRNA expression of three subunits of ENaC was as follows: alpha > beta > gamma in both groups. The mRNA expression of alpha, beta, gamma subunit of ENaC in NP group was higher than that in ECM group(P < 0.01). The expression of three subunits of ENaC was correlated respectively with that of mRNA in NP group.

Conclusions: The up-regulation of ENaC in human NP was associated with the expression of ENaC mRNA, that made hydrops and might be one of the most important cause of the develop of nasal polyp.
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October 2009

[Clinical observation of the elbow joint function after shortening fixation of the comminuted olecranon fractures].

Authors:
Ming-jiang Yi

Zhongguo Gu Shang 2008 Aug;21(8):572-3

The Peoples Hospital of Ba-State, Ba-State 841000, Xinjiang, China.

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August 2008

[Surgical treatment of shotgun injuries of the sciatic nerve].

Zhonghua Wai Ke Za Zhi 2004 Jan;42(2):81-3

Department of Orthopaedic Surgery and Traumatology, Beijing Jishuitan Hospital, Medical School, Peking University, Beijing 100035, China.

Objective: To explore the clinical characteristics and the effect of surgical therapy for shotgun injuries of the sciatic nerve.

Methods: From 1996 to 2000, 19 sciatic nerve injuries resulted from shotgun were observed. Among 19 cases of shotgun sciatic nerve wounds, the gluteal wound was in 2 cases, thigh wound in 15 cases, and knee wound in 2 cases. The firing distance was between 0.5-9 m. According to Shermen classification of shotgun injury, 4 cases belonged to type I injury, 11 cases type II, 4 cases type III. The time from injury to admission was between 2 months-14 months except 1 patient who underwent emergency operation 4 hours after injury, and 1 patient was treated with debridement and epineurial neurorrhaphy, 7 cases with nerve trunk grafting, 6 cases with nerve cable grafting, 4 cases with neurolysis, 1 case with arthrodesis of ankle.

Results: Nineteen cases were followed-up for 0.8-3.5 years (mean, 19 months). The excellent and good nerve functional recovery was found in 52.6% according to MCRR.

Conclusions: Shotgun injuries of the sciatic nerve are very severe and complicated, and injuries in most patients were usually complicated by open fracture, vascular injury, soft-tissue loss and infection; the character of nerve injury was classified as 4-5 degree according to Sunderland Standard, nerve transfer is effective in the treatment of shotgun injuries of the sciatic nerve, but outcome is poor; the recovery of the sciatic nerve should be observed continually after injury; selecting correct initial treatment after injury, strict minimally invasive surgical procedure, physical therapy and reasonable preoperative and postoperative medication can improve the surgical results.
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January 2004