Are you Xiao-Lei Shi?

Claim your profile

Publications (54)

  • Shuai Wang · Xiao-Lei Shi · Min Feng · [...] · Yi-Tao Ding
    [Show abstract] [Hide abstract] ABSTRACT: Liver fibrosis, which is the pathophysiologic process of the liver due to sustained wound healing in response to chronic liver injury, will eventually progress to cirrhosis. Puerarin, a bioactive isoflavone glucoside derived from the traditional Chinese medicine pueraria, has been reported to have many anti-inflammatory and anti-fibrosis properties. However, the detailed mechanisms are not well studied yet. This study aimed to investigate the effects of puerarin on liver function and fibrosis process in mice induced by CCl4. C57BL/6J mice were intraperitoneally injected with 10% CCl4 in olive oil(2 mL/kg) with or without puerarin co-administration (100 and 200 mg/kg intraperitoneally once daily) for four consecutive weeks. As indicated by the ameliorative serum hepatic enzymes and the reduced histopathologic abnormalities, the data collected showed that puerarin can protect against CCl4-induced chronic liver injury. Moreover, CCl4-induced development of fibrosis, as evidenced by increasing expression of alpha smooth muscle actin(α-SMA), collagen-1, transforming growth factor (TGF)-β and connective tissue growth factor(CTGF) in liver, were suppressed by puerarin. Possible mechanisms related to these suppressive effects were realized by inhibition on NF-κB signaling pathway, reactive oxygen species(ROS) production and mitochondrial dysfunction in vivo. In addition, these protective inhibition mentioned above were driven by down-regulation of PARP-1 due to puerarin because puerarin can attenuate the PARP-1 expression in CCl4-damaged liver and PJ34, a kind of PARP-1 inhibitor, mimicked puerarin's protection. In conclusion, puerarin played a protective role in CCl4-induced liver fibrosis probably through inhibition of PARP-1 and subsequent attenuation of NF-κB, ROS production and mitochondrial dysfunction.
    Article · Sep 2016 · International immunopharmacology
  • [Show abstract] [Hide abstract] ABSTRACT: This study was designed to evaluate the efficacy, tolerability, and sequential administration of abiraterone acetate (AA) and enzalutamide (Enz) for metastatic castration-resistant prostate cancer (mCRPC). A literature search was performed with PubMed, Embase, and Web of Science databases to identify relevant studies. Reviewed literature included published phase III trials of AA or Enz in mCRPC and studies regarding their sequential administration. Given the difference in control arms in AA (active comparator) and Enz (true placebo) randomized phase III studies, indirect comparisons between AA and Enz in mCRPC showed no statistically significant difference in overall survival in prechemotherapy and postchemotherapy settings (HR: 0.90, 95% CI, 0.73-1.11; HR: 0.85, 95% CI, 0.68-1.07). Compared with AA, Enz may better outperform control arms in treating mCRPC both before and after chemotherapy regarding secondary endpoints based on indirect comparisons: time to prostate-specific antigen (PSA) progression (HR: 0.34, 95% CI, 0.28-0.42; HR: 0.40, 95% CI, 0.30-0.53), radiographic progression-free survival (HR: 0.37, 95% CI, 0.28-0.48; HR: 0.61, 95% CI, 0.50-0.74), and PSA response rate (OR: 18.29, 95% CI, 11.20-29.88; OR: 10.69, 95% CI, 3.92-29.20). With regard to the effectiveness of Enz following AA or AA following Enz, recent retrospective case series reported overall survival and secondary endpoints for patients with mCRPC progression after chemotherapy. However, confirmatory head-to-head trials are necessary to determine the optimal sequencing of these agents.
    Article · May 2016 · Asian Journal of Andrology
  • Jian-Feng Sang · Xiao-Lei Shi · Bing Han · [...] · Yi-Tao Ding
    [Show abstract] [Hide abstract] ABSTRACT: AIM: To study the therapeutic effects of mesenchymal stem cells (MSCs) and an interleukin-1 receptor antagonist (IL-1Ra) in acute liver failure. METHODS: Chinese experimental miniature swine (15 ± 3 kg, 5-8 mo) were obtained from the Laboratory Animal Centre of the Affiliated Drum Tower Hospital of Nanjing University Medical School. Acute liver failure was induced via 85% hepatectomy, and animals were treated by MSC transplantation combined with IL-1Ra injection. Blood samples were collected for hepatic function analysis, and the living conditions and survival time were recorded. Liver injury was histologically analyzed. Hepatic cell regeneration and apoptosis were studied by Ki67 immunohistochemistry and terminal deoxynucleotidyl transferase dUTP nick end labeling, respectively. The levels of protein kinase B and nuclear factor-κB expression were analyzed by Western blotting. RESULTS: MSCs were infected with a lentivirus for expression of green fluorescent protein (GFP) for subsequent identification; 97.3% of the MSCs were positive for GFP as assessed by flow cytometry. Additional flow cytometric analysis of cell surface marker expression demonstrated that > 90% of GFP-expressing MSCs were also positive for CD29, CD44, and CD90, indicating that most of these cells expressed typical markers of MSCs, and the population of MSCs was almost pure. Transplantation of MSCs in combination with 2 mg/kg IL-1Ra therapy significantly improved survival time compared to the acute liver failure model group (35.3 ± 6.7 d vs 17.3 ± 5.5 d, P < 0.05). Combined therapy also promoted improvement in serum inflammatory cytokines and biochemical conditions. The observed hepatic histopathologic score was significantly lower in the group with combined therapy than in the model group (3.50 ± 0.87 vs 8.17 ± 1.26, P < 0.01). In addition, liver cell apoptosis in the combined therapy group was significantly inhibited (18.1 ± 2.1% vs 70.8 ± 3.7%, P < 0.01), and hepatic cell regeneration increased. A significant increase in protein kinase B expression and decrease in nuclear factor-κB expression were observed (P < 0.01), which supports their important roles in liver regeneration. CONCLUSION: MSCs and IL-1Ra had a synergistic effect in liver regeneration via regulation of inflammation and apoptotic signaling.
    Article · Apr 2016 · World Journal of Gastroenterology
  • Hu-Cheng Ma · Xin Wang · Min-Na Wu · [...] · Xiao-Lei Shi
    [Show abstract] [Hide abstract] ABSTRACT: STAT3 expression in normal rats and ALF rats injected with/without MSCs. (a) Western blotting analysis of liver tissues at 7th day after injecting D-Gal. (b) The band intensities of scanning densitometry. *P < 0.05 versus ALF group. STAT3: Signal transducer and activator of transcription 3; pSTAT3: Phosphorylated STAT3; MSCs: Mesenchymal stem cells; ALF: Acute liver failure.
    File available · Data · Apr 2016
  • Hu-Cheng Ma · Xin Wang · Min-Na Wu · [...] · Xiao-Lei Shi
    [Show abstract] [Hide abstract] ABSTRACT: ALT and AST levels of ALF rats (n = 6). *P < 0.05. ALT: Alanine aminotransferase; AST: Aspar tate aminotransferase; ALF: Acute liver failure.
    File available · Data · Apr 2016
  • Source
    Hu-Cheng Ma · Xin Wang · Min-Na Wu · [...] · Xiao-Lei Shi
    [Show abstract] [Hide abstract] ABSTRACT: Background: Mesenchymal stem cells (MSCs) transplantation has been proven to have therapeutic potential for acute liver failure (ALF). However, the mechanism remains controversial. Recently, modulation of inflammation by MSCs has been regarded as a crucial mechanism. The aim of the present study was to explore the soluble cytokines secreted by MSCs and their therapeutic effects in ALF. Methods: MSCs isolated from Sprague-Dawley rats were identified by fluorescence-activated cell sorting analysis. Conditioned medium derived from MSCs (MSCs-CM) was collected and analyzed by a cytokine microarray. MSCs and MSCs-CM were transplanted into rats with D-galactosamine-induced ALF. Liver function, survival rate, histology, and inflammatory factors were determined. Exogenous recombinant rat interleukin (IL)-10, anti-rat IL-10 antibody, and AG490 (signal transducer and activator of transcription 3 [STAT3] signaling pathway inhibitor) were administered to explore the therapeutic mechanism of MSCs-CM. Statistical analysis was performed with SPSS version 19.0, and all data were analyzed by the independent-sample t-test. Results: There are statistical differences of the survival curve between ALF+MSCs group and ALF+Dulbecco's modified Eagle's medium (DMEM) group, as well as ALF+MSCs-CM group and ALF+DMEM group (all P < 0.05). Serum alanine aminotransferase (ALT) level in the ALF+MSCs and ALF+MSCs-CM groups was lower than that in the ALF+DMEM group (865.53±52.80 vs. 1709.75±372.12 U/L and 964.72±414.59 vs. 1709.75±372.12 U/L, respectively, all P < 0.05); meanwhile, serum aspartate aminotransferase (AST) level in the ALF+MSCs and ALF+MSCs-CM groups was lower than that in the ALF+DMEM group (2440.83±511.94 vs. 4234.35±807.30 U/L and 2739.83±587.33 vs. 4234.35±807.30 U/L, respectively, all P < 0.05). Furthermore, MSCs or MSCs-CM treatment significantly reduced serum interferon-γ (IFN-γ), IL-1β, IL-6 levels and increased serum IL-10 level compared with DMEM (all P < 0.05). Proteome profile analysis of MSCs-CM indicated the presence of anti-inflammatory factors and IL-10 was the most distinct. Blocking of IL-10 confirmed the therapeutic significance of this cytokine. Phosphorylated STAT3 was upregulated after IL-10 infusion and inhibition of STAT3 by AG490 reversed the therapeutic effect of IL-10. Conclusions: The factors released by MSCs, especially IL-10, have the potential for therapeutic recovery of ALF, and the STAT3 signaling pathway may mediate the anti-inflammatory effect of IL-10.
    Full-text available · Article · Apr 2016 · Chinese medical journal
  • Xiao-Lei Shi · Yimeng Gao · Yupeng Yan · [...] · Lijian Hui
    [Show abstract] [Hide abstract] ABSTRACT: Stability of hiHeps in the bioreactor
    File available · Data · Feb 2016
  • Xiao-Lei Shi · Yimeng Gao · Yupeng Yan · [...] · Lijian Hui
    [Show abstract] [Hide abstract] ABSTRACT: Consistency of large-scale-expanded hiHeps between different batches
    File available · Data · Feb 2016
  • Xiao-Lei Shi · Yimeng Gao · Yupeng Yan · [...] · Lijian Hui
    [Show abstract] [Hide abstract] ABSTRACT: Establish the D-gal-induced ALF model in Bama miniature pigs
    File available · Data · Feb 2016
  • Xiao-Lei Shi · Yimeng Gao · Yupeng Yan · [...] · Lijian Hui
    [Show abstract] [Hide abstract] ABSTRACT: Characterization of hiHep-BAL-treated ALF pigs
    File available · Data · Feb 2016
  • Xiao-Lei Shi · Yimeng Gao · Yupeng Yan · [...] · Lijian Hui
    [Show abstract] [Hide abstract] ABSTRACT: Stability of hiHep cells during the large-scale expansion
    File available · Data · Feb 2016
  • Xiao-Lei Shi · Yimeng Gao · Yupeng Yan · [...] · Lijian Hui
    [Show abstract] [Hide abstract] ABSTRACT: Supplemental Experimental Procedures
    File available · Data · Feb 2016
  • Xiao-Lei Shi · Yimeng Gao · Yupeng Yan · [...] · Lijian Hui
    [Show abstract] [Hide abstract] ABSTRACT: The BAL support system
    File available · Data · Feb 2016
  • Xiao-Lei Shi · Yimeng Gao · Yupeng Yan · [...] · Lijian Hui
    [Show abstract] [Hide abstract] ABSTRACT: Optimized hiHeps show increased hepatic gene expression and functions
    File available · Data · Feb 2016
  • Xiao-Lei Shi · Yimeng Gao · Yupeng Yan · [...] · Lijian Hui
    [Show abstract] [Hide abstract] ABSTRACT: Determine the cell number of hiHeps for hiHep-BAL
    File available · Data · Feb 2016
  • Xiao-Lei Shi · Yimeng Gao · Yupeng Yan · [...] · Lijian Hui
    [Show abstract] [Hide abstract] ABSTRACT: Optimization of hiHeps
    File available · Data · Feb 2016
  • Source
    Xiao-Lei Shi · Yimeng Gao · Yupeng Yan · [...] · Lijian Hui
    [Show abstract] [Hide abstract] ABSTRACT: Acute liver failure (ALF) is a life-threatening illness. The extracorporeal cell-based bioartificial liver (BAL) system could bridge liver transplantation and facilitate liver regeneration for ALF patients by providing metabolic detoxification and synthetic functions. Previous BAL systems, based on hepatoma cells and non-human hepatocytes, achieved limited clinical advances, largely due to poor hepatic functions, cumbersome preparation or safety concerns of these cells. We previously generated human functional hepatocytes by lineage conversion (hiHeps). Here, by improving functional maturity of hiHeps and producing hiHeps at clinical scales (3 billion cells), we developed a hiHep-based BAL system (hiHep-BAL). In a porcine ALF model, hiHep-BAL treatment restored liver functions, corrected blood levels of ammonia and bilirubin, and prolonged survival. Importantly, human albumin and α-1-antitrypsin were detectable in hiHep-BAL-treated ALF pigs. Moreover, hiHep-BAL treatment led to attenuated liver damage, resolved inflammation and enhanced liver regeneration. Our findings indicate a promising clinical application of the hiHep-BAL system.Cell Research advance online publication 15 January 2016; doi:10.1038/cr.2016.6.
    Full-text available · Article · Jan 2016 · Cell Research
  • [Show abstract] [Hide abstract] ABSTRACT: Prostate cancer antigen 3 (PCA3) is a biomarker for diagnosing prostate cancer (PCa) identified in the Caucasian population. We evaluated the effectiveness of urinary PCA3 in predicting the biopsy result in 500 men undergoing initial prostate biopsy. The predictive power of the PCA3 score was evaluated by the area under receiver operating characteristic (ROC) curve (AUC) and by decision curve analysis. PCA3 score sufficed to discriminate positive from negative prostate biopsy results but was not correlated with the aggressiveness of PCa. The ROC analysis showed a higher AUC for the PCA3 score than %fPSA (0.750 vs 0.622, P = 0.046) in patients with a PSA of 4.0-10.0 ng ml-1 , but the PCA3-based model is not significantly better than the base model. Decision curve analysis indicates the PCA3-based model was superior to the base model with a higher net benefit for almost all threshold probabilities, especially the threshold probabilities of 25%-40% in patients with a PSA of 4.0-10.0 ng ml-1 . However, the AUC of the PCA3 score (0.712) is not superior to %fPSA (0.698) or PSAD (0.773) in patients with a PSA >10.0 ng ml-1 . Our results confirmed that the RT-PCR-based PCA3 test moderately improved diagnostic accuracy in Chinese patients undergoing first prostate biopsy with a PSA of 4.0-10.0 ng ml-1 .
    Article · Jan 2015 · Asian Journal of Andrology
  • [Show abstract] [Hide abstract] ABSTRACT: Objective To discuss the safety and efficacy of simultaneousbilateral flexible ureteroscopy (SBFU) with holmium laser lithotripsy for bilateral renal or ureteral calculi. Methods The clinical data of 78 patients (51 males, 27 females; average age [43 ± 12] years, range 22 to 74 years) who underwent SBFU with holmium laser lithotripsy for bilateral renal or ureteral calculi in our hospital between January 2004 and February 2013 were retrospectively reviewed. The mean number of stones per case was 3. 0±0. 5 (range 2 to 5), and the mean diameter of the largest stone was (2. 5±1. 2) cm (range 1. 0 to 5. 0 cm). The operation was conducted under intravenous anesthesia. The upper ureteral calculi was removed firstly by ureteroscopy with holmium laser when it existed. After the ureteral access sheath was placed, flexible ureteroscopy was inserted into the renal pelvis, and then a 200 ^m holmium laser fiber was used for fragmentizing stones and the large pieces was removed by stone basket. The operation was considered successful if no residual stone existed or residual stones were less than 4 mm in diameter during postoperative examination. Clinical data including operation time, stone-free rate and complications were analyzed. Results The flexible ureteroscopy was successfully placed in all the 78 cases, and the average operation time per case was (74. 0±40. 4) min (range 40 to 312 min), with no bleeding, ureteral perforation, avulsion or rupture during operation. The success rate of stone fragmentation was 93. 6% (146/156) and the stone-free rate was 86. 0% (134/156). Seven cases (9. 0%, 7/78) required a second stage flexible ureteroscopy with holmium laser lithotripsy. The postoperative fever (>38°C) was found in 2 cases (2. 6%, 2/78). Conclusion SBFU with holmium laser lithotripsy is a safe and effective treatment for bilateral renal or ureteral calculi. This procedure is a reliable treatment option for bilateral renal or ureteral calculi.
    Article · Dec 2014 · Academic Journal of Second Military Medical University
  • Hu-Cheng Ma · Xiao-Lei Shi · Hao-Zhen Ren · [...] · Yi-Tao Ding
    [Show abstract] [Hide abstract] ABSTRACT: Aim: To improve the colonization rate of transplanted mesenchymal stem cells (MSCs) in the liver and effect of MSC transplantation for acute liver failure (ALF). Methods: MSC was modified with the chemokine CXC receptor 4 (CXCR4) gene (CXCR4-MSC) or not (Null-MSC) through lentiviral transduction. The characteristics of CXCR4-MSCs and Null-MSCs were determined by real-time quantitative polymerase chain reaction, Western blotting and flow cytometry. CXCR4-MSCs and Null-MSCs were infused intravenously 24 h after administration of CCl4 in nude mice. The distribution of the MSCs, survival rates, liver function, hepatocyte regeneration and growth factors of the recipient mice were analyzed. Results: In vitro, CXCR4-MSCs showed better migration capability toward stromal cell-derived factor-1α and a protective effect against thioacetamide in hepatocytes. In vivo imaging showed that CXCR4-MSCs migrated to the liver in larger numbers than Null-MSCs 1 and 5 d after ALF. Higher colonization led to a longer lifetime and better liver function. Either CXCR4-MSCs or Null-MSCs exhibited a paracrine effect through secreting hepatocyte growth factor and vascular endothelial growth factor. Immunohistochemical analysis of Ki-67 showed increased cell proliferation in the damaged liver of CXCR4-MSC-treated animals. Conclusion: Genetically modified MSCs expressing CXCR4 showed greater colonization and conferred better functional recovery in damaged liver.
    Article · Oct 2014 · World Journal of Gastroenterology