Lijun Dai

Wuhan University

Author Statistics

Papers

Citation

H-Index

i-10 index

Research Trends

Author Order

Document Type

Co-Authors

Bohao Zhang

Tianjin Huanhu Hospital

C. Roger White

Memorial Sloan Kettering Cancer Center

Xingxu Zhao

Gansu Agricultural University

Quanwei Zhang

Jiangnan University

Himanshu Gupta

Valley Health System

Xu Bai

Gansu Agricultural University

Jun Shi

Shanghai University of Traditional Chinese Medicine

Zhentao Zhang

Wuhan University

G.M. Anantharamaiah

Birmingham VA Medical Center

Yueling Huang

Guangzhou Medical University

Cooperative Institutions

Wuhan University

Renmin Hospital of Wuhan University

University of Alabama at Birmingham

Sun Yat-sen University

Peking University

Sichuan University

Shanghai Jiao Tong University

Gansu Agricultural University

Guangzhou Medical University

Chinese Academy of Medical Sciences & Peking Union Medical College

Author Statistics

Papers

Citation

H-Index

i-10 index

Research Field

The cholesterol 24-hydroxylase CYP46A1 promotes α-synuclein pathology in Parkinson’s disease

PLoS Biology (2025)

Lijun Dai Jiannan Wang Lanxia Meng Xingyu Zhang Tingting Xiao

Parkinson’s disease (PD) is a neurodegenerative disease characterized by the death of dopaminergic neurons in the substantia nigra and the formation of Lewy bodies that are composed of aggregated α-synuclein (α-Syn). However, the factors that regulate α-Syn pathology and nigrostriatal dopaminergic degeneration remain poorly understood. Previous studies demonstrate cholesterol 24-hydroxylase (CYP46A1) increases the risk for PD. Moreover, 24-hydroxycholesterol (24-OHC), a brain-specific oxysterol that is catalyzed by CYP46A1, is elevated in the cerebrospinal fluid of PD patients. Herein, we show that the levels of CYP46A1 and 24-OHC are elevated in PD patients and increase with age in a mouse model. Overexpression of CYP46A1 intensifies α-Syn pathology, whereas genetic removal of CYP46A1 attenuates α-Syn neurotoxicity and nigrostriatal dopaminergic degeneration in the brain. Moreover, supplementation with exogenous 24-OHC exacerbates the mitochondrial dysfunction induced by α-Syn fibrils. Intracerebral injection of 24-OHC enhances the spread of α-Syn pathology and dopaminergic neurodegeneration via elevated X-box binding protein 1 (XBP1) and lymphocyte-activation gene 3 (LAG3) levels. Thus, elevated CYP46A1 and 24-OHC promote neurotoxicity and the spread of α-Syn via the XBP1–LAG3 axis. Strategies aimed at inhibiting the CYP46A1-24-OHC axis and LAG3 could hold promise as disease-modifying therapies for PD.

Neurotoxicity

10.1371/journal.pbio.3002974

Cite

Citations (0)

Sulfur Amino Acid Metabolism and the Role of Endogenous Cystathionine-γ-lyase/H2S in Holstein Cows with Clinical Mastitis

Animals (2022)

Bohao Zhang Ting Lin Xu Bai Xiao-Xiao An Lijun Dai

H2S plays an important role in various inflammatory diseases. However, the role of H2S and synthetic enzymes in Holstein cows with CM is unknown. The aim of this study was to identify DEPs associated with sulfide metabolism and further investigate their roles in dairy cows with CM. From 3739 DEPs generated by data-independent acquisition proteomics, we identified a total of 17 DEPs included in 44 GO terms and five KEGG pathways related to sulfide metabolism, including CTH and cystathionine-β-synthase (CBS). Immunohistochemical and immunofluorescence staining results showed that CTH and CBS proteins were present mainly in the cytoplasm of mammary epithelial cells. Endogenous H2S production in the serum of the CM group was significantly lower than that of the healthy Holstein cows. CTH and CBS mRNA and protein levels in the mammary glands of the CM group were significantly downregulated compared to those of the healthy group. These results indicate that CTH and H2S were correlated with the occurrence and development of CM in Holstein cows, which provides important insights into the function and regulatory mechanism of CTH/H2S in Holstein cows.

Cystathionine gamma-lyase

10.3390/ani12111451

Cite

Citations (6)

[Ex vivo inducing cultured Epstein-Barr virus specific cytotoxic T lymphocytes and evaluation of their killing effect].

PubMed (2013)

Guanghua Chen Bin Gu Feng Chen Ying Wang Man Qiao

This study was aimed to explore the method for induction and expansion of EB virus specific cytotoxic T lymphocytes (EBV-CTL) in vitro, and to detect their killing effect. Peripheral blood mononuclear cells (PBMNC) were collected from 6 EBV seropositive healthy donors, and EBV-transformed B lymphoblastoid cells (BLCL)were used as the antigen-presenting cells and antigen stimulant which was irradiated by 40 Gy (60)Co irradiator. The autologous PBMNC and irradiated BLCL were cultured to induce and expand the EBV-CTL, and the immunophenotype was identified by the flow cytometry. The killing effect of the EBV-CTL against the autologous BLCL (autoBLCL), the autologous PHA cultured B lymphoblastoid cells( PHA-BLCL), the allogeneic BLCL (alloBLCL) and the K562 cells were measured with LDH release assay under different effector-to-target ratio. The results showed that the 6 cell lines of EBV-CTL were induced and expanded from the EBV seropositive healthy donors, the overall increase in cell numbers varied from 18.6 to 55.0 times. After 10 stimulations, the specific killing efficiency of the EBV-CTL for the autoBLCL were 59.4%, 43.2% and 29.0% under the effector-to-target ratio of 20: 1, 10: 1 and 5: 1. The nonspecific killing efficiency for the PHA-blast, alloBLCL and K562 cells were 7.1%, 9.4% and 10.3% (P < 0.05) under the 20: 1 ratio; 6.6%, 8.3% and 8.1% (P < 0.05) under 10: 1; 5.4%, 7.3% and 6.3% (P < 0.05) under 5: 1, respectively. It is concluded that the EBV-CTL can be successfully induced and expanded ex vivo for specific killing of HLA matched BLCL and may become a potential treatment for EBV related post-transplant lymphoproliferative disorders.

CTL*

Lymphoblast

K562 cells

10.7534/j.issn.1009-2137.2013.06.043

Cite

Citations (0)

B Lymphoblastoid Cell Lines as Efficient APC to Elicit CD8+ T Cell Responses Against a Cytomegalovirus Antigen

The Journal of Immunology (2000)

Qi Sun Robert L. Burton Lijun Dai William J. Britt Kenneth G. Lucas

Abstract Potent and readily accessible APC are critical for development of immunotherapy protocols to treat viral disease and cancer. We have shown that B lymphoblastoid cell lines (BLCL) that stably express CMV phosphoprotein 65 (BLCLpp65), as a result of retroviral transduction, can be used to generate ex vivo CTL cultures that possess cytotoxicity against CMV and EBV. In this report, we demonstrate that the EBV-specific cytotoxicity in the BLCLpp65-primed culture had a spectrum of EBV-Ag recognition similar to that of the BLCL-primed counterpart, suggesting that retroviral transduction and expression of the CMV Ag would not compromise the Ag-presenting capacity of BLCL. In addition, BLCLpp65 appeared to present multiple natural pp65 epitopes, because pp65-specific CTL, which recognized different CMV clinical isolates, were generated in BLCLpp65-primed cultures from individuals with various HLA backgrounds. Consistent with a polyclonal expansion of virus-specific CTL, T cell lines established from the BLCLpp65-primed CTL cultures expressed different TCR-Vβ. Although most of the virus-specific T cell isolates were CD8+, EBV-specific CD4+ lines were also established from BLCLpp65-primed cultures. Western blot analysis revealed that the CD8+ lines, but not the CD4+ line, expressed granzyme B, consistent with features of classic CTL. Thus, our results suggested that BLCL stably expressing a foreign Ag might be used as a practical APC to elicit CD8+ T cell responses.

CTL*

10.4049/jimmunol.165.7.4105

Cite

Citations (33)

[Expression of iNOS in the testis of Fmr1 knockout mice in different developmental stages].

PubMed (2012)

Yi Yang Xu-Hong Liu Bo Lin Xu-Dong Tan Shengqiang Chen

To analyze the expression of inducible nitric oxide synthase (iNOS) in the testis tissues of Fmr1 (fragile X mental retardation 1) knockout and wild-type male mice in different developmental stages, and provide background information for researches on fragile X syndrome.This study included 4, 6, 8 and 10 weeks old Fmr1 knockout and wild-type male mice, 6 in each age group. We identified the genotype of the mice by PCR, and detected and compared the expression of iNOS in the testis tissues of the Fmr1 knockout and wild-type mice by immunohistochemistry.The iNOS expression was weakly positive in the Leydig cells of the 4-week-old mice, moderately positive in the 6-week-old ones, and strongly positive in 8- and 10-week-old ones, significantly weaker in the Fmr1 knockout than in the wild-type ones.The expression of iNOS significantly decreases in the testis of Fmr1 knockout mice, suggesting that iNOS may be involved in the pathogenesis of fragile X syndrome.

FMR1

Knockout mouse

Fragile X Syndrome

Wild type

Pathogenesis

Source

Cite

Citations (0)

L‐4F, an apo A‐I mimetic peptide, prevents lipopolysaccharide‐induced changes in vascular function

The FASEB Journal (2006)

Zhenghao Zhang Lijun Dai Himanshu Gupta Jaideep Honavar G.M. Anantharamaiah

Previous studies show that HDL and apo A-I limit lipopolysaccharide (LPS)-induced inflammatory injury. In the current study, we tested the hypothesis that the apo A-I mimetic peptide L-4F prevents LPS-induced changes in arterial pressure and vascular reactivity. Systolic blood pressure (SBP) was measured at baseline, 6 and 48 hrs after intravenous injection of LPS (10mg/kg) in Sprague-Dawley rats. At 6 and 48 hrs, SBP was reduced by 27 and 37% respectively. Intraperitoneal injection of L-4F (10mg/kg) significantly blunted the LPS-induced decrease in SBP at these time points (16 and 19% reduction). In vitro studies revealed that LPS administration reduced the vasoconstrictor response to phenylephrine (PE) in isolated aortic ring segments. This response was completely reversed by in vivo treatment of LPS-injected rats with the iNOS inhibitor 1400W. Similar to 1400W, IP administration of L-4F restored the response to PE in LPS-treated rats to levels similar to those observed in vehicle treated animals. Western blot analyses of aortic tissues from LPS-treated rats revealed increased NOS II protein expression that was normalized by concurrent L-4F treatment. L-4F administration was also associated with a significant reduction in plasma levels of the NO metabolites nitrate and nitrite. It is proposed that L-4F, similar to HDL, neutralizes LPS, thus preventing hemodynamic changes associated with the induction of NOS II. Supported by NIH DK070040.

Phenylephrine

Intraperitoneal injection

10.1096/fasebj.20.5.a1073

Cite

Citations (1)

Gas/Liquid Chromatography–Mass Spectrometry Analysis of Key Functional Substances Regulating Poll Gland Secretion in Male Camels during Seasonal Estrus

Animals (2023)

Lijun Dai Bao Yuan Bohao Zhang Wenli Chen Xixue Yuan

Increased poll gland secretion is a major characteristic and indicator of estrus in male Bactrian camels; however, research on these poll glands and their secretion is extremely rare. In this study, we determine the chemical composition of poll gland secretions and identify the key functional substances that regulate seasonal estrus in male camels. A GC/LC-MS dual platform was used to analyze ventral hair (control) and neck mane samples containing poll gland secretions from male Bactrian camels during estrus. Multidimensional and single-dimensional analyses were used to screen differentially expressed metabolites (DEMs) between groups. Functional prediction of enriched metabolites was performed using a Human Metabolome Database comparison and Kyoto Encyclopedia of Genes and Genomes pathway enrichment analysis, which were then compared with a behavioral analysis of male Bactrian camels in estrus. A total of 1172 DEMs and 34 differential metabolic pathways were identified. One metabolite group was found to relate to steroid synthesis and metabolism, and another metabolite group was associated with neural metabolism. Therefore, we speculate that steroids and neurochemicals jointly regulate estrous behavior in male Bactrian camels, thus providing theoretical insights into the development and function of poll glands in Bactrian camels.

Metabolome

KEGG

10.3390/ani13122024

Cite

Citations (2)

Radiation-induced Vaginal Injury After Treatment for Cervical Cancer

International Journal of Radiation Oncology*Biology*Physics (2020)

Z. Liu T. Wang K. Zhang Y. Wang Lichun Wei

External beam radiotherapy

Chemoradiotherapy

Vaginal cancer

Univariate analysis

10.1016/j.ijrobp.2020.07.2609

Cite

Citations (1)

Inhibition of Lipopolysaccharide-Induced Inflammatory Responses by an Apolipoprotein AI Mimetic Peptide

Circulation Research (2005)

Himanshu Gupta Lijun Dai Geeta Datta David W. Garber Hernan E. Grenett

Previous studies suggest that high-density lipoprotein and apoAI inhibit lipopolysaccharide (LPS)-induced inflammatory responses. The goal of the current study was to test the hypothesis that the apoAI mimetic peptide L-4F exerts antiinflammatory effects similar to apoAI. Pretreatment of human umbilical vein endothelial cells (HUVECs) with LPS induced the adhesion of THP-1 monocytes. Incubation of cells with LPS and L-4F (1 to 50 microg/mL) reduced THP-1 adhesion in a concentration-dependent manner. This response was associated with a significant reduction in the synthesis of cytokines, chemokines, and adhesion molecules. L-4F reduced vascular cell adhesion molecule-1 expression induced by LPS or lipid A, whereas a control peptide (Sc-4F) showed no effect. In contrast to LPS treatment, L-4F did not inhibit IL-1beta- or tumor necrosis factor-alpha-induced vascular cell adhesion molecule-1 expression. The inhibitory effect of L-4F on LPS induction of inflammatory markers was associated with reduced binding of LPS to its plasma carrier molecule, lipopolysaccharide binding protein, and decreased binding of LPS to HUVEC monolayers. LPS and L-4F in HUVEC culture medium were fractionated by fast protein liquid chromatography and were localized to the same fractions, suggesting a physical interaction between these molecules. Proinflammatory responses to LPS are associated with the binding of lipid A to cell surface receptors. The current studies demonstrate that L-4F reduces the expression of inflammatory markers induced by LPS and lipid A and suggest that apoAI peptide mimetics may be useful in the treatment of inflammation associated with endotoxemia.

Proinflammatory cytokine

Lipid A

10.1161/01.res.0000176530.66400.48

Cite

Citations (109)

Number of Treatment Cycles Influences Development of Cytotoxic T Cells in Metastatic Breast Cancer Patients – A Phase I/II Study

Immunological Investigations (2010)

Stephen E. Wright Kathleen Rewers‐Felkins Imelda S. Quinlin Catherine Phillips Mary K. Townsend

The influence of the number of apheresis-stimulation-infusion(s) cycles, and the time in culture before the infusion (one vs. two weeks), on the generation of tumor antigen-specific cytotoxic T-lymphocytes (CTL) was investigated in a phase I/II clinical adoptive immunotherapy trial. Two previously treated metastatic breast cancer patients with no evidence of disease, in complete remission (CR), were enrolled. Each apheretic peripheral blood mononuclear cell (PBMC) sample was stimulated twice with MUC-1 before infusion back into the patients. Killer T-cells responses against MUC-1-expressing MCF-7 (CTL), nonspecific natural killer (NK) and lymphokine-activated killer (LAK) target cell lines, as well as, cytokine production were measured before each infusion. Patients received 2 infusions per month for 4 months. There were no tumor recurrences or toxicity. CTL, NK and LAK cells, type 1 cytokine, gamma-interferon (G-INF), and CD4+ and CD8+ memory T-lymphocytes were initially generated, produced or induced, respectively, and then declined. The CTL, NK and LAK cells were only induced at the first infusion of the first month. Thus, maintaining PBMC in culture longer than the first infusion was of no benefit with regards to retaining functional killer T-cells. In conclusion, this study implies that one treatment is optimal.

Lymphokine-activated killer cell

CTL*

10.3109/08820131003713798

Cite

Citations (5)