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Featured researches published by Ruilong Lan.


Toxicology reports | 2014

Potential toxicity of quercetin: The repression of mitochondrial copy number via decreased POLG expression and excessive TFAM expression in irradiated murine bone marrow

Ruiqing Chen; Jingan Lin; Jingshen Hong; Deping Han; Addison D. Zhang; Ruilong Lan; Lengxi Fu; Zhao-Yang Wu; Jianhua Lin; Weijian Zhang; Zeng Wang; Wei Chen; Chun Chen; Hengshan Zhang

The cytotoxicity of quercetin is not well understood. Using an ICR murine model, we unexpectedly found that mice exposed to 7 Gy total body irradiation (TBI) exhibited general in vivo toxicity after receiving quercetin (100 mg/kg PO), whereas this result was not observed in mice that received TBI only. In order to understand the involvement of alterations in mitochondrial biogenesis, we used a real-time qPCR to analyze the mitochondrial DNA copy number (mtDNAcn) by amplifying the MTRNR1 (12S rRNA) gene in murine bone marrow. We also utilized reverse transcription qPCR to determine the mRNA amounts transcribed from the polymerase gamma (POLG), POLG2, and mammalian mitochondrial transcription factor A (TFAM) genes in the tissue. In the mice exposed to TBI combined with quercetin, we found: (1) the radiation-induced increase of mtDNAcn was inhibited with a concurrent significant decrease in POLG expression; (2) TFAM expression was significantly increased; and (3) the expression of POLG2 was not influenced by the treatments. These data suggest that the overall toxicity was in part associated with the decrease in mtDNAcn, an effect apparently caused by the inhibition of POLG expression and overexpression of TFAM; unaltered POLG2 expression did not seem to contribute to toxicity.


International Journal of Nanomedicine | 2015

Sensitive electrochemical immunosensor based on three-dimensional nanostructure gold electrode.

Guang-Xian Zhong; Ruilong Lan; Wenxin Zhang; Fei-Huan Fu; Yiming Sun; Hua-Ping Peng; Tianbin Chen; Yishan Cai; Ai-Lin Liu; Jianhua Lin; Xinhua Lin

A sensitive electrochemical immunosensor was developed for detection of alpha-fetoprotein (AFP) based on a three-dimensional nanostructure gold electrode using a facile, rapid, “green” square-wave oxidation-reduction cycle technique. The resulting three-dimensional gold nanocomposites were characterized by scanning electron microscopy and cyclic voltammetry. A “sandwich-type” detection strategy using an electrochemical immunosensor was employed. Under optimal conditions, a good linear relationship between the current response signal and the AFP concentrations was observed in the range of 10–50 ng/mL with a detection limit of 3 pg/mL. This new immunosensor showed a fast amperometric response and high sensitivity and selectivity. It was successfully used to determine AFP in a human serum sample with a relative standard deviation of <5% (n=5). The proposed immunosensor represents a significant step toward practical application in clinical diagnosis and monitoring of prognosis.


Oncotarget | 2017

DcR3, a new biomarker for sepsis, correlates with infection severity and procalcitonin

Liqin Gao; Bin Yang; Hairong Zhang; Qishui Ou; Yulan Lin; Mei Zhang; Zhenhuan Zhang; Sunghee Kim; Bing Wu; Zeng Wang; Lengxi Fu; Jingan Lin; Ruiqing Chen; Ruilong Lan; Junying Chen; Wei Chen; Long Chen; Hengshan Zhang; Deping Han; Jingrong Chen; Paul Okunieff; Jianhua Lin; Lurong Zhang

Early diagnosis of sepsis is critical for successful treatment. The clinical value of DcR3 in early diagnosis of sepsis was determined in a dynamic follow-up study. Alterations in plasma levels of DcR3, PCT, CRP, and IL-6 were measured by ELISA and compared among patients with sepsis (n = 134), SIRS (n = 60) and normal adults (n = 50). Correlations and dynamic patterns among the biomarkers, APACHE II scores, clinical outcomes, and pathogens were also examined. Plasma DcR3 was significantly increased in sepsis compared to SIRS and normal adults (median 3.87 vs. 1.28 and 0.17 ng/ml). The elevated DcR3 could be detected in 97.60% sepsis patients 1–2 days prior to the result of blood culture reported. For diagnosis of sepsis, the sensitivity was 97.69% and specificity 98.04%; and for differential diagnosis of sepsis from SIRS, the sensitivity was 90.77% and specificity 98.40%. DcR3 level was positively correlated with severity of sepsis (rs = 0.82). In 41 patients who died of sepsis, DcR3 elevated as early as 1–2 days before blood culture and peaked on day 3 after blood culture performed. In 90% of sepsis patients, the dynamic alteration pattern of DcR3 was identical to that of PCT, while pattern of 10% patients differed in which clinical data was consistent with DcR3. In 13% sepsis patients, while PCT remained normal, DcR3 levels were at a high level. DcR3 levels had no difference among various pathogens infected. DcR3, a new biomarker, will aid in early diagnosis of sepsis and monitoring its outcome, especially when sepsis patients were PCT negative.


OncoImmunology | 2018

δ-Catenin peptide vaccines repress hepatocellular carcinoma growth via CD8+ T cell activation

Fei Huang; Junying Chen; Ruilong Lan; Zeng Wang; Ruiqing Chen; Jingan Lin; Lurong Zhang; Lengxi Fu

ABSTRACT As classical therapy method of advanced hepatocellular carcinoma (HCC) is not effective enough, HCC immunotherapy is a hot spot for research in recent years. Although in recent years, immune checkpoint inhibitors are focused in cancer therapy, vaccines and adoptive cell therapy (ACT), as traditional immunotherapy methods for HCC are still promising. We found that δ-Catenin might be a new tumor-associated antigen for HCC, for it could be upregulated as a stress associated protein under hypoxia and irradiation treatment. δ-Catenin peptide vaccines could inhibit the growth of subcutaneous hepatocellular tumors in vivo. According to our work, δ-Catenin peptide vaccines could stimulate the activation of cytotoxic T lymphocytes (CTLs) and enhance the infiltration of CD8+ T cells into tumors. Moreover, δ-Catenin peptide vaccines could enhance the secretion of IFN-γ and the killing of tumor cells by T cells. Mechanistically, δ-Catenin peptide vaccines, presented by antigen-presenting cells to T cells, could enhance the activation of T cells via MAPK/ERK signaling and the transcriptional factors Eomes and T-bet. Our research results indicate new potential peptide vaccines, which can be applied in clinical HCC therapy.


Environmental Toxicology and Pharmacology | 2018

18β-Glycyrrhetinic acid mitigates radiation-induced skin damage via NADPH oxidase/ROS/p38MAPK and NF-κB pathways

Li Su; Zeng Wang; Fei Huang; Ruilong Lan; Xiuying Chen; Deping Han; Lurong Zhang; Weijian Zhang; Jinsheng Hong

Radiation-induced inflammation plays an important role in radiation-induced tissue injury. 18β-glycyrrhetinic acid (18β-GA) has shown an anti-inflammatory activity. This study aimed to assess the activity of 18β-GA against radiation-induced skin damage, and explore the underlying mechanisms. In vitro assay revealed 18β-GA treatment decreased the production of IL-1β, IL-6, PGE2 and decreased p38MAPK phosphorylation, DNA-binding activity of AP-1, and NF-κB activation in irradiated RAW264.7 macrophages. Additionally, 18β-GA suppressed NF-κB activation by inhibiting NF-κB/p65 and IκB-α phosphorylation and alleviated ROS overproduction in irradiated RAW264.7 macrophages. In vivo assay showed 18β-GA alleviated severity of radiation-induced skin damage, reduced inflammatory cell infiltration and TNF-α, IL-1β and IL-6 levels in cutaneous tissues. Our findings demonstrate that 18β-GA exhibits anti-inflammatory actions against radiation-induced skin damage probably by inhibiting NADPH oxidase activity, ROS production, activation of p38MAPK and NF-κB signaling, and the DNA binding activities of NF-κB and AP-1, consequently suppressing pro-inflammatory cytokine production.


Cancer Biotherapy and Radiopharmaceuticals | 2018

Influence of POLG on Radiosensitivity of Nasopharyngeal Carcinoma Cells

Ruiqing Chen; Zeng Wang; Ruilong Lan; Fei Huang; Jinrong Chen; Yuanteng Xu; Hengshan Zhang; Lurong Zhang

BACKGROUND AND OBJECTIVE There is a high incidence of nasopharyngeal carcinoma (NPC), malignant head and neck tumors, in southern China. Radioresistance is the main cause affecting the efficacy of NPC treatments. The POLG gene particularly plays an important role in radiation-induced damage repair. In this study, the authors established RNAi CNE-1 and CNE-2 knockdown in two NPC cell lines to observe whether this gene affects the radiosensitivity of NPC cells. MATERIALS AND METHODS Four short hairpin RNA (shRNA) expression plasmids targeting POLG gene were constructed and transfected into the NPC cell lines CNE-1 and CNE-2. Screening was performed to evaluate the stable expression of cloned cells, which were named CNE-1/POLG-shRNA1, CNE-1/POLG-shRNA2, CNE-2/POLG-shRNA1, and CNE-2/POLG-shRNA2. The negative controls CNE-1/Neg-shRNA and CNE-2/Neg-shRNA were additionally used. The MTT method, flow cytometry, clone formation analysis, cell migration, and other experimental methods were employed to verify changes in the radiosensitivity of the NPC cells. RESULTS Fluorescent quantitative PCR and Western blot confirmed the downregulation of the PLOG gene through diminished PLOG messenger RNA and protein levels. Consequently, the authors report the stable knockdown of the POLG gene in an NPC model. Dose-dependent radiation exposure of POLG inhibited NPC cell growth and increased apoptosis compared with control cells (p < 0.01), as demonstrated through colony formation assay and flow cytometry. Functional assays indicated that knockdown of the POLG in CNE-1 and CNE-2 cells remarkably reduced cell viability and proliferation. Specifically, POLG knockdown led to G1 phase arrest and apoptosis. CONCLUSIONS Overall, the authors conclude that POLG downregulation alters the radiosensitivity of NPC cells, indicating that the gene is likely involved in conferring the radiation response of the cells. In addition, findings in this study suggest a novel role for POLG as a potential predictive marker for NPC radiotherapy efficiency. POLG gene can be used as a potential clinical target to effectively improve the radiosensitivity of NPC.


Oncology Reports | 2017

Comparison of three different methods for the detection of circulating tumor cells in mice with lung metastasis

Weifeng Xu; Bing Wu; Lengxi Fu; Junying Chen; Zeng Wang; Fei Huang; Jinrong Chen; Mei Zhang; Zhenhuan Zhang; Jingan Lin; Ruilong Lan; Ruiqing Chen; Wei Chen; Long Chen; Jinsheng Hong; Weijian Zhang; Yuxiong Ding; Paul Okunieff; Jianhua Lin; Lurong Zhang

Circulating tumor cells (CTCs) represent the key step of cancer cell dissemination. The alteration of CTCs correlates with the treatment outcome and prognosis. To enrich and identify CTCs from billions of blood cells renders a very challenging task, which triggers development of several methods, including lysis of RBC plus negative or positive enrichment using antibodies, and filter membrane or spiral microfluidics to capture CTCs. To compare the advantages of different enrichment methods for CTCs, we utilized the 4T1 breast cancer cells transfected with both green fluorescent protein (GFP) and luciferase to trace CTCs in the experimental lung metastasis model. Three methods were used to detect CTCs at the same time: bioluminescence assay, smearing method, and membrane filter method. The in vivo alive mouse imaging was used to dynamically monitor the growth of lung metastases. The sensitivity and accuracy of three detection methods were compared side-by-side. Our results showed that 1) the sensitivity of bioluminescence assay was the highest, but there was no information of CTC morphology; 2) the smearing method and membrane filter method could observe the detail of CTC morphology, such as in single or in cluster, while their sensitivity was lower than bioluminescence assay; 3) A dynamic observation at a 7-day intervals, the lung metastatic cancer grew at a log speed, while CTCs were increased at a low speed. This might be due to the activated immune cells eliminating the CTCs at a speed much faster than CTCs were generated. This comparison of three CTC detection methods in mouse model suggests that bioluminescence assay could be used in quantitative study of the effect of certain agent on the suppression of CTCs, while GFP-based morphological assays could be used to study the dissemination mechanism of CTCs. The combination of both bioluminescence assay and GFP-based assay would generate more information for quantity and quality of CTCs.


Molecular Immunology | 2017

TLR9 mediated regulatory B10 cell amplification following sub-total body irradiation: Implications in attenuating EAE

Jinsheng Hong; Jie Fang; Ruilong Lan; Qi Tan; Yeping Tian; Mei Zhang; Paul Okunieff; Lurong Zhang; Jianhua Lin; Deping Han

&NA; Autoimmunity and inflammation are controlled in part by regulatory B (Breg) cells, including the recently identified IL‐10‐competent B10 cell subset that represents 1%–3% of mouse spleen B cells. In this study, the influence of irradiation on Breg/B10 cell generation and IL‐10 production mediated by TLR9 signaling pathways was investigated. Spleen and peritoneal cavity Breg/B10 cell frequencies were significantly expanded three weeks after sub‐total body irradiation (sub‐TBI, 5 Gy or 10 Gy) in adult male wild type (WT) C57BL/6(B6) mice but not in TLR9−/− mice. TLR9 agonist ODN1826 stimulation in vitro for 5 h induced more B10 cells to express cytoplasmic IL‐10 in sub‐TBI WT mice than in TLR9−/− mice. Prolonged ODN1826 stimulation (48 h) induced additional spleen CD19hiCD5+CD1dhi B cells to express IL‐10. TLR9‐dependent signaling molecules, MyD88, TRAF6 and IRF8 are involved in sub‐TBI induced Breg/B10 cells development and expansion. Furthermore, using a mouse model for multiple sclerosis, we show here that sub‐TBI induced Breg/B10 cells dramatically inhibit disease onset and severity when transferred into mice with established experimental autoimmune encephalomyelitis (EAE). Adoptively transferred sub‐TBI induced Breg cells significantly suppress inflammatory T cell responses of TH17 and TH1 types in EAE mice. In conclusion, sub‐TBI can drive Breg/B10 cell development and expansion, which could be used as a novel tool for suppressing undesirable immunity. The ex vivo expansion and reinfusion of autologous Breg/B10 cells may provide a novel and effective in vivo treatment for severe autoimmune diseases that are resistant to current therapies. HighlightsSpleen Breg/B10 cell frequencies were expanded three weeks after Sub‐TBI in wild type mice but not in TLR9‐/‐ mice.Sub‐TBI induced Breg/B10 cells dramatically inhibit disease onset and severity when transferred into mice with established EAE.Adoptively transferred Sub‐TBI induced Breg cells significantly suppress responses of TH17 and TH1 in EAE mice.


Oncology Reports | 2017

δ-Catenin promotes tumorigenesis and metastasis of lung adenocarcinoma

Fei Huang; Junying Chen; Zeng Wang; Ruilong Lan; Lengxi Fu; Lurong Zhang


Journal of Orthopaedic Surgery and Research | 2016

Verification of TREX1 as a promising indicator of judging the prognosis of osteosarcoma

Jinyi Feng; Ruilong Lan; Guanxiong Cai; Jinluan Lin; Xinwen Wang; Jianhua Lin; Deping Han

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Jianhua Lin

Fujian Medical University

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Zeng Wang

Fujian Medical University

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Lurong Zhang

Fujian Medical University

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Deping Han

Fujian Medical University

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Fei Huang

Fujian Medical University

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Lengxi Fu

Fujian Medical University

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Ruiqing Chen

Fujian Medical University

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Jingan Lin

Fujian Medical University

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Junying Chen

Fujian Medical University

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