Yunlong Gao

Harbin Medical University

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Co-Authors

Xuejie Han

Harbin Medical University

Yue Li

Fudan University

Song Zhang

Harbin Medical University

Xinbo Zhao

Harbin Medical University

Yingchun Luo

Harbin Medical University

Yongtai Gong

First Affiliated Hospital of Harbin Medical University

Yu Duan

First Affiliated Hospital of Harbin Medical University

Wei Xu

Yancheng Institute of Technology

Shiqi Zhao

BOE Technology Group (China)

Yun Zhang

Harbin Medical University

Cooperative Institutions

Harbin Medical University

First Affiliated Hospital of Harbin Medical University

Xinxiang Medical University

Xinxiang University

Shandong University

Chinese Academy of Medical Sciences & Peking Union Medical College

Nanjing Medical University

Chinese Academy of Sciences

Sun Yat-sen University

Peking University

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ChemInform Abstract: Thiadiazole‐Based Thioglycosides as Sodium‐Glucose Co‐Transporter 2 (SGLT2) Inhibitors.

ChemInform (2010)

Yunlong Gao Guilong Zhao Wei Liu Yuli Wang Weiren Xu

Abstract A series of 16 thiadiazole‐based thioglycosides of type (IV) or (VI) are prepared and tested in vivo as sodium‐glucose co‐transporter 2 (SGLT2) inhibitors.

10.1002/chin.201036195

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The role of IDO/TTS mediated tryptophan metabolic pathway in patients with immune thrombocytopenia

Shiyong yixue zazhi (2014)

Qiu-jie Chen Yu Zeng Yunlong Gao Yan Ma Xinzhong Wu

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Lnc-C2orf63-4-1 Confers VSMC Homeostasis and Prevents Aortic Dissection Formation via STAT3 Interaction

Frontiers in Cell and Developmental Biology (2021)

Song Zhang Shiqi Zhao Xuejie Han Yun Zhang Xuexin Jin

Emerging evidence indicates that long non-coding RNAs (lncRNAs) serve as a critical molecular regulator in various cardiovascular diseases. Here, we aimed to identify and functionally characterize lncRNAs as potential mediators in the development of thoracic aortic dissection (TAD). We identified that a novel lncRNA, lnc-C2orf63-4-1, was lowly expressed in aortic samples of TAD patients and angiotensin II (Ang II)-challenged vascular smooth muscle cells (VSMCs), which was correlated with clinically aortic expansion. Besides, overexpression of lnc-C2orf63-4-1 significantly attenuated Ang II-induced apoptosis, phenotypic switching of VSMCs and degradation of extracellular matrix both in vitro and in vivo. A customized transcription factor array identified that signal transducer and activator of transcription 3 (STAT3) functioned as the main downstream effector. Mechanistically, dual-luciferase report analysis and RNA antisense purification (RAP) assay indicated that lnc-C2orf63-4-1 directly decreased the expression of STAT3, which was depend on the reduced stabilization of STAT3 mRNA. Importantly, up-regulation of STAT3 efficiently reversed the protective role of lnc-C2orf63-4-1 against Ang II-mediated vascular remodeling. Therefore, lnc-C2orf63-4-1 negatively regulated the expression of STAT3 and prevented the development of aortic dissection. Our study revealed that lnc-C2orf63-4-1 played a critical role in vascular homeostasis, and its dysfunction exacerbated Ang II-induced pathological vascular remodeling.

Homeostasis

10.3389/fcell.2021.792051

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Citations (13)

[Higher procalcitonin level in diabetic nephropathy patients compared with healthy volunteers].

PubMed (2014)

Zemin Wan Weiye Chen Miaolian Lu Haitao Zhou Yunlong Gao

To investigate the difference of procalcitonin (PCT) level between uninfected diabetic nephropathy patients and healthy volunteers.This study enrolled 76 patients with diabetes only [DM group, 24 h urinary micro albumin (mALB) < 30 mg/24 h], 81 patients with early DN (EDN group, mALB 30-300 mg/24 h), 87 DN patients (DN group, mALB > or = 300 mg/24 h), and 82 age- and sex-matched healthy volunteers. All the patients were free of systemic infection. PCT levels and various laboratory parameters including metabolic and kidney functions as well as inflammatory element profiles were assessed.The PCT level of DN group was significantly higher than that of healthy control group, DM group and EDN group (P < 0.001 or P < 0.05). Spearman's test showed a significant positive correlation between PCT and serum lactate dehydrogenase (LDH, r = 0.541, P < 0.01), Urine acid (UA) (r = 0. 320, P < 0.01), Urea (r = 0.324, P < 0.01), creatinine (Cr) (r= 0.403, P < 0.01), alpha-hydroxybutyrate dehydrogenase (alpha-HBD) (r = 0.791, P < 0.01) and C-reactive protein (CRP) (r = 0.694, P < 0.001) in diabetic nephropathy patients respectively.Serum PCT level of patients with diabetic nephropathy is higher than that of healthy volunteers, which may be associated with minimal inflammation and kidney function damage.

Procalcitonin

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3D-QSAR, molecular docking, and molecular dynamics simulation study of thieno[3,2-b]pyrrole-5-carboxamide derivatives as LSD1 inhibitors

RSC Advances (2020)

Yongtao Xu Zihao He Hongyi Liu Yifan Chen Yunlong Gao

Histone Lysine Specific Demethylase 1 (LSD1) is overexpressed in many cancers and becomes a new target for anticancer drugs. In recent years, small molecule inhibitors with various structures targeting LSD1 have been reported. Here we report the binding interaction modes of a series of thieno[3,2-b]pyrrole-5-carboxamide LSD1 inhibitors using molecular docking, and three-dimensional quantitative structure-activity relationships (3D-QSAR). Comparative molecular field analysis (CoMFA q2 = 0.783, r2 = 0.944, rpred2 = 0.851) and comparative molecular similarity indices analysis (CoMSIA q2 = 0.728, r2 = 0.982, rpred2 = 0.814) were used to establish 3D-QSAR models, which had good verification and prediction capabilities. Based on the contour maps and the information of molecular docking, 8 novel small molecules were designed in silico, among which compounds D4, D5 and D8 with high predictive activity were subjected to further molecular dynamics simulations (MD), and their possible binding modes were explored. It was found that Asn535 plays a crucial role in stabilizing the inhibitors. Furthermore, ADME and bioavailability prediction for D4, D5 and D8 were carried out. The results would provide valuable guidance for designing new reversible LSD1 inhibitors in the future.

ADME

Docking (animal)

Molecular descriptor

Molecular model

Carboxamide

10.1039/c9ra10085g

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Citations (26)

Design, synthesis and evaluation of dipeptides as probes for studies of gastrointestinal tract dipeptide transport system

Yunlong Gao

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Gut microbiota dysbiosis promotes age-related atrial fibrillation by lipopolysaccharide and glucose-induced activation of NLRP3-inflammasome

Cardiovascular Research (2021)

Yun Zhang Song Zhang Bolin Li Yingchun Luo Yongtai Gong

Abstract Aims Ageing is the most significant contributor to the increasing prevalence of atrial fibrillation (AF). The gut microbiota dysbiosis is involved in age-related diseases. However, whether the aged-associated dysbiosis contributes to age-related AF is still unknown. Direct demonstration that the aged gut microbiota is sufficient to transmit the enhanced AF susceptibility in a young host via microbiota-intestinal barrier-atria axis has not yet been reported. This study aimed to determine whether gut microbiota dysbiosis affects age-related AF. Methods and results Herein, by using a faecal microbiota transplantation (FMT) rat model, we demonstrated that the high AF susceptibility of aged rats could be transmitted to a young host. Specially, we found the dramatically increased levels of circulating lipopolysaccharide (LPS) and glucose led to the up-regulated expression of NOD-like receptor protein (NLRP)-3 inflammasome, promoting the development of AF, which depended on the enhanced atrial fibrosis in recipient host. Inhibition of inflammasome by a potent and selective inhibitor of the NLRP3 inflammasome, MCC950, resulted in a lower atrial fibrosis and AF susceptibility. Then, we conducted cross-sectional clinical studies to explore the effect of ageing on the altering trends with glucose levels and circulating LPS among clinical individuals in two China hospitals. We found that both of serum LPS and glucose levels were progressively increased in elderly patients as compared with those young. Furthermore, the ageing phenotype of circulating LPS and glucose levels, intestinal structure and atrial NLRP3-inflammasome of rats were also confirmed in clinical AF patients. Finally, aged rats colonized with youthful microbiota restored intestinal structure and atrial NLRP3-inflammasome activity, which suppressed the development of aged-related AF. Conclusions Collectively, these studies described a novel causal role of aberrant gut microbiota in the pathogenesis of age-related AF, which indicates that the microbiota-intestinal barrier-atrial NLRP3 inflammasome axis may be a rational molecular target for the treatment of aged-related arrhythmia disease.

Dysbiosis

10.1093/cvr/cvab114

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Citations (171)

2-[2-Hydroxy-4-(pyrrolidin-1-yl)benzoyl]benzoic acid

Acta Crystallographica Section E Structure Reports Online (2009)

Yunlong Gao Jianwu Wang

The title compound, C(18)H(17)NO(4), crystallizes with two indepen-dent mol-ecules in the asymmetric unit. The pyrrolidine ring in one mol-ecule is disordered over two positions, with refined site-occupancy factors of 0.853 (5) and 0.147 (5). The dihedral angles between the planes of the benzene rings in the two independent mol-ecules are 56.8 (2) and 68.2 (5)°. The mol-ecular conformations are stabilized by intra-molecular O-H⋯O hydrogen bonds. In the crystal structure, mol-ecules are linked by inter-molecular O-H⋯O hydrogen bonds, forming dimers and generating rings of graph-set motif R(2) (2)(8).

Benzoic acid

10.1107/s1600536809011349

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Evolocumab prevents atrial fibrillation in rheumatoid arthritis rats through restraint of PCSK9 induced atrial remodeling

Journal of Advanced Research (2023)

Xuejie Han Yunlong Gao Meijiao He Yingchun Luo Ying Wei

Proprotein convertase subtilisin/kexin type 9 (PCSK9) is implicated in the pathogenesis and progression of autoimmune disease. Patients with rheumatoid arthritis (RA) are at high risk of developing atrial fibrillation (AF), while whether PCSK9 is involved in the onset of AF among RA patients remains unclear. To explore the role of PCSK9 in the occurrence of AF in RA patients and decipher the underlying mechanism. We established a rat model of collagen-induced arthritis (CIA) by immunization with type II collagen in Freund's incomplete adjuvant. Atrial electrophysiological test was used to evaluate AF susceptibility. We performed a clinical study to examine the correlation between PCSK9 level and AF, which recruited healthy control, RA patients and RA patients complicated with AF. Evolocumab (a monoclonal antibody of PCSK9) is administered via intraperitoneal injection in CIA rats to assess the role of PCSK9 in RA-related AF. LPS-RS (LPS inhibitor), clodronate liposomes (depletion of macrophages), and cell co-culture model were used to dissect the mechanism underlying PCSK9 promotes AF. AF inducibility and duration were higher in CIA rats, accompanied by elevated plasma and atrial PCSK9. Interestingly, compared with healthy control subjects, patients with RA showed an increase in PCSK9, and the PCSK9 is much higher in RA patients complicated with AF. The level of PCSK9 was independently associated with AF risk in RA patients. In the in vivo experiment, evolocumab reduced AF susceptibility, and ameliorated atrial structural remodeling of CIA rats. Mechanistically, augmented LPS in CIA rats led to an increase in PCSK9, which exacerbated fibrosis of cardiac fibroblasts and apoptosis of cardiac myocytes by enhancement of M1 macrophages polarization and inflammation, thereby contributing to AF. This study suggests that elevated PCSK9 causes atrial structural remodeling by enhancement of M1 macrophages polarization in atria, and evolocumab can effectively protects CIA rats from AF.

Evolocumab

PCSK9

10.1016/j.jare.2023.09.007

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Design and Identification of Two Novel Resveratrol Derivatives As Potential LSD1 Inhibitors

Future Medicinal Chemistry (2021)

Yongtao Xu Yunlong Gao Min Yang Meiting Wang Jiarui Lu

Background: Overexpression of LSD1 is associated with the occurrence of many diseases, including cancers, which makes LSD1 a significant target for anticancer drug research. Methodology & Results: With the aid of 3D quantitative structure–activity relationship models established with 34 reported resveratrol derivative LSD1 inhibitors, derivatives 35–40 were designed. Absorption, distribution, metabolism and excretion calculations showed that they may have good bioavailability and drug likeness. Additionally, 35 and 37 presented good antitumor effects in an in vitro antiproliferative assay. Molecular docking and molecular dynamics simulation results indicated that 35 and 37 can establish extensive interactions with LSD1. Conclusion: The results of computational prediction and experimental validation suggest that 35 and 37 are effective antitumor inhibitors, which provides some ideas and directions for the development of new anticancer LSD1 inhibitors.

Anticancer drug

Docking (animal)

Drug Development

ADME

10.4155/fmc-2021-0105

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Citations (7)